Aliphatic Organosulphur Compounds, Compounds with Exocyclic Sulphur Functional Groups, and their Selenium and Tellurium Analogues

BY G. C. BARRETT

In spite of the large number of literature citations included in this Chapter, many of the routine papers on preparative chemistry have been excluded. The fact that so much work has been considered worthy of inclusion in this review on the basis of novelty and importance testifies as much to the intricacies and surprises still being found in the chemistry of sulphur- and selenium-containing functional groups as to the continuing growth in importance of these compounds in organic synthesis.

1 Textbooks and Reviews

Books published recently include several that are wholly devoted to organosulphur compounds and others in which specific chapters are relevant to the coverage in this chapter. Reviews have appeared that deal with applications of organosulphur compounds in synthesis (including uses of β-keto-sulphides, vinyl sulphones, and vinyl sulphides) and the synthesis of organosulphur compounds, sulphenyl compounds, indolethiols, allenic sulphides and sulphenamides, organosily sulphides, selenides, and tellurides, optically active sulphur compounds, sulphur-centred radicals, episulphonium intermediates, barriers to S–N bond rotation in sulphenamides, l,2-phenylthio-shifts, thio-Claisen rearrangements. Pummerer reactions, and Ramberg–Bäcklund rearrangements. A review of nucleofugacity of different leaving groups in elimination reactions concerns several sulphur-containing functional groups.

Organoselenium chemistry has been reviewed from the point of view of applications in synthesis in general, and for mild oxidative transformations, as well as for its relevance in biochemistry. Coverage of the 1976–7 literature for organotellurium chemistry has been published.

2 Spectroscopic and Other Physical Properties of Organosulphur, Organoselenium, and Organotellurium Compounds

Molecular Orbital Calculations and Conformational Analysis. — syn Conformations are preferred for vinyl mercaptan, for methyl vinyl sulphide, and for methyl allenyl sulphide. Similar M.0. studies of 1,1-bis(methylthio)ethylene, simple dithioacetals, and 1,2-dithiols and l,2-bis(methylthio)ethane relate to conformational aspects. Continuing themes are represented in alternative explanations for the role of the sulphur atom in determining which proton is most readily released from unsymmetrical sulphides R1CH2SCH2Ri (both hyperconjugation and C–S polarization are involved). The stabilization of the α-carbanion is accounted for by the ability of the sulphur atom to allow excess negative charge to encroach into its sp-valence shell. Activation of dioxygen by sulphonium salts arises through orbital interactions.

Molecular Orbital (M.O.) studies of reaction intermediates have been reported for the rearrangement of 1-propenethiol, for the addition of sulphenyl halides to ethylene (sulphurane rather than thiiranium salt as intermediate), and for similar additions to alkynes (thiirenium ions or β-alkylthiovinyl cations, depending upon the substituents). Electronic effects of substituents on energy levels of orbitals of sulphur provide the motivation for M.0. studies of substituted phenyl methyl sulphides, aryl trifluoromethyl sulphones, and substituted styryl sulphones.

Force-field analysis assigns the gauche conformation to H2S4 and Me2S4 Continuing studies (see Vol. 5, pp. 2, 7) indicate a preference for the equatorial orientation of the MeS substituent in 5-methylthio-1,3-dithians, although comparison of experiment with theory indicates the limited success of the calculations, since the equatorial preference is substantially larger than predicted. The dangers of generalizations are implied in the results of conformational analysis of asubstituted cyclohexanones, since the order PhS02, PhS, PhSO emerges for the preferred adoption of the axial conformation, in contrast to the order MeS, MeSO, MeSO2 established earlier for the corresponding cyclohexanones.

Ultraviolet Spectra, Circular Dichroism, and Optical Rotatory Dispersion. — Routine u.v. studies of the effects of sulphur-containing groups on the spectral absorption characteristics of substituted benzenes (references are collected at the end of this section) continue along familiar lines (see Vol. 5, p. 4). A model for the thioindigo chromophore, i.e. MeCOC(SMe)=C(SMe)COMe, has been shown by X-ray studies to be non-planar, as a result of repulsion between methyl groups.

