Thiols heteroaromatic, oxidation

Under aprotic conditions, prototropic transformations of thiols are relatively slow, so one can observe distinct waves of the oxidation of the protonated form and of its parent base [19, 20]. Normally, the oxidation of thiols (aliphatic, aromatic, and heteroaromatic) affords diorganyl-disulfides. So various aliphatic and aromatic thiols are easily converted into the corresponding disulfides upon oxidation in MeOH/MeONa with the yields ranging... 

Fortunately, there is now a comprehensive body of knowledge on the metabolic reactions that produce reactive (toxic) intermediates, so the drug designer can be aware of what might occur, and take steps to circumvent the possibility. Nelson (1982) has reviewed the classes and structures of drugs whose toxicities have been linked to metabolic activation. Problem classes include aromatic and some heteroaromatic nitro compounds (which may be reduced to a reactive toxin), and aromatic amines and their N-acylated derivatives (which may be oxidized, before or after hydrolysis, to a toxic hydroxylamine or iminoquinone). These are the most common classes, but others are hydrazines and acyl-hydrazines, haloalkanes, thiols and thioureas, quinones, many alkenes and alkynes, benzenoid aromatics, fused polycyclic aromatic compounds, and electron-rich heteroaromatics such as furans, thiophenes and pyrroles. 

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. 

Malonomonoamides can be condensed with aldehydes to give acrylamides or cinnanamides, but condensation with malonodiamides is of only minor impjortance. In contrast to Meldrum s acid (58), Knoevenagel reactions of barbituric acid (56) and A A -dimethylbarbituric acid have been less explored. However, several aliphatic, aromatic and heteroaromatic aldehydes are known to react easily and with high yields in most cases. Reactions of 1,2-dimethyl-3,5-pyrazolidinedione (93) with several aliphatic and aromatic aldehydes using standard conditions yield Knoevenagel products in good yield. A similar reactivity is observed with 2-phenyl-3,5-dioxoisoxazolidine (94) and oxazepanediones (45 see Section 1.11.2.5). Recently, the oxidations of alcohols to carbonyl compxiunds and thiols to disulfides with 5-arylidene-l,3-dimethylbarbituric acids (95) have been described Mechanistically (95) mimics enzymic oxidation by flavin adenine dinucletide (FAD). ... 

Disulfides play a prominent role in pharmaceuticals, pesticides, and rubber vulcanization reagents. In biological systems, disulfide bonding is essential for peptides and proteins to fold into their active conformation. Noel et al. reported a mild batch and continuous-flow method to access disulfides by the aerobic oxidation of thiols [48]. Initially, an open flask batch procedure with Eosin Y (1 mol%) as catalyst resulted in near quantitative yields for a variety of thiophenols and heteroaromatic and aliphatic thiols, within 16 h. Moreover, it was found that the... 

A particular example of overoxidation is the oxidative desulphurization of heteroaromatic thiols by hydrogen peroxide which may lead to the... 

The synthesis of thioesters through the coupling aldehydes with thiols has been achieved using common iron salts as catalysts (Scheme 5.33) [54], The reactions required an oxidant, and tert-butyl hydroperoxide was found to be effective tmder the reaction conditions. The reactions were carried out in pure water and afforded moderate to excellent yields of the thioesters. The scope of the chemistry was quite broad as both alkyl and aryl aldehydes as well as alkyl- and arylthiols were successfully coupled as well as several heteroaromatic aldehydes. Overall, this is a practical approach to the preparation of thioesters. 

Additionally, the C-S bond must be preformed prior to oxidation. Though milder methods have been developed for oxidative chlorination, many of these methods offer a limited substrate scope and heteroaromatic sulfonyl chlorides are sometimes inaccessible. Both atyl and allqrl sulfonyl chlorides may be accessed by oxidative chlorination of thiols. One approach for the preparation of heteroatyl sulfonyl chlorides from heteroatyl thiols using inexpensive aqueous sodium hypochlorite has been reported (Scheme 13.5). ° Furthermore, the use of sodium hypochlorite obviates the use of chlorine gas and facilitates control of oxidant stoichiometry, preventing product decomposition. 

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