Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of quinazolinones
An acceptorless coupling of o-aminobenzamides with methanol has been accomplished in the presence of the metal-ligand bifunctional catalyst [Cp*Ir(2,2′-bpyO)(H2O)] to provide quinazolinones in good yields.
F. Li, L. Lu, P. Liu, Org. Lett., 2016, 18, 2580-2583.
CuI/4-hydroxy-l-proline catalyzed coupling of N-substituted o-bromobenzamides with formamide affords 3-substituted quinazolinones at 80░C. Other amides only provided simple coupling products, which can be converted into 2,3-disubstituted quinazolinones via a subsequent HMDS/ZnCl2 mediated condensative cyclization.
L. Xu, Y. Jiang, D. Ma, Org. Lett., 2012, 14, 1150-1153.
A copper-catalyzed imidoylative cross-coupling/cyclocondensation reaction between 2-isocyanobenzoates and amines efficiently provides quinazolin-4-ones. The reaction utilizes Cu(II) acetate as an environmentally benign catalyst in combination with a mild base and proceeds well in anisole, a sustainable solvent. The use of aromatic amines as nucleophiles requires microwave heating.
J. W. Collet, E. A. van der Nol, T. R. Roose, B. U. W. Maes, El Ruijter, R. V. A. Orru, J. Org. Chem., 2020, 85, 7378-7385.
A copper-catalyzed radical methylation/sp3 C-H amination/oxidation reaction provides quinazolinone via a cascade reaction, in which dicumyl peroxide acts not only as an oxidant but also as an efficient methyl source.
Y. Bao, Y. Yan, K. Xu, J. Su, Z. Zha, Z. Wang, J. Org. Chem., 2015, 80, 4736-4742.
An n-Bu4NI-catalyzed reaction of 3-methylindoles with primary amines using TBHP as the unique oxidant provides broad range of quinazolinones in very good yields. The reaction involves oxygenation, nitrogenation, ring-opening, and recyclization.
J. He, J. Dong, L. Su, S. Wu, L. Liu, S.-F. Yin, Y. Zhou, Org. Lett., 2020, 22, 2522-2526.
A Cu-catalyzed nucleophilic addition of readily available 2-halobenzamides to nitriles followed by SNAr reaction enables a convenient synthesis of quinazolin-4(3H)-ones. The reaction proceeds smoothly in the presence of tBuOK as a base.
X. Yu, L. Gao, L. Jia, Y. Yamamoto, M. Bao, J. Org. Chem., 2018, 83, 10352-10358.
A visible-light-promoted C-H alkylation of nitrogen-containing heteroarenes with C4-alkyl 1,4-dihydropyridines (DHPs) as radical precursors enables an efficient late-stage functionalization at ambient temperatures. A broad scope of heteroarenes, including those bearing electron-donating or electron-withdrawing groups, can be successfully alkylated in good yields.
X. Chen, X. Luo, K. Wang, F. Liang, P. Wang, Synlett, 2021, 32, 733-737.
A novel and efficient Cu(I)-catalyzed ligand- and base-free multipathway domino strategy for the synthesis of 2-substituted quinazolinones utilizes TMSN3 as a nitrogen source, 2-bromobenzamide and multiform substrates such as aldehydes, alcohols, and methyl arenes for a one-pot protocol.
K. Upadhyaya, R. K. Thakur, S. K. Shukla, R. P. Tripathi, J. Org. Chem., 2016, 81, 5046-5055.
A simple metal-ligand cooperative approach enables dehydrogenative functionalization of benzylic alcohols to various substituted quinolines and quinazolin-4(3H)-ones in good yields under relatively mild reaction conditions using simple and easy-to-prepare air-stable Cu(II) complexes featuring redox-active azo-aromatic scaffolds.
S. Das, S. Sinha, D. Samanta, R. Mondal, G. Chakraborty, P. Branda§, N. D. Paul, J. Org. Chem., 2019, 84, 10160-10171.
Molecular iodine catalyzes a metal-free oxidative coupling of 2-aminobenzamides with aryl methyl ketones to yield 2-aryl quinazolin-4(3H)-ones. The selectivity of the reaction strongly depends on the quantity of iodine.
S. Mohammed, R. A. Vishwakarma, S. B. Bharate, J. Org. Chem., 2015, 80, 6915-6921.
An efficient anodic dehydrogenative oxidation/cyclization of benzylic chlorides and 2-aminobenzamides selectively provides quinazolin-4(3H)-ones in good yields.
Y. Yao, X.-J. Meng, Q.-H. Teng, Y.-Y. Chen, Synlett, 2020, 31, 1795-1799.
Efficient reactions of α-keto acids with 2-aminobenzamides, 2-aminobenzenethiols, benzene-1,2-diamines, and 2-aminophenols provide quinazolinones, benzothiazoles, quinoxalinones, and benzoxazinones under catalyst-free conditions, using water as the solvent. Products can be easily purified through filtration and washing with ethanol (or crystallized).
