USlNG ISOTOPE EFFECTS TO MODEL TRANSITION STATES

FOR CARBOCATION-NUCLEOPHILE COMBINATION REACTIONS

Thuy Van Pham

A thesis submitted in conformity with the requirements

for the degree of Doctor of Philosophy

Graduate Department of Chemistry

University of Toronto

Canada

O Copyright by Thuy Van Pham 1999

National Library Bibliothèque nationale du Canada

Acquisitions and Acquisitions et Bibliographie Services services bibliographiques

395 Wellington Street 395. rue Wellington Ortawa ON K1A ON4 Ottawa O N K1A ON4 Canada Canada

The author has granted a non- exclusive licence dowing the National Library of Canada to reproduce, loan, distribute or sell copies of this thesis in microfoxm, paper or electronic formats.

The author retains ownership of the copyright in this thesis. Neither the thesis nor substantial extracts fkom it may be printed or otherwise reproduced without the author' s permission.

L'auteur a accordé une licence non exclusive permettant à la Bibliothèque nationale du Canada de reproduire, prêter, distribuer ou vendre des copies de cette thèse sous la fome de microfiche/fh, de reproduction sur papier ou sur format électronique.

L'auteur conserve la propriété du droit d'auteur qui protège cette thèse. Ni la thèse ni des extraits substantiels de celle-ci ne doivent être imprimés ou autrement reproduits sans son autorisation.

For my famiiy

ACKNOWLEDGMENTS

I would like to express my deepest gratitude to professor R. A. McClelland for his

guidance and encouragement throughout my studies.

I am deeply indebted to rny parents, my brothers and sisters, and friends such as

M. Stroyan and E. MacKnight, without whose spiritual support this would not

have been possible.

I would like to thank the members of my research group, in particular, Eddy Low,

Pratima Sukhai, and Dr. A. Davidse for their advice and assistance during this

project.

I wish to thank the Department of Chemistry and the University of Toronto

for providing financial support and the facilities needed for this research.

And 1 would also like to thank the technical staff at Lash Miller

for their help throughout my

studies.

Using Isotope Effects to Model Transition States

For Carbocation-Nucleophile Corn bination Reactions

Doctor of Philosophy 1999

Thuy Van Pham

Graduate Department of Chem istry

University of Toronto

ABSTRACT

The transition state structures for the carbocation-nucleophile combination

reactions of (4-substituted-4'-methoxydipheny1)methyl cations with water,

chloride and bromide ions in various acetonitrile-water (AN:W) mixtures at 25 OC

have been investigated by measuring the secondary alpha deuterium kinetic

isotope effects (sadKIEs, Ri + Nu - RNu) and secondary alpha deuterium

equilibrium isotope effects (sadElEs, RNu - R' + Nu).

The sadKlE and sadElE results for the three nucleophiles with (4Lmethoxy-

dipheny1)methyl cation in 20:80 AN:W show that the transition state becomes

looser when the nucleophile is changed from water to chloride and to brornide

ions. Thus, with increased nucleophilicity, the transition state occurs earlier

along the reaction coordinate, in accordance with the Hammond postulate.

The identical sadKIEs of 0.89 for the reactions of Cmethyl, 4hydrogen

and (4-trifluorornethyl-4methoxydiphenyl)methyl cations with water in 20:80 and

90:lO AN:W indicate that the Ca-Ob transition state bond is constant when

either the substituent in the carbocation or the solvent is altered. This is not in

accordance with the Hammond postulate which predicts an early transition state,

Le., a longer Cu-OH2 transition state bond, for a change in substituent in the

carbocation from Crnethyl to 4-trifiuoromethyl. A normal secondary alpha

deuterium EIE of 1.20 was found for these reactions, written in the direction

ROH + H+ R++ HzO

A comparison with the secondary alpha deuterium KIE shows that there is

approximately 60 percent of Ca-OH2 bond making in the transition state.

The sadKlEs for the reactions of Cmethyl and (4-hydrogen-4'-methoxy-

dipheny1)rnethyl cations with bromide ion in 20:80 AN:W also indicate that the

transition states for these reactions are insensitive to a change of substituent in

carbocation. With the comparison between sadKlE of 0.97 (R' + B i - RBr)

and sadEKIE of 1.215 (for RBr - R+ + Bi ) proves that the Ca--Br bonds

were advanced to 20 percent in the transition state for these reactions.

The sadKlE of 0.94 and sudElE of 1.1 5 (for RCI - RR' + Cl-) were

measured for the reaction between chloride ion and (4'-rnethoxydiphenyl)rnethyl

cation in 20:80 AN:W. This also indicates that there was 40 percent of Ca-CI

bond forming in the transition state.

Finally, when the solvent was altered from 20:80 to 100:O AN:W the sudKlE

for the bromide reaction changed from 0.97 to 1.00. This indicates that when the

reaction reaches the diffusion controlled rate in the latter solvent there is no KIE,

Le., no Ca-NU bond forming in the transition state.

T A B L E O F C O N T E N T S

Page

A INTRODUCTION

A-l APPLICATION OF TRANSITION STATE THEORY TO THE SNI AND CARBOCATION-NUCLEOPHILE COMBINATION REACTIONS

A-2 KlNETlC ISOTOPE EFFECTS

A-3 KlNETlC ISOTOPE EFFECT EQUATIONS

A-3.1 REACTION RATE EQUATION

A-3.2 KlNETlC ISOTOPE EFFECT EQUATION

A-4 METHOD FOR PREDlCTlNG HOW CHANGING A SUBSTITUENT AFFECTS THE STRUCTURE OF THE SNI AND CARBOCATION-NUCLEOPHILE COMBINATION TRANSITION STATES

A-4.1 LEFFLER AND GRUNWARD POSTULATE

PREDlCTlON FOR SNI REACTIONS -

PREDlCTlON FOR CARBOCATION-NUCLEOPHILE COMBINATION REACTIONS

A-5 EXPERIMENTAL RESULTS: EFFECTS OF SUBSTITUENTS, 22 SOLVENTS AND NUCLEOPHILES ON TRANSIT1ON STATE STRUCTURE

FOR SNI REACTIONS

A-5.1.1 SOLVENT EFFECTS ON THE KIE OF SOLVOLYSIS REACTIONS

A-5.1.2 SUBSTITUENT EFFECTS ON THE KlES

A-5.1.3 THE EFFECT OF CHANGING THE LEAVING GROUP IN SUBSTRATES ON THE KIE

A-5.2 FOR CARBOCATION-NUCLEOPHILE COMBl NATION REACTIONS

A-6 LASER FLASH PHOTOLYSIS STUDIES OF CARBOCATION REACTlVlTlES

A-7 PLAN OF THESIS

B RESULTS AND DISCUSSION

B-1 SYNTHESIS

B-2 LASER FLASH PHOTOLYSIS

B-3 SECONDARY ALPHA DEUTERIUM KlES

B-3.1 REACTIONS WITH WATER

RWCTIONS WITH BROMIDE AND CHLORIDE IONS

B-4 SECONDARY ALPHA DEUTERIUM EQUlLlBRlUM ISOTOPE EF FECTS

B-4.1 WATER REACTION, DIARYLMETHANOLS IN SULFURIC ACID

vii

B-4.2 FOR REACTIONS WlTH BROMIDE ION

B-4.3 FOR REACTIONS WITH CHLORIDE ION

B-5 MODEL OF THE SN2(C') TRANSITION STATES

B-5.1 REACTIONS WlTH WATER

B-5.2 REACTIONS WITH BROMIDE AND CHLORIDE IONS

STUDY OF SOLVENT AND SUBSTITUENT EFFECTS ON THE RATE OF REACTIONS OF DIARYLMETHYL CATIONS WITH VARIOUS NUCLEOPHILES

B-6.1 SOLVENT EFFECTS

8-6.1.1 ON ANlONlC NUCLEOPHILES

B-6.1.2 ON SUBSTITUENTS

B-6.2 HAMMETT PLOTS

C CONCLUSION

D EXPERIMENTAL

D-1.1 DETERMINATION OF THE hm,, FOR UV DETECTION TO BE USED IN KINETIC STUDY

D-1.2 SECONDARY ALPHA DEUTERIUM KIE MEASUREMENTS

D-1.2.1 REACTIONS OF WATER WlTH 4-SUBSTITUTED SUBSTRATES

D-1.2.2 BROMIDE AND CHLORIDE ION REACTIONS

D-1.3 SECONDARY ALPHA DEUTERIUM EIE MEASUREMENT

D-1.3.1 DIARYLMETHYL CATIONS WITH WATER IN SULFURIC AClD

D-1.3.2 (4-METHYL-4'-METH0XYDIPHENYL)METHYL CATION WITH BROMIDE ION

D-1.3.3 SECONDARY ALPHA DEUTERIUM KI€ MEASUREMENTS FOR THE SOLVOLYSIS REACTIONS OF UNDEUTERATED AND DEUTERATED (4'-METH0XYDlPHENYL)METHYL CHLORIDE IN 98:2 AN:W.

D-1.4 KINETIC MEASUREMENTS FOR STUDIES OF THE EFFECTS OF SOLVENT AND SUBSTITUENT ON THE RATES OF THE RFACTIONS OF (4SUBSTITUTED- 4'-METH0XYDIPHENYL)METHYL CATIONS WlTH WATER, BROMIDE, CHLORIDE AND ACETATE IONS IN VARIOUS AQUEOUS ACETONITRILES

D-2.1 PREPARATION OF UNDEUTERATED AND DEUTERATED 4-SUBSTITUTED 4'-METHOXY- DIPHENY1)METHYL CHLORIDE

D-2.1.1 PREPARATION OF UNDEUTERATED AND DEUTERATED (4- METH0XYDIPHENYL)METHYL CHLORIDE

D-2.1.2 PREPARATION OF (4-METHYL-4'METHOXY- D1PHENYL)METHYL CHLORIDE

D-2.1.3 PREPARATION OF UNDEUTERATED AND DEUTERATED (4TRIFLVOROMETHYL- 4'-METH0XYDIPHENYL)METHYL CHLORIDE

D-2.1.4 PREPARATION OF (3,4'DIMETHOXYPHENYL) METHYLCHLORI DE

D-2.2 PREPARATION OF (4-SUBSTITUTED-4'-METHOXY- D1PHENYL)METHANOLS

D-2.2.1 PREPARATION OF (4, 4'DIMETHOXYPHENYL) METHANOL

D-2.2.2 PREPARATION OF (4METHOXYDIPHENYL)- METHANOL

D-2.2.3 PREPARATlON OF (4-METHY L-4LM ETHOXY- D1PHENYL)METHANOL

D-2.2.4 PREPARATION OF (4TRIFLUOROMETHYL- 4'METHOXYDIPHENYL)METHANOL

D-2.2.5 PREPARATION OF (3,4'-DIMETHOXYPH ENY L) METHANOL

D-2.3 PREPARATION OF 4-SUBSTITUTED-4'- METHOXY- BENZOPHENONES

D-2.3.1 PREPARATION OF 4-METHYL-4'-METHOXY- BENZOPHENONE

D-2.3.2 PREPARATION OF 4TRIFLUOROMETHYL- 4'-METHOXYBENZOPHENONE

D-2.4 PREPARATlON OF (4-SUBSTITUTED-4'-METHOXY- DI PHENYL)METHAN-d-OLS

D-2.4.1 PREPARATION OF (4-4'DIMETHOXYPHENYL) METHAN-d-OL

D-2.4.2 PREPARATION OF (CMETHYL-4'METHOXY- D1PHENYL)METHAN-d-OL

D-2.4.3 PREPARATION OF (4-METHOXYDIPHENYL) METHAN-d-OL

D-2.4.4 PREPARATION OF (4-TRIFLUOROMETHYL- 4'METHOXYDIPHENYL)METHAN-d-OL

D-2.5 PREPARATION OF SODIUM 4CYANOPHENOXIDE

D-2.6 PREPARATION OF (4-SUBSTITUTED-4IMETHOXY- D1PHENYL)METHYL 4"CYANOPHENYL ETHERS

D-2.6.1 PREPARATION OF (CMETHYL-4'METHOXY- D1PHENYL)METHYL 4"XYANO-PHENYL ETHER

D-2.6.2 PREPARATION OF (4METHOXYDIPHENYL)- METHYL 4-CYANOPHENYL ETHER

D-2.6.3 PREPARATION OF (4TRIFLUOROMETHYL- 4'-METH0XYDIPHENYL)METHYL 4"-CYANO- PHENYL ETHER

D-2.7 PREPARATION OF (4-SUBSTITUTED-4IMETHOXY- DIPHENYLIMETHYL-d 4"-CYANO-PHENYL ETHERS

D-2.7.1 PREPARATION OF (4METHYL-4kMETHOXY- D1PHENYL)METHYL-d 4XYANOPHENYL ETHER

D-2.7.2 PREPARATION OF (4-METHOXYDIPHENYL) METHYL-d 4"-CYANOPHENYL ETHER

D-2.7.3 PREPARATION OF (4TRIFLUOROMETHYL- 4'-METH0XYDIPHENYL)METHYL-d 4"XYANO- PHENYL ETHER

D-2.8 PREPARATION OF UNDEUTERATED (4-SUBSTITUTED 4'-METH0XYDIPHENYL)METHYL ACETATES

D-2.8.1 PREPARATION OF (4METHOXYDIPHENYL) METHYL ACETATE

D-2.8.2 PREPARATION OF (4-METHYL-4'-METHOXY- D1PHENYL)METHYL ACETATE

D-2.8.3 PREPARATION OF (4TRIFLUOROMETHYL- 4'-METH0XYDIPHENYL)METHYL ACETATE

D-2.9 PREPARATION OF DEUTERATED (4-SUBSTITUTED 4'-METH0XYDIPHENYL)METHYL-d ACETATE

D-2.9.1 PREPARATION OF (4-METHOXYDIPHENYL) METHYL-d ACETATE

D-2.9.2 PREPARATION OF (4-METHYL-4LMETHOXY- D1PHENYL)METHYL-d ACETATE 156

D-2.9.1 PREPARATION OF (4-TRIFLUOROMETHYL- 4'-METH0XYDIPHENYL)METHYL-d ACETATE

APPENDIX

1) DOUBLE EXPONENTIAL DECAY

2) PERCENT OF BOND FORMATION IN TRANSITION STATE

3) ERROR CALCULATION

4) THE 'H AND 13c NMR, MS AND IR SPECTRA

4.1) The 'H and NMR and MS spectra of diarylrnethvl Chlorides -

4.2) The 'H and 13c NMR and MS spectra of diandmethano&

4.3) The 'H and j3c NMR. MS and IR spectra of 4-substituted-4'-methoxybenzophenones

4.4) The 'H and I3c NMR and MS spectra of diawlmethvl 4-cyanophenyl ethers

REFERENCES

xii

L I S T O F T A B L E S

Page

Table 1: Rate constants (kH) and secondary alpha deuterium KIEs for the solvolysis reactions of undeuterated and deuterated 23 3,3-dimethyl-2-butyl brosylates in various aqueous solvents at 25 OC.

Table 2: Rate constants and secondary alpha deuteriurn KlEs for the solvolysis reactions of 2-adarnantyl 2,2,2-trifluoroethyl- sulfonate in various aqueous solvents at 25 OC.

Table 3: Rate constants (kH) and secondary alpha deuterium KlEs for the solvolysis reactions of undeuterated and deuterated isopropyl brosylates in various aqueous solvents at 25 OC.

Table 4: Rates and secondary alpha deuterium KlEs for solvolysis of 3-pentyn-2-yl substrates in various aqueous ethanol and 2,2,2-trifluoroethanol at 25 O C .

Table 5: Relative rate constants and secondary alpha deuterium KIEs for the solvolysis of 1-(substituted phenyl)ethyl chlorides in various solvents at 25 O C .

Table 6: Secondary alpha deuterium KlEs for solvolysis of 7-(substituted phenyl)ethyl bromide in various solvents at 25 O C .

Table 7: Secondary alpha deuterium KIEs for soivaiysis of 7-(substituted pheny1)ethyl chloride and brornide in various solvents at 25 O C .

Table 8: Rates and secondary alpha deuterium KlEs for the solvolysis of 3-pentyn-2-yl su bstrates in va rious rnixtu res of aq ueous ethanols and 2,2,2-trifîuoroethanols at 25 OC.

Table 9: Rates and secondary alpha deuteriurn KIEs for solvolysis of dfierent substrates in trifluoroacetic acid, and various mixtures of aqueous ethanols and 2,2,2-trifiuoroethanols at 25 OC.

Table 10: Rate constants (kH) and secondary alpha deuterium KlEs for the reactions of undeuterated and deuterated diferrocenyl- methyl cations with various nucleophiles in 56:44 % (vh) AN:W at 25OC.

Table 11 : Rate constants and secondary alpha deuteriurn KlEs for the reactions between undeuterated and deuterated (4-methoxydiphenyl)methyl cation and some alkene nucleophiles in dichloromethane at -70.0°C

Table 12: Rate constants, secondary alpha deuteriurn KlEs and ElEs for solvolysis of undeuterated and deuterated ferrocenyl- 4-methoxyphenylmethyl and diferrocenylmethyl cations in several solvents at 25OC.

Table 13: Secondary alpha deuterium KIEs and EIEs for reactions between (4,4'-disubstituted dipheny1)rnethanol and water in aqueous sulphuric acid at 25 O C .

Table 14: Rate constants for decay of diarylmethyl cations in 20:80 acetonitrile : water (AN:W) and 2,2,2-trifiuoroethanol at 20 OC.

Table 15: The hmax's for the (4-substituted-4'-methoxydiphenyl)methyl cations.

Table 16: Rate constants and secondary alpha deuterium KIEs for the reactions between undeuterated and deuterated (4-rnethoxydiphenyl)methyl cations and water in 20:80 AN:W at 25OC.

Table i 7: Secondary alpha deuterium KI Es for the reactions between undeuterated and deuterated diarylmethyl cations and water in 20:80 and 90:lO AN:W at 25OC.

Table 18: Rate constants and secondary alpha deuterium KlEs for the reactions between undeuterated and deuterated (4-methoxydiphenyl)methyl cations and bromide ion in 20:80 AN:W at 25OC.

xiv

Table 19: Rate constants and secondary alpha deuterium KIEs for the reactions between undeuterated and deuterated (4rnethoxydiphenyl)methyl cations and chlofide ion in 20230 AN:W at 25OC.

Table 20: Rate constants and secondary alpha deuterium KIEs for the reactions between undeuterated and deuterated (4-substituted-4'-methoxydiphenyl)methyl cations and bromide and chloride ions in 20:80 and 100:O AN:W at 25OC.

Table 21: UV absorbance at hm, = 464 nrn and secondary alpha deuterium ElEs for (4-methoxydiphenyl)methanols at 25 O C .

Final concentrations of undeuterated and deuterated substrates are 7.403E-6 M and 7.285E-6 M, respectively.

Table 22: Secondary alpha deuterium ElEs for (4methoxydiphenyl)- methanol.

Table 23: UV absorbance at hm, = 464 nm and secondary alpha deuterium ElEs for (4-methoxydiphenyl)methanol at 25 OC. The concentrations of undeuterated and deuterated substrates are 6.8E-6 M and 7.3E-6 M, respectively.

Table 24: Average secondary alpha deuterium EIEs for the ionization of (4-substituted-4'-rnethoxydiphenyl)methanols at 25 O C .

Table 25: Exponential coefficients for the reaction of bromide ion with the (4-methyl-4'-methoxydiphenyl)methyl cation in 20:80 AN:W at 25 O C .

Table 26: Rate constants, equilibrium constants and KlEs and ElEs for the reactions between undeuterated and deuterated (4-methyl-4'-methoxydiphenyl)methyl cations and bromide ion and solvent in 20:80 AN:W at 25 O C .

Table 27: Rate constants for solvolysis rnonitored with UV absorption at h = 249 nm and the secondary alpha deuterium KIE for (4-methoxydiphenyl)rnethyl chlorides in 2 % aqueous acetonitrile and 0.001 M tetramethylammonium hydroxide at 25 OC.

Table 28: The secondary alpha deuterium KlEs and average KIE for solvolysis reaction of the undeuterated and deuterated (4-methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.001 3 M tetramethylammonium hydroxide, at 25 OC.

Table 29: Rate constants for solvolysis monitored with UV absorption at = 249 nm and secondary alpha deuterium KIE for (4methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and sodium azide and different concentrations of tetramethylamrnonium hydroxide at 25 OC.

Table 30: Rate constants for solvolysis monitored with UV absorption at h = 249 nm and secondary alpha deuterium KIE for (4methoxydiphenyl) methyl chlorides in 2 % aqueous acetonitrile and 0.001 3 M tetramethylammonium hydroxide at 25 OC.

Table 31: Rate constants for solvolysis monitored with UV absorption at h = 249 nm and secondary alpha deuterium KIE for (4-rnethoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.001 M sodium azide at 25 OC.

Table 32: Second order rate constants and secondary alpha deuterium KIE for the reactions between (4-methoxy- dipheny1)methyl cations and chloride ion in 98:2 AN:W at 25 OC.

Table 33: Rate constants, KIEs, ElEs and percent of bond making of the &-OH2 bond in the transition state for the reactions of undeuterated and deuterated (diferrocenyl), (ferrocenyl- Cmethoxyphenyl) and (4-methoxydiphenyl)methyl cations with water at 25 OC.

Table 34: Rate constants, secondary alpha deuteriurn KIEs, EIEs and percent &-Nu bond making in the transition state for the reactions of undeuterated and deuterated (4-methoxy- diphenyl)methyl cations with water, chloride and bromide ions in 20:80 AN:W at 25 OC.

Table: 35 Rate constants for the reactions of (4-methyl-4'methoxy- dipheny1)methyl cation with various nucleophiles in aqueous acetonitrile at 25 OC.

xvi

Table: 36 Rate constants for the reactions of (4methoxydiphenyl)- methyl cation with various nucleophiles in aqueous acetonitrile at 25 OC.

Table: 37 Rate constants for the reactions of (4-trifluoromethyl- 4'methoxy dipheny1)methyl cation with various nucleophiles in aqueous acetonitrile at 25 OC.

Table 38: Second order rate constants for the reactions between (3-substituted and 4-substituted-4'-methoxydiphenyl)- methyl cations and bromide ion in 50:50 and 90:10 AN:W at 25 OC.

Table 39: Sigma plus values and first order observed rate constants for the reactions between (3-substituted and 4-substituted- 4'-methoxydipheny1)methyl cations and water in 50:50 and 90:lO AN:W at 25 O C .

Table 40: UV wavelengths used to monitor the disappearance of (4-substituted-4'-methoxydiphenyl)methyl cations.

Table 41: UV wavelengths and time-windows used to monitor the disappearance of Cmethoxy, Cmethyl, 4hydrogen. and (4-trifluoromethyl-4'-methoxydiphenyl)methyl cations

Table 42: Volumes of nucleophile stock solution used to prepare fourteen 25 mL solutions for determining the KIE for the reactions of (4-substituted-4'-methoxydipheny1)methyl cations with bromide and chloride ions in 20:80 AN:W at 25 O C .

xvii

L I S T O F F I G U R E S

Page

Figure 1 : Reaction coordinate diagram for an SNI reaction ig noring ion pairs.

Figure 2: Reaction coordinate diagrarn for a carbocation-nucleophile combination reaction ignoring ion pairs.

Fiaure 3: Reaction coordinate diagrams showing how the magnitude of the secondary alpha deuteriurn KIE is related to transition state structure when, (a) the transition state is less sterically crowded around the alpha carbon than the reactant and kH/kD > 1, and (b) the transition state is more sterically crowded around the alpha carbon than the reactant and k ~ / k ~ < 1.

Figure 4: Reaction coordinate diagrams showing transition state structure close to (a) the reactant in an exothemic reaction, (b) the product in an endothermic reaction.

Fiqure 5: Reaction coordinate diagrams showing how the change of substituent affects the change of activation energy (from AG*^ to AG*^) and position of transition state (+ to +,) of an SNI reaction according to the Hammond postulate.

Fiqure 6: Transient absorption spectrum following 248 nm excitation of (4methoxydiphenyl)methyl acetate in argon-saturated 1 :2 acetonitri1e:water.

Fiqure 7 : Schematic diagram of nanosecond laser Rash photolysis apparatus.

Figure 8: Absorbance (482 nrn) versus tirne for the decay of the (4-meth yl-4'-methoxydip henyl)rnethyl cation in 90: 1 0 AN :W at 25 OC. The precursor was (4-methyl-4Lmethoxy- dipheny1)methyl 4"-cyanophenyl ether. The data labeled "substrate" and "solvent' are experimental data for solutions with and without substrate- The data labeled "correctedn is the difference. The insert shows the fit to a single experimental decay.

Fiqure 9: Observed first-order rate constants (s") versus concentrations of bromide ion (M) for the reactions of deuterated (D) and undeuterated (H) (4methoxydiphenyl)- methyl cations with bromide ion in 20330 AN:W at 25 O C .

Fiqure 10: UV absorption of diarylmethyl cations versus aqueous sulfuric acid concentrations. The curve labeled OMe, Me and H are for the (4.4'-dirnethoxyphenyl)methyl, the (4-methyl-4'-methoxydiphenyl)methyl and the (4'methoxy- dipheny1)methyl cations. respectively.

Figure 1 1 : LFP traces for reaction between (4-rnethyl-4y-methoxy dipheny1)methyl cation with bromide ion in 20:90 AN:W at 25 OC. The trace labeled Men is the observed decay with substrate. The trace labeled Solvent is the baseline obtained with solvent and tetra-n-butylammonium brornide solution. The trace Iabeled Corrected is the difference. The insert shows the fit to double exponential decay.

Figure 12: Sum of the exponential coefficients ( d ) versus concentrations of brornide ion (M) for the reactions of deuterated (D) and undeuterated (H) (4-methyl- 4'-methoxydiphenyl)methyl cations with bromide ion in 20:80 AN:W at 25 OC.

Figure 13: First order observed rate constants (s-') versus concentrations of chloride ion (M) for the reactions of deuterated (D) and undeterated (H) (4-methyl-4'-methoxy- dipheny1)methyl cations with chloride ion in 98:2 AN:W at 25 OC.

Figure 14: Logarithrn of first order observed rate constants (s-') of reactions between diarylrnethyl cations and water versus their log KR+. The dope of the straight line is 0.56.

xix

F i~u re 15: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-methyl-4'-methoxydiphenyl- methyl cation and bromide, chloride and acetate ions at 25 O C .

Figure 16: Logarithrn of the rate constant versus % acetonitrile for the reactions between (4-methoxydiphenyl)methyl cation and bromide, chloride and acetate ions at 25 OC.

Figure 17: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-trifluoromethyl-4'-rnethoxy- dipheny1)rnethyl cation and bromide, chloride and acetate ions at 25 O C .

F i~u re 18: Logarithm of the rate constant versus % acetonitrile for the reactions between (3,4'-dimethoxyphenyl)methyl cation and n-propyl, Bcyanoethyl, 2,2,2-trifluoroethyl amines at 25 OC.

Fiaure 19: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-substituted-4'-methoxy- dipheny1)methyl cation and acetate ion at 25 OC.

Fiaure 20: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-su bstituted-4'methoxy- dipheny1)methyl cation and chloride ion at 25OC.

Fiqure 21: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-substituted-4'-methoxy- diphenyl)methyl cation and bromide ion at 25 O C .

Figure 22: Pseudo first order rate constants (se') versus bromide ion concentrations (M) for the reactions between (4-substituted-4'-methoxydiphenyl)methyl cations and bromide ion and water in 50:50 AN:W at 25 OC.

Figure 23: Pseudo first order rate constants (s-') versus bromide ion concentrations (M-') for the reactions between (4-substituted-4'-methoxydiphenyl)methyl cations and bromide ion and water in 90: 10 AN:W at 25 OC.

Fiaure 24: Hammett plot for the reactions between (4substituted- 4'-methoxydipheny1)rnethyl cations and bromide ion and water in 5050 and 90:lO AN:W at 25 O C . The values of p' (dopes) are 0.30, 0.68, 0.895 and 0.887, respectively, for the bromide ion reactions in 90:10, 50:50 AN:W and the water reactions in 50:50, 90:lO AN:W

Figure 25: A typical extrapolation of UV readings to zero tirne for (4,4 '-dimethoxyp heny1)methyl cation (labeled OMe, OMe), (4-methyl-4'-methoxydiphenyl)methyl cation (labeled Me, OMe), and (4-methoxyd ip henyl)methyl cation (labeled Hl OMe) in 8.23, 8.23 and 9.82 % aqueous sulfuric acid solutions, respectively, at 25 OC.

Fiaure 26: UV absorption of carbocations versus aqueous sulfuric acid concentrations. The cuwe labeled OMe, OMe is for (4,4'-dimethoxyphenyl)methyl cation. The curve labeled Me, OMe is for (4-methyl-4'-methoxydipheny1)methyl cation. The cuwe labeled H, OMe is for (4-methoxy- diphenyl)methyl cation. The curve labeled CF3, OMe is for (4-trifluoromethyl-4methoxydip henyl)rnethyl cation.

Figure 27: Optical density change and fitted curve for the solvolysis reaction of (4-methoxyd ip henyl)methyl chloride in 97:3 AN:W at 25 O C

xxi

A INTRODUCTION

In 1933, Hughes, lngold and ~ a t e l ' were the first to propose two different

mechanisms for nucleophilic substitution (SN) reactions. One of these is the

concerted bimolecular SN2 (S: substitution, N: nucleophilic, 2: bimolecular)

mechanism. In this mechanism, a leaving group, LG-, is roplaced by a

nucleophile, Nu-, at a saturated carbon atorti, Ca, in a single step (equation 1).

That means that in the SN2 mechanism, the formation of the Nu-Ca bond is

concurrent with the breaking of the Ca-LG bond and no intenediate is formed.

This occurs in such a way that the N u supplies two electrons to form a new

covalent bond, and LG- departs with the pair of electrons from the old covalent

bond.

The second mechanisrn is the unimolecular SNI (S: substitution, N:

nucleophilic, 1 : unimolecular) mechanism. In the slow step of this mechanism,

equation 2, the C,LG bond breaks to form a carbocatioti and a negatively

charged leaving group.

The carbocation reacts rapidly with a nucleophile to forrn the product in the

second step (equation 3).

Winstein and CO-workers2 added hvo more intermediates into the SNI

mechanism (Scheme 1).

ks NU I ks Nu- l

Scheme 1

One of these intermediates is the intimate ion pair, C,'LG-, where the covalent

Ca-LG bond is completely broken and the hnlp ions are held tightly together in

il

i i)

iii)

solution by electrostatic attraction. The second intermediate is the solvent

separated ion pair, c,' 11 LG-, which has several solvent rnolecules sandwiched

between the two ions.

Depending on the nature of the reactants and the reaction conditions, the

reaction c m occur by several combinations of the steps in Scheme 12. The

reaction is said to occur via a carbocation (SNI) mechanism if either kl, k2 or ks is

the slow step of the reaction. The reaction is said to occur by an s ~ ~ ( c + )

mechanism3, if one of k4, k5 or k6 is the rate determining step.

A-1 APPLICATION OF TRANSITION STATE THEORY TO THE SNI AND

CARBOCATION-NUCLEOPHILE COMBINATION REACTIONS

Activated complex or transition state theory was originally developed by Eyring

and CO-workers4. The central concepts of this theory are as ffillows:

Some activated complex species, called the transition state, rnust be attained in

passing from the reactants to the products, or vice versa, of every elernentary

step of a reaction.

The transition state structure iç in thermodpnamic equilibriurn with the reactants.

Once forrned, the transition state decompcses to products with a universal rate

constant equal to ~ T l h , where K is Boltzmann constant, T is the absolute

temperature, and h is Planck's constant.

iv) The transition state has one less vibrational degree of freedom than a normal

molecule constructed with the sarne number of atorns. The vibrational energy

associated with this degree of freedorn is converted into translational energy

along the reaction coordinate.

According to assumptions i) and ii) of transition state theory, the elementary

steps kl and kg of the reactions in Scheme 1 are related to two transition state

structures as in equations 4 and 5, respectively.

Reaction CO-ordinate diagrams represent the change in free energies that occurs

as the reactants are converted into products, Le., as the reactants move along the

reaction CO-ordinates in the SNI and carbocation-nucleophile combination

reactions, respectively, Figures 1 and 2. The free energy barriers separate the

reactant regions from the product regions. The species with the highest energies

in these diagrams are the transition states of the reactions.

According to collision theory5, the carbocation-nucleophile combination

reaction occurs when the nucleophile and the carbocation collide with the proper

orientation and enough energy to pass over the energy barrier. As the reaction

progresses, the Nu-C, bond begins to form. The energy increases until it reaches

a maximum at the transition state. As the reaction proceeds the Nu-Ca bond

continues to f o m and the energy decreases.

From a quantitative point of view concepts iii) and iv) are very useful in

developing equations for rate constants and especially for kinetic isotope effects.

The latter comprises the major topic of this thesis and will be discussed in detail in

the next few sections.

RJ R2 + Nu-

b Reaction coordinate

Figure 1: Reaction coordinate diagram for an SNI reaction ignoring ion pairs.

- Rection coordinate

Figure 2: Reaction coordinate diagram for a carbocation- nucleophile combination reaction ignoring ion pairs.

A-2 KINETIC ISOTOPE EFFECTS

Kinetic Isotope Effects (KIEs) have been widely used to study both the basic

mechanisms of organic reactions and the detailed structures of transition states.

This technique involves measuring the effect of isotopic substitution on the rate

constant for a reaction. The KIE is defined as the ratio of the rate constant for the

reaction containing the lighter isotope, kli,ht, to the rate constant for the reaction

with the heavier isotope. kheavy (equation 6).

KIE = klis ht

hemy

A KIE is only observed if the bond to the atom undergoing isotopic substitution is

changed in going from the reactants to the transition state of the reaction6. One of

the two kinds of KlEs is a primary KIE. This KlE refers to reactions where the

bond to the isotopically labelled atom is actually breaking or forming in the rate

determining step of the reaction. The absolute magnitude of a primary KIE varies

from close to unity to much greater than unity depending upon the kind of atom

being isotopically substituted, and the change in bonding that occurs to this atom

as the reactants are converted into the transition state. The primary KIE is greater

than unity when the bonding to the isotope is decreased at the transition state

relative to the reactant. The value may be smaller than unity when the bonding to

the isotope is increased in going to the transition state.

The primary KIE when hydrogeni is replaced by deuteriurn (kH/ko) is normally

much greater than oneii* 7. Experimentally, this k d o is usually determined by the

comparative technique. This involves separately measuring the rate constants for

the undeuterated and deuterated reactants in different experiments. On the other

\~hroughout this thesis the term "hydrogen" is employed for the 'H isotope. " The maximum primary kH/kD has been estimated to be 7, at 25°C with no tunnelling.

hand. primary KIEs for heavy atoms (S, CI, O, N, or C) are small. These are

usually detemined by a competitive technique, i.e., a mixture containing both

isotopically labelled molecules is concurrently reacted in the same reaction.

A second kind of KIE is the secondary KIE. This KIE is observed when the

bonds to the isotopes do not break or fom in the transition state of the slow step of

the reaction. Sewndary KlEs are much srnaller than prirnary KIEs. Thus, in

practice, only secondary hydrogendeuterïurn or hydrogen-trithrn KlEs can be

measured with any accuracy. Although smallil these KIEs are often large enough

to be measured by either the competitive or the comparative technique. With

respect to substitution reactions such as the SNI and SN2 reactions, two types of

secondary KlEs that are commonly measured are the alpha and the beta

hydrogen-deuterium KIE. The alpha kHkD refers to the case where the hydrogen

and deuterium atoms are bonded to the carbon atom undergoing substitution

(equation 7). The beta kHkD refers to the situation where the hydrogen and

deuterium atorns are bonded to the carbon next to the reaction centre (equation 8).

' Le., the maximum secondary deuterium KIE is approximately 25 % per deuterium.

A-3 KlNETlC ISOTOPE EFFECT EQUATIONS

A-3.1 REACTION RATE EQUATlON

Transition state theory indicates that a carbocation-nucleophile combination

reaction occurs via a transition state which is in themodynamic equilibrfum with

the reactants (equation 9),

where N, c', T*, and P, are the nucleophile, the carbocation, the transition state,

and the product, respectively. Transition state theory14 then, expresses the rate

constant for the reaction as

The first terrn in brackets contains the transmission coefficient, the tunnelling

coefficient and the symrnetry coefficient, respectively. The transmission

coefficient, k, represents the probability that a given transition state is converted

into the product. The value of this coefficient is between zero and one. The

tunnelling coeffcient (7) accounts for reactants which have insufficient energy to

pass over the energy barrier but which can tunnel through the barrier to form

products. Should this phenornenon occur, the value of r is greater than one. For

carbocation-nucleophile combination reactions, tunnelling is not thought to be a

factor and r = 1.00. Finally, the symmetry coefficient (s) is a statistical factor

representing the number of equivalent ways a given orientation of the reactant

produces indistinguishable transition states. The s terrn is equal to or greater than

one.

The second terni in brackets contains Boltzmann's constant, K, Planck's

constant, h, and the absolute temperature, T.

The last terni, K*, is the equilibriurn constant for the equilibrium between the

reactants and the transition state. Statistical thermodynarnicsg can be applied to

this equilibrium, to produce equation 1 1,

where Q*, QN, and Qc+ are the rnolewlar partition functions per unit volume for

the transition state, nudeophile, and the çubstrate, respectively and AE* is the

energy of activation for the reaction. The tems R and T are the gas constant and

absolute temperature, respectively. Substituting equation 1 1 into equation 10

gives equation 12 for the rate constant.

A-3.2 KINETIC ISOTOPE EFFECT EQUATION

The rate constant equation, equation 12, is used to develop the KIE equation.

This involves the use of the subscripts "ligh< and to designate the light and

heavy isotopically labelled molecules. Application of equation 12 for each of these

molecules gives the expression for the KIE as follows.

klight - KIE = - -

heavy

The assurnption is made that isotopic substitution does not affect the energy

barrier, the transmission coefficient, and the syrnrnetry of the reactants. Quantum

mechanical tunnelling is assurned to be absent (except when dealing with

reactions involving the transfer of a hydrogen atom).' Thus al1 of the terrns except

the molecular partition functions cancel. In addition, only one of the reactants is

isotopically substituted. Thus the molecular partition coefficients for the other

reagents cancel, and equation 13 reduces to equation 14

* heavy

where QccheaW and QC+light are the molecular partition functions of the labelled and

* unlabelled reagents, and Q*,,~~, and Q light are the molecular partition functions

of the labelled and unlabelled transition states. Acwrding to statistical

themodynamics, the molecular partition function is defined by equation 15.

where gi is the degeneracy of the i" energy state and is the total energy of the im

energy state with respect to the ground state. The Born-Oppenheimer

states that the total energy of the molecule can be expressed as

the sum of the electronic, vibrational, translational and rotational energies of the

molecule (equation 16).

Since the total energy of the molecule can be expressed as a sum of independent

energy terms. the partition function Q is the product of the electronic, vibrational,

translational and rotational partition functions" (equaf on 17).

Q = q el gvib q bans q rot

This gives a very cornplex expression for KIE. However, when one is considerhg

a secondary alpha hydrogen-deuterium KIE the expression can be simplified using

the light isotope approximation. 12.13 Acwrding to the light isotope approximation

most ternis cancel. and the only term that is important is the zero point energy

difference (equation 18).

where üi

The quantity Aui = u i ~ - U~D, is the zero-point energy difference for the Ca-H(D)

vibrations in the undeuterated and deuterated reactants; AU,* = u~H* - U& is the

zero-point energy difference for the Ca-H(D) vibrations in the undeuterated and

deuterated transition states, v and ki are, respectively. the frequency and the

force constant for the i" vibration, and is the reduced mass of the Ca-H(D) bond.

Changing hydrogen for deuterium does not alter the force constant of the

Ca-H(D) bond, but it does change the reduced mass of the bond and the

vibrational frequency. This means that the zero-point energy for the Ca-D bond is

smaller than the zero-point energy of the Ca-H bond. The change in the Ca-H(D)

vibrations in going from the reactants to the transition state determines the

magnitude of the secondary KIE.

Equation 18 may be simplified to give equation 19 by using the empirical relation

vo=vdl .3514.

Equation 19 shows that a vibrational mode for which the frequency decreases on

going to the transition state (vHi > V*Hi) will contribute a factor greater than unity to

(kH/kD)a. Conversely a vibrational mode where the frequency increases will

contribute a factor less than unity. The former is comrnonly observed for SNI

reactions where formation of the transition state leads to a weakening of the bond

to the alpha hydrogen atom. In contrast, the secondary alpha KIE for a

carbocation-nucleophile combination reaction is less than unity since the alpha

hydrogen vibrational frequency increases on going from the carbocation state to

the transition state. This occurs because formation of the Ca-Nu bond in the

transition state increases the steric crowding about the C, carbon, strengthening

the bond to the hydrogen atom (vide infra).

Streitwieser and coworkers14 analysed these processes in terrns of the isotope

effect for the maximum change from sp3 to sp2 hybridisation (and vice-versa).

Three C-H vibrations were considered, the stretching vibration (A), an in-plane

bending vibration (B) and an out-of-plane bending vibration (C).

AG;

C-H \

C-D

AG:

C-H \

C-D i

Reaction coordinate (a)

Reaction coordinate

Figure 3 : Reaction coordinate diagxams showing how the magnitude of the seconüary alpha deuterium K I E is related to transition state structuse when, (a) the transition s ta te is less sterically crowded around the alpha carbon than the reactant and ka/kD > 1, and (b) the transit ion state is more s ter ica l ly crowded around the alpha carbon than the reactant and ka& < 1.

\ - C-H

/;sp3

\ I C-H

Csp3 1

\ - C-H

As noted from the data in the figures, only vibration (C) exhibits a significant

difference between sp3 and sp2. Thus the magnitude of the secondary alpha

deuterium KIE depends mainly on the change of the frequency of the Ca-H out-of-

plane bending vibration in going from the reactants to the transition state.

Streitwieser and CO-workers initially concluded that the maximum kHkD for an SNI

reaction would be 1.41, based upon the change in out-of-plane bending vibration

from 1 350 cm-' to 800 cm-'.

However, ~ a r t e l l ' ~ pointed out that steric crowding at the alpha carbon can alter

the out-of-plane bending vibrational frequencies. In an SNI reaction, steric

crowding at the alpha carbon of the substrate increases as the size of either RI,

or the LG" is increased (equation 20).

This increased stenc crowding increases the out-of-plane bending frequency of the

Ca-H(D) bond in the starting material resulting in a larger KIE.

Similarly, the steric crowding at the alpha carbon of the transition state for

carbocation-nucleophile combination also increases as the size of either Ri, R2, or

Nu is increased (equation 21).

I;I(D)

This increased steric crowding increases the out-of-plane bending frequency of the

Ca-H(D) bond in the transition state resulting in a more inverse KIE.

Secondary alpha deuterium KlEs have proved useful in the study of substituent

effects on transition state structure, since their magnitudes are determined by the

steric crowding around the C,H(D) bonds. Thus the k& can be related to the

Ca-LG (equation 20) or Nu-Ca (equation 21) distance.

A94 METHOD FOR PREDICTING HOW CHANGING A SUBSTITUENT

AFFECTS THE STRUCTURE OF THE SNI AND CARBOCATION-

NUCLEOPHILE COMBINATION TRANSITION STATES

4 LEFFLER AND GRUNWALD POSTULATE:

A method widely used to predict how the transition state is altered by a change

in substituent is the Hammond ost tu la te'^, or to be more precise, the modification

suggested by Leffier and ~ninwald'~. The Hammond postulate states that "if a

transition state and an unstable intermediate occur consecutively along the

reaction CO-ordinate and have nearly the same energy, their interconversion will

involve only a small change in structure". In a similar manner, the postulate also

states that "if the starting materials are of high energy and there is relatively little

change in energy in achieving the transition state, the structure of the transition

state will resemble that of the reagents". Thus, for a highly exothennic reaction

with a small AG*, the Hammond Postulate predicts that there will be littie change

in structure when the reactants are converted into the transition state and that the

transition state will be reactant-like, Figure 4 (a). An endotherrnic reaction with a

large AG*, on the other hand, will undergo a large change in structure in going

from the reactants to the transition state and have a product-like transition state,

Figure 4 (b).

The postulate, as originally stated by Hammond, applies only to the two cases

- rapid, highly exothennic, reactions with reactant-like transition states and slow,

Reaction coordinate

Fiare 4: Reaction coordinate diagrams showing transition state structure close to (a) the reactant in an exothermic reaction, (b) the product in an endothermic reaction.

highly endothermic, reactions with produd-like (or intemediate-like) transition

states. Leffler and Grunwald, then, proposed that it was possible to predict srnall

changes in transition state structure based upon the effect of a substituent on the

rate constant, and thus, on the free energy of activation.

Since the free energy of activation is inversely related to the rate (rate

constant), a substituent which increases the rate (rate constant) leads to a more

reactant-like transition state. This is shown in Figure 5 below for an endothermic

reaction where a substituent in reaction 2 lowers the energy of the intermediate

and the transition state. The Leffler-Grunwald postulate says that the transition

state for the reaction 2 is more reactant-like.

1 /

Reaction coordinate

F i a u r e 5: Reaction coordinate diagrams showing how the change of

substituent affects the change of ac t iva t ion e n a r m (from AG*, to AG*^) and position of transition state (8 , to 8,) of an S,l reaction according to the Hammond postulate.

A-4.2 PREDlCTlON FOR SNI REACTIONS:

In the SN1 reaction, adding an electron donating substituent to the leaving group

decreases the rate of the reaction. The postulate predicts that a reaction with a

poorer leaving group wiII have a more product-like transition state with a longer

C,LG bond. Conversely, an electron withdrawing substituent in the leaving

group (better leaving group) increases the rate constant and leads to a more

reactant-like transition state with a shorter Ca-LG bond.

Similarly, adding an electron donating substituent at Ca of the substrate

increases the rate constant of the reaction. The postulate predicts that the

reaction will have a more reactant-like transition state with a shorter Ca-LG bond.

Conversely, an electron withdrawing substituent in the substrate decreases the

rate constant and leads to a more product-like transition state with a longer

Ca-LG bond.

19-4.3 PREDICTION FOR CARBOCATION-NUCLEOPHILE COMBINATION

In carbocation-nucleophile combination reactions, adding an electron donating

substituent to the nucleophile increases the rate constant of the reaction. Thus,

the prediction is made that a reaction with a better nucleophile will have a more

reactant-like transition state with a longer Nu-Ca bond. Conversely, an electron

withdrawing substituent in the nucleophile decreases the rate constant and leads

to a more product-like transition state with a shorter Nu-Ca bond.

Similarly, adding an electron donating substituent to the carbocation decreases

the rate constant of the reaction. Thus for a given nucleophile, the postulate

predicts that a reaction with a more stable carbocation will have a more

product-like transition state with a shorter Nu-Ca bond. Conversely, an electron

withdrawing substituent in the carbocation increases the rate constant and leads to

a more reactant-like transition state with a longer Nu-C, bond.

A-5 EXPERIMENTAL RESULTS: EFFECTS OF SUBSTITUENTS, SOLVENTS

AND NUCLEOPHILES ON TRANSITION STATE STRUCTURE

The mechanism of a carbocation-nucleophile combination reaction is the

reverse process of an SN1 reaction. Therefore it follows, from the Principle of

Microscopie Reversibility, that the transition states for both reactions are the same.

The results of KIE studies for SNI reactions can therefore be useful in

understanding carbocation-nucleophile combination reactions.

A-5.1 FOR SNI REACTIONS

Many previous investigators have applied secondary deuteriurn KIEs to

characterise the mechanism for solvolysis reactions. Although a large review of

this area exists in the ~iterature,'~ this thesis will wver the secondary alpha

deuterium KIEs for solvolysis reactions with an SNI mechanism.

A-5.1.1 SOLVENT EFFECTS ON THE KIE OF SOLVOLYSlS REACTIONS

Most studies in this area were contributed by Shiner and his CO-workers. The

solvent effects on the KIE of solvolysis reactions were divided into two types. In

the fint type, the KIE is constant when the solvent is changed; the second type

demonstrates that the KIE significantiy changes when the solvent is varied.

Shiner, Fisher and Dowd measured the KlEs for the solvolysis of undeuterated

and deuterated 3,3dimethyl-2-butyl and isopropyl brosylates, and 2-adamantyl

2, 2, 2-trifluoroethyisulfonate in various aqueous solutions of 2,2,2-trifluoroethanol (a

reasonably polar but less nucleophilic solvent), and ethanol (a less polar and more

nucleophilic solvent), equations 22 and 23. These results are presented in Tables

1 and 2.

Table 1: Rate constants (kH) and secondary alpha deuterium KlEs for the solvolysis reactions of undeuterated and deuterated 3,3-dimethyl-2-butyl brosylates in various aqueous solvents at 25 OC. (Shiner, V. J., Jr; Fisher, R. D.; Dowd, W. J. Am. Chem. Soc. 1969,91,7748.)

Solventa ionizing power Ob kH (lad s-') ~HI~D

a 70% CF3CH20H is 70 volume % of 2, 2, 2-trifluoroethanol and 30 volume % of water etc. Shiner, V. J., Jr et al J. Am. Chem. Soc. 1969, 91, 4838. and references cited in this

paper.

u tn\ Slow

Table 2: Rate constants and secondary alpha deuterium KlEs for the solvolysis reactions of 2-adamantyl 2, 2, 2-trifluoroethylsulfonate in various aqueous solvents at 25 OC. (Shiner, V. J., Jr.; Fisher, R. D. J. Am. Chem. Soc. 1971, 93, 2553.)

Solventa ionizing power Ob kH se') k ~ k ~

a 70% CF3CH20H is 70 volume % of 2, 2, 2-trifluoroethanol and 30 volume % of water etc. Shiner, V. 3.. Jr. et ai J. Am. Chem. Soc. 1969, 91, 4838. and references cited in this

paper.

Varying the solvent resulted in a small change of the first order rate constant for

3.3-dimethyl-2-butyl brosylate (Table 1 ) and a large change for Badamantyl

2,2,2-trifiuoroethylsulfonate (Table 2) but the KIE was unchanged for both

reactions. 2-adarnantyl 2,2,2-trifluoroethylsulfonate (Table 2) but the KIE was

unchanged for both reactions. The KlEs for the two reactions were found to be

1.15 and 1.22-1.23, respectively. These results suggest that the transition states

for these reactions are not affected by the nature of the solvent.

The second type of solvent effect on KIEs is illustrated by the results presented

x X = Br (brosylate), CH3 (Tosylate)

Table 3: Rate constants (kH) and secondary alpha deuterium KIEs for the solvolysis reactions of undeuterated and deuterated isopropyl brosylates in various aqueous solvents at 25 OC. (Shiner, V. J., Jr.; Fisher, R. D ; Dowd, W. J. Am. Chem. Soc. 1969,91,7748.)

Solventa lonizing power ( Y ) ~ ~ H I ~ D

a 70% CF3CH20H is 70 volume % of 2, 2, 2-trifluoroethanol and 30 volume % of water etc. b Shiner, J. V., Jr. et al J. Am. Chem. Soc. 1969, 91, 4838, and references cited in this paper.

in Tables 3, 4, and 5. In this case, the KIE changed when the solvent was varied.

In the solvolysis of deuterated and undeuterated isopropyl brosylates,

(equation 24, Table 3) the KIE significantly varied when the solvent was changed.

The first order rate constant increased when the water concentration was

increased in both solvent systems ( aqueous 27272-trifluoroethanol or aqueous

ethanol). The KIE changed, however, in opposite directions, Le., for the

2,2,2-tnfluoroethanol solvent system (more polar and less nucleophilic solvent), the

KIE decreased from 1.16 to 1.14 to 1.12, and the rate constant increased from

0.21~1 od, to 1.41x10-~ and to 1 . 8 3 ~ 1 0 ~ s" when the water concentration was

increased from 3%, to 30% to 50%. These rate constant and KIE changes due to

the change in solvent system are what one would predict according to the

Hammond postulate.

In the ethanol solvent system (less polar and highly nucleophilic solvent) the

KIE increased frorn 1.08 to 1 . I O to 1.1 1' and the rate constant increased from

-5 -1 0.64~10" to 1 -45x1 O-' to 7.20~10 s when the water concentration was increased

from 10% to 20% to 50%, respectively. The changes seen in these rate constants

and KIEs when the solvent was varied would not be predicted by the Hammond

postulate. The change of the KIE, however, was not proportional to the change of

the rate constant in both solvent systems. In fact, in the 2,2,2-trifluoroethanol

solvent system, when the water concentration was varied from 3% to 30% and

from 30% to 50%, the rate constant increased, respectively, 6.7 and 1.3 times but

the KIE decreased by the same amount, 2% (i.e., a difference of 0.02). The same

observation applied in the ethanol solvent system. It is also worth noting that

changing the solvent from 70% 2,2,2-trifluoroethanol to 50% ethanol resulted in an

' Some chemists have suggested an explanation for the smailer KIEs is that there is a mixture of SN1 and SN2 mechanisms for the reactions in more nucleophilic solvents.

-5 -1 increase in the rate constant from 1 .41x105 to 720x1 0 s (Table 3) for the

solvolysis of isopropyl brosylates whereas the rate constant decreased from

lU.64xl0" to 10.1 1 XI 0" s-' (Table 1) for 3,3dimethyl-2-butyl brosylate, and

-5 -1 from 29.79~10" to 8.1 7x1 0 s for 2-adamantyl 2,2,2-trifluoroethyls~~lfonate. This

behaviour is dificuit to explain.

