RAPID COMMUNICATIONS IN MASS SPECTROMETRY, VOL. 9, 13-17 (1995)

Control of Internal Proton Transfers on Ion-dipole Complexes from [M - HI- Ions of Diphenol Esters' F. Fournier, M.-C. Perlat and J.-C. Tabet* Laboratoire de Chimie Organique Structurale I , ERS 73, Universite Pierre et Marie Curie, Paris Cedex 05, France

The behaviour of 3',4'-dihydroxybenzyl fatty acid ester towards the NHJNH; system has been investigated under negative-ion chemical ionization (NICI) conditions. Under NICI, proton abstraction takes place regioselec- tively at one phenol site rather than from the enolizable position. Analysis of specific fragmentations of the isotopically labelled phenoxide species prepared in the gas phase by ND, indicates that isomerization into an ion-dipole intermediate (via charge-promoted cleavage) takes place prior to fragmentation. Its dissociation provides fatty acid carboxylate ions (the charge is stabilized by coiling of the side chain). The acidity of the phenol group must be enhanced by the presence of a second group at the position ortho to the first. This explains why the previous ion-dipole complex isomerizes by proton transfer into a second isomeric form which decomposes yielding the phenoxide species, as shown by labelling experiments. Stabilization of the negative charge by hydrogen bonding (Ar-0- . . . H+. . .O--Ar) from the phenoxide form is possible. A similar situation character- izes 3' ,4'-dihydroxybenzyl phenyl ethyl ester and 3',4'-dihydroxybenzyl benzyl ester. Their behaviour was also studied to find the influence of the side chain structure on the pathway of ion-dipole dissociation under low- energy collision conditions.

Recently, different studies have been undertaken on the collisional dissociation of deprotonated molecules [M - HI- prepared under negative-ion chemical ioniza- tion (NICI) and fast-atom bombardment (FAB) con- ditions from long-chain fatty acid esters containing a hydroxy group sterically distant from the ester group.'-3 According to the preparation mode, deprotonation can take place competitively at both acid sites (i.e. -OH and -CH2C02-) leading to unconvertible isomeric [M-HI- ions [i.e. enolate and phenoxide ions] as shown in Reaction (1).

HO-Ar-CH20CO-CH2R

HO- Ar-CH,OCO-( R)CH- -0- Ar-CH,OCO-CH,R

The coexistence of both isomeric forms of molecular anions (generated by different preparation methods), when the acidities of the functional groups differ suffi- ciently, has been shown (i) by comparison of their respective low-energy collision-induced dissociation (CID) spectra since they display different fingerprints according to the method of ion preparation and, alter- natively, (ii) by studying decompositions of deproton- ated labelled hydroxy-esters (such as the DO- or -CD,-COO- labelled compounds) prepared by using gas-phase labelling conditions (with ND3). Both phe- noxide (Md - D)- and enolate (Md - H)- ions were produced in different abundances according to the relative acidities of both sites, since deprotonation occurs under thermodynamic control. Submitted to low-energy collisions, the isomeric deprotonated spe- cies decompose along specific pathways which depend upon the charge location, demonstrating that isomeric structure interconversion (enolate e phenoxide forms) does not take place. Prior to dissociation, these iso-

NH+ r( I N H i (1)

'Presented at the 11th Annual Meeting of the French Mass Spectrometry Society, held at Rouen, 20-22 September 1994. * Author for correspondence.

meric ions transpose into different ion-dipole com- plexes via ester cleavages which depend upon the charge location, since this first ~ t e p ~ . ~ is promoted by negative charge as illustrated for the 4'-hydroxy-benzyl stearate ester (Scheme 1).

The CID spectra of [M - HI- ions display two series of complementary fragment ions: phenide/carboxylate and phenoxidelynolate, used as evidence of the charge location in the deprotonated molecule. The relative efficiency of each isomeric ion-dipole complex depends on the acidity difference between the phenol and ester groups. For instance, the relative acidities of ketene and p-hydroxy benzyl alcohol neutrals which constitute the ion-dipole complex, strongly influence the realtive abundances of their corresponding anions (i.e. phenox- ide less abundant than y n ~ l a t e ) . ~ , ~ Conversely, the methylenequinone being less acid than carboxylic acids, the carboxylate ion is observed rather than the phenide ion.

In the present work, the role played by such ion- dipole complexes over the initial [M - HI- form during formation of the fragment phenoxide and carboxylate ion pairs has been investigated. In particular, the aci- dity of the phenol site has been reinforced by introduc- tion of a second -OH group at the position ortho to the first substituent, in order to enhance significantly the phenoxide fragment production. For this purpose, the following phenol esters have been studied by the low- energy CID process:

0-( HO)2ChH3-CH2-O-CO-CH2-(CH,) 16H 1 (MW 406)

O-(HO)~C&-CH,-OCO-(CH,),-C,H, 2 (MW 272)

0-( H0)2ChH3-CH?-O-CO-CH?-C6H5 3 (MW 258)

ccc 0951-4198/~5/010013-05 0 1995 by John Wiley & Sons, Ltd

Received 3 October 1994 Accepied (reoised) 3 November I994

14 ION-DIPOLE COMPLEXES FROM DIPHENOL ESTERS

Isomerization Reversible { 0 = CgHq = CH-,HOzC-CH2R}

J Proton transfer {O=CgHq=CH2,-02C-CH2R)

Form A Form B

HO-C6Hq-CH2-O-CO-C(R)H- with R=(CH2)16H

(HO-CgHq-CH2O-,O = C = CHR } Form A'

Irreversible Proton transfer

Reversible roton

a { -O-C6H&H20H,HO-C=C-R} Form C'

{ HO-C6Hq-CH2OH; 0-CEC-R} Form B'

Scheme 1. Isomerization pathways of the deprotonated hydroxy-ester.

EXPERIMENTAL Mass spectrometry and tandem mass spectrometry experiments were performed on a triple quadrupole mass spectrometer (R30-10 Nermag, Rueil Malmaison, France). The NICI mass spectra were obtained using direct introduction (DCI) with amonia as reagent gas, where 1 yL of solution of sample (1 pg yL-' in metha- nol) was placed on a heated tungsten filament that was maintained at 390 "C. The following source operating conditions were used: emission current, 100 mA; repeller voltage, 0 V; source temperature, 180 "C; and ammonia reagent gas pressure, 2 x

In tandem mass spectrometry experiments, low- energy CID spectra of deprotonated molecules were recorded by using argon as the collision gas at 6 X

Torr (measured just inside the collision cell) to yield single-collision conditions. Ion kinetic energy was increased from OeV to 100eV in order to study the ERMS (energy resolved mass spectrometry) break- downs. Each reported CID spectrum is an average of at least 50 consecutive scans to obtain good signal-to- noise ratio.

Torr.

RESULTS AND DISCUSSION Site of deprotonation as evidenced by diagnostic ions produced by dissociation of the specific ion-dipole com- plex As shown in Scheme 1, production of both ion-dipole complexes reflects the competitive deprotonation at the phenol and enolizable sites. Their formation can be evidenced by the observation of the two pairs of com- plementary ions in the CID spectra of the deprotonated molecules. These pairs are expected at mlz 283 and rn lz 121, and at rn lz 255 and mlz 139, due respectively to decompositions of an ion-dipole complex either with the A form (deprotonation at the phenol site) or char- acterized by the A' form (loss of a proton from the enolizable position of the ester group). However, only the former fragment ion pair is generated either in low-

collision conditions (Elab = 15 eV) or at higher energy (i.e. 80 eV) as shown in Table 1.

The selective formation of the complementary frag- ments rnlz 283 and mlz 121 indicates that deprotona- tion takes place at a phenol site (as form A) rather than at the enolizable position (i.e. the A' form that would be characterized by the mlz 255 and rnlz 139 ion pair). Moreover, deprotonation can occur from either -OH site, since the proton can migrate from one -OH group to the other phenoxide site via hydrogen bonding (via the -O-. . H + . * 0-- form), but most probably, the one at the position para to the benzylic group is respon- sible for the phenoxide isomerization into the ion- dipole complex. Indeed, the cleavage of the benzylic C-0 bond which leads to the A form (Scheme 2) is promoted by charge migration from the para phenoxide site through the aromatic skeleton to the oxygen atom of the fatty acid ester. According to Scheme 2, this ion- dipole complex dissociates either directly into the car- boxylate rnlz 283 ion or, after isomerization, into the B form (via an internal proton transfer) providing rn lz 121.

