Oxamides imidazoles, 5-chloro

The earliest example of this type of synthesis was probably the Wallach synthesis 70AHC(12)103> in which an A, A/ -disubstituted oxamide underwent ring closure with phosphorus pentachloride. The chloro-containing intermediate which formed was reduced by hydriodic acid to give a 1-substituted imidazole. An adaptation of this reaction to the synthesis of 5-chloro-l-methylimidazole is shown in Scheme 1. 

Although yields of imidazoles are not always good, and the 5-chloro products may be contaminated with polychlorinated products, the method can be useful. If symmetrical oxamides are heated at 60-95°C with 2.1 mol eq. of phosphorus pentachloride in phosphoryl chloride (with cooling to moderate the exothermic reaction), followed by further heating at around 100°C for 30 min, high yields of (1) are achievable [5]. Some unsymmetrical oxamides have also been shown to give good yields on occasion [8] (Table 2.1.1). 

Imidazoles.—Formation. Several new syntheses of imidazoles from isocyanides have been reported these include the formation of 1-alkyl-imidazoles (396) by the action of primary amines on 2-isocyano-2-tosylstyrene, PhCH=C-(NOTos, the cyclization of the enamine Me2NCH=C(NC)C02Me to compound (397) in the presence of methyl iodide,and the preparation of the ethers or thioethers (398) from isocyano-cyanides R CH(NC)CN by their reaction with alcohols or thiols R XH, respectively.Aromatic aldehydes are converted into 2-aryl-4,5-dichloroimidazoles (399) by the combined action of cyanogen and hydrochloric acid. 5-Acetyl-4-methylimidazole (400) results when form-amido-acetylacetone, AC2CHNHCHO, is heated with formamide and formic acid. Exhaustive chlorination of tetramethyldithio-oxamide leads to the tri-chloro-imidazolium cation (401). ... 

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