JOURNAL OF MASS SPECTROMETRY, VOL. 31, 955-960 (1996)

Intermolecular Alkyl Transfer Reactions in the Fast Atom Bombardment Mass Spectrometry of Esters

Zbong-ping Yao,? Han-hui Wen, Qing-min Zha and Shan-kai Zhao Instrumentation Analysis and Research Center, Zhongshan University, Guangzhou 510275, China

Fast atom bombardment mass spectrometry (FABMS) of five neat phthalates (dimethyl, diethyl, diallyl, dibutyl and dinonyl) were investigated and intermolecular alkyl transfer reactions were observed in the mass spectra. FABMS of some related compounds was also studied and the results indicate that intermolecular alkyl transfers can occur in the FABMS of esters, the transferred alkyl group being associated with the carboxylate group in the adduct ion [ M + R J +. A possible mechanism is proposed which suggests that the transalkylation reactions in these non-ionic compounds arise from two routes: (i) nucleophilic attack by the electron-rich moiety of one energized desorbed molecule on to the electron-poor moiety of another and (ii) dissociation of the internally excited desorbed molecules. The study also demonstrated that the transalkylation reaction could be effectively controlled by addition of a suitable matrix, such as 3-nitrobenzyl alcohol.

KEYWORDS : intermolecular alkyl transfer; fast atom bombardment mass spectrometry; mechanism; esters; phthalate

INTRODUCTION

Since its introduction by Barber et al.',' in 1981, fast atom bombardment (FAB) has become one of the most important ionization methods in mass spectrometry (MS). Despite its extensive application for more than 10 years, the underlying mechanism of FABMS is still not completely clear. Numerous model^^-^ have been pro- posed, and although some debates still remain, several common aspects of the FAB mechanism are recognized: (i) the energy of the primary beam is converted via a collision cascade into vibrational and ultimately trans- lational energy of secondary ions and molecules; (ii) chemical reactions (e.g. ion-molecule and electron- transfer reactions) occur in the selvedge zone and (iii) unimolecular dissociation of internally excited gas- phase ions and molecules leads to fragmentation.

Positive-ion FABMS almost always provides quasi- molecular ions (e.g. [M + HI+ and [M + Na]+) that can be used to determine the molecular mass of organic compounds. If this is not the case, there will be mis- interpretation of mass spectra. Unexpected chemical reactions have been reportedg*" to occur between analytes and matrices accompanying desorption ioniza- tion, e.g. [M + nH]+ and [M + 01' ions were observed in the FAB mass spectra of some compounds due to reduction1' and oxidationI2 reactions, that may sometimes leads to the erroneous determination of the molecular masses of compounds, and some compounds may be wrongly concluded to be impure owing to

t Author to whom correspondence should be addressed.

reduction reactions such as dehalogenationl 3,14 and dehydr~xylation.~.'

Another kind of unexpected reaction can occur between analyte molecules themselves during the FAB process. Liguori et ~ 1 . ' ~ and Larsen et ~ 1 . ' ~ have report- ed the transmethylation reactions of L-carnitine and betaine hydrochloride, respectively, under FAB condi- tions. Various analogous intermolecular alkyl transfers have been reported in field desorption MS,' 8-22 second- ary ion MS23,24 and laser desorption MS.25,26 The compounds that were reported to undergo this type of reaction are zwitterions (e.g. carnitine) or organic salts (e.g. aminoalkanecarboxylate hydrochlorides), and the driving force of the intermolecular alkyl transfer is sug- gested to be minimization of the total number of charges desorbed into the gas phase.23

In a study of matrices for the FABMS of f~llerenes,~' we observed an unusual intermolecular alkyl transfer in some non-ionic compounds. Here we report the results in detail, and discuss the mechanism involved.

EXPERIMENTAL

All chemicals were of analytical-reagent grade from commercial sources and were used without further puri- fication.

All mass spectra were acquired on a VG ZAB-HS mass spectrometer (VG Analytical, Manchester, UK) equipped with an Ion Tech (Teddington, UK) FAB atom gun. Xenon was used as the bombardment gas, and typically the FAB atom gun was operated with a current of 1 mA and an accelerating voltage of 8 kV. The accelerating voltage in the mass spectrometer was 7

CCC 1076-5 174/96/0!?0955-06 0 1996 by John Wiley & Sons, Ltd.