Note that the latter phenoxide appears at an abun- dance of 35% of the base peak, contrary to what is observed from the monophenol ester3 (for discussion vide infra). To obtain significant evidence, the deproto- nation reaction is performed from the labelled ldZ

Table 1. Low energy CID spectra of the [M-HI- ions pre- pared by NICI from the different phenol esters studied (1, 2 and 3)

Deprolondred EM, Fragment ions esters (eV) IM - Hi ~ Phenoxides Carboxylates Other

405 121 (35)" 283(100) { ii 405 121(100) 283 (31) [ l - H ] -

[ Z - H ] . 15 271 121 (60) 149(100) [3 - HI 15 257 121 (29) 135(100) 91 (24)

"miz (Relative abundance).

ION-DIPOLE COMPLEXES FROM DIPHENOL ESTERS

-O(DO)C6H3-CH2-O-CO-CH2-(CH2) 16H Ion [Idz-D]' m/Z 406

Molecular G> 1 Isomerization

{O=(DO)C~HJ=CH~,-OCO-CHZ-(CH~)~~H} - = -0-CO-CHZ-(CH2)16H Form A m/z 283

{ O = (-O)C~H~=CHZ,DOCO-CH~-(CH~)~~H} ___) O = (-O)C6H3=CH2 Form B m/z I21

Scheme 2. Formation of the complementary mlz 121 and m/z 283 ions via isomerization into the ion-dipole complex within the A and B forms from the labelled [ld2-H]- ion ( m / z 406).

molecules prepared under NICI-ND, conditions. 3' ,4'- dihydroxy benzene was deuterated (by HlD exchange) at both hydroxyl groups. Under these labelling con- ditions, specific loss of a deuteron occurs, to produce the [ld2 - D]- ion (mlz 406) which confirms that depro- tonation is regioselective at one phenol site. In the CID spectrum of this labelled species, the peak at mlz 121 is not shifted to mlz 122 which confirms the formation of the ion-dipole A complex. Its isomerization into the B form via proton transfer from the intact phenol site to the carboxylate fragment ion, specifically leads to an unlabelled phenoxide species as shown in Scheme 2.

This regioselective deprotonation is expected, since introduction of a second -OH group (1,2-dehydro- quinone form) increases the acidity of the phenol site (AGZcl,< 1400 kJlmo1, Table 2)3,9 relatively to that of the monophenol in which competitive de- protonations take place from the phenolic and enolic sites (AG~c,d= 1438 kJlmol and AGicId = 1478 kJlmo1, respectively) .3,y From the decompositions of the de- protonated monophenol, the abundance of the mlz 105 phenide ion3 is very weak, resulting from the lowering of the acidity of methylenequinone (AGicld> 1500 kJ/m01)~,~ relative to that of carboxylic acids (AGycld = 1379 kJ/m01).~ This contrasts with the result of collisions on [I - HI- which gives rise to formation of the mlz 121 phenoxide ion (AGycld< 1420 kJlmo1, Table 2)."' The higher acidity of the carboxylic acid towards that of the HO(O=)C,H3=CH2 neutral which composes the ion-dipole complex (within the A form) explains the lower abundance characterizing the phen- oxide relative to that of carboxylate.

Table 2. Estimated acidity values (AG,",,d in kJ/mol) of substi- tuted phenols, dehydroquinone and various carboxy- lic acids (from Refs 3 and 9)

A G d A G ;;id

C,H,OH - 1438' H(CH,),,COOH 1379

H2C=C,H4=0 > 1500" C,H,CH,COOH 1398' H,C=C,H?(OH)=O - 1420" C,HcCOOH 1388"

'' Estimated values from Refs 9 and 10.

Cornpound (k l imol ) Compound (klimol)

(OH)GH?R < 1400" C,H5(CH?)?COOH 1410"

Influence of the ester side-chain on the orientation of the ion-dipole dissociation

A similar behavior towards the NH; reagent ion char- acterizes compounds containing a shorter (and aroma- tic) ester side-chain, such as phenylpropionate, 2, and phenylacetate, 3, because deprotonation takes place at the phenolic position and not at either the enolizable position or the benzylic site. Under collision, each selected [2-H]- and [3-H]- ester ion leads to a unique pair of complementary ions, mlz 121 and mlz 149 or mlz 121 and rnlz 135 ions, respectively (Table 1). They result from decomposition of the selective A and B ion-dipole complexes (after isomerization). From fragmentations of the selected [2 - HI- ion having two CH, groups in the ester side-chain, the abundance of the -O(O=)C6H3=CH2 phenoxide ion (mlz 121) relative to the 3-phenylpropanoate C6H5(CH2),C00- ion (mlz 149) reaches 6070, which means, very probably, that the acidities of both neutrals composing the ion-dipole forms are more simi- lar than those of neutrals formed from cleavage of the selected [l-H]- and [3-H]- ions. The acidity difference between O=(HO)C6H3=CH, and C6HsCH,-COOH increases in favour of the latter (according to Table 2), which explains the mlz 135 ion abundance enhancement observed from the [3 - HI- ion relative to [2 - HI-. Note that the observed mlz 91 ylide results by consecutive fragmentations by loss of CO, from the carboxylate C6HsCH2COO- fragment ion from [3 - HI-. Indeed, its abundance increases as the collision energy rises (consecutive process).

