A Synthesis of Alibendol, 2-Hydroxy-N-(2-hydroxyethyl)-3-methoxy-5-(2-propenyl)benzamide via m-CPBA Oxidation of o-Vanillin

Abstract

A large number of methods for the conversion of aldehydes to esters have been reported in the literature over the last thirty years. 2 Baeyer-Villiger oxidation of ketones and aldehydes using peracid is frequently chosen due to its easy manipulation and high productivity. 3 However, the reaction of acyclic acetal derived from a ketone (a ketal) with peracid is known to be sluggish and to provide the orthocarbonate as the result of dual Baeyer-Villiger oxidation. 4 Several methods of direct oxidation of acetal to esters with oxidizing agents such as, peracetic acid, 5 chromium trioxide, 6 ozone, 7 tert-butylhydroperoxide, 8 PDC/ t-BuOOH, 9 NBS, 10 peroxymonosulfuric acid, 11 dimethyldioxirane, 12 or hydrogen peroxide 13 have been reported. Recently, we reported a facile procedure for the conversion of aldehydes to the corresponding esters via acetal formation from aldehydes and subsequent oxidation by m-CPBA with BF3·OEt2. 14 Based on our recent reports, we wish to utilize this methodology for the synthesis of biologically important compounds. Alibendol, 2-hydroxy-N-(2-hydroxyethyl)-3-methoxy-5(2-propenyl)benzamide is known as antispasmodic, chleretic, and cholekinetic active pharmaceutical ingredient (API) which is useful in treatment of dyspepsia due to biliary insufficiency, alimentary intolerance, urticaria, pruritus, migraine, and constipation of hepatic origin. 15