Table 4 contains the results for the solvolysis of 3-pentyn-2-y1 compounds.

equation 25. In this study , Shiner and ~ o w d ~ ' found that the solvent significantly

influenced the KIE for three different leaving groups. The solvent change from

least to most ionizing power (Y=1 A24 to 1 .65g2') increased the rate of reactions

and the KIEs. This effect of solvent on the KIE is contradicted by the results for

the isopropyl brosylates shown in Table 3.

Results for solvolysis of undeuterated and deuterated 7-(substitutedphenyl)

ethyl chlorides are presented in Table 5 (equation 26), with the solvents listed in

increasing order of the ionizing powei from top to bottom. The effect of changing

the solvent on the KIE was very small for these reactions. For example, for the

solvolysis of 7-(pheny1)ethyl chloride, changing the solvent from 80% ethanol to

50% ethanol to 97% 2,2,2-triflouroethanol changed the KIE from 1.147 to 1.153 to

1 -1 58, respectively. Similar examples exist for 1-(4phenoxyphenyl)ethyl, 7-(4-

methylphenyl) ethyl and 1-(4-trifluoromethy1phenyl)ethyl chlorides.

' This order of ionizing power is based on the increasing order of first order rate constants for solvolysis of substituted benzyl chlorides in these solvents.( see Shiner, V. J., Jr. et al J. Am. Chem. Soc., 1969, 91, 4838.)

slow YD) step y(D> HOS

CH3-C%C-Ç-CH3 - C&--=C-Ç-C& + LG' -

LG- = C ~ ~ S O S , Br-. I- HOS = &O, C&Ct+QH, CF3CH20H

Table 4: Rate constants and secondary alpha deuterium KIEs for solvolysis of 3- pentyn-2-yl substrates in aqueous ethanol and 2,Z.Z-trifluoroethanol at 25 OC. (Shiner and ~ o w d ~ ' )

LG Solventa ionizing power rate kH (s-')~ kHlkD

a 60 E is 60 % ethanol and 40 % water, etc. Errors are of the order of 0.1-0.2 %. Errors in the range of 0.2-0.4 % (cited in the reference). OTS is ptoluenesulfonate.

Table 5: Relative rate constants and sewndary alpha deuterium KIEs for the solvolysis of 7-(substituted pheny1)ethyl chlorides in various solvents at 25 OC.

Substituent X 4- &Ph0 4-Me 4-F 3-Me H 3-Br 4-CF3 4-NO2

Me0 a

Relative rate constantsb IO"XIO~ 60 3 2 1 6x1 O~ 3x1 o5

40T 1.124 a Extrapolated from measurements at 45 OC assuming normal temperature dependence. b Corrected relative rate constant to 50 % ethanol and 25 O C . relative to compound with X=H.

93A. 95E were 93%. 95% volume of acetone and ethanoi in water, respeclively. 40T is 40% weig ht trifluoroethanol in water. d Kinetic reproducibilities were within 0.1% or better except for reaction of the 4-phenoxy (4-Ph0) derivative in 93% acetone, 80% acetone, and 95% acetone, where the reproducibilities were 0.7, 0.5 and 0.3%, respectively.

A-5.1 -2 SUBSTITUENT EFFECTS ON THE KlES

Shiner's groupZ2 has studied the effects of substituents on the secondary alpha

deuterium KlEs for the solvolysis of 1-arylethyl chlorides and bromides at 25 OC,

(equations 26 and 27) and the results are presented in Tables 5 and 6.

In Table 5 the relative rate constants when corrected to the same conditions,

50% ethanoli, 25 OC, varied in magnitude by as much as 10". The change in the

KlE with substituent was divided into two categories. ln the first category, the

Table 6: Secondary alpha deuterium KlEs k r solvolysis of 7-(substituted pheny1)ethyl bromide in various solvents at 25 OC.

Substituent Xa sclventb

93% acetone

80% ethanol

5% acetone

a 4-Ph0 is Cphenoxy b The solvents were mixtures with water Error is standard deviation of the mean.

change of substituent affected the relative rate of solvolysis iri 50% ethanol by six

--

' See Shiner, V. J., Jr., et ai. J Am. Chem. Soc. 1968; 90,418.

KI€ was constant at 1 -15 for a change of substituent from 4methoxy to

hydrogen. This orders of magnitude (frorn 106 to 1). In the second category. the

KIE varied from 1.15 to 1.1 1 when the substituent changed from hydrogen to 4-

nitro. This substituent change caused the relative solvolysis rate to decrease by

five orders of magnitude (from 1 to 3x10-~). From these results, certain

conclusions were drawn. Firstly, the KIE was less sensitive to a change of

substituent. Secondly, the KIE and reactivity of 7-(aryl)ethyl chlorides were not

consistent with the Hammond postulate for the first category but were consistent

for the second category. The postulate predicts a smaller KIE for the less reactive

7-arylethyl chlorides. It seems that the KIE reached a maximum value of 2.15 for

the solvolyses of 1-arylethyl chlorides (vide supra). This suggests that the Ca-CI

bond was completely broken in the transition state of the rate determining step

(slow step) for the reactions with a KIE of 1.15. The KlEs which were 1.12, 7-(4-

trifluoromethylphenyl), and 1.1 1, 7-(4-nitrophenyI)ethyl, indicate that the C&I

bond was only partially broken in the transition state. Moreover, the transition state

for the former was slightly looser with a longer Ca-CI bond than for the latter

substrate.

The results in Table 5 above indicate that the effect of solvent on KIE is very

srnall for the solvolysis of 7-(substitutedpheny1)ethyl chloride, and it is assumed

that this can be applied for 7-(substituted phenyl)ethyl bromide. The different KlEs

in Table 6 were therefore attributed to changing the substituent from Cphenoxy

to hydrogen to Cnitro. This change is similar to that for 7-(substituted phenyl)ethyI

chloride, ie, the KIE remains constant when the substituent is changed from an

electron donating group to a hydrogen atom and the KIE becornes smaller when

the substituent is changed from a hydrogen atom to an electron withdrawing group.

A-5.1 .S THE EFFECT OF CHANGING THE LEAVING GROUF il4

SUBSTRATES ON THE KIE

The results in Tables 7, 8 and 9 show that the KiEs are different for different

leaving groups even for reactions performed in the same solvent. Additionally,

when the KIE has reached a maximum for each leaving group, it is then

independent of solvent, substituent or substrate structure changes. This finding

agrees with theoretical calculations in which shineP3 and CO-workers computed

the maximum KlEs of 1.22, 1.15, 1.13 and 1.09 for halide leaving groups of

fluoride, chloride. bromide, and iodide ion, respectively.

Table 7: Secondary alpha deuterium KIEs for solvolysis of 7-(substituted pheny1)ethyl chloride and bromide in various solvents at 25 OC.

Substituent Xa solventb ( ~ H / ~ D ) c I ( k ~ / k d ~r C

#-Ph0 93% acetone 1.147 1.126 I 0.010

4-NO2 05% acetone 1.114 1 .O85 + 0.001

a #-Ph0 is Cphenoxy The solvents were mixtures with water The error is the standard deviation of the mean.

Table 8: Rate constants and secondary alpha deuterium KlEs for the solvolysis of 3-pentyn-2-yl substrates in various mixtures of aqueous ethanols and 2,2,2- trifluoroethanols at 25 OC. (Shiner and ~ o w d ~ ' )

LG 60% ethanol 70% 2,2,2-trifiuoroethanol

k~ ~H/I<D C kH (s-')~ ~ H I ~ D

a 60 E is 60 % ethanol and 40 % water, etc. Errors are of the order of 0.1-0.2 %. Errors in the range of 0.2-0.4 %. OTS is p-toluenesulfonate.

In conclusion, the data for SNI solvolytic displacements illustrate the important

features of secondary alpha deuterium KlEs for limiting reactions; they are not

very dependent upon the structure of the substrate or upon the solvent, but they

do show a characteristic variation with the nature of the leaving group.

Arenesulphonates give the largest value of kHAD (1.23), followed by chlorides

(1 .AS), bromides (1.12), and iodides (1 .O9). This leaving group effect can be

quantitatively accounted for in ternis of the differences in the HCX bending

vibrations of ground states-

Table 9: Rate constants and secondary alpha deuteriurn KlEs for the solvolysis of different substrates in tnfluoroacetic acid, and various mixtures of aqueous ethanols and 2,.2,2-trifluoroethanols at 25 OC. (Shiner and DOW^^^)

Solventa substrate k~ (s-')

100% CF3COOH isopropyl tosylate 1.5~1 o 5 1 Zc

97% CF3CHflH 1 7.05 XI O" 1.228 + 0.001 2-adamantyl

70% CF3CH20H 2,2,2-trifluoroethyl 29.79 XI 0" 1.225 k 0.007 sulfonate

50% CH3CH20H 8.1 72 xIo-~ 1.225 + 0.001

70% CF3CH20H 3-pentyn-2-yl 8.775 x 1 O-' 1.226 tosy Iate

a 70% CF3CH20H is 70 volume percent of 2,2,2-trïfluoroethanol and 30 volume percent of water etc. b estimated at 12 OC. 4-Toluenesulfonate. Error is 2% and from Streitwieser, A. Jr.; Daffom, G. A. Tetrahedron

Letf. 1969,1263.

A-5.2 FOR CARBOCATION-NUCLEOPMLE COMBINATION REACTIONS

In contrast to the SNI reaction, there has been little study of the secondary

alpha deuterium KIEs for carbocation-nucleophile combination reactions.

Bunton and & - ~ o r k e r s ~ ~ studied the effects of changing the nucleophile for

the reactions of undeuterated and deuterated diferrocenylmethyl cations with

several anionic and neutral nucleophiles in aqueous acetonibile at 25 O C (equation

28 and Table 10). As can be seen in Table 10, rate constants for the three anionic

nucleophiles increased in the order HO-< BH f c Nc. However, the KIEs were the

same within the experimental error and equal to unity. This indicated that the

transition state C,Nu bond was insensitive to the type of anionic nucleophile. In

fact, the transition state was not very advanced in going from reactants to product.

In terms of equation 19, L(vHi - v ~ i * ) is unchanged, and equal to zero when the

nucleophile is varied. One possible explanation that was suggested was that

either kJ or k2" in Scheme 1 was the rate determining step of the reaction. In

other words formation of an ion-pair was rate-limiting, so that the rate determining

transition state did not involve any making of the Ca-NU bond.

For the primaiy amine nucleophiles, the nucleophile was varied from MeONH2

-1 -1 to MeNH2. The rate constant increased from 21.8 to 653 M s due to the

greater nucleophilicity of the more basic amine, but the KIE was not changed

(0.957 + 0.010 to 0.955 k 0.010). In these cases the KIEs were not unity,

indicating that there is some degree of Ca-NU bond formation in the transition

state of these reactions. The vibrational frequencies of the Ca-H bond are

increased in going from reactants to transition state as expected. Thus the L(vHi -

* VHi ) terms are different from zero. The value, however, does not depend on

amine nucleophile.

The results in Table 10 also show that the KIE changed very little or remained

constant when a very bulky nucleophile was used. Thus, when the bulkier

Table 10: Rate constants (kH) and secondary alpha deuterium KIEs for the reactions of undeuterated and deuterated diferrocenylmethyl cations with various nucleophiles in 56Ma % (vlv) acetonitrile : water (AN:W) at 25OC.

Nucleophile -1 -1 Rate constant (M s ) k ~ / k o

HO- 38.7 0.987 t 0.020

a 56:44 is percent ratio by volume and converted from an original value of 1:1 (by weight). Units are s-'.

nucleophile, BU'NH~, replaœd MeNHz the KIE was 0.969 + 0.014. Although the

value is slightly different from the one for MeNH2, the errors are too large to

differentiate the KIEs.

When water was uçed as the nucleophile, the KIE was decreased to 0.915. Le.,

more inverse. This result implied that Ca-NU bond making was more progressed

* in the transition state, and the absolute value of the C(vHi - V H ~ ) term was iarger for

the water reaction than those for the amine reactions.

It can be seen that the KIE results are not consistent with the Leffier-Grunwald

postdate. For the amine reactions, the rate constant was decreased from 653 to

-1 -1 21.8 M s when the substituent changed from Me to MeO. The KIE, however,

was unchanged. The prediction is that the formation of the C,Nu bond in the

transition state is less advanced for the more reactive nucleophile readion than for

the less reactive nucleophile reaction. Therefore the predidion is that for the more

reactive nucleophile, the absolute magnitude of the KIE should be smaller (less

inverse) than that for the less reactive nucleophile.

Mayr and CO-~orkers*~ are the other group to study the effects of changing the

nucleophile on the transition state of a carbocation-nudeophile combination

reaction. They measured the secondary alpha deuterium KlEs for the readions

between undeuterated and deuterated (4methoxydiphenyl)methyl

tetrachloroborates with several alkene nudeophiles in dichloromethane at -70.0

O C , equation 29. The results are given in Table 1 1.

These results are interesting for several reasons. First, al1 of the KlEs are very

large and inverse. This suggests that the transition states for these reactions are

very tight, i.e., product-like. In the reactant carbocation (sp2 hybridization) the out-

of-plane bending vibrations of the Ca-H(D) bonds are low energy so that v n is

small. In the transition state. the steric crowding caused by the alkene nucleophile

coming very close to the alpha carbon rnakes the out-of-plane bending vibrations

of very high energy. Therefore the vHi* term is large. Thus the absolute

magnitude of the C(vHi - VHi*) term in equation 19 is large, and there is a relatively

large inverse KIE.

a%ii OMe

Table 11 : Rate constants and secondary alpha deuterium KIEs for the reactions between undeuterated and deuterated (4-methoxydiphenyl)methyl cation and some alkene nucleophiles in dichloromethane at -70.0°C

Nucleophile kH (L mol-' se') k ~ / k $

a The estimated error for the KIE was 3 %, assuming that the average k~ and kD errors were 2 %.

The second observation is that there is no relationship between the KIE and

nucleophilicity. When the nucleophile was altered from 2-methyl-7-pentene to

3-trimethyisilyl-1-propene to 2-rnethyl-2-butene, the rate constant changed from

25.8 to 187 to 247 L mol-' s-'. The KIE was, however, unchanged within the

experimental error. Thus, for this series, the KIE is insensitive to a change in

reactivity of the nucleophile. This suggesis the Ca-NU bond making in the

transition state is the same for the three reactions. This is true even for 2-methyl-

Bbutene, which might be regarded as a more crowded nucleophile than the two

others.

Bunton, Watts and CO-workers2' studied how a change of solvent and substrate

affects the transition state by measuring the secondary alpha deuterium KlEs for

solvent addition to ferrocenyl-4-rnethoxyphenylmethyl and diferrocenylmethyl

cations in several solvents (equation 30, Table 12).

In the diferrocenylrnethyl cation reaction, when the solvent was changed from

an acetonitrile-water (AN:W) mixture to a methanol-water (Me0H:W) mixture, the

rate of the reaction was increased from 2.56 x IO-* to 0.177 sd'. 'The KIE varied

from 0.915 4 0.024 to 0.896 f 0.010. Meti~anol is more nucleophilic than water,

explaining why the rate constant was increased approximately seven times. The

KIEs, however, were the sarne within the experimental error. These results

suggest the KI€ is insensitive to the change in nucleophilicity of the solvent. This

suggests that the solvent does not alter the degree of bond rneCing in the transition

state for the cation-solvent combination.

Table 12: Rate constants, secondary alpha.deuterium KIES and ElEs for solvolysis of undeuterated and deuterated feri-ocenyl-4-methoxyphenylmethyl and diferrocenylmethyl cations in several solvents at 25OC.

~ c ~ r m e t h y l ~ cation Diferrocenylmethyl cation in water 5644 AN:^ 36: 64 MeOH:w

Nucleophile )-f20 H20 MeOH

7

" Fc and Ar are ferrocenyl and 4-methoxyphenyl, respectively. 56:44 is % ratio by volume and converted from an original value of 1:l (by weight). 36:64 is % ratio by volume and converted from a value of 0.695, mole fraction of water.

d The errors were standard deviations of the means (Bunton et al, 1980). This ratio is the EIE and it is calculated from ratio of (kH/k&( k&&, (Bunton et al, 1980);

and the error was calculated from the equation l/(kdk& x { ( [ ~ ( k d k ~ ) ~ ' + [ (kdk~)~(kdk&]~ x [ ~ ( k d k ~ ) ~ ] ~ ) ' ~ , see Appendk

When a ferrocenyl group was replaœd by a Cmethoxyphenyl group, the rate

constant changed from 2.66~10" to 43.2 s-' while the KIE changed from 0.9A5 + 0.024 to 0.874 + 0.016. The Cmethoxyphenyl group is not as stabilizing as

ferrocenyl, and thus the rate constant was increased by over three orders of

magnitude. The KIE was slightly decreased. However the difference is not

outside the experimental error.

Bunton and cm-workers also obtained values of the secondary alpha deuterium

equilibrium isotope effects (EIEs, w K H , Table 12). While these were different for

the two carbocations, the errors were very large.

Other workers 27, 28 rneasured equilibrium isotope effects for the ionization

of (4,4'-disubstituted diphenyl)rnethanol in aqueous sulphuric acid (equation 31).

For one system the KIE was also measured. This KIE value was measured

indirectly, being obtained in the course of an investigation of the kinetics of

oxidation of this alcohcl by acidic potassium permanganate. There is the

indication from the data (Table 13) that the EIE is increased with a more electron

withdrawing substituent. However the authors did not provide the errors in their

measurements. Without knowledge of these, we cannot conclude whether the

trend is real.

Table 13: Secondary alpha deuterium KlEs and ElEs for cation formation from 4,4'-disubstituted diphenylmethanol in aqueous sulphuric acid at 25 OC.

a (kH/k& is KIE for fonivard reaction. Data were from Banoo. F.; Stewart, R. Can. J. Chem. 1969,47,3199. b These data were from Mocek, M. M.; Stewart, R. Can. J. Chem. 4963,41, 1641.

A-6 LASER FLASH PHOTOLYSIS STUDIES OF CARBOCATION

REACTlVlTlES

The technique of flash photolysis provides for the direct observation of a

short-lived species, often under conditions where the species has been proposed

as a reactive intenediate. More importantly, it provides direct kinetic information

about the reactions of the intemediate. A number of neutral reactive

intemediates - free radicals, diradicals, carbenes, nitrenes, ketenes, enols - have

been intensively studied in this regard. More recently a variety of approaches have

been developed for the laser flash photolysis study of carbocations. 29.30

These approaches have provided direct kinetic information on the reactions of

carbocations in solvolytic media, Le., in water and simple alcohols as the solvent.

The decay in the solvent alone provides the rate constant for the reaction with the

solvent nucleophile, usually expressed as an unimolcular rate constant with the

units of s". Added nucleophiles accelerate the decay. The second order rate

constant for the reaction with the nucleophile is obtained as the slope of a plot of

the observed rate constant versus the concentration of added nucleophile.

A number of photochemical reactions have served to generate carbocations in

these studies. This thesis involves diarylmethyl cations, which have been

observed following irradiation of diarylmethyl acetates and diarylmethyl

4cyanophenoxides in water and alcohols.

This method involves heterolysis of a C-LG bond following excitation. and is the

photochemical analog of the cation - forrning step of an SNI reaction. As shown

in Scheme 2, homolysis also occurs, and both radical and cation transients are

observed. Fortunately for the study of diarylmethyl cations, the radicals absorb at

a completely different wavelengths from the cations, so that the observation of the

decay of the cations is not affected.

Scheme 2

400 500

Wavetength (nm)

Figure 6: Transient absorption spectrum following 248 nm excitation of (4-methoxydiphenyl) methyl acetate in argon- saturated 1 : 2 acetonitrile : w a t e r (AN : W) . This Figure was f rom McClelland, R. A. Tetrdzedron, 1996, 52, 6823-6858.

Rate constants obtained by nanosecond laser flash photolysis (nLFP) for the

deczy of some diarylmethyl cations are given in Table 14. In aqueous solution,

these cations are quite short-lived, the parent diarylrnethyl cation for example,

having a lifetime of less than 1 nanosecond.

Table 14: Rate constants for decay of diarylrnethyl cations in 20:80 acetonitrile : water (AN:W) and 2,2,2-trifluoroethanol at 20 OC. (McClelland et al3')

Substituents kWa (Cl) kc~c~2o1-1 (s-')

a Measured in 20:80 AN:W.

A-? PLAN OF THESIS

The objective of this research was to measure secondary alpha deutenurn KlEs

and equilibrium isotope effects (EIEs) for the reactions of (4-substituted-4-

methoxydipheny1)methyl cations with water, bromide ion and chloride ion in water

0, aœtonitriie (AN) and in acetonitrile : water (AN:W) mixtures.

These isotope effects provide information about the nature of the transition state

for these cation-nucleophile combination reactions, and in particular show how this

is affected by changing i) the substituent in the substrate, ii) the nucleophile and iii)

the solvent. The cations were chosen since previous work3* has shown that these

can be generated by laser flash photolysis and studied in aqueous acetonitrile.

x = OMe, H, Me, CF3 Nu = H20, CI, Br-

Scheme 3

The KlEs were measured by the comparative technique. This invoived

measuring separately the rate constants for the reactions of the undeuterated and

deuterated carbocations. The rate constant ratios were then calculated by dividing

the rate constant for the undeuterated carbomtion by the rate constant for the

deuterated carbocation.

As will be discussed, considerable effort was taken to ensure that the isotope

effects were measured with as small an error as possible.

% RESULTS AND DISCUSSION

B-1 SYNTHESIS

The diarylmethyl cations were generated by laser flash photolysis from

acetate and 4cyanophenoxide precursors as has been previously described (see

Scheme 2)

Generally, diarylmethyl acetates were prepared by refluxing diarylmethanol

with acetic anhydride at 100 OC for a day using pyridine as a catalyst and under

an argon atmosphere. The diarylmethyl acetates were purified by vacuum

distillation. Another route which was used to prepare the diarylmethyl-d acetates

was that diarylmethan-d-01s were converted into diarylmethyl-d chloride using

hydrogen chloride gas at low temperature and dichloromethane as a solvent.

The diarylmethyl-d chlorides were then reacted with sodium acetate at 80 O C for

3 hours using acetic acid as a solvent. The diarylmethyl-d acetates were purified

by vacuum distillation.

Ccyanophenoxide precursors were prepared in two steps. In the first step,

diarylmethanols were refiuxed with thionyl chloride for 3 hours to generate

diarylmethyl chlorides. In the second step the diarylmethyl chlorides were

refluxed with sodium Ccyanophenoxide in THF solution for a few days under an

argon atmosphere. The products then were purified on a silica gel column using

hexane-ethyl acetate mixtures as eluents.

%-2 LASER FLASH PHOTOLYSIS

Laser flash photolysis experiments were camed out with an apparatus at

University of Toronto. A schematic diagram of this apparatus is shown below

REFLECTING - MIRROR 248 nrn

PULSED MONITORING SHUlTER

\ SAMPLE , T I

\ I

, Monitoring ,I

/ -

\ light path 0 \ \

/

MONOCHROMATOR I

Dl-

/ - - - - - /

SAMPLE \

R \ \ #' CUVETTE

/ /

\

/ ,

1 Filling \

/

I port ~ x ~ a n d ' ,

, I laser \

TEKTRO N IX DX 386

COMPUTER

Figure 7 : Schematic diagram of a nanosecond laser flash photolysis (nLFP) apparatus.

Solutions of the precursor were placed in a 4 x 1 x 1 cm cuvette, which was

then placed against a block cell holder thermostated at 25.0 I 0.1 OC by

circulating water. The solutions had previously been placed in the thermostating

bath. The cuvette was placed in the ceIl block for a further two minutes to

ensure temperature equilibrium. The cuvettes were irradiated on the 4 x 1 cm

side by 248 nrn light from a Lumonics Excimer-500 lasei (KrF emission).

Transients produced by this irradiation were rnonitored by absorption

spectroscopy. A pulsed xenon source set at 90' to the laser beam passed

through the cuvette (4 cm path length) to an Oriel monochromato~' set at the

wavelength corresponding to the Am, of the carbocation (Table 15)

Table 15: The hm& for the (4-substituted-4'-methoxydiphenyl)rnethyl cations.

Cation hmax nm

' Lumonics Excimer-500, mode1 EX-5 10 (May 199 1 ), output 6 J, duration 0.002- 1.5 ps, Class IV laser. " Oriel Corporation, Mode1 77250, MFD May 1991, Stratford, Conn. 06497 USA.

An On'el photomutiplier tubei was employed as the detector. The signal from

this detector was passed through a device which arnplified the signal and at the

sarne time applied a voltage equivalent to the signal just before the laser fired.

The purpose of this base Iine compensation was to allow the signal received by

the digitizer to be magnified so as to take full advantage of the digital range. The

digitization was carried out with a Textronix SCD-1000 digitizer with at 2024 bit

vertical resolution and 512 bit horizontal resolution (512 tirne points). The

digitized signal was then saved in the Tektronic DX-386 computer hard disk.

The data were later converted into a Microsoft Excel readable file using a

Tektronix Digfit program. Because of a small base line drift, the digitized signal

for an experiment where the cuvette contained only the solvent was obtained.

This was then subtracted from the digitized signal for the decay of the cation.

The rate constant for cation decay was calculated by fitting the absorbance

versus tirne data to the equation Abs = Abs (initial) x exp(-kt) + Base using the

&afitii computer program.

The results of a typical experirnent are shown in Figure 8. A very small drift in

the base-line absorbance was observed, due to instability of the monitoring

lamp. This was corrected for by substracting the reading obtained with no

substrate from the decay traces with substrate. Excellent fits to the single

exponential equation were obtained, except with bromide ion (see later).

' Mode1 70680, Oriel Corporation, Sîratford, Corn. 06497 USA. " Gra6it is a Data Analysis and Graphics program, Copyright O 1989-1 992 Erithacus Software LTD. Portion copyright Q Microsoft Corp. 1984-1 992.

O Substrate

Solvent

corrected

O 4e-006 8e-006 1.2e-005 1.6e-005 2e-005

Time (s)

Figure 8 : Absorbante (482 nm) versus t h e for the decay of the (4-methyl-4'-methoxyfiphenyl)~thyl cation in 90:lO 2 W : W at 25

O C . The ptecursor was (4-methyl-4 t-methoxydiphenylmethyl 4 '-cyanophenyl ether . The data labeled \\subs trateu and "solvent' are experimental data for solutions with and without substrat@. The data labeled \îcoxrectedu are the difference. The insert shows the fit to a single experimnntal decay.

%-3 SECONDARY ALPHA OEUTERIUM KlES

%-3.1 REACTIONS WlTH WATER

A typical set of data is shown in Table 1 6. In order to O btain good precision,

rate constants were measured on different days, five different days for the set in

Table 16. The first order rate constants did Vary slightly from day to day,

probably due to small fluctuations in the temperature. The secondary alpha

deuterium KlEs however did not Vary as much. When calculated as the average

over several days (always at least 4 days), the errors were always less than two

percent.

