Ethyl 2-amino-l-methylimidazole-5-carboxylate hydrochloride

2-Aminopropanal diethylacetal (5.0g, 34 mmol) and ethyl 4-fluorobenzimidate (5.7 g, 34 mmol) combined with glacial acetic acid (4ml) are heated at I00°C (2h) before addition of 5m HCl (14 ml) and further heating at 100°C (30 min). The solution is then diluted with water (150 ml) and extracted with ether (3 X 150 ml). The ethereal solution is then dried (Na2S04) and evaporated, to give a residue (3.5 g), which on recrystallization from acetonitrile gives the pure product (2.4 g, 39%), m.p. 185-187°C. 

General procedure for 1,4-disubstituted imidazoles using formamide [12] 

To a stirred solution containing aminomalonodinitrile p-toluenesulfonate (Aldrich or Fluka) (5.1 g, 20 mmol), sodium acetate (1.6 g. 20 mmol) and acetic acid (30 ml), the ethyl formimidate (20 mmol) is added portionwise over 20 min. The solution is stirred at room temperature (16h), before addition of ice-water (200 ml). The precipitate is filtered, washed with water (100 ml) and recrystallized from ethyl acetate-hexane. Typical products (7) (R, yield) 2-pyridyl, 28% 3-pyridyl, 30% 2-pyrimidinyl, 30% P-CIC6H4, 11% o-CIC6H4, 33% 2,4-Cl2C6H3, 21% 5-Cl-2-pyridyl, 29%. 

RING SYNTHESES INVOI VING FORMATION OF TWO BONDS 

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