J. Huang, W. Chen, J. Liang, Q. Yan, Y. Fan, M.-W. Chen, Y. Peng, J. Org. Chem., 2021, 86, 14866-14882.
A facile and mild method for the preparation of 2,3-dialkyl-substituted quinazolinones from readily available N-arylamides and commercial isocyanates involves a chemoselective activation of the secondary amide with Tf2O/2-Br-Pyr, addition of isocyanate, and cyclization. This reaction is general for a wide range of substrates and can be run on a gram scale.
Y. Lin, S.-F. He, H. Geng, Y.-C. Xiao, K.-L. Ji, J.-F. Zheng, P.-Q. Huang, J. Org. Chem., 2021, 86, 5345-5353.
A copper-catalyzed tandem reaction of 2-aminobenzamides with tertiary amines provides quinazolinone derivatives. A broad range of substrates reacted under the standard conditions to give the corresponding quinazolinone derivatives in good yields.
W. Xu, X.-R. Zhu, P.-C. Qian, X.-G. Zhang, C.-L. Deng, Synlett, 2016, 27, 2851-2857.
A general and efficient phosphorous acid-catalyzed cyclocondensation of β-ketoesters with o-aminobenzamides provides 2-subsituted quinazolinones via selective C-C bond cleavage under metal- and oxidant-free conditions in excellent yields. This strategy can also be applied to the synthesis of other N-heterocycles, such as benzimidazoles and benzothiazoles.
Z. Li, J. Dong, X. Chen, Q. Li, Y. Zhou, S.-F. Yin, J. Org. Chem., 2015, 80, 9392-9400.
An operational simple palladium-catalyzed three-component reaction of readily available 2-aminobenzamides, aryl halides, and tert-butyl isocyanide efficiently constructs quinazolin-4(3H)-ones in good yields via a palladium-catalyzed isocyanide insertion/cyclization sequence.
X. Jiang, T. Tang, J.-M. Wang, Z. Chen, Y.-M. Zhu, S.-J. Ji, J. Org. Chem., 2014, 79, 5082-5087.
A palladium-catalyzed oxidative three-component coupling of easily accessible N-substituted anthranilamides with isocyanides and arylboronic acids provides 2,3-disubstituted quinazolinones with a wide substrate scope and good functional group tolerance.
C. Qian, K. Liu, S.-W. Tao, F.-L. Zhang, Y.-M. Zhu, S.-L. Yang, J. Org. Chem., 2018, 83, 9201-9209.
An efficient and facile reaction of quinazoline-3-oxides with primary amines provides a broad range of quinazolin-4(3H)-ones under metal-free and mild reaction conditions employing tert-butyl hydroperoxide as the oxidant. Remarkably, a precursor for the synthesis of bioactive evodiamine and rutaempine was conveniently obtained in good yield.
J. Luo, J. Wan, L. Wu, L. Yang, T. Wang, J. Org. Chem., 2022, 87, 9864-9874.
A copper-catalyzed reaction of easily available 2-arylindoles and amines or ammonium provides various quinazolinones in very good yields in the presence of oxygen. This simple and mild reaction tolerates a broad range of functional groups.
Y. Feng, Y. Li, G. Cheng, L. Wang, X. Cui, J. Org. Chem., 2015, 80, 7099-7107.
A synergetic tert-butyl hydroperoxide/K3PO4-promoted oxidative cyclization enables a facile synthesis of various functionalized quinazolin-4(3H)-ones from commercially available isatins and amidine hydrochlorides at room temperature.
F.-C. Jia, Z.-W. Zhou, C. Xu, Y.-D. Wu, A.-X. Wu, Org. Lett., 2016, 18, 2942-2945.
A visible-light-driven photoredox-catalyzed nonaqueous oxidative C-N cleavage of N,N-dibenzylanilines provides 2░ amides. The protocol also enables the conversion of 2-(dibenzylamino)benzamide to quinazolinones in the presence of (NH4)2S2O8 as an additive.
N. Neerathilingam, M. B. Reddy, R. Anandhan, J. Org. Chem., 2021, 86, 15117-15127.
A microwave-assisted method for the palladium-catalyzed direct arylation of quinazolin-4-one has been developed under copper-assistance. This method is applicable to a wide range of aryl iodides and substituted (2H)-quinazolin-4-ones. This protocol provides a simple and efficient way to synthesize biologically relevant 2-arylquinazolin-4-one backbones.
S. Laclef, M. Harari, J. Godeau, I. Schmitz-Afonso, L. Bischoff, C. Hoarau, V. Levacher, C. Fruit, T. Besson, Org. Lett., 2015, 17, 1700-1703.
