Synthesis of Novocainamide by Hydrogenation of 4-Nitro-N-[2-(Diethylamino)Ethyl]Benzamide on Pd-Containing Anion Exchangers

Abstract

The synthesis of novocainamide by hydrogenation of 4-nitro-N-[2-(diethylamino)ethyl]benzamide on Pd-containing anion exchangers was studied. An improved method for synthesizing novocainamide under mild conditions that was more efficient than the industrial method was proposed based on the experimental results. Novocainamide{4-amino-N-[2-(diethylamino)ethyl]-benzamide} (I) differs chemically from novocaine by the presence of an amide instead of an ester. Their pharmacological properties are also similar. However, I is more preferred as an antiarrhythmic because the amide is more difficultly hydrolyzed by blood plasma esterases and, as a result, has a longer duration of action. The key step in the synthesis of I is reduction of 4-nitro-N-[2-(diethylamino)ethyl]benzamide (II) [1]. The overall process efficiency depends largely on the nature of the reductant. Thus, a large amount of side products and intermediates results from incomplete reduction of the nitro group in II. Catalytic hydrogenation of II on heterogeneous catalysts is accompanied by hydrogenolysis of the amide to form its cleavage products. These drawbacks are the main reason for the reduced yield of I and the increased materials consumption during its manufacturing.We studied the hydrogenation of II in the presence of Pd-containing polymers in order to reduce the number of intermediate steps and increase the yield of I (Scheme 1). Scheme 1. Synthesis of I by hydrogenation of II on Pd-containing anion exchangers.Previous research showed [2 -4] that the amount and formation rate of products of incomplete reduction of the nitro group in the aromatic ring depended on the reaction conditions, the nature of the reductant, and the solvent.The catalysts were anion exchangers AV-17-8-Pd, AN-1-Pd, and AN-108-e-Pd that contained Pd-nanoparticle active centers that were strongly bound in the three-dimensional polymer matrices [5,6]. Preliminary studies showed that hydrogenation of II under the selected conditions was kinetically controlled and was first-order in catalyst and H 2 .

Nanostructured particles of palladium in the synthesis of biologically active nitrogencontaining compounds

“…Однако более эффек-тивному изучению и применению биологически активных аминов препятствует отсут-ствие простых, но эффективных методових синтеза. Поэтому является актуальным по-иск новых, более эффективных каталитических способов получения аминов разнооб-разного строения [1-8], в т. ч. местных анестетиков [9-14] и других биологически ак-тивных азотсодержащих органических соединений [15][16][17][18][19][20].…”