An efficient and ecofriendly synthesis of highly functionalized pyridones via a one-pot three-component reaction.

Hajar Hosseini,Mohammad Bayat

doi:10.1039/c8ra05690k

Abstract

A simple and convenient protocol has been developed for the synthesis of N-amino-3-cyano-2-pyridone derivatives by a one-pot reaction of cyanoacetohydrazide, activated nitrile substrates (malononitrile, ethyl cyanoacetate, cyanoacetamide) and aromatic aldehydes in the presence of piperidine in water or a mixture of water and ethanol. The sequence of cascade reactions includes Knoevenagel condensation, Michael addition, intramolecular cyclization, imine-enamine tautomerization and oxidative aromatization. The main advantages of this procedure are availability of starting compounds, simple procedure, mild conditions, easy purification of products and the use of water or water/ethanol as green solvents.

Highlights

Continuing our research on multi-component reactions using cyanoacetohydrazide, we will describe in this paper a very efficient and environmentally benign strategy for the synthesis of N-amino-3-cyano-2-pyridone derivatives by a one-pot three component reaction of cyanoacetohydrazide 1, acetonitrile derivatives 2 and aromatic aldehydes 3 (Scheme 3)
We report a one-pot three-component reaction between cyanoacetohydrazide, acetonitrile derivatives and aromatic aldehydes. This strategy led to the N-amino-3-cyano-2-pyridones in good yields via a multicomponent reaction
Ethyl 1,6-diamino-4-aryl-3cyano-2-pyridone-5-carboxylate derivatives 5a–e were synthesized via the reaction of cyanoacetohydrazide 1, ethyl cyanoacetate 2b and the ve aldehydes 3 (Table 2)

Summary

Introduction

The chemistry and applications of pyridine structures have recently attracted a lot of attention due to their uses as synthetic intermediates and their biological importance as agrochemicals,[1,2,3] pharmaceuticals,[4,5,6,7,8] dye intermediates,[9,10] insecticides, adhesives,[11] antifungals, antibacterials,[12,13,14] antidepressant agents,[15,16] and antitumor agents.[17]. Continuing our research on multi-component reactions using cyanoacetohydrazide, we will describe in this paper a very efficient and environmentally benign strategy for the synthesis of N-amino-3-cyano-2-pyridone derivatives by a one-pot three component reaction of cyanoacetohydrazide 1, acetonitrile derivatives 2 (malononitrile 2a, ethyl cyanoacetate 2b, cyanoacetamide 2c) and aromatic aldehydes 3 (Scheme 3).

Results

Conclusion