Disulfides, from sulfenyl chlorides

Another -activation of amino acids for peptide synthesis is achieved by preparing sulfenamides from sulfenylimidazoles. A sulfenylimidazole is formed in situ from the sulfenyl chloride (prepared from the disulfide and chlorine) and imidazole, which reacts further with an amino acid ester to give a sulfenamide in high yield. Conversion of such sulfenamides with IV-acyl amino acids by means of triphenylphosphine affords dipeptides with racemization of less than 0.5%.[481... 

The disulfide derived from a thioglycerol was converted into the corresponding sulfenyl chloride (step a) and allowed to react with 2-triethylsily-loxy-l,3,2-dioxaphospholane to give a cyclic thiophosphate (step b). Reactions a and b were performed as a one-flask procedure and the crude thiophosphate was transformed into the desired thiophosphocholine by opening the phospholane ring with trimethylamine (step c). 

N-Arylamidines act as 1,5-dinucleophiles towards sulfur dichloride, N-sulfinyltosylamide and bis(N-tosyl)sulfur diimide. The products are 1,2,4-benzothiadiazines (Scheme 14) (73ZOR2038, 68LA(715)223), and in the case of sulfur dichloride, chlorination of the aromatic ring also occurs. 1,2,4-Benzothiadiazines can also be prepared from N-arylamidines by reaction with sulfenyl chlorides or disulfides in the presence of NCS. Thus N-phenylben-zamidine and benzenesulfenyl chloride give the 1,2,4-benzothiadiazine (182) (78CC1049). 

Peril uoro-fc /V-butyI methyl sulfide was synthesized by treatment of the silver derivative with trifluoromethylsulfenyl chloride. The disulfide was also obtained from initial reaction with elemental sulfur, followed by treatment with the sulfenyl chloride (Scheme 1.13).43... 

Various oxidation reagents have been used iodine (148, 149). ammonium persulfate (149), and HIOj (149). Unsymmetrical disulfides (137) result from the action of a mercaptan on a sulfenyl chloride (Scheme 70) (320). 

Thiazolyl sulfamic acids, rearrangement of sulfonic acid, 70 rearrangement to sulfonic acid, 75 by sulfonation, 75 2-Thiazolyl sulfenyl chloride, transformation to, thiazolyl disulfides. 412 2-Thiazolyl sulfide, in hydrocarbon synthesis, 406 oxidation of, with m-chloroperbenzoic acid, 415 with CrOj, 415 with Hj02,405,415 with KMn04,415 physical properties, infrared, 405 NMR, 404 pKa, 404 ultraviolet, 404 preparation of, from 2-halothiazoles and 5-Thiazolyl sulfides, bis-5-thiazolyl sulfide, oxidation of, 415 general, 418 5-(2-hydroxythiazolyl)phenyl sulfide case, 418 physical properties, 418 preparation of, 417-418 table of compounds, 493-496 uses of. 442 2-Thiazolyl sulfinic acid, decomposition of, 413 preparation of, from 2-acetamidothiazole sulfonyl chloride, 413 from A-4-thiazoline-2-thione and H, 0, 393,413 table of compounds, 472-473 5-Thiazolyl sulfinic add, preparation of,... 

They are also good soft electrophiles. Sulfenyl chlorides (RSC1) are easily made from disulfides (RS-SR) and sulfuryl chloride (SO2CI2). This S(VI) chloride has electrophilic chlorine atoms and is attacked by the nucleophilic disulfide to give two molecules of RSCl and gaseous SO2. There s a lot of sulfur chemistry here We start with a nucleophilic attack by one sulfur atom of the disulfide. 

A large class of compounds derived from sulfur dichlorides are the sulfenyl chlorides, RSCI. They are most commonly obtained by chlorination of a disulfide (RSSR) using CI2 or SO2CI2. They have a large organic chemistry that has been reviewed selected reactions are illustrated in Figure 40. 

In contrast to the free acids, sulfenate esters, amides and halides are more stable. Disulfides (52) can be obtained from thiols by mild oxidation (see p. 57), and sulfenyl chlorides () can in turn be prepared from disulfides (52) by treatment with chlorine (Scheme 30). Sulfenyl chlorides (51) react with alcohols to give esters, e.g. the methyl sulfenate (53) which on alkaline hydrolysis yields the sulfenic acid (45) (Scheme 30). 

Sandmeyer reaction, synthesis, of bromo compound, 36, 39, 45, 48, 52, 75, 217 of chloro compound, 48, 110, 113 of cyano compound, 90, 91, 216 of iodo compound, 182, 183, 184, 185 use of mercuric nitrate in, 52 Saponification of an ester, 113, 152 Schiemann reaction, 165, 167 Schotten-Baumann reaction, 145 Skraup reaction, 28, 85, 193, 204, 235 Sommelet reaction, 281 Sulfenyl chloride, formation from chlorine and disulfide, 214... 