Table 17 shows a summary of sadKlEs for the reactions of undeuterated and

deuterated (4-substituted-4'-methoxydiphenyl)methyl cations with water in 20:80

and 90:lO AN:W. The substituent was varied from methyl to hydrogen and to

trifluoromethyl, but within experÏmental error, the sadKlEs were identical.

Similarly when the solvent was changed from 20 percent by volume acetonitrile

in water, a more polar solvent, to 10 percent water in acetonitrile, a less polar

solvent, the sudKlEs were the same within the experimental errors. From these

results one could draw a conclusion that transition states for these reactions

were unaffected by a change either in substituent or solvent. These results will

be discussed in more detail in a later section.

Table 16: Rate constants and secondary alpha deuterium kinetic isotope effects for the reactions behnreen undeuterated and deuterated (4methoxy dipheny1)methyl cations and water in 20:80 AN:W at 2 5 ' ~ .

Entnes 6 -1 kH I O s ko 1 o6 s-' ~ H I ~ D

Average

Average

Average

Average

Average

2.173 2.140 2.149 2.155

2.154+0.014 Average kH/ko 0.886+0.01 la

a The error is the standard deviation of the mean. b llko[(hkn)' + (kH/kol2 x ( ~ k ~ ) ~ ] ' ~ where Akn and A ~ D are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345).

Table 17: Secondary alpha deuteriurn KlEs for the reactions between undeuterated and deuterated diarylmethyl cations and water in 20:80 and 9030 AN:W at 25OC.

Substituent (20:80 AN:W) (90: 10 AN:W) X

kH 1 o6 S-' kH/kD a kH 1 o6 S-' kn/kD a

a The error is the standard deviation of the mean.

%-5.2 REACTIONS WITH BROMIDE AND CHLORIDE IONS

The second-order rate constants for reactions of the cations with bromide

and chloride ions were calculated as the slopes of the linear regression line of

plots. such as shown in Figure 9. These plots were constructed by measuring

six to seven first-order decay rate constants for six to seven different

concentrations of tetra-n-butylammonium bromide or chloride. At each

concentration, the first-order rate constant was the average obtained from three

to five transients which were generated from the same 25 mL solution. The

correlation coefficients of the least squares lines were at least 0.999. As shown

in Tables 18 and 19 the second order rate constants obtained on different days

varied by as much as five percent. To minimize the experimental error,

therefore, values of kH and kD, and their ratio kH/ko were generated each day.

Figure 9: Observed first-order rate constants (s-l) versus concentrations of bromide ion (M) for the reactions of deuterated (D) and undeuterated (H) (4-methoxydiphenyl) methyl cations w i t h bromide ion in 2 0 : 8 0 AN:W at 25 O C .

The kH/kD values showed a much smaller variation. The final kH/kDSs were

averaged from at least four k /kD data. -

Table 20 contains final kHlkols measured in 20:80 and 100:O AN:W. The

standard deviation in the secondary alpha deuterium KlEs was less than two

percent, except for the reactions of the (4-methyl-4'-methoxydipheny1)rnethyl

cations with bromide ion in 20:80 AN:W. When the substituent was varied from

Cmethyl to Chydrogen, the kH/kDts were the same within the experimental error

with a value of 0.96 for the reactions with bromide in 20:80 AN:W and 1.00 for

the reactions with bromide in 100:O AN:W.

Table 18: Rate constants and secondary alpha deuterium KlEs for the reactions between undeuterated and deuterated (4-methoxydiphenyl)rnethyl cations and bromide ion in 20:80 AN:W at 25 OC.

Entries kH (1 o8 M-A s-') ko (1 o8 M-1 S-') ~ H I ~ D

Average 3.777H.1 18a 3.90910.1 2Sa 0.966+0.007~ (3.13 %) (3.20 %) (0.72 %)

a The error is the standard deviation of the mean. l ~ k ~ ( ( ~ k ~ ) ~ + (kH/kD)* x ( A ~ D ) ~ ] ' ~ where AkH and A ~ D are the standard dcviations for the

rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Cam J. Chem., 67, 345, 1989).

lnterestingly there is a difference in k d D in the two solvents, with the value

unity, within experimental error in 100:O AN:W, changing to slightly inverse, kH/kD =

0.96 in 20:80 AN:W. The latter value implies that there is some progress in Ca-Br

bond making in the transition state in the aqueous environment. The value in 100

% acetonitrile, however, implies that there is no bonding in the transition state. A

conclusion could be drawn that kl of Scheme 5 was the rate determining step for

the reaction in 20:80 AN:W, and either or IQ for the reaction in 100 %

acetonitrile. Finally, results in Table 20 also show that for different anionic

nucleophiles there are different KlEs and different transition states for the

reactions in 20:80 AN:W. Changing from bromide to chloride ion, the KIE for

Scheme 5'

Table 19: Rate constants and secondary alpha deuterium KlEs for the reactions between undeuterated and deuterated (4-methoxydipheny1)methyl cations and chloride ion in 20:80 AN:W at 25'C.

Entries kH (lo7 M-y s-I) kD ( 1 o7 M-~ s-' ) ~ H I ~ D

Average 5.421 k0.308~ 6.767k0.31 7a 0.940+0.003~ (5.68 %) (5.50 %) (0.27 %)

a The error is the standard deviation of the mean. 2 in I /~~[(A~H)~ + (kH/kD12 x (AkD) ] where AkH and AkD are the standard deviations for the

rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345).

' This Scheme was modified fiom the Scheme I, and applies to carbocation-nucleophile combination reactions.

Table 20: Rate constants and secondary alpha deuterium KIEs for the reactions between undeuterated and deuterated (4-substituted-4'-methoxydiphenyl)methyl cations and brornide and chloride ions in 20:80 and 100:O AN:W at 25 OC.

H Br' 3.78t0.12 0.96610.007 2.7310.03 a 1.007k0.007~

H CI' 0.54k0.03 0.940+0.003 1.6810.16~*~ 0.999k0.021

'The error is the standard deviation of the mean of two KIEs. The error is the standard deviation of the mean of three KIEs. Measured in 9 8 2 AN:W.

the reaction varies from 0.96 to 0.94. These differences will be discussed in a

later section.

The KlEs for the reactions of undeuterated and deuterated (4'methoxy-

diphenyl)methyl cations with the three different nucleophiles water, chloride and

brornide are different in 20:80 AN:W. As the nucleophile is changed from water

to chloride ion and to bromide ion, the KIE changes from 0.886 to 0.940 and to

0.966. These results suggest that steric crowding decreases at Ca in the

transition state as the nucleophile is changed from water, to chloride ion and to

bromide ion. There are two possible reasons for this. The difference in steric

crowding can be caused by a different size of the attacking atom or it can be

caused by different Ca-Nu bond lengths in the transition state. The

polarizability of the attacking nucleophile increases frorn oxygen to chlonne to

bromine, and so does the nucleophilicity as measured by the absolute rates.

However it is still difficult to know whether the structure of the transition state is

changing. Knowledge of the equilibrium kinetic isotope effect would provide

important information in this respect. These deteminations will be discussed in

the next section.

8-4 SECONDARY ALPHA DEUTERIUM EQUILIBRIUM ISOTOPE EFFECTS

%-4.1 WATER REACTION, DIARYLMETHANOLS IN SULFURIC AClD

The EIEs for the reactions of (4-substituted-49~1ethoxydiphenyl)rnethyl cations

with water refer to the pseudo acid:base equilibrium of equation 32. This

equilibrium is established in moderately concentrated sulfuric acid solutions.33

The symbol K has conventionally been employed for this equilibrium. This

equilibrium constant refers to a wholly aqueous standard state. Since

. measurements are made with a large amount of sulfuric acid present, it is

necessary to write the expression in terms of activities, Le.,

where YR+ and YROH are the activity coefficients for the cation and alcohol. The

EIE is a ratio, that is

There should be little effect of isotopes on the activity coefficients y ~ + and y ~ o ~ .

and thus this expression simplifies to

Thus, measurement of the ratio [R+]/[ROH] for the undeuterated and deuterated

systems in the same acid solution fumishes directly the desired EIE. These

ratios were obtained by preparing solutions of the same total concentration of

alcohol in various sulfuric acid solutions.

The UV absorbanœs at the A, of the cation were monitored with a

cornputerized DX-1200 Cary UV spectrophotometer. These results in a "titration

curve" such as that shown in Figure 10, by plotting the optical density versus the

concentration of sulfuric acid.

Figure 10 : W absorption of diarylmethyl cations versus aqueous sulfuric acid concentrations. The curve labeled OMe, Me and H are for the ( 4 , 4 ' -aimnthoxymethoxydiphenyl) methyl cation, the ( 4 - methyl-4 '-methoxydiphenyl) methyl cation and the (4-methoxy- dipheny1)methyl cation, respectively.

For a given system, the ratio of the cation to alcohol is obtained from such an

experiment as follows,

where kad, is the optical density at high concentration where there is only cation

in the solution, Adil is the optical density at low acid concentration where there is

only alcohol present and A is the optical density at an intermediate

concentration. Since the alcohol does not absorb in the visible region, hl was

equal to zero. To obtain the EIE, the absorbances at several intermediate acid

concentrations were measured for both the undeuterated and deuterated

alcohol. Equation 37 was employed to calculate the EIE.

Table 21 contains data for a typical measurement. The data were obtained

within one day and in that day three measurements were taken for each

substrate and for each sulfuric acid concentration. Table 22 shows the data

obtained for four sulfuric acid concentrations in the middle of the curve in Figure

10. The standard deviation in KH/K~ obtained in this way was 2.6 percent. This

error was reduced to less than one percent by caiculating the average EIE from

the four ElEs for the four different sulfuric concentrations for each day (Table 23)

and the final average KH/Ko from at least four average ElEs for at least four

days. The final ElEs which were measured with the later method are given in

Table 24'.

Table 21: UV absorbance at Am= = 464 nm and secondary alpha deuterium ElEs for (4-methoxydiphenyl)methanols at 25 OC. Final concentrations of undeuterated and deuterated substrates are 7.403E-6 M and 7.285E-6 M, respectively.

Isotope OD for 18.38 M sulfuric acid OD for 10.36 M sulfiiric acid KH/Ko (Aacid) (A)

Run Average a Run Average a

a The error is the standard deviation of the mean.

' Tables 21 and 22 show the results for the nrst method used in these experiments. This method gave a large error (2.6 %) in the ElE, The second method gave a mialler error. So the second method was used to obtain al1 results (in Tables 23 and 24).

Table 22: Secondary alpha deuterium ElEs for (4-methoxydiphenyl)methanol.

sulfuric acid (M)

WdKo), Average (&/KD)= a

10.36 1.173

10.07 1.203

9.82 1.245

9.69 1.183

a The error is the standard deviation of the rnean.

Table 23: UV absorbance at A,, = 464 nm and secondary alpha deuterium ElEs for (4-methoxydiphenyl)methanol at 25 OC. The concentrations of undeuterated and deuterated substrates are 6.8E-6 M and 7.3E-6 M, respectively.

sulfuric O D of undeuterated acid (M) su bstrate

O D of deuterated substrate

average (&/KD)~ 1.206 + 0.01 3'

a Average for three runs and the error is the standard deviation of the mean. b Average for four runs and the error is the standard deviation of the rnean.

Table 24: Average secondary alpha deuterium ElEs for the ionization of (4-substituted-4'-methoxydiphenyl)methanols at 25 OC.

kubstituted Average (KdKo), a

0CH3 1.203 t 0.004

CH3 1.220 I 0.003

H 1.203 t 0.003

a The error is the standard deviation of the rnean

Although the KH/Ko of 1.22 obtained for the 4-methyl substituted compound was

different from the of 1.20 obtained for the other two compounds these

ElEs are considered to be the sarne.

%-4.2 FOR REACTIONS WITH BROMIDE ION

The EIE for the reaction of the (4-methyl-4'-methoxydiphenyl)methyl cation

with bromide ion in 20:80 AN:W could be measured directly by nanosecond

Laser Flash Photolysis (nLFP). The approach takes advantage of the fact that

this cation-anion combination in this solvent is reversible. The kinetic system

that applies in this case is shown in Scheme 4.

Scherne 4

Bromide ion combines with the cation with a pseudo first-order rate constant

equal to ke,[Brl (since bromide is in excess). On the same time scale, the

diarylmethyl bromide is undergoing ionization back to the cation with a first-order

rate constant of kion. The alternative fate of the cation is addition of water, which

occurs with a first-order rate constant kW.

Evidence that this behavior is occurring is the appearance of decay traces

that are no longer fit by a single exponential function, but which are better fit by a

double exponential equation?

OD - - Aekat + Bekbt + c Pa]

where ka and kb are the two exponential coefficients (kpk,), A and B are the

corresponding pre-exponentials and C iç the optical density after complete

decay. An example of the double exponential decay, showing the excellent fit to

equation 38, is shown in Figure 11. Values of C were invariably within

experimental error equal to zero.

-

- e Solvent

- IJ Corrected -

-

I -I

i i i l r ~ i l i ~ i l i i i l ~ ~ ~ I I

O 4e-006 &-O06 1.2e-005 1.6e-005 2e-005

Time (s)

Figure 11: nLFP traces for the reaction between (4-methyl- 4'-meUloxydipheny1)memyl cation and bromide ion i n 20:90 AN:W at 25 OC. The trace labeled Men is the observed decay w i t h substrate. The trace labeled Solvent is the baseline obtained w i th solvent and tetra-n-butylrrimnonium bromide solution. The trace labeled Corxected i s the difference. The insert shows the f i t to double exponential decay.

The kinetic system of Scheme 4 corresponds to differential equations as

foIlows:

These can be solved exactly to give the following equationsi for the concentration

of the cation as a function of time

where

In terms of the equation 38 employed to fit the data for optical density versus

' I am gratefd to Professor S. Fraser for providing this solution. A detailed derivation o f this equation is in Appendix 1

time, the larger exponential coefiîcient kb is equal to 12, and the smaller ka is hl.

To obtain the individual rate constants kim and ksr, equations 43 and 44 are

added together. This gives

Thus, a plot of the sum of the two exponential coefficients versus the

concentration of bromide ion is predicted to be linear with a dope equal to ksr

and an intercept equal to kion plus kW.

Experiments were performed in which the undeuterated and deuterated

(4-methyl-4'-methoxydiphenyl)methyl cations were generated by nLFP and

reacted in the presence of five to six different concentrations of bromide. Three

to five different traces were obtained at each brornide concentration. Each trace

was fit to a double exponential, and the values of the two exponential coefficients

averaged. A typical data set is shown in Table 25.

Examples of plots of (ka + kb) versus the concentration of bromide ion are

given in Figure 12. As shown in this Figure, excellent linear correlations were

obtained with correlation coefficients of at least 0.995. The rate constant kBr for

the cation-bromide combination is obtained directly as the slope of the line. The

intercept provides (kim + kW). The rate constant kW refers to trapping of the cation

by solvent in the absence of any added bromide ion. This was measured on the

same day, and combined with the intercept to provide kion. The ratio kioJksr then

provides the equilibrium constant for the equiiibriurn wntten in the direction

Ar2CHBr - A ~ ~ C H ' + Br-.

Such experiments were perfomed seven times on seven different days,

generating the data given in Table 26. The average value of KdKD is 1.215.

This has an error of 10 % and indtcates that this value is not reliable. As will be

discussed, the magnitude of the value of KHIKD is very different from the

maximum value for kH/kD (1.130) for ionization suggested by other ~ o r k e r s ~ ~ for

studies of the solvolysis reactions of secondary alkyl bromides.

Table 25: Exponential coefficients for the reaction of bromide ion with the (4-methyl-4'-methoxydiphenyl)methyl cation in 20:80 AN:W at 25 OC.

6 -1 [Br] 1 0-3 M (lq,=k2) a (1 0 s ) 5 -1 (ka=hl) a (10 S ) (11 + ~ 2 ) ~ (10 6 s -1 )

a The error is the standard deviation of the mean.

The problem with this analysis likely lies in the detemination of kim. This is

obtained from the intercept of plots such as those shown in Figure 12, by

subtracting kW. Since kW is approximately two fold larger than kio,, there is a

substantial error in kion-

Figure 12: Sum of the exponantial coefficients (o-l) versus concentrations of bromide ion (M) 50r the reactions of deutexated (D) and undeuterated (H) ( 4-methyl- 4 f-methoxydîphenyl) m e t h y l cations with bromide ion i n 2 0 : 8 0 A N : W st 25 OC.

Table 26: Rate constants, equilibrium constants and KIEs and ElEs for the reactions between undeuterated and deuterated (4-methyl-4'-methoxydipheny1)- methyl cations and bromide ion in 20:80 AN:W at 25 OC.

Run kion 1 K=kiodk& (k~/k~)ion ( k ~ / k ~ ) ~ r KH/KD s-'

ksr 1 o8 M-l s-l 1 0"

Average al1 points

" The error is the standard deviation of the mean.

%-4.3 FOR REACTIONS WlTH CHLORIDE ION

The secondary alpha deuterium EIE for the reactions of the undeuterated and

deuterated (4-rnethoxydiphenyl)rnethyl cations with chloride ion. equation 46,

was measured by a comparative technique in 98:2 AN:W (v:v) at 25 OC.

This involved the measurement of the KlEs (kH/ko) for the forward and

reverse reactions. Then, the EIE was calculated from these KlEs by dividing

( k d b ) i o n by (~H/~D)cI -

The solvolysis reactions of undeuterated and deuterated (4-methoxy-

dipheny1)methyl chlorides in 98:2 AN:W containing 0.001 M tetramethyl-

ammonium hydroxide were chosen to determine the (kHIkD)ion, equation 47.

The addition of hydroxide was necessary, in order to prevent the back reaction of

the cation with chloride ion. The disappearance of the undeuterated and

deuterated (4'-methoxydiphenyl)methyl chlorides versus time was followed with

the computerized DX-1200 Cary UV spectrophotorneter at a wavelength of 249

nm. The absorbance-time traces were digitized and later analyzed with the

computer program Grafit to give the first-order rate constants. Four runs were

performed with each substrate within a day and the (kHko)ion was calculated from

the averages of the four values of (kbJH and four (ko&, Table 27.

Table 27: Rate constants for solvolysis monitored with UV absorption at h = 249 nm and the secondary alpha deuterium KIE for (4-methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.001 M tetramethyiammonium hydroxide at 25 OC.

average 3.492 + 0.031 2.996 + 0.038

a The error is the standard deviation of the rnean bi~kD[(~kH)2 + (kdkD12 x ( ~ k ~ ) ~ ] ' ~ where AkH and AkD are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively. (Westaway and Lai, Can. J. Chem.1989, 67, 345).

To minimize the experimental error, this procedure was repeated seven

times (Table 28). The average KIE has a value of 1.154 and an error of less

than 1 %. In order for this kHkD to refer to the ionization process of equation 46,

the solvolysis must be proceeding via a carbocation mechanism (SNI) with either

kl or k2 or k3 of Scheme 1 the rate determining step. In fact, the rate constant for

the solvolysis reaction was not affected by either varying the concentration of

hydroxide ion or changing to a better nucleophile (azide) (Table 29). This

Table 28: The secondary alpha deuterium KIEs and average KIE for solvolysis reaction of the undeuterated and deuterated (4-methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.001 M tetrarnethylammonium hydroxide at 25 O C .

Entry k d k ~ Average kH/ko

2 112 a l ~ k ~ [ ( ~ k ~ ) ~ + ( k ~ / k ~ ) ~ x (Ako) ] where AkH and AkD are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345). b The .error is the standard deviation of the mean.

behavior is characteristic of an SNI solvolysis mechanism. Tables 30 and 31

describe experiments with hydroxide and azide ions as the trapping nucleophiles.

The KIE of 1-1 54 is also consistent with a carbocation mechanism.

Table 29: Rate constants for solvolysis monitored with UV absorption at A = 249 nm and secondary alpha deuterium KIE for (4rnethoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and sodium azide and different concentrations of tetramethylammonium hydroxide at 25 OC.

a The error is the standard deviation of the mean of four to five runs. b

I ~ D [ ( A ~ H ) ' + ( k ~ l k ~ ) ~ x ( ~ k ~ ) ~ ] ' ~ where AkH and AkD are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345).

Table 30: Rate constants for solvolysis monitored with UV absorption ai A = 249 nm and secondary alpha deuterium KIE for (4-methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.0013 M tetramethylammonium hydroxide at 25 oc.

average 3.524 _t 0.028 a 3.058 + 0.051 a

(0.8%) (1.6%)

a The error is the standard deviation of the rnean. b 1 1 k ~ [ ( ~ k ~ ) ~ + (knkD)2 x ( ~ k ~ ) * ] ' ~ where AkH and AkD are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345).

The cation-nucleophile combination reactions of undeuterated and

deuterated (4-methoxydiphenyl)methyl cations with chloride ion in 98:2 AN:W

were chosen to determine the (kH/k&, Scheme 6.

The cations were generated in situ using the nLFP technique and their

disappearance was followed as descrîbed above. The cations reacted with

water and chloride ion in this solvent system, and the first order observed rate

constants of the reactions were calculated from the transients. Seven first order

Table 31: Rate constants for solvoiysis monitored with UV absorption at h = 249 nm and secondary alpha deuterium KI€ for (4-methoxydiphenyl)methyl chlorides in 2 % aqueous acetonitrile and 0.001 M sodium azide at 25 OC.

average 3.602 + 0.01Oa 3.123 + 0.027a

a The error is the standard deviation of the mean bl/kD[(~kH)2 + (kdkD)? x ( ~ k ~ ) ' ] ' ~ where A ~ H and AkD are the standard deviations for the rate constants for the undeuterated and deuterated substrates, respectively (Westaway and Lai, Can. J. Chem. 1989, 67, 345).

Scheme 6

Figure 13: F i r s t order observed rate constants (s-l) versus concentrations of chlozide ion (M) for the reactions of deuterated (D) and undeterated (Hl ( 4-mathoxydiphenyl) methyl cations with chloride ion i n 98:2 AN:W at 25 OC.

observed rate constants for seven different tetra-n-butylammonium chlonde

concentrations were measured for the undeuterated and deuterated cations on

the same day. The second order rate constants for cation-chloride combination

reactions were calculated from the dopes of the lines which were constructed by

plotting the first order observed rate constants versus chloride ion

concentrations, Figure 13. The correlation coefficient in al1 cases was at least

0.997. The results are given in Table 32.

Table 32: Second order rate constants and secondary alpha deuterium KIE for the reactions between (4-methoxydiphenyl)rnethyl cations and chloride ion in 98:2 AN:W at 25 OC.

average 1 -679 + 0.1 56a 1.682 + 0.183~ 0.999 + 0.021 a

(9.3%) (1 0.9%)

a The error is the standard deviation of the mean

The average KIE ((kH/ko)o) in Table 32 for reactions between undeuterated

and deuterated substrates (4-rnethoxydiphenyl)methyl cations and chloride ion in

98:2 AN:W was equal to unity. Therefore the EIE defined above was equal to

( k n n < ~ ) ~ ~ , Le., 1.154. This result agrees with the conclusion of previous

researchers for the studies of KlEs for some alkyl chlorides s o l ~ o l ~ s e s ~ ~ .

lt can be seen that the ElEs were different for different nucleophiles. The

EIE was 1.203 for water, 1.1 54 for chloride and 1.215 for bromide ion. In other

words each nucleophile (or leaving group) has a specific value.

B-5 MODEL OF THE s~~ (c ' ) TRANSITION STATES

The KlEs and ElEs can change because of either a difierent size of the

attacking atoms in the nucleophiles or because of different distances between

Cgs and nucleophiles in the transition state. To eliminate the differences in KlEs

caused by the former, a cornparison between KlEs and related ElEs can be

used. This method can help to monitor the change in transition state structures

when the nucleophiles are varied.

The percentage of bond formationi in a transition state of a reaction can be

calculated as follows. A ratio is calculated by dividing the logarithm of the KIE by

either the logarithm of the EIE for the reaction in the same direction (labeled f) or

the logarithm of (VEIE) where the EIE refers to the reaction in the reverse

direction (labeled r). This ratio is then multiplied by one hundred, equation 48".

In term of energy, this calculates a ratio of differences in free energy as shown in

' Treatment in terrns of bond order is found in Schowen R L.J: Am. Chem. Soc. 1980, 102,7530-7534. " Details of how to derive this equation are in Appendix 2 and the error calculation in Appendix 3.

the last terni of equation 48. The logarithm of the KIE is the difference in

activation energy between the reactions of undeuterated (H) carbocation and

deuterated (D) carbocation. The logarithm of the EIE is the difference in the

overall free energy for complete reaction. The former thus represents partial

bond formation in the transition state, and the latter complete bond formation.

Wth the assumption that the isotope effect on the free energy parallels bond

order. equation 48 provides a measure of the percent bond making in the

transition state.

%-5.1 REACTIONS WlTH WATER

The secondary alpha deuterium KIE for the reactions of undeuterated and

deuterated (4methoxydiphenyl)methyl cations is 0.886. The EIE for the reaction

in the reverse direction is 1.203, so that the EIE in the forward direction is 0.831.

From equation 48, this means that there is (65 f 7") percent Ca-OH2 bond

rnaking in the transition state. The calculation for the (4-methyl-4'-methoxy-

-

' Details of how to denve this equation are in Appendix 2 and the error calculatiori in Appendix 3. " Details of how to calculate this error are in Appendix 3.

dipheny1)methyl cation gives a percentage of (54 + 9). These results also agree

with those obtained by the Bunton group25 for the diferrocenylmethyl and

(ferrocenyl-4rnethoxyphenyl)methyl cations. As summarized in Table 33, within

the experimental error, Ca-OH2 bond making in the transition state for the four

carbocation reactions is the same, in the range from 50 to 65 percent. This is an

interesting finding because there is a 1 o8 fold change in reactivity throughout this

series, and yet the transition state is not altered. It is also interesting that the

same conclusion, 50 - 65% bond making independent of reactivity, has been

reached using a rate - equilibrium correlation to determine the position of the

transition state for the reactions with water. 29:35.' In this relationship the logarithm

of rate constants for the reactions between substituted carbocations and water

are plotted versus the log KR+ for the equilibria involving the same cations. The

dope of this relationship (Alog kW 1 Alog KR+) rneasures the degree of bond

formation in the transition state. This can be explained as follows, Scheme 6

Alog KR+ measures difference between +1 and O L

Alog kw measures difference between +1 and 6+

measures 1 - S+ Alog KR+

Scheme 6

-- - -

' Reference 29 and other references cited in this reference.

