Mass spectra of stereoisomers

Stereochemical aspects in mass spectrometry have aroused more and more interest. El mass spectra of stereoisomers are practically indistinguishable. However, the use of soft ionization methods (chemical ionization, field ionization, etc.) accompanied by tandem mass spectrometry allows important and reliable conclusions on the molecular structures to be drawn. 

This stereoelectronic effect may explain other cases of different mass spectra of stereoisomers. The more pronounced loss of axial versus equatorial methyl groups in heteroatom-containing decalin systems, which has been attributed... 

Systematic studies on the mass spectra of alditol acetates have revealed a simple mode of fragmentation for this class of compound. Alditol acetates do not give a molecular ion, but (M — CH3CO0 ) is found in a low abundance. The mass spectra of stereoisomers are almost identical and, therefore, the mass spectrum of D-glucitol hexaacetate (see Fig. 1) is representative of all peracetylated hexitols. 

The use of mass spectrometry in the structural analysis of carbohydrates, first reported in 1958 (114), was developed in detail by Kochetkov and Chizhov (115). They showed that, under electron impact, the acetylated and methyl ether derivatives of monosaccharides provided a wealth of structural information through analysis of typical fragmentation pathways of the initial molecular ion. This has proved of enormous utility in the structural elucidation of polysaccharides and complex oligosaccharides sequential permethylation, hydrolysis, reduction to the alditol, and acetylation, affords mixtures of peracetylated, partially methylated alditol acetates that can be separated and analyzed by use of a gas chromatograph coupled directly to a mass spectrometer (25). The mass spectra of stereoisomers are normally identical, while the gas chromatographic retention times readily permit differentiation of stereoisomers. 

Since the early days of mass spectrometry it has been proposed, that the release of steric strain results, in many cases, in lower abundances of the molecular ions and in higher abundances of fragments in the El mass spectra of the thermochemically less stable isomers in numerous systems. The differences between the mass spectra of stereoisomers in those systems are usually not large, and there are numerous exceptions which cast doubt on the reliability of this approach in real problems of configurational assignments. 

In many systems, variations in the abundances of certain fragment ions in the mass spectra of stereoisomers have been ascribed to anchimeric assistance. The loss of bromine from the molecular ions of stereoisomeric 1,2-dibromocyclopentanes... 

One of the early reported cases of distinctive mass spectra of stereoisomers was the El-induced behaviour of deacetylcyclindrocarpol 23a and of its epimer at C-19, 23b (Scheme 20). The more pronounced loss of the hydrogen atom from position 19 of the molecular ion of 23b, as compared with that of 23a (10.6% versus 1.7%), was attributed to the antiperi-planar relationship of the 19-C-19-H bond and the p-orbital of the adjacent nitrogen atom in 23b, in contrast to the epimer 23a. 

Mass spectra of the cis- and /ram-isomers of the pyrimido[2,TA [l,3]thiazin-6-ones 294 and 295 were studied. Retro-Diels-Alder fragmentation of the hydrocarbon ring was of medium to low stereospecificity. A number of highly selective processes were discovered allowing differentiation between stereoisomers <1996RCM721>. The mass spectral fragmentation pattern of 296 was studied in detail <1996PS(113)67>. 

A number of systematic structural analyses have been described for families of saturated oxazolones. First, as mentioned previously, detailed smdies of NMR long-range coupling in 2,4-disubstimted-5(47/)-oxazolones and in 5(27/)-oxazo-lones have been reported." Similarly, detailed NMR studies of the kinetics of racemization of 2,4-disubstimted-5(47/)-oxazolones have been performed. A theoretical study of the spectral-luminescence properties of some 4-alkyl-2-phenyl-5(47/)-oxazolones has been reported and an investigation of the infrared (IR) and Raman spectra of 5(4//)-oxazolones, particularly of the carbonyl group vibration, has been reported. Electron impact mass spectra of saturated 5(47/)-oxazolones have been published. More recently this technique has been used to distinguish between the stereoisomers of some spirocyclopropane oxazolones 352 (Fig. 7.36). Finally, several studies of the HPLC behavior of 5(47/)-oxazolones complete a general view for this family of compounds. " " ... 

To many, mass spectrometry is synonymous with El mass spectrometry. This view is understandable for two reasons. First, historically, El was universally available before other ionization methods were developed. Much of the early work was El mass spectrometry. Second, the major libraries and databases of mass spectral data, which are relied upon so heavily and cited so often, are of El mass spectra. Some of the readily accesible databases contain El mass spectra of over 390,000 compounds and they are easily searched by efficient computer algorithms. The uniqueness of the El mass spectrum for a given organic compound, even for stereoisomers, is an almost certainty. This uniqueness, coupled with the great sensitivity of the method, is... 

The diastereoisomers can be separated by GC on a nonchiral column because they have different retention times. However, the mass spectra of diastereoisomers are identical. As an example, in Figure 4.1.2 are shown four peaks that have identical mass spectra and are stereoisomers generated from the pyrolysis of poly(vinyI ethyl ether). Four diastereoisomers correspond to eight stereoisomers and consequently to a set of compounds with three chiral centers. 

