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A facile synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinones catalyzed by scandium(III) triflate
Chinese Chemical Letters 18 (2007) 536–538 www.elsevier.com/locate/cclet
A facile synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinones catalyzed by scandium(III) triflate Jiu Xi Chen a, Hua Yue Wu a, Wei Ke Su a,b,* a
b
College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, China College of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical Engineering, Hangzhou 310014, China Received 27 December 2006
Abstract 2,3-Dihydro-2-aryl-4(1H)-quinazolinones were prepared in good yields via condensation of o-aminobenzamide with aldehydes promoted by a catalytic amount of Sc(OTf)3 under mild conditions. # 2007 Wei Ke Su. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Scandium(III) triflate; 2,3-Dihydro-2-aryl-4(1H)-quinazolinones; o-Aminobenzamide
2,3-Dihydro-2-aryl-4(1H)-quinazolinones are a class of fused heterocycles that have drawn much attention due to their potential biological and pharmaceutical activities as anti-tumor, diuretic, and herbicidal agents, as well as plant growth regulators [1]. Many classical methods for the construction of 2,3-dihydro-2-aryl-4(1H)-quinazolinones were reported in the literature [2–5]. A general procedure for the preparation of 2,3-dihydro-2-aryl-4(1H)-quinazolinones involves condensation of the appropriate derivatives of o-aminobenzamide with aldehyde using p-toluenesulfonic acid as a catalyst under vigorous conditions [2]. And other methods such as condensation of o-aminobenzamide with benzil followed by base catalyzed hydrolysis [3], reductive cyclization of o-nitrobenzamide [4], reduction of quinazolin4(3H)-ones are also reported for the synthesis of these compounds [5]. Very recently we reported a novel method for the synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinones by reductive cyclization of o-nitrobenzamide or oazidobenzamide with aldehydes and ketones promoted by metallic samarium and catalytic amount of iodine [6a] or SmI2 [6b]. Compared to conventional Lewis acids, metal triflates have advantages of water-tolerant, air-stable, recoverability of the agent from water, operational simplicity (not requiring anhydrous treatment), strong tolerance to oxygen, nitrogen, phosphorus, and sulfur-containing reaction substrates and functional groups [7]. Recently, we have successfully applied metal triflates into the synthesis of tetrazoles [8a], Biginelli reaction [8b] and Paal–Knorr condensation [8c] under solvent-free conditions. In continuation of our interest in green chemistry and Lewis acidcatalyzed organic reactions [8], herein we developed a green, simple and practical method for the synthesis of 2,3dihydro-2-aryl-4(1H)-quinazolinones from o-aminobenzamide compound and aldehyde using Sc(OTf)3 as catalyst (Scheme 1). * Corresponding author at: College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, China. E-mail address: [email protected] (W.K. Su). 1001-8417/$ – see front matter # 2007 Wei Ke Su. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.03.037
J.X. Chen et al. / Chinese Chemical Letters 18 (2007) 536–538
537
Scheme 1. Table 1 Synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinonesa Entry 1 2 3 4 5 6 7 8
c
a b c
R1
R2
Product
Time (min)
Yieldb (%)
mp (8C) (Lit.)
H H H H Cl Cl Cl Cl
C6H5 p-(OCH3)C6H4 p-(Cl)C6H4 p-(F)C6H4 C6H5 p-(CH3)C6H4 p-(F)C6H4 p-(NO2)C6H4
3a 3b 3c 3d 3e 3f 3g 3h
25 20 25 35 30 30 25 40
92, 89, 85 89 91 92 87 86 89 86
221–222 191–192 206–207 200–201 249–250 251–252 250–251 221–222
(220–222 [4e]) (180–182 [4e]) (205–206 [4e]) (248–249 [6a])
Reaction conditions: o-aminobenzamide compound 1 (5 mmol), aldehyde 2 (5 mmol), and Sc(OTf)3 (123 mg, 5 mol%), 70 8C. Isolated yield. Catalyst was reused for three times.