Received 1 June 1995 Accepted 18 March 1996

956 Z.-P. YAO ET AL.

kV with a resolving power of 1000 and a mass range of 40-800 u. Mass spectrometric data were recorded on a PDP 11/250 data system.

_ _ RESULTS AND DISCUSSION

FABMS of neat phthalates

Figure 1 shows the positive-ion FAB mass spectrum of neat diallyl phthalate. In addition to the characteristic [M + HI+ ion, where M indicates the intact molecule, an unexpected ion corresponding to [M + 411 + is also present. It seems that an intermolecular allyl transfer occurs between diallyl phthalate molecules.

In order to confirm the occurrence of intermolecular alkyl transfer in phthalates under FAB conditions and to study the effect of alkyl groups on the reaction, we investigated the FABMS of neat phthalates with differ- ent alkyl groups C6H,(COOR), (R = allyl, methyl, ethyl, butyl and nonyl). As shown in Table 1, [M + R]+ ions are observed in the FAB mass spectra of all the phthalates and with evident abundance in the spectra of diallyl, dimethyl and diethyl phthalate, which indicates that beam-induced alkyl transfer occurs in phthalates. The ratio [M + R]+/[M + HI', which to some degree indicates the extent of intermolecular alkyl transfer, is

Table 1. Positive-ion FAB mass spectra of neat phthalates C,H,(COOR)2a

R Ion (mp)

Ally1 [M +HI+ (247) [M +41]+ (287)

Methyl [M +HI+ (195) [M + 15]+ (209)

Ethyl [M +HI+ (223) [M +29]+ (251)

Butyl [M +HI+ (279) [M + 57]+ (335)

Nonyl [M +HI+ (419) [M + 127]+ (545)

Relative abundance (%) [M + R]+/[M +HI+ (YO)

25 59 15 25 35 9 45 17 8 35 3 1 10 0.6 0.06

"Only ions in the region of the molecular ion are included.

59%, 35%, 17%, 3%, 0.6% for diallyl, dimethyl, diethyl, dibutyl and dinonyl phthalate, respectively. It is inter- esting that the ratio decreases as the length of the alkyl chain increases. Ally1 transfer is strongest in all the phthalates, which is probably connected with the partic- ular structure of the allyl group.

When diallyl phthalate (DAP) is mixed equally with dimethyl phthalate (DMP), the ratios of [DAP + 411' us. [DAP + H I + and [DMP + 151' us. [DMP + HI+ decreases and adduct ions [DMP + 411' and [DAP + 151' are observed in the spectrum (Fig. 2). This result again demonstrates the occurrence of inter- molecular alkyl transfers and this time it occur between two different molecules. Figure 2 shows that [DMP + 41]+/[DMP + H I + + [DAP + lS]+/[DAP + HI+ and also indicates that allyl transfer occurs much more easily than methyl transfer.

Investigation of some related compounds

It is of great interest to investigate why intermolecular alkyl transfers can occur in phthalates and with which position the transferred alkyl group is associated in the adduct ion [M + R]'. The FAB mass spectra of some related compounds were investigated and the results are summariz,ed in Table 2. Most compounds in Table 2 were investigated in the neat form and some solid com- pounds were analyzed with 3-nitrobenzyl alcohol (NBA) as matrix.

Maleates are diesters having analogous structures to phthalates, but without a phenyl ring. Diethyl and dioctyl maleate were investigated and evident [M + R]+ ions were observed in their FAB mass spectra. Fumarates are trans isomers of maleates and dimethyl fumarate also shows evident intermolecular methyl transfer in its FAB mass spectrum. These results indicate that the phenyl ring does not play an impor- tant role in intermolecular alkyl transfers of phthalates, i.e. the transferred alkyl group in the adduct [M + R]+ ion is not associated with the phenyl ring. The results support the contention that an alkyl group is associated with the carboxylate group and the ortho effect of two carboxylate groups is not a crucial factor for the associ- ation of the alkyl group. The same conclusion can be drawn from the FABMS of succinates, methyl laurate and methyl stearate, which indicate the occurrence of

la A I 280 268 388

Figure 1. Positive-ion FAB mass spectrum of neat diallyl phthalate. In addition to quasi-molecular ion [M + H]+ (m/z 247) and fragment ions, an abundant [M + 411' ion is present at m/z 287.

