chem 450 final report

Investigation of Methods of Oxidative Aromatization of 1,3,5-

trisubstituted Pyrazolines to Corresponding 1,3,5-trisubstituted

Pyrazoles

Kevin Schindelwig Francaƚ

ƚCHEM 450 Research Laboratories, Department of Chemistry, Roger Williams University,

1 Old Ferry Rd., Bristol, RI 02809, United States

ABSTRACT: This study was an investigation of previous reported methods for the oxidative

aromatization of 1,3,5-trisubstututed pyrazolines to synthesize the corresponding pyrazole of the

previously synthesized pyrazoline inhibitor 3-(4-chlorophenyl)-5-phenyl-1-(4-

chlorophenylcarboxamide)-2-pyrazoline 1. Microwave conditions were also utilized to improve

on some of the oxidative methods. Overall the successful synthesis of 3-(4-chlorophenyl)-5-

phenyl-1-(4-chlorophenylcarboxamide)-2-pyrazole 2 was probably achieved only with the

oxidative reagents, DDQ indicated by formation of new singlet peaks at 6.8, 6.25 ppm in 1H

NMR analysis.

INTRODUCTION

Pyrazoles are important nitrogen heterocycles

that have relevance in pharmaceuticals.

These compounds show a broad spectrum of

pharmacological activities such as

antibacterial, antihyperglycemic, anti-

inflammatory, analgesic and hypoglycemic

and sedative-hypnotic activities.1 We are

interested in synthesizing pyrazoles due to

their probable use as antiamoebic agents.

Several 1,3,5-trisubstitued pyrazolines have

been synthesized by Dr. Rossi’s Research

Lab to be investigated as antiamoebic agents,

and it has been reported that pyrazolines can

be oxidized to pyrazoles utilizing several

different reaction conditions. These reaction

conditions were used to attempt the oxidation

of the pyrazolines from Dr. Rossi’s research

to the corresponding pyrazole.

Ananthnag, et al. utilized ferric

chloride as a catalyst for the oxidation of

pyrazolines. A 10 mL screw-cap tube was

charged with pyrazoline (1 equiv.), acetic

acid (2 mL), and FeCl3 and the mixture was

stirred for 6-10 h at 120˚C. Ananthnag, et al.

reported high yields from 89-97% for the

oxidation of the pyrazoline derivatives used

in the study. The pyrazoline compounds used

in this research were 1,3,5-trisubstituted

pyrazolines mostly with substituted phenyl

substitutions. The substituents on the phenyl

groups were varying electron donating and

withdrawing groups. Electron withdrawing

groups, nitro- and halo- substituents gave

good to excellent yields but took longer time

to completely react, 8-10 h.2

The major difference between the

pyrazolines used in the Ananthnag, et al.

study and the pyrazoline used in this study is

the substituent located on the nitrogen of the

heterocycles in the 1 position. Rather than an

aromatic substituent directly bound to the

nitrogen of the pyrazoline the pyrazoline

derivative in this study has a carbamoyl

substituent with a phenyl group on the

nitrogen of the carbamoyl. This electron

withdrawing group directly bound to the

heterocycle of the pyrazoline may affect the

reactivity of the pyrazoline in the oxidation

reaction and result in varying results

compared to those reported by Ananthang, et

al.

The faculty of science of the

Chemistry department at Kobe University

successfully converted 1,3,5-trisubstituted

pyrazolines to the corresponding pyrazoles

using a catalytic amount of Pd/C in acetic

acid. After screening a variety of reaction

conditions it was determined that acetic acid

was an essential solvent for the effective

oxidative conversion of pyrazolines to

pyrazoles. 1,3,5-triphenylpyrazoline with 20

wt % 10% Pd/C in acetic acid at 80◦C for

6.5h produced the 1,3,5-triphenylpyrazole in

86% yield.3

The pyrazolines used in the Kobe

University study had phenyl substituents

located on the nitrogen of the heterocycles,

and phenyl or substituted hexyl substituents

on the 3,5 positions of the heterocycles. The

pyrazoline derivative in this study has a

substituted carbamoyl substituent on the

nitrogen of the heterocycle, a chlorinated

phenyl substituent in the 3 position and

phenyl in the 5 position of the heterocycle.

The fact that the electron withdrawing

carbamoyl is directly bonded to the

heterocycles rather than on a phenyl group on

the heterocycle can change the reactivity of

the pyrazoline.

