Synthesis of 4-quinazolinones by transition metal-catalyzed processes (microreview)

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

“…[1,2] Hence, av ariety of methods have been developedf or quinazolinones keleton construction. Air could be employeda sa ne ffective oxidant under mild conditions, generating water as the only byproduct.…”

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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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“…Air could be employeda sa ne ffective oxidant under mild conditions, generating water as the only byproduct. Moreover, transition-metal-catalyzed coupling reactions of o-haloarylamides with amides, nitriles, amines,o ra ldehydee quivalents with an itrogen source (Scheme 1E) [13] as well as other annulation reactions [2,14] have also received much attention recently.A lcohols are known as ac lass of greener, more available, more economic, more stable, and less toxic chemicals. Possible reaction paths were also proposed according to controlr eactions.…”

“…[1,2] Hence, av ariety of methods have been developedf or quinazolinones keleton construction. For example, the quinazolinone motif and derivatives are abundant in numerous synthetic compoundsa nd natural alkaloids with diverse biological and pharmacological activities such as antimalarial, antimicrobial, anti-inflammatory,a nticonvulsant, antihypertensive, anti-diabetic, anticancer,a ntitumor, cholinesteraseinhibitory, dihydrofolate reductase-inhibitory,a nd kinase-inhibitory properties.…”

“…For example, the quinazolinone motif and derivatives are abundant in numerous synthetic compoundsa nd natural alkaloids with diverse biological and pharmacological activities such as antimalarial, antimicrobial, anti-inflammatory,a nticonvulsant, antihypertensive, anti-diabetic, anticancer,a ntitumor, cholinesteraseinhibitory, dihydrofolate reductase-inhibitory,a nd kinase-inhibitory properties. Moreover, transition-metal-catalyzed coupling reactions of o-haloarylamides with amides, nitriles, amines,o ra ldehydee quivalents with an itrogen source (Scheme 1E) [13] as well as other annulation reactions [2,14] have also received much attention recently.A lcohols are known as ac lass of greener, more available, more economic, more stable, and less toxic chemicals. [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).…”