CHAPTER 1
Aliphatic Organosulphur Compounds, Compounds with Exocyclic Sulphur Functional Groups, and their Selenium and Tellurium Analogues
BY G. C. BARRETT
There has been an increase in the number of entries in Chemical Abstracts from 7.5 × 105, for the corresponding period reviewed for the previous volume in this series, to 7.85 × 105 for the current period. However, a more substantial increase has occurred in the number of papers eligible for citation in this chapter. The layout used in previous volumes is retained for this chapter, for which further compression of a larger number of references into a smaller number of pages has led to more terse descriptions of topics which have been dealt with more fully in previous volumes. Readers may therefore find it helpful to refer to previous volumes in this series when encountering discussion which has been severely compressed in parts of the present chapter.
1 Textbooks and Reviews
Textbook coverage of sulphur functional groups continues to keep pace with the increasing interest in organosulphur chemistry. Reviews have appeared dealing with organosulphur chemistry in general, sulphur-containing natural products, thiols (mercapto-ketones, 4-mercapto-azetidinones, heterocyclic thiols, estimation of SH groups in proteins), ylide formation from sulphides and carbenes, sulphuranes and selenuranes, 'umpolung' via sulphur-containing reagents, stereochemistry of sulphoxides, sulphones, triflones, thiocyanates, sulphoximines, nucleophilic substitution at tricoordinate sulphur, reaction of disulphides with tervalent phosphorus compounds, (O-mesitylenesulphonyl)hydroxylamine as an aminating agent,2q and named reactions in organosulphur chemistry. A thorough survey of modern organoselenium chemistry has appeared and also a review of the use of organoselenium reagents for the introduction of C=C bonds under mild conditions.
2 Characteristics of Sulphur Functional Groups
Methylthio- and phenylthio-groups have larger acidifying effects than would be calculated on the basis of polarizability, for the C-acids R1SCH2R2 in DMS0. Conjugative stabilization of the α-sulphenyl carbanion appears to be significant. This is a theme of continuing interest in theoretical terms, and is now seen to be a result of a greater two-electron stabilization of the whole carbanionic system of an α-alkylsulphenyl carbanion because of its enhanced electron-accepting ability compared with its oxygen analogue. (p-d)π Conjugation need not be postulated to explain this fact. The lone pair in an α-alkylselenenyl carbanion preferentially adopts an equatorial position due to anomeric-type stabilization involving the σ*-orbital of the Se — C bond. Stabilization by Se is ca. 3 kcal mol-1 greater than that by S in these systems, and specific d-orbital effects are not involved.
Based on X-ray crystallographic data, bivalent sulphur appears to prefer nucleophiles to approach along the direction of the extrapolated bond to sulphur from one of the adjacent atoms, and electrophiles to approach in a direction ca 20° from the perpendicular to the plane formed by the sulphur atom and its two neighbouring atoms.
Axial preference for the substituent at C-5 in 2-isopropyl-5-(CH2)nX-substituted 1,3-dioxans (X = MeS, MeSO, MeSO2, Me2S+, or OMe) is greatest when the adjacent exocyclic atom is fractionally positively charged (e.g. n= 0, X = MeSO) due to attractive interactions involving the ring oxygen atoms. The overall space requirement of the MeSO group lies between that of MeS and MeSO2.
Incidental comparisons between functional group characteristics are mentioned further in later sections of this chapter.
3 Analysis of Total Sulphur or Selenium in Organic Samples
Microdetermination of S in plant tissue using barium chloranilate, and of Se at ng levels, based on ftuorimetry of derived 4,5-benzopiazselenol or using 2,3-diaminonaphthalene as reagent, illustrate the continuing development of analytical methods.
