GB1088246A - A process of producing hypoxanthine - Google Patents

Abstract

Hypoxanthine is obtained by subjecting 4-amino-6-hydroxy-5-nitroso pyrimidine or salt thereof to reduction with a reducing agent to convert the nitroso group to amino to form the corresponding 4,5-diamino compound and subjecting the latter to imidazole ring closure by means of formamide to convert it to hypoxanthine, the reaction being carried out in the presence of formamide and without isolation of any intermediate product. The 4-amino-6-hydroxy -5-nitroso-pyrimidine or salt thereof may be obtained by subjecting 4-amino-6-hydroxy -pyrimidine or salt thereof to nitrosation by means of a nitrosating agent in the presence of formamide and is then directly reduced without isolation. The nitrosation may be carried out either (a) by adding a stirred solution or suspension containing a nitrite, e.g. ammonium, sodium or potassium nitrite, in formamide to the 4-amino-6-hydroxy pyrimidine or salt (e.g. Na salt) thereof, followed by dropwise addition of formic, acetic or mineral acid (e.g. HCl or H SO4) while stirring, or (b) by passing gaseous HNO2 through 4-amino-6-hydroxy-pyrimidine or a salt thereof (e.g. Na salt) together with an acid to free the 4-amino-6-hydroxypyrimidin from the salt. The reduction of the nitroso compounds may be carried out by treating with a suitable reducing agent or by hydrogenation in the presence of a catalyst. Several suitable reducing agents are specified including sodium hydrosulphite, sodium thiosulphate, potassium sulphite, organic dithionites, sodium sulphide, ammonium hydrosulphide or polysulphide, sodium bisulphite, hydrazine sulphate or hydrate, formaldehyde-sodium bisulphite, stannous chloride, aluminium amalgam, and various catalytic hydrogenation procedures are also specified. The final ring closing reaction is suitably effected at above 150 DEG C. and the entire process is preferably carried out in an inert atmosphere, e.g. nitrogen.