One-pot green synthesis of 3-amino-1-(5-nitro-1H-indol-2-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile

Rama Koteshwar Rao,Shravankumar Kankala

doi:10.17628/ecb.2018.7.324-328

Abstract

Synthesis of 3-amino-1-(5-nitro-1H-indol-2-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitriles by one-pot green and eco-friendly reaction of phthalic acid, hydrazine hydrate, indole-3-carboxaldehydes and malononitrile/ethyl cyanoacetate in the presence of Et 3 N as catalyst and Glycerol mediated at 100-105 o C for 45-60 min. This one-pot reaction preceeded in short time with good yields and the desired products obtained without using column purifications.

Highlights

Multi-component reactions (MCRs) are one-pot processes in which three or more compounds react in a single reaction vessel to form a product containing substantial components of all the reactants
Firstly, we have initiated the optimization of the one-pot four-component reaction by using phthalic acid (1) and hydrazine hydrate (2) to in-situ formation of phthalic hydrazide as intermediate in the presence of Et3N and glycerol medium
It was found that the one-pot reaction of 1 (10 mM), 2 (10 mM), 3a (10 mM) and 4a (10 mM) in the presence of Et3N (2 mM) as catalyst and glycerol (50 ml) as medium for 45 min at 100 °C gave the highest yield (88 %) and clean product (5a) (Table 1, entry 1). 1H-NMR, IR and mass spectroscop5ay have confirmed the structure of the compound 5a

Summary

INTRODUCTION

Multi-component reactions (MCRs) are one-pot processes in which three or more compounds react in a single reaction vessel to form a product containing substantial components of all the reactants. design of highly efficient chemical reaction sequences that provide maximum structural complexity and diversity with a minimum number of steps in the synthesis of compounds with interesting properties is essential for drug discovery and synthesis of natural products. MCRs have attracted much attention in combinatorial and medicinal chemistry and have been designed to produce biologically active compounds.. Design of highly efficient chemical reaction sequences that provide maximum structural complexity and diversity with a minimum number of steps in the synthesis of compounds with interesting properties is essential for drug discovery and synthesis of natural products.. MCRs have attracted much attention in combinatorial and medicinal chemistry and have been designed to produce biologically active compounds.. Carling et al reported the synthesis of 3phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogs which were found to be a critical structural element of specific CNS - active drugs. Jain et al reported the synthesis of keto-glutamine tetrapeptide analogs containing a 2-oxopyrrolidine ring as a glutamine side chain mimic which showed improved inhibition against hepatitis A virus 3C proteinase. Nomoto et al reported the synthesis of 6,7dimethoxyphthalazine derivatives which showed relatively potent cardiotonic activity comparable to that of amrinone. Keeping above discussion in our mind, we wish to report 3-amino-1-(5-nitro-1H-indol-2-yl)-5,10-dioxo-5,10dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile derivatives by reaction of phthalic acid, hydrazine hydrate, indole-3-carboxaldehydes and malononitrile/ethyl cyanoacetate in the presence of Et3N as catalyst and glycerol as a medium at 100-105 °C for 30-60 min

RESULTS AND DISCUSSION

EXPERIMENTAL SECTION

CONCLUSION