Effect of Solvents on 1-Butyl-1,2,4-Triazolium Trifluoroacetate Triggered Synthesis of 2,3-Dihydroquinazolin

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. Method: 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 condensation of anthranilamide with the corresponding aldehyde in the presence of organocatalyst and solvent is done. Using benzaldehyde as the parent aldehyde, to validate the outcome, the benzaldehydes were selected as follows a) benzaldehyde, b) 4-methoxybenzaldehyde – electron releasing group and c) 4-nitrobenzaldehyde – electronwithdrawing group. Solvent study has been done with solvents varied from polar to apolar. Both polar protic and polar aprotic solvents are 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 are ethyl acetate, DMF,acetonitrile, and DMSO. The moderately apolar solvents used are DCM, carbon tetrachloride, 1,4 dioxane, and chloroform. Results: The synthesized triazolium salts are found soluble in polar aprotic, polar protic solvents and few moderately apolar solvents such as DCM, chloroform, acetonitrile, water, methanol and ethanol whereas insoluble with 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 electron-donating group, is less than 2-(4-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one, where the aromatic benzaldehyde had an electron-withdrawing group. Conclusion: Substituted benzaldehyde gave better yields than benzaldehyde. And nitro group which is electrowithdrawing attached to benzaldehyde enhanced the electrophilic nature at carbonyl center showed higher yields than methoxy group which is electron donating attached to benzaldehyde as it deactivates the carbonyl carbon. The polar protic solvents like water, ethanol and methanol stabilizes the ionic intermediates and gave better yield. Even the moderately apolar solvents like DCM, 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 got an effect on product yield. As the carbon chain increases in solvent, the yield decreases due to the separation difficulties. The polar aprotic solvents did gave better yields but not as good as polar protic solvents.