CuO Nanoparticle Catalyzed Synthesis of 2,3-Disubstituted Quinazolinones via Sequential N-Arylation and Oxidative C–H Amidation

Abstract

CuO nanoparticle catalyzed synthesis of 2,3-disubstituted quinazolinones has been accomplished from 2-halobenzamides and (aryl)methanamines under an air atmosphere. This synthesis of the N-heterocycle involves a sequential Ullmann coupling [between 2halobenzamide and (aryl)methanamine], oxidation of the in situ generated secondary amine to imine. This is then followed by an intramolecular nucleophilic attack of the amidic N−H on to the imine carbon (C−N bond formation) resulting in the synthesis of 2,3disubstituted quinazolinones. The recyclability of the catalyst and tolerance of a wide range of functional groups makes this method efficient and cost-effective.

Efficient Synthesis of Quinazolinones by Transition‐Metal‐Free Direct Aerobic Oxidative Cascade Annulation of Alcohols witho‐Aminoarylnitriles

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Am ild and atom-economic method was developed for direct and efficient synthesis of quinazolinones through at ransitionmetal-free aerobic oxidativec ascade annulation reaction of widely available o-aminoarylnitriles and alcohols. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Among the methods reported, annulation reactions of o-aminoaryl acids and derivatives may be the most employed strategies, which include the condensation of o-aminoaryl acids with amides, nitriles, or acidd erivatives with an itrogen source (Scheme 1A), [2,3] the dehydrogenative or oxidative annulation of o-aminoarylamides with aldehydes, [4] masked aldehydes, [5] ketones, [6] imines, [7] or amines [8] (Scheme 1B), the carbonylative annulation of o-aminoarylamides with aC Os ource and aryl halides( Scheme 1C), [9] and the annulation of o-aminoarylnitriles with acid derivatives, [10] aldehydes, [11] or ketones [12] (Scheme 1D). Possibly owing to the "cesium effect", the water-soluble base CsOH was found to be crucial in all key steps of the reactionm echanism.B ecause a wide range of substrates can be used to prepare substituted quinazolinones withoutc ontamination by transition-metal residues, this method mayb eo fi nterestf or application in pharmaceutical synthesis.

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“…Similarly,t he reactions of alcohols with o-nitroarylamides [19] or o-nitroarylnitriles [20] were also described recently.A lthough variousq uinazolinones and derivatives can be obtained by the above-mentioned methods, many still have inherent drawbacks that are difficult to overcome. For example, some require tedious multistep procedures, [2,3] rather harsh reaction conditions, [2,3,19,20] transitionmetal catalysts or ligands [4-9, 11,13, 16] that can lead to metal residues in the products and limit their applicationsi nd rug synthesis, or excessa mounts of bases, [10,13] oxidants, [5,8,17] or reactants [19,20] that can lead to production of large amounts of wastes. Therefore, the development of direct, efficient, atomeconomic,a nd transition-metal-and waste-free methods that employ greener substrates and O 2 or even air as the oxidant remains of great importance.…”

“…In contrast, without CsOH, ac onsiderable amount of an ew product was observed instead of 3aa in an incomplete reaction of 4a and 5a.T his was determined to be annulated 8aa, possibly formed via the imine intermediate 7aa,a sc onfirmed by GC-MSa nd NMR analysis [Scheme 2 (7)]. [4,28] The low yield of 8aa in this reactionm ay be attributed to the incomplete reaction of 4a and 5a,t he easy decomposition of 8aa to reactants 4a and 5a,a nd slow oxidation to 3aa in the presence of air [Scheme2 (8)]. [28] Therefore, it may be concluded from the above reactions [Scheme 2(6)- (8)] that, without CsOH, the blank reactiono f4 and 5 to 8 is an equilibrium, [4] and further aerobic oxidationo f8 to 3 is as low process.…”

“…[4,28] The low yield of 8aa in this reactionm ay be attributed to the incomplete reaction of 4a and 5a,t he easy decomposition of 8aa to reactants 4a and 5a,a nd slow oxidation to 3aa in the presence of air [Scheme2 (8)]. [28] Therefore, it may be concluded from the above reactions [Scheme 2(6)- (8)] that, without CsOH, the blank reactiono f4 and 5 to 8 is an equilibrium, [4] and further aerobic oxidationo f8 to 3 is as low process. In contrast, the annulation of 4 and 5 can be greatly facilitated by CsOH to finally afford 3 through aC sOH-promoted aerobic oxidation of intermediate 8.…”

CuO nanoparticle‐catalyzed diaminations for synthesis of benzimidazole derivatives

“…Nanoparticles have emerged as robust and high‐surface‐area heterogeneous catalysts, which serve as sustainable alternatives to conventional materials . CuO nanoparticles have drawn attention due to their stability and availability . For example, Punniyamurthy and co‐workers reported the synthesis of substituted benzimidazoles via CuO nanoparticle‐catalyzed intramolecular C–N coupling .…”