Studies of the circular dichroism of acyl derivatives of thioglycerols and of 2- or 3-phenylalkyl isothiocyanates constitute extensions of earlier work.

Infrared, Raman, and Microwave Spectra. — Brief details of studies which provide information on conformations and electron distributions are summarized at the end of this section. A comparison of the polarized Raman spectra for (C2H3)2SO2 with far-i.r. data for Me2SO2 and polarized i.r. spectra for aryl thiocyanates and selenocyanates represent less routine studies.

Nuclear Magnetic Resonance Spectra. — Long-range coupling involving the thiol proton and ring protons in 2-methoxybenzenethiol, halogenobenzenethiols, and 2-hydroxybenzenethiol has been suggested to indicate an out-of-plane conformational preference for the SH group in thiophenols (see also Vol. 5, p. 6), and hence reveals an important contrast with the analogous phenols. Other non-routine 1H n.m.r. studies include those of lanthanide-induced shifts of sulphonium salts and of alkylsulphinylmethyl alkyl sulphides and assignment of the zwitterionic structure (1) to the Schiff bases derived from o-formylbenzenethiol. Brief details of other 1H n.m.r. work (but excluding data compilations) are collected together at the end of this section, where details of 13C n.m.r. studies are also to be found. More complete coverage of the 13C n.m.r. literature has been attempted, since missing details are still being located, with the objective of providing a full assessment of the influence of adjacent sulphur-containing functional groups on chemical shifts.

Nitrogen-15 n.m.r. spectra of alkanesulphonamides, benzenesulphonamides, and isothiocyanates have been reported. Nitrogen-14 n.q.r. data on methane-sulphonamide and NN-disubstituted analogues have established a valuable application of the technique, i.e. to assess the degree of delocalization of the lone

[FORMULA OMITTED] (1)

pair that is formally located on nitrogen in such compounds. Chlorine-35 n.q.r. studies on α-chloroalkyl sulphides have been reported.

Selenium-77 n.m.r. data for selenols, selenides, selenomum salts, diselenides, and selenoxy-acids have been obtained under conditions (i.e. on the same spectro-meter) which allow reliable comparisons of spectral parameters to be made. Benzeneseleninic acids and selenolesters have also been studied by this technique, and Se spin–lattice relaxation times of organoselenium compounds have been collected in a pioneering study.

Tellurium-125 n.m.r. spectra of telluroesters have been determined.

Mass Spectra. — A continuing investigation into the finer details of the structures of secondary fragmentation products from thiols and sulphides (see Vol. 5, p. 7) involves several research groups. The ion CH2=[??]H that is formed from primary thiols by α-cleavage has been shown by collisional activation mass spectrometry to be more stable than CH3S+; the same technique has been used to show the occurrence of substantial C–S bond cleavage in sulphenyl cations (RS+) after their formation by field desorption. Broer and Weringa have carried further their painstaking study of the alternative fragmentation course available to sulphide molecular ions, and have used 2H- and 13C-labelled sulphides to establish the formation of Me[??]=CH2 and MeCH=[??]H by loss of the methyl radical from the molecular ion of ethyl methyl sulphide. They have also ascertained which of the isomeric C3H7S+ ions fragments further into H2S and ethylene. The formation of methane from EtS+ and of hydrogen from Mes+ liberates the species [CHS]+.

Ion cyclotron resonance studies of 3-methoxyalkanethiols and homologous sulphides MeO(CH2)nSMe (n = 1 — 3) have provided information on the reactivity profile of the methoxymethyl cation towards alcohols, thiols, and amines, and on the preferential abstraction of hydride ion from the carbon atoms that are alpha to sulphur (confirming that, in gas-phase reactions, S is more able than O to stabilize a neighbouring carbonium ion). Gas-phase acidities of dimethyl sulphoxide and representative aliphatic sulphones reveal a lower degree of stabilization of the α-sulphonyl carbonium ions.

Photoelectron Spectra. — Organosulphur compounds are appropriately represented in the broad evaluation of this technique. The dihedral angle for the C–S–S–C grouping in di-t-adamantyl disulphide is 103°, which is on the way to a fully trans configuration, favoureds for disulphides only when bulky substituents are involved.

