Effects of Functional Group Interactions on the Gas-Phase Methylation and Dissociation of Acids and Esters

CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Effects of Functional Group Interactions on the Gas-Phase Methylation and Dissociation of Acids and Esters John J. Isbell and Jennifer S. Brodbelt Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas, USA Functional group interactions have been observed to affect gas-phase ion-molecule chemistry in a quadrupole ion trap mass spectrometer. Gas-phase methylation and collision- activated dissociation reactions of a series of related acids and esters allows an evaluation of the structural factors that influence reactivity and functional group interactions of these compounds. Examination of the [M + HI+ or [M + 15]+ product ions by collision-activated dissociation has provided insight into the conformations from which diacids and diesters undergo electrophilic addition. Collision-activated dissociation has provided not only more detailed information on the structures of the ions, but also the data necessary for confident mechanistic interpretation. Labeling studies were done to probe fragmentation pathways. Upon activation of the [M + CD,]+ products of dimethyl maleate and dimethyl succinate, formed from reaction of the neutrals with CD,OCD$ ions, a rapid interfunctional group methyl transfer causes scrambling of the methyls prior to elimination of dimethyl ether or methanol. The [M + 151 ’ ions of dimethyl maleate are believed to lose dimethyl ether through a rate-determining 1,6-methyl transfer, whereas the [M + 15]+ ions of dimethyl succinate eliminate methanol through a rate-determining 1,5-proton transfer. (J Am Sot Mass Spectvom 2996, 7, 565-572) unctional group interactions are among the most molecular ion and sizcable losses of H,O and HDO. important classes of substituent effects in both There was no H/D scrambling for either diacid and F solution and gas-phase chemistry [l-18]. The these losses were postulated to occur via different term “intramolecular catalysis” has been used to de- pathways. Tajima et al. [15] found that the molecular scribe those types of functional group interactions that ions of both dimethyl maleate and fumarate lose facilitate specific reactions or dissociation channels [17]. methoxy radical via a direct cleavage, and the latter Such effects have been observed for a variety of di- molecular ion also rearranged to lose formaldehyde functional molecules, which include diols and amino and CH,CO radical. Labeling experiments showed no alcohols [3-7, 18~1. kinetic isotope effect for the direct cleavage, but the Some of the most striking functional group interac- rearrangement seen for the fumarate had an inverse tions have been observed for dicarboxylic acids and isotope effect, which was attributed to a rate-determin- esters. For instance the ability of a functional group to ing cyclization. interact with another can be correlated with distinctive The chemistry of these acid ions changes dramati- fragmentation patterns upon electron ionization [l] or cally when open-shell species formed by electron ion- with the extent of dehydration of the diacids upon ization are compared to the closed-shell ions formed protonation by chemical ionization (CI) [9]. Similar from protonation upon chemical ionization. For exam- results have been reported for related esters [ 13, 14, 19, ple, Harrison et al. [9] found that under methane or 201 and fatty acids 121. Extensive work has been done hydrogen chemical ionization conditions, protonated via electron ionization to cxaminc functional group Z-diacids eliminated water preferentially, whereas the interactions [17]. For example, by using 2, 3-dideutero protonated E-diacids remained intact. The rationale for maleic and fumaric acids, Benoit et al. [l] observed the this result was attributed to the ability of the Z-diacid former decarboxylates after an intramolecular hydro- to donate a proton to the other functional group prior gen transfer and the resulting ion can dehydrate, and to dehydration and, second, the stability of the result- lose water-d,. The latter isomer exhibited an abundant ing product ion. Under the same CI conditions, diethyl fumarate formed predominantly the intact [M + HI+ ion, whereas its Z-isomer lost ethanol from the analo- gous ion [9]. The argument Harrison put forth in this Address reprmt rrques+s to Profrvmr Jrnmfrr 5. Brodbclt, Depart- ment of Chemistry and Biochemistry, University of Texas at Austin, study agreed with earlier work [14] in which a series Austin, TX 78712-1167. of variable alkyl chain diacids and the corresponding 0 1996 American Society for Mass Spectrometry liecelved IXovember 10, 1995 1044-0305/96/$15.00 lievised January 19, 1996 PI1 S1044-0305(96)00016-5 Accepted January 19, 1996 566 ISBELL AND BRODBELT J Am Sot Mass Spectrom 1996, 7,565-572 dimethyl esters exhibited, on protonation under ity of the analyte exceeds that of dimethyl ether. The methane CI, increased dehydration or methanol elimi- latter can either methylate or effect a methylene substi- nation with increasing chain length. In