Heterocyclic compounds formation from saturated substituted

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

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