Imidazole 4.5- dichloro-2-substituted

In both imidazoles and their /V-substituted derivatives, halogenation occurs preferentially in the 4(5)-positions there is a slight preference for 5-substitution in 1-substituted substrates. Although the 2-position is much less reactive, it is difficult to prevent substitution at that site. Indeed, polyhalogenation is so facile that it is seldom feasible to make monohalogenated imidazoles directly. Both sodium hypochlorite and NCS convert imidazole into its 4,5-dichloro derivative contaminated by the 2,4,5-trichloro product. Even very mild conditions are unlikely to promote monochlorination, and bromination and iodination arc similar. Mechanisms can vary, however, from substrate to substrate. It is likely that C-2 halogenations are the result of addition-elimination [1]. 

Dichloro-2/f-l,4-oxazin-2-one 1513 reacts with a-amino ketones e.g. 1514 to yield bicyclic imidazo-fused intermediates 1516 via an intramolecular cyclization reaction. Reaction of lactones such as 1516 with various nucleophiles generates substituted l//-imidazoles such as 1517 (Scheme 392) <1999T3987>. 

Common sources of phenyl radicals are A-nitrosoacetanilide, diazoaminobenzene, or benzoyl peroxide which induce 2-phenylation of imidazoles and benzimidazoles. The 2-position is frequently the most susceptible to nucleophilic attack (CHEC-I). Most photochemically induced arylations also probably involve radical substitution, for example, photolysis of l,3-dialkyl-4,5-dichloro-2-imidazolone (95) in benzene (Scheme 47) <81AG(E)6I2>. Under photolytic conditions pentafluoro-... 

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