Synthesis of quinazolines
Molecular iodine catalyses a benzylic sp3 C-H bond amination of 2-aminobenzaldehydes and 2-aminobenzophenones with benzylamines to provide quinazolines in very good yields. The use of oxygen as an oxidant combined with the transition-metal-, additive- and solvent-free conditions makes the methodology green and economical. 2-Amino≠benzyl alcohols could also used as starting materials.
D. S. Deshmukh, B. M. Bhanage, Synlett, 2018, 29, 979-985.
A mild o-iodoxybenzoic acid (IBX) mediated tandem reaction of readily available o-aminobenzylamine and aldehydes enables a facile synthesis of diversely substituted quinazolines and 3,4-dihydroquinazolines in very good yields.
S. Hati, S. Sen, Synthesis, 2016, 48, 1389-1398.
An efficient iridium-catalyzed acceptorless dehydrogenative coupling (ADC) reaction of 2-aminoarylmethanols and amides or nitriles provides various quinazolines in excellent yields. This method offers high atom-economy, mild reaction conditions, and simple operation.
H. Shui, Y. Zhong, L. Ouyang, N. Luo, R. Luo, Synthesis, 2022, 54, 2876-2884.
Readily available Co(OAc)2∑4 H2O catalyzes convenient and efficient dehydrogenative cyclizations of 2-aminoaryl alcohols and ketones or nitriles to provide quinolines or quinazolines in good yields in one pot under mild conditions. The present protocols offer an environmentally benign approach for the synthesis of N-heterocycles in good yields.
Z. Hao, X. Zhou, Z. Ma, C. Zhang, Z. Han, J. Lin, G.-L. Lu, J. Org. Chem., 2022, 87, 12596-12607.
An atom-economic nickel-catalyzed [4 + 2] annulation of benzylamines and nitriles provides a wide variety of multisubstituted quinazolines via C-H/N-H bond activation. The Ni catalyst is directed by an in situ formed amidine to activate the C-H bond in ortho.
R. Sikari, G. Chakraborty, A. K. Guin, N. D. Paul, J. Org. Chem., 2021, 86, 279-290.
A palladium(II)-catalyzed≠ cascade reaction of 2-aminobenzonitriles with triethyl orthocarboxylates and boronic acids provides 4-arylquinazolines in good yields. The method involves C(sp)-C(sp2) coupling followed by intramolecular C-N bond formation. The reaction was readily scaled up to gram quantity.
Z. Wang, W. Chen, C. He, G. Zhang, Y. Yu, Synthesis, 2021, 53, 1356-1364.
The condensation of 2-nitrobenzyl alcohols with arylacetic acids provides substituted quinazolines under mild conditions in the presence of urea as a nitrogen source, elemental sulfur as a promoter, DABCO as a base, and DMSO as a solvent. The reaction tolerates functionalities such as chloro, fluoro, trifluoromethyl, thienyl, and indolyl groups.
K. X. Nguyen, D. K. Nguyen, P. H. Pham, H. V. Le, T. T. Nguyen, N. T. S. Phan, Synlett, 2020, 31, 1112-1116.
Singlet diradical Ni(II) featuring two antiferromagnetically coupled singlet diradical diamine type ligands catalyzes simple, straightforward, and atom economic syntheses of quinolines, 2-aminoquinolines, and quinazolines in good yields via biomimetic dehydrogenative condensation/coupling reactions.
G. Chakraborty, R. Sikari, S. Das, R. Mondal, S. Sinha, S. Banerjee, N. D. Paul, J. Org. Chem., 2019, 84, 2626-2641.
An efficient copper-catalyzed cascade reaction of (2-aminophenyl)methanols with aldehydes using the combination of cerium nitrate hexahydrate and ammonium chloride leads to a wide range of 2-substituted quinazolines in good yields. The method tolerates a various functional groups and represents a convenient and practical strategy for synthesis of 2-substituted quinazoline derivatives.
Z. Chen, J. Chen, M. Liu, J. Ding, W. Gao, X. Huang, H. Wu, J. Org. Chem., 2013, 78, 11342-11348.
Acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol and 2-aminobenzylalcohol with benzonitrile enables the synthesis of quinazolines. The reactions are catalyzed by cheap and easy to prepare nickel catalysts, containing tetraaza macrocyclic ligands. A wide variety of substituted quinazolines were synthesized in good yields.
S. Parua, R. Sikari, S. Singha, G. Chakraborty, R. Mondal, N. D. Paul, J. Org. Chem., 2018, 83, 11154-11166.
A commercially available Ru3(CO)12/Xantphos/t-BuOK catalyst system enables a straightforward ruthenium-catalyzed dehydrogenative synthesis of 2-arylquinazolines. Various 2-aminoaryl methanols were efficiently converted in combination with different types of benzonitriles into the desired products in good yields. The synthetic protocol offers operational simplicity, high atom efficiency and broad substrate scope.
