Abstract

Background: Quinazolinones are a class of heterocyclic compounds that have a wide variety of applications. They are also used in agrochemicals. There are several methodologies reported for the synthesis of 2,3-dihydroquinazolines using various catalysts.

Methods: Here, by using 1-butyl-1,2,4-triazolium as cation and trifluoroacetate as anion, 2,3- dihydroquinazolin-4(1H)-one has been synthesized. For the synthesis of 2,3-dihydroquinazolin- 4(1H)-one, the condensation of anthranilamide with the corresponding aldehyde in the presence of organocatalyst and solvent was done. Using benzaldehyde as the parent aldehyde, to validate the outcome, the benzaldehydes were selected as follows: a) benzaldehyde; b) 4-methoxybenzaldehyde, an electron-releasing group; and c) 4-nitrobenzaldehyde, an electron-withdrawing group. A solvent study has been done with solvents varying from polar to apolar. Both polar protic and polar aprotic solvents have been used for the reactions. The polar protic solvents used were water, methanol, ethanol, isopropanol, butanol, hexane-1-ol, and glycerol. The polar aprotic solvents used were ethyl acetate, DMF, acetonitrile, and DMSO. The moderately apolar solvents used were DCM, carbon tetrachloride, 1,4 dioxane, and chloroform.

Results: The synthesized triazolium salts have been found to be soluble in polar aprotic and polar protic solvents, and a few moderately apolar solvents, such as DCM, chloroform, acetonitrile, water, methanol and ethanol, whereas insoluble in apolar solvents, like toluene, benzene, and hexane. The yield of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one was low for 1-butyl-1,2,4-triazolium trifluoroacetate- based organocatalyst. But for substituted benzaldehyde, the yield was comparatively high. Comparatively, the yield for 2-(4-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one, where the aromatic benzaldehyde had an electron-donating group, was less than 2-(4-nitrophenyl)-2,3- dihydroquinazolin-4(1H)-one, where the aromatic benzaldehyde had an electron-withdrawing group.

Conclusion: Substituted benzaldehyde provided better yields than benzaldehyde. The nitro group, which is an electron-withdrawing group, when attached to benzaldehyde, enhanced the electrophilic nature at the carbonyl center, providing higher yields than the methoxy group, which is an electron-donating group; when it attaches to benzaldehyde, it deactivates the carbonyl carbon. The polar protic solvents, like water, ethanol and methanol, stabilize the ionic intermediates, providing a better yield. Even the moderately apolar solvents, like DCM and chloroform, resulted in good yields; green solvents, like water, ethanol and methanol, would be a better choice as solvents. The carbon chain on the solvent has an effect on the product yield. As the carbon chain increases in the solvent, the yield decreases due to the separation difficulty. The polar aprotic solvents provided better yields but not as good as polar protic solvents.

Keywords: Organocatalysts, Ionic liquids, Heterocyclic compounds, Quinazolinones, Dihydroquinazolin, Solvents

Graphical Abstract