Table 33: Rate constants, KIEs, ElEs and percent of bond making of the Ca-OH2 bond in the transition state for the reactions of undeuterated and deuterated (diferrocenyl)rnethyl, (ferrocenyl-4-methoxyphenyl)rnethyl, (4methyl- 4'-methoxydiphenyi)methyl and (4-methoxydiphenyl)methyl cations with water at 25 OC.

cationa kc+ (s-') ~ H & D KH/KD % bond makingb

diferro 2.7~1 O" 0.915 I 0.024 1.180 k 0.038 53 I 22

ferro 4 . 3 ~ 1 O' 0.874 + 0.01 6 1.316 + 0.084 49 t 21

a Diferro, ferro. Mediaryl and H-diaryl are short forms of (diferrocenyl), (ferrocenyl-4- rnethoxyphenyl) (4-methyt-4'-methoxydiphenyl) and (4'-rnethoxydipheny1)methyl cations.

Details of how to calculate % bond making and the error are in Appendix 3.

In simple terms the overall reaction represents a change from the cation

where there is a full positive charge (il) on the central carbon to the carbinol

where there is no charge (O). Thus Alog KR+ for a change in substituent X to X'

measures how these substituents interact with systems where there is a change

in charge of (-1). The rate constant refers to change from the cation (+1) to the

transition state where the charge on the central carbon has decreased to 6+.

Thus Alog kW measures the substituent effect where the charge has changed

(6' -1). Therefore the siope = (Alog kW I Alog k ~ + ) measures (1 - 63. If the slope

has a value of zero there is no bond formation in the transition state of the

reaction. If the dope has a value between zero to one there is some degree of

bond formation in the transition state, and if the slope is equal to one the bond is

completely formed in the transition state. As shown in Figure 14, ~ c ~ l e l l a n d ~ ~

constructed a linear free energy correlation of log kW for hydration of diarylmethyl

cations covering a ver- wide range of reactivity. There are two features to this

plot. Fiistly, it is linear over the entire range. This suggests that the position of

the transition state is independent of the reactivity of the carbocation. Secondly,

Figure 14: Logarithm of first order observed rate constants of reactions betwaen diarylmethyl cations and watet versus their log KR+. The slope of the straight line is 0 . 5 6 .

the slope is 0.56 + 0.02'. 36. In other word, this suggests about 56% bond making

in the transition state. Both conclusion are in excellent agreement with the ones

reached in this study. This is an important cornparison since equation 48 and

the linear free energy correlation provide completely different measures of bond

formation, with completely differmt assumptions in each. That the two do agree

provides confidence that the isotope effects are providing the degree of bond

making.

%-5.2 REACTIONS WlTH BROMIDE AND CHLORIDE IONS

RI = , Rp = +OM~, N u = Br, CI-

The secondary alpha deuterium KlEs of 0.966 I 0.007 and 0.940 f 0.003,

Tables 18 and 19, for the reaction of the undeuterated and deuterated

(4methoxydiphenyl)methyl cations with bromide and chloride ions, respectively,

in 20:80 AN:W at 25 O C indicates that there is some Ca-NU bond making in the

transition state. The ElEs are 1.215 I 0.123 (for RBr R' + Br-) and 1.153 I

The error is the standard deviation which calculated fiom the equation o = b((l4 r 1 )[(I-?)/(M-2)]'"). Where cr, b, r and M are the dope error, slope, correlation coefficient and number of data points, respectively. (Ref. 36)

0.009 (for RCI R' + CI-) (Tables 26 and 28). Therefore using equation 48

the Ca-Nu bonds in the transition state are formed to the extent of 18 + 10 %

and 43 + 3 %, respectively, for the bromide and chloride ion reactions. These

results are different from those found for the anionic nucleophile reactions by

Bunton and his CO-workers. Table 10. The latter group observed KlEs equal to

unity, indicating that there is no Ca---NU bond making in the transition state for

these reactions with anions.

According to the results summarized in Table 34, the KlEs and ElEs indicate

there are three different transition states for the reactions of the three different

nucleophiles. For a change of nucleophile from H20 to CI- and to BF, the

percentage of Ca-Nu bond making changed from 65 to 43 and to 18,

respectively. This shows that the transition state becomes looser when a better

nucleophile is used. Rate constants for water, chloride and bromide ion

reactions are 2.6~ 1 o6 se', 54x1 o7 and 3.8~10~ M" s-', respectively. These

results are in accord with the Hammond postulate prediction which predicts a

earlier (more reactant-like) transition state for the reaction with a better

nucleophile.

Table 34: Rate constants, secondary alpha deuteriurn KIEs, ElEs and percent Ca-NU bond making in the transition state for the reactions of undeuterated and deuterated (4-rnethoxydiphenyl)rnethyl cations with water, chlofide and bromide ions in 20:80 AN:W at 25 OC.

Nucleophile kN, (M" s-') k ~ / k o KHI& % bond making in transition

state

a Dimension in s".

B-6 STUDY OF SOLVENT AND SUBSTITUENT EFFECTS ON THE RATE OF

REACTIONS OF DIARYLMETHYL CATIONS WlTH VARIOUS

NUCLEOPHILES

The results in the previous section show that the reactions of bromide and

chloride ions with diarylmethyl cations are different, both in rate and KIE, whether

the reaction is carried out in 100 % AN or 20 % AN : 80 % water. In this section,

the effect of solvent on the rate constant is considered for the entire range of

acetonitrile composition frorn O % to 100 %. The oxyanion, acetate ion, is

included for comparison.

Absolute second order rate constants for the reactions studied in this section

were measured the same way as in the KlE study, and were obtained from the

slopes of the linear regression plots which were constructed from five to seven

averages of pseudo first order rate constants versus five to seven different

concentrations of nucleophiles.

B-6.1 SOLVENT EFFECTS

B-6.i.i ANlONlC NUCLEOPHILES

Tables 35-37 contain second order rate constants for the reactions between

three (4-substituted-4'-methoxydiphenyl)methyl cations and brornide, chloride

and acetate ions in various aqueous acetonitrile solvents. Figures 15-1 7 were

constructed frorn these data. The change of solvent has a qualitatively similar

effect for the different nucleophiles. The logarithrns of the second order rate

constants increase in an approximately linear fashion from zero to sixty percent

AN, and then there is a relatively more rapid increase from eighty to one hundred

percent acetonitrile.

In 100 % AN the three nucleophiles react with virtually the same rate

constant within experimental error. There is also little dependence of the rate

constants on the substituents in the cations. These rate constants are also very

close to those found by Bart1 and CO-workers3' for the reactions of anionic

nucleophiles with the parent diphenylmethyl cation in 100 % AN. This is

consistent with the conclusion of the previous chapter that the reactions are

diffusion mntrolled.

Table: 35 Rate constants for the reactions of (4-rnethyl-4J-methoxydiphenyl) methyl cation with various nucleophiles in aqueous acetonitrile at 2S°C.

Table: 36 Rate constants for the reactions of (4-methoxydiphenyl)rnethyl cation with various nucleophiles in aqueous acetonitrile at 25 OC.

Table: 37 Rate constants for the reactions of (4-trifiuoromethyl-4'-methoxy- dipheny1)methyl cation with vanous nucleophiles in aqueous acetonitrile at 25 OC.

O 20 40 60 80 100

% Acetonitrile

Figure 15: Logarithm of the rate constant versus % acetonitrile for the reactions between (4-methyl-4 '-methoxydiphenyl) methyl cation and bzromide, chloride and acetate ions a t 25 O C .

O 20 40 60 80 100

% Acetonitrile

Figure 16: Logarithm of the rate constant versus % acetonitri le for the reactions between (4-methoxydipheny1)methyl cation and bromide, chloride and acetate ions at 25 OC.

% Acetonitrile

Figure 17 : Logarithm of the rate constant versus % acetonitrile for the reactions between (4-tr i f luoromethyl-4 '-methoxydiphenyl) - methyl cation and bromida, chloride and acetate ions at 25 OC.

The addition of a small amount of water has a large rate retarding effect.

This can be explained by solvation or hydration of the anions by water molecules

decreasing the r e a c t i ~ i t ~ ~ ~ . 39r 40. What is interesting is that even in 97 % AN,

there is a difference in the rate constants for the three anions reacting with the

same cation. There is also a substituent effect for the reaction with a given

anion. This means that the hydrating effect causes an almost immediate change

from diffusion controlled to a reaction which is at least partly activation controlled.

The rate retarding effect of hydration continues to increase with increasing

water concentration. Even in water-rich solutions the greater the water

concentration the slower the reaction.

Considering the three ions the hydration effect follows the order that the

oxyanion is more retarded than chloride which is more retarded than bromide.

This is the expected hydration order3! The highly electronegative but poorly

polarizable oxyanion is the most strongly hydrated, and the less electronegative

and highly polarizable bromide ion is the least hydrated.

The effect of solvent on the rates of diarylmethyl cations and anionic

nucleophile reactions can also be compared to the reactions between these

same cations and primary amines4', Figure 18. As with the anions, the rate

constants decrease with increasing water content. There is a smaller solvent

effect in the water-rich region, and larger effect in the acetonitrile-rich region.

There is also the interesting effect that the more basic the amine, the greater the

effect of water. This is explained by a mode1 where there is a hydrogen-bond

between a hydrogen atom of water and the electron lone pair on nitrogen atom

of the amine.40 This ties up the amine lone pair of electrons which are needed to

react with the cation. The stronger the amine, the stronger this hydrogen-bond

and thus the greater the hydration effect.

O 20 40 60 80 100

% Acetonitrile

Figure 18: Logarithm of the rate constant versus % acetonitrile for the reactions between (3,4r-aimethoxyphenyl)methyl cation and n-propyl, 2-cyanoethyl, 2,2,2-trifluoroethyl amines at 25 O C .

8-6.1.2 ON SUBSTITUENTS

Figures 19-21 were also constnicted from the data in Tables 35-37, and

indicate the effect of solvent on the rates of reactions in which the substituent on

the Cposition of one phenyl group of the diarylmethyl cation was varied. This

shows the manner in which the rate constants "spread outn as water is added.

I I I I I 1 1 I I

-

-

-

-

- CF, c A H - - Me

1

i I I 1 I 1 I I I I

O 20 40 60 80 100

% Acetonitrile

Figure 19: L o g a r i t h m of the rate constant versus % acetonitri le for the reactions between (4-substituted-4 ' -methoxydiphenyl) - methyl cation and acetate ion at 25 OC.

O 20 40 60 80 1 O0

% Acetonitrile

Figure 2 0 : Logarithm of the rate constant versus % acetonitrile for the reactions between ( 4-substi tuted-4 '-methoxydiphenyl) - methyl cation and chlotide ion a t 25 O C .

2Q - - - - 4 0 - - - - 60 80 1 0 0

% Acetonitrile

Figure 21 : Logarithm of the rate constant versus % acetonitrile for the reactions between ( 4-substituted-4 ' -methoxydiphenyl) - methyl cation and bromide ion at 25 O C .

B-û.2 HAMMETT PLOTS

Rate constants for a series of diarylmethyl cations reacting in the presence of

bromide ion were determined in two solvents, 50:50 and 90:10 AN:W. Figures

22 and 23 show that the observed rate constants fit perfectly to a straight line.

The results obtained from these graphs are presented in Tables 38 and 39,

which contain second order rate constants and first order rate constants for

reactions of (4-sub~tituted-4~-methoxydip heny1)methyl cations with bromide ion

and with water, respectively, in 50:50 and 90:10 AN:W. The logarithms of these

rate constants were plotted against the sigma-plus (d) constants to give

Hammett plots as shown in Figure 24.

For the reactions between (4-substit~ted-4~-rnethoxydiphenyl)methyl cations

and brornide ion in 50:50 AN:W and 90:10 AN:W, the Hammett plots show that

the substituent effects are greater for the reactions in 50:50 AN:W than for the

reactions in 9O:lO AN:W. The slope of the Hammett plot for 50:50 AN:W is 0.68,

compared with 0.30 for reactions in 90:lQ AN:W. These results show that there

is a difference in transition state structure for the reactions in these two different

soivent systems. The transition state for the reactions in the more water rich

mixture is later than that for the reactions in the acetonitrile-rich solvent. This

conclusion agrees with that in the KIE section.

For the reactions between (4-substituted-4'-methoxydipheny1)rnethyl cations

and water, the Hammett plots show there is the same substituent effect for 50:50

AN:W and 9030 AN:W. The slopes of the Hammett plots are 0.89 in both

solvents. This shows that the transition state structures are the same for the

reactions in these two different solvent systems. This supports the KIE results.

Figure 22 : Pseudo f i r s t order rata constants (s-') varsus btomide concentrations (M) for the reactions between (3-substituted and 4-subs tituted-4 /-methoxydiphenyl) methyl cations and bromide ion and water i n 5 0 : 5 0 AN:W at 25 OC.

Figure 23: Pseudo first order rate constants versus bromide concentrations for the reactions between (3-substituted and 4- substituted-4 '-methoxydiphenyl) methyl cations and bromide ion and w a t e r in 90:lO AN:W at 25 O C .

Table 38: Second order rate constants for the reactions between (3-substituted and 4-substituted-4'-methoxydiphenyl)methyl cations and bromide ion in 50:50 - .

and 90: 10 AN:W at 25 O C .

Substituent X 2nd order rate ( correlation (1 o8 M%') ; coefficient

1

90:10 AN:W I I 1 2nd order rate , correlation

(log M-'s") coefficient I

Table 39: Sigma plus values and first order observed rate constants for the reactions between (3-substituted and esubstituted-4'-methoxydipheny1)methyl cations and water in 50:50 and 903 0 AN:W at 25 OC.

Substituent X of Rate ( I O s ) Rate (1 o6 se') 6 -1

50:50 AN:W 90:lO AN:W

3 A h g k (90:10) Br

M + Log %,(5050) Q

O Log k (5050) W

Figure 24 : H a m m a t t p l o t for the reactions between (4-substituted- 4'-methoxydiphenyl) mathyl cations and bromide ion and w a t e r in 5 0 : 5 0 and 90:10 AN:W at 25 OC. The values of d (slopes) ara 0.30, 0.68, 0.895 and 0.887, respectively, for the bromide ion reactions in 90 : 10 (labeled Log kW (90 : 10) ) , 50 : 50 (labeled Log kb (50:50)) AN:W and the water reactions i n 5 0 : 5 0 (labeled Log kW (50:50)), 90:10 ( labeled Log kW (90:lO)) AN:W.

C CONCLUSION

The results of the secondary alpha deuterium KIE and EIE studies for the

reactions of (4-substituted-4'-methoxydipheny1)methyl cations with water.

chloride ion and bromide ion in various water-acetonitrile mixtures at 25 OC were

studied.

The identical secondary alpha deutenum KlEs and ElEs for water reactions

in 20:80 and 90:10 AN:W, and for changes in substituent. show that the

transition state is insensitive to a change in either the substituent in the

carbocation or solvent. The KIE of 0.90 (R' + H20 - ROH + H+) and

secondary alpha deuterium EIE of 1.20 (ROH + H' === R' + H20) indicates the

Ca---Nu bond was 60 % advanced in the transition state of these reactions.

These results agree with those found by Bunton and by McClelland in previous

studies of the reactivity of carbocations.

The transition state is constant for a change of substituent in carbocation for

bromide ion reactions in 20:80 AN:W, since the KlEs were 0.97 when the

substituent changed from rnethyl to hydrogen. A cornparison between

secondary alpha deuterium KIE of 0.97 (R' + Br- - RBr) and secondary

alpha deuteriurn EIE of 1.215 (RBr R' + Br-) indicates that, the &--Br bond

has progressed to only 18 percent in the transition state for these reactions.

The secondary alpha deuteriurn KIE of 0.94 (R' + CI- - RCI) and

secondary alpha deuteriurn EIE of 1.1 5 (RCI - R+ + CI-) for the reaction

between (4-rnethoxydiphenyl)rnethyl cation and chloride ion in 20:80 AN:W

indicates that there is 40 percent of Ca-CI bond forming in the transition state.

In the (4methoxydiphenyl)methyi cation reaction, the transition state

becomes looser, Le., the CCNu bond rnaking is 60, 40 and 18 percent, when

the nucleophile is changed from water to chloride and to bromide ion. A simple

explanation is that bromide ion, the best nucleophile, does not need to be as

close to the carbocation to react. Thus there is less steric crowding at C, in the

* transition state and the magnitude of Z(vHi - VHi ) term is small.

Finally, the secondary alpha deutenurn KIE changed frorn 0.94-0.97 to 1.00

when the solvent changed from 20:80 to 100:O AN:W for both the bromide and

chloride ion reactions. This indicates a change in rate determining step. lt can

-1 -1 be noted that the rate constants in 100% acetonitrile are al1 around 2x1 0" M s .

This is close to or at the diffusion control limit for cation-anion combination

reactions in this solvent. Thus, when the reaction reaches the diffusion control

there is no KIE, since there is no C,Nu bond forming in the transition state.

Le., the Z(vHi - VHi*) term is zero. This result c m be explained by a change in rate

determining step from kl to either k3, or t in Scheme 5.

D EXPERIMENTAL

D-1 KINETIC STUDlES

D1.1 DETERMINATION OF THE Am, FOR UV DETECTION TO BE USED

IN KINETIC STUDY

A UV cell, containing approximately 3.5 mL of concentrated sulfuric acid to

which had been added 1 pL of a solution containing 0.05 M (4-substituted-4'-

rnethoxydipheny1)methanol in glacial acetic acid, was placed in a UV

spectrophotometer. A UV spectrurn was obtained by scanning the solution from

200 to 600 nm. The hm,, for maximum absorption of the related carbocation,

was found to be in the 400-500 nm regioni* 32. Table 40 contains hm,, values for

(Csubstituted-4'-methoxydiphenyl) methyl cations obtained by this procedure.

Table 40: UV wavelengths used to monitor the disappearance of (4-substituted- 4'-methoxydiphenyl)methyl cations.

Substituent X Substituent X

' These k ' s are very close to those found by McCleliand and CO-workers( Bartl, J.; Steenken, S.; Mayr, H.; McClelland, R A. J. Am, Chern. Soc. 1990, 1 12, 6918) with the nLFP technique.

D-1.2 SECONDARY ALPHA DEUTERIUM KIE MEASUREMENTS

P1.2.1 REACTIONS OF WATER WlTH 4-SUBSTITUTED

A 500 mL master stock solution of 20:80 AN:W was prepared by mixing

exactiy 100 mL of HPLC grade acetonitrile (AN, Aldrich) with deionized watei in

a 500 mL volumetric flask. Another 500 mL master stock solution was also

prepared for 90:10 AN:W. Acetonitrile was added slowly into a 500 mL

volumetric fiask containing exactly 50 mL of deionized water. These solvent

solutions were used to measure the KIEs for reactions between (4-substututed-

4'-methoxydiphenyl) methyl cations and water as follows.

1) Seven labeled 25 rnL volumetric flasks each containing exactly 25 mL of the

20:80 AN:W solvent mixture were prepared. One flask was to contain solvent

only and serve as the blank, three were to contain undeuterated substrate and

the other three deuterated substrate. The blank solution was injected with 20 pL

of pure acetonitrile. and the others with 20 pL acetonitrile solutions containing

approximately 0.05 M of the appropriate substrates. These solutions were

thermostated at 25 OC in a water bath for 2 hours.

2) A nanosecond laser flash spectrophotometer system was prepared by

flushing the laser and filling with fresh helium, fluorine and krypton gas with a

combination required to obtain a laser wavelength of 248 nm.

3) After the solutions were temperature equilibrated, kinetic measurements

were peiformed by transferring 4 mL of the blank solution into a 1 x 1 x 4 cm UV

' Water was added slowly and the flask was filled at room temperature since the temperawe decreased when water was mixing with acetonitriie.

cell using a long stem Pasteur pipette. The cell was placed into a sample holder

which was thermostated at 25 O C , and the rernaining 25 mL solution was

returned to the water bath.

4a) After the cell was held in the sample holder for 2 minutes, a 20 ns laser

beam pulse perpendicular to the cell was applied and the absorption in the cell

was followed by a UV beam through the long axis of the ceIl into a detector

which was set at the A,, of the cation. The voltage output was digitized by a

Tetronix SCD-1000 transient digitizer pre-set to a tirne-window of 20 ps, and

interphased with a Tetronix DX-386 corn puter, where the digitized signal was

stored. A baseline voltage reading from 0.90 to 1.1 0 volts was maintained.

4b) The solution was rernoved from the UV cell and a fresh 4 mL of the 25 mL

stock solution containing undeuterated 4-methyl substrate was added. The cell

and the remaining 25 ml stock solution were returned to the sarnple holder and

the water bath, respectiveiy. Then step 4a) was repeated.

4c) The procedures 4b) and 4a) were repeated two to four more times and

then the ceil was washed several times with acetone and dried with a stream of

air.

5) The dried UV cell was refilled with the other 25 mL stock solution containing

the deuterated Cmethyl substrate and steps 4a), 4b) and 4c) were repeated.

6) Steps 3) through 5) were repeated for undeuterated and deuterated

4-hydrogen and 4-trifluoromethyl substrates with their appropriate UV detector

hm,, and digitizer time-windows pre-set (Table 41).

Table 41 : UV wavelengths and time-windows used to monitor the disappearance of 4-methoxy, 4-methyl, ehydrogen, and (4-trifluoromethyl-4'-metho~diphenyl)- rnethyl cations.

Substrate LI, (nm) Tirne-window (p) 20:80 AN:W 90:10 AN:W

-

OMe 502

Me 482 20 20

H 464 5 10

CF3 436 5 5

7) Ali steps above were repeated to measure KIEs for the reactions of water

with Cmethyl, 4-hydrogen and 4-trifluoromethyl substrates in 90:lO AN:W.

8) After fourteen 25 mL volumetric flask stock solutions were completed each

digitized transient was converted into a readable Microsoft Excel computer file

with 512 data points, using the computer prograrn Digfit. A solvent corrected

transient was calculated for each spectrum by subtracting each substrate

transient data point frorn each solvent data point using the computer program

Microsoft Excel. Then the computer program Grafit was used to fit ail solvent

corrected transients using equation 48; each fitted curve was given a first order

rate constant

where At, &, A, are absorption of the carbocation at time t, t=O and t = q

respectively, and Ih, is the first order observed rate constant for the reaction.

Finally, an averaged kn or kD was calculated from the three to five first order

rate constants for each 25 mi volurnetric flask stock solution containing the

undeuterated or the deuterated substrate. A kH/ko was obtained from the

averaged kH and kDfor each esubstituted substrate in each solvent mixture. Six

kHlkDs were, therefore, measured for three 4substituted substrates in one day;

three for 20:80 AN:W and three for 90:lO AN:W.

D-1.2.2 BROMIDE AND CHLORIDE ION REACTIONS

The pseudo-first-order rate technique was used to measure the second

order rate constants and the sadKlEs for reactions of undeuterated and

deuterated diarylrnethyl cations with tetra-n-butylamrnonium bromide and

chloride in 20:80 and 100:O AN:W solutions at 25 OC.

According to this technique excess bromide and chloride ions were used to

generate the pseudo first order observed rate constants for the reactions in six to

seven different concentrations of bromide and chloride ions. The concentrations

of brornide and chloride ions were prepared in such a way that they resulted in

incrernental increases of approximate 0.5 units of the lowest pseudo first order

observed rate. Normally, these concentrations were varied in a range of (3 x IO-^

to 2 x 10' M) and (O to 5 x I o 3 M)' for the reactions of the 4-Me and 4-H

substrates with bromide ion, respectively, and (O to 6 x 1 O-' M) for the reaction of

the 4-H substrate with chloride ion in 20:80 AN:W. In 90:lQ AN:W only one

concentration range of (5 x 108 to 1 x 10-~ M) was used for the reactions of the

4-Me, 4-Hl and 4-CF3 substrates with bromide ion. The second order rate

constants were obtained from the least squares straight lines of the plots which

were constructed by graphing the averaged pseudo first order observed rate

constants versus the bromide and chloride concentrations. The linear correlation

coefficients of these lines were at least 0.997. One K1E was calculated from one

k~ and one kD which were rneasured the same day.

A typical KIE measurement in 20:80 AN:W was perforrned using master

stock solutions of bromide and chloride ions prepared by dissolving respectively

1.91 0 and 5.1 12 g of tetra-n-butylamrnonium bromide and chloride with two 250

mL aliquots of deionized water into two 250 mL volumetric fiasks. These master

solutions were used to prepare the other 25 mL stock solutions below using the

amounts indicated in Table 42.

' in one controiied experiment sodium perchlorate (NaC104) was used to maintain a ionic strength of 0.005 for a11 solutions; the pseudo first order rate and second order rate constants were the same as those of the reactions without sodium perchlorate. This showed that there was no ionic strength effect in these reactions.

Table 42: Volumes of nucleophile stock solution used to prepare fourteen 25 mL solutions used for detemining the KIE for the reactions of (4-substituted-4'- methoxydiphenyl)methyl cations with bromide and chloride ions in 20230 AN:W at 25 OC.

Numbered 25 mL flask O 1 2 3 4 5 6

Nucl. Subst. Volume (mL)

Br' Me mL O 3 6 9 12 15 18

Br' H mL O 1 2 3 4 5 6

C 1' H mL O 1.3 2.6 3.9 5.2 6.5 7.8

Fourteen 25 mL volumetric flasks were used; seven flasks were labeled H

and numbered frorn O to 6 for the undeuterated substrate and the other seven

were labeled D and nurnbered frorn O to 6 for the deuterated substrate. Five mL

of acetonitrile and the appropriate volume of the stock aqueous nucleophile

solution (Table 42) were transferred into each fiask using a 5 rnL Hamilton

syringe fitted with a 12 inch needle. Deionized water was then slowly added to

the mark of each flaski. These solutions were thermostated at 25 OC in a water

bath for 2 hours. After the solutions were equilibrated to 25 OC, the pseudo first

order observed rates were measured as outlined below.

1) A 1 x 1 x 4 cm UV ceIl was filled with 4 mL of solution which was contained in

the 25 mL volurnetric flask labefed H and numbered 6, and placed into a

sample holder which was thermostated at 25 O C . The remaining solution

' The temperature decreased when water was mixed with acetonitrile.

was injected with 16 pL of an acetonitnle solution containing 0.05 M

undeuterated 4-substituted substrate and then returned to the water bath.

After the UV ceil was held in the sample holder for 2 minutes, a 20 ns laser

pulse was applied perpendicularly to the ceIl and the absorption in the cell

was followed by a UV beam through the long axis of the cell into a detector

which was set at a wavelength A,, of the particular carbocation (Table 41).

The baseline signal with solvent alone was recorded and digitized by a

Tetronix SCD-1000 transient digitizer which was pre-set to a time-windowi.

This was connected to a Tetronix DX-386 computer where the digitized

signal was stored. A baseline voltage reading from 0.90 to 1.10 volt was

maintained and recorded for the transient.

The solution was removed from the UV cell and a fresh 4 mL of the labeled

H number 6 solutionii was placed in the cell. The cell and the remaining 25

mL stock solution were returned into the sample holder and the water bath,

respectively. Then step 2) was repeated.