4 Natural Occurrence of Organosulphur Compounds
Simple compounds are represented by methanethiol (Coryneform bacteria), dimethyl sulphide in beer, and di-n-propyl disulphide, which, when released from freshly cut leek leaves, stimulates egg laying by the leek moth. Besides asparagusic acid, (HSCH2)2CHCO2H, Asparagus officinalis contains 3-mer-capto- and 3-methylthio-isobutyric acid, di-2-(1-carboxypropyl) disulphide, and 3-S-acetylthio-methacrylic acid. 4-Methylthiopropylamine and (R)-3-methylsulphinylpropylamine have been isolated from Iberis amara, and further sources (fruiting bodies of Lentinus edodes) have been found for the extraordinary lentinic acid, the Nα-γ-glutamyl derivative of MeSO2(CH2SO)3- CH2CH(NH2)CO2H. Approaches to the synthesis of sparsomycin, which contains the MeSCH2SO- moiety, have been published.
Sulphur compounds must have played important roles in chemical evolution, and H2S, thiols, and sulphides were likely components of the primaeval soup.
5 Spectroscopic and Other Physical Properties of Organosulphur Compounds
Molecular Orbital Calculations. — -CND0/2 Calculations for alkyl isopropyl sulphides aimed at deducing the preferred torsion angles for the C — S — C bonds are typical of several studies with similar objectives on simple organosulphur compounds. Energetic aspects and electronic structures are also featured in these projects, the latter including an analysis of the electronic structure of sulphuranes SR4 which reveals many analogies with phosphoranes.
Ultraviolet Spectra. — Studies yielding structural information have been reported for vinyl sulphides, which have been shown to possess a lower p-π conjugation energy than vinyl ethers, and for alkali-metal arenethiolates, where the negative charge has been shown to be localized mainly on the sulphur. In charge-transfer complexes involving TCNE with aryl alkyl sulphides, the order Me ≈ Et>Pri [much greater than] But describes the order of decrease in εmax and of the increase in ionization potential, while corresponding complexes with aryl phenylethynyl chalcogenides ArXC[equivalent to]CPh and their vinyl analogues confirm that the order of electron donation from X is Te>Se>S.
Circular Dichroism. — Comparison of data for (S)-(-)-o-methoxyphenyl p-tolyl sulphoxide with those for the corresponding (-)-sulphimides ArAr'S=NR (λmax 240, 272 nm) can be used to confirm the assignment of the (S)-configuration. The Cotton effects due to the disulphide chromophore in proteins have been analysed for human somatotropin.
Infrared, Raman, and Microwave Spectra. — In addition to studies involving one or other of these techniques at a sophisticated level, several of the papers cited here describe the results of combined i.r./Raman or i.r./n.m.r. investigations, the latter being aimed particularly at gaining conformational information. I.r., Raman, and microwave spectroscopic studies are briefly summarized, with information on the compound types involved. Points of interest include the first i.r. data on a simple alkanetellurol, analysis of the tautomeric equilibrium Cl3C(O)SH [??] Cl3C(S)OH, which contains 1% of the latter tautomer at 75-93 °C, hydrogen-bonding [for thiolacids, DMSO with amides, mercaptoethanol, and o-(dimethylaminocarbonyl)benzenethiol], association of p-hydroxybenzenesulphonates, and through-bond interaction of the sulphur lone pair with the carbonyl group in γ- and δ-keto-sulphides.
Nudear Magnetic Resonance Spectra. — Schaefer and Parr have employed long-range spin-spin coupling constants for deducing an internal rotation barrier of 1.1 [+ or -] 0.3 kcal mol-1 for benzenethiol, based on coupling between the SH proton and the para-hydrogen atom. The Se analogue, 2-nitro-benzenethiol, and 3,5-dichlorobenzyl mercaptan have been treated similarly. More routine 1H n.m.r. studies include points of interest in terms of conformation, uses of additive shielding increments for the sulphinyl and sulphonyl groups, and the internal rotation order of S < Se < Te for diphenyl dichalcogenides, based on spin-lattice relaxation times T1. Solvent-induced shifts for bis(methylsulphonyl)methane and lanthanide-induced shifts for sulphoxides have been reported. In the latter case an attractive interaction between the phenyl and methyl groups in benzyl t-butyl sulphoxide has been suggested. The sulphonyl oxygen atom distal to the ortho-substituent is the site of lanthanide complex formation in aryl sulphones. Further work (see Vol. 4, p. 7) on hydrogen-bonding between haloforms and di-n-octyl sulphide has been described, and new results relating to the properties of sulphide complexes reveal the propensity for pyramidal inversion at sulphur in Et2S with BF3 and metal fluorides, but not for Et2S-BCl3.
