Synthesis and Kinetics of the Cyclization of 3-(Dialkylaminophenyl)-2-(phenylcarbonyl)-prop-2-enenitriles

Abstract

The considerable interest in tetrahydroquinolines and their derivatives is primarily due to the biological activity of tetrahydroquinolines themselves [1,2], as well as their remarkable reactivity and the variety of chemical transformations, which make these compounds convenient building blocks in the synthesis of other structures with high biological activity [3]. One method for the synthesis of tetrahydroquinoline systems is the cyclization of N,N-dialkyl-o-vinylanilines proceeding through a tert-amino effect mechanism [4][5][6][7].We studied the reaction of 2-dialkylaminobenzaldehydes 1a-i with benzoylacetonitrile (2), leading to N,N-dialkyl-o-vinylanilines 3a-i, which, in turn, cyclized to the condensed 1,2,3,4-tetrahydroquinolino-5-carbonitriles 4a-i. Examination of the literature showed that an analogous reaction has been carried out only using o-piperidinobenzaldehyde as the starting reagent [8].Knoevenagel condensation products 3a-e,h,i could not be isolated in the condensation of 2-piperidinobenzaldehydes 1a-e,h,i, since the cyclization to give 1,2,3,4-tetrahydroquinolino-5-carbonitriles 4a-e,h,i dominated under these reaction conditions [9]. Knoevenagel condensation products 3f,g, that did not undergo cyclization in toluene, were isolated only in the case of benzaldehydes 1f,g. This finding may be attributed to the lower basicity of the morpholine and piperazine dialkylamino groups. 1,2,3,4-Tetrahydroquinolino-5-carbonitriles 4f,g were obtained by the cyclization of N,N-dialkyl-o-vinylanilines 3f,g upon heating in 1-butanol at reflux. 1,2,3,4-Tetrahydroquinolino-5-carbonitriles 4a-i contain from two to four asymmetric sites.