ALKYL TRANSFERS I N FABMS OF ESTERS 957

'ii [DAP+H]+

Figure 2. FAB mass spectrum of diallyl phthalate (DAP) mixed equally with dimethyl phthalate (DMP).

intermolecular alkyl transfers in fatty acid esters and even monoesters.

The FABMS of some simple aromatic monoesters, viz. 4-hydroxybenzoates, was also investigated. Com- pared with diesters, monoesters show lower [M + R]+ peaks in their FAB mass spectra. Another reason for lower [M + R]' peaks is that added matrix NBA lowers the probability for reaction between 4- hydroxybenzoate molecules.

The above results indicated that carboxylate esters can undergo intermolecular alkyl transfers under FAB conditions. Further, we suggest that transalkylation can also occur in other analogous alkyl esters. As shown in Table 2, the FABMS of several p-toluenesulfonates, phosphates and sulfates was investigated. Trimethyl and triethyl phosphate and dimethyl sulfate fail to provide significant FAB mass spectra owing to their higher volatility. The other esters investigated show evident intermolecular alkyl transfers in their FAB mass spectra. Figure 3 shows the FAB spectra of methyl and ethyl p-toluenesulfonate, in which abundant [M + 151'

and [M + 29]+ ions are observed, respectively. We intend to investigate more related compounds in order to strengthen our conclusions.

Mechanism

Our results indicated that the carboxylate group plays an important role in the intermolecular alkyl transfers of esters, and the transferred alkyl group is associated with a carboxylate group in the adduct ion [M + R]+. It is understandable that the association force arises from the interaction of the electron-rich carboxylate group with an alkyl cation which can be produced from the dissociation of esters under FAB conditions.

The compounds that have previously been reported to undergo intermolecular alkyl transfer during various desorption ionizations are mainly zwitterions or organic salts, and the reaction is suggested16v20s23 to result from nucleophilic attack by the electron-rich moiety of one molecule on the positively charged moiety of another.

Table 2. Summary of [M + HI+ and IM + R] + ions observed in various compounds investigated

Compound [M +HI ' a [ M + R ] + ' [M + R]*JCM +HI+ (X)

Dimethyl maleate Dioctyl maleate Dimethyl fumarate' Dimethyl succinate Diethyl succinate Dibenzyl succinate' Methyl laurate Methyl stearate' Methyl 4- hydroxybenzoate" Ethyl 4-hydroxybenzoate' Butyl4-hydroxybenzoate' Methyl p-toluenesulfonate Ethyl p-toluenesulfonate Trimethyl phosphate Triethyl phosphate Tributyl phosphate Dimethyl sulfate

(1 73) 40 (341) 64 (145) 39

b

b

(299) 16 (21 5) 100 (299) 100 (153) 100 (167) 100 (195) 100 (187) 100 (201) 100

b

b

(267) 95 b

(201) 5 (453) 0.4 (1 59) 11

-

(389) 0.5 (229) 3 (313) 3 (167) 3 (195) 1 (251 ) 2

(229) 1 3 (201 ) 1 1

-

-

(323) 4

13

28 0.6

- 3 3 3 3 1 2

11 1 3 - -

4

"Mass to charge ratios (m/z) of the ions are given in parentheses: the other numbers are the relative abundances of the ions (%). bNo significant FAB mass spectrum is obtained owing to the high volatility of the compound. ' 3-Nitrobenzyl alcohol as matrix.

958

Figure 3. FAB mass spectra of (a) methyl and (b) ethyl p-toluenesulfonates showing an abundant EM + 151' ion at m/z 201 (a) and an [M + 29]+ ion at m/z 229 (b) due to transmethylation and transethylation, respectively.

