Reactions of Active Methylene Compounds with Benzhydrol During Solvolysis in Formic Acid

Abstract

Formic acid reacts with benzhydrol to give benzhydryl formate, which reacts with active methylene compounds in refluxing formic acid to give either C-alkylation or Ritter reaction products. The product formed is determined by the equilibrium enol content of the active methylene compound. These reaction conditions avoid the use of halogenated reaction solvents, and the pure products are isolated without recourse to chromatography.

A Rational Approach towards the Nucleophilic Substitutions of Alcohols “on Water”

“…[3] Although coupling reactions between benzylic halides and nucleophiles are possible in water, [4] in general, alcohols are not reactive substrates under these conditions. [5] In fact, the reaction between benzhydrol and the strong p nucleophile 1-methylindole is not promoted in water, and common Brønsted acids (AcOH, trifluoroacetic acid, trifluoromethanesulfonic acid) are also ineffective catalysts for this reaction in water. [6] Nevertheless, a number of methods for the promotion of direct catalytic nucleophilic substitution of alcohols in organic solvents have been reported.…”

Synthesis ofN-Benzhydrylamides from Nitriles by Ritter Reactions in Formic Acid

“…During attempted alkylations of benzhydrol with ethyl cyanoacetate and malononitrile in refluxing formic acid, conditions under which ethyl acetoacetate gives the product of C-alkylation, 3 we observed that the product was not the expected C-alkylation product, but the N-benzhydrylamide of the carboxylic acid (12). This product clearly arises from the Ritter reaction of the nitrile with the benzhydryl cation, with the product initially formed from ethyl cyanoacetate undergoing subsequent ester hydrolysis and decarboxylation.…”

“…The reactions between benzhydrol and ethyl cyanoacetate or malononitrile were carried out as reported elsewhere. 3…”

Direct Substitution of Alcohols in Pure Water by Brønsted Acid Catalysis

“…Moreover, the catalytic activation of alcohols is a difficult task since the hydroxy group is a poor leaving group and usually an excess of Brønsted acid or a stoichiometric amount of Lewis acid is required to achieve this goal [ 14 , 15 , 16 ]. The development of catalytic methods using Brønsted or Lewis acids is therefore highly desirable.…”