Azarifar, et al. also researched a

microwave assisted method of aromatization

oxidation of 1,3,5-trisubstituted pyrazolines,

with Bi(NO3)3 • 5H2O as an oxidizing agent

in acetic acid. It was found that under

microwave irradiation Bi(NO3)3 was an

effective oxidant resulting in high yields of

the pyrazole product, 92-99%, with a short

reaction time (35-60 s). The pyrazoline

derivatives in these reactions had a phenyl

substituent located on the nitrogen of the

heterocycles and varying electron

withdrawing and electron donating groups on

the 3,5 sites of the heterocycles.4

The

pyrazoline in this study has an electron

withdrawing carbamoyl directly bound to the

nitrogen of the heterocycle unlike the

pyrazoline derivatives used by Azarifar, et al.

which had a phenyl substituent.

Kumar et al. conducted a study on the

electrochemistry and optical properties of

1,3,5 trisubstituted pyrazolines and pyrazoles.

In this study Kumar et al. synthesized first

pyrazolines and then using 2,3-dichloro-5,6-

dicyano-1,4-benzoquinone (DDQ) as an

oxidant in dry dichloromethane reacted the

pyrazoline to the corresponding pyrazole.

After 8-9 h of reaction at room temperature

the study reported yields of 49-69%.5

The pyrazolines oxidized by Kumar et

al. were 3-ferrocenyl pyrazolines with a

sulfonamide substituent bonded to the

nitrogen of the heterocycles. The pyrazoline

derivatives studied by Kumar et. al had more

complex substituents compared to 3-(4-

chlorophenyl)-5-phenyl-1-(4-

chlorophenylcarboxamide)-2-pyrazoline used

in this study which has a carbamoyl

substituent in the place of a sulfonamide and

chlorinated phenyl substituent on site 3 of the

heterocycle rather than a ferrocene

substituent.

EXPERIMENTAL SECTION

General Information. All solvents (except

for chromatography mixed solvents) and

reagents were of reagent-grade quality.

Oxidation of 3-(4-chlorophenyl)-5-phenyl-

1-(4-chlorophenylcarboxamide)-2-

pyrazoline (1) by FeCl3. In a 5 mL glass

conical vial equipped with a magnetic stirring

bar were added 143.2 mg (0.35 mmol)

pyrazoline 1, 5.5 mg (0.034 mmol) FeCl3, 1

mL of acetic acid. Vial was equipped with a

reflux condenser left open to air and the

reaction mixture was heated at 120˚C with

stirring. The reaction was monitored by Thin

Layer Chromatography (TLC) (1:1 hexane:

ethyl acetate). The reaction was removed

from heat after 11 hours of reaction and left

to cool. Reaction mixture was neutralized

with a saturated solution of sodium carbonate

and product was extracted 3X with 10 mL

portions of ethyl acetate. Washed organic

layer 3X with brine and then dried over

anhydrous sodium sulfate. Product was

isolated and sodium sulfate removed by

vacuum filtration and ethyl acetate layer with

product was left to evaporate in hood over

the week. Residual ethyl acetate was

removed with the rotary evaporator to afford

a pale yellow crystalline solid.



pyrazoline (1) by FeCl3 under Argon

In a 5 mL glass conical vial equipped with a

magnetic stirring bar were added 143.4 mg

(0.35 mmol) pyrazoline 1, 14 mg (0.086

mmol) FeCl3, and reagents were thoroughly

mixed and 1 mL of acetic acid was added.

Vial was equipped with a reflux condenser

and placed under an argon balloon and the

reaction mixture was heated at 120˚C with

stirring. The reaction was monitored by TLC

(1:1 hexane: ethyl acetate). The reaction was

removed from heat after 11 hours of reaction

and left to cool. Reaction mixture was

neutralized with a saturated solution of

sodium carbonate and product was extracted

3X with 10 mL portions of ethyl acetate.

Washed organic layer 3X with brine and then

dried over anhydrous sodium sulfate. Product

was isolated and sodium sulfate removed by

vacuum filtration and ethyl acetate layer with

product was left to evaporate in hood over

the week. Residual ethyl acetate was

removed with the rotary evaporator to afford

a pale yellow crystalline solid.

