The use of mass spectrometric techniques to distinguish and characterize isomeric substances is surveyed. Mass spectral differences between isomers can arise because of differences in ionization, ion kinetics, hydrogen transfer and other reactions, anchimeric assistance and stereo-electronic effects. The special case of recognition of enantiomers is also covered. Many examples are provided.

Second Edition of the Encyclopedia of Spectroscopy and Spectrometry pulls key information into a single source for quick access to answers and/or in-depth examination of topics. SPEC-2 covers theory, methods, and applications for researchers, students, and professionals - combining proven techniques and new insights for comprehensive coverage of the field. The content is available in print and online via ScienceDirect, the latter of which offers optimal flexibility, accessibility, and usability through anytime, anywhere access for multiple users and superior search functionality. No other work gives analytical and physical (bio)chemists such unprecedented access to the literature. With 30% new content, SPEC-2 maintains the 'authoritative, balanced coverage' of the original work while also breaking new ground in spectroscopic research. The key features of the book include: incorporates more than 150 color figures, 5,000 references, and 300 articles (30% of which are new), for a thorough examination of the field; highlights new research and promotes innovation in applied areas ranging from food science and forensics to biomedicine and health; and features a new co-editor: David Koppenaal of Pacific Northwest National Laboratory, Washington, USA, whose work in atomic mass spectrometry has been recognized internationally.

This chapter contains sections titled: Introduction Ionization Methods Appearance Potentials and Thermochemical Measurements Theoretical Treatments and Fundamental Aspects of Fragmentation Processes of Simple Acetylenes Location of the Triple Bond by Mass Spectrometry Decomposition of Acetylenes under Electron Impact Ion-Molecule Reactions References

This work involves the preparative separation of some isomeric dicarboxylic acids using pH-zone-refining counter-current chromatography (CCC), a relatively new preparative technique for the separation of ionizable compounds. The paper concentrates especially on the separation of a synthetic mixture of closely related cis and trans pairs of 1-methyl- and 1,3-dimethyl-1,3-cyclohexanedicarboxylic acids. The elution sequence of the isomers is discussed in terms of their relative acidities (pK(a) values) in solution and gas phase, hydrophobicities, and steric configuration. Two possible explanations are suggested for the mechanism of separation. They both involve the amount of retainer acid used, as it affects the separation and plays a role in the chemohydrodynamic equilibrium of the dicarboxylic acids in the column.

1,4-Dialkoxybutanes afford very abundant [MH–ROH]+ ions upon isobutane chemical ionization (CI) and collision induced dissociation (CID), in contrast to other primary mono-ethers or 1,ω-diethers of long chain diols. This behavior suggests involvement of anchimeric assistance in the mechanism of alcohol elimination from the MH+ ions of 1,4-dialkoxybutanes. This concerted mechanistic pathway finds support in the CI and CID behavior of the [MH–ROH]+ ions, obtained from isomeric mixed 1,4-dialkoxybutanes (1-ethoxy-4-methoxy- and 1-methoxy-4-ethoxy) substituted at position 2 with alkyl groups or with deuterium atoms. Density functional (DFT) calculations at B3LYP/6-31G** level of theory also support the anchimerically assisted elimination mechanism. The isomeric mixed 1,4-dialkoxybutanes, substituted at position 2 with alkyl groups of variable bulkiness, exhibit preferential elimination of alcohol from position C-4 rather than from C-1, and this tendency increases with the size of the substituents. This steric effect is explained by a more hindered transition state involved in the anchimerically assisted elimination of alcohol from C-1 due to interaction of the substituent(s) at position 2 with the protonated alkoxy group at position 1. Calculations show the energies of transition states resulting in 4-elimination products are lower than those leading to the elimination of alcohol from position 1, and the difference significantly increases with the increase of the bulkiness of the 2-substituents.

