The mechanochemical synthesis of quinazolin-4(3 H)-ones by controlling the reactivity of IBX

Abstract

Performing any synthesis using several arylamines and hypervalent iodine(V) reagents by direct mixing is unrealistic because of the high exothermic reaction or explosion. Herein we demonstrate, when anilines were substituted with an amide group at the ortho-position, successful chemical reactions could be performed due to intramolecular control. At maximum contact of the reacting substances, i.e., under solvent-free mechanochemical conditions, 2-aminobenzamides, aryl-, alkylaldehydes and the iodine(V) reagent o-iodoxybenzoic acid (IBX) led to substituted quinazolin-4(3H)-one derivatives in fair yields.

Keywords: IBX; ball-mill; contact explosive; mechanochemical synthesis; quinazolin-4(3H)-one.

Figure 1

a) Explosion was observed when an arylamine was mixed with aldehydes in the presence of IBX. b) Benzamide was found to be unreactive with IBX. c) Treatment of 2-aminobenzamide with IBX did not lead to any explosion. d) Reaction of 2-aminobenzamide and aldehydes in the presence of IBX as oxidant afforded quinazolin-4(3H)-ones at maximum interaction of the reactants, i.e., under ball-milling conditions.

Figure 2

Comparison of the current work with the existing literature reports.

Figure 3

Synthesis of quinazolin-4(3H)-one derivatives from the reaction of 1 with liquid aldehydes. ^aYields with respect to recovered aldehydes, for compound 3k IBX was added after 1 h.

Figure 4

Synthesis of quinazolin-4(3H)-one derivatives from reaction of 1 and solid aldehydes. ^aYields with respect to recovered aldehydes, for compound 3y, IBX was added after 1 h.

Figure 5

Crystal structure of 3a (CCDC No. 1823611).

Figure 6

Plausible mechanism for the quinazolin-4(3H)-ones synthesis using IBX.

Scheme 1

Large scale synthesis of 3a.