Polymer-Supported Carboxylate as a New Polymeric Reagent for Synthesis of Alkyl Esters

Abstract

Polymer supported reagents especially anion exchange resins have been widely applied in organic synthesis. These polymeric reagents are generally used in single step reactions. Their main advantage over monomeric reagents is their insolubility in the reaction medium and consequently the easier workup by a simple filtration. The reactions can often be driven to completion by using excess of these reagents without the fear of separating the unspent reagent from the desired products. The spent polymeric reagents can usually be removed quantitatively and regenerated. In addition, anions bound to the macroporous resin have the advantage that they often react successfully in non-polar solvents. The ester group is an important functional group that can be synthesized in a number of different ways such as acylation of alcohols, oxidation of aldehydes, addition of carboxylic acids to alkenes, reaction of carboxylic acids with diazomethane, Bayer-Villiger oxidation of ketones, reaction of organoboranes with α-halo esters, rearrangement of α-haloketones (Favorskii reaction) and especially for large scale operation by reaction of carboxylate salts or Amberlite IRA-904 supported carboxylate ion with alkyl halides or tosylates. Sodium carboxylate, however, has been the reagent most widely used. Unfortunately, each of these methods suffer from at least one of the following disadvantages: (1) the yields of the reactions are low, (2) the reaction has to be carried out in the presence of phase transfer catalyst, (3) the reaction mixture has to be acidified or the reaction has to be catalyzed by a base such as pyridine, and (4) tedious work-up procedure. Polymer-supported carboxylate ion overcomes most of the above mentioned disadvantages. In this study we wish to report an important, efficient, and easy method for preparation of alkyl acetate or alkyl formate esters from crosslinked poly(4-vinylpyridinium) acetate (I) or crosslinked poly(4-vinylpyridinium) formate (II) with alkyl halides (Scheme 1). While there are numerous applications of solid-supported reagents and scavengers only a few examples for the formation of esters were described. Solid-supported acids were used as catalysts in the esterification of carboxylic acids with alcohols. Carboxylates, generated with solidsupported organic bases, were alkylated with alkyl halides. Solid-supported organic bases were also used as scavenger resins in the esterification of benzyl alcohol with benzyl chlorides, giving clean benzyl esters in high yields. A modification of the Mitsunobu reaction with resin-bound triphenylphosphine and soluble di-t-butylazodicarboxylate was described, that allowed for the isolation of pure products without chromatography. A very recent report described the alkylation of carboxylic acids with carbenium ions, generated from polymer-supported triazines, for the ester formation. We report here a convenient and general procedure for the synthesis of esters from alkyl halides and polymer-supported carboxylate ion that readily prepared from employing the commercially available poly(4-vinylpyridine) (2% crosslinked with DVB) resin as the solid-supported condensation reagent. Crosslinked poly(N-methyl-4-vinylpyridinium) acetate (I) and crosslinked poly(N-methyl-4-vinylpyridinium) formate (II) were prepared by an exchange reaction between crosslinked poly(N-methyl-4-vinylpyridinium) iodide with a slight excess of sodium acetate or sodium formate solution in water. Using these heterogeneous reagents converted benzyl halides to benzyl acetate or benzyl formate esters in acetone under reflux condition. The advantages of this method are: 1) the reaction can be performed in non-aqueous medium; 2) an excess of the reagent can be used; 3) the product can be obtained by simple filtration and evaporation of the solvent; and 4) the polymeric reagent is easily regenerable with a sodium acetate or sodium formate solution. Crosslinked polymers (I) and (II) can be easily prepared and used as mild and efficient polymeric reagents for conversion of benzyl halides to the corresponding benzyl acetate and benzyl formates. It was proved that acetone is the best solvent for these reactions. In these conversions, the best molar ratio of reagent/substrate proved was 1.5, but