Oxamides, symmetrical

The earliest method of this type was the old Wallach synthesis, which formed the imidazole ring by cyclization of an MiV -disubstituted oxamide with phosphorus pentachloride the usual product was a 1-substituted 5-chloroimidazole (1) (Scheme 2.1.1) [1-4]. Although initially thought to be rather limited in its application, the method was later extended to cyclization of higher symmetrical and unsymmetrical oxamides, and now provides access to a variety of 5-chloroimidazoles [5-8]. 

Symmetrically substituted oxamides can be made in 84-94% yields from diethyl oxalate and primary amines [5], whereas the unsymmetrical A-alkyl-A -arylmethyloxamides are available in high yields by initial treatment of an ethanolic solution of diethyl oxalate with a benzylamine at 0°C, followed by... 

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). 

Like formamides, homologous carboxamides may also be used for the acylation of organometallics unless the latter are sterically crowded. 2,6-Dichlorophenyllithium and other 2,6-disubstituted aryllithiums can only combine with dimethylformamide. If tetramethyloxalamide is treated with one equivalent of organolithium prior to hydrolysis, a 2-oxocaui>oxamide is obtained, with two equivalents symmetrical v/c-diketones. ... 

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