DDQ in mechanochemical C-N coupling reactions

Abstract

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a commonly known oxidant. Herein, we report that DDQ can be used to synthesize 1,2-disubstituted benzimidazoles and quinazolin-4(3H)-ones via the intra- and intermolecular C-N coupling reaction under solvent-free mechanochemical (ball milling) conditions. In the presence of DDQ, the intramolecular C(sp²)-H amidation of N-(2-(arylideneamino)phenyl)-p-toluenesulfonamides leads to 1,2-disubstituted benzimidazoles and the one-pot coupling of 2-aminobenzamides with aryl/alkyl aldehydes resulted in substituted quinazolin-4(3H)-one derivatives in high yields.

Keywords: 1H-benzo[d]imidazole; C(sp2)–H amidation; DDQ; ball mill; mechanochemistry; quinazolin-4(3H)-one.

Figure 1

Our work on mechanochemical C–N coupling reactions using DDQ. The newly formed C–N bonds are shown as red lines for clarity. a) The intramolecular C(sp²)-H amidation leading to 1,2-disubstituted benzimidazoles. b) One-pot coupling to synthesize substituted quinazolin-4(3H)-ones.

Figure 2

Scope of the mechanochemical synthesis of substituted benzimidazoles.

Figure 3

Synthesis of quinazolin-4(3H)-one derivatives.

Figure 4

The substrate scope for the synthesis of quinazolin-4(3H)-one derivatives.

Figure 5

a) Control experiment and b) Plausible mechanism.

Figure 6

Large-scale synthesis. a) 1,2-Disubstituted benzimidazoles. b) Substituted quinazolin-4(3H)-ones. Reaction conditions: reactants were milled at 21 Hz in a 25 mL milling jar containing one stainless-steel grinding ball (15 mm in diameter).