M. Chen, M. Zhang, B. Xiong, Z. Tan, W. Lv, H. Jiang, Org. Lett., 2014, 16, 6028-6031.
A novel and efficient copper-catalyzed cascade method for the synthesis of quinazolines in good yields uses readily available substituted (2-bromophenyl)methylamines and amidine hydrochlorides as the starting materials, inexpensive CuBr as the catalyst, and economical and environment friendly air as the oxidant. The procedure underwent sequential intermolecular N-arylation, intramolecular nucleophilic substitution and aerobic oxidation.
Q. Liu, Y. Zhao, H. Fu, C. Cheng, Synlett, 2013, 24, 2089-2094.
A simple and efficient, ligand-free copper-catalyzed approach to quinazoline derivatives uses readily available substituted (2-bromophenyl)methylamines and amides as starting materials. The cascade reaction includes a sequential Ullmann-type coupling and aerobic oxidation and provides a convenient and practical strategy for the synthesis of quinazoline derivatives.
C. Wang, S. Li, H. Liu, Y. Jiang, H. Fu, J. Org. Chem., 2010, 75, 7936-7938.
CuCl/DABCO/4-HO-TEMPO as the catalysts and oxygen as the terminal oxidant enabled an efficient aerobic oxidative synthesis of 2-substituted quinazolines and 4H-3,1-benzoxazines from the one-pot reaction of aldehydes with 2-aminobenzylamines and 2-aminobenzyl alcohols, respectively.
B. Han, X.-L. Yang, C. Wang, Y.-W. Bai, T.-C. Pan, X. Chen, W. Yu, J. Org. Chem., 2012, 77, 1136-1142.
An aerobic, iodine-catalyzed oxidative C(sp3)-H amination/C-N cleavage of tertiary amines affords a route to a wide range of quinazolines and quinazolinones in good to excellent yields via a domino ring annulation. The method is metal-free, peroxide-free, and operationally simple and represents a new avenue for multiple C-N bond formations.
Y. Yan, Y. Xu, B. Niu, H. Xie, Y. Liu, J. Org. Chem., 2015, 80, 5581-5587.
An in situ formed ruthenium catalyst enables a highly selective dehydrogenative coupling reaction of 2-aminophenyl ketones with amines to form quinazoline products. The deaminative coupling reaction of 2-aminobenzamides with amines provides quinazolinone products. The reactions work without using any reactive reagents or forming any toxic byproducts.
P. T. K. Arachchige, C. S. Yi, Org. Lett., 2019, 21, 3337-3341.
A facile and efficient method for the synthesis of 2-phenylquinazolines from 2-aminobenzophenones and benzylamines is catalyzed by ceric ammonium nitrate (CAN)-TBHP in acetonitrile. The corresponding 2-phenylquinazolines were obtained in good to excellent yields.
K. Karnakar, J. Shangkar, S. N. Murthy, K. Ramesch, Y. V. D. Nageshwar, Synlett, 2011, 1089-1096.
A facile approach allows the synthesis of 2-phenylquinazolines via a tandem reaction following sp3 C-H functionalization. Twenty-five examples of 2-phenylquinazolines were obtained from easily available 2-aminobenzophenones and benzylic amines with good to excellent yields.
J. Zhang, D. Zhu, C. Yu, C. Wan, Z. Wang, Org. Lett., 2010, 12, 2841-2843.
An iron-catalyzed C(sp3)-H oxidation, intramolecular C-N bond formation, and aromatization enables an efficient synthesis of quinazolines from 2-alkylamino N-H ketimine derivatives, which can be prepared by addition of various organometallic reagents to 2-alkylamino benzonitriles.
C.-y. Chen, F. He, G. Tang, H. Yuan, N. Li, J. Wang, R. Faessler, J. Org. Chem., 2018, 83, 2395-2401.
A palladium-catalyzed, three-component tandem reaction of 2-aminobenzonitriles, aldehydes, and arylboronic acids provides diverse quinazolines in good yields. The reaction tolerates bromo and iodo groups.
K. Hu, Q. Zhen, J. Gong, T. Cheng, L. Qi, Y. Shao, J. Chen, Org. Lett., 2018, 20, 3061-3064.
A copper-catalyzed reaction of benzonitriles and 2-ethynylanilines gave substituted quinazolines in the presence of molecular oxygen (O2) as sole oxidant via cleavage of the C-C triple bond and construction of new C-N and C-C bonds.