A transition-metal-free, K2S2O8-mediated intramolecular oxidative nitrogenation/oxygenation of C(sp3)-H in N-aryl benzylic amines followed by oxidation at the benzylic center provides an expedient access to quinazolin-4(3H)-ones, N-aryl-2-arylbenzimidazoles, and 4H-3,1-benzoxazin-4-ones.
J. K. Laha, K. S. S. Tummalapalli, A. Nair, N. Patel, J. Org. Chem., 2015, 80, 11351-11359.
In a simple one-pot procedure for the preparation of 2-(het)arylquinazolin-4(3H)-ones from readily available 2-nitrobenzamides and aryl aldehydes, sodium dithionite is used as the reducing agent for the nitro group. Sodium dithionite also decomposes in aqueous N,N-dimethylformamide under air to form sulfur dioxide, which is the oxidant in the final oxidation step that leads to the desired heterocyclic compounds.
A. H. Romero, J. Salazar, S. E. Lˇpez, Synthesis, 2013, 45, 2043-2050.
Copper(I) bromide catalyzes a domino reaction of alkyl halides and anthranilamides under air to afford 2-substituted quinazolin-4(3H)-ones in good to excellent yields and with wide functional group tolerance. A mechanism via a four-step domino reaction is proposed.
H. Wei, T. Li, Y. Zhou, L. Zhou, Q. Zeng, Synthesis, 2013, 45, 3349-3354.
Cyclization of 2-aminobenzamides and aldehydes catalyzed by p-toluenesulfonic acid followed by an efficient PIDA-mediated oxidative dehydrogenation enables the synthesis of various 4(3H)-quinazolinones - including quinazolinones bearing an N-alkoxy substituent. The method offers mild reaction conditions.
R. Cheng, T. Guo, D. Zhang-Negrerie, Y. Du, K. Zhao, Synthesis, 2013, 45, 2998-3006.
Key to a facile synthesis of 2,3-disubstituted quinazolin-4(3H)-ones is a tandem strategy involving introduction of a 2-substituent and construction of the quinazolinone framework via C-nucleophilic addition to a carbodiimide cumulenic carbon followed by intramolecular nucleophilic substitution by the newly formed NH moiety at the proximal ester group.
H. Nakano, N. Kutsumura, T. Saito, Synthesis, 2012, 44, 3179-3184.
The iron(III) chloride catalyzed reaction of isatoic anhydride with various amidoxime derivatives enables a simple and highly efficient synthesis of 2-substituted quinazolin-4(3H)-ones. The conversion of several aryl and alkyl amidoximes demonstrates the scope of the methodology.
R. Mekala, R. Akula, R. R. Karmaju, C. K. Bannoth, S. Regati, J. Sarva, Synlett, 2014, 25, 821-826.
Benzyl halides, that are first oxidized to aldehydes under mild Kornblum conditions, undergo a three-component reaction with isatoic anhydride and primary amines to produce 4(3H)-quinazolinones in excellent yields.
M. Adib, E. Sheikhi, H. R. Bijanzadeh, Synlett, 2012, 23, 85-88.
In a convenient one-pot sequential cascade synthesis of 2-trifluoromethylquinazolin-4(3H)-ones, trifluoroacetic acid serves as inexpensive and readily available CF3 source. Condensation of anthranilic acids with TFA in the presence of T3P followed by condensation with amines provides the desired products in good yield.
S. Almeida, R. Marti, E. Vanoli, S. Abele, S. Tortoioli, J. Org. Chem., 2018, 83, 5104-5113.
The use of trifluoroacetic acid as a CF3 source provides 2-(trifluoromethyl)quinazolin-4-ones and 4-(trifluoromethyl)pyrrolo/indolo[1,2-a]quinoxalines without any catalysts or additives in very good yield.
S. Li, Y. Lv, J. Ren, L. Feng, C. Ma, Synthesis, 2022, 54, 3989-3998.
An efficient FeCl3-mediated cascade coupling/decarbonylative annulation reaction of readily available isatins with trifluoroacetimidoyl chlorides provides 2-(trifluoromethyl)quinazolin-4(3H)-ones derivatives in very good yields. A plausible reaction pathway has been proposed.
L.-C. Wang, S. Du, Z. Chen, X.-F. Wu, Org. Lett., 2020, 22, 5567-5571.
A convenient and efficient synthesis of 2-aminoquinazolin-4(3H)-ones and N1-substituted 2-aminoquinazolin-4(1H)-ones proceeds via carbonylative coupling of readily available ortho-iodoanilines with cyanamide followed by in situ ring closure of an N-cyanobenzamide intermediate. The products were easily isolated by precipitation in good yields for a wide range of substrates.
L. ┼kerbladh, L. R. Odell, J. Org. Chem., 2016, 81, 2966-2973.