Disulphides reactions with sulphoxides

Reaction of sulphoxides with disulphides 493 in the presence of BuLi or NaH yields mono-, and disulphenylated products (equation 297). The formation of monosulpheny-lated sulphoxide as the main reaction product (55%) takes place only when Et2S2, sulphoxide and BuLi are used in a 1 3 3 ratio556. 

Aminopenicillanic acid (8) was converted to 6(5)-bromopenicillanic acid by trapping of the diazo-intermediate with hydrogen bromide. Esterification of the dicyclohexylamine salt (93) with p-methoxybenzyl bromide, followed by oxidation, afforded the sulphoxide (94) in 60% yield from 6-APA. Elaboration of this sulphoxide to the disulphide (96) was effected by the procedure established by Kamiya et al. [98] the sulphenic acid (95), formed by heating the sulphoxide to reflux in toluene, was intercepted by reaction with 2-mercaptobenzothiazole to yield the disulphide (96). The latter was transformed by base-catalysed double bond isomerization to the conjugated ester disulphide (97) [95% yield from (94)]. Reductive formylation of disulphide (97) then provided the formylthio-derivative (98). Cyclization of the oxalimide (99), obtained by ozonolysis of... 

The autoxidation of mono- and disulphides has also been studied to some extent, largely because of the role of sulphoxide inhibitors and the possibility of hydrolysis and/or oxidation of disulphides produced in the thiol oxidation reaction. Reaction with conventional chemical oxidants is reviewed by Savige and Maclaren 148] with particular reference to cystine, but it is to the work of Bateman and coworkers that we owe much of our present understanding of the autoxidation of sulphides. 

The second bridgehead substituent was introduced in a protected form [— (56)] and this intermediate subjected to the sequence of steps worked out for the construction of the disulphide bridge. Thus oxidation to a sulphoxide followed by reaction with a Lewis acid, also in this case usefully cleaving the two methyl ethers, afforded dehydrogliotoxin (49). 

The oxidation of thiols with sulphoxides presents several attractive features like the simplicity of the reaction, the high yield and the selectivity of disulphide formation. It has to be noticed, however, that tertiary thiols do not react with sulphoxides or they give very little disulphide even in the presence of amine catalysts. Reaction temperatures higher than 100°C give rise to extensive decomposition ... 

Few racemic alkyl p-tolyl sulphoxides were prepared in rather low yields (16—40%) by the reaction of Grignard reagents with mixed anhydrides 108, 109 and compound HO formed in situ from p-toluenesulphinic acid and 3-phthalimidoxy-l,2-benzoisothiazole 1, 1-dioxide167 (equation 59). The mixed anhydrides 109 or 110 when reacted with cyclopen-tene and cyclohexene enamines 111 gave the corresponding a-ketocycloalkyl sulphoxides 112 in low yields (10-41%) along with small amounts of several by-products such as disulphides and thiosulphonates167 (equation 60). 

Compounds of sulphur(II) undergo the expected oxidations with DIB thiols to disulphides and sulphides to sulphoxides. Thiols form initially unstable iodine(III) intermediates which react with alkynes (Section 3.7). With some sulphides, DIB proved to be uniquely efficient, for example in the oxidation of thioxanthone [132]. The best conditions for high yields involved the use of acetic acid as solvent and catalytic amounts of sulphuric acid no heating was required and the reaction was completed in about 5 minutes [133]. 

Sulphonic acids may normally be obtained in 65-75% yields upon oxidation of thiols, thiolates or disulphides with 30% hydrogen peroxide234-240. Higher yields are realized if a tertiary thiol is used. The same products may also be realized by reaction of either thiols or disulphides with aqueous dimethyl sulphoxide (equation 37), in the presence of a catalytic amount of bromine, iodine or a hydrogen halide241,242. In this latter oxidation, dimethyl sulphide is formed as a by-product, but is easily removed by aspiration. 

However, there is some evidence that the acidity or alkalinity of the solution has a profound effect even on the low temperature reaction. Thus Ogata and Suyama [91] report that sulphoxides react with organic hydroperoxides in non-aqueous alkaline solution to produce sulphones, which have no antioxidant activity. In acids, as stated above, disulphides are the major sulphur-containing products. 

From Benzothiazolyldithioazetidinone Type C). The disulphides (6), which are obtained by the reaction of penicillin sulphoxides and 2-mercaptobenzothiazole, give different products with bases, dependent on the structure of the substituents on the -lactam nitrogen e.g., [6 R = CH(C02H)C(Me)=CH2] gives (7) whilst [6 R = C(=CH2)C02CH2CCl3] gives (8). "... 

Reactions.—A variety of interesting and useful syntheses have been published involving the reaction of dimsyl anion [MeS(0)CHa ] with esters and lactones,with disulphides, with chlorosilanes, with sulphinate esters, with organoboranes, and with stilbenes. Simple and functionalized a-sulphinyl carbanions can be condensed with carbonyl compounds or alkylated, often in a stereocontrolled manner, as in a nicely conceived synthesis of biotin. Considerable attention has been given to methods for the removal of the sulphoxide function following carbon-carbon bond formation. Among the methods used are reduction by aluminium amalgam (with j3-keto-sulphoxides), reduction with Raney nickel, pyrolytic elimination of sulphenic acid, elimination of sulphur dioxide from sultines, e.g. (64), and sulphoxide-... 

Sulphenyl Halides.—Sulphenyl chlorides are readily available by chlorinolysis of disulphides, and this remains the most commonly used method of synthesis. Chlorinolysis of penicillin esters gives the sulphenyl chloride, and a route to an azetidinone sulphenyl chloride has been devised in which the relatively unstable sulphenic acid produced by penicillin sulphoxide pyrolysis is treated with SOCh in CCl, to give [43 R =C1, R =CH(C02Me)CMe=CH2]. Sulphenyl iodides may be important intermediates in reactions at disulphide bridges in peptides and proteins, and a report of the preparation of a stable sulphenyl iodide is notable. The observation that methanesulphenyl chloride dimerizes (in SO2 in the presence of a Lewis acid) to give MeSSMeCl Cl MeS=SMeCl Cl may be useful in explaining the course of certain electrophilic reactions of sulphenyl chlorides, and should stimulate a search for new reactions of aliphatic compounds of this series. 

---