From CID of [Md2-D]- ions (for 2d2 and 3d,), no labelled mlz 122 fragment ions are produced and speci- fically only mlz 121 is observed. This confirms the proposed stepwise mechanism in which the formation of an ion-dipole complex occurs. This complex isomer- izes by D transfer from the -OD position to the carboxylate site leading to the rnlz 121 ion free of labelling.

The relative abundances of fragment ions are not significantly influenced by collision energy change. This particular behavior may suggest, by comparison with the different trend observed from the [I -HI- ion, that very likely: (i) formation of the ion-dipole complex with the A

16

Isomerization

ION-DIPOLE COMPLEXES FROM DIPHENOL ESTERS

n = 2 ; Ion [2-H]-, m/z 271

(ii)

n=2;m/z149

reversible proton transfer I

{-o(o = )C@3 = CH~,HOZC-(CH~) , -C~H~} ___) 0 = (-O)C6H3= CHz Form B m/z I21

Scheme 3. Competitive decompositons of the A and B ion-dipole complexes prepared from [2-H]- and [3-H]-.

90-

80-

70- m 0 u

-0 c, 9 60-

3 50- 4 .z 40- 0

cd c) - 2 30-

20-

10,

form occurs prior to the collision processes; and, consequently,

(ii) a reversible isomerization (form A s f o r m B) takes place readily since AG& of components of the complex A (and B) are sufficiently similar to allow a fast proton transfer (Scheme 3).

Origin of the favorable formation of phenoxide at higher collision energy For compound 1, having a fatty acid ester chain, there has been observed to be a strong influence of the Elab values on to the relative abundances of complementary ions rnlz 283 and mlz 121 (Fig. 1). At higher collision energies, formation of the rnlz 283 ion (direct cleavage) relative to mlz 121 (via proton transfer) should be

O m/z121

0- I E l a b 0 10 20 30 40 50 60 65

Figure 1. Dependence of relative abundances of both the fragment ions of the [ l - HI- ion on the values.

enhanced. However, a reverse situation is observed, since above 60eV the rnlz 283 carboxylate is un- favoured relatively to the rnlz 121 phenoxide ion. This decrease of carboxylate abundance as Elab rises, is unexpected (Fig. 1). It should be noted that the frag- mentation orientations of the A and B complexes favour the phenoxide rnlz 121 ion at higher collision energies, opposite to the prediction from the relative rate constants of the competitive decompositions. In fact, variation of the isomerization A+ B reversibility as Elab rises may be one possible explanation. This implies the existence of a non-negligible intrinsic bar- rier as transition state. A priori, this is surprising because proton transfer generally proceeds without a strong geometry change in the intermediate state.

On the other hand, in order to give a possible origin of this phenomenon which favours the A -+ B isomeri- zation (i.e. enhancing the phenoxide ion formation) with rise of the collision energy, it may be considered that the acidity of the fatty acid intrinsically decreases when the internal energy of the ion-dipole complexes is raised (within the A forms). Actually, the increase of the vibrational internal energy as the collision energy rises probably leads to the unwinding of the long-chain conformation. Indeed, a coiling phenomenon has been proposed to rationalize the acidity increases due to the enlargement of the side-chain (effect of the solvation of the negative charge) of various aliphatic compounds (i.e. alcohols,"' acids," k e t e n e ~ , ~ oligopeptides'* etc). Thus, if vibrational energy does not favour the coiling conformation then, (i) this should confer a weaker stability of the carboxylate ion and (ii) the A form isomerization into the B form may be favoured, enhancing formation of the phenoxide rnlz 121 ion.