X. Wang, D. He, Y. Huang, Q. Fan, W. Wu, H. Jiang, J. Org. Chem., 2018, 83, 5458-5446.
C-H activation of arenes enables the synthesis of heterocycles via annulations between arenes and unsaturated coupling partners. Whereas nitriles fail to act as coupling partners, dioxazolones can be employed as synthons of nitriles, and subsequent coupling with arenes such as N-sulfinylimines and benzimidates bearing a functionalizable directing group provides two classes of quinazolines under Co(III)-catalysis.
F. Wang, H. Wang, Q. Wang, S. Yu, X. Li, Org. Lett., 2016, 18, 1306-1309.
An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2)-H bonds enables the constructions of quinazolines in good yields from N,N'-disubstituted amidines, which are readily prepared. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale.
Z. Lv, B. Wang, Z. Hu, Y. Zhou, W. Yu, J. Chang, J. Org. Chem., 2016, 81, 9924-9930.
A metal-free visible light-mediated oxidative coupling catalyzed by a photoredox organocatalyst enables a fast synthesis of multisubstituted quinazolines from readily available amidines. The protocol features low catalyst loading.
Z.-c. Shen, P. Yang, Y. Tang, J. Org. Chem., 2016, 81, 309-317.
Manganese triacetate mediates an oxidative C-4 arylation of 2-aryl-quinazoline 3-oxides with arylboronic acids to provide 2,4-diarylated quinazoline 3-oxides in very good yields. The method tolerates various substituents on both aromatic rings.
R. Samandram , M. «. KorukÁu, N. Coşkun, Synthesis, 2022, 54, 210-216.
An efficient route to 4-arylquinazolines in very good yields is carried out under mild conditions by the palladium-catalyzed arylation of quinazolin-4-ones with arylboronic acids in the presence of TsCl.
G. Qiu, P. Huang, Q. Yang, H. Lu, J. Xu, Z. Deng, M. Zhang, Y. Peng, Synthesis, 2013, 45, 3131-3136.
A fast and simple reaction of amidines gave benzimidazoles via iodine(III)-promoted oxidative C(sp3)-C(sp2) bond formation in nonpolar solvents, whereas the use of polar solvents favoured a C(sp2)-N bond formation to yield quinazolines. Further selective synthesis of quinazolines in polar solvent was realized using TEMPO as catalyst and K2S2O8 as the oxidant. No metal, base, or other additives were needed.
J.-P. Lin, F.-H. Zhang, Y.-Q. Long, Org. Lett., 2014, 16, 2822-2825.
The use of vinyl ethers as robust, inexpensive acetyl sources enables a mild, operationally simple Minisci C-H acetylation of N-heteroarenes. The reaction does not require a catalyst or high temperature and is therefore significantly more sustainable than previously reported methods in terms of cost, reagent toxicity, and waste generation.
J. Dong, J. Liu, H. Song, Y. Liu, Q. Wang, Org. Lett., 2021, 23, 4374-4378.
A Rh(III)-catalyzed tandem reaction of 2,1-benzisoxazoles with α-azido ketones provides (quinazolin-2-yl)methanone derivatives via denitrogenation of the α-azido ketones, aza-[4 + 2] cycloaddition, ring opening, and dehydration aromatization processes.
S. Liu, A.-J. Wang, M. Li, J. Zhang, G.-D. Yin, W.-M. Shu, W.-C. Yu, J. Org. Chem., 2022, 87, 11253-11260.
A Cu/Ag-catalyzed annulation of 3-aryl-2H-azirines with anthranils provides (quinazolin-2-yl)methanone derivatives. The copper-catalyzed cleavage of both the N-C2 azirine bond and the N-O anthranil bond is followed by a 1,3-hydroxyl migration and a β-N elimination.
Y. Sun, H. Sun, Y. Wang, F. Xie, Org. Lett., 2020, 22, 6756-6759.
A Rh(II)-catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with 2,1-benzisoxazoles provides quinazoline derivatives. Meanwhile, a Rh(II)-catalyzed formal [3 + 2] cycloaddition of N-sulfonyl-1,2,3-triazoles with 1,2-benzisoxazoles enables a rapid synthesis of functionalized imidazole derivatives.
X. Lei, M. Gao, Y. Tang, Org. Lett., 2016, 18, 4990-4993.
An efficient copper-catalyzed reaction of substituted 2-bromo-benzonitriles with amidines or guanidine allows an economical and practical synthesis of 4-aminoquinazoline and 2,4-diaminoquinazoline derivatives.
