Acid catalyzed three-component one-pot synthesis of substituted six membered heterocyclic compounds of biological interest

Abstract

p-Toluenesulphonic acid is a highly effective and efficient catalyst for the one-pot multicomponent coupling of phenylaminoethylacrylate derivatives, substituted amines and substituted aldehydes in ethanol at ambient temperature to give highly functionalized piperidines in high yields. This one-pot reaction has some important advantages such as the easy workup procedure, simple and relatively available precursors and inexpensive catalyst and high yields. The multicomponent one-pot products showed moderate to good antibacterial and antifungal activity against Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Citrobacter freundii, Aspergillus niger and Tricoderma harzianum.

Scheme 1: Synthesis of substituted six membered heterocyclic compounds

Fig. 1: Synthesis of piperidine derivative Table-1: Synthesis of Piperidine derivatives SI. No Starting Material Product M.P.(°C) % Yield 1

178-182 92 2

185-187 91 3

161-163 93 4

210-212 88 5

190-192 92 6

175-177 90 Antibacterial and Antifungal Tests Piperidine derivatives showed moderate to good antibacterial and antifungal activity against Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Citrobacter freundii, Aspergillus niger and Tricoderma harzianum. All the compounds were tested at 300 µg/disc concentration.

Table 2: List of antimicrobial tested compounds’ names Sample Code on Petri Plates Compound no Sample / compounds’ names 15 13 N-(4-bromophenyl)-2,6-diphenyl-3-ethylacetato-4(4-bromophenylamino)-piperidine-3-ene 16 15 N-phenyl-2,6-di(4-chlorophenyl)-3-ethylacetato-4-phenylamino-piperidine-3-ene 17 10 N-phenyl-2,6-diphenyl-3-ethylacetato-4-phenylamino-piperidine-3-ene