Simultaneous C- and N-Alkylation of 2-Oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carbonitrile Under Solid–Liquid Phase-Transfer Conditions

Abstract

The alkylation of 2-oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carbonitrile 1 has been carried out using different alkyl/arylating agents in solid–liquid phase-transfer catalysis conditions. The aim was to study the effect of steric hindrance offered by the aryl group in the sixth position of the pyridine ring on the ambient N- vs. O-alkylation ratio. Simultaneous C- and N-alkylation was encountered and confirmed by x-ray crystallography. Our study to gain exclusive regiocontrol for simultaneous alkylation was carried out. An alternative route for C‒C bond formation was also established by the removal of the cyano functionality.

Keywords:

• N- vs. O-alkylation
• simultaneous C- and N-alkylation
• solid–liquid phase-transfer conditions

ACKNOWLEDGMENTS

We thank the Regional Sophisticated Instrumentation Center, Central Drug Research Institute, Lucknow and Chandigarh, India, for ¹H NMR and mass spectral analysis and Dishman Pharmaceuticals and Chemicals Ltd. for their support.

Notes

^a Alkyl/arylating agents, methyl iodide, ethyl bromide, benzyl chloride.

^b Isolated yields.

^a TEBA, triethylbenzylammonium chloride; TBAB, tetrabutylammonium bromide; Aliquat 336, tricaprylmethylammonium chloride.

Dedicated to the memory of Dr. Chaitanya G. Dave.