Oxidation aromatization of 3-(4-


chlorophenylcarboxamide)-2-pyrazoline

(1) by 10%Pd/C. A 25 ml round bottom

flask was charged with 127.6 mg (0.311

mmol) pyrazoline 1, 10 mL glacial acetic

acid, and 25.3 mg (0.238 mmol) of 10%

Pd/C. The flask was equipped with a reflux

condenser and the reaction mixture heated to

80˚C. The reaction ran for 6.5 hr and

monitored by TLC (1:1 hexane: ethyl

acetate). 10% Pd/C was removed by filtration

through Celite and filtrate was neutralized

with a saturated sodium bicarbonate solution.

The neutralized filtrate was extracted 3X

with 40 mL ethyl acetate. Ethyl acetate

fractions were combined and dried over

anhydrous magnesium sulfate. Magnesium

sulfate was removed by vacuum filtration.

The dried organic phase containing the

desired product was rotary evaporated to

afford a pale orange, yellow oil residue.




(1) by DDQ Prepared a solution of 68.4 mg

(0.30 mmol) DDQ in 10 mL of

dichloromethane in a 25 mL Erlenmeyer

flask. In a separate flask equipped with

magnetic stir bar, dissolved 102.7 mg (0.25

mmol) pyrazoline 1, in 20 mL of dry

dichloromethane and stirred at room

temperature. To the stirring pyrazoline

solution the DDQ solution was added

dropwise and the stirring reaction solution

was sealed and flushed with argon gas, and

kept under argon gas. The reaction was left to

stir at room temperature under argon for a

week. The reaction was monitored by TLC

(1:1 hexane: ethyl acetate). The reaction

mixture was filtered through a pad of neutral

alumina using 2% methanol in chloroform as

an eluent. The filtrate containing the pyrazole

product was recrystallized with hot

dichloromethane to yield the analytically

pure product, a dark orange brown solid. The

final product was analyzed by 1H NMR.




(1) by Bi(NO3)3 • 5H2O To a microwave vial

added 291.6 mg (0.60 mmol) Bi(NO3)3•

5H2O, 410.3 mg (1 mmol) pyrazoline 1, and

5 mL glacial acetic acid and small magnetic

stirring bar. The reaction mixture was

thoroughly mixed and then irradiated by

microwave at 150˚C for 5 minutes. TLC of

reaction mixture in 9:1 hexane: ethyl acetate

was obtained. The reaction was quenched

with a 5% solution of sodium bicarbonate

and extracted 2X with 10 mL of

dichloromethane. Dichloromethane fractions

were combined and dried over anhydrous

magnesium sulfate. Magnesium sulfate was

removed by vacuum filtration.

Dichloromethane was evaporated off

resulting in a yellow flaky solid.

1H NMR analysis indicated lack of

oxidation of pyrazoline to pyrazole so

reaction was conducted again but irradiated

for 10 minutes. Charged a microwave vial

with 291.3 mg (0.60 mmol) Bi(NO3)3•5H2O,

410.1 mg ( 1 mmol) pyrazoline 1, and 5 mL

glacial acetic acid and a small magnetic stir

bar. The reagents were thoroughly mixed and

irradiated by microwave at 150˚C for 10

minutes. TLC of reaction mixture in 9:1

hexane: ethyl acetate was obtained. The

reaction was quenched with a 5% solution of

sodium bicarbonate and extracted 2X with 10

mL of dichloromethane. Dichloromethane

fractions were combined and dried over

anhydrous magnesium sulfate. Magnesium

sulfate was removed vacuum filtration.

Dichloromethane was evaporated by rotary

evaporator, and a yellow flaky solid

remained.

Chromatography of Bi(NO3)3•5H2O

reaction product. Isolated product from 10

min. microwave oxidation reaction with

Bi(NO3)3•5H2O was absorbed into 1.7 g of

silica gel, with use of minimal

dichloromethane to transfer contents of vial

into 100 mL round bottom flask; solvent was

evaporated by rotary evaporator to absorb

product into silica. Flash chromatography

column prepared by blocking end with cotton

and 1 cm layer of sand and filling with slurry

of 65 g of silica gel in toluene. Silica gel was

packed by collecting excess toluene until

meniscus was at top of silica. Evaporated

reaction mixture absorbed into silica was

added on top of packed silica column

followed by additional 1 cm layer of sand.

Crude product was separated from reaction

mixture by eluting the column with toluene.

