Aliphatic Organo-sulphur Compounds, Compounds with Exocyclic Sulphur Functional Groups, and their Selenium and Tellurium Analogues

BY G. C. BARRETT

The literature covering compounds containing organosulphur functional groups is reviewed in this chapter, which is split, as in previous Volumes, into sections dealing with the different classes of organosulphur compounds. Preliminary sections list textbooks and reviews, and spectroscopic and other physical properties, dealt with in an integrated manner. Later chapters in this volume review the literature of organosulphur compounds containing thiocarbonyl functional groups, and compounds enclosing organosu1phur functional groups as integral parts of cyclic systems.

1 Textbooks and Reviews

Specialist textbook coverage is becoming less sparse in this area of organic chemistry; the plenary lectures and abstracts of papers presented at the VIth International Symposium on Organic Sulphur Chemistry have been published, and a number of specific topics have been reviewed in monograph form. Thorough coverage of organoselenium and organotellurium chemistry has been published.

Recent developments in organosulphur chemistry have been broadly reviewed, and other more general reviews cover applications of electron spectroscopy and dynamic conformational analysis of organosulphur compounds.

General comments on the problems of handling organotellurium compounds, which are sensitive to oxygen in solution, are given in ref. 138.

Reviews of the following topics have appeared: alkynethiols and thioketens, addition of SCl2 to unsaturated systems, pyridyl sulphides and selenides, 1-lithiocyclopropyl phenyl sulphide and diphenylsulphonium cyclopropylide as alkylating agents, sulphuranes, α-halogenosulphoxides and related compounds, allylic sulphoxides and sulphides in organic synthesis, stereo-chemistry of sulphoxides, α-sulphinylcarbanions, aliphatic diazosulphones, base-induced rearrangements of sulphones, sulphoximides, stereochemistry of substitution reactions at sulphur, insertion of SO2 into Si — C and transition-metal-carbon bonds, 1,3-dipolar cycloaddition reactions of isothiocyanates, aromatic sulphenic acid derivatives, and sulphenamides.

2 Spectroscopic and Other Physical Properties

Like the preceding section, relatively little beyond a statement of the content of each paper is provided for most of the citations dealing with spectroscopic and other physical studies of organosulphur compounds in the following paragraphs. However, all the references include interpretation of the data in terms of conformation, bonding, or insight into reactivity; mere data compilations are excluded.

Spectroscopic methods for the study of thiols, sulphides, and disulphides have been reviewed.

General Conformational Studies and Molecular Orbital Calculations. — Factors favouring the increasing proportion of the trans, trans-rotamer through the series divinyl sulphide, sulphoxide, and sulphone have been considered. The molecular mechanics (or force-field) method has been extended to thiols and sulphides, leading to reasonable agreement between predicted conformations and those established by physical studies. Conformational characteristics of sulphoxides suggest repulsion, rather than non-bonded attraction, between sulphoxide oxygen and nearby hydrogen atoms. Attractive forces between sulphur and carbon atoms which have a 1,4-relationship in aliphatic sulphides and disulphides are implied by M.O. calculations of dihedral angle-energy relationships.

Stabilization of an α-carbanion by divalent sulphur is the result of the polarizability of the sulphur atom rather than pπ-dπ conjugation; and the same basis is suggested for the nhanced acidity of an α-proton in aliphatic sulphides. π-Donating abilities for various heteroatoms towards an adjacent carbonium ion centre follow the series P > S ≥ N > 0 > Cl > F, implying (in contrast to current ideas) that a Period 3 element in the system X–CH2+ is a better π-electron donor than the corresponding Period 2 element.

Ultraviolet Spectra. — Interaction between the chromophores in phenylsulphonyl-guanidines through an empty d-orbital on S, and between the sulphone π-system and the guanidine chromophore, is indicated by u.v. spectra, while related studies show the lack of homoconjugation (through-space conjugation) in aryl benzyl sulphides. U.v. fluorescence and phosphorescence data indicate exciton interaction between the phenyl chromophores in diphenyl sulphide.