Step 3) was repeated for two to three more times and then the ce11 was

washed several times with acetone and dried with a compressed air stream.

Steps 1, 2, 3 and 4 were repeated with the new 25 mL stock solution labeled

D and number 6 for the deuterated substrate.

Al1 of the above steps were repeated for the rest of the 25 mL stock

solutions.

The pseudo-first-order observed rate constants were calculated exactly the

same way as described above for the water reactions. The average first order

observed rate constants were calculated from three to four rate constants - - -

' The-windows were found fkom trial experiments before the actual kinetics were performed. " Since the power of the laser was slowly reduced (fiom 150 to 80 mJ) a better resdt was achieved in ordering the nucleophile concentrations fiom hi& to low. This is because the signal magnitude is proportional to the laser power.

obtained from the same 25 mL labeled and numbered solutions. These average

rate constants were plotted versuç the concentrations of bromide and chloride

ions to find the second order rate constants for these reactions (equation 49).

One kH, ko, and the KlEs were obtained for the reactions of either bromide ion or

chloride ion with one undeuterated and deuterated 4substituted substrate.

D-1.3 SECONDARY ALPHA DEUTERIUM EIE MEASUREMENT

Pl 3 . 1 DIARYLMETHYL CATIONS WlTH WATER IN SULFURIC

Before measuring the secondary alpha deuterium EIE, a "titration curve ,ri, 42

for each (4-substituted-4'-rnethoxydiphenyl)methanol had to be constructed from

the OD of the carbocation versus sulfuric acid concentration. From this plot the

midpoint for each curve was approximately determined. Then, three to four

sulfuric acid stock solutions near the midpoint and the maximum were prepared.

A typical titration curve, illustrated for (4-methoxydiphenyl)methanol, was

constructed as fo[lows

Fifteen sulfuric acid stock solutions were prepared by diluting concentrated

sulfuric acid to approximately 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35,

30, and 20 with distilled water in meen 250 mL volumetric flasks. Then

the exact sulfuric acid concentrations of these solutions were determined by

titrating with 1.00 N standard sodium hydroxide solution using phenolphthalein

as an indicator.

' Application of method C in the paper of Deno et al, ref. # 42. " These percentages were converted into molarity when these solutions were titrated with 1 .O0 N sodium hydroxide standard solution.

The fiifteen sulfuric acid stock solutions and 18.38 M (100 %) sulfuric acid

solution were transferred to sixteen 25 mL volumetric flasks. and equilibrated at

25 OC for two hours in a water bath.

A 5 x 10'~ M stock solution of (4-methoxydiphenyl)methanol was prepared by

dissolving 18 mg of (4rnethoxydiphenyl)methanol in 2 ml of glacial acetic acid.

A computerized Cary DX-2200 UV-Vis spectrophotometer was set to A,, =

464 nrn (Table 41). and the UV cuvette holder was thermostated at 25 OC. Then,

a sulfuric acid solution was transferred to a 1 x 1 x 4 cm UV cell and its UV

reading was balanced to zero and saved by the spectrophotorneter.

When the temperature was equilibrated, 50 pL of the 5 x Ioe3 M (4-methoxy-

dipheny1)methanol solution was carefully injected within 3 seconds into the 25

mL volumetric flask with a 50 pl Hamilton syringe fitted with a 3 inch needie, and

a digital dock was started. The reaction flask was shaken for ten seconds and

placed back in the water bath for 2-6 minutes', depending on the viscosity of the

acid solution. After al1 bubbies in the 25 ml flask had cleared, the solution was

transferred to the UV cell with a short-stem Pasteur pipette. The cell was placed

in the sample chamber and the UV absorption was recorded for five minutes.

The UV reading was extrapolated to zero time using the cornputer programs

Microsoft Excel and Grafit. It can be noted that the carbocation is unstable in

these solutions, as indicated by a decrease in the UV absorbante shown in

Figure 25. A curve was then constructed by plotting the exh-apolated readings

versus the sulfuric acid concentrations (Figure 26). The midpoint for this cation

is around 9.7 M (53 %) sulfuric acid.

' T i e depended on the viscosity of the suIhic acid solutions, Le., high sulfunc acid concentrations needed longer times to eliminate the bubbles.

Figure 25: A typ ica l extrapolat ion of W xeadings t o zero time for ( 4 , 4 '-dimethoxyphenyl) methyl cat ion ( labeled OMe, OMe) , (4-methyl-4 r-methoxydiphenyl) y cation ( labeled Me, OMe) , and (4-rnethoxydiphenyl) methyl cation (labeled 8, OMe) in 6.36, 8 - 23 and 9.82 M aqueous sulfuric acid solutions, respectively, at 25 Oc.

Thus, four 500 mL sulfuric acid stock solutions' near this midpoint, (9.52,

9.82, 10.08, 10.36 M) and the 18.38 M (100 %) sulfuric acid solution were used

to measure the secondary alpha deuterium equilibrium KIE for this substrate.

Three 25 mL volumetric flasks were used for each sulfuric acid solution; one for

a blank, the other two for undeuterated and deuterated substrates. Seven 25 mL

volumetric flasks were used for the 100 % sulfuric acid solution; one for a blank,

' These solutions were prepared by diluting concentrated s u h i c acid with distilled water in 500 rnL volumetric fiasks and titrated with 1.00 N standard sodium hydroxide solution using phendphthalein as a indicator.

Me. Me0 o H,MeO a CF3. Me0 1

Figure 26: W absorption of carbocations versus aqueous sulfuric acid concentrations. The curve labeled OMe, OMe is for (4'4'- dimethoxyphenyl) methyl cation. The cuzve labeled M e , OMe is for (4-methyl-4 '-methoxydiphenyl) methyl cation. The curve labeled H,

OMe is for (4-methoxydipheny1)methyl cation. The curve labeled CF3, OMe is for (4-trif luoromethyl-4 '-methoxy diphenyl) methyl cation.

three for undeuterated, and three for deuterated compounds. After al1 these 25

mL flask solutions had equilibrated to 25 OC in a water bath for two hours, UV

measurements were started by injecting 50 pL of acetic acid into each blank

solution. The procedure described above was employed. UV readings were

extrapolated to zero time (Figure 25), and these values were used to calculate

the secondary deuteriurn EIE for this substrate using the following equation 50.'.

where H and D subscripts are for the undeuterated and deuterated substrates,

respectively, K is the equilibrium constant, and A, &il. and Aacid are the

extrapolated UV readings for sulfuric acid solution near the midpoint, in dilute

sulfuric acid solution and in 18.38 M sulfuric acid solution, respectively. The

value of Adil was in fact equal to zero, since the alcohol has no absorbance at the

A,,,= of the cation. AaUd had a maximum value in the curve and was the average

value for three runs. Finally, A had a value in the middle of the curve. The

secondary deuterium EIE for this substrate was the average of four calculated

values corresponding to four sulfuric acid solutions near the midpoint of the

curve.

The secondary alpha deuterium EIE for (4,4'dimethoxyphenyl)methanol was

measured at hm,= 502 nm, and the sulfuric acid solutions were 6.36, 6.54, 6.73,

and 9.72, 10.17, 10.51 M. The Aacid had a maximum value between 9.35 and

12.16 M sulfuric acid.

The secondary alpha deuterium EIE for (4-rnethyl-4'-methoxydiphenyl)

methanol was measured at hm, =482 nm, and the sulfuric acid solutions used

were 8.00, 8.30, 8.68 and 18.38 M.

Modification of equations in the text book of Lowry and Richardson, and Beer's Law.

The secondary alpha deuterium EIE for (4-trifiuoromethyl-4'-rnethoxydiphenyl)

methanol was measured at A,, = 436 nrn, and the sulfuric acid solutions used

were 1 1.03, 11 -22, 1 1.37 and 78-38 M. Since the viscosities of the 1 1.03, II -22

and 11.31 M sulfuric acid solutions were high, and the OD of the undeuterated

and deuterated cations changed rapidly with tirne, there was a large error in the

extrapolation. Accordingly, the EIE could not be detemined.

P1.3.2 (4-METHYL-4iMETHOXYDIPHENYL)METHYL CATION

WlTH BROMIDE ION

This EIE was measured using the same method as described in the KIE

measurements, but the data analysis differed. The decay traces for this cation

with bromide ion were double exponentials. This can be explained by Scheme 7

in which the reaction of the cation with bromide is reversible. The transients

were therefore fitted with a double exponential decay function, equation 51, to

solve for ka and kb using the Grafit program. Then plotting (ka + kb) versus

bromide concentrations yielded k8r as the slope and (kW + k,,) as the intercept.

The first order rate constant, kW, was measured at the same time from the

reaction without bromide ion. The ratio kioJkBr provided the equilibriurn constant.

D-1.3.3 SECONDARY ALPHA DEUTERIUM KIE MEASUREMENTS

FOR THE SOLVOLYSlS REACTIONS OF UNDEUTERATED

AND DEUTERATED (4'-METHOXYD1PHENYL)METHYL

CHLORIDE IN 98:2 AN:W.

The kinetics for the undeuterated and deuterated methyl chlorides were

simultaneously measured four times for each substrate in one day using the

procedure described below.

Fifty mL of 0.001 M hydroxide ion stock solution was prepared by slowly

mixingi 1 mL of a 0.05 M aqueous tetramethylammonium hydroxide master

solution' with acetonitrile in a 50 mL volumetric flask. This solution was

l Since the temperature decreased when acetonitrile was added and mixed with water, the density of the solution was larger at low temperature. " This solution was prepared by dissolving 0.2286 g of tetramethylammonium hydroxide pentahydrate

themostated at 25 OC in a water bath for 2 hours. Afier the temperature

equilibrated, 4 mL of the solution was transferred into a 1 x 1 x 4 cm UV ceIl

using a Pasteur pipette. The UV ce11 was placed into the sample chamber of the

computerized Cary DX-2200 UV-Vis spectrophotometer which was thermostated

at 25 O C and the remaining 50 mL stock solution was returned to the water bath.

After the cell was held in the chamber for 2 minutes, the UV reading was set to

zero at h = 249 nm fo i the blank solvent, and 3 pL of the acetonitrile solution

containing 0.05 M undeuterated (4-rnethoxydipheny1)methyl chloride was quickly

injected into the cell' using a 5 pL Hamilton syringe. The computer program

which was immediately started and the disappearance of the methyl chloride was

followed for 6 minutes. The data for the kinetic run was stored in the computer

hard drive. The solution was discarded, the cell was washed several times with

water, and finally acetone and dried under a pressured air stream. A new 4 mL

solution was again added to the cell to be used for the kinetic measurement of

the deuterated methyl ch loride.

After eight kinetic runs were performed for both deuterated and undeuterated

substrates, the data were converted into readable files for the Grafit program.

These files were fitted to a first order decay function (Abs = Abs (initial) x exp(-kt)

+ base, Figure 27) to give first order observed rate constants (kH and kD). The

KIE was calculated from the averages of the J<Hs and k ~ s .

(M~JN'OHSH~O, 99 % pure, Aldrich) with 25 mI, of deionized water in a 25 mL volumetric flask. i The controlled reactions shown the injection and mWng was performed within 10 to 15 seconds.

Reduced Chi squaied =1.T71e-006

VariaMe Valie SU. Er-

&t 1-1 6C9C58UX lnital 214û2e-Cû1 32524eUX

Figure 2 7 : Out put data for the optical density change and f i t t e d cume for the solvolysis reaction of (4-methoxydipheny1)methyl chloride in 97 : 3 AN:W at 25 O C .

D-f .4 KINETIC MEASUREMENTS FOR STUDIES OF THE EFFECTS OF

SOLVENT AND SUBSTITUENT ON THE RATES OF THE

REACTIONS OF (4-SUBSTITUTED-4'-METHOXYDIPHENYL)

METHYL CATIONS WlTH WATER, BROMIDE, CHLORIDE AND

ACETATE IONS IN VARIOUS AQUEOUS ACETONITRILES.

The preparation of the solvents and the determination of the absolute second

order rate constants in this section were similar to the methods described in the

KIE measurements for bromide and chloride ion reactions.

Solvents were prepared as stock solutions by mixing the required amount of

HPLC grade acetonitrile with deionized water in 2 L or 1 L volumetric flasks.

Then, these solvents were used to prepare the nucleophile master stock

solutions by dissolving the appropriate arnount of tetra-n-butylammonium salt of

these nucleophiles in the 250 mL volurnetric flasks. Six 25 mL volumetric flasks

were used to prepared six different nucleophile concentrations for each

nucleophile by mixing the required amount of these nucleophile master stock

solutions with appropriate solvents. The average of three or four pseudo-first-

order rate constants was calculated for each 25 mL nucleophile solution. Then,

one absolute second order rate was obtained from these six different nucleophile

concentrations by plotting the six averages of pseudo first-order-rate constants

versus the nucleophile concentrations.

D-2 SYNTHESIS

D-2.1 PREPARATION OF UNDEUTERATED AND DEUTERATED

JCSUBSTITUTED 4'-METH0XYDIPHENYL)METHYL CHLORIDE

D-2.1 .l PREPARATION OF UNDEUTERATED AND DEUTERATED

(4-METH0XYDIPHENYL)METHYL CHLORIDE.

HCI - CH2CI2

Al1 undeuterated and deuterated substrates were prepared by modification of

the method described by Schneider and Wlayr4=. A typical preparation of (4'-

rnethoxydiphenyl)methyl chloride was as follows.

Previously prepared (Q.methoxydiphenyl)rnethanol, 0.4461 g, (2.08 mrnol)

was dissolved in a 100 mL round bottorn flask containing 30 mL of

dichloromethane, 2 g of finely ground anhydrous calcium chloride and a teflon

coated magnetic stirring bar. The flask was sealed with a rubber septum and

tightened with copper wire. The flask was connected to an 4ldrich compressed

hydrogen chloride gas cylinder with a teflon tube and a 12 inch stainless steel

needle. After stirring the solution in a dry ice-acetone bath in a fume hood for 10

minutes, a strearn of hydrogen chloride gas was carefully and slowly bilbbled

into the reaction solution in portions by opening and closing the valve of the

cylinder for 3 minutes. The reaction solution was continuously stirred until the

acetone bath reached room temperature. The excess gas was carefully

released inserting a 2 inch needle into the rubber septum, and the reaction Rask

was opened. The reaction solution was gravity filtered into another cleaned and

dried 100 m l round bottom flask and the solvent was removed in a rotary

evaporator. The pale yellow solid (4-methoxydiphenyl)rnethyl chloride was

vacuum distilled at 10 torr and 1 iO-l75 OC giving 0.31 0 g of white solid. The

white solid was recrystallized with pentane and yielded 0.1 1 g of white powder.

The mp. was 60-61 O C . ~ i t . ~ * mp. 61-62 OC, 62-63 Oc4! 'H NMR (200 MHz,

CDCI3) 6 : 3.82 (s, 3H), 6.18 (s, 1 H). 6.91 (m, 2H). 7.37 (m, 5H), 7.48 (m, 2H).

l3c NMR (200 MHz, CDC13) S : 55.25, 64.19, 113.83, 127.59, 127.84, 128.37,

129.02, 133.30, 141 -1 5, 159.24. MS (70 eV): 232 (M+, 7), 197 (M+-CI, 1 OO), 182

(14). 165 (19). 153 (24).

(4-Methoxydiphenyl)methan-d-01, 0. 251 g gave 0.185 g of white solid

((4-methoxydiphenyl)methyl-d chloride) after distilling at 10 torr and 170-1 75 OC.

The yield was 0.105 g after recrystalizing in pentane and the mp was 62-63 OC.

1 H NMR (200 MHz, CDC13) 6 : 3.82 (s, 3H), 6-91 (ml 2H), 7.37 (m, 5H), 7.48 (m,

2H). MS (70 eV) 233 (M', 7), 198 (M-CI, 1 OO), 183 (14)) 154 (23), 84 (17). When

the 'H NMR spectrum (200 MHz, CDCI3) was recorded at a high spectrum

amplitude, a very srnall peak at 6 = 6.18 ppm, was observed. A calculation

based on the integraüon of the peaks ai 6 =6.18 and 3.78 ppm indicated that the

alcohol was approximately 98 % deuterated at the alpha carbon.

D-2.1.2 PREPARATION OF UNDEUTERATED AND DEUTERATED

(4-METHYL-4'-METH0XYDfPHENYL)METHYL CHLORIDE

Undeuterated and deuterated (4-methyl-4'-methoxydiphenyl)methyl chloride

were prepared using the method described above.

HCI - fVle--@-OMe CH2CI2 I

(4-Methyl-4'-methoxydiphenyl)methyl chloride

'H NMR (200 MHz, CDCI3) 6 : 2.45 (S. 3H), 3.86 (s, 3H), 6.23 (s, 1 H), 6.98 (m.

2H), 7.26 (ml 2H), 7.46 (ml 4H). I3c NMR (200 MHz, CDCI3) 6 : 21.00, 55.12,

64.15, 113.68, 127.45, 128.88, 128.97, 133.35, 137.53, 138.24, 159.08. MS :

246 (M*, 3), 226 (7). 217 (M+-CI, IOO), 196 (20). 181 ( I l ) , 165 (14), 153 (16),

135 (16).

(4-Methyl-4'-methoxydiphenyl)methyl-d chloride

'H NMR (200 MHz. CDC13) 6 : 2.45 (S. 3H), 3.86 (s, 3H), 6.98 (ml 2H). 7.26 (m,

2H), 7.46 (m, 4H). MS : 247 (M', 3), 226 (27), 212 (M'- CI, 100). 197 (22), 182

(IO), 166 (13). 154 (23), 135 (40). When the 'H NMR spectrum (200 MHz,

CDC13) was recorded at a high spectrum amplitude. a very small peak at 6 = 6.23

ppm, was obsewed. A calculation based on the integraüon of the peaks at 6

=6.23 and 2.45 ppm indicated that the alcohol was 98 % deuterated at the alpha

carbon.

P2.1.3 PREPARATION OF UNDEUTERATED AND DEUTERATED

(4TRIFLUOROMETHYL-4'-METH0XYDIPHENYL)METHYL

CHLORIDE.

Undeuterated and deuterated (4-triflu0romethyl-4~-methoxydiphenyl)methyl

chloride were prepared using the same method that was used for the preparation

of the undeuterated and deuterated (4-methoxydiphenyl)methyl chloride

described above.

(4-Trifluoromethyl-4'-methoxydiphenyl)methyl chloride

1 H NMR (200 MHz, CDC13) 8 : 3.82 (s, 3H). 6.18 (S. IH), 6.92 (s, 2H). 7.32 (m,

ZH), 7.6 (m, 4H). 13c NMR (200 MHz, CDCW S : 55.29. 63.79, 1 14.07, 125.36,

127.98, 129.00, 130 (q), 132.43, 145.04, 159.55. MS: 300 (MI, 5), 265 (M+-CI,

IOO), 233 (9), 196 (6), 181 (7). 165 (7). 153 (16), 109 (5).

(4-Trifluoromethyl-4'-methoxydiphenyl)methyl-d chloride

'H NMR (200 MHz, CDCI3) 6 : 3.80 (s, 3H), 6.90 (ml 2H), 7.32 (m. ZH), 7.63

(m, 4H). MS: 301 (M', 5), 266 (M+-CI, 100), 249 (?), 234 (8)) 197 (8), 166 (7),

154 (16). When the 'H NMR spectrum (500 MHz, CDCl3) was recorded at a high

spectrum amplitude, a very small peak at 6 = 6.18 pprn, was observed. A

calculation based on the integration of the peaks at 6 =6.18 and 6.92 ppm

indicated that the alcohol was approxirnately 98 % deuterated at the alpha

carbon.

P2.1.4 PREPARATION OF (3,4'-DIMETH0XYPHENYL)METHYL CHLORIDE.

HCI - CH2CI2

1 H NMR (200 MHz. CDCI3) 6 : 3.82, (S. 3H), 3.83 (s, 3H), 6.16 (s, 1H). 6.92 (ml

3H), 7.06 (ml 2H), 7.35 (ml 3H). 13c NMR (200 MHz, CDC13) 6 : 55.08, 55.14,

113.15, 113.43, 113.78, 119.90, 128.95, 127.49, 129.40, 133.10, 142.80,

P2.2 PREPARATION OF (4-SUBSTITUTED-4LMETHOXYDIPHENYL)

METHANOLS

PZ.2.l PREPARATION OF (4,4'-DIMETH0XYPHENYL)METHANOL

O H Et20

M~oQ&-@M~ + LNH4 - THF M e O e w O M e

Two grams (8.0 mmol) of 4,4'-dimethoxybenzophenone (Aldrich, 97 % pure)

was dissolved in 50 mL of distilled THF, and added dropwise into a 250 mL two

neck round bottom flask containing 0.75 g (19.8 mmol) of lithium aluminum

hydride and 50 mL of anhydrous diethyl ether under an argon atmosphere. After

refluxing for one hour, the reaction was cooled in a dry ice-acetone bath and

quenched with 100 mL of a 5 % sulfuric acid solution. Then, the organic solution

was separated frorn the aqueous layer in a 500 mL separatory funnel and the

aqueous solution was extracted with two portions of 50 mL of diethyl ether. The

combined organic solution was washed three times with 200 mL water to remove

any sulfuric acidi and dried over anhydrous magnesium sulfate. After the

magnesium sulfate was removed by gravity filtration, the solvent was rernoved

with a rotary evaporator, and the product was recrystallized with diethyl ether and

.

' Acid may cause two molecules of diarylmethanol to couple to give an ether.

hexane. The yield of (4.4'-dimethoxypheny1)methanol was 1.50 g (6.1 mmol,

76%, white solid compound), and the mp was 65.5-66.5 OC. 'H NMR (200 MHz,

CDCI3) S : 3.4 (s, IH, OH), 3.9 (s, 6H, 0CH3), 5.8 (s, IH, methine), 7.0-7.4 (m,

8H, aryl). 13c NMR (200 MHz, CDCI3) 6 : 55.0. 74.9, 1 13.5. 127.6, 136.3. 158.5.

MS (5.2~) mfz = 244 (M+, 53), 227 (M'-OH. 46), 21 3 (M+-OME. 15). 184 (M+-

20ME, 5) 135 (M+C7H90, IOO), 109 (M+-Ce~702, 51), 77 ( M + - c ~ H ~ ~ o ~ , 38).

P2.2.2 PREPARATION OF (4-METtI0XYDIPHENYL)METHANOL

D-leOMe OMe + LiAIH4 - THF

This compound was prepared using the procedure desxibed above.

4-Methoxybenzophenone (Aldrich, 97 % pure), 4.00 g (1 8.3 mmol), were reacted

with 1.509 (39.5 mmol) lithium aluminum hydride. The yield of (4-methoxy

dipheny1)methanol was 3.25 g (15.2 rnrnol, 81 %, white needles) and the mp was

63.5-65 OC. 'H NMR (400 MHz, CDCI3) 6 : 2.65 (d, 1 H, OH), 3.77 (s, 3H. OC&),

5.74 (dl 1 Hl methine), 6.84-7.37 (m. 9H, aryl). 13c NMR (400 MHz, CDCI3) 6 :

55.15, 75.58, 113.68, 126.26, 127.20, 127.76, 128.24, 136.d6, 143.89, 158.75.

MS (325 mv) mlz = 214 (M+, 63). 197 (M'-OH, 19), 183 (M+-0Me, I l ) , 135 (M+-

60), 109 (M*-c~H~O. 1 00). 77 (Mf-C8H902, 67).

P2.2.3 PREPARATION OF (CMETHYL-4'-METHOXYDIPHENYL)

METHANOL

The Grignard reagent was prepared by adding 15 rnL of a mixture consisting

of 120 mL of anhydrous diethyl ether and 12.00 g (64.53 mrnol) of Cbromo-

anisole (Aldrich, 99 % pure) into a three necked 500 mL round bottom flask

containing 2.00 g (83.39 rnmo!) of magnesium. The solution was stirred under

an argon atmosphere and warmed in an oil bath until the reaction started. The

remainder of ether solution was added at a constant rate. After the Grignard

reaction had refluxed for three houn, it was cooled in a dry ice-acetone bath, a

solution of 6.50 g (54.14 mrnol) of 4-tolualdehyde (Aldrich, 97 % pure) in 50 mL

of anhydrous diethyl ether was gradually added. The reaction was then worked

up by slowly adding 200 mL of 5 % aqueous sulfuric acid, and the ether layer

was separated from the aqueous layer in a 500 mL separatory funnel. After the -

aqueous layer was extracted two times with 100 mL of diethyl ether, the ether

layers were combined and washed with three portions of 200 mL of water and

then dried over anhydrous magnesium sulfate. The combined ether layers were

filtered and the filtrate was concentrated on a rotary evaporator. The product

was purified by passing through a silica gel column using 15 % by volume of

ethyl acetate in hexane as a mobile phase. The fraction was concentrated to a

crystalline product and then recrystallized from a minimum amount of diethyl

ether followed by a minimum amount of hexane (to the point of cloudiness). The

yield was 9.58 g (42.00 mrnol, 78 %) and the rnp of the white needle-like crystais

was 59.5-61 OC. 'H NMR (200 MHz, CDC13) 6 : 2.28 (dl 1 Hl OH). 2.33 (s, 3H,

CH3), 3.78 (s, 3H, 0CH3), 5.75 (d, 1 H, CH, methine), 6.84-7.27 (m, 8H. aryl). I 3 c

NMR (400 MHz, CDCI3) 6 : 21 -1 1, 55.24, 75.57, 11 3.73, 126.28, 127.70, 129.01,

136.24, 136.97, 141 .O7, 158.80. MS (2.5 v) m/z = 228 M+, 71), 21 1 (M'OH, 40),

197 (M+-OM~, 18), 135 (M+-c~H~, 100). I l 9 (M+-C~H~O, 80). IO9 (M+-C~H~O,

79). 91 (M+-C~H~O~, 42), 77 ( M + - c ~ H ~ ~ O ~ , 44)

This compound was prepared using the same method that was used to

prepare (4-rnethyl-4'-methoxydiphenyl)methanol, was above. The Grignard

reagent was prepared by reacting 8.00 g (43.02 mmol) of 4bromoanisole

(Aldrich, 99 % pure) with 1.50 g (62.54 mrnol) of magnesium. Then, 6.50 g

(37.35 mmol) of a, a,a-trifl~0r0-4-t0l~aldehyde (Aldrich, 98 % pure) was added

into the Grignard reagent. The product was purified by passing through a silica

gel column using 15% by volume of ethyl acetate in hexane as a mobile phase

and recrystallized with diethyl ether and hexane. The yieid was 8.18 g (29.00

mmol, 77.6 %, white solid) and the mp was 74-75 OC. 'H NMR (400 MHz,

CDCI3) 6 : 2.25 (dl IH, OH). 3.78 (s, 3H. OCH3), 5.82 (dl IH, CH, methine), 6.84-

7.58 (ml 8H, aryl). 13c NMR (400 MHz, CDC13) 6 : 55.31 (s), 75.29 (s), 114.07

(s), 124.05 (q, l ~ ~ F = 272.4 HZ), 125.27 (q, 3 ~ ~ . ~ = 3.7 HZ) , 126.46 (s). 127.97

(s), 129.10 (q, ' J C ~ = 32.2 Hz), 135.40 (s), 147.67 (s), 159.30 (s). MS (3.8 v) mlz

= 282 (M+, 56). 265 (M'OH, 20), 251 (M+-OMe. 1 l) , 173 (M+-c~HsO, 44), 145

(M+-C~H~O~, 59), 137 (M+-c~H~F~, 59), 124 (M+-C~H~F~, 41), 109 (M+-C~H~OF~,

1 OO), 94 (M'-C~H~OF~, 20), 77 (M ' -c~H~O~F~, 32).

D2.2.5 PREPARATION OF (3.4'-DIMETH0XYPHENYL)METHANOL

1 H NMR (200 MHz, CDCI3) S : 2.74 (s, OH), 3.77, (s, 3H), 3.78 (dl 3H, 8~n-H=3.6

Hz), 5.72 (s, IH), 6.88 (m, 5H), 7.25 (m, 3H). I3c NMR (200 MHz, CDCl3) 6 :

55.04, 55.09, 55.15, 111.85, 112.68, 113.73, 118.69, 126.56. 127.49, 129.30,

136.03, 145.69, 158.91, 159.55.

