Multi Component Reactions under Increased Pressure: On the Mechanism of Formation of Pyridazino[5,4,3-de][1,6]naphthyridine Derivatives by the Reaction of Malononitrile, Aldehydes and 2-Oxoglyoxalarylhydrazones in Q-Tubes.

Majdah Al-Johani,Sameera Mousally,Mohamed Elnagdi,Norah Alqahtani,Noha Elnagdi,Khadijah Al-Zaydi

doi:10.3390/molecules22122114

Abstract

Efficient synthesis of phenanthridin-6(5H)-one derivatives 12a–n in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in good yields. Potential routes leading to formation of compounds 12 are discussed. The structures of the synthesized compounds could be unequivocally established via X-ray crystal structure determination and spectroscopic methods.

Highlights

The considerable biological and medicinal activities of pyridazines has stimulated considerable research on efficient syntheses of these derivatives in past years [1,2,3,4]
This be the eliminated as incarbonyl our hands could dimerized dimer
Synthesis of 2-amino-1,4-dihydropyridazines by reacting arylhydrazonals, active methylene nitriles and aromatic aldehydes has been found of very limited scope

Summary

Introduction

The considerable biological and medicinal activities of pyridazines has stimulated considerable research on efficient syntheses of these derivatives in past years [1,2,3,4]. Elnagdi et al reported synthesis of 2-amino-1,4-dihydropyridazine, an isoelectronic derivative of 1,4-dihydropyrimidines of established biological activities [5,6,7,8], via 3 + 3 atom combination of arylhydrazones 1a and α,β-unsaturated nitriles 2 [9] or by reacting a mixture of 1, 4 and 5 in one pot (Scheme 1). Subsequent studies [10,11] on this novel route revealed that it is of a limited scope as the reaction products proved to be dependent on the nature of the reacting aryl hydrazones. Multicomponent reaction of 1a–c with α,β-unsaturated nitriles 2 in presence of a base has been reported to yield 3, while the reaction of 1f with 2 in basic medium afforded the new substituted pyrazolo[40 ,30 -5,6]pyrimido[2,1-a]phthalazine-9-carbonitriles ring system 7 [12] (Scheme 1). We noted that microwaves technology is expensive to scale up [17], in contrast to using “Q-Tube” pressure reactors, which proved to accelerate reactions of negative activation volume in a more optimal and safer manner, compared to microwaves [18]

Methods

Discussion

Conclusion