Benzimidazole 1- substituted, hydroxylation

Hydroxyl-substituted naphthimidazoles, benzothiazoles, benzimidazoles, benzotriazoles, benzoselenazoles and benzoxathiolones may be regarded as substituted phenolic couplers. Compound (121) is a specific example of the latter type which yields intense brown images (51USP2547843). In the absence of hydroxyl groups, alkyl-substituted derivatives of imidazoles or thiazoles may be couplers in their own right by virtue of their active alkyl substituent. 

The presence of a pharmacophore at 5(6)-position of 2-substituted benzimidazole is an important factor for determining the biological profile of the compounds of this class. The substituents at this position not only prevent the molecule to undergo facile 5-hydroxylation to form weakly active or inactive metabolites, but also helps in segregating the therapeutic response against enteric and tissue-dwelling helminths. The major structural changes carried out at this site are discussed below. 

Keywords Alkyl hydroperoxides Amination Ammonia Benzimidazole Benzisoxazole Carbanions Heterocycles Hydroxylation Indole Nitro compounds Nucleophiles Nucleophilic substitution Oxidation Phenazine Potassium permanganate Pyridine Quinoline Sulfones Vicarious... 

Reactions.— The nucleophilic reactivity of the thiocarbonyl sulphur atom in thioureas has been further exemplified in a series of papers reporting on S-alkylation reactions of open-chain " as well as cyclic thioureas using alkyl halides. Ried and his co-workers have reported that (4-quinazolyl)thioureas (315) react smoothly with methylene iodide in the presence of triethylamine to yield the 1,3-thiazetidines (316). The ready formation of (316) was attributed to the special effect of the intramolecular hydrogen bonding in (315), as common thioureas usually did not enter into this reaction in a well-defined and profitable way. 5,5-Diphenyl-2-thio-hydantoin reacted with symmetrical ao>-dibromo-alkanes to yield the cyclization products (317). The action of excess of methyl iodide on N -substituted N-(o-aminophenyl)thioureas afforded the benzimidazoles (318), alternatively obtainable by treatment of the same thioureas with mercuric chloride." " In a similar manner, l-amino-6,7-dimethoxy-3,4-di-hydroisoquinolines were formed by the action of mercuric chloride on the thioureas (319)" or their S-methyl derivatives (320). " A recent paper by Klayman and his co-workers deals with the reactivity of S-methiodide derivatives of thioureas that are activated by electron-withdrawing groups towards hydroxylic compounds. "... 

---