Oxadiazole carbonyl chloride

The initial retrosynthetic analysis of 1 resulted in the cleavage of the two amide bonds and a C-N bond leading to the four components oxadiazole carbonyl chloride 2, methyl iodide, 4-fluorobenzylamine (4-FBA) and the densely functionalized hydroxypyrimidinone 3 (Scheme 6.1). These synthetic disconnections were reasonable and should be applicable for long term route development. 

Scheme 6.11 Preparation of oxadiazole carbonyl chloride fragment 2.

Numerous other five-membered heterocycles have been found to produce herbicidal effects (74ZN(C)232), such as pyrazolones, thiadiazolones, polyhaloimidazoles and 1,3,4-oxadiazol-2-ones, an important example of which is oxadiazon (14) (68BRP1110500). This is synthesized by cyclization of the 2-(pivaloyl)phenylhydrazine (15) with carbonyl chloride (Scheme 5). 

The energetic 1,3,4-oxadiazole (22) is synthesized from the reaction of the tetrazole (20) with oxalyl chloride. In this reaction the tetrazole (20) undergoes a reverse cycloaddition with the expulsion of nitrogen and the formation of the 1,3-dipolar diazoalkane (21) which reacts with the carbonyl groups of oxalyl chloride to form the 1,3,4-oxadiazole rings. 

Most reactions of oxadiazolinones (62) involve nucleophilic attack at the carbonyl group. This is typically followed by opening of the ring, often with subsequent rccyclization to a different heterocycle. Simple nucleophilic displacement occurred on conversion of oxadiazolinone (62a R = R) into chloro-oxadiazole (63) on treatment with a mixture of phosphorus oxychloride and phosphorus pentachloride <84JIC436) or with thionyl chloride <90AP(323)595>. 

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