2- Bromoimidazoles

Amino-2-bromoimidazoles (77) have been prepared by the action of hydrogen bromide on a-cyanoalkylcyanamides (74) and were found to display preemergent herbicide activity (64JOC153). These 4-aminoimidazoles (77) are unstable in the presence of water and undergo rapid decomposition on treatment with base. 

Reaction of 4,5-disubstituted imidazole 1-oxides 263 with POCl3 or POBr3 produces 2-chloro or 2-bromoimidazole 301 (Hal = Cl or Br) (1975JCS(P1)275, 2002AG(E)2290). A possible mechanism in line with that in play by acylation comprises O-phosphorylation to be followed by addition of halogenide ion and subsequent elimination of halophosphoric acid as outlined in Scheme 89. 

Similar imidazolium ylides are implicated in the aroylation of T-phenylbenzimidoyl chlorides and in reactions of 1-substituted imidazoles with cyanogen bromide to form 2-cyano- or 2-bromoimidazoles. 

Among the possible approaches to the preparation of 4-aminoimidazoles is the cyclization of a-cyanoalkyl cyanamidcs (34). When treated with anhydrous hydrobromic acid they give 4(5)-amino-2-bromoimidazoles (35) in a process which bears formal similarities to amidine cyclizations (Scheme 2.2.12). The instabilities of many 4(5)-aminoimidazolcs necessitates their conversion into the more easily handled acetyl derivatives using acetic anhydride [46] (see also Section 3.1.1). Table 2.2.4 lists some examples. 

The alternative 5-amino-1-substituted imidazoles are usually made by reactions between primary amines and alkyl 7/-cyanoalkylimidates (see Section 3.2). Other possibilities include ring closure of formylglycineamidines by heating them alone or with phosphoryl chloride (yields are usually low) (see Section 2.1.1), cyclization of or-cyanoalkylcyanamides (to form 5-amino-2-bromoimidazoles) (see Section 2.2), alkylation of arylamino-methylene cyanamides or cyanoimidothiocarbanates with or-halogenocarbonyl compounds (gives 4-acyl-5-aminoimidazoles) (see Section 2.3), and cycliza-tions of DAMN with amidrazones (to 1,5-diaminoimidazoles) (see Section 2.2.1). 

N-l-Substituted iodoimidazoles behave normally with arylboronic acids to give cross-coupled products <2005T6056>. N-l-Substituted-2-bromoimidazoles also coupled efficiently with aryl boronic acids and alkenyl boronic acids to give cross-coupled products in high yields (Scheme 95) <2004JOC8829>. 

Direct displacement reactions of 2-bromoimidazoles with nucleophiles are very difficult. For example, 1-methyl-2,4,5-tribromoimidazole fails to react with NaOMe <2003S659>. However, intramolecular ipso substitution reactions such as during the synthesis of 2,3-dihydroimidazo[2,l-/ ][l,3]oxazoles 952 (Scheme 230) via 951 work well <200282691>. 

Alkylation of (585b) with a phenacyl bromide produced (589), which can be cyclized with hydrazine to (590) (77JHC59). Similar cyclizations have been carried out on a 1-phenacyl-2-bromoimidazole derivative (74UKZ99), a l-phenacyl-2-methanesulfonyl-imidazole derivative (74CHE1492) and l-(2-chloroethyl)-2-bromo-4,5-diphenylimidazole (75CHE371) to afford imidazo[2,l-c][l,2,4]triazines. 

Interest in cyanogen bromide as a brominating agent for imidazoles has been rekindled. It seems that bromo products can be made in this way, for example, 1-benzylimidazole reacts with cyanogen bromide in the presence of 4-dimethylaminopyridine to give l-benzyl-2-bromoimidazole, perhaps via an ylide mechanism. Cyanogen chloride and the pre-formed adduct of cyanogen bromide and... 

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