One‐Pot Synthesis of p‐Amino‐Substituted Unsymmetrical Benzils and Benzil Derivatives

Abstract

An efficient iodine/copper(II) oxide co‐promoted direct oxidative coupling of anilines and methyl aryl ketones has been developed for the synthesis of p‐amino‐substituted unsymmetrical benzils and their iodo‐substituted derivatives. The chemoselectivity of the reactions can be easily controlled by adjusting the amount of iodine. This method exhibits good functional group tolerance for various substituents on the aromatic rings of the methyl aryl ketones. A possible mechanism for this reaction has been proposed based on control experiments. A couple of representative quinoxalines were synthesized from the benzil products in order to demonstrate the utility of this approach.magnified image

Two‐Step One‐Pot Synthesis of Unsymmetrical (Hetero)Aryl 1,2‐Diketones by Addition‐Oxygenation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles

“…1‐(Naphthalen‐2‐yl)‐2‐phenylethane‐1,2‐dione (3h): [14e] Employing GP‐A and a reaction time of 6 h afforded 3h (105 mg, 81 % yield) as a brown solid; m.p. 82–84 °C; R f = 0.7 (hexanes/EtOAc, 9.8:0.2).…”

“…Some of the derivatives also show good antitumor activity . As a consequence of their diverse applications, several classical and modern synthetic protocols, which use various precursors such as olefins, both α‐halo and α ‐hydroxy, and alkynes along with different oxidants, have been developed for their preparation …”

Benzils: A Review on their Synthesis

“…A highly efficient, one‐pot, oxidative coupling of aryl methyl ketones 94 with anilines 95 to p ‐amino‐substituted benzils 96 and their iodo derivatives 97 was reported [152] . It is interesting to note that the amino group remains unaltered without any chemical change in this reaction with a scope to utilize further.…”

“…A highly efficient, one-pot, oxidative coupling of aryl methyl ketones 94 with anilines 95 to p-amino-substituted benzils 96 and their iodo derivatives 97 was reported. [152] It is interesting to note that the amino group remains unaltered without any chemical change in this reaction with a scope to utilize further. After optimization using various mole percent of iodine, additives such as CuO, TBHP, DTBP, Oxone, MnO 2 , CuBr 2 , CuCl 2 , Cu(OAc) 2 , CuI, the optimization was observed to be aniline 95 (1.6 equiv) to acetophenone 94 in presence of iodine (1 equiv) with CuO (1 equiv) as the additive and a reaction temperature of 100 °C.…”

Synthesis of α-keto aldehydes via selective Cu(i)-catalyzed oxidation of α-hydroxy ketones

“…α-Keto aldehydes, containing two adjacent carbonyl groups, are versatile intermediates, widely used for synthesizing dicarbonyls, 1 α-keto esters, 2 α-keto amides, 3 morpholinones, 4 quinoxalines, 5 and other compounds 6 via simple approaches with high yields (Scheme 1). Further, these compounds are important units in many commercially important pharmaceuticals, such as, Rivaroxaban, 7 Tacrolimus, 8 Everolimus, 9 and Selexipag.…”