One-Pot Cascade Synthesis of Quinazolin-4(3H)-ones via Nickel-Catalyzed Dehydrogenative Coupling of o-Aminobenzamides with Alcohols

Abstract

In this paper, we report a general, efficient, and environmentally benign method for the one-pot cascade synthesis of quinazolin-4(3H)-ones via acceptorless dehydrogenative coupling of o-aminobenzamide with alcohols catalyzed by a simple Ni(II) catalyst, [Ni(MeTAA)], featuring a tetraaza macrocyclic ligand (tetramethyltetraaza[14]annulene (MeTAA)). A wide variety of substituted quinazolin-4(3H)-ones were synthesized in high yields starting from readily available benzyl alcohols and o-aminobenzamides. Several controlled reactions along with deuterium labeling studies were carried out to establish the acceptorless dehydrogenative nature of the reactions.

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

“…The chemistry of iodine(V) reagents has been well documented in a number of reviews [18–20]. In continuation of our research focus on the development of synthetic methods using iodine-based reagents [21–26], we here report a method for the synthesis of quinazolin-4(3 H )-ones [27–28] (Fig. 1) from 2-aminobenzamide and aldehydes in the presence of o -iodoxybenzoic acid (IBX) [29].…”

Nickel‐Catalyzed Dehydrogenative Couplings

“…The dehydrogenative pathway possibly proceeds through the initial formation of alkoxy nickel species which undergo β‐elimination to form reactive aldehyde and nickel hydride species. Then sequential coupling with o ‐aminobenzamides and oxidization with the released nickel hydride species deliver quinazolin(3 H )‐4‐ones (Scheme ) …”

Nickel‐Catalyzed Synthesis of Pyrimidines via Dehydrogenative Functionalization of Alcohols

“…The catalysts 1 a and 1 b represent two tetraaza macrocyclic nickel(II)‐complexes, whereas catalysts 2 a and 2 b are two diamine‐based nickel(II)‐complexes. During our recent works, we observed that the nickel catalysts 1 a and 1 b involve exclusively nickel‐centered redox events during catalysis and the dehydrogenation of alcohols proceeds via two‐electron hydride transfer process involving energetically demanding nickel centered redox states at high temperature . On the other hand, in presence of 2 a and 2 b dehydrogenation of alcohols proceed via one‐electron hydrogen atom transfer (HAT) process (avoiding the unfavourable nickel centered two‐electron process) where the coordinated redox‐active ligand abstract a α‐hydrogen atom of the alcohol to form an O‐coordinated ketyl radical intermediate which undergo rapid one‐electron oxidation to yield the respective carbonyls .…”