.beta.-Aminocinnamonitriles as potential antiinflammatory agents

Abstract

A number of beta-aminocinnamonitriles have been prepared by the reaction of salts of acetonitrile and propionitrile with benzonitrile. These materials were evaluated in the carrageenan antiinflammatory screen in Royal Hart, Wistar strain rats. Despite good weight gains in the parent molecule, beta-aminocinnamonitrile (1), only marginal activity was found in related compounds and some possible "metabolites."

Temperature controlled condensation of nitriles: efficient and convenient synthesis of β-enaminonitriles, 4-aminopyrimidines and 4-amidinopyrimidines in one system

“…The percent conversion of nitrile was examined in a temperature range of 60-140 C (entry 6,[12][13][14], and the temperature of 120 C was determined as standard condition according to the transformation efficiency of compound 2a. Lower temperature would decrease the yield dramatically down to 3% at 60 C (entry 12), and higher temperature might not help to improve the efficiency of production (entry 14).…”

“…In our lab, the reactions run smoothly with four typical type of 4-amidinopyrimidines and the products were obtained in yields over 76%. All the compounds were characterized by 1 H NMR, 13 C NMR, mass spectra and X-ray crystallography (Fig. 2).…”

“…b-Enaminonitriles were commonly synthesized by condensation of two functional amide/nitrile molecules under high temperature and/or strong base conditions (Scheme 2a and b). 1,12,13 Other methods were also developed to obtain b-enaminonitriles, including the reuxing of methylenecarbonitriles with triethyl orthoformate and amine (Scheme 2c), 14 the metal-catalysed condensation of active nitriles with isocyanides or cyclopropanes (Scheme 2d and e), 15,16 the cyclization of chloromethyl p-tolyl sulfoxide with cyanomethyl lithium and (Scheme 2f), 17 and the Thorpe-Ziegler condensation of aliphatic nitriles (Scheme 2g). 18 However, all these reactions show limited tolerance for the synthesis of various enaminonitriles due to the rigorous reaction conditions and/or limited reaction substrates.…”

“…18 However, all these reactions show limited tolerance for the synthesis of various enaminonitriles due to the rigorous reaction conditions and/or limited reaction substrates. 1,[12][13][14][15][16][17][18] Thus, the utilization of b-enaminonitriles for the synthesis of different substituent 4-aminopyrimidines is rarely described. 4-Aminopyrimidines and their derivatives are an important building blocks found in the molecules of natural products.…”

Cyanophenylation of Aromatic Nitriles by Terephthalonitrile Dianion: Is the Charge‐Transfer Complex a Key Intermediate?

“…We have shown that the cyanomethyl anion, generated from acetonitrile by treatment with sodium amide in liquid ammonia and which, to some extent, models the fragment of dianion 1 2-that bears the main part of the negative charge (compare with the charge distribution in the dianion of 9-cyanoanthracene [26] ), reacts with 2 to give β-aminocinnamonitrile (11). [29,30] This result shows that the carbanion adds to the cyano group of 2 and suggests that the interaction of dianion 1 2-with an aromatic nitrile proceeds through a mechanism that is different from that typical for α-cyano-substituted carbanions (see Scheme 2). On this basis, while considering the mechanism of the interaction of dianion 1 2-with aromatic nitriles within the dichotomy between straight nucleophilic attack, on the one hand, and electron transfer (ET), on the other, the latter seems preferable.…”