Infrared, Raman, and Microwave Spectra. — Interpretation of i.r. data in terms of hydrogen-bonding equilibria has . been reported for thiols, sulphides, and MeSO2NMe2. A diminished H-bonding capacity is demonstrated for a sulphonamide compared with the corresponding carboxamide.

Aliphatic thiols have been subjected to i.r., Raman, and microwave spectroscopic studies. Methyl and ethynyl groups are gauche in ethyl vinyl sulphide, as judged from microwave data. I.r./Raman studies of aliphatic sulphides and disulphides similarly include interpretation in terms of conformation or bonding. Comparative i.r./Raman studies of dimethyl sulphide, sulphoxide, and sulphone and the corresponding diphenyl series have been described. I.r. spectra of selenuranes and sulphones and sulphimides have been interpreted in terms of deformation modes of these functional groups. I.r. spectroscopic studies with a similar objective have been reported for isothiocyanatosters, ethyl thiocyanate, selenocyanates, methanesulphenyl chloride, diaryltellurium dihalides, N-alkyl sulphinamides, anilinesulphonic acids, their sodium salts, and deuteriated analogues; bis(aryl) sulphonimides, methanesulphonyl chloride, and methanesulphonamide.

Nuclear Magnetic Resonance Spectra. — A broad study of 77Se n.m.r. chemical shifts in selenides, diselenides, and selenocyanates has been published. 13C N.m.r. data have been collected for 2-adamantanethiol, alkyl vinyl sulphides, and ring-substituted methyl phenyl sulphides, sulphoxides, and sulphones.

Eu(fod)3 forms weak complexes with 2-adamantanethiol, and with sulphides and disulphides. Larger shifts for sulphides and disulphides are induced by Eu(tfn)3, in which the Lewis acidity of the lanthanide atom is enhanced by the larger degree of fluorination of the organic moiety. The chemical shift non-equivalence observed in isopropyl methanesulphinate is larger than that of the analogous sulphoxide, and is enhanced further by complex formation with benzene.

2-Substituted 2-fluoroethyl phenyl sulphones, RCHF·CH2·SO2Ph (R = SPh, SOPh, SO2Ph, or Br), exist predominantly in the conformation in which the most bulky groups are anti-periplanar. N.m.r. spectra give more reliable conformational information for di-4-pyridyl disulphide than that deduced from Kerr-effect data. Full details have now been published 52 on the empirical relationship between ΔJgem and the relative orientation of a –CH2– group attached to O, S, SO, or SO2. The chemical shifts of the CH2 protons in para-substituted phenyl alkyl and phenylsulphonyl alkyl sulphones correlate well with Hammett substituent constants, indicating the transmission of electronic effects through the sulphone grouping. Analogously, the MeSO2 substituent is shown to possess a lower mesomeric electron-accepting power than a NO2 group when substituted in the 4-position of NN-dimethyl-2-nitro-aniline. N.m.r. provides a particularly direct technique for the study of the kinetics of proton exchange, exemplified in studies of arenethiols in AcOH.

Both 1H and 19F n.m.r. data have been employed in the assignment of 2,5-difiuorophenyl methyl sulphide as the structure of the product of reaction between Mes- Na+ and 1,2,5-trifluorobenzene.

Mass Spectra. — Organosulphur compounds are well represented in mass spectro-metric studies, and the various sulphur functional groups promote individualistic rearrangement behaviour in certain molecular ions. While mercaptopyridines, dialkyl sulphoxides, and dithioacetals and xanthates undergo unspectacular fragmentation (although the formation of sulphenium ions in the latter classes is notable), rearrangements of (arylsulphonyl)methyl arenesulphonates to α-disulphones with extrusion of HCHO, of aryl propargyl sulphones to the SO2-extrusion product, of methyl- or benzyl-sulphonylmethyl methyl sulphones to analogous Ramberg-Bäcklund rearrangement products, and O to S migration in N-substituted sulphoximides under electron impact illustrate more involved processes. A further example, the rearrangement of thiolsulphonates to sulphenylsulphinates after electron loss, proceeds through an unprecedented [2,2,1]-bicyclic transition state.