General procedure: to a solution of o-aminobenzamide compound 1 (5 mmol) and aldehyde 2 (5 mmol) in EtOH (2 mL), Sc(OTf)3 (123 mg, 5 mol%) was added. The mixture solution was stirred at 70 8C for an appropriate time as indicated in Table 1. After completion of the reaction, as indicated by TLC. The corresponding solid product 3 was obtained through simple filtration, which did not require further purification. The filtrate could be reused for the next batch reaction. As an example, compound 3a was obtained without any decrease of yield with the addition of compounds 1a and benzaldehyde and Sc(OTf)3 in a molar ratio of 1:1:0.05 in all three subsequent runs. The results are showed in Table 1. Compounds 3a–e are known, compounds 3f–h are new [9]. In summary, a new catalytic protocol to synthesize 2,3-dihydro-2-aryl-4(1H)-quinazolinones has been developed. Compared to previous reported methodologies, the present protocol features simple work-up, short reaction time, environmentally benign, easy recovery and mild reaction conditions with good yields. Currently, studies on the extension of this protocol are ongoing in our laboratory. Acknowledgments We are grateful to the National Basic Research Program (No. 2003CB114402), the National Natural Science Foundation of China (Nos. 20476098 and 20676123) and Wenzhou University Post-graduate Innovation Foundation (No. YCX0515) for financial support. References [1] (a) M.G. Biressi, G. Cantarelli, M. Carissimi, A. Cattaneo, F. Ravenna, Farmaco Ed. Sci. 24 (1969) 199; (b) P.R. Bhalla, B.L. Walworth, American Cyanamid Co., Eur. Pat. Appl. EP 58,822, Chem. Abstr. 98 (1983) 1669; (c) P.R. Bhalla, B.L. Walworth, American Cyanamid Co., U.S. Patent 4,431,440, Chem. Abstr. 100 (1984) 174857 (d) E. Hamel, C.M. Lin, J. Plowman, H. Wang, K. Lee, K.D. Paull, Biochem. Pharmacol. 51 (1996) 53; (e) M. Hour, L. Huang, S. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel, K. Lee, J. Med. Chem. 43 (2000) 4479. [2] S.D. Sharma, V. Kaur, Synthesis (1989) 677. [3] J.A. Moore, G.J. Sutherland, R. Sowerby, E.G. Kelly, S. Palermo, W. Webster, J. Org. Chem. (1969) 887. [4] (a) D.Q. Shi, L.C. Rong, J.X. Wang, X.S. Wang, S.J. Tu, H.W. Hu, Chem. J. Chin. Univ. 25 (2004) 2051; (b) D.Q. Shi, J.X. Wang, L.C. Rong, Q.Y. Zhuang, S.J. Tu, H.W. Hu, J. Chem. Res. Synop. (2003) 671; (c) D.Q. Shi, L.C. Rong, J.X. Wang, Q.Y. Zhuang, X.S. Wang, H.W. Hu, Tetrahedron Lett. 44 (2003) 3199; (d) D.Q. Shi, C.L. Shi, J.X. Wang, L.C. Rong, Q.Y. Zhuang, X.S. Wang, J. Heterocyclic Chem. 40 (2005) 173; (e) G.P. Cai, X.L. Xu, Z.F. Li, W.P. Weber, P. Lu, J. Heterocyclic Chem. 39 (2002) 1271.
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J.X. Chen et al. / Chinese Chemical Letters 18 (2007) 536–538
[5] H. Asakawa, M. Matano, Chem. Pharm. Bull. 27 (1979) 1287. [6] (a) W.K. Su, B.B. Yang, Aust. J. Chem. 55 (2002) 695; (b) W.K. Su, B.B. Yang, J. Chem. Res. Synop. (2002) 604. [7] S. Kobayashi, M. Sugiura, H. Kitagawa, W.L. Lam, Chem. Rev. 102 (2002) 2227. [8] (a) W.K. Su, J.J. Li, Z.G. Zheng, Y.C. Shen, Tetrahedron Lett. 46 (2005) 6037; (b) W.K. Su, Z. Hong, W.G. Shan, X.X. Zhang, Eur. J. Org. Chem. 2 (2006) 723; (c) J.X. Chen, H.Y. Wu, Z.G. Zheng, C. Jin, X.X. Zhang, W.K. Su, Tetrahedron Lett. 47 (2006) 5383; (d) J.X. Chen, H.Y. Wu, C. Jin, X.X. Zhang, Y.Y. Xie, W.K. Su, Green Chem. 8 (2006) 330. [9] Selected data of 3f: 1H NMR (400 MHz, DMSO-d6 d ppm): 2.29 (s, 3H), 5.74 (s, 1H), 6.77 (d, 1H, J = 8.4 Hz), 7.19 (d, 2H, J = 8.0 Hz), 7.26– 7.31 (m, 2H), 7.19 (d, 2H, J = 8.0 Hz), 7.54 (d, 1H, J = 2.4 Hz), 8.44 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 20.7, 66.2, 116.1, 116.4, 120.7, 126.8, 128.9, 129.2, 133.0, 137.9, 142.7, 146.6, 162.5; MS (EI) m/z (%): 273 ([M + 2]+, 32), 271 (M+, 95), 181 (100), 183 (25), 154 (34); elemental analysis Calcd. for C15H13ClN2O: C, 66.06; H, 4.80; found: C 66.01; H 4.88; 3g: 1H NMR (400 MHz, DMSO-d6 d ppm): 5.84 (s, 1H), 6.80 (d, 1H, J = 8.4 Hz), 7.22–7.31 (m, 3H), 7.35 (s, 1H), 7.54–7.57 (m, 