Matrine Group.—Further information is now available on the structure of neosophoramine cf. Vol. 6). Comparison of the mass spectra of sophoramine and neosophoramine shows that the two alkaloids are stereoisomers. The presence of an axial proton at C-5 in neosophoramine was apparent from the n.m.r. spectrum, and the absence of Bohlmann bands in the i.r. spectrum indicated a cis a/b ring junction. Since sophoramine has jS-hydrogen at C-5, C-6, and C-7 and in isosophoramine all three ring junctions are trans, neophoramine was assigned structure (21). 

Mass Spectra.—A computer analysis of mass spectra of progesterone and twenty-nine of its stereoisomers and alkylated derivatives has established the main fragmentation pathways and their dependence on configurations, particularly at C-10 and C-17, and on the substitution pattern. Mass spectra of 17a-acetoxy-, Ha-hydroxy-, and 17a-methoxy-progesterones are dominated by fragmentations J. Dillon and K. Nakanishi, J. Amer. Chem. Soc., 1975,97, 5409, 5417. 

The structure XIV for villalstonine receives convincing support from the prolonged reduction with lithium aluminum hydride which affords villalstonine triol (XXVII) and isovillalstonine triol, two stereoisomers which presumably differ by the configuration at C-19. The mass spectra of villalstonine triol and its triacetate are completely in accord with the structures proposed, and demonstrate that in these molecules the attachment of the two halves is by means of one single carbon-carbon bond. Consequently, the carbon-oxygen bond must have been severed during... 

The behavior of alditol methyl ethers on m.s. has been studied by using permethylated pentitols and hexitols. The mass spectra for stereoisomers are virtually identical, and the molecular ion was not observed. Primary fragments are formed by a-cleavages of the alditol chain (14), or by elimination of methanol from the molecular ion (m/ e 234). 

The mass spectra of per (trimethylsilyl )ated alditols showed that this class of compounds is fragmented in a manner closely related to that obtaining for alditol methyl ethers. Thus, primary fragments are formed by a-cleavage of the alditol chain, and secondary fragments are produced by subsequent elimination(s) of trimethylsdanol. The number of carbon atoms in the alditol chain can be determined from the (M — CH3) and (M — McsSiOH) ions. The base peak in the spectra was the trimethylsilyl ion (m/e 73). Small variations in peak intensities were found between stereoisomers, but these diflferences are probably too small to permit the identification of stereoisomers. 

Only small variations in peak intensities for stereoisomers were observed, and these differences could not be used for identification purposes. The per(trimethylsilyl)ated inositols are fragmented by single or consecutive eliminations of CH3 , McsSiO , and MesSiOH from the molecular ion. Most of the other ions in the spectra are commonly found also in the mass spectra of per(trimethylsilyl)ated hexoses. The variation in peak intensities in the spectra of stereoisomers was considerable these differences were attributed to the bulky trimethylsilyl groups, which restrict the thermal interconversion between different conformations. Furthermore, certain elimination reactions for trimethylsilyl groups proceed by way of cyclic intermediates, and thus may be influenced by the stereochemistry. 

Perspectives and suggestions for further research New approaches to the interpretation and verification of mass spectra, to stereoisomer and conformer generation, normal forms for patents in chemistry and CASE using high resolution mass spectrometry. 

The NIST/EPA/NIH Mass Spectral Library is probably the most popular and most widely distributed library for GC-MS instruments. The 2011 edition has been largely expanded by the number of El (electron-ionization) mass spectra with the addition of Kovats RIs. MS/MS mass spectra are increasingly included. Extensive spectra evaluation and quality control has been involved in the new edition of the NIST database. Each spectrum was critically examined by experienced mass spectrometrists, and each chemical structure has been examined for correctness and consistency, using both human and computer methods (Ausloos etal., 1999). Spectra of stereoisomers have been intercompared, chemical names have been examined by experts and lUPAC names provided. CAS registry numbers have been verified. 

Two substances with the same molecular sum formula, but different structural formula, or different spatial arrangement of the atoms (stereoisomers). Isomers differ chemically and physically. Frequently mass spectra of isomers caimot be differentiated, but because of different interactions with the stationary phase, they can be chromatographically separated. 

Numerous additional examples of a distinctive mass spectral behaviour of stereoisomers, which have been attributed to anchimeric assistance both under El and Cl conditions, have been proposed in the literature. In some cases, particularly upon Cl, additional factors may be responsible for the distinctive behaviour. For instance, the higher abundance of the [MH-CH3COOHJ+ ion in the Cl mass spectra of the mws-diacetate 211 could also be attributed (at least in part) to the greater stability of the internally hydrogen bonded MH+ ion of the ds-isomer. 

Singly and doubly interlocked [2]catenanes can exist as topological stereoisomers (see p. 144 for a discussion of diastereomers). Catenanes 35 and 36 are such stereoisomers and would be expected to have identical mass spectra. Analysis showed that 35 is more constrained and cannot readily accommodate an excess of energy during the mass spectrometry ionization process and, hence, breaks more easily. 

---