The isomeric 3- and 4-dehydrobenzenesulfonic acid anions b and c were prepared by collision induced dissociation (CID) of the [M - H](-) ions of isomeric sulfobenzoic acids obtained by negative electrospray ionization (ESI). The CID spectra (MS(3)) of anions b and c are different from each other, and both are different from that of the isomeric benzenesulfonate anion a, obtained from benzenesulfonic acid. The stability of ions b and c shows that 1,2-proton transfer does not take place in this system under the conditions of the CID experiment. Density functional (DFT) calculations at B3LYP/6-31+G(2d,p) level of theory show that benzenesulfonate anion a is the most stable isomer, and the energies of isomers b and c are higher by more than 65 kcal mol(-1). The calculated energies of the transition states involved in the 1,2-hydrogen migration leading to the interconversion of the isomeric anions are very high (>120 kcal mol(-1)relative to ion a, barrier energies >55 kcal mol(-1)), much higher than those of transition structures leading to fragmentation. This situation does not allow isomerization of ions b and c to a, under the conditions of the CID experiments. The isomeric 2-dehydrobenzenesulfonic acid anion isomerizes to the benzenesulfonate anion a by a facile proton transfer from the SO(3)H group to the adjacent position 2. The results of this work indicate that the gas phase deprotonation of meta- and para-sulfobenzoic acids is a kinetically controlled process.

A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical ionization and collision-induced dissociation of their MH(+) ions, whereby a new bond is formed between the two benzyl groups, giving rise to abundant [C(14)H(13)](+) (m/z 181) ions. This rearrangement has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an ion-neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A similar highly efficient intramolecular electrophilic substitution takes place in di-alpha- and beta-naphthylmethyl adipates affording m/z 281 [C(22)H(17)](+) ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient rearrangement occurs in benzyl alpha- and beta-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl alpha- and beta-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of the O-R bond heterolysis of the protonated functionalities, the ability of the neutral R' groups (non-dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic substitution processes and the electrophilicity of the R(+) ions.

Isomeric mixed methyl ethyl esters of 2-methylmaleic acid (citraconic acid) show different electron ionization (EI) mass spectra. Methyl radical is exclusively lost from the M+ ion of one isomer ((Z)-methyl 3-ethoxycarbonyl-2-butenoate), while the elimination of methanol is more efficient in the other ((Z)-ethyl 3-methoxycarbonyl-2-butenoate). Mechanistic pathways have been proposed for these two specific reactions based on the results of deuterium labeling and collision-induced dissociation (CID) studies. The initial step in both fragmentation processes is the hydrogen transfer from position 2 of the ethoxy group to the oxygen atom of the adjacent carbonyl. The proposed ion structures and mechanistic pathways were supported by theoretical calculations using hybrid B3LYP density functional (DFT) method with the 6-31G(d,p) basis set.

An enhanced elimination of methanol under isobutane-chemical ionization (CI) conditions, resulting in highly abundant [MHCH3OH]+ ions, has been observed in several primary and secondary methyl ethers having a tertiary β-position (methine), as compared with those with β-methylene. This elimination is stereospecific in stereoisomeric 2-methyl-1-methoxycyclohexanes and in other ethers affording significantly more abundant [MHCH3OH]+ ions in the cis-isomers than in their trans-counterparts. These findings suggest involvement of a 1,2-hydride migration from the β- to α-position in the course of the alcohol elimination from the MH+ ions of the above cis-ethers, resulting in stabilized tertiary carbocation structures. The possible pathways of methanol elimination from protonated cis-2-methyl-1-methoxycyclohexane were explored by density functional calculations at the B3LYP/6-31+G(d,p) level of theory. The transition states for MeOH elimination involving 1,2-hydride migration were located and the activation energy of the process was evaluated. The activation barrier of the alcohol elimination assisted by 1,2-hydride migration is lower by ∼10kcal/mol than the simple bond cleavage (9.6kcal/mol vs. 20.5kcal/mol). These computational results support the mechanistic pathway involving the 1,2-hydride transfer. A step-wise mechanistic pathway is proposed for the less efficient elimination of methanol from protonated trans-2-methyl-1-methoxycyclohexane.