Elution was accelerated by gently applied air

pressure to top of column, and 5 mL fractions

were collected in separate 12 mL test tubes.

37 fractions were collected and analyzed by

TLC on precoated glass-backed TLC plates

evolved in 1:1 hexane: ethyl acetate and

visualized under a UV lamp (254 nm).

Product Isolation of Bi(NO3)3•5H2O

reaction. Fractions with TLC Rf values close

to 0.85 (fractions 11-14) and fractions with

TLC Rf values close to 0.75 (fractions 26-36)

were combined and fractions with multiple

spots (fractions 15-25) were combined and

solvent was rotary evaporated off. The final

product from fractions 11-14 was an orange

oil residue, the product from fraction 15-25

was a mixture of yellow and white flaky

solid, and fraction 26-36 yielded a yellow

crystalline solid. Each sample was analyzed

by 1H NMR.

Nuclear Magnetic Resonance Spectra. 1H

NMR spectra recorded on a 300 MHz

spectrometer. 1H NMR spectra were

referenced to CDCl3 (δ 7.26 ppm). Peak

multiplicities are designated by the following

abbreviations: s, singlet; bs, broad singlet; d,

doublet; t, triplet; q, quartet; m, multiplet; ds,

doublet of singlets; dd, doublet of doublets;

td, triplet of doublets. All signal shifts, δ,

reported in ppm.

Results

3-(4-chlorophenyl)-5-phenyl-1-(4-


White crystalline solid. 1H NMR (300 MHz,

CDCl3) δ 8.07 (s, 1H), 7.65 (d, 2H), 7.44 (m,

2H), 7.25 (m, 2H), 5.57 (dd, 1H), 3.81 (dd,

1H), 3.22 (dd, 1H). The three dd peaks

located at δ 5.57, 3.81, 3.22 ppm are

diagnostic peaks of the pyrazoline derivative

that are lost when the pyrazoline is oxidized

due to increased conjugation of the nitrogen

heterocycle of the pyrazoline. The pyrazole

will have a diagnostic singlet (s, 1H) further

downfield at around 6.5 ppm.



pyrazoline (1) by FeCl3

TLC Rf, (1:1 hexane: ethyl acetate) : 1.5hr

(pyrazoline = 0.75; co-spot & reaction =

0.59, 0.25), 4 hr (pyrazoline = 0.81; co-spot

& reaction = 0.69, 0.36), 8.5 hr (pyrazoline =

0.77; co-spot & reaction = 0.69. 0.36) 9.5 hr

(pyrazoline = 0.81; co-spot & reaction: 0.67,

0.37). Final product a pale yellow crystalline

product of mass 0.169 g. 1H NMR (300 MHz,

CDCl3) δ 8.07 (s, 1H), 7.65 (d, 2H), 7.43 (m,

2H), 7.25 (m, 2H), 5.59 (dd, 1H), 3.81 (dd,

1H), 3.23 (dd, 1H), 2.41 (s, 2H).



pyrazoline (1) by FeCl3 under Argon

TLC Rf , (1:1 hexane: ethyl acetate): 1 hr

(pyrazoline = 0.70; co-spot & reaction =

0.47, 0.23), 4 hr (pyrazoline = 0.77, co-spot

& reaction = 0.63, 0.31), 7.5 hr (pyrazoline =

0.78, co-spot & reaction = 0.66, 0.43), 9 hr

(pyrazoline = 0.77, co-spot & reaction = 0.61,

0.39). Final product a pale yellow crystalline

solid of mass 0.3 g. 1H NMR (300 MHz,

CDCl3) δ 8.07 (s, 1H), 7.65 (d, 2H), 7.43 (m,

2H), 7.26 (m, 2H), 5.59 (dd, 1H), 3.82 (dd,

1H), 3.24 (dd, 1H), 2.42 (s, 2H).




(1) by 10%Pd/C

TLC Rf , (1:1 hexane: ethyl acetate): 10, 20,

30 min. (reaction = 0.89, 0.80, 0.66), 1 hr

(reaction = 0.64), 2 hr (reaction = 0.76, 0.66),

6 hr (reaction = 0.66). Final product a pale

orange, yellow oil residue of mass 0.1 g. 1H

NMR (300 MHz, CDCl3) δ 8.81 (bs, 1H),

8.08 (s, 1H), 7.65 (d, 2H), 7.43 (m, 2H), 7.25

(m, 2H), 5.57 (dd, 1H), 3.82 (dd, 1H), 3.22

(dd, 1H).




