Hydrolysis of the 2-cyano or 2-carbethoxy group

The nitrile or ester is heated under reflux with concentrated hydrochloric acid (20-25 ml per gram of substrate) for 4h. The iV-oxide hydrochloride which separates from the cooled solution is recrystallizcd, then decomposed by dissolving it in aqueous ammonia (d. 0.88 40ml per gram of hydrochloride), and tire solution is concentrated at 50°C under reduced pressure until Crystallization commences. After cooling, the A -oxidcs are filtered. 

In view of the observation that A-o-nitrophenyl derivatives of glycine and other a-amino acids could be converted into benzimidazolones by the action of heat, and the assumption that iV-oxides were intermediates in the thermolysis [156], it was thought tliat flash vacuum pyrolysis with a very short reaction time might allow isolation of the IV-oxides. This approach, however, did not turn out to be as synthetically efficient as the base treatment method [97]. Indeed, heating such compounds in sand at 200° C is probably of more use for making benzimidazoles or benzimidazolones [156]. Benzimidazole iV-oxides can be made from acid-catalysed thermal or photochemical reactions of AyV-dialkyl-o-nitroanilincs, but not from purely thermal reactions. 

Photolysis of A-(2,4-dinitrophenyl) derivatives of amino acids gives mixtures of 4-nitro-2-nitrosoanilines and 5-nitrobenzimidazolc A -oxides. In acidic media the A-oxides predominate with typical yields in the range 30-80% [80, 143, 157]. A related reaction which also appears to proceed 

Base-induced conversion of lV,iV-disubstituted-o-nitroanilines (59) into benzimidazole A/-oxides may occur provided that one of the carbon substituents can be removed subsequently (e.g. cyano or arylsulfonyl). The reaction products, however, may well differ from those obtained from the monosubstituted analogues, e.g. cyclization of lV-alkyl(or aryl)-iV-cyanomethyl-onitroanilincs gives not the 2-cyanobenzimidazole M-oxides, but the 2- hydroxy derivatives [148J. These processes do not seem to have great synthetic utility. 

Tricyclic benzimidazole 3-oxides (60) made by heating various (59) in acid  

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