Alkyl halides crown-ether catalysis

The use of phase-transfer catalysis in the alkylation of imidazoles and benzimidazoles has already proved its value in ether, 18-crown-6 catalysis gives 64-86% yields of JV-methyl products with basic aqueous solutions of the heterocycles and alkyl halides (79TL4709, 76BSF1861, 80JOC3172). 

Although the hydrolysis of alkyl halides to alcohols has been extensively investigated, an alternative two-step sequence involving substitution with carboxylate ion is more practical for the preparation of alcohols. Activation of the carboxylate anion prepared by the reaction of the acid with a base can be achieved (i) by use of a polar aprotic solvent and (ii) by use of aprotic apolar solvents under phase transfer catalysis, polymer conditions, or with crown ethers. 

Similar studies by Regen [ 148] confirmed that PEG catalysis was superior to that by crown ethers and tetraalkylammonium salts. Alkylation rates decreased with increasing PEG molecular weight and increasing alkyl halide chain length and branching. 

The phase transfer method facilitates the dissolution of carboxylates in nonpolar media. In these solutions, due to relatively poor solvation of anions, carboxylate is an effective nucleophile and reacts readily with alkyl halides. The catalysis of such reactions by amines, ammonium salts and crown ethers and the synthesis of esters by the phase transfer technique is the subject of this chapter. 

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