Functional Group-Selective Ion-Molecule Reactions of Ethylene Glycol and Its Monomethyl and Dimethyl Ethers
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Functional Group-Selective Ion-Molecule Reactions of Ethylene Glycol and Its Monomethyl and Dimethyl Ethers Erika S. Eichmann and Jennifer S. Brodbelt Department of Chemistry and Biochemistry, University of Texas, Austin, Texas, USA The selective methylation and methylene substitution reactions of dimethyl ether ions with ethylene glycol, ethylene glycol monomethyl ether, and ethylene glycol dimethyl ether were investigated in a quadrupole ion trap mass spectrometer. Whereas the reactions of ethylene glycol and ethylene glycol monomethyl ether with the methoxymethylene cation 45+ gave only [M + 131 product ions, the reaction of ethylene glycol dimethyl ether with the same reagent ion yielded exclusively [M + 151+ ions. The relative rates of formation of these products and those from competing reactions were examined and rationalized on the basis of structural and electronic considerations. The heats of formation for various relevant species were estimated by computational methods and showed that the reactions leading to the [M + 13]+ ions were more energetically favorable than those leading to the [M + 15]+ products for cases in which both reactions are possible. Finally, the collision-induced $yck$n behavior of F [M + HI*, [M + 13]+, and [M + 15]+ ions indicated that the and [M + 151 rons dissociated by analogous pathways and were thus struc- turally similar, whereas the [M + 13]+ ions possessed distinctly different structural charac- teristics. (1 Am Sot Mass Spectrom 1993, 4, 97-105) he importance of functional group interactions bilities, associative properties, and the favorabilities of and substituent effects in determining the out- competitive dissociative channels of various types of T comes of reactions both in solution [l-4] and in ions with a variety of functional groups [l-14, 16, 171. the gas phase has long been recognized [S-8]. For An understanding of such functional group interac- example, the interactions between various functional tions is important not only from a physical organic groups in diol [9], diacid [lo], diester [ll], and other perspective in predicting reaction outcomes and mech- simple systems [12-141 have been shown to have im- anisms but also from a biological standpoint. For ex- portant consequences on the physical properties and ample, hydroxyl groups and ether linkages are among reactive and dissociative patterns of these ions. In the most ubiquitous functional groups [18], and virtu- some cases, remote group participation can promote ally all possible combinations, relative positions, and reactive channels inaccessible to related molecules orientations of these functionalities can be found in lacking the interaction [15]. The converse is also true: sugars, steroids, antibiotics, and other biologically rele- The presence of an additional functional group can vant molecules. prevent certain reactions, either through steric or elec- Mass spectrometric methods have been increasingly tronic interactions or by promotion of competition be- applied to the characterization of such types of tween reactions that would otherwise be expected to biomolecules; however, the structural elucidation of predominate. these complex molecules remains deficient. The devel- The type and extent of interaction and consequent opment of activation techniques, such as collision- enhancement or inhibition of the reactions naturally induced dissociation [19] and surface-induced dissoci- depends on the nature, position, and orientation of all ation [20], for promoting fragmentations of functional groups involved. The large body of previ- biomolecules in characteristic patterns has assisted in ous work in this area has helped to establish generally solving this problem. The design of selective accepted correlations of functional group interactions ion-molecule reactions also holds promise for reveal- with gas-phase basicities and proton affinities, ion sta- ing structurally diagnostic information. Chemical ion- ization [21,22] reactions with novel reagent gases have been shown to offer great potential, and tremendous interest has therefore been stimulated in the characteri- Address reprint requests to Jennifer S. Brodbelt, Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712. zation of new site-selective reagents [23]. 