Several positional isomers of 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids prepared as reference materials for development of analytical methods involved in FDA certification of D&C Yellow No. 10 (Quinoline Yellow) were found consistently to show [MH + 14](+) ions when their electrospray- or atmospheric pressure chemical ionization-prepared MH+ ions were subjected to collisional activation. The source of these ions was found to be the methanol used as solvent in these procedures which combined with their [MH - H2O](+) ions under chemical ionization conditions. The reaction was found to be sensitive to their isomeric and chemical structures and other examples of this process are reviewed. Copyright (C) 2002 John Wiley Sons, Ltd.

The isobutane chemical ionization (CI) mass spectra of cis- and trans-1,4-di(alkoxymethyl)cyclohexanes, with a tertiary alkoxy group ROH and a primary group R'OH, are identical, and they exhibit exclusive elimination of the alcohol ROH originating from the tertiary alkoxyl. The high abundance of the [MH - ROH](+) ion and the absence of [MH - R'OH](+) and MH+ ions is unexpected in the case of trans-diethers, and it suggests proton transfer from the primary alkoxyl OR' to the tertiary OR group prior to the elimination of ROH, despite the large distance between them in the trans configuration. Various isomerization pathways were explored in order to account for the similar behavior of the cis- and transisomers upon chemical ionization. The results show that the hydrogens at positions 1 and 4 are not involved in the elimination of ROH. Methyl substitution at positions 1 and 4 leads to the competitive elimination of ROH and R'OH, indicating suppression of the proton transfer. Methyl substitution at position 1 adjacent to the primary alkoxy group has a minor effect on the chemical ionization behavior of the diethers. On the other hand, methyl substitution at position 4, adjacent to the tertiary alkoxy group, suppresses the proton transfer, (i.e. both [MH - ROH](+) and [MH - R'OH](+) are abundant in the CI mass spectra of the trans-isomers), indicating an effect of steric hindrance. The results suggest that direct proton transfer via a strained proton-bound transition-state occurs, and methyl substitution at positions 1 and 4 can affect the relative stability of the transition-state structures involved. Similar behavior has been observed in the CI and collision-induced dissociation spectra of 1,4-hydroxy ester cyclohexanes. Copyright (C) 2001 John Wiley &, Sons, Ltd.

Tetrahydropyranyl (THP) ethers of cis-1-methoxymethyl-, 1-benzyloxymethyl-, and 1-hydroxymethyl-4-cyclohexane methanols and of cis-1,4-dihydroxycyclohexane, and THP ester of cis-1,3-cyclohexane dicarboxylic acid (cis-3–cis-7, respectively) exhibit low abundance MH+ ions and undergo efficient elimination of dihydropyran (DHP) upon isobutane chemical ionization (CI). In contrast to this behavior, the trans isomers give rise to highly abundant MH+ ions, whereas the elimination of dihydropyran affords low abundance [MH−DHP]+ ions. A similar stereospecific behavior has been also observed under collision-induced dissociation (CID) conditions. Tetrahydropyranylium ion (m/z 85), obtained by a simple CO bond dissociation, is abundant in the CI and CID mass spectra of both stereoisomers in all the examined systems. The high stereoselectivity suggests intermediacy of internal proton bridging of the two adjacent basic sites in the formation of the [MH−DHP]+ ions from the MH+ ions of the cis isomers. Thermochemical analysis indicates stabilized proton bridged structures for the [MH−DHP]+ ions. A mechanistic pathway has been proposed for the DHP elimination, based on the stereospecificity of this process and on its thermochemistry.

Positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids give rise to similar electrospray ionization (ESI) and atmosphere pressure chemical ionization (APCI) mass spectra, which show very abundant MH(+) ions and negligible fragmentation. The MH(+) ions of these isomeric acids exhibit notably different behavior under collision-induced dissociation (CID) conditions. The acids with a sulfonic group at position 8' in the quinoline moiety, adjacent to the N-atom, exhibit highly abundant [MH - H(2)SO(3)](+) ions (m/z 272 for the mono- and m/z 352 for the disulfonic acids), which are of lower abundance in the CID spectra of isomers with the SO(3)H group at other positions, remote from the nitrogen atom. The latter isomers undergo efficient eliminations of SO(3) and HSO(3). The isomeric diacids with one SO(3)H group at position 4 of the indene-1,3(2H)-dione moiety, adjacent to one of the carbonyl groups, undergo highly efficient elimination of H(2)O. Mechanistic pathways, involving interactions between adjacent groups, are proposed for the above regiospecific fragmentations. Pronounced different behavior has been also observed in negative ion tandem mass spectrometric measurements of the sulfonic acids. The distinctive behavior of the isomeric acids was strongly pronounced when the measurements were performed with an ion trap mass spectrometer (LCQ), and much less so with a triple-stage quadrupole instrument (TSQ).