3H), 8.51 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 65.9, 115.2 (d, 2JCF = 21.2 Hz), 116.1, 116.5, 121.0, 126.5, 129.1 (d, 3JCF = 8.3 Hz), 133.2, 137.4, 146.6, 162.2 (d, 1JCF = 243.4 Hz), 162.5; MS (EI) m/z (%): 278 ([M + 2]+, 5), 276 (M+, 15), 181 (100), 183 (25), 154 (30); elemental analysis Calcd. for C14H10ClFN2O: C, 60.77; H, 3.64; found: C 60.82; H 3.69; 3h: 1H NMR (400 MHz, DMSO-d6 d ppm): 6.01 (s, 1H), 6.85 (d, 1H, J = 8.8 Hz), 7.32 (dd, 1H, J = 2.4, 8.8 Hz), 7.58 (m, 2 H), 7.77 (d, 2H, J = 8.8 Hz), 8.29 (d, 2H, J = 8.8 Hz), 8.76 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 65.2, 116.0, 116.6, 121.2, 123.7, 126.5, 128.0, 133.4, 146.0, 147.5, 148.9, 162.2; MS (EI) m/z (%): 305 ([M + 2]+, 10), 303 (M+, 31), 181 (100), 183 (31), 154 (39); elemental analysis Calcd. for C14H10ClN3O3: C, 55.37; H, 3.32; found: C 55.32; H 3.25.
A facile synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinones catalyzed by scandium(III) triflate Jiu Xi Chen a, Hua Yue Wu a, Wei Ke Su a,b,* a
b
College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, China College of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical Engineering, Hangzhou 310014, China Received 27 December 2006
Abstract 2,3-Dihydro-2-aryl-4(1H)-quinazolinones were prepared in good yields via condensation of o-aminobenzamide with aldehydes promoted by a catalytic amount of Sc(OTf)3 under mild conditions. # 2007 Wei Ke Su. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Scandium(III) triflate; 2,3-Dihydro-2-aryl-4(1H)-quinazolinones; o-Aminobenzamide
2,3-Dihydro-2-aryl-4(1H)-quinazolinones are a class of fused heterocycles that have drawn much attention due to their potential biological and pharmaceutical activities as anti-tumor, diuretic, and herbicidal agents, as well as plant growth regulators [1]. Many classical methods for the construction of 2,3-dihydro-2-aryl-4(1H)-quinazolinones were reported in the literature [2–5]. A general procedure for the preparation of 2,3-dihydro-2-aryl-4(1H)-quinazolinones involves condensation of the appropriate derivatives of o-aminobenzamide with aldehyde using p-toluenesulfonic acid as a catalyst under vigorous conditions [2]. And other methods such as condensation of o-aminobenzamide with benzil followed by base catalyzed hydrolysis [3], reductive cyclization of o-nitrobenzamide [4], reduction of quinazolin4(3H)-ones are also reported for the synthesis of these compounds [5]. Very recently we reported a novel method for the synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinones by reductive cyclization of o-nitrobenzamide or oazidobenzamide with aldehydes and ketones promoted by metallic samarium and catalytic amount of iodine [6a] or SmI2 [6b]. Compared to conventional Lewis acids, metal triflates have advantages of water-tolerant, air-stable, recoverability of the agent from water, operational simplicity (not requiring anhydrous treatment), strong tolerance to oxygen, nitrogen, phosphorus, and sulfur-containing reaction substrates and functional groups [7]. Recently, we have successfully applied metal triflates into the synthesis of tetrazoles [8a], Biginelli reaction [8b] and Paal–Knorr condensation [8c] under solvent-free conditions. In continuation of our interest in green chemistry and Lewis acidcatalyzed organic reactions [8], herein we developed a green, simple and practical method for the synthesis of 2,3dihydro-2-aryl-4(1H)-quinazolinones from o-aminobenzamide compound and aldehyde using Sc(OTf)3 as catalyst (Scheme 1). * Corresponding author at: College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, China. E-mail address: [email protected] (W.K. Su). 1001-8417/$ – see front matter # 2007 Wei Ke Su. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.03.037
J.X. Chen et al. / Chinese Chemical Letters 18 (2007) 536–538
537
Scheme 1. Table 1 Synthesis of 2,3-dihydro-2-aryl-4(1H)-quinazolinonesa Entry 1 2 3 4 5 6 7 8
c
a b c
R1
R2
Product
Time (min)
Yieldb (%)
mp (8C) (Lit.)