Detailed studies of mass spectrometric behaviour of aryl methyl and aryl chloromethyl sulphones, chlorosulphonylmethyl methyl sulphones, and α-diazosulphones have been reported. Broad studies of mass spectrometric behaviour of di- and tri-sulphides and α-disulphones are described in a key reference for this area. A limited study of di-organotellurium dicarboxylates has been reported. The α-cleavage fragmentation path is followed by the molecular ion from methyl alkanesulphinates, resulting in parent ions of low abundance and the hydrocarbon ion as the base peak.

Modified mass spectrometric techniques are illustrated in chemical ionization studies of methanethiol and in field desorption studies of sulphonic acids and esters.

Photoelectron Spectra. — The practitioners of this technique are now moving from the simplest representative compounds to bifunctional series, providing useful information on preferred conformations. Studies of methanethiol and dimercaptomethane have been described, and suggest that the latter compound preferentially adopts a non-planar conformation in the gas phase. 2,4-Dithia-pentane, MeSCH2SMe, has been shown to be planar.

Fundamental information on bonding is provided by photoelectron spectro-scopy of thioanisoles and other alkyl aryl sulphides. Two conformers are predominant for these compounds, RSPh, and the proportion of the conformer with maximum p-π overlap decreases through the series R = H, Me, Et, Pr1 or But. Related studies for sulphoxides provide correlation diagrams for the effects of substituents R in RS(O)R, as well as information on preferred conformations. An orienting survey of hexavalent sulphur functional groups, viz. alkyl, vinyl, and aryl sulphones, SS-dialkyl sulphimides, sulphuryl halides, sulphoximides, and sulphurdi-imides, is available.

Electron Diffraction. — Bond-length and bond-angle data have become available for trifluoromethanethiol, phenyl vinyl sulphide, dimethyl disulphide, ethyl methyl disulphide, dimethyl sulphurdi-imide, and benzenesulphonyl chloride.

Dipole-moment and Kerr-effect Studies. — Information on preferred conformations is provided by these techniques, although only a relatively limited precision is possible in estimates of molecular geometry.

Aromatic disulphides and diselenides adopt a conformation in which the torsion angle between the C — S — S — and — S — S — C'— planes lies between 70 and 90°. Related studies of aliphatic disulphides have also been undertaken. Comparisons of S, Se, and O analogues represented by ArXMe, (Ar = Ph or meta-substituted phenyl) and aryl diarylmethyl sulphides have been made, in terms of their conformational behaviour. Studies of diaryl ditellurides ArTeTeAr and phenyl tellurobenzoates PhCOTeR provide dipole-moment data consistent with a non-planar C2 conformation and planar Z conformation, respectively. The series RXXR and RCOXR (X = O, S, Se, or Te) adopt the non-planar and planar conformations respectively, and in this connection the Group VI atom exerts an insignificant effect. Routine collection of data for diphenyl sulphone, dialkyl sulphoxides, substituted benzenesulphonamides, and aryl selenocyanates has been undertaken. The additional information available from dipole-moment data is illustrated in the last-mentioned study, which confirms the electron-withdrawing property of the —SeCN grouping as a substituent on an aromatic ring system.

Optical Rotatory Dispersion and Circular Dichroism Spectra. — The chirospectroscopic properties of derivatives of optically active thiols have been surveyed. This provides a valuable background for the assignment of absolute configuration to chiral thiols by o.r.d. and c.d. methods, requiring the thiol to be converted into a sulphide, disulphide, Δ2-thiazoline, or S-acyl derivative, and exploiting the Cotton-effect behaviour of these classes of organosulphur compound. Continuing interest in the o.r.d. behaviour of chiral disulphides of natural origin, particularly L-cystine and its derivatives, is confirmed by detailed calculations of the Cotton-effect parameters associated with various conformations of the disulphide chromophore in L-cystine.

