Mercapto compounds, oxidation

Mercapto compounds, oxidation of, 7 242-243 Mercaptodicyanamides, reaction with hexafluoroacetone, 30 267... 

The free mercapto compounds (72) are extremely stable towards alkalis and acids, but they are quickly attacked by oxidizing agents.15,126 Disulfides (73) or disulfonic acids (74) are obtained, depending upon the conditions. On melting with alkali the latter compounds do not yield 2,6-dihydroxy derivatives but cleavage products. 

A better clue comes from knowledge that several vital cell constituents, particularly mercapto-compounds [such as dihydrolipoic acid (2.25), see Section 11.7.3] are easily oxidized by atmospheric oxygen if traces of iron or copper are present. These oxidations lead to the formation of hydrogen peroxide and superoxide radicals ( O2 ) which, in the presence of the metal cations, produce a fulminating chain reaction so that a very small amount of metal can catalyse widespread destruction. In some model reactions of this kind, traces of cobalt have been found to act as a chainbreaker which greatly moderates the destruction (see Fig. 11.10). ... 

Thiazolo[5,4-d]p3rriinidine-l-N-oxides, ready to obtain from 6-chloro-l,3-dimethyl-5-nitro-pyrimidinone by reaction with mercapto compounds, monitored by base catalyzed dehydra-tive cyclization, can be simply deoxygenated to produce thiazolop5n imidines. Reductive deoxygenation by treatment of the thiazolopyrimidine oxides with sodium dithionite or oxidative deoxygenation with dimethylformamide at reflux temperature can produce the anticipated thiazolopyrimidines [137]. 

Among other pyridine derivatives 2-hydroxy-pyridine-AT-oxides, 2-mercapto-pyridine- -oxides and 8-hydroxyquinolines are described in this section which may be looked at as membrane-active microbicides with chelating properties. The following pyridine compounds with antimicrobial activity but without significant importance for the protection of materials shall only be mentioned ... 

A problem associated with the use of abrasive metal poHshes is that the fresh metal, which has been exposed by the cleaning, rapidly oxidizes or tarnishes. Thus, many modem poHshes contain inhibitors. Sulfur compounds, eg, alkyl benzyl thiols, commonly are used, as are mercapto esters such as lauryl thioglycolate [3746-39-2] and dialkyldisulfides (52—54). 

Hydroxy and mercapto substituents at the 3- and 5-positions can also exist in tautomeric forms (see Section 4.01.5.2) and can be alkylated at either the substituent or the ring nitrogen atom. 3-Methoxy groups are not replaced by nucleophiles, but both 3- and 5-alkylthio groups react readily, as does 3-methoxy-l,2-benzisothiazole. Alkylthio compounds can be oxidized to sulfoxides and sulfones, and the latter readily undergo nucleophilic replacement. All the hydroxy compounds react with phosphorus pentachloride to give the chloro derivatives. 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

Oxidation of 2-mercapto-l,2,4-triazolo[l,5-c]pyrimidines (174) with chlorine or bromine in water (64BRP951652 65JCS3369), with hydrogen peroxide and chlorine (95MIP1), as well as with sodium chlorate in hydrochloric acid (94JMC2371) gave the corresponding 2-sulfonyl halide derivatives 175. Oxidation of the 2-alkylmercapto compounds 176 to the 2-alkylsufonyl derivatives 177 was made with ammonium peroxodisulfate and sulfuric acid... 

This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a /3-dicarbonyl group, either intact or as the corresponding ketal. The usefulness of the 2-mercaptopyrimidines is enhanced by the ease of removal of the mercapto group by desulfurization 9 or oxidation 10 and its replacement by other functional groups.1 ... 

The thiol group was displaced from 3-mercapto-l,2,4-triazoles 59 using oxidation to yield the corresponding 3-unsubstituted compounds 60a-d in good yield (Equation 19) (Table 5) <2006S156>. 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

Qualitative spot tests for aldehydes, in the presence of ketones, are generally only reliable for water-soluble compounds. This problem can be overcome by the use of 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald , Aldrich Chemical Company) in the presence of Aliquat (Scheme 5.27). Under aerial oxidation, the initially formed colourless cyclic adduct changes colour through red to purple. The colourless cyclic aminal can also be formed by ketones, but only the adducts derived from the aldehydes are oxidized to the purple bicyclic aromatic system [28]. Weakly electrophilic aldehydes, e.g., 4-methoxybenzaldehyde, reacts slowly, but will give the positive coloration upon gentle heating to ca. 70°C for one or two minutes. 

Although demethylation, which occurs in the liver, is normally considered to be a catabolic process, it may result in conversion of an inactive form of a drug to the active form. Thus 6-(methylthio)purine (XXXIX) is demethylated by the rat to 6-mercaptopurine [205]. This demethylation occurs in the liver micro-somes and is an oxidative process which converts the methyl group to formaldehyde [204, 207]. The 1-methyl derivative of 4-aminopyrazolo[3,4-d] pyrimidine (XLI) is demethylated slowly, but 6-mercapto-9-methylpurine (XLII) not at all [208]. The A -demethylation of puromycin (XLlIl) [209, 210], its aminonucleoside (XLIV) [211], and a number of related compounds, including V-methyladenine and V,V-dimethyladenine, occurs in the liver microsomes of rodents [212]. In the guinea-pig the rate-limiting step in the metabolism of the aminonucleoside appears to be the demethylation of the monomethyl compound, which is the major urinary metabolite [213]. The relationship of lipid solubility to microsomal metabolism [214], and the induction of these demethylases in rats by pre-treatment with various drugs have been studied [215]. 

A unique utilization of an activated methylene group to form a thiophene derivative is represented in the cyclization in acidic xylene of (95), formed by Michael addition of 2-mercapto diethyl acetal, to cyclohexenone. Compound (96), produced as a crystalline solid in better than 80% yield, was readily converted to the corresponding thiophene (97) or benzothiophene (98) by oxidation. Oxidation of (96) with chloranil gave (97) in 63% yield (70JHC393). 

Evers, et al. (34) identified several S-substituted furans having meaty aroma including 3-mercapto-2-methylfuran and 3-mer-capto-2,5-dimethylfuran from Maillard reaction mixtures. These compounds were readily oxidized to sulfides, some of which retained meaty odors. All furans having the sulfur atom bound to the 8-carbon had meaty aromas, whereas those with sulfur bound to the a-carbon had hydrogen sulfide-like odors. 

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