Pteridine studies. Part XXXIX. Pteridines unsubstituted in the 4-position; a new synthesis from pyrazines, via 3,4-dihydropteridines

Abstract

3-Aminopyrazine-2-carboxamide (IIa), warmed in phosphoryl chloride and dimethylformamide, gave 3-aminopyrazine-2-carbonitrile (IV), which was hydrogenated to give 2-amino-3-aminomethylpyrazine (I). This diamine was cyclised to 3,4-dihydropteridine and its 2-methyl-, 2-hydroxy-, and 2-amino-derivatives by treatment with ethyl orthoformate, ethyl orthoacetate, ethyl chloroformate, and S-methylisothiouronium hydrochloride, respectively. Similarly 2-amino-3-aminomethyl-5-methylpyrazine, obtained from 3-amino-6-methylpyrazine-2-carbonitrile by hydrogenation, furnished 3,4-dihydro-6-methylpteridine. All these 3,4-dihydropteridines were selectively oxidised (e.g. by manganese dioxide) to the corresponding pteridines, including the long-sought 6-methylpteridine.

2-Amino-3-ethoxalylaminomethylpyrazine (XIII) was made from the diamine (I) and ethyl triethoxyacetate. Hydrogenation of 3-ethoxalylaminopyrazine-2-carbonitrile (XIVb), prepared from the nitrile (IV) and ethoxalyl chloride, gave ethyl 3,4-dihydropteridine-2-carboxylate (VId) and ethyl 1,2,3,4-tetrahydropteridine-2-carboxylate (XVa). The former (VId) was hydrolysed to 3,4-dihydropteridine-2-carboxylic acid (VIe) and also oxidised to ethyl pteridine-2-carboxylate. The diamine (I) and formaldehyde furnished 1,2,3,4-tetrahydropteridine (XVb).

8-Aminoimidazo[1,5-a]pyrazine-3-thiol (XIIa), unexpectedly obtained from the diamine (I) and carbon bisulphide, was desulphurised with nickel to give 8-aminoimidazo[1,5-a]pyrazine.

Ionisation constants and u.v. spectra are reported and discussed. The covalent hydration of 6-methylpteridine and ethylpteridine-2-carboxylate is described.