Recent 13C n.m.r. spectroscopic studies include several points of interest. The shifts of 13C resonances of α-carbon atoms to lower field occur in the order thiol < sulphide < disulphide. The transmission of electronic effects decreases in the order ArSR>ArSeR = ArR>ArOR (R = vinyl), but the order becomes ArR>ArOR> ArSR> ArSeR when taking account of the activating effect of O and the deactivating effect of S or Se. Selenium, in alkyl phenyl selenides, is shown to be a weaker electron donor than O or S, and to possess no appreciable π-acceptor properties. The chemical shift of the carbonyl carbon atoms of thiolesters occurs 15 — 20 p.p.m. further downfield compared with other carboxylic acid derivatives; the α-carbon resonance is also shifted ~10 p.p.m. further downfield compared with these derivatives. Charge-transfer interaction between iodine and a sulphide or a sulphoxide is consistent with a π-bond polarization mechanism.
Early results for 77Se n.m.r. of selenides, diselenides, and selenophens reveal little correlation of trends of chemical shift with structural features. The [FORMULA OMITTED] and [FORMULA OMITTED] coupling constants are always positive except in compounds where the Se atom does not carry a lone pair. Te-1H chemical shift data have been collected. 19F n.m.r. data for trifluoromethyl derivatives CF3XR reveal a decreasing effect in the order O>N>S for the effect of X on the 19F chemical shifts, and 35Cl n.q.r. spectra have been obtained for alkyl p-chlorophenyl sulphides.
Mass Spectra. — Points of interest in recent papers include an explanation for the formulation of the ion having m/e = 61 from alkanethiols as (CH2)2SH rather than CH3CH2S+, which has been shown to isomerize within 10-5 s; a similar formulation for C3H7S+ from the same source has been attempted. The fragment of m/e = 60 (C2H4S+ interconverting MeCHs+· and CH2=CHSH+ ions. Electron stripping from PhS- ions gives PhS+ ions, and c.i.m.s. studies of alkanethiols using I+2, I+ and Xe+ ions have been described. Loss of CO from methyl phenyl sulphoxide involves C-1 of the phenyl group. Rearrangements follow the ionization of sulphones and sulphoxides.
Ion–molecule reactions following photoionization of aliphatic thiols, sulphides, and disulphides have been studied.
Photoelectron Spectra. — A modest increase in the number of papers reporting uses of this technique is noted. This is perhaps smaller than might have been expected in view of the structural information available through this technique. No definite evidence could be found for conjugation between the S atoms and the triple bond in di-(methylthio)ethyne, and π-conjugation in methyl phenyl telluride is apparently much smaller than in the 0, S, and Se analogues.52 Other studies report spiroconjugation in tetrakis-(t-butylthio )methane and examine diaryl sulphides.
Electron Diffraction. — Compounds studied include Me2S, MeSC [equivalent to] CSMe, CH2=CHSO2Cl, and CC13SO2Cl.
Dipole Moments; Kerr-effect Studies. — Conformational and electronic structural properties continue to be sought through these techniques.
Electron Spin Resonance Spectra. — Studies of the reactions of organosulphur radicals are mentioned elsewhere in this chapter, and frequently rely on e.s.r. monitoring. Photolytic and thermolytic generation of radicals from aliphatic sulphides and disulphides, diaryl sulphoxides,60 aromatic thiolsulphonates, and N-bromo-N-t-butyl-sulphonamides been described, and cation radicals from bis-(4-hydroxy- and -methoxy-phenyl) sulphides have been studied.62
Mössbauer Spectra. — Te Mössbauer parameters of organotellurium compounds can be interpreted in terms of the relative populations of the 5s- and 5p-orbitals on the Te atom, and can provide structural information (e.g. ArTeOCl involves four-co-ordinate Te).
6 Thiols
Preparation. — The main routes to thiols continue to be used, and recent references are grouped together on this basis. Newer methods and unusual results from applications of well-known procedures are given more space here.
