Sulfenamides disulfides

Metal Ion-Promoted Reactions of Thiols. Metal ion-promoted reactions of thiols have been reviewed (53). The bulk of the coverage concerns metal ion promoted aspects of sulfur chemistry. The main topics of interest are the formation of sulfenamides, sulfides, and disulfides using metal-mediated reactions. 

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... 

A new stable sulfenylating reagent 3-phenylsulfenyl-2-GV-cyano-imino)thiazolidine 57 has been described. It reacts with amines or thiols to give sulfenamides or disulfides in excellent yields. a-Sulfenylation of carbonyl compounds also proceeds smoothly and if an optically active 4-diphenylmethyl substituent is attached to the thiazolidine ring (58), the cyclic (3-ketoester 59 can be sulfenylated in high yield with an ee of 96% to give the sulfide 60 <00SL32>. 

Captax (Structure 15.21) is used to the extent of 1% with hevea rubber and accounts for the major part of the over 30,000 t of accelerators used annually in the United States. Other accelerators widely used include 2-mercaptobenzothiazole sulfenamide (Santocure Structure 15.22), used for the vulcanization of SBR dithiocarbamates and thiuram disulfides. Thiuram disulfide (Structure 15.23) is a member of a group called ultra-accelerators, which allow the curing of rubber at moderate temperatures and may be used in the absence of sulfur. 

The proton pump inhibitors are lipophilic weak bases (pKa 4-5) and after intestinal absorption diffuse readily across lipid membranes into acidified compartments (eg, the parietal cell canaliculus). The prodrug rapidly becomes protonated within the canaliculus and is concentrated more than 1000-fold by Henderson-Hasselbalch trapping (see Chapter 1). There, it rapidly undergoes a molecular conversion to the active form, a reactive thiophilic sulfenamide cation, which forms a covalent disulfide bond with the H +, K+ ATPase, irreversibly inactivating the enzyme. 

The instability of /V - ary I -S-al k y I s UI fen am ides observed in the reaction mixture was shown to be due to hydrolysis and a more rapid reaction with nucleophiles. In the presence of millimolar concentrations of GSH isolated sulfenamides yielded the arylamine and the thiol disulfide within a few minutes35,72. 

Their synthesis can also be carried out as a two-phase electrolysis, using ammonium salts 326). Sulfenamides can be produced by oxidizing tetraalkylthiuram disulfides in the presence of amines 321 ... 

Many free radical-generating compounds have been disclosed as synergists which may be used in place of peroxides to enhance the selfextinguishing action of bromine compounds. Examples of some of these materials are the disulfides, sulfenamides, a,a -diphenyl-a-methoxybi-benzyl, N-nitroso-N-methylaniline, tetraethyllead, pentaphenylphosphine, 1,2-diphenyltetramethylethane, tetraphenylhydrazine, and heavy metal salts or chelates (7, 9, 40, 41, 42, 55, 59 71, 90, 132). 

As the H+, K+-ATPase inhibition is associated with the modification of mer-capto groups in the enzyme, the disulfide adduct (ESSR) can be considered as a model of the enzyme-inhibitor complex, and the sulfenamide, or possibly the sulfenic acid (C), formed from omeprazole can be considered to be the active inhibitor, which binds covalently to cysteine residues of the H+, K+-ATPase. 

There are currently four racemic PPIs available on the market omeprazole, lansoprazole, pantoprazole, and rabeprazole. (More recently, enantiomerically pure versions have also been studied and developed, e.g., S-omeprazole, marketed by AstraZeneca as esomeprazole see Chapter II-2.) Proton pump inhibitors share the same core structure, the substituted pyridylmethyl-sulfmyl-benzimidazole, but differ in terms of substituents on this core structure. The absolute requirements of the core structure for the activity of PPIs was not understood until it became clear that the active PPIs are derived from inactive prodrugs the prodrugs are transformed, in the acid-secreting parietal cells, by a unique cascade of chemical structural transformations leading to the active principle, a cyclic sulfenamide species. Inhibition of acid secretion in turn is then achieved by formation of covalent disulfide bonds with key cysteines of the (H+/K+)-ATPase. 

Silver salts are also utilized to perform nucleophilic additions to disulfide bonds to yield sulfenamides (146). If alkyl halides are treated with stoichiometric AgBF4 in dimethyl sulfoxide solvent (DMSO, solvent), the corresponding aldehydes/ ketones will form in good yields. This reaction is an alternative to the well-known Swern oxidation (147). In addition, silver can drive the formation of dialkylper-oxonium ions from alkyl halides, which then oxidizes sulfoxides or sulfides (148,149). In the presence of AgN03, sulfides can be oxidized into a-chloro sulfoxides by SO2CI2 (Fig. 36) (150). 

Secondary amines can be converted into sulfenamides by reaction of the lithium dialkylamides with disulfides. Perchlorylamines (36) have been prepared in good yields from piperidine and other secondary amines by reaction with chlorine(VII) oxide. ... 

When an A -t-butyl group was present, attack occurred at carbon forming the usual four-membered oxaphosphorane. Analogously, sulfenamides were the first-formed products from thiols but they reacted with additional thiol and benzaldehyde to finally produce imines and disulfides. 

In the case of the double NPS-protected lysine methyl ester, oxidation selectively takes place at the 6-sulfenamide function under spontaneous cyclization via the a-sulphe-namido group as nucleophile. Only one diastereoisomer of the A,A -bis(NPS)-protected methyl 6-amino-piperidine-2-yl-carboxylate seems to be formed. The transformation of a-amino alkanoates and diaryl or dialkyl disulfides to the aryl- or alkylsulfenimine derivatives can be performed electrochemically using MgBr2 as a mediator system. This reaction can either proceed in one step or starting from the corresponding sulfenamide [170]. 

Besides sulfur, during the vulcanization process other chemical compounds are commonly added. One group of such compounds consists of vulcanization accelerators. Substances such as diphenylguanidine, mercaptobenzothiazole, tetramethythiuram disulfide, N-oxydiethylene-2-benzothiazolylsulfenamide, N-oxydiethylenethiocarbamoyl-N -oxidiethylenesulfenamide, cyclohexylbenzothiazolyl-sulfenamide, etc. are utilized for this purpose. The structures of two sulfenamide accelerators are shown below ... 

When both atoms that constitute the single bond possess nonbonding electron pairs, the barrier often is in the observable range. The high barrier may be due to electrostatic interactions or repulsions between lone pairs. For example, the barrier to rotation about the sulfur-sulfur bond in dibenzyl disulfide (C6H5CH2S-SCH2C6H5) is 7 kcal moF Similar high barriers have been observed in hydrazines (N-N), sulfenamides (S-N), and aminophosphines (N-P). 

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