X. Yang, H. Liu, R. Qiao, Y. Jiang, Y. Zhao, Synlett, 2010, 101-106.
A highly efficient one-pot synthesis of 4-aminoquinazolines from easily available 2-iodo- or 2-bromobenzimidamides, aldehydes, and sodium azide proceeds via consecutive copper-catalyzed SNAr substitution, reduction, cyclization, oxidation and tautomerization.
L. Yang, H. Luo, Y. Sun, Z. Shi, K. Ni, F. Li, D. Chen, Synthesis, 2017, 49, 2535-2543.
A highly efficient Fe/Cu relay-catalyzed domino protocol for the synthesis of 2-phenylquinazolin-4-amines from commercially available ortho-halogenated benzonitriles, aldehydes, and sodium azide involves consecutive iron-mediated [3 + 2] cycloaddition, copper-catalyzed SNAr, reduction, cyclization, oxidation, and copper-catalyzed denitrogenation sequences. The formed structure is the privileged core in drugs and bioactive molecules.
F.-C. Jia, Z.-W. Zhou, C. Xu, Q. Cai, D.-K. Li, A.-X. Wu, Org. Lett., 2015, 17, 4236-4239.
An efficient method enables a synthesis of 4-amino-2-aryl(alkyl)quinazolines from readily available N-arylamidines and isonitriles via palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion.
Y. Wang, H. Wang, J. Peng, Q. Zhu, Org. Lett., 2011, 13, 4596-4599.
An efficient direct amination of quinazolin-4(3H)-ones using N,N-dimethylformamide as a nitrogen source affords the corresponding 4-(dimethylamino)quinazolines in high yields via efficient 4-toluenesulfonyl chloride mediated C-OH bond activation at room temperature.
X. Chen, Q. Yang, Y. Zhou, Z. Deng, X. Mao, Y. Peng, Synthesis, 2015, 47, 2055-2062.
A copper-catalyzed direct amination of cyclic amides in DMF forms aromatic heterocyclic amines with readily available reagents via a radical mechanism. The coordinating effect of the N1 atom provides assistance to the copper ions for the activation and amination of C-O bonds.
P. Chen, K. Luo, X. Yu, X. Yuan, X. Liu, J. Lin, Y. Jin, Org. Lett., 2020, 22, 6547-6551.
In an efficient redox-neutral [Cp*RhCl2]2/AgBF4 catalyzed double C-N bond formation sequence to prepare highly substituted quinazolines from benzimidates and dioxolanes as coupling partners, dioxazolones work as an internal oxidant to maintain the catalytic cycle. N-Unsubstituted imine not only acts as a directing group but also functions as a nucleophile in the postcoupling cyclization.
J. Wang, S. Zha, K. Chen, F. Zhang, C. Song, J. Zhu, Org. Lett., 2016, 18, 2062-2065.
An efficient rhodium- and copper-co-catalyzed C-H bond activation and [4 + 2] annulation enables the construction of bioactively important quinazolines. This aerobic oxidative protocol provides a useful application of simple azides in N-heterocycle synthesis with N2 and H2O as byproducts.
X. Wang, N. Jiao, Org. Lett., 2016, 18, 2150-2153.
A rapid and convenient free-radical-based synthesis of functionalized quinazolines relies on microwave-promoted reactions of O-phenyl oximes with aldehydes in the presence of ZnCl2. The method worked well with alkyl, aryl, and heterocyclic aldehydes and for a variety of substituents in the benzenic part of the molecule.
F. Portela-Cubillo, J. S. Scott, J. C. Walton, J. Org. Chem., 2009, 74, 4934-4942.
A photochemically induced Fries rearrangement of anilides gave several ortho-aminoacylbenzene derivatives that were acylated. These acylamides underwent rapid microwave-assited cyclization to 2,4-disubstituted quinazolines (and benzoquinazolines) in the presence of ammonium formate.
S. Ferrini, F. Ponticelli, M. Taddei, Org. Lett., 2007, 9, 69-72.
A tandem condensation of a cyanoimidate with an amine followed by reductive cyclization in an iron-HCl system enables an efficient route to N4-substituted 2,4-diaminoquinazolines. An additional N-alkylation can produce two fused heterocycles in a one-pot procedure.
P. Yin, N. Liu, Y.-X. Deng, Y. Chen, Y. Deng, L. He, J. Org. Chem., 2012, 77, 2649-2658.
Novel 10-membered pyrimidine enediynes were synthesized in seven and eight steps, respectively. These compounds were compared for their abilities to undergo Bergman cyclization both thermally and photochemically and to cleave dsDNA under the appropriate conditions.
N. Choy, B. Blanco, J. Wen, A. Krishan, K. C. Russel, Org. Lett., 2000, 2, 3761-3764.