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A new preparative method of obtaining guanine from 3-methylxanthine has been developed.Guanine [2-amino-6-hydroxypurine (VI)] is the starting material for the synthesis of the drugs thioguanine, acyclovir, gancyclovir, and several other biologically active substances [1, 2].Natural sources for obtaining guanine include guano, fish scales, and yeast (yeast RNA), however the manufacture of this amine from these forms of raw material is complex, careful purification from contaminants is required, and it leads to a low yield of the final product.Synthetic methods are known for obtaining guanine from derivatives of pyrimidine [3][4][5][6][7][8], imidazole [9][10][11], and purine [12, 13]. The drawbacks of the majority of the synthetic methods described for obtaining, guanine are their multistage nature and the difficult availability of the starting substances.Other studies have reported unsuccessful attempts to synthesize guanine from derivatives of pyrimidine and purine. Thus, on boiling 2,4,5-trimino-6-hydroxypyrimidine with formaldehyde a nitrogen-containing compound of unestablished structure was isolated in place of guanine [14]. On heating 2-methylmercaptohypoxanthine with alcoholic ammonia solution at 130°C no reaction occurred, only the starting material was isolated [15].The point of our investigation was the development of a method of obtaining guanine from 3-methylxanthine, one of the purine derivatives available as an intermediate from the synthesis of the alkaloids theobromine and caffeine [16, 17].For this purpose 7-benzyl-2-chlorohypoxanthine (IV) was obtained from the potassium salt of 3-methylxanthine (I) by the method of [18]. Several improvements were introduced into the method enabling the synthesis of (IV) to be simplified and its yield increased.When studying the amination of compound (IV) it was noted that the chlorine atom in position 2 of the purine bicycle possessed a significantly lower lability than that in position 6 of 7-benzyl-2,6-dichloropurine (III) [18]. Consequently m0)e forcing conditions are required to replace it by an amino group, viz. a temperature of 140-160°C and conducting the reaction in an autoclave. Ammonia may be used either in alcoholic or aqueous solution. For preparative purposes it is convenient to use a 25% aqueous solution of industrial manufacture. 7-Benzylguanine (V) is formed in high yield (80-82%) by reacting compound (IV) with ammonia. This compound had previously been obtained by more complex routes and in low yield from 3-benzylguanine [19], N(2)-acetylguanine [19], and guanosine [20].The debenzylation of the amine (V) occurs readily on catalytic reduction in aqueous alkaline solution at 85-90°C with atmospheric pressure of hydrogen in the presence of palladium. The yield of guanine was 88 % calculated on amine (V) and 51-52% on the initial salt (I). *Deceased.

Die Xanthine (I) und (IV) reagieren mit w‐Chlor‐alkyl‐estern (II) zu den Xanthinen (III) und (V).

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