Protonated molecules of a variety of benzyl diethers, diesters and ether-esters, produced by chemical ionization (CI), undergo a unique rearrangement yielding relatively abundant m/z 181 C14H13+ ions, both in the ion source and under collision-induced dissociation (CID) conditions. This highly general rearrangement involves an intramolecular C-C bond formation between the two benzyl groups, and the resulting C14H13+ ions have been shown by the analysis of their CID spectra to be an almost equimolar mixture of isomeric alpha-omicron-tolylbenzyl, alpha-p-tolylbenzyl and p-benzylbenzyl cation structures in all cases. This structural information suggests that this process may be viewed as gas-phase aromatic substitution of the non-charged benzoxy group by the benzyl cation originating from the protonated ether function involving a series of pi- (and/or ion-neutral) and sigma-complexes. The extent of this rearrangement process strongly depends on the nature of the benzyl bond heteroatoms. Tt is dramatically suppressed in the MH+ ions of benzyl disulfides and absent in diamines, diamides and amino-amides. The different behaviour of the O-derivatives vs. S- and N-analogues is explained in terms of the energies of the benzyl-XH+ bond heterolytic cleavages, which have been shown to increase in the order: O < S < N.

The abundant [MH - MeOH](+) ions in the isobutane-chemical ionization (CI) mass spectra of trans-4-amino-1-methoxycyclohexanes (where proton transfer between the two sites does not take place, in contrast to the cis-isomers) indicate protonation at the two basic sites, affording two isomeric MH+ ions in each case, one protonated at the dimethylamino group, MH+(N), and the other at the less basic oxygen function, MH+(O), This result shows that the isobutane-CI protonation of the aminoethers is a kinetically controlled process, occurring competitively at both basic sites (despite the large difference between their proton affinities, -105-145 kJ mol(-1)), and the ion abundance ratio [MH+] / [MH - MeOH](+) reflects the ratio of abundances of the isomeric MH+ ions, MH+(N) and MH+(O), initially protonated at one of the two sites. The latter ion abundance ratio decreases with the bulkiness of the N-substituents (by a factor of more than 10 between N,N-dimethyl- and N,N-diisopropyl-derivatives), indicating lower rates of protonation at the amino group when the approach of the protonating reagent (C4H9+ ion in our measurements) to the nitrogen atom is increasingly hindered by the N-substituents. Another effect of steric hindrance in the CI process involves enhanced formation of the molecular radical cations M+. (presumably by a charge exchange mechanism), in competition with the usual protonation, in aminoethers with bulky N-substituents.

The elimination of methanol from the MD+ ion of 2,3-cis-3-methoxytricyclo[6.2.2.0(2.7)]dodeca-9-ene, endo-2, upon chemical ionization (CI) gives rise to both [MD - MeOD](+) and [MD - MeOH](+) ions. Only the [MD - MeOH](+) ion is formed under collision-induced dissociation (CID) conditions. This is in contrast with the behavior of the 2,3-trans-stereoisomer exo-2 and with saturated analogs which undergo exclusive elimination of MeOD, The unusual elimination of MeOH from endo-2 indicates transfer of the external deuteron in the MD+ ion from the oxygen atom to the interior of the organic moiety and a back transfer of a hydrogen from the organic moiety to the oxygen atom prior to the C-O bond dissociation step. A deuterium labeling study showed that the hydrogen atom involved in this elimination process originates at position 3 (formal 1,1-elimination). These results suggest a multi-step mechanism for this unique stereospecific methanol elimination, initiated by a proton transfer from the methoxy group to the double bond followed by a 1,4-methoxyl migration from C-3 to C-10, The proposed mechanism finds support in the CI and CID study of deuterium-labeled analogs which have a methoxy group at position 10. Copyright (C) 1999 John Wiley & Sons Ltd.

