In 1993,Stoilov, Ivan; Watt, David S.; Goodman, Jack P.; St. Pyrek, Jan published 《Synthesis of detomidine and medetomidine metabolites: 1,2,3-trisubstituted arenes with 4′(5′)-imidazolylmethyl groups》.Journal of Heterocyclic Chemistry published the findings.Electric Literature of C8H7BrO2 The information in the text is summarized as follows:
Two synthetic strategies permitted the synthesis of various metabolites of detomidine (I, R = H, X = Me) and medetomidine I (R = X = Me), potent α-2 adrenoceptor agonists that undergo rapid oxidative metabolism at the aromatic Me group distal to the imidazole ring. In the detomidine series, the addition of a Grignard reagent prepared from 2-[(3′,4′-dimethoxyphenyl)methoxy]methyl-6-bromotoluene to imidazole-4(5)-carboxyaldehyde provided 2-(((3′,4′-dimethoxyphenyl)methoxy)methyl)-6-(1′-hydroxy-1′-(5”-imidazolyl)methyl)toluene. In a subsequent reduction, it was possible to differentiate between the secondary benzylic hydroxyl group and the primary benzylic hydroxyl group protected as a 3,4-dimethoxybenzyl ether. Removal of the protecting group provided 3-(hydroxymethyl)detomidine (3-HD) I (R = H, X = CH2OH) and an oxidation furnished 3-carboxydetomidine (3-CD) I (R = H, X = CO2H). However, in the medetomidine series, a similar hydrogenolysis of 2-(((3′,4′-dimethoxyphenyl)methoxy)methyl)-6-(1′-hydroxy-1′-(5”-imidazolyl)methyl)toluene failed, and an alternate, longer route involving dehydration and reduction was necessary to secure 3-(hydroxymethyl)medetomidine (3-HM) I (R = Me, X = CH2OH) and following an oxidation, 3-carboxymedetomidine (3-CM) I (R = Me, X = CO2H). Finally, an expeditious route to 3-CM involved the addition of the Grignard reagent prepared from 2-(3-bromo-2-methylphenyl)-4,4-dimethyl-2-oxazoline to 4-acetyl-1H-imidazole and the hydrogenolysis and hydrolysis of 2-(1-(4,4-dimethyl-2-oxazolyl))-6-(1′-oxo-1′-(5′-imidazolyl)methyl)toluene. The experimental process involved the reaction of 3-Bromo-2-methylbenzoic acid(cas: 76006-33-2Electric Literature of C8H7BrO2)
3-Bromo-2-methylbenzoic acid(cas: 76006-33-2) belongs to organobromine compounds.The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Electric Literature of C8H7BrO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary