The mechanochemical synthesis of quinazolin-4(3H)-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.

Catalytic Room‐Temperature C−N Coupling of Amides and Isocyanates by Using Mechanochemistry

“…A similar preference for mechanochemical reaction conditions was previously noted for the related C−N coupling reactions of sulfonamides . Such behavior differs from, for example, bimolecular Schiff base condensations, palladium‐catalyzed Suzuki coupling reactions, or multicomponent formation of N ‐heterocycles, which often readily proceed in solution or through ball milling. Consequently, it is tempting to consider certain classes of reactions, for example, the herein‐demonstrated family of C−N coupling reactions of amides and sulfonamides, as mechanochemically favored.…”

Sustainability Assessment of Mechanochemistry by Using the Twelve Principles of Green Chemistry

“…Mechanochemical reactions involving contact-unstable reactants should be considered on a case-by-case basis. [222,223] This has to be strongly emphasized since most of these examples were only carried out in small scale. And mechanochemical reactions involving energetic materials that exhibit explosive properties would require major safety precautions, especially upon upscaling of the experiments.…”

“…Moreover, although some studies have reported that materials such as azides, [219] diazonium salts, [220] or contact‐unstable mixtures [221] undergo ball milling reactions without incident, precaution is always recommended! Mechanochemical reactions involving contact‐unstable reactants should be considered on a case‐by‐case basis [222,223] . This has to be strongly emphasized since most of these examples were only carried out in small scale.…”

DDQ in mechanochemical C–N coupling reactions

“…Various methodologies are available in the literature toward constructing quinazolin-4(3 H )-one derivatives [ 40 , 45 – 46 ]. Quinazolin-4(3 H )-ones and its derivatives possess several biological activities such as antibacterial [ 47 ], antiviral [ 48 ], antitumor [ 49 – 50 ], antimalarial [ 51 ], anti-inflammatory [ 52 ], etc.…”

“…Herein, we disclose the DDQ-mediated oxidative C–N coupling toward the synthesis of 1,2-disubstituted benzimidazoles [ 39 ] under mechanochemical (ball milling) conditions ( Figure 1a ). In addition, the one-pot coupling of 2-aminobenzamides with aryl/alkyl aldehydes in the presence of DDQ resulted in substituted quinazolin-4(3 H )-one [ 40 ] derivatives ( Figure 1b ).…”