Benzyl chloride aralkylation with

The method described is successfully used for the alkylation and aralkylation of ethyl and /-butyl phenylacetate.3 The alkylation of ethyl phenylacetate with methyl iodide, M-butyl bromide, benzyl chloride, and a-phenylethyl chloride affords the corresponding pure monoalkylation products in 69%, 91%, 85%, and 70% (erythro isomer) yields, respectively. The alkylation of /-butyl phenylacetate with methyl iodide, M-butyl bromide, a-phenylethyl chloride, and /3-phenylethyl bromide gives the corresponding pure monoalkylated products in 83%, 86%, 72-73%, and 76% yields, respectively. 

Certain of the monoalkylated ethyl phenylacetates have been further alkylated with alkyl and aralkyl halides to produce the corresponding disuhstituted phenylacetic esters.4 Ethyl 2-phenyl-propanoate has been alkylated by methyl iodide to give pure ethyl 2-methyl-2-pheny]propanoate in 81% yield. Similarly, the alkylations of ethyl 2-phenylhexanoate with methyl iodide, M-butyl bromide, and benzyl chloride gave the corresponding pure dialkylated products in 73%, 92%, and 72% yields, respectively. 

Benzimidazoles, too, are readily alkylated either in neutral or basic medium. As with the uncondensed compounds, the former conditions are complicated by salt formation, but to a lesser extent since benzimidazoles are less basic. It is often valuable to vary the initial amounts of alkali and alkyl halide in order to improve yields. The best yields of 1-alkylbenzimidazole (76-83% for primary and 50-60% for secondary alkyl and aralkyl bromides) result with two moles of bromide and 1.5 moles of alkali per mole of benzimidazole (66RCRI22). There is severe steric hindrance to the alkylation of 2-arylben-zimidazoles in alkaline medium, but reactions with the silver salts seem more successful. The rapid and almost quantitative reaction between a benzimidazole and dimethylphenyl-alkylammonium chlorides in aqueous sodium hydroxide provides a very convenient method of introducing a primary aralkyl group (benzyl, a-naphthylmethyl). There has been little systematic study of the dkylation of unsymmetrical benzimidazoles, though much the same criteria should apply as in the uncondensed compounds. In this respect the observation that 1-bromopropane reacts with the anion of 2,6-dimethyl-4-nitrobenzimidazole to give... 

The parent, 8-azapurine, has been made only by nitrosation of 4,5-di-aminopyrimidine, which is an item of commerce. - - The 7- and 8-alkyl derivatives of 8-azapurine, whether with or without further substituents, require 1,2,3-triazole starting materials (Section IV,B), of which the best source is Hoover and Day s historic condensation of benzyl azide with ethyl cyanoacetate or (better) cyanoacetamide. An 8-aralkyl group has been introduced similarly. In favorable cases, an 8-aryl group can be derived from the action of a benzenediazonium chloride on a pyrimidine that bears enough electron-releasing substituents to activate the 5 position (the Benson synthesis Section IV,A). 

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