An efficient synthesis of N-alkyl-N-arylputrescines and cadaverines

Abstract

N-Alkylation is conceptually the most straightforward disconnection towards secondary and tertiary amines. Although this transformation seems rather simple, the factthat the newly formed amines are also nucleophilic brings about the formation of bisand/or polyalkylation by-products. Thus, the crude reaction mixture often contains the desired product together with the starting amine and variable amounts of collateral products, all of them with similar Rf values, a fact that complicates the chromatographic purification of the desired compounds. In this context, new methodologies combining operational simplicity, high yields, readily available starting materials and low cost reagents are desirable for the high throughput preparation of the target compounds. Thiswork describes a practical method for the synthesis of tertiary N-alkyl-N-aryltetra- and pentamethylenediamines 3, by selective monoalkylation of N-alkylanilines with ω−haloalkylnitriles followed by reduction. The optimized reaction conditions resulted in an efficient procedure, of remarkable selectivity in the alkylation step and high overall yields of the diamines.