Preparations based on H2S, such as addition reactions and its use in the direct or indirect conversion of alcohols into thiols, and other simple sulphur reagents which convert alkyl halides into thiols are described in papers which include descriptions of further work on the synthesis of sulphur and selenium analogues of triangulic and squaric acids (see also Vol. 4, p. 8). The aromatic substitution reactions used for the synthesis of thiols have employed simple sulphur reagents. Methods based on thiolcarbamates Et2NCOSCH2CN + RX + OH- [right arrow] Et2NCOSCHRCN) and the thionocarbamate-thiolcarbamate (Newman-Kwart) rearrangement (see also Vol. 4, p. 7) are accompanied in the recent literature by examples of the use of related thiocarbonyl compounds for the synthesis of thiols. Conversion of ketones into thiones using H2S and HCl can be regarded as a synthetic route to enethiols because the tautomeric equilibrium favours these compounds in many cases. Reduction to thiols accompanies the addition of Grignard reagents to thiones. Ring-opening reactions leading to thiols include the sequence thiiranone to α-mercapto-ester or -amide [R1R2C(COX)SH (X = OMe or NHR3). Reduction of a sulphonyl chloride to a thiol with LiAlH4 is illustrated in ref. 78.
Thiols as Nudeophiles. — Thiols and thiolate anions show a very high nucleophilicity compared with other nucleophilic species, which is illustrated by the addition of thiols or Na2S to ArNCS, giving dithiocarbamates. An attempt to set up a comprehensive nucleophilicity scale has been frustrated by the substantial effects of solvents. A procedure for the preparation of PhS-Cu(But)Li from ButLi and PhSCu (itself prepared from PhSLi + CuI) has been described; the compound is useful in ketone synthesis (PhCOCl gives 85% ButCOPh). Thiosilanes, selenosilanes, and analogous derivatives of other Group IVA elements may be prepared from RC[equivalent to]CSLi or PhSeLi with a chlorosilane or a bis-(dimethylamino)silane or the corresponding Ge or other Group IVA element chloride; RSeMgBr has been used for the preparation of β-hydroxy-selenides from chlorohydrins, and several related reactions have been described involving the displacement of halide from saturated and alk-1-enyl compounds. The reaction of RS- with an α-chloro-sulphone gives either the substitution product or the α-sulphonyl carbanion. Vicinal dihalides can give either the alkene and disulphide, or the substitution product, on similar treatment. Vinyl halides are generally less reactive than aryl halides in photostimulated SRN1 reactions with benzenethiolates, and the reductive substitution reactions of α-bromo-cinnamates and vinyl fluorides, e.g. (CF3)2C=CFCF2CF3, are noteworthy. Ring-opening of oxirans by thiols and selenols is catalysed by Al2O3 Conformational differences between crotepoxide and its di-deacetyl analogue account for opposing modes of oxiran ring-opening in these two cases.
Unusual examples of nucleophilic attack by thiolate anions at sp3-hybridized carbon atoms are provided by cyclopropane ring-opening in activated bicyclo[3.1.0]hexanes, which leads to cyclopentanones of possible use in prostanoid or jasmonoid synthesis, and conversion of 2,5-dimethyl-3,4dinitrothiophen into 2-arylthiomethyl-4-nitro-5-methylthiophen, which is an unprecedented side-chain substitution with a concomitant displacement of a ring nitro-group. Aromatic substitution reactions by thiolates include further studies of the partial substitution of ring fluorine atoms in reactions of C6F5X (X = NH2 or Cl).
The high nucleophilicity and low basicity of thiolates lead to applications in synthesis (cleavage of ethers and hindered esters), for which lithium thiomethoxide, with its good shelf life and ease of preparation, is preferable to LiSPr and NaSEt. Lithium alk-1-ynethiolates R1C[equivalent to]CSLi react with halides of the Group IVA elements to give R1C[equivalent to]CSMR23 (M = Si or Sn). Aryl selenide anions formed by the cleavage of diselenides with Na and THF are more effective in the cleavage of esters than anions, e.g. Na+{(PhSe)BH3}-, formed by reduction with NaBH4.
Further examples of reactions of thiols as nucleophiles are included in the later section dealing with the synthesis of sulphides.
