Nucleophilic sulfur

Glutathione-Mediated and Other Reactions Involving Nucleophilic Sulfur... 

The Hammett p values in Table 28, found by changing the p-substituent on the nucleophile in DMF and methanol, support this conclusion. The larger p value in DMF indicates that the change in charge on the nucleophilic sulfur atom is greater on going from the reactant to the transition state in DMF. Therefore, the S—Ca transition state bond is shorter in DMF than in methanol. 

JAP(K)48664. 4-Diazo-5-thiocarbamoylimidazole at pH 5 intramolecu-larly cyclized with the more nucleophilic sulfur to give the imidazo-thia-diazine 228 instead of the imidazotriazine-4-thione 229, which was expected by analogy with the 4-diazoimidazole-5-carboxamide (73KGS1292) (Scheme 65). 

The achiral dicarbonyl complex 1 has been shown to undergo facile 1,4-addition of amines and thiols to generate the elaborated acyl complexes 2. The more nucleophilic sulfur atom of 2-mercaptoethanol selectively adds to such complexes45. 

In delineating the scope of the bromination-nucleophilic sulfur reaction, two difficulties have been encountered. Bromination with bromine is not successful with tertiary hydrogens such as those present in prolyl derivatives (72CB625). Bromination can be accomplished by means of N-bromosuccinimide in presence of 2,2 -azobisisobutyronitrile however, in this case, 3,6-dialkylpiperazine-2,5-diones yield tetrabromo derivatives. These could be successfully utilized for the required purpose, as shown in Scheme 37. The trick consisted of displacing the bromine atoms attached to the ring by methoxy groups, followed by debromination and thiolation (75BCJ605). 

The order of the steps can be reversed. Thus, reaction of (18-4) with the tetrazole-thione (20-1) results in the displacement of the allylic group by nucleophilic sulfur... 

The reaction of trans-Pt with two equivalents of GSH results in a monomeric complex in which two GS units are coordinated via the cys-S atom [Eq. (10)] (76,131,189). The unstable intermediate species, [trans-Pt(NH3)2(GS)Cl] and [frans- Pt(NH3)2Cl 2GS], could also be detected by Berners-Price (189). The reaction of [Pt(NH3)3Cl]Cl with two equivalents of GS- initially yields [Pt(NH3)3GS], which reacts further, eventually forming [irans-Pt(NH3)2(GS)2] and free NH3 [Eq. (11) (131). This is rationalized by the large trans effect of the coordinated sulfur and the presence of a second nucleophilic sulfur. Therefore, the amine ligand is easily substituted by a second GS" unit. 

In organo-fluorine compounds fluorine atoms can be eliminated by nucleophilic sulfur species to form C —S bonds. In principle, the fluorine to be eliminated can be bonded to aliphatic or araliphatic compounds, as well as to aromatic or heterocyclic compounds however, the replacement proceeds more efficiently the more the fluorine is activated. Therefore, the synthetic usefulness of these reactions is the broadest with fluoroaromatic compounds, including heteroaromatics, with which the reactions often proceed smoothly under mild conditions. The nucleophilic sulfur compound to be reacted is. in most cases, an aliphatic or aromatic thiol or a metal sulfide, but reactions with, for example, thiourea or ammonium thiocyanate have also been described. The sulfur introduced this way can be either oxidized or removed by reduction, opening additional possibilities for modifications of the original fluoro compounds. 

Fluoroaromatic compounds react with nucleophilic sulfur species, resulting in single, multiple, or complete replacement of fluorine, to form C —S bonds. The extent of fluorine substitution depends on (1) the solvent used, (2) the nature of the sulfur reagent, (3) the ratio RS / ArF, (4) the reaction time and temperature, and (5) the nature of the fluoroaromatic compound. 

Reviews which cover heterocyclization of unsaturated sulfur compounds have been published recently.16 Cyclizations of sulfur systems can also be effected by radical chain mechanisms or by reactions in which the sulfur acts as an electrophile. Examples of nucleophilic sulfur functional groups used in heterocyclization reactions are shown in Figure 3. ... 

When benzylbromide is allowed to react with 4-(3-mercapto-5-phenyl-[l,2,4]triazol-4-ylmethyl)-benzamide (32) in order to synthesize the corresponding thiobenzyl adduct 4-(3-benzylsulfanyl-5-phenyl-[l,2,4]tria-zol-4-ylmethyl)-benzamide (33), a nucleophilic sulfur-based resin (34) is employed to trap excess benzylbromide from the reaction mixture affording a final clean product (33).28 In addition, a basic Amberlite (OH-) is added to assist in the efficient deprotonation of the mercapto functionality in (34) as depicted in Fig. 13. 

J. H. Rigby, Vinyl Isocyanates as Useful Building Blocks for Alkaloid Synthesis, Synlett 2000, 1-12. W. D. Rudorf, Reactions of Carbon Disulfide with C-Nucleophiles, Sulfur Rep. 1991, 11, 51-141. 

The activity of sulfur towards platinum complexes has led to investigation of so-called rescue agents to ameliorate the side effects of platinum therapy, without compromising its anti-tumor activity. These nucleophilic sulfur compounds include sodium thiosulfate (STS), sodium diethyldithio-carbamate (Naddtc), (S)- 2-[(3-aminopropyl)amino]ethyl phosphorothioic acid (WR-2721, Ethyol , amifostine), glutathione (GSH), methionine, thiourea, cysteine, -acetylcysteine, penicillamine, biotin, sulfathiazole, sodium 2-mercaptoethanesulfonate (mesna), and its dimer (di)mesna (BNP-7787). The protective effect of these compounds is either due to prevention, or reversal of Pt-S adducts in proteins. Some of the more promising of the above-mentioned compounds (see Fig. 1) will be discussed below. 

Cyclooctyne (14) adds bromine to give l,2-dibromo-cis-cyclooctene93) this is presently the only route to prepare a pure 1,2-dihalocyclooctene. The addition of bromine and iodine to (31) leads to the unexpected products (54) apparently trans-annular attack of the cationic intermediate (55) by the nucleophilic sulfur produces a strained sulfonium ion which stabilizes itself by ring opening to (54)201). 

Other approaches to Cr-mediated aromatic thiation have been studied [24], and quenching of lithiated arenetricarbonylchromium complexes by electrophilic sulfur has been compared to halogen displacement by nucleophilic sulfur. 

Phosphorus pentasulfide has often been used for converting an O—S—S sequence into an S—S—S one <71AHC(13)161,p. 192,77AG(E)403,80JOC3909). Similarly, an O—S—O sequence can be transformed into an O—S—S one and an O—Se—Se sequence into an S—Se—Se one. All these reactions involve an attack at position 2 by a nucleophilic sulfur atom, while the oxygen atom in position 1 is removed by fixation on phosphorus. In the same way, phosphorus pentaselenide converts O—S—S sequences into Se—S—S ones. 

---