Amino compounds, methylation diazomethane

Methylation of 2-amino-3-hydroxypyrazine (62) with methyl iodide and sodium methoxide afforded 3-amino-l-methyl-2-oxo-1,2-dihydropyrazine (63), and when an excess of methyl iodide was used, a mixture of compound (63) and its methio-dide (64) was isolated. Reaction with dimethyl sulfate and alkaU gave compound (63) and l,4-dimethyl-2,3-dioxo-l,2,3,4-tetrahydropyrazine (66) the latter was presumed to be formed by hydrolysis of an intermediate quaternary salt since it was also obtained by treatment of the methiodide (64) with aqueous sodium hydroxide. Reaction of 2-amino-3-hydroxypyrazine with ethereal diazomethane produced a mixture of N- and 0-methyl derivatives, (63) and 2-amino-3-methoxy-pyrazine (65). With methyl toluene-p-sulfonate the quaternary salt 2-amino-3-hydroxy-1-methylpyrazinium toluenesulfonate (67) was obtained on alkaline hydrolysis it gave 3-hydroxy-l-methyl-2-oxo-l,2-dihydropyrazine (68) (832). Pulcherriminic acid with diazomethane gave a dimethyl derivative (99). 

A method involving SPE was developed for the determination of ten A-nitroso amino acids in cured meat products. These compounds were derivatized with diazomethane followed by O-acylation of hydroxyl groups with acetic anhydride-pyridine reagent. The methyl esters and their acylated derivatives were separated by GC on a DB-5 fused silica capillary column and quantified with a TEA-CLD specific for the nitric oxide derived from the thermal denitrosation of nitrosamines recovery exceeded 75% at the 10 ppb level579. 

Another useful method for the elucidation of the hydroxypyrazine-pyrazinone tautomerism is UV spectral analysis. The objective structure in solution is easily estimated by comparison with the UV spectra of the proton-fixed compounds of two tautomers, O-methylated (22) and A-methylated derivatives (23), which are prepared by methylation of the hydroxypyrazines or pyrazinones with diazomethane (Scheme 2). For example, 6-amino-5-benzyl-3-methyl-2(177)-pyrazinone (21 R = Me, R = CHzPh, X = NH2) has been shown to predominate over the hydroxy form (20) because of its nearly identical UV spectrum with the corresponding V-methylated derivative (23) <93JOC7542>. In contrast, 6-chloro-2-hydroxypyrazines (20 R, R = Me or Ph, X = Cl) exist in the hydroxy form rather than as the tautomeric amide, which is an exceptional example of predominance of the hydroxy form with parallels in the chloro-pyridinone field <7UCS(C)2977>. 

Alkylation can also be performed with diazomethane. The reaction of diazomethane with amino groups is rather slow and long reaction times are required to obtain the quartemary ammonium compounds. Other functional groups in the molecules react faster, the carboxyl groups to give methyl esters, and the hydroxyl groups to give methyl ethers. 

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