Photoelectron spectral data have been collected for MeSCl, MeSBr, MeSCN, and MeSeCN. The trigonal-bipyramidal structure has been established for methylenesulphur tetrafluoride through p.e. spectroscopy, electron diffraction, and X-ray analysis.

Electron Diffraction. — Among completed electron-diffraction studies are ethyl methyl sulphide, chloromethyl methyl sulphide, methyl phenyl sulphide di(2-pyridyl) sulphide, sulphones, sulphoxides and sulphones, and trifluoro-methanesulphonyl chloride. A number of precise analyses of gas-phase conformational equilibria have emerged. Methyl ethyl sulphide shows a preference for the gauche conformation rather than for the trans form.

Dipole Moments and Studies of the Kerr Effect. — A number of references, together with brief details, have been collected from the recent literature:

S. G. Gagarin and R. Z. Zakharyan, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 31 [MeSH, EtSH, Me2S, and Et2S); D. M. Petkovic and J. S. Markovic, Glas. Hem. Drus., Beograd, 1979, 44, 535 (Chem. Abstr., 1980, 92, 146 131)[thiols]; V. Baliah and V. M. Kanagasabapathy, Indian J. Chem., Sect. B, 1978, 16, 810 [diaryl sulphides]; B. A. Arbuzov, A. M. Salikhova, S. M. Shostakovskii, A.N. Vereshchagin, and N. S. Nikolskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 2786 (gem-dichlorocyclopropyl sulphides]; 0. Exner and J. B. F. N. Engberts, Collect. Czech. Chem. Commun., 1979, 44, 3378 [halogenomethyl sulphones and N-nitro-N-methylarenesulphonamides]; M. S. R. Naidu, S. G. Peeran, and D. B. Reddy, Indian J. Chem., Sect. B, 1978, 16, 1090 [unsymmetrically substituted 1,2-di-(arylsulphonyl)-1,2-diphenylethylenes]; P. Ruostesuo, Finn. Chem. Lett., 1978, 159 and 166 [benzenesulphenamides]; G. G. Butenko, A. N. Vereshchagin, A. B. Remizov, and R. N. Nurulllna, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1763 and G. G. Butenko, A. N. Vereshchagin, and D. M. Nasyrov, ibid., p. 2034 [methyl arenesulphonates and arenesulphonamides]; R. V. Sendega and T. A. Protsailo, Ukr.Khim. Zh., 1978, 44, 844 (Chem. Abstr., 1979, 89, 196 491) [alkyl and alkenyl benzenesulphonates]; A. M. Kamalyutdinova-Salikhova, T. G. Mannafov, R. B. Khismatova, S. G. Vulfson, and A. N. Vereshchagin, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1757 [gem-dichlorocyclopropyl aryl selenides].

X-Ray Crystal Analysis. — The host–guest partnership arrangements for hexakis-(alkylthiomethyl)benzenes including chiral guests and for the corresponding sulphones with l,4-dioxan and squalene as guests have been elucidated by X-ray analysis. Diethyl and diphenyl dithioacetals of D-ribose and N-sulphinyl benzenesulphonamide have also been studied, the latter compound being revealed as adopting the cis configuration and possessing an electron-rich S–N bond. A simple empirical relationship between the S–S bond lengths and the X–C–S–S torsion angles has emerged from a study of the crystal structures of 21 symmetrical disulphides.

The mono- and di-hydrates of Ph3SeCl are ionic compounds of five-co-ordinate selenium.

Electron Spin Resonance Spectra. — Radicals arisingfrom photolysis of diaryl disulphides (ArS·), and of reaction mixtures of ButSH and SCl2 (ButSS·) have been studied by e.s.r. (a routine monitoring technique used in several of the studies of sulphur radicals mentioned later in this Chapter). Arenesulphonyl cation radicals, formed from 2-alkoxy-5-methylbenzenesulphonyl fluorides and sulphonic acids on treatment with PbO2 and FS03H, provide a further example of sulphur-centred radicals, while a variation on this aspect is provided by the report of the influence of the alkylthio-group in p-(alkylthio )nitrobenzenes on the hyperfine splitting in the spectra of derived radical anions and nitroxides. The alkylthio-group has thus been shown to behave as a π-electron acceptor when a suitable angle exists between the vacant σ* orbital of the S–R bond and the π-orbital of benzene.

