General method for preparing imidazoles or 1-imidazolamines

The a-acylaminoketimine or a-acylaminohydrazone (10 mmol) and triethyl-amine (3.67 g, 36 mmol) together with hexachloroethane (3.55 g, 15mmol) are treated at —25°C in acetonitrile (30 ml) with triphenylphosphine (3.93 g, 15 mmol). After stirring (5h) at around 23°C, the solid is filtered and washed with a little THF, and the filhate is evaporated to dryness. The residue is treated with 10% hydrochloric acid (40 ml), diluted with water (250 ml) and exhaustively extracted with ether. The aqueous phase is saturated with sodium chloride, made strongly alkaline with solid KOH, and again exhaustively extracted with ether. The dried ether extracts are concentrated, and the residue is either reciystallized or distilled. 

Ring closure of formylglycine amidines, induced by heating alone or in the presence of phosphoryl chloride, bears similarities to the general method 

Methods of imidazole synthesis based on the use of diaminomaleonitrile (DAMN (13), R = II) have proliferated in recent years. The reagent is now readily available from chemical distributors at a price which makes its use reasonably economical. Some of these methods of synthesis fall under the present heading others involve 1,5 bond formation (see Section 2.2), or 1,2 and 2,3 bond formation (see Section 3.1.1). 

If DAMN is mono-N-alkylated before reaction with the carbonyl reagent the method gives 1-alkylimidazoles [15]. For example, 4,5-dicyano-l-(2, 3, 5 -tri-0-benzoyl-)S-D-ribofuranosyl)imidazole (57%) has been made by treatment of the ribosylamino-DAMN with triethyl orthoformate at 90°C in anisole under nitrogen for 5h. The intermediate enamine is not isolated in this case [42]. When DAMN is treated with AyV-dialkylamides in the presence of phosphoryl chloride, the Schiff base (14) (R = NR R ) cyclizes to give 2-dialkylaminoimidazoles (15) (R = NR R ), including 4,5-dicyanoimidazole (15) (R = H) when DMF is used [15], Imidazoles (15) (R = OR, NR R ) can be made in one step when DAMN reacts with orthoesters or iminoether hydrochlorides. Under mild reaction conditions the intermediate alkoxyimines (14) (R = OR ) or amidines (14) (R = NR R ) can be isolated before oxidation to (15) [46, 47, 49], Table 2.1.4 lists some examples. 

2-AniinoimidazoIes are also formed when DAMN is treated with isocyanide dichlorides (e.g. cyanogen chloride) (see Section 3.1.1). 

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