0 1993 American Society for Mass Spectiometry Received June 29,1992 104&0305/93/$6.00 Revised September 25,1992 Accepted September 26,1992 98 EICHMANN AND BRODBELT J Am Snc Mass Spectmm 1993,4,97-105 We are particularly concerned with the develop- Results and Discussion ment of site-specific reactions for characterization of antibiotics, and a firm understanding of the fundamen- Comparison of Reactions tal reactions between the commdn substituents is Two reactive ions are tvoicallv formed on ionization of therefore a necessity. We have undertaken this study DME-the methoxyme;h;lene’cation and the proto- of simple disubstituted ethanes to illustrate that the (1) nated DME (2). Previous studies in our group [24, 311 reactive and dissociative properties of structurally and have shown that on reaction with the ions of m/z 45 electronically similar ions can be dramatically differ- and 47 from DME, substrates typically yield one or ent. To correlate and contrast the reactivities of more of several product ions, depending on the nature, methoxyl and hydroxyl groups, we have compared the position, and orientation of their functional groups: ion-molecule reactions of dimethyl ether ions with [M + l]+, [M + 13]+, [M + 15]+, [M + 45]+, and [M ethylene glycol and its mono- and diethers and exam- + 47]+. Although the [M + 451’ and [M + 47]+ ined the formation mechanisms for each product adduct ions, or collision complexes, are not always observed. In addition, we have made a qualitative observable in the ion trap, previous work has demon- comparison of the formation rates and relative favora- strated that the [M + I]+, [M + 13]+, and [M + 15]+ bilities of formation for the observed products and ions all originate directly from these ions [12, 311. investigated the thermodynamic properties that pre- sumably govern the reactions observed. The two reactions of interest in this study are meth- ylene substitution and methyl cation attachment. The former has been recently described for other small +A organic systems [9, 12, 241. The methyl cation attach- H,C' 'CH, ment process has also lately been of interest in studies concerning sites of electrophilic additions [25-271. 45+ 47+ 1 2 Experimental The [M + l]+ ions arise predominantly from simple A Finnigan ion trap mass spectrometer (Finnigan-MAT, proton transfer from the protonated DME molecule San Jose, CA) [28, 291 was used for all experiments. (m/z 47) to the substrate. These products presumably The samples (Aldrich Chemical Co., Milwaukee, WI) arise through initial formation of a proton-bound colli- were introduced through a heated leak valve system, sion complex at [M + 47]+, which fragments to give and typical pressures used were 1.3 X lop4 Pa. the protonated analyte (Scheme Ia). In most of the Dimethyl ether (DME) (MG Industries, Valley Forge, systems studied to date in our laboratory, including PA) reagent gas pressure was generally 1.2 x lo-” Pa, the three systems under study here, the proton affmi- and helium buffer gas was admitted at approximately ties of the substrates have exceeded that of the neutral 0.13 Pa. The ions produced by electron ionization of DME. Therefore, dissociation of the loosely bound [M DME were stored and reacted with the neutral sample -t 47]+ collision complex generally gives preferentially vapor. The ion-molecule reaction times were varied the [M + l]+ product ion. between 0 and 500 ms. Alternately, individual reagent Likewise, the [M t 131” and [M + 15]+ ions have gas ions were trapped and isolated by application of been shown to result from fragmentation of an [M + appropriate radiofrequency and dc voltages [30] and 451’ adduct that arises from the collision complex allowed to react with the neutral analyte molecules for formed between the neutral analyte and the DME varying periods of time (O-500 ms). In either case, the reagent ion at m/z 45 [12]. The complex either rear- ions formed were selectively isolated, and activated to ranges to allow transfer of a methyl group to the produce collision-induced dissociation (CID) spectra. substrate (Scheme lb, upper path) and simultaneous All thermochemical values not available in the liter- loss of formaldehyde or undergoes a different rear- ature were estimated by computer calculations. The rangement followed by loss of methanol (Scheme Ib, computational programs PCMODEL and MOPAC were lower path), resulting in a net substitution of a methy- obtained from Serena Software (Bloomington, IN) and lene group onto the substrate. were run on a Macintosh IIsi personal computer. The For ethylene glycol, ethylene glycol monomethyl molecular modeling program PCMODEL was first used ether, and ethylene glycol DME, the [M + 451’ and to approximate the minimum-energy structure, and [M + 47]+ ions are not directly observable, presum- the resulting coordinates were entered into the ably because they are formed with excessive internal semiempirical program MOPAC. The AM1 Hamilton- energy and are not sufficiently deactivated by colli- ian operator and default parameters were used in all sions with the helium buffer gas. Rather, they dissoci- cases. Calculations were performed at least three times, ate spontaneously on formation, giving [M + l]+, [M and consistent values were obtained.