Such an assumption is consistent with the absence of the collision energy effect on the competitive fragmen- tations of the [2 - HI- and [3 - HI- ions (except on the consecutive processes by loss of CO, from the phenyla- cetate ion). This trend is expected, since the C,H,-(CH,)2-COOH and C&-CH,-COOH neutrals cannot lead to such a chain coiling (too short a chain to increase the acidity) and, mainly, the polar and hyper- conjugation effects influence the acidity strength for

ION-DIPOLE COMPLEXES FROM DIPHENOL ESTERS 17

these carboxylic acids in which the entropic effect plays a minor role.

CONCLUSION This study on the decompositions of the various depro- tonated diphenol esters demonstrates that the deproto- nation reaction proceeds regioselectively at one phenol site rather than from the enolizable position of the ester function as it occurs from monophenol esters. This behaviour indicates an acidity increase of the diphenol esters due to an eventual stabilization by hydrogen bonding (-0- . . -H+ . . -O--) of the phenoxide form.

Furthermore, experiments using labelled -OD com- pounds provide additional evidence on the production of a particular ion-dipole complex promoted by the negative charge located at the phenol position. Actually, from the different [Md2 - D]- ion decompo- sitions, deuterium is seen not to be retained in the fragment ions, confirming (i) the isomerization into the A complex form prior to dissociation and (ii) that proton (or deuteron) transfer takes place specifically from the phenol site to the carboxylate ion. The latter finding confirms the acidity increase of O=(HO)C6H3=CH2 relative to O=C6H,=CH, (insufficiently acid to allow proton transfer to the car- boxylate RCOO- moiety).

Finally, from the study of the observed influence of the collision energy, it appears that the abundance of the fatty acid carboxylate (produced by direct cleavage) decreases relative to the phenoxide species as Elab rises. This suggests a particular effect based upon the influence of the polarizability of a long chain on mole- cule acidity. This considers that the long chain confor-

mation is uncoiled by increasing the internal vibrational energy of the deprotonated molecules (either in the initial structure or within the ion-dipole complex form). The latter preliminary finding merits further study to verify the pertinence of such an assumption.

REFERENCES

1.

2.

3.

4.

5 .

6. 7.

8

‘ J

10

11

4 -

F. Fournier, C. Salles, J . C. Tabet, L. Debrauwer, D. Rao, A. Paris and G. Bories, Anal. Chim. Acfa 241, 265 (1990). F. Fournier, J . C. Tabet, L. Debrauwer, D. Rao, A. Paris and G. Bories, Rapid Commun. Mass Spectrom. 6 , 44 (1991). F. Fournier, B. Remaud and J . C. Tabet, J . Amer. Mass Spectrom. Soc. 4, 343 (1993). P. Longevialle and R. Botter, J . Chem. SOC., Chem. Commun. 823 (1980). R. N. Hayes, J . C. Sheldon, J . H. Bowie and D. E. Lewis, J . Chem. Soc., Chem. Commun. 1431 (1984). D. J . McAdoo, Mass Spectrom. Reoiews 7 , 367 (1988). M. B. Stringer, J . H. Bowie, P. C. H. Eichinger and G. J . Currie, J . Chem. SOC., Perkin Trans I 1 385 (1987). A. G. Harrison and R. B. Young, Inf. J . Mass Spectrom. Ion Processes 94, 321 (1989). S ( I I [;I\. .I I Iktrtiiic\\, . I . I. I.iclman. I . I.. lloliiic\. I<. I). Levin and W. G. Mallard, J . Phys. Chem., Ref. Dafa 17, Suppl. 1 (1988). (a) G. Boand, R. Houriet and T. Gaumann, J . Amer. Chem. Soc. 105, 2203 (1983); (b) A. G. Harrison, in Fundamentals of Gas Phase Ion Chemistry, K. R. Jennings (Ed.), NATO AS1 Series, Series C, Vol. 347, p. 289 (1991); (c) K. T. Majumdar, F. Clairet, J. C. Tabet and R. G. Cooks, J . Amer. Chem. SOC. 114, 2897 (1992). L. G. Wright, S . A. McLuckey and R. G. Cooks, Int. J . Mass Spectrom. and Ion Phys. 42, 115 (1982).

IL. (a) J . Wu and C. B. Lebrilla, J . Amer. Chem. Soc. 115, 3270 (1993); (b) 2. Wu and C. Fenselau, Tetrahedron 49,9197 (1993); (c) K. Zhang, D. M. Zimmerman, A. Chung-Phillips and C. J . Cassady, J . Amer. Chem. SOC. 115, 10812 (1993).