(1) by Bi(NO3)3 • 5H2O

TLC Rf, (1:1 hexane: ethyl acetate): 5 min.

microwave (pyrazoline = 0.15; reaction =

0.51, 0.23, 0.07; co-spot = 0.62, 0.29, 0.10).

Final product a yellow flaky solid of mass

0.3315 g. 1H NMR (300 MHz, CDCl3) δ

11.51 (s, 1H), 8.74 (d, 2H), 8.08 (s, 2H), 7.73

(d, 2H), 7.44 (m, 2H), 7.26 (m, 2H), 5.59 (dd,

1H), 3.85 (dd, 1H), 3.28 (dd, 1H), 2.32 (s,

2H).

TLC Rf, (1:1 hexane: ethyl acetate): 10 min.

microwave (pyrazoline = 0.16; reaction =

0.55, 0.44, 0.28, 0.09) TLC Rf , (toluene): 10

min. microwave (reaction = 0.91, 0.80, 0.71,

0.49, 0.36, 0.26). Final product a yellow

flaky solid of mass 0.3315 g. 1

H NMR (300

MHz, CDCl3) δ 11.51 (s, 1H), 8.77 (d, 2H),

7.74 (d, 2H), 7.45 (m, 2H), 7.25 (m, 2H),

5.59 (dd, 1H), 3.85 (dd, 1H), 3.30 (dd, 1H),

2.29 (s, 2H). TLC Rf, (1:1 hexane: ethyl

acetate): flash chromatography fractions 6-10

= 0.82, 0.74; fractions 11-14 = 0.87; fractions

15-20 = 0.87, 0.68; fractions 21-25 = 0.89,

0.78; fractions 26- 30 = 0.69; fractions 31-35

= 0.72; fractions 36-37 = 0.62. 1

H NMR (300

MHz, CDCl3) fraction 13: δ 7.95 (d, 1H),

7.45 (m, 2H), 7.25 (m, 2H), 2.35 (s, 2H), 2.28

(s, 2H). 1

H NMR (300 MHz, CDCl3) fraction

27: δ 11.51 (s, 1H), 8.77 (d, 2H), 8.23 (d,

2H), 7.74 (m, 2H), 7.45 (m, 2H), 7.31 (m,

2H), 5.59 (dd, 1H), 3.85 (dd, 1H), 3.28 (dd,

1H), 2.64 (s, 1H), 2.35 (s, 1H).




(1) by DDQ

TLC Rf , (1:1 hexane: ethyl acetate): 6 hr

(pyrazoline = 0.56; reaction = 0.56, 0.67), 1

week (pyrazoline = 0.42; reaction = 0.45,

0.68, 0.75). Final product a dark orange

brown flaky solid of mass 0.2 g. 1H NMR

(300 MHz, CDCl3) δ 8.07 (s, 1H), 7.65 (d,

2H), 7.43 (m, 2H), 7.24 (m, 2H), 6.8 (s, 1H),

6.25 (s, 1H), 5.57 (dd, 1H), 3.81 (dd, 1H),

3.23 (dd, 1H), 1.27 (s, 1H).

Discussion & Conclusions

The overall goal of the project was

the successful oxidative aromatization of 3-

(4-chlorophenyl)-5-phenyl-1-(4-

chlorophenylcarboxamide)-2-pyrazoline to

the corresponding pyrazole. To determine if

the oxidation reaction conversion was

successful 1H NMR of each reaction product

was analyzed looking for an indicative loss of

three dd peaks located at δ 5.57, 3.81, 3.22

and the appearance of a new singlet peak

around 6.5 ppm. The 1H NMR of the

oxidation reaction with FeCl3 product

showed a new singlet at δ 2.41 which is too

up field to be indicative of the formation of

the pyrazole, and the three dd peaks of the

pyrazoline were still visible indicating a lack

of conversion to the pyrazole. The 1H NMR

of the reaction with 10% Pd/C showed no

new singlets, and the three dd were still

visible indicating the reaction was

unsuccessful.