P2.3 PREPARATION OF 4-SUBSTITUTED-4'- METHOXYBENZO-

PHENONES

P2.3.1 PREPARATION OF 4-METHYL-4'-METHOXYBENZO-

PHENONE

OH acetone

This compound was synthesized by following the rnethod described by Jones

and Lemin et

Chrornic acid solutioni, 25 mL, was cooled in a dry ice-acetone bath. Then, 50

mL of acetone solution containing 5.00 g (21.92 mmol) of (4-methyl-4'methoxy-

dipheny1)methanol waç added dropwise with a Pasteur pipette. After stirring at

room temperature for two days, the reaction mixture was poured into a 500 m l

separatory funnel containing 200 m l of water. The product was extracted with

three portions of 75 mL of diethyl ether. After the combined ether fractions were

dried over anhydrous magnesium sulfate, the mixture was filtered and the ether

' This acid was prepared by mixing 6.67 g (43.92 mmol) of chromium trioxide with 6 mL of concentrated sulfuric acid and 19 mi, of distilied water.

was removed on a rotary evaporator. The cnide 4-methyl-4'methoxybenzo-

phenone was purified by passing it through a silica gel column chrornatography

using 20 % ethyl acetate in hexane as a mobile phase and recryçtallizing it with

acetone and hexane mixture. The yield and the mp were 3.78 g (16.72 mmol,

76.3 %, needle like) and 88-89.5 O C ,respectively. 'H NMR (200 MHz, CDC13.)

6 : 2.44 (S. 3Ht CH3), 3.89 (s, 3H, 0CH3), 6.96 (d, 2H, aryl), 7.28 (d, 2H, aryl),

13 7-68 (dl 2H, aryl), 7.82 (dl 2H, aryl). C NMR (200 MHz, CDCI3) 6 : 21.51,

BENZOPHENONE

OH acetone

This compound was synthesized following the method described above.

Chromic acid, 25 mL, was reacted with 50 mL of an acetone solution containing

4.02 g (14.25 mmol) (4-trifluoromethyl-4'-methoxydiphenyl)metanol The yield

and the mp were 3.11 g (11.10 mmol, 77.9 %) and 119-119.5 OC. 'H NMR (200

MHz, CDCI3.) F : 3.90 (s, 3H, 0CH3), 6.96 (dl 2H. aryl), 7.79 (ml 6H, aryl). 13c

NMR (200 MHz, CDCI3.) 6 : 55-51, 11 3.79, 123.72 (q, 'JCF = 272.6 HZ), 725.22

(q, 3 ~ C ~ = 3.8 Hz), 129.34, 129.75, 132.58, 133.21 (q, 2~C.F = 32.7 Hz), 141.51,

163.71. 194.1 8. MS (1 -7 v) rnh = 280 (M'. 47), 173 (M+-C~H~OCH~, 8), 145 (M+-

COC6H40CH3, 18). 135 (M'-c~H~F~, 100!, 1 O7 (M+-COC~H~CF~, 8), 92 (M+-

C9H70F3, 14), 77 ( M - c ~ H ~ O ~ F ~ , 1 7).

D-2.4 PREPARATION OF (4-SUBSTITUTED-4'METHOXYDf P H E W

METHAN-d-OLS

~2.4.1 PREPARATION OF (4-4'DIMETHOXYPHENYL)METHAN-d-

The procedure which was used to synthesize this compound was rnodified

from the method described by ~ h a r n ~ ~ . In a glove bag (AtmosBag, Aldrich) filled

with argon gas, a mixture consisting of 3.00 g (12.20 mmol) of 4,4'-dimethoxy-

benzophenone (Aldrich, 97 % pure) and 50 mL of distilled THF was slowly added

into a 500 mL two necked round bottom flask which contained 100 mL

anhydrous diethyl ether and 1 g (23.78 mmol) of lithium aluminum deuteride

(Aldrich, 98 atom % D). After refluxing for one hour, the reaction was cooled in a

dry ice-acetone bath and quenched with 200 mL of a 5 % sulfuric acid solution.

Then, the organic layer was separated from the aqueous layer in a 500 mL

separatory funnel, and the aqueous layer was extracted three times with 75 mL

of diethyl ether. The combined organic layen were dried over anhydrous sodium

sulfate. Sodium sulfate was then removed by gravity filtering, and the filtrate was

concentrated on a rotary evaporator. The crude product was recrystallized from

diethyl ether and hexane. The yield was 2.34 g (9.54 mmol. 78 %, white solid),

and the mp was 65.5-66.~~C. 'H NMR (200 MHz. CDCI3) 6 : 3.52 (s, IH, OH).

3.90 (S. 6H, 0CH3), 6.95-7.92 (m, 8H. aryl). 13c NMR (200 MHz. CDCI3) 6 : 54.9

(s). 74.9 (t, ' J C - ~ = 21.5 Hz), 127.5 (s). 136.3 (s), 158.5 (s). MS (2.1 v) m h = 245

(M', 40). 228 (M'OH, IOO), 21 3 (M+-CH40, 25), 185 (M+-C2H40zI 8). 170 (M:

CZH3O3, 14). 135 (M+-C~H~OCH~, 84). 110 (M+-C~H~O~, 37). 92 (M*-C9~11~02,

12), 77 (M ' -C~H~~DO~, 18). When the 'H NMR spectrum (200 MHz. CDC13) was

i-E-:ordaci at a high spectrurn amplitude, a very small peak at 6 = 5.8 ppm, was

observed. A calculation based on the integration of the peaks at 6 = 5.8 and 3.9

pprn indicated that the alcohol was 98 % deuterated at the alpha carbon.

D-2.4.2 PREPARATION OF (4-METHYL-4'METHOXYDIPHENYL)

Et20 ____)

THF

This compound was prepared using the procedure described above. The

previously synthesized 4-methyl-4'-methoxybenzophenone, 2.00 g (8.85 mmol),

reacted with 0.75 g (17.83 mmol) of lithium aluminum deuteride (Aldrich, 98

atom % D). The yield was 1.76 g (7.38mmol. 82 %, white needle like solid) and

the mp was 59-61 OC. 'H NMR (200 MHz, CDCI3) 6 : 2.12 (S. IH , OH). 2.33 (S.

3H, CH3), 3.79 (S. 3H, 0CH3), 6.85-7.31 (m. 8H, aryl). 13c NMR (400 MHz,

CDCI3) 6 : 21.13 (s), 55.27 (s), 75.32 (t, ' J G ~ = 21.5 HZ), 113.76 (s). 126.27 (s),

127.70 (s), 129.03 (s), 136.18 (s), 137.01 (s), 141.01 (s), 158.84 (s). MS (6.8)

m/z = 229 (M+, 16), 212 (M'OH, IOO), 197 (M+-cH~o, 16). 182 ( M + - ~ 2 ~ 7 0 , 9),

166 (M+-C~H~O~, 14), 154 ( ~ ' ~ ~ ~ 7 0 2 , 16), 135 (M+-c~H~cH~, 22), 119

(COC6H4CH3, 16), 1 10 (M+-C~H~O, 15), 91 (C6H4CH3, 9), 77 (C6Hs, 7). When the 1 H NMR spectrum (200 MHz, CDCI3) was recorded at a high spectrum

amplitude, a very srnall peak at 6 = 5.75 ppm, was obsewed. A calculation

based on the integration of the peaks at 6 = 5.75 and 2.34 ppm indicated that the

alcohol was 98 % deuterated at the alpha carbon.

P2.4.3 PREPARATION OF (4-METH0XYDIPHENYL)METHAN-d-OL

Et20 OMe + LAID4 -

THF

The synthesis of this compound followed the same method that was used for

the synthesis of (4,4'-dimethoxyphenyl)methan-d-01, was above. Two g (9.43

rnmol) of 4-methoxybenzophenone (Aldrich, 97 % pure) reacted with 0.75 g

(17.83 mmol) of lithium aluminum deuteride (Aldrich, 98 atom % D). The crude

product was purified by passing it through a silica gel column chromatography

using 15 % (v/v) of ethyl acetate in hexane as a mobile phase and recrystallizing

it in diethyl ether and hexane. The yield was 1.60 g ( 7.44 mmol, 79 %, white

powder) and the mp was 63.5-64.5'C. 'H NMR (400 MHz, CDCI3) 6 : 2.58 (s,

IH, OH). 3.77 (s, 3H, 0CH3), 6.84-7.37 (m, 8H, aryl). I3c NMR (400 MHz,

CDC13) G : 55.17 (s), 75.18 (t, ' J ~ ~ = 22 Hz), 1 13-69 (s), 126.26 (s), 127.22 (s),

127.76 (s), 128.26 (s), 135.99 (s), 141.83 (s), 158.77 (s). MS (864 mv) mlz =

215 (M+, 74), 198 (MCOH, 25). 184 (M+-OCH~, 9), 166 (M'-CH~O~, IO), 154 (M+-

C2H5O2. 15). 138 (M+-C&. 62), 110 (M+-C-IH~~, 100). 105 (M'c~H~Do, 52). 95

(19), 77 (C6H5, 47). When the 'H NMR spectrum (200 MHz, CDC13) was

recorded at a high spectrurn amplitude, a very small peak at 6 = 5.74 ppm, was

observed. A calculation based on the integration of the peaks at 6 = 5.8 and

3.75 ppm indicated that the alcohol was 98 % deuteralzd at the alpha carbon.

This compound was prepared using the sarne method that was used for

the synthesis of (4,4'-dimethoxyphenyl)methan-d-01, was above. 4-Trifluoro-

methyl-4J-methoxybenzophenone, 0.304 g (1 -08 mmol), reacted with 0.250 g

(5.95 mmol) of lithium alurninurn deuteride (Aldrich, 98 atom % D). The product

was recrystallized from diethyl ether and hexane. The yield was 0.1 5 g (0.53

mmol, 49 %, white solid) and the mp was 74-74.5 O C . 'H NMR (400 MHz.

CDCI3) 6 : 2.36 (s, 1 H, OH), 3.77 (s, 3H, 0CH3), 6.84-7.56 (m, 8H1 aryl). 13c

NMR (400 MHz, CDC13) 6 : 55.30 (s), 74.87 (t, = 22.3 HZ), 114.07 (s),

123.94 (q. J ~ . ~ = 272.4 Hz), 125.26 (q, 3 ~ C F = 5-8 Hz), 126.47 (s), 127.95 (s).

129.44 (q, 2 ~ ~ . ~ = 32.2 Hz), 135.35 (s). 147.63 (s). 159.30 (s). MS (5.3 v) mfz =

283.0932 (M', 41), 266.091 1 (~q5Hiq DOF~+=M+-OH, 13), 252 (M'-OCHj, 17).

I73.02l5 (COCsH4CF3, 48) 138-0634 (C6H7DF3=~+-~6~4~F3 , 75). 135-0450

( ~ 8 ~ 7 0 2 ) . 1 l O . O ï 4 l (C~H~DO=M+-C~H~OF~, 1 OO), 95.0489 (1 5). 78 (1 2). When

the 'H NMR spectrurn (200 MHz. CDCI3) was recorded at a high spectrurn

amplitude, a very small peak at 6 = 5.8 ppm, was observed. A calculation based

on the integration of the peaks at 6 = 5.8 and 3.8 ppm indicated that the alcohol

was 98 % deuterated at the alpha carbon.

P2.5 PREPARATION OF SODIUM 4-CYANOPHENOXIDE

N C ~ O H + N ~ + M ~ o - - MeOH N C ~ O - N L

4-Cyanophenol. 11.8 g (99.12 mmol, Aldrich), was dissolved with 100 mL of

rnethanol in a 500 mL round bottom flask and this solution was cooled in an ice-

water bath for 15 minutes. Ninety mL of a methanol solution containing 1 M

sodium methoxide (90.0 mmol, Aldrich) was added into this 500 mL round

bottom Rask. After stirring for 5 minutes with a magnetic stirrer, the methanol

was removed on a rotary evaporator, and 100 mL of diethyl ether was added into

the flask. The reaction mixture was vacuum filtered and the white powder was

washed several times with 50 mL of diethyl ether to remove any unreacted

4cyanophenol. The salt was then dried in a vacuum desiccator over night. The

yield of purified product was 11.43 g (90 % in sodium 4-cyanophenoxide).

P2.6 PREPARATION OF (4-SUBSTITUTED-4'-METH0XYDIPHENYL)-

METHYL 4"XYANOPHENYL ETHERS

D-2.6.1 PREPARATION OF (4-METHYL-4'METHOXYDIPHENYL)-

METHYL 4"-CYANOPHENYL ETHER

~ c ~ o - l r l a + H SOCh - M e e @ - O M e

THF 1

Thionyl chloride, 3.0 mL (Aldrich, 99 %), was added into a 25 mL round

bottorn flask containing 3.52 g (1 5.43 mmol) of (4-methyl-4'-methoxydipheny1)-

rnethanol. After the reaction was refluxed for three hours, the excess thionyl

chloride was removed. The (4-methyl-4'-methoxydipheny1)methyl chloride' was

not purified and was immediately used in the next step.

Sodium 4-cyanophenoxide, 3.49 g (24.78 mrnol) was dissolved in 200 mL of

distilled THF in a 500 mL two necked round bottom flask under an argon

atmosphere. Then, the crude (4-methyl-4'-methoxydiphenyl)methyl chloride

which was dissolved in 20 mL of distilled THF was added, and the reaction was

refluxed for another three days. The reaction mixture was poured into a 500 mL

separatory funnel containing 200 mL of water and the organic layer was

separated from the aqueous layer. The aqueous solution was extracted with

three portions of 50 mL of ether. The combined THF and ether fractions were

washed with 200 mL of 0.2 N sodium hydroxide solution to removed any excess

Ccyanophenol. The organic layer was dried over anhydrous sodium sulfate and

' A controlled reaction found the hydrogen chlonde method described by Deno,J. Am. Chem. Soc. 1955, 77) to give a better yield.

gravity filtered. The filtrate was then concentrated in a rotary evaporator. The

produd was purified by passing it through a silica gel column chrornatography

using a 5, 10, 15, 20 % ethyl acetate in hexane as a mobile phase. The product

was then recrystallized with hexane and diethyl ether. The yield was 2.38 g

(7.25 mmol, 47%) and the rnp was 78.5-8I0C. 'H NMR (400 MHz, CDCI3) 6 :

2.37 (S. 3H. CH3), 3.82 (s, 3H. 0CH3), 6.25 (S. 1 H, CH, methine), 6.91-7.54 (m.

12H, aryl). ' 3 ~ NMR (400 MHz. CDCI3) 6 : 21.1 (5). 55.21 (s), 81.59 (s), 103.88

(s), 114.06 (s), 116.62 (s), 119.14 (s), 126.56 (s), 128.12 (s). 129.39 (s), 132.23

(s), 133.78 (s), 137.1 7 (s), 137.80 (s), 159.30 (s), 161 -32 (s). MS (9.3 v) m/z

= 329 (M', l ) , 211 (M+-oC~H&N, IOO), 196 (M'-C~H~ON, I l ) , 181 (M'-

C9HioON, 7), 165 (M+-c~H~oo~N, 10). 153 J M ' - C ~ ~ H ~ ~ O ~ N , 14), 11 9 ( M + - c ~ ~ H ~ ~ o ,

6).

D2.6.2 PREPARATION OF (4METHOXYDIPHENYL)METHYL

4-CYANO-PHENYL ETHER

This compound was prepared using the procedure described above. Two mL

of thionyl chloride, 2.1 1 g (9.86 mrnol) of (4-methoxydiphenyl)methanol, and 2.78

g (19.72 mrnol) of sodium 4cyanophenoxide were used in this synthesis. The

crude compound was purified by passing it through a silica gel column with 20 %

ethyl acetate in hexane as a mobile phase. After the solvent was removed from

the fraction, a thick oil was crystallized with diethyl ether and hexane. The yield

was 2.14 g (6.78 mmol, 69 %). The mp was 74.5-77 OC. 'H NMR (400 MHz,

CDCl3) 6 : 3.77 (S. 3H, 0CH3), 6.23 (S. 1 H. CH, methine), 6.87-7.50 (m, 13H,

aryl). 13c NMR (400 MHz, CDCI3) 6 : 55.19 (s), 81.65 (s), 103.99 (s), 1 14.08 (s),

116.59 (s), 119.08 (s), 126.54 (s), 127.97 (s), 128.17 (s), 128.69 (s), 132.01 (s),

133.78 (s), 140.12 (s), 159.34 (s), 161.21 (s). MS (10 v) m/z = 315 (M', 3), 197

(M+-OGHGN, 1 OO), 182 (M+-c~H~ON, 36), 165 (M+-C~H~O~N, 59), 153 (M'-

C9H7O2Nl 72), 128 (22), 119 (M+-C&l~20, 21), 115 (15), 102 (13). 90 (18). 77

( M * - c ~ ~ H ~ ~ o ~ N , 14), 63 (16).

D2.6.S PREPARATION OF (4-TRIFLUOROMETHYL-4'-METHOXY-

D1PHENYL)METHYL 4"-CYANOPHENYL ETHER

This compound was synthesized using the same method that was used to

prepare the (4-methyl-4'-methoxydipiieny1)methyl 4"-cyanophenyl ether. The

yield and rnp of the ether were 1-64 g and 93.5-95.5 OC, respectively. 'H NMR

(400 MHz, CDC13) 6 : 3.78 (s, 3H, 0CH3), 6.29 (s, 1 Hl CH, methine), 6.89-7.00

(ml 12H, aryl). 13c NMR (400 MHz, CDCI3) 6 : 55.18 (s), 80.95 (s), 104.44 (s),

114.29 (s), 116.57 (s), 118.92 (s), 123.85 (q, 'JCF = 272.4 HZ), 125.65 (q. 3~~~ =

3.6 Hz), 126.75 (s), 128.14 (s), 130.08 (q, 2~~~ = 21.7 Hz), 131.16 (s), 133.85

(s), 144.27 (s), 159.62 (s). 160.77 (s). MS (1 -4 v) mfz = 383 (M', 3), 265 (M'-

0C6H4CN, 100). 250 (M'-csH70N, 4), 233 (M+-C~H~O~N, 5), 196 (M+-C~H~ONF~.

3), 181 (4), 153 (IO), 135 (M+-CI~H~NF~, 5), 119 ( ~ + - ~ 1 1 ~ q 1 0 ~ 3 , 15).

P2.7 PREPARATION OF (4-SUBSTITUTED-4'-METHOXYDIPHENYL)

METHYL-d 4"CYANO-PHENYL ETHERS

D2.7.1 PREPARATION OF (4-METHYL-4'METHOXYDlPHENYL)

METHYL-d 4"-CYANOPHENYL ETHER

(4-Methyl-4~methoxydiphenyl)rnethyl-d chloride was synthesized from 0.52 g

(2.27 mmol) of (4-methyl-4'-methoxydipheny1)methan-d-ol by following the

method described in the preparation of undeuterated and deuterated (4-

substituted-4'-methoxydiphenyl)methyl chloride section. The product was not

further purïfied after dichloromethane was removed on a rotary evaporator but it

was immediately used in the next step.

The (4-methoxy-4'-rnethy1diphenyl)methyl-d chloride was then diluted with 3

mL of distilled THF and added into a 100 rnL two necked round bottom flask

containing 0.64 g (4.54 mmol) of sodium Ccyanophenoxide and 50 mL of

distilled THF under an argon atmosphere. After the reaction mixture had

refluxed at 50 O C for three days, it was poured into a 500 mL separatory funnel

containing 200 mL of water. The product was extracted three times with 50 mL

of diethyl ether. The ether fractions were washed with 200 mL of 0.2 N sodium

hydroxide solution to removed any excess 4cyanophenol. The organic layer

was dried over anhydrous sodium sulfate and gravity filtered. After the filtrate

was concentrated on a rotary evaporator, the thick oil was purified by passing it

through a silica gel column chromatography using a 5, 10, 15, 20 % ethyl acetate

in hexane as the mobile phase. The yield yellow oil which slowly crystallized at

room temperature was 0.45 g (1 -36 mmol, 60%). The Mp was 77-79 OC.

1 H NMR (200 MHz, CDC13) 6 : 2.37 (s, 3H, CH3), 3.80 (s, 3H, 0CH3), 6.92-7.54

(ml 12H, aryl). I3c NMR (400 MHz, CDC13) 6 : 20.89 (s), 54.96 (s), 81 -1 0 (t),

103.71 (s), 1 13-90 (s), 11 6.46 (s), 11 8.96 (s), 126.40 (s), 127.95 (s), 129.23 (s),

132.07 (s), 133.58 (s), 137.04 (s), 137.56 (s), 159.15 (s), 161.13 (s). MS m/z =

330 (~',0.5), 212 (M'-OC~H~CN, IOO), 197 (M'-C~H~ON, 17), 182 (M+-C~H~OON,

I I ) , 166 ( M + - C ~ H ~ ~ O ~ N , 14), 154 (M+-c~oH~~O~N, 20), 119 ( M + - c ~ ~ H ~ ~ D O , 14).

When the 'H NMR spectrum (200 MHz, CDCI3) was recorded at a high spectrum

amplitude, a very small peak at 6 = 6.25 ppm, was observed. A calculation

based on the integration of the peaks at 6 = 6.25 and 2.37 ppm indicated that the

alcohol was 98 % deuterated at the alpha carbon.

This compound was synthesized using the procedure described above.

(4-Methoxydipheny1)rnethan-d-01, 2.00 g (9.30 mmol) and 2.62 g (18.60 mmol) of

sodium 4cyanophenoxide were used in this synthesis. After passing the product

through a silica gel column chromatography, the pale yellow oil was crystallized

in ether and hexane. The yield of purified white solid was 2.06 g (6.51 mmol, 70

%), and the mp was 78.5-81 OC.

'H NMR (400 MHz, CDCI3) 6 : 3.77 (s, 3H, 0CH3), 6.87-7.50 (m, 13H, aryl). 13c NMR (400 MHz, CDCi3) 8 : 55.15 (s), 81.22 (t), 103.99 (s), 114.08 (s), 116.57 (s),

119.08 (s), 126.53 (s), 127.97 (s), 128.15 (s), 128.68 (s), 131.95 [s), 133.78 (s),

140.05 (s), 159.34 (s), 161.20 (s). MS (10 v) m/z = 316 (M', 4), 198 (M'-

OCsH&N, IOO), 183 (M+-C~H~ON, 25), 166 (M+-C~H~O~N, 37), 154 (M'-

C9He02N, 44), 129 (13), 119 (M+-c~~H~~DO, 12), 90 (12), 77 (CsH5, 8). When the

'H NMR spectrum (400 MHz, CD&) was recorded at a high spectrum

amplitude, a very srnall peak at 6 = 6.24 pprn, was observed. A calculation

based on the integration of the peaks at 6 = 6.23 and 3.77 ppm indicated that the

alcohol was 98 % deuterated at the alpha carbon.

DIPHENYL) METHYL-d 4"-CYANOPHENYL ETHER

-' 3 T -""

chci2 THF OH CaCI2

T - - - - -

O '6%

This compound was prepared using the same method that was used in the

synthesis of (4-methyl-4'-methoxydiphenyl)methyl 4"-cyanophenyl ether.

(4-Trifluoromethyl-4'-methoxydiphenyl)methan-d-oll 1.60 g (5.65 mmol) and 1.59

g (11.30 mmol) of sodium 4-cyanophenoxide were used to prepare this

cornpound. The yield after purification was 1.35 g (3.52 mmol, 62 %). The mp

was 83-90 OC. 'H NMR (200 MHz, CDCI3) 6 : 3.79 (s, 3H, 0CH3), 6.89-7.61 (ml

12H, aryl).

MS (7.3 v) m h = 266 (M4-0C6H4CNl IOO), 251 (M+-C~H~ON, 6), 247 (6), 234

(IO), 223 (8) , 197 (M+-c~H~oNF~, 6), 182 (M+-C~H~ONF~, IO), 166 (M+-

C9H702NF3, 1 1)1 154 (M+-C&l702NF3, 23). 1 19 (M+-Cq5HloDOF3, 3), 90 (1 0).

When the 'H NMR spectrum (200 MHz, CDCI3) was recorded at a high spectrum

amplitude, a very small peak at 6 = 6.29 ppm, was observed. A calculation

based on the integration of the peaks at 6 = 6.29 and 3.79 ppm indicated that the

alcohol was 98 % deuterated at the alpha carbon.

D-2.8 PREPARATION OF UNDEUTERATED (4-SUBSTITUTED

4'-METHOXYD1PHENYL)METHYL ACETATES

~2.8.1 PREPARATION OF (4-METHOXYD1PHENYL)METHYL

AC ETATE

I

OAc

(4-Methoxydiphenyl)methanol, 1 -00 g (4.67 rnmol), was dissolved in 1 0 rnL

acetic anhydride and 2 mL of pyridine in a 25 mL round bottom flask. The

reaction mixture was refluxed over night at 100 O C under an argon atmosphere

and quenched in a 250 mL separatory funnel containing 100 mL of distilled

water. The organic compounds were extracted with three portions of 50 mL of

diethyl ether and the cornbined ether layers were washed with 100 mL of 0.1 N

aqueous sodium hydroxide solution followed by 100 mL of a 5 % aqueous

sulfuric acid solution to remove any remaining acetic acid and pyridine,

respectively. The combined ether layers were washed twice with 100 mL of

distilled water and dried over anhydrous magnesium sulfate. After gravity

filtration, the solvent was removed on a rotary evaporator. The oil was vacuum

distilled at 10 torr at 170-1 75 O C to yield 1.160 g (4.53 mmol, 97 %) of a colorless

highly viscous liquid. 'H NMR (200 MHz, CDC13) 6: 2.12 (s, 3H. CH3), 3.75 (S.

