One-pot multicomponent synthesis of highly substituted pyridines using hydrotalcite as a solid base and reusable catalyst

Sandip R Kale,Santosh Kumar Surve

doi:10.5267/j.ccl.2021.1.001

Abstract

One-pot synthesis of highly substituted pyridines has been demonstrated via multicomponent reaction of aldehydes, malononitrile and thiophenol using Mg-Al hydrotalcite as a solid base and reusable catalyst. The catalytic activity is intimately connected to the basicity of the catalyst. The best activities were observed with the Mg/Al: 5 catalyst. The catalyst could be reused for further run without a significant loss in activity. The protocol was also applicable for various aromatic aldehydes which affords desired product in good to excellent yield.

Highlights

The synthesis of highly substituted pyridine moieties through multicomponent reaction[1-4] of aldehydes, malononitrile and thiol is of considerable interest as the pyridine ring is the key intermediate in pharmaceutical chemistry
A convenient route for the synthesis of highly substituted pyridine ring was developed by Evdokimov et al.[15-16]
It is found that the Mg/Al Hydrotalcite with Mg/Al ratio 5.0 is an effective catalyst for the synthesis of compound 4

Summary

Introduction

The synthesis of highly substituted pyridine moieties through multicomponent reaction[1-4] of aldehydes, malononitrile and thiol is of considerable interest as the pyridine ring is the key intermediate in pharmaceutical chemistry. Various synthetic methods[9-14] have been developed for the synthesis of pentasubstituted pyridine ring using different protocols such as hetero-Diels-Alder reaction of 3-siloxy-1-aza-1,3-butadiene, Mannich reaction of aldehydes and iminium salts, ruthenium-catalyzed cycloisomerization of 3-azadienynes, Vilsmeier-Haack reaction of α-hydroxyketenedithioacetals. A convenient route for the synthesis of highly substituted pyridine ring was developed by Evdokimov et al.[15-16]. In continuation of our efforts to develop an efficient catalytic protocol for various multicomponent reactions[19-23], we report the synthesis of a highly substituted pyridine using malononitrile, aldehydes and thiophenol in the presence of Mg/Al-hydrotalcite as a solid base catalyst (Scheme 1). To the best of our knowledge the synthesis of substituted pyridine using hydrotalcite catalyst has not been explored previously

Results and Discussions

Conclusion

General

Preparation of the hydrotalcite catalysts

General procedure for the formation of substituted pyridine

Recycling of the catalyst