contrast, by tution. Earlier work on amino alcohols has shown the using an alternate ionizing technique-fast-atom bom- [M + 15]+ product to result from an S,2 reaction, bardment-the protonated maleic acid showed less whereas the [M + 13]+ stems from an addition- dehydration than the [M + HI’ of fumaric acid, which elimination reaction, and this latter reaction was found also yielded those products that result from subse- to require the presence of a labile proton [21]. In this quent decarbonylation and from decarboxylation [ 161. report, the CAD spectra of the [M + HI+ ions and the The reduced degree of fragmentation observed for the [M + 151 + ions are examined with the aim of deter- Z-acids relative to their E-isomers was attributed to mining the reactive conformers and elucidating the the ability for intramolecular hydrogen-bond forma- mechanisms of fragmentation. tion. A concern in these types of studies has been the possibility of isomer interconversion in the course of Experimental the experiments. A charge-exchange study done by A Finnigan quadrupole ion trap mass spectrometer Harrison et al. [19] presented results that demon- (ITMS; Finnigan-MAT, San Jose, CA) was used in this strated that the molecular ions of diethyl maleate and study. The chamber was heated to 393 K and all liquid fumarate do not interconvert at high internal energies, samples were introduced through heated leak valves but that they do at low internal energies. However, at a nominal pressure of l-2 x 10e6 torr (uncorrected). Weisz et al. [20] examined the products of collisional Solids were introduced via a heated direct insertion activation of the protonated esters in a triple stage probe. Dimethyl ether served as the reagent gas and quadrupole mass spectrometer and found that proto- was added to increase the pressure to l-2 X lop5 torr nated diethyl maleate exhibited [M + H - EtOH]+ (uncorrected). Helium buffer gas was added to bring and [M + H - EtOH - C2H4]+ fragment ions, up the total pressure into the millitorr regime. With whereas protonated diethyl fumarate lost one or two the exception of freeze-pump-thaw cycles to remove ethylene units. Thus, low energy collision-activated noncondensible gases, all analytes were used as re- dissociation (CAD) of the protonated diethyl esters of ceived from Aldrich Chemical Company (Milwaukee, fumaric and maleic acids resulted in stereospecific WI). Labeled compounds were synthesized from the dissociation pathways, which thereby demonstrated corresponding acid and the perdeutero alcohol via that these two isomers did not interconvert on colli- esterification [23]. Dimethyl ether-d,, obtained from sional activation. Isotec (Miamisburg, OH), was used to generate [M + The primary goal of our systematic study of func- CD,] ’ ions in the ITMS. Prior to collisional activation, tional group interactions is to gain a better understand- the appropriate reagent ion of dimethyl ether was ing of structure-reactivity relationships in gas-phase isolated and permitted to react with the analyte for a reactivity and fragmentation pathways of resulting time sufficient to maximize the desired ion current. ion-molecule reaction products. For example study of The ion of interest was isolated by using the apex the CAD spectra of diacid ions and their correspond- isolation method [24] and subjected to CAD. Typical ing methyl ester ions enables the effect of methyl collisional activation conditions consisted of excitation substitution on reactivity to be determined and the of the ion of interest at its resonant frequency at extent of functional group interactions to be evaluated. 200-450 mV for 10 ms. Such studies can lead to a better understanding of the Semiempirical molecular orbital calculations were factors that mediate ion-molecule reaction products, done by using MOPAC 6.0 [25] on a DEC Alpha AXP pathways, and reactivities. because functional group 4000/620 (Digital Equipment Corp., Maynard, MA). interaction is central to the success of many reactions All geometries were optimized by using the AM1 in biochemical systems, these mass spectrometric in- hamiltonian [26, 271 and analytical derivatives of the vestigations may provide new insight into understand- energy. The ground state structures were obtained by ing the intrinsic reactivities of complex substrates. The minimization of chemically reasonable structures. main objective of the present work is to determine the effects on the reactivity of the acid and ester functionalities toward dimethyl ether ions [447, 21, 221 as a DISCUSSION function of conjugation, the presence of electron- withdrawing groups, and functional group interac- The structures of the compounds used in this study are tions, such as hydrogen bonding. Dimethyl ether was shown in Figure 1. An array of substrates that possess chosen as a selective chemical ionization reagent be- one or two acid or ester functionalities and varying cause it has proven capabilities as a probe of functional rigidity were chosen to allow a complete systematic group interactions [4-7, 21, 221.

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