Synthesis of quaternary ammonium salts based on quinuclidin-3-ol and pyridine-4-aldoxime with alkyl chains

Doris Crnčević,Renata Odžak

doi:10.48188/so.1.8

Abstract

Aim: In search of a new class of potential antimicrobial agents, novel ammonium salts based on quinuclidine-3-ol and pyridine-4-aldoxime with different lengths of alkyl chains were synthesized and analyzed. In addition to their potential biological application, newly synthesized salts containing terminal bromine could possibly be used for the synthesis of more potent bisquaternary salts. Methods: The commercially available quinuclidine-3-ol and pyridine-4-aldoxime were used for the synthesis of new derivatives with the appropriate alkyl chains. The purity of the synthesized salts was tested by thin-layer chromatography on an aluminum plate where aluminum oxide was used as a stationary phase. Melting points were determined in open capillaries using an instrument for melting point determination and the obtained values were left uncorrected. The FTIR spectra were recorded with a spectrometer and the data were analyzed in cm-1. Results: All the synthesized compounds, which contained heterocyclic moiety and alkyl chains (with or without a terminal bromine atom), were obtained in very good yields under the simple quaternization conditions. The better product yields were observed in reactions with quinuclidine3-ol (46-95%) compared to those with pyridine-4-aldoxime (49-59%). The obtained products were analyzed and confirmed by the thin-layer chromatography, the melting point measurement and the FTIR spectra. Conclusion: The observed difference in product yields could be explained by the different basicity of the nitrogen atom of quinuclidin-3-ol than that of pyridine-4-aldoxime. All prepared salts have a positively charged nitrogen atom as a part of their polar “head” and a long hydrocarbon chain as the non-polar “tail”. Such a structure allows electrostatic interaction with the negatively charged bacterial membrane and causes it to be disrupted. The structure of the prepared salts containing long alkyl chains could be crucial for their antimicrobial activity.

Highlights

Quaternary ammonium salts have a wide range of applications across a variety of industries; due to their pronounced antimicrobial activity, they can be used as ingredients in surfactants, such as cationic surfactants, or incorporated into drugs, such as antibiotics [1]
The aim of this paper is to present a synthesis of new quaternary ammonium salts, which had not been described in the literature
Thin-layer chromatography determined a Rf value corresponding to the formation of a quaternary ammonium salt which, due to the high polarity, did not deviate from the starting value, unlike the reactants

Summary

Introduction

Quaternary ammonium salts have a wide range of applications across a variety of industries; due to their pronounced antimicrobial activity, they can be used as ingredients in surfactants, such as cationic surfactants, or incorporated into drugs, such as antibiotics [1]. The structure of these heterocyclic compounds features a nitrogen atom, most commonly as part of a cyclic structure, and may occasionally contain other heteroatoms. We used quaternization reactions of quinuclidin-3-ol and pyridine-4-aldoxime with alkyl chains containing three to eight carbon atoms and one or two terminal bromine atoms

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