The oxidation reaction with Bi(NO3)3

yielded a new product indicated by TLC

analysis, with several new spots being visible

with Rf values of 0.55, 0.44, 0.28, 0.09. A

separation of the product by flash

chromatography resulted in two compounds

with Rf 0.87 and 0.69. 1H NMR analysis of

the fractions with Rf 0.69 showed three dd

peaks indicating the identity of the compound

was the original pyrazoline. 1H NMR

analysis of the fractions with Rf 0.87 lacked

the three dd peaks of the pyrazoline and had

two singlet peaks at δ 2.35, 2.28 with

integration that indicates two hydrogens in

that environment, whereas for the pyrazole

we expect one hydrogen in that singlet

environment; therefor this isolated compound

was not the desired pyrazole. Improvements

that could be made to the reaction with

Bi(NO3)3 oxidant is increase the reaction

time, which seemed to have resulted in better

yield when the reaction time was increased

from 5 min. to 10 min. Increasing the amount

of available Bi(NO3)3 oxidant could also

increase the reactivity and pyrazole

formation. It also may be beneficial to also

perform and flash chromatography column of

the product from the FeCl3 reaction and

separate the compounds formed for

individual analysis.

The oxidation reaction with DDQ

resulted in a product with two singlets at 6.8

ppm and 6.25 ppm, with integration of 1H.

Either of the singlets seen in the 1H NMR of

the DDQ reaction product could be the

diagnostic peak of the pyrazole. A flash

chromatography column could be run as to

separate the pyrazole product from the

unreacted pyrazoline, and then further 1H

NMR analysis of the fractions would better

identify the compound as the pyrazole, or as

some other byproduct. This reaction was

probably more successful due to the fact that

DDQ was a potent oxidizer and also the

pyrazoline used in the study by Kumar et al.

was more similar to the pyrazoline we

studied compared to the pyrazolines utilized

in the other studies referenced. Their

pyrazoline had a sulfonamide bonded to the

nitrogen of the pyrazoline and ours had a

carbamoyl bonded to the nitrogen both

electron withdrawing groups and therefore

more similar reactivity.

Further analysis of the products from

the Bi(NO3)3 and FeCl3 such as GCMS or

LCMS can further elucidate the identity of

the compound produced and further 1H NMR

analysis techniques such as COSY. The DDQ

reaction can be conducted again this time

ensuring dry conditions are achieved with dry

DCM which were not achieved in this study.

If the dry conditions are achieved as in the

literature from Kumar et al. hopefully

increased reactivity will be seen and

complete consumption of the pyrazoline

achieved. Overall complete consumption of

the original pyrazoline and formation of the

corresponding pyrazole by oxidation proved

difficult, and none of the reactions showed

complete consumption of the original

pyrazoline. Future studies that can be

conducted may look at other novel oxidants

or further improvement of the reactions

conducted here. An attempt at performing the

FeCl3 reaction under microwave conditions

can be made which may promote the reaction

and result in increased product yield and

pyrazoline consumption. Other oxidants that

have shown success in converting

pyrazolines to the corresponding pyrazole are

bis-bromine-1,4-diazabicyclo[2.2.2]octane

complex (DABCO-Br2)6, KMnO4

7, MnO2

8,

and iodobenzene diacetate (IBD)9.

References

(1) Schmidt, A.; Dreger, A. Curr. Org.

Chem. 2011, 15, 1423-1463

(2) Ananthnag, G. S.; Adhikari, A.;

Balakrishna, M. S. Catalysis

Communications. 2014, 43, 240-

243.

(3) Nakamichi, N.; Kawashita, Y.;

Hayashi, M. Org. Lett. 2002, 4(22),

3955-3957.

(4) Azarifar, D.; Maleki, B. Synthetic

Communications. 2006, 35(19),

2581-2585.

(5) Kumar, Ch. K.; Trivedi, R.; Kumar,

K. R.; Giribabu, L.; Sridhar, B.

Journal of Organometallic

Chemistry. 2012, 718, 64-73.

(6) Azarifar, D.; Khosravi, K.; Veisi, R.

A. ARKIVOC. 2010, 9, 178-184.

(7) Smith, L. I.; Howard, K. L. J. Am.

Chem. Soc. 1943, 65, 159.

(8) Bhatnagar, I.; Georgem, M. V.

Tetrahedron. 1968, 1293.

(9) Singh, S. P.; Kumar, D.; Prakash

O.; Kapoor, R. P. Synthetic

Communications. 1997, 27(15),

2683-2689.

chem 450 final report

Documents