Cyclic disulphide

Figure 11.15. Typical chemical groupings in a sulphur-vulcanised natural rubber network, (a) Monosulphide cross-link (b) disulphide cross-link (c) polysulphide cross-link (j = 3-6) (d) parallel vicinal cross-link (n = 1-6) attached to adjacent main-chain atoms and which have the same influence as a single cross-link (e) cross-links attached to common or adjacent carbon atom (f) intra-chain cyclic monosulphide (g) intra-chain cyclic disulphide (h) pendent sulphide group terminated by moiety X derived from accelerator (i) conjugated diene (j) conjugated triene (k) extra-network material (1) carbon-carbon cross-links (probably absent)...

Polarography has been successfully applied to the investigation of structural problems involving sulphur compounds. The presence of a disulphide bond has been established by means of the polarographic reduction waves of cytochrome C (156) and lipoic acid (757), and in cyclic disulphides of the oxytocine and vasopressine type (158). The elucidation of the process responsible for the reduction wave of lipoic acid was carried out by comparison with reduction waves of cyclic disulphides, where the disulphide bond was incorporated into rings of various size. The similarity indicated that in lipoic acid an S—S bond which is a part of a larger cyclic system is reduced. 

In addition to the reactions discussed in the previous section, the free radical produced photochemically from PhI(02CAd)2 reacted with alkyl or aryl or cyclic disulphides to afford the corresponding adamantyl sulphides in good yield [79] ... 

Dithiols are readily converted into cyclic disulphides (68)... 

Lipoic acid is a five-membered cyclic disulphide ring with a five-carbon carboxylic add chain. When reduced it provides a constrained dithiol centre. This disulphide-dithiol cofactor is covalently bound to one of the enzymes in a multienzyme complex which catalyses oxidative decarboxylation of a-keto acids. In the course of the reaction three forms of the prosthetic group participate the cyclic disulphide, the dithiol and a thio-ester of the dithiol form. 

The really unique reaction of the lipoate centre in ct-keto acid metabolism is the oxidative thioester formation from a thiamine-coordinated active aldehyde . Thiol transacetylase and dithiol-disulphide oxidation reduction roles are well-known attributes of other biological thiols. Unfortunately mechanistic studies on this reductive acylation of a cyclic disulphide have so far received little attention. Proposals that a lipoic acid-thiamine pyrophosphate compound was the functional entity in a-keto acid oxidation have been completely abandoned, but data supporting this concept remain unexplained. Investigations in this area might have some relevance for the reductive acylation process. 

Cyclic Disulphides and Cyclic Diselenides.—Formation. No fundamentally new methods of synthesis of this class of compounds have been reported in the past two years. For l,2>dithiolan the oxidation of l,3>dithiols remains a favoured method, the use of iodine in the presence of triethylamine leading smoothly to 1,2-dithiolans without attendant polymerization. cis- and tra/ -l,2-Dithiolan-3,5-dicarboxylic acids were prepared from a diastereo-isomeric mixture of dimethyl 2,4-dibromoglutarates by sequential treatment with potassium thioacetate and potassium hydroxide in the presence of iodine,and jyn-2,3-dithiabicyclo[3,2,l]octan-8-ol was formed from 2,6-dibromocyclohexanone by successive treatment with potassium thiocyanate, lithium aluminium hydride, and iodine. The stereoselective formation of the less thermodynamically stable alcohol in this case was attributed partly to the formation of chelates with sulphur-aluminium bonds. 2,2-Dimethyl-l,3-dibromopropane was converted into 4,4-dimethyl-l,2-diselenolan on treatment with potassium selenocyanate at 175 °C, but at 140 °C the product was 3,3-dimethylselenetan. Reductive debenzylation of 2-alkylamino-l,3-bis(benzylthio)propanes with lithium in liquid ammonia and oxidation of the resultant dithiols with air afforded 4-dialkylamino-l,2-dithiolans, whilst treatment of a-bromomethyl-chalcone with sodium hydrosulphide gave, as minor product, trans-3 phenyl-4-benzoyl-l,2-dithiolan. Among the many products of thermal decomposition of /ra/ -2,4-diphenylthietan was l,4,5,7-tetraphenyl-2,3-dithiabicyclo [2,2,2]octane. ... 

Properties and Reactions. The desulphurization of a variety of cyclic disulphides to the corresponding sulphides on treatment with aminophos-phines followed second-order kinetics, and was attended by inversion of configuration at one of the carbon atoms adjacent to the disulphide group. For example, m-3,6-di(methoxycarbonyl)-l,2-dithian (130) gave rm f-2,5-di(methoxycarbonyl)thiolan (131), most probably by the depicted mechanism, whilst the /ra j-isomer of (130) gave the c/j-isomer of (131). 

The electronic structure and transitions of cyclic disulphides have been calculated by a semi-empirical method, which indicated that absorption at 250—300 nm was due to -> absorption maxima were related to the dihedral angles about the sulphur-sulphur bond. The optical properties of 1,2-dithiolans and 1,2-dithians have also been accounted for in a theoretical treatment, and the photo-catalysed homolytic scission of the sulphur-sulphur bond in cyclic disulphides has been investigated spectroscopically. Spectrophotometry indicated that there was particularly strong interaction between ethylene chloride and 1,2-dithian, compared to that observed for acyclic disulphides. ... 

Reviews have appeared on structure and bonding in unsaturated five-membered cyclic disulphides, and on the chemistry of 1,3-dithiolium salts. Although published in 1970, these reviews contain few references to work published after 1966. 

The cyclic disulphide shown above has been collected in significant amounts from products purposely cured to give a substantial proportion of mercaptide groups in the polymer backbone [4]. 

This reagent has also been used in similar conversions of a dithiol to a cyclic disulphide in the synthesis of oxytocin(II) and the A6-12 sequence of sheep insulin [88]. The utility of this reagent for the formation of opcncystine derivatives has also been recently examined [92] (Table 7.8). 

N-ammonia in methanol. Upon oxidation to the cyclic disulphide Wittinghofer noted the formation of small amounts of di o-nitrophenyl disulphide which may have resulted from -> S-o-nitrophenylsulphenyl group migration during the alkaline removal of the S-ethylcarbamoyl group. 

The conformation of lle SnSPh in the gas phase is determined by UVPE spectroscopy, cyclic disulphides result from oxidising 3u SnS(CH2) SSnBu 2 using while L Me2(PhS)SrQ2 assists the photolytic reductive couplitig of... 

Cyclic Disulphides.—A number of papers dealing with the properties of lipoic acid (73) have appeared. When irradiated in an aldehyde solvent (e.g. acetaldehyde, propionaldehyde), the monoacetylated products (74) of S—S bond fission were obtained in 70—80% yield. The reaction was successfully extended to a series of 3,3-dialkyl-l,2-dithiolans, 1,2-dithians, and acyclic disulphides. Oxidation of (73) with a variety of reagents, including singlet oxygen, t-butyl... 

NaBHiSj has sulphuration properties towards oxirans " to give bis-(2-hydroxyethyl) disulphides, and towards aldehydes (PhCHO PhCH SS-CHaPh) cyclic disulphides are formed with a 3-unsaturated ketones. ... 

Cyclic Disulphides.— Most of the syntheses of these types of compounds involved oxidation of the open-chain dithiols. Asparagusic acid, or 1,2-di-thiolan-4-carboxylic acid, a new plant-growth inhibitor, has been isolated from extracts of etiolated asparagus and its structure confirmed by synthesis. Brugeriol and isobrugeriol, trans- and cis-4-hydroxy-l,2-dithiolan... 

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