The driving force of this kind of reaction is proposedz3 to be neutralization of the extra charge per molecule of salt. The compounds investigated here are non-ionic, so a mechanism is proposed to explain the phenomenon described above. This possible mechanism is depicted in Scheme 1, where the intact molecule M is considered to be composed of two moieties, an electron-poor moiety A (e.g. alkyl group) and an electron-rich moiety B (e.g. carboxylate group). On bombardment by an atom beam, analyte molecules energize and desorb and the internally excited desorbed molecules tend to dissociate. In the selvedge zone, the internally excited desorbed molecules frequently collide with each other, moiety B of one molecule nucleophilically attacks moiety A of another and the attacked internally excited molecule dissociates, leading to the production of ion pairs [A- B -A] + and B-. The [A-B-A] + ion corresponds to the [M + R]+ ion in the FAB mass spectra of esters. That is, the occurrence of intermolecular alkyl transfer in non-ionic compounds during desorption ionization arises from two routes: (i) nucleophilic attack by the electron-rich moiety of one internally excited desorbed molecule on the electron-poor moiety of another and (ii), dissociation of internally excited desorbed mol- ecules.

On the basis of this mechanism, the intermolecular reaction is expected to be favored when the electron- poor moiety A of the molecule is sterically favorable to nucleophilic attack and when the A+ ion is more stable. Of the phthalates, allyl phthalate is most favorable for

intermolecular alkyl transfer owing to the delocalization of the allyl group to positive charge. Another reason is that the allyl group has two positions (ct and y) for nucleophilic attack:

CH 1 =CH-CH,-O--- l Y , 2u

In terms of the proposed mechanism, there will exist a B- ion accompanying the production of an [A-B- A] + ion. We investigated the negative-ion FABMS of five phthalates. Dibutyl and dinonyl phthalate failed to produce a negative-ion FABMS signal, and [M - 41]-, [M - 151- and [M - 291- ions were observed as base peaks in the negative-ion FAB mass spectra of diallyl, dimethyl and diethyl phthalate, respectively. Of course, these ions can also arise from simple alkyl loss.

Elimination of [M + R] + ions

When a compound i s physically mixed with other com- pounds, e.g. the FAB matrix, the probability of collision between the analyte molecules reduces and the internal energy of the analyte molecules may also be lowered, and these two factors will lead to a great reduction in intermolecular alkyl transfer. We investigated the FAB mass spectra of diallyl phthalate (DAP) mixed with NBA, glycerol, 15-crown-5, triethanolamine, p - toluenesulfonic acid and NH,Cl, and the most evident

M = A-0 X e beam

[A-B-A] + + 6- , A-B . . . A + . . . B- -. A-0 -+ A-0 Scheme 1. Proposed mechanism of intermolecular alkyl transfer.

ALKYL TRANSFERS IN FABMS OF ESTERS

40

38 28 la 0

959

C

mss 7

Figure

?

decrease was observed when DAP was mixed with NBA. As can be seen in Fig. 4, increasing the ratio of NBA us. DAP causes an evident decrease in the ratio of [M + 411' us. [M + HI'. When DAP is mixed with a tenfold amount of NBA, the [M + 411' ion is almost missing from the spectrum. This also demonstrates that the [M + 411' ion comes from intermolecular ally1 transfer under FAB conditions.

CONCLUSION

' (m/z 287) for diallyl

alkyl group in the compounds. The study has also demonstrated that the extent of intermolecular trans- alkylation reactions in these compounds can be effec- tively controlled by suitable addition of a matrix such as 3-nitrobenzyl alcohol.

Intermolecular alkyl transfer in the investigated com- pounds also enables us to see the action of compounds during FAB. The mechanism proposed in Scheme 1 suggests that when a compound contains an electron- rich moiety and an electron-poor moiety, intermolecu- lar transfer of an electron-poor moiety may occur under FAB conditions. Further research on these problems is in progress.

Intermolecular alkyl transfers occur in the FABMS of the esters investigated. The alkyl transfers produce abundant corresponding ions in the spectra even if the samples are mixed witha matrix, e.g. NBA, which prob- ably leads to misinterpretation of the FAB suectra. This Acknowledgements

960 Z.-P. YAO ET AL

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