3H, CH3), 6.87 (m, 2H, aryl), 6.9 (s, AH, CH, methine), 7.31 (m. 7H, aryl) 13c

NMR (200 MHz, CDCI3) 6: 21.20 (s), 55.10 (s), 76.43 (s), 113.76 (s), 126.73 (s),

127.64 (s), 128.35 (s), 128.59 (s), 132.31 (s), 140.32 (s), 159.21 (s), 169.95 (s).

MS (high): 256.1394 (M', 23), 213 (8), 196.0888 (M+-CH~CO~H, IOO), 181 (43),

165.0718 ( C ~ ~ H ~ + , 27), 153.071 5 (Ci2Ha*, 35), 135-0448 (CsH702+, 1 O), IO5 (8),

77 (C6Hs+, 16).

~ 2 . 8 . 2 PREPARATION OF (CMETHYL-4'-METH0XYDIPHENYL)METHYL

ACETATE

(CH3C0)20 - Pyridine

10O0c

(4-Methyl-4'-methoxydiphenyl)methyl acetate recrystallized slowly in hexane

yield a white needle crystal. The mp was 80-82 OC. 'H NMR (200 MHz, CDC13)

6: 2.18 (S. 3H1 CH3), 2.37 (s, 3H, CH3), 3.80 (s, SH, CH3), 6.90 (ml 3H, aryl, and

CH, methine), 7.1 5-7.40 (ml 6H, aryl). I3c NMR (200 MHz, CDCI3) 6: 20.95 (s),

21.13 (s), 55.05 ( s ) 76.36 (s), 113.71 (s), 126.76 (s), 128.42 (s), 128.99 (s),

132.49 (s), 137.31 (s), 137.43 (s), 159.1 1 (s), 169.87 (s). MS (low): 270 (M', 1 A),

210 (M*-cH~co~H, 100), 195 (48), 181 (16), 165 (23), 153 ( 9 ) 3 5 ( 1 ) 121

(7), 105 (8), 91 (15). 84 (8), 77 ( C ~ H ~ * , 11). 69 (1 l), 57 (14), 55 (17).

~2.8.3 PREPARATlON OF (4-TRIFLUOROMETHYL-4'-METHOXY-

D1PHENYL)METHYL ACETATE

Pyridine OH -looOc

'H NMR (200 MHz. CDCI3) 6: 2.17 (s, 3H), 3.80 (s, 3H), 6.87 (m, 3H, 2 aryl, 1

methine), 7.26 (m. 2H). 7.47 (m, 2H). 7.60 (m, 2H). 13c NMR (200 MHz, CD&)

6: 20.99 (s), 55.10 (s). 75.88 (s), l l4 .Ol (s), 123.92 (q, l ~ C F = 272 HZ), 125.35 3 (4, Jc-F = 3.87 HZ), 126.97 (s), 128.72 (s), 129.13 (q, *J~-F = 32.62 HZ), 131.53

(s), 144.45, 159.56 (s), 169.74 (s). MS (Iow): 324 (M*, 13), 264 (M*-CH~CO~H.

IOO), 249 (27), 233 (13). 221 (14). 201 (6), 195 (17), 181 (6). 165 (14), 152 (15),

84 (6), 77 (csHs', 6).

P2.9 PREPARATION OF DEUTERATED (4SUBSTITUTED 4LMETHOXY-

D1PHENYL)METHYL-d ACETATE

P2.9.1 PREPARATION OF (4-METH0XYDIPHENYL)METHYL-d

ACETATE

? HCI cH$oo-N~' (O>-C*~M~ - - 1 cH2c12 CH3COOH OH CaC12 80 OC

OAc

(4-Methoxydipheny1)methyl-d-01, 0.263 g ( 1.22 mmol), was converted to

(4-methoxydiphenyl)methyl-d chloride using the hydrogen chloride gas method,

described above. After dichloromethane was removed, the chloride was

dissolved in 5 mL of glacial acetic add which contained 0.310 g (3.78 mmol) of

sodium acetate. The reaction mixture was then refluxed under an argon

atmosphere at 80 O C for 3 hrs. After the reaction mixture had cooled to room

temperature, it was poured into a 250 mL separatory funnel containing 100 mL of

distilled water and extracted three times with 50 mL of diethyl ether. The organic

layers were combined, and washed with three portions of 80 mL of distilled water

to remove any remaining sodium acetate and acetic acid and then dried over

anhydrous rnagnesiurn sulfate. The mixture was then gravity filtered and the

solvent was removed on a rotary evaporator and under vacuum for 2 hrs. The

pale yellow oil was vacuum distilled at 10 tgrr and 170-175 OC to give 0.295 g

(1.15 mmol, 94 %) of a colorless oil. 'H NMR (200 MHz, CD&) 6: 2.18 (s, 3H),

3.78 (s, 3H), 6.95 (ml 2H), 7.38 (m. 7H). l3c NMR (500 MHz, CDCI3) 6: 20.89

(s,), 54.79 (s), 75.57 (t), 1 13.55 (s), 126.52 (s), 127.43 (s), 1 28.15 (s), 128.37 (s),

132.06 (s), 140.14 (s), 158.98 (s), 169.91 (s). MS (high): 257.1 174 (M', 23). 214

(7). 1 98.1 O26 ( C ~ ~ H ~ ~ D O + , 57). 196.0886 ( C ~ ~ H ~ ~ O + , 1 OO), 1 8 1.0664 (~13~90* ,

40), 166 (25). 153 (30). 135 (IO), 1 O5 (9), 77 ( c ~ H ~ + , 20). When the 'H NMR

spectrum (500 MHz, CDCI3) was recorded at a high spectrum amplitude, a very

small peak at 6 = 6.99 ppm, was observed. A calculation based on the

integration of the peaks at S =6.99 and 6.95 ppm indicated that the alcohol was

99 % deuterated at the alpha carbon'.

METHYL-d ACETATE

(4-Methyl-4'-methoxydipheny1)rnethyl-d acetate recrystallized çlowly in

hexane yield a white needle crystal. The mp was 76-79 OC. 'H NMR (200 MHz,

CD&) 6: 2.21 (S. 3H, CH3), 2.41 (S. 3H, CH3), 3.83 (s, 3H, CH3), 6.95 (m. 2H,

aryl), 7.22 (m, 2H, aryl), 7.36 (m. 4H1 aryl). 13c NMR (200 MHz, CDCI3) 6: 20.94

(s), 21.10 (s), 55.03 (s), 75.45 (t, JcD = 21 Hz), 113.71 (s), 126.76 (s), 128.41

(s), 128.98 (s), 132.44 (s), 137.30 (s), 137.37 (s), 159.12 (s), 169.83 (s). MS

(Iow): 271 (M', 14). 210 (M+-cH~co~~, IOO), 195 (46), 8 ( I l ) 6 7 ( 4 ) 166

(14), 165 (9), 154 (15), 153 (1 l ) , 135 (6), 86 (20), 84 (31), 77 (C6Hs+, 6), 51 (14).

' In another reaction where îhe alcohol was reacted with acetic anhydride and pyridine at 1 10°C over night the hydrogen at the alpha carbon was up to 19 % scrambled.

P2.9.3 PREPAKATION OF (4-TRIFLUOROMETHYL-4LMETHOXI-

D1PHENYL)METHYL-d ACETATE

1 H NMR (200 MHz, CDCb) 6: 2.18 (s, 3H), 3.80 (S. 3H), 6.90 (m, ZH), 7.30 (m,

2H), 7.50 (m, 2H), 7.63 (m, 2H). NMR (200 MHz, CDC13 6: 21 -01 (s), 55.1 1

(s), 75.52 (t, Jc-D = 23 Hz), 1 14.00 (s), 123.95 (q, JC.F = 274 HZ), 125.35 (q, 3 ~ C - ~

= 3.66 Hz), 126.96 (s), 128.70 (s), 129.79 (q, 2 ~ C . ~ = 33.34 HZ), 131.44 (s).

144.35. 159.53 (s), 169.75 (s). MS (Iow): 325 (M+, 14), 264 (M+-cH~co~D, 100).

249 (24), 234 (Il), 221 ( I l ) , 195 (14), 182 (6), 165 (10). 154 (13), 86 (13), 84

(21 ), 77 ( ~ 6 ~ 5 ' . 6).

APPENDIX

1 DOUBLE EXPONENTIAL DECAY

rate expression for the equation above:

Arrange equation 1 for B to get equation 4

differentiate equation 4 with respect to time t to have equation 5

Substitute equations 4 and 5 into equation 2 leading to equation 6

rearrange equation 6 to give equation 7

A + (kl + h + k3)À + k h A - - O [71

According to the theoiy of First Order Linear Differential ~ ~ u a t i o n ~ ' , equation 7

has a solution such as equation 8, and with a character equation 9

A - - + *2eA2t P l

where

-m il K h = 2 ; and A = (-m)2-4n; m = (kl + k2+ k3); and n = klk3

Boundary t=O, A. = O, then A1 = -A2, and substituted into equation 9, and

rearrange to give equation 10

Differentiate equation 10 to give equation 1 1

substitute equations 10 and 1 1 into equation 4 to have

Boundary t=O, B=Bo and rearrange equation 12 to become

titute equation 13 into 12 and rearrange to become

B - (kl + hi) e12t (kl + hl) - - - Bo (A2 - 1.1) (A2 - 11)

apply into the reaction between R' and B i

l3+1 - - - !kion + hiIe~2t - (km + b) IR+] 0 (hz - hl) (hz - hi)

2) PERCENT OF BOND FORMATION IN TRANSITION STATE

Consider a following equilibrium reaction:

+ Nu-

where k is the rate constant, and subscripts f and r are referred to foward and

reverse reactions. The rate constant relates to Boltzmann's (k), Planck's (h) and

gas (R) constants, absolute temperature (T), and activation energy (AG? by

equation 18

Secondary alpha deuterium KIE is defined

Secondary alpha deuterium ElEs for the forward (f) and reverse (r) reactions in

equation 17 are calculated

But

Therefore

Percent of bond formation in the transition state of the fontvard reaction is

calculated

Ethere is a h c t i o n f(xr, xz, ... xn), then the error is determimed Af = - n

a) Error calculation for KIE:

6f - but - 8f and - 1 = -kH7 6 k ~ - KD 6 k ~ k~

Substitute t ,.

rearrange

' See John Andraos J. Chem. Ed., 1996.73,150

b) Error calculation for % bond formation in transition state

Let x = Log KIE, y = Log EIE and f(x,y) = 100 (x/y) then

s (100+) and =

6~

= Log KIE

= Log EIE

AX = ' a(KIE) 2.303 KIE

4) THE 'H AND "C NMR, MS AND IR SPECTRA

4.1) The 'H and 13c NMR and MS spectra of diawlmethyl chlorides.

a) The 'H and 13c NMR (200 MHz, CDCI3) and MS spectra of

undeuterated and deuterated (4-rnethoxydiphenyl)rnethyl chlorides.

iio - $00 d i ~i 6hm

?ile Text rThuy Van Pham BHCl

=9

z e: ent : q: - - . - + : - L1 P i l e Text:Thuy Van P h a m HDCl

1

154

84 166

15 183 10

63 77 8 99 110 129 13 5 2 .OES O 1 O *OEO

O 8 0 1 0 1 0 1 0 m/ z

b) The 'H and I3c NMR (200 MHz. CDC13) and MS spedra of

undeuterated (4-methyl-4'-m-.thoxydiphenyl)methyl chloride.

File:TGBm 1dent:ll Acq:21- *6750 - . . 1 - 70s EI+ Magner BpI:4751136 TIC:22244648 F1ags:HALL File Text:Thuy Van Pham MeK-Cl

c) The 'H and ' 3 ~ NMR (200 MHz, CDC13) and MS spectra of

undeuterated and deuterated (4-trifluorornethyl-4'-methoxydiphenyl)

methyl chlorides.

TMS

Frle: - 3 6 . 5 0 . . + 0 ° w 7 5 0 1 - 70s EI+ mgnet BpI:1334906 TIC:5235454 F1ags:HALL File Text:Thuy Van Phm CFD-Cl

2 6

d) The 'H and l3c NMR (200 MHz, CD&) spedra of undeuterated

(3,4'-dimethoxyphenyl)methyl and chloride .

4.2) The 'H and 13c NMR and MS s~ectra of diawlrnethanols

a) The 'H and ' 3 ~ NMR (200 Mhz, CDC13 and MS spectra of

(3.4-dimethoxyphenyl)methanol.

I " ' ' l ' ' ' ' I ' ' - . l ~ . ~ L ~ ~ ~ L r L i ' ~ i ~ ~ . ~ ~ , ~ r r l , . , i ~ ~ i . . l l 7

. b I I ,

w 5 4 1 - - zm Y Y.? ILI

M l 1 1 1 1 xl @d-9 3-MIR-95 lB:Q8*8:88:22 78-2595 E l - - I=4.1v H A ht:I I IXlELMN Sys:LREI H M : T .MN PHRR 3M-OH PT= 80 CaL : 1ç58758 MSS:

b) The 'H and I3c NMR (200 Mhz, CDCI3) and MS spectra of undeuterated

and deuterated (4,4'-dimethoxyphenyl)methanols

Acnt : iiCCLELLflN Sys4REI HMR- 34891000 PT= 8' CaL:lS58758 MISS: 135

c) The 'H and 13c NMR (200 and 400 Mhz, CDCI3) and MS spectra of

undeuterated and deuterated (4-rnethyl-4'-rnethoxydiphenyl)methanols

Rcnt . HCLELLRNO Sys. LREI HISR Iô225030 PT- Bo C3L LSSk??SCi URSS 135

b

) ' I i , . 1 . " 8 r i , . . , , S . , . , . , , r i , 7

*

A I ' I ' < - 5 5 3' C ! u O PPM

m.5 29.5 I C I

6.7 44-4 .! fi

EOC1828t3 xl Bgd=l S-OCT-94 10~41-0:80:06 78-258s €1- 8pH=0 ï=6 .Bu H a 4 TIC=28S224000 Rcnt:fiCLELLRHO Sys:LREI HRR : 44272808 THUY VRN PHAR REOOH PT- e0 CAL: lSS875fl HASS : ' X 1 'O

212

. . . . --

s'a 150

d) The 'H and NMR (200 and 400 Mhz, CDCI3) and MS spectra of

undeuterated and deuterated (4-methoxydiphenyl)methanols

ras

THUY URN PHRn CF30H ' X I .O

:O2 +O134 ~ a l : 1 ~ 5 G p - Pile Text:Thuy Van Pham CPD-OH

1 :.

60 :

55

5 O

45

40

3 5

3 O,

145 266

60 à0 100

4.3) The 'H and I3c NMR 1200 Mhz. CDC13. MS and IR (powder mixed with KBr,

com~ressed into a thin film) spectra of 4-methvl-4'-methoxvbenzophenone

and 4-trifluoromethvl-4'-methoxybenzophenone.

TMS

ORZlBl7t2 xl Bgd=l 3-OCT-94 18 : 53-8-08 :%4 78-2585 CI- Bgil=O 1=7.Bu Hn=0 TiC=S635620@@ flcnt -RCLELLRHO Sys: LRE [ HRR 45598808

PT= 0' CaL ,155B758 ~ A S S 135

TMS

o f l z t a ~ ~ r i 3 x 1 B C J ~ = ~ 3-OCT-94 L L ~83-8 .80-53 70-258s €1- BpR=0 f=l .?u Hm=@ TIC=34881U88 Acnt - ~ C L E L L ~ ~ N O Sys:LREI HHR : 1 1224880 THUY VAN PHfiH fF3CO PT= 8' CaL ; 1SS8758 flRSS - 135 - x 1 * 0

4.4) The 'H and I 3 c NMR and MS spectra of undeuterated and deuterated

(4-substituted-4'-methoxydiphenvl)methvI 4"-cvanophenyl ethers.

a) The 'H and 13c NMR (200 MHz, CDC13) spectra of undeuterated

(3.4'-dimethoxyphenyl)methyl 4'kyanophenyl ethers.

b) The 'H and I 3 c NMR (200 and 400 MHz, CDC13) and MS spectra of

undeuterated and deuterated (4-rnethyl-4'-methoxydiphenyl)methyl

4"-cyanophenyl ethers.

c) The 'H and l3c NMR (200, 400 MHz) and MS spectra of Undeuterated

and deuterated (4-methoxydiphenyl)methyl 4"-cyanophenyl ethers.

flcn t :tiCLELLfiNU Sqs : LREI HnR : 65534808 PT= 0' Cal :lSSB7SB lifiSS - 197

THUY VflN PHRM HOH - X I 'O

55

90

85

80

7s

d) The 'H and 13c NMR (200 and 400 MHz, CDC13) and MS spectra of

undeuterated and deuterated (4-trifluoromethyl-4'-methoxydiphenyl)methyl

4'kyanophenyl ethers.

CLIL~CUJIIO XI Üga=tc i 4-HUG-96 09 :58*8:88 331 78-258s CI- B p M I=l.lv Hn=0 TiL=28524@08 k c t :PltLiLLRHO Sys: LRE 1 THUY URH PHRn CFHH - x i * O PT= eO C ~ L - ~ S S ~ ~ S B

4.5) The 'H and 13c NMR and MS spectra of undeuterated and deuterated

J4-substituted-4'-methoxydiphenylhnethvl acetates.

The 'H and 13c NMR (200 MHz, CDCI3) spectra of undeuterated and

deuterated (4-methy-4'-methoxydiphenyi)rnethyl acetates.

, . , m . , . . r s , . , . . n . , , , , , . .

7 E: 5 ) " ' r " ' 41 3 2 ! PPM . ' ' i uu u

66.4 31.4 P- 8 F 2 y 32.2

LO.

I

TMS

LOO

95

90

85

80

75

7 0

65

1 . dE5 5 5 1.3E5

50 1.2E5

45 195.2 1 . O E 5

4 O 9.384

3 5 8.2E4

3 0 84.0 7.OE4

25 5.884

2 0

I I , / 5 .?E4

15: 1 5 4 . 1 271-2 3. SE4 101 182.1

165.1 2.334

228.2 1.2E4

O . OEO 210 260 2ko 2~ 3,,0 m/ 2

b) The 'H and 13c NMR (200 and 500 MHz, CDCI3) spectra of undeuterated

and deuterated (4-methoxydiphenyl)methyl acetates.

TMS F

?ile T e x t :Thw Van Pham HHAC

TMS

c) The 'H and 13c NMR (500 MHz, CDC13 spectra of deuterated

(4-methoxydipheny1)methyl acetate show the effect of hydrogen

scramble at methine carbon.

TMS

d) The 'H and 13c NMR (200 MHz, CD&) spectra o i undeuterated and

deuterated (4-trifluorornethy-4'-rnethoxydiphenyl)methyl acetates.

1dent:ll ~cq:19--8 10:16:28 +0:26 Cal:1~56750 - 1 'OS EI+ Magnet Bpf:69048 TICt335986 l? lags :HAL~ pile Text:?

264.2 ,6.9E4

6.6E4

6.204

5.9E4

5.5E4

s.2m 4.8E4

4. SE4

C.lE4

3.8E4

3 . SE4

3 - 1E4

2.8E4

2.4E4

2,134

1.7E4

90 '3 8 5

8 0

7 5

70

6 5

6 O

55

50

45

4 O

3 5

3 0

2 5

2 O1 84. O

153 1 5 4 . 1 195. 2 325.2

10: 165.1 221.1

234.1

I , , 2ko 2Qo 3b0 3S0 360

249.1

1.4E4

S.. OL4

6.9E3

3.5E3

O. OEO m/ z

REFERENCES

1 Hughes, E. D.; Ingold, C. K.; Patel, C . S. J. Chem. Soc. 1933, 526.

Winstein, S.; Clippinger, E.; Fainberg, A. H.; Heck, R.; Robinson, G. C. J. Am. Chem. Soc. 1956, 78, 328.

3 Hartshom, R. S. Aliphatic Nucleophilic Substitution, Cambridge University Press, Cambridge, 1973; page 12.

4 Glasstone S.; Laidler K.; Eyring H. The Theory of Rate Processes. McGraw Hill, New York, NY., 1941.

Eyring, H.; Lin, H. S.; and Lin, M. S . Basic Chernical Kinetics, Wiley-Interscience. John Wiley & sons, New York, N'Y., 1980; pages 242.

Kirsch, J. F. Isotope Eflects on Enryme-CrrtalyzedReactions, Cleland, W . W.; O'Leary, H. M.; Northrop, B. D., Editors, Universiiy Park Press, Baltimore, MD., 1977; pages 3 and 100.

7 Melander, L.; Saunders, W. H., Jr. Reaction rates of Isotopic Molecules; Wiley- Interscience, John Wiley & sons, New York, NY., 1980; pages 26 and 140.

Westaway, K. C. Tetrahedron Leu. 1975,4232.

9 Atkins, P. W. Physical Chemisîry, second Ed., W . H. Freeman and Company, San Francisco, CA., 1982; page 703.

10 Waszczylo, Z. M. Sc. Thesis, Laurentian University, Sudbury, Ontario, 1981; page 11.

I I Atkins, P. W. Physical Chernistry, second Ed., W . H. Freeman and Company, San Francisco, CA., 1982; page 696.

l 2 Melander, L.; Isotope Eficts on Reaction Rates, Ronald Press, New York, NY., 1960; page 19.

13 Melander, L.; Saunders, W. H., Ir.; Reaction rates of Isotopic Molecules; Wiley- Interscience, John Wiley & sons, New York, NY., 1980; pages 20-26.

l4 Streitwieser, A., Jr.; Jagow, R. H.; Fahey R C.; Suzuki, S. J. Am. Chem. Soc. 1958, 80, 2326

l 5 Bartell, L. S. J Am. Chem. Soc. 1961,83,3567.

16 Joly, H. A.; Westaway, K. C. Cm. J. Chem. 1986,64, 1206.

17 Westaway, K. C. and Ali, S. F. Can J. Chem. 1979,57, 1354.

'* Hamrnond, G. S.J. Am. Chem. Soc. 1955,77,334.

l 9 Leffler, E. J.; Grunwald, E. Rates and Equilibria of Organic Reactions Wiley: New York, 1963; page 26.

20 Collins C. J.; Bowman, N. S. Isotope Effects in Chemical Reactions, ACS Monograph 167; Van Nostrand Reinhoid Co. 1970.

21 Shiner, V. J., Jr.; Dowd, W. J Am. Chem. Soc. 1971, 93, 1029.

7 7 -- Collins C. J.; Bowrnan, N. S. Isotope Effects in Chemical Reactions, ACS Monograph 167; Van Nostrand Reinhold Co. 1970; page 1 O6 and references cited. Qhiner, V. J., Jr.; Buddenbaurn, W. E.; Murr, B. L.; and Lamaty, G. J. Am. Chem. Soc. 368, 90,4 18.

Shiner, V. J., Jr.; Rapp, M. W. J. Am. Chem. Soc. 1968, 90, 7 171.

%unton, C. A.; Watts, W. E.; Carrasco, N.; Davoudzadeh, F. J. Chem. Soc. Perkin Trnns

2 1980, 1520.

' 5 Collins C. J.; Bowman, N. S.; Isotope Effects in Chemical Reactions, ACS Monograph 167; Van Nostrand Reinhold Co. 1970; page 109.

26 Mayr, H.; Schneider, R.; Schade, C.; Bartl, J.; Bederke, R. J. Am. Chem. Soc. 1990, 112,4446.

27 Banoo, F.; Stewart, R. Can. J. Chem. 1969,47,3199.

l8 Mocek. M. M.; Stewart, R. Can. J. Chem. 1963,41, 1641.

l9 McClelland, R. A.; Banait, N., Steenken, S.; J. Am. Chem. Soc. 1989, 1 11,2929.

3 O McClelIand, R. A.; Kanagasabapathy, M. V.; Banait, S. N., Steenken, S. J. Am. C'hem. Soc. 1989, 1 1 1,3966.

'' McClelland, R. A.; Kanagasabapathy, V. M.; Steenken, S. J. Am. Chem. Soc. 1988, 110,6913-6914.

32 Bartl, J.; Steenken, S.: Mayr, H.; McClelland, R. A. J. Am. Chern. Soc. 1990, 1 12' 69 18.

33 Deno, N. C.; Jaruzelski, J. J.; Schriesheirn, A. J. Am. Chem. Soc. 1955,77,4044.

34 McClelland, R. A.; Banait, N., Steenken, S.; J. Am. Chem. Soc. 1986, 108, 7023.

35 McClelland, R. A. Tetrahedron 1996, 52,6823.

j6 N ~ g g ~ l e , J. H. Physical Chemistry on a Microcornputer, Little, Brown and company, Toronto, On., (1985), page 65.

3 7 Bartl, J.; Steenken, S.; and Mayr, H. J. Am. Chern. Soc. 1991, 1 13,7106.

" Bathgate, R. H. and Moelwyn-Hughes, E. A. J. Chem. Soc. 1959,2642.

j9 Parker, A. J. Chem. Rev. 1969,69, 1 and references cited there in. Parker, A. J. and Brody, D. J. Chem. Soc. 1963,4061.

'O Tanaka, K.; Mackay, G. L; Payzant, J. D. and Bohrne, D. K. Can. J. Chem. 1976,54, 54?. B o h e , D. K. and Mackey, G. 1. J. Am. Chern. Soc. 1981, 103,978-981.

4 I McClelland, R. A.; Kanagasabapathy, M X ; Banait, S. N.; and Steenken S. J. Anz. Chern. Soc. 1992, 1 14, 18 16.

42 Deno, N. C.; Janizeiski, J. J.; Schriesheim, A.; J. Am. Chem. Soc. 1955, 77,4044, method C.

43 Lowry, T. H.; Richardson, K. S. Mechanisrn and Theory in Organic C h e r n i s ~ ; Third Edition, Harper & Row, Publisher, New York 1987; pages 267,268.

44 Kennedy, J. H. Anabtical Chemistry Principles; Harcourt Brace Jovanovich, Publishers, London, Sydney, Toronto 1984; page 389,398.

4 5 Schneider, R.; Mayr, H., Ber. Bunsenges. Phys. Chem. 1987, 9 1 , 1369.

C6 3artlctt, P. D.; Nebel, R. W. J. Am. Chem. Soc. 1940, 62, 1345.

57 Bowers, A.; Halsall, T. G.; Jones, E. R. FL; Lemin, A.J. J. Chem. Soc. 1953,2548.

" Pham, T. V.; M. Sc. 7%esis, Laurentian University, Sudbury, Ont. 1993; page 143 and references cited there in.

'' Finizio, N . and Ladas, G.; An Introduction ro Urdinary Differentiai equations. with Dzrerence Equations, Fourier Series, and Partial dgferentinl equations, Wadswoah, Publishing Company, Belmont, California. A division of Wadswoah, Inc., U.S.A., 1982, page 87.