2- Mercaptopyrazine

Hydroxypyrazine with phosphorus pentasulfide in refluxing pyridine for 45 minutes was readily converted to 2-mercaptopyrazine (46%) (55) (its 1-methyl analogue was prepared similarly) (821,1100) and 5-mercapto-2,3-diphenylpyrazine was prepared likewise (834, 1008). 2-Amino-3-mercaptopyrazine was prepared from 2-amino-3-hydroxypyrazine and phosphorus pentasulflde in refluxing 0-picoline(llOl). 

The structure of 2-mercaptopyrazine (1, R = H) in aqueous solution has been examined by comparison of its ionization constants and ultraviolet spectra with... 

IONIZATION CONSTANTS AND ULTRAVIOLET SPECTRA" OF 2-MERCAPTOPYRAZINE AND ITS N- AND SJdETHYL DERIVATIVES... 

Mercaptopyrazine on heating to 220° decomposed to hydrogen sulfide and dipyrazinyl sulfide (7) (821) and was oxidized by iodine in aqueous potassium iodide to dipyrazinyl disulfide (9) (821). 

Mercaptopyrazine in aqueous hydrochloric or acetic acids was chlorinated to give the sulfonyl chloride which with excess liquid ammonia gave 2-sulfamoyl-pyrazine (1006, 1153). Direct sulfonation of the pyrazine ring has never been reported (819) but 2-sulfopyrazine (17) has been prepared from 2-chloropyrazine and aqueous sodium sulfite at 150° (819), and from 2-fluoropyrazine and aqueous sodium sulfite at reflux for 2 hours (882, 884). 2-Amino-3-mercaptopyrazine in aqueous sodium hydroxide with concentrated ammonia and sodium hypochlorite has been shown to give 2-amino-3-sulfamoylpyrazine (1101). 

Ultraviolet spectra have been used extensively in a study of tautomerism in 2-hydroxy- (821, 1081) and 2-mercaptopyrazines (821, 1100) (see Sections VI. 5 and VI1.3, respectively) and both compounds have been shown to exist predominantly in the form (2, X = 0, S). The wavelengths of the first and second absorption maxima of the different species of 2-mercaptopyrazine (neglecting the effect of methyl substitution) follow the sequence, cation > thioamide > anion > thiol... 

This sequence was also observed for the long wavelength maxima of the corresponding species of 2-hydroxypyrazine (821) and was in accord with a molecular-orbital theory developed by Mason (1480). Cullen and Harrison (905) have found a broad maximum in the 380-400 nm region for a series of C-methyl 2-mercaptopyrazines and 3-mercaptopyrazine 1-oxides. This was shifted to shorter wavelengths by about 40 nm in the spectrum of the anion. 

A comparison of 13C and JH spin-coupling constants for pyrazine-2( l//)-thione establishes the thione tautomer as the dominating structure. A small amount (ca. 5%) of the thiol tautomer is also detected in DMSO-J5. In CD3N02 solution, the tautomeric mixture contains about 3% of the thiol form (82TL4785). The relative energies of tautomers of 2-mercaptopyrazine were calculated by the AMI method. The predominance of the thiol tautomer is predicted for the gas phase however, the significant contribution of the thione tautomer in polar solvents is indicated (92MI7). 

Mercaptopyrazine (151a) is best prepared by the action of sodium hydrogen sulfide on chloropyrazine in dimethylformamide.147 It decomposes on heating with evolution of hydrogen sulfide and formation of di-2-pyrazinyl sulfide. The latter compound is also obtained together with mercaptopyrazine on treatment of chloropyrazine with aqueous potassium hydrogen sulfide solution. Comparison of the... 

The major preparative routes to hydrazinopyrazines have been covered already by primary synthesis (see Chapters 1 and 2) and by hydrazinolysis of halogenopy-razines (see Sections 4.2.1 and 4.4). Minor routes (like the hydrazinolysis of alkylthio-, alkylsulflnyl-, alkylsulfonyl-, or mercaptopyrazines) appear to be unrepresented in the recent literature. 

Halogenopyrazines may react with sodium (or potassium) hydrogen sulfide or polysulfide to give the mercaptopyrazine and in some cases the corresponding sulfide. 

By using thiourea in 2N sulfuric acid, Cullen and Harrison (905) were able to convert 2-chloro-3-methylpyrazine at reflux for 30 minutes to 2-mercapto-3-methylpyrazine (55%), and 3-chloro-2,5-dimethylpyrazine similarly treated gave 3-mercapto-2,5-dimethylpyrazine together with another higher molecular weight compound, postulated as either (60) or (61). 2-Amino-3-chloropyrazine refluxed with thiourea in alcohol, and the thiouronium salt refluxed with aqueous sodium hydroxide, produced 2-amino-3-mercaptopyrazine (535). 2-Chloropyrazine failed to react with thiourea (821) under the mild conditions that converted 2-chloro-quinoxaline to 2-mercaptoquinoxaline (1014). 

The preparation of mercaptopyrazines (1) by the reaction of halogenopyrazines with sodium (or potassium) hydrogen sulfide or sodium polysulfide in various solvents (780, 790, 799, 805, 809, 821, 858, 890, 892, 993, 1006-1011), by reaction with phosphorus pentasulfide in pyridine (1013), and by reaction with thiourea in acid (905) and in alcohol followed by alkali (535) has been described in Section V.5G. 

Preparations of mercaptopyrazines from hydroxypyrazines by reaction with phosphorus pentasulfide in boiling pyridine or 3-picoline have been reported in Chapter VI.6B. 

Methyl-2-oxo-l, 2-dihydropyrazine with phosphorus pentasulfide in pyridine at reflux was converted into l-methyl-2-thio-l,2-dihydropyrazine (18) (821,1100), and 3-chloropyrazine 1-oxide with sodium hydrogen sulflde in ethanol at room temperature gave 3-mercaptopyrazine 1-oxide (19) (1035). Whereas 3-chloro-2,5-dimethyipyrazine 1-oxide reacted slowly with thiourea in ethanol, and the use of water in place of ethanol caused some increase in reaction rate, the reaction in 2A sulfuric acid at reflux for 30 minutes gave 3-mercapto-2,5-dimethylpyrazine 1-oxide (85%), and 3-mercapto-2-methylpyrazine 1-oxide was prepared similarly (905). 

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