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Palladium catalysts in the synthesis of local anesthetics (review)

“…The possibility of combining hydrogenation of I and trans-esterification of VII generated in situ was studied [15]. We demonstrated several times the ability in principle to perform simuntaneous hydrogenation of the nitro group and trans-esterification of the ester over Pd-containing polymers [7,16,17].…”

“…Conditions: EtOH 10 -50 mL, 45°C, H 2 pressure 1 atm, 0.1 -0.5 g catalyst (Pd content 4 mass %, particle size 0.075 -0.102 mm), concentration of I 0.1 -0.7 M, reaction time 4 -6 h. Our experience with the synthesis of drugs containing an amine, hydrogenation [5,15], hydroamination [22], and reductive acylation [29] over Pd catalysts led to the production of the target products in high yields. The selectivity and activity of the process was determined by various process factors, mainly the nature of the reagents, catalyst, solvent, temperature, pH, etc.…”

“…The catalysts were Pd-containing anion-exchangers AV-17-8 and AN-1. They were demonstrated to be highly effective in such processes [5,15,22,29].…”

“…This clearly indicates that the target products are being destroyed. It should be noted that the heterogeneous analog Pd/C has a characteristic tendency toward hydrogenolysis and rapid deactivation due to leaching of Pd from the catalyst surface or poisoning by polymerization products [5,15,22,29].…”

Preparation of lidocaine, bipuvacaine, mepivacaine, trimecaine, and pyromecaine by reductive acylation on palladium catalysts

“…Our accumulated experience in the synthesis of medicinal substances containing amino groups by hydrogenation [1,2], hydroamination [3], and reductive acetylation [4] on palladium catalysts allows us to obtain target products at high yield. We have investigated the potential of the catalytic synthesis of an important group of pharmaceutical agentslocal anesthetics [5]: lidocaine (a-diethylamino-2,6-dimethylacetanilide, I), bipuvacaine (1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide, II), mepivacaine (1-methyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide, III), trimecaine (a-diethylamino-2,4,6-trimethylacetanilide, IV), and pyromecaine (1-butyl-2,4,6-trimethyl-2-pyrrolidinecarboxamide, V).…”