This synthesis of sulfenyl chlorides can also be used in the aliphatic series although here the limitation applies that most alkylsulfur halides are too unstable to be isolated from solution. In general, and also in the aromatic series, sulfenyl chlorides are easier to prepare than the bromides, whilst the iodides are known only in a few cases and the fluorides not at all. As an example, Schneider,665 chlorinating methanethiol in anhydrous carbon tetrachloride at —15°, obtained dimethyl disulfide dichloride [chloro(methyl)(methylthio)-sulfonium chloride] which passed into methanesulfenyl chloride when allowed to warm slowly to room temperature ... 

Dipotassium cyanodithioimidocarbonate (269) is readily produced from cyanamide and carbon disulfide in alkali, and affords the S-alkyl derivatives (280) in good yield upon treatment with a variety of primary and secondary alkyl halides.219,220 The action of chlorine converts the parent salt (269) to 3-chloro-l,2,4-thiadiazole-5-sulfenyl chloride(282,85-100%), and the bromo analog is similarly accessible.209,221,222 Dipotassium perthiocyanate (270, obtained from 269 and sulfur209) is chlorinated to the stable bissulfenyl... 

The formation of trifluoromethyl sulfides (and other chalcogenides) from thiocyanates or disulfides, CF SiMej, and Bu NF is possible. The combination of sulfenyl chlorides. 

Fluorothiiranes are also prepared by cyclization of open-chain precursors. Treatment of sulfenyl chloride 92 with the triethylamine-boron triiluoride complex gave thiirane 30 in 68% yield. Tris(diethylamino)phosphine transformed disulfide 94, prepared from alkene 93 and sulfur monochloride, into thiirane 95. An indirect route from a chlorodisulfide that has the advantage of utilizing both halves of the molecule is exemplified by the transformation of 96 into thiirane 97. ... 

Replacement of hydrogen by organothio groups with sulfenyl chlorides generated in situ from disulfides... 

The resin-bound fragment preparation starts with the chlorine displacement from the chloromethylene function on chloromethylated polystyrene by the cesium salt of Z-L-Cys(Trt)-OH. The resulting benzyl ester is treated with methoxy-carbonyl sulfenyl chloride (Scm-Cl) to form the active intermediate sulfenyl thiocarbonate which is allowed to react with 4-acyloxy-6-mercaptodibenzofuran, preferably in dichloro-methane-hexafluoro-2-propanol, with or without catalytic triethy-lamine to afford the unsymmetrical disulfide (eq 2) ... 

In 2006, Ranu reported on an t/ fz-Markovnikov hydro-thiolation of styrene derivatives 205 with disulfides using indium(I) iodide and ZnCl2. Whereas the proposed mechanism invoked the formation of indium(III) thiolate species, the regiochemical outcome of the reaction was opposite to that of In(III)-cataIyzed hydrothiolation of alkenes. It is, thus, reasonable to propose the in situ generation of sulfenyl chloride from ZnCl2 and diaryl sulfides followed by the formation of a thiiranium intermediate 207 that is reductively opened by Ini to give 208. This explanation corresponds to no reaction observed in the absence of either Ini or ZnCL. 

Sulfenyl cldorides, sulfinic acids and sulfinyl chlorides were reduced in good yields by lithium aluminum hydride to disulfides [680], The same products were obtained from sodium or lithium salts of sulfinic acids on treatment with sodium hypophosphite or ethyl hypophosphite [507]. Sulfoxy-sulfones are intermediates in the latter reaction [507]. 

The proposed mechanism of the oxidative cleavage of S-protecting groups by the chlorosilane/sulfoxide procedure is outlined in Scheme 8. 95 The first reaction is considered to be formation of the sulfonium cation 9 from diphenyl sulfoxide (7) and the oxygenophilic silyl compound 8. The formation of a sulfonium ion of this type is known and has been utilized for the reduction of sulfoxides. 97 Subsequent electrophilic attack of 9 on the sulfur atom of the S-protected cysteine residue leads to the formation of intermediate 10, whereby the nature of the silyl chloride employed should be the main factor that influences the electrophilicity of 9. The postulated intermediate 10 may then act as the electrophile and react with another S-protected cysteine residue to generate the disulfide 11 and the inert byproduct diphenyl sulfide (12). This final step is analogous to the reaction of a sulfenyl iodide as discussed in Section 6.1.1.2.1. 

Hydrogen chloride N-Sulfenyl- from N-chloro-quinonemonoimines and disulfides... 

Formation of Unsymmetrical Disulfides. This facile protocol (eq O proceeds through sulfenyl thiocarbonate intermediates obtained in very good yields from equimolar amounts of thiols and alkoxycarbonylsulfenyl chlorides (of which methoxycarbonylsulfenyl chloride is widely used) at low temperature (generally 0-10 °C), in solvents such as methanol, chloroform, dichloromethane, and dioxane. An oxygen-free atmosphere of nitrogen is recommended. ... 

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