3 Thiols, Selenols, and Tellurols

Preparation. — An important addition to methods for the reduction of sulphonyl compounds to sulphenyl analogues, i.e. the direct reduction of sulphonic acids to thiols using trifluoroacetic anhydride and Bun4N+1-, has been reported. A mixture of thiol and the corresponding trifluorothiolacetate is obtained; this, on hydrolysis, yields the thiol and easily separable elaboration products. Most of the other recent papers describing preparations of thiols are collected together at the end of this section since, although often describing improved methodology, they are based on well-tried procedures. Among methods using H2S as reagent is an interesting study that has established a Meerwein–Ponndorf–Verley-type mechanism (Scheme 1) for the conversion of an alcohol into the corresponding thiol, using H2S and Al2O3, with a ketone as co-catalyst.

Thiocarbonyl compounds offer reliable entries to thiols, and thiourea has been used for the conversion of chloromethylated polystyrene into the corresponding polymeric thiol. NN-Dimethylthioformamide and sodium NN-dimethyldithio-carbamate have been used similarly, the latter leading to pyridine-2,4- and -2,5-dithiols from diazotized amino-chloropyridines. Another well-established route, i.e. conversion of phenols into benzenethiols via thionocarbamate intermediates and rearrangement at 200 — 280 °C, has been used for the synthesis of 4-alkyl- and 4-cyano-derivatives. Reduction of di-t-butyl selenone with LiAlH4 gives the corresponding selenol, and the reduction by NaBH4 of 2-aryl-3piperidino-indane-1-thione gives the 2-arylindene-1-thiol; an unusual reductive cleavage of an enamine. The thiol (2) is one of several trimers of dithioacetic acid.

A conventional route from an alkanol to a thiol, via the trifluoromethane-sulphonate and treatment with MeCOS- Na+, has been used for the synthesis of the surfactant C16H33[??]Me2CH2CH2SH Cl-.

Ring-opening reactions of sulphur-containing heterocyclic compounds which lead to thiols include Birch reduction of thiophen-2-carboxylic acid, to give a mixture of products that includes HO2CCH2CH=CHCH2SH and and HO2CCH=CH-CHMeSH; photolysis of 4-thiochromanone enol acetate to give (3) by a novel 1,5-acyl migration in the intermediate o-thioquinone methylide; and cleavage (by Na in NH3) of s-trithians and related compounds [(CH2S)3 [right arrow] MeSCH2SCH2S-Na+].

Reactions of Thiols, Selenols, and Tellurols. — Many of the reactions of thiols depend on the high nucleophilicity of the thiolate anion, and lead to sulphides or other sulphur-containing functional groups. Reactions of this type are therefore discussed in later sections of this Chapter.

Alkylthiolate anions are more reactive by a factor of 104-105 than OH- towards tropylium cations and carbonyl compounds. Furthermore, PhSe- is at least five times more nucleophilic than PhS-, but the latter nucleophile, paradoxically, is capable of dealkylating PhSeMe and tertiary amines when in the presence of Pd, PdCl2, Pd(OAc)2, or RuC13. Demethylation of methyl ethers and esters by treatment with a thiol in the presence of an aluminium trihalide has been reported.

The simplest method yet uncovered for the replacement of the diazonium group by H (or 2H) is the use of PhSH (or PhS2H); so far, the reaction seems to be limited to arenediazonium cations. Further reductive processes that are mediated by thiols are the conversion of 1-nitro-alkenes into alkenes (+ NaNO2 + PhSSPh + S8) by PhSH and Na2S, corrole-catalysed photoreduction of benzaldehyde by PhSH, reduction of benzyl halides by RS- Et3NH+ or RSe- Et3NH+, and the use of propane-1,3-dithiol in the presence of triethylamine for the reduction of azides to amines.