Synthesis of 1-phenyl-3-pyrroline in water

Abstract

Pyrrolines are bioactive compounds and can be used as starting materials or as intermediates in the synthesis of natural products [1,2]. N-phenyl-pyrrolines have been prepared by reaction of N-propargylanilines catalyzed by Cu(I) [3] or the ring-closing metathesis of allylamines [4]. We present a simple, efficient and low cost new methodology to prepare 1-phenyl-3-pyrolines through nucleophilic displacement reaction SN2. Three parameters were studied, namely, solvent (acetonitrile, dioxane, DMSO, THF and water), bases (DBU, CsCO3, K2CO3, NaHCO3) and reaction time. The reaction conditions were tested with 1,4-dibromobutene and aniline. The best results were obtained with two experimental conditions: (i) in organic medium (acetonitrile) and sodium borohydride (with or without base) and (ii) in water (scheme 1) the reaction presented a conversion of 96% (GC), without the need for purification because the product precipitates. In both conditions only trace amounts of N-phenylpyrrole were observed. The aqueous condition is more interesting due to the use of green solvent, good yield and easy purification. To ascertain the scope of this new methodology we are testing it with other aromatic amines and aliphatic amines in order to obtain pyrroline derivates.