Microwave-assisted Quaternization of Various Pyridine Derivatives and their Antibacterial Activity

Valentina Bušić,Dražen Vikić-Topić,Dajana Gašo-Sokač,Sunčica Roca,Hrvoje Pavlović

doi:10.5562/cca2937

Valentina Bušić, Dražen Vikić-Topić + Show 3 more

Open Access

https://doi.org/10.5562/cca2937

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Abstract

Numerous pyridinium derivatives have been investigated concerning their biological and pharmacological activities. Their importance lies in their effective antimicrobial, antiviral, antihypertensive and immunostimulating activities. Some of pyridinium aldo xime derivatives are potential antidotes against organophosphate poisoning. In this study, reactions of quaternization under microwave heating of pyridine, α - picoline, pyridine-4-aldoxyime, pyridine-2- aldoxime, nicotinamide, isonicotinamide and pyridoxal oxime with different electrophiles: 2-bromo-4'-nitroacetophenone, 2-amino-4-chloromethylthiazole hydrochloride, methyl iodide, 1, 3-diiodopropane and 1, 3-dibromopropane are reported. The synthesis yield by microwave dielectric heating is improved and reaction time shortened compared to conventional heating. Some of the synthesized compounds were tested regarding their potential antibacterial activity against two Gram-positive and two Gram-negative bacteria. Antibacterial assessment showed a relatively high efficacy of 1-[2-(4-nitrophenyl)-2-oxoethyl]pyridinium bromide against G-positive and G-negative bacteria.

Highlights

I N recent decades, a large number of reports on synthesis of heterocycles compounds containing N, O and S have been published due to their wide range of biological activity
Numerous data concerning synthesis of heterocycles under microwave conditions have been published.[1−3] Pyridinium salts belong to the category of cationic surfactants consisting of a hydrophilic part, such as a quaternary nitrogen moiety which is able to interact in polar chemical milieu, and a hydrophobic part which can penetrate into non-polar molecular agglomerates
The results indicate that quaternary pyridinium salts exhibit weak antibacterial activity and, as such, cannot be used to control bacterial

Summary

INTRODUCTION

I N recent decades, a large number of reports on synthesis of heterocycles compounds containing N, O and S have been published due to their wide range of biological activity. Slow cooling of the reaction mixture promoted formation of pure yellowish pearlescent crystals They were washed with ethanol and recrystallized from 40 mL of the solvent mixture of EtOAc : EtOH = 1 : 1. To a solution of isonicotinamide (0.5 g, 4.09 mmol) in 10 mL of acetone, 2.36 mL of 1,3-diiodopropane was added dropwise and the reaction mixture was irradiated for 2 minutes at 250 W. Yield 1.709 g (48.6 %); m.p. 216.6–217 °C, IR (KBr) ṽmax/cm−1: 3371, 3190–3022, 1668, 1126, 602; 1H NMR (600 MHz, DMSO-d6) δ/ppm: 9.26 (d, J = 6.71 Hz, 2H, H-2/6), 8.65 (br s, 1H, NH-1), 8.44 (d, J = 6.71 Hz, 2H, H-3/5), 8.26 (br s, 1H, NH-2), 4.71 (t, J = 7.09 Hz, 2H, H-7/7'), 3.27 (t, J = 7.09 Hz, 2H, H-9/9'), 2.55−2.48 (m, 2H, H-8/8'). Gentamicin sulfate (Sigma-Aldrich ®, Saint Louis, USA) was used as positive control

RESULTS AND DISCUSSION

Hole formation

CONCLUSION