The elimination of acetic acid from the MH(+) ions of acetates of stereoisomeric 2-methyl-1-cyclohexanols and 1-hydroxy-trans-decalins exhibits a significant degree of stereospecificity under isobutane chemical ionization and collision-induced dissociation (CID) conditions, resulting in more abundant [MH - AcOH](+) ions in the cis-isomers 4c and 5tc than in their trans-counterparts 4t and 5tt. These findings suggest the involvement of a 1,2-hydride shift from the beta- to the alpha-position in the course of the acetic acid elimination from the MH(+) ions of the above cis-acetates, resulting in tertiary carbocation structures. The proposed mechanism of the elimination is supported by a considerable deuterium isotope effect detected in beta-deuterium-labeled cis-2-methyl-1-acetoxycyclohexane and by a CID study of the structures of the [MH - AcOH](+) ions obtained from cis- and trans-1,2-diacetoxycyclohexanes. Copyright 1999 John Wiley & Sons, Ltd.

It has recently been shown that in the 3-methoxytricyclo[6.2.2.0(2.7)]dodeca-9-ene system the 2,3-cis-isomer (endo-1) undergoes a unique multi-step methanol elimination under chemical ionization (CI) and collision-induced dissociation (CID) conditions, involving a 1,4-migration of a methoxy group from position 3 to 10, which is possible only in that particular stereoisomer. The epimeric 2,3-trans-stereoisomer (exo-1) and saturated analogues undergo elimination of MeOH by different pathways. In the present work the mechanistic pathways of alcohol elimination were examined in analogous stereoisomeric protonated mixed ethyl-methyl 3,6-diethers (2) by an extensive deuterium labeling and CID study. The cis-endo isomer endo-2 with both endo-alkoxy groups undergoes methanol and ethanol elimination partly by the multi-step pathway, involving the 1,4-migration of an alkoxy group from position 3 or 6 to 10 or 9, respectively, under both CI and CID conditions. In the two trans-diethers, the elimination of alcohol involving the endo-alkoxyl occurs mainly via the multi-step pathway involving the 1,4-migration, whereas that involving the exo-alkoxy group takes place by different routes, which have been also investigated. The results of this work show the diversity and often complexity of mechanistic pathways of alcohol elimination from protonated cyclic secondary ethers, where the simple C-O bond cleavage leading to a secondary cation is a relatively high-energy process. Copyright (C) 1999 John Wiley & Sons, Ltd.

Protonated molecules of a variety of benzyl diethers, produced by chemical ionization (CI), undergo a unique rearrangement yielding relatively abundant m/z 181 C14H13+ ions, both in the ion source and under collision-induced dissociation (CID) conditions. This highly general rearrangement involves an intramolecular C-C bond formation between the two benzyl groups, and the resulting C14H13+ ions have been shown by the analysis of their CID spectra to be an almost equimolar mixture of isomeric alpha-o-tolylbenzyl, alpha-p-tolylbenzyl and p-benzylbenzyl cation structures in all cases. This structural information suggests that this process may be viewed:as gas-phase aromatic substitution of the non-charged benzyloxy group by the benzyl cation originating from the protonated ether function involving a series of pi- (and/or ion-neutral) and sigma-complexes. The extent of this fragmentation in alkane benzyl diethers PhCH2O(CH2)(n)OCH2Ph (n = 2-10,12) is strongly affected by the alkane chain length. Stereoisomeric benzyl diethers display an unusual steric effect: the trans-isomers give rise to more abundant C14H13+ ions than their cis-counterparts. The latter two effects are explained in terms of intramolecular hydrogen bonding between the two alkoxy groups. Bis(benzyloxy)benzenes and -naphthalenes exhibit very low abundance C14H13+ ions in contrast to the aliphatic analogues. This behavior is attributed to competing intramolecular benzylation involving the aromatic skeletons of these compounds.