Eco-Friendly Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones Catalyzed by FeCl3/Al2O3 and Analysis of Large 1 H NMR Diastereotopic Effect

Isabel Monreal,Mariano Sánchez-Castellanos,Gabriel Cuevas,Karla Espinoza,Ignacio Rivero,Karla Ramírez-Gualito

doi:10.21577/0103-5053.20180161

Abstract

In the present study, we have carried out a condensation reaction for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones from 2-amino-N-benzylbenzamide and different aromatic aldehydes using FeCl3 catalyst supported on Al2O3. It was demonstrated that this material can be used successfully for the nucleation of quinazolinones with good to excellent yield; furthermore, the FeCl3/Al2O3 catalyst can be recovered and reused. This catalyst was used before in the synthesis of imidazole with very good yields. The synthesized quinazolinones showed a large range diastereotopic effect over the methylene group and, this anomalous difference was studied through nuclear magnetic resonance (NMR) and computational calculations.

Highlights

Quinazolinone (QZ) heterocycles and their derivatives are a very important group of molecules
The synthesis of DQZ was carried out with OAB and different benzaldehydes as a starting material in MeOH, using the base reaction shown on Table 1
The remarkable advantages of this method are simple experiments, mild reaction conditions, excellent yields and catalyst recovery. This catalyst is highly recommended to be used in the synthesis of quinazolinones

Summary

Introduction

Quinazolinone (QZ) heterocycles and their derivatives are a very important group of molecules. One of the first QZ’s synthesized was methaqualone (Figure 1), originally used as an antimalarian drug.[1] The sedative-hypnotic activity of methaqualone was observed since 1951; and later was used for the treatment of insomnia, as a sedative and muscle relaxant.[2] QZ’s have a wide extent of biological actions[3] such as central nervous system activity,[4] anticonvulsant and antidepressant agents,[5] they have been used for biological evaluation and docking studies (Alzheimer’s disease),[6] in nuclear medicine as potential labeler.[7] Their analgesic and anti-inflammatory properties have been evaluated[8] in endocrinology as inverse agonist for the human thyroid-stimulating hormone receptor,[9] as enzymatic inhibitors of thermolysin[10] and chorismate.

Methods

Results

Conclusion