Other Physical Properties. — -Conformational information for thiols and sulphides can be obtained from enthalpy of formation data. Proton-transfer of benzyl-mercaptan (protonation at sulphur with CF3SO3H, and de-protonation by imidazole) has been studied. Thermodynamic parameters for acidity constants of substituted benzenethiols, and for hydrogen-bonding interactions between alkanols and di-n-octyl sulphide and the analogous ether and N-methylamine, reveal a dominant electronic influence of the ortho-substituent, and substantially higher hydrogen-bond acceptor ability for the aliphatic sulphide than is generally assumed.

3 Thiols

Preparation. — Standard procedures developed in recent years have been used for the synthesis of 2-mercaptophenol from catechol, and 3,5-dimethoxybenzene-thiol from 3,5-dimethoxyphenol by way of the thionocarbamate-thiol-carbamate rearrangement (ArOH -> ArOCSNMe2 -> ArSCONMe2 -> ArSH). Further development of 'sulphurated sodium borohydride' (NeBH2S3) as a reagent for the preparation of thiols from benzyl halides, giving high yields of both α-toluenethiols and benzyl polysulphides, has been reported.

While thiones give sulphides through thiophilic addition of alkyl- or aryl-lithiums (see also Chapter 3, p. 131), di-t-butyl thioketone reacts through an alternative reaction path (Scheme 1), leading to hindered thiols. β-Phenylethyl thiones, e.g.(1), give cyclopropanethiols on irradiation with light of wavelength longer than ca. 460 nm.

Long-established methods for synthesis of thiols for which modified procedures have been worked out include the use of Na235SSO3 for the synthesis of S-labelled thiols from alkyl bromides, the use of Na2S + S in DMF for synthesis of dithiols from dihalides or disulphonates, and the analogous use of xanthates for the synthesis of optically active thiols from toluene-p-sulphonates under mild conditions. Modifications of known methods were also used in the syntheses of glucopyranoside-6-thiols and l,3,4,6-tetrathio-D-iditol. Related substitution processes have been illustrated in the recent literature, leading to 2,3-dimercaptopropanoic acid and the corresponding alcohol, and to mono- and di-thiosquarate dianions (2) and (3) from diethoxy- or bis(alkyl-amino)-precursors, and to the dithiocyclobutenedithione dianion analogue. A novel synthesis of thiols from α-alkylamino-nitriles by reaction with H2S probably proceeds by way of the gem-dithiol:

R1R2CH(NHR3)CN -> R1R2CHSH

Ring-opening reactions leading to thiols involve 6-nitrobenzothiazole with Meo-, 2-nitrothiophen with secondary amines, 2-alkylthiothiazolium salts with OH-, 2-aminothiazole and 2-aminothiazoline with [PtCl4]2- or [Pd2Cl6]2-, and mixtures of thiols (4) — (6) from penicillin derivatives by reaction with mercury(n) acetate followed by treatment with H2S. More conventional ring-opening procedures involve the reactions of oxirans with xanthates and of thiirans with RSH. A route to 1-amino-2-methylpropane-2-thiol has been re-worked, so as to provide authentic material.

Ethane-1,2-diselenol, HSeCH2CH2SeH, is accessible through reduction of the corresponding di-selenocyanate with H3PO2.

Heterocyclic Thiols. — Representative synthetic methods described in the recent literature cover the synthesis of tetrachloropyridine-2-thiol from pentachloro-pyridine N-oxide and thiourea, the synthesis of 2-phenylthiazole-5-thiols from the S-acetyl compounds, and syntheses of 4-phenyl-1,2-dithiolan-3-thione-5-thiol, and of the pyrrole-3-thiols (7), totally unexpectedly, by thiation reactions involving S8.

(6H)-l,3,4-Thiadiazines rearrange to pyrazole-4-thiols with LiPr12N in THF at -110°C.

The thiol tautomeric form predominates for pyrazole-5-thiols, and for 2-phenylthiazole-5-thiols, in contrast to the behaviour of their oxygen analogues.