H H H H Cl Cl Cl Cl
C6H5 p-(OCH3)C6H4 p-(Cl)C6H4 p-(F)C6H4 C6H5 p-(CH3)C6H4 p-(F)C6H4 p-(NO2)C6H4
3a 3b 3c 3d 3e 3f 3g 3h
25 20 25 35 30 30 25 40
92, 89, 85 89 91 92 87 86 89 86
221–222 191–192 206–207 200–201 249–250 251–252 250–251 221–222
(220–222 [4e]) (180–182 [4e]) (205–206 [4e]) (248–249 [6a])
Reaction conditions: o-aminobenzamide compound 1 (5 mmol), aldehyde 2 (5 mmol), and Sc(OTf)3 (123 mg, 5 mol%), 70 8C. Isolated yield. Catalyst was reused for three times.
General procedure: to a solution of o-aminobenzamide compound 1 (5 mmol) and aldehyde 2 (5 mmol) in EtOH (2 mL), Sc(OTf)3 (123 mg, 5 mol%) was added. The mixture solution was stirred at 70 8C for an appropriate time as indicated in Table 1. After completion of the reaction, as indicated by TLC. The corresponding solid product 3 was obtained through simple filtration, which did not require further purification. The filtrate could be reused for the next batch reaction. As an example, compound 3a was obtained without any decrease of yield with the addition of compounds 1a and benzaldehyde and Sc(OTf)3 in a molar ratio of 1:1:0.05 in all three subsequent runs. The results are showed in Table 1. Compounds 3a–e are known, compounds 3f–h are new [9]. In summary, a new catalytic protocol to synthesize 2,3-dihydro-2-aryl-4(1H)-quinazolinones has been developed. Compared to previous reported methodologies, the present protocol features simple work-up, short reaction time, environmentally benign, easy recovery and mild reaction conditions with good yields. Currently, studies on the extension of this protocol are ongoing in our laboratory. Acknowledgments We are grateful to the National Basic Research Program (No. 2003CB114402), the National Natural Science Foundation of China (Nos. 20476098 and 20676123) and Wenzhou University Post-graduate Innovation Foundation (No. YCX0515) for financial support. References [1] (a) M.G. Biressi, G. Cantarelli, M. Carissimi, A. Cattaneo, F. Ravenna, Farmaco Ed. Sci. 24 (1969) 199; (b) P.R. Bhalla, B.L. Walworth, American Cyanamid Co., Eur. Pat. Appl. EP 58,822, Chem. Abstr. 98 (1983) 1669; (c) P.R. Bhalla, B.L. Walworth, American Cyanamid Co., U.S. Patent 4,431,440, Chem. Abstr. 100 (1984) 174857 (d) E. Hamel, C.M. Lin, J. Plowman, H. Wang, K. Lee, K.D. Paull, Biochem. Pharmacol. 51 (1996) 53; (e) M. Hour, L. Huang, S. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel, K. Lee, J. Med. Chem. 43 (2000) 4479. [2] S.D. Sharma, V. Kaur, Synthesis (1989) 677. [3] J.A. Moore, G.J. Sutherland, R. Sowerby, E.G. Kelly, S. Palermo, W. Webster, J. Org. Chem. (1969) 887. [4] (a) D.Q. Shi, L.C. Rong, J.X. Wang, X.S. Wang, S.J. Tu, H.W. Hu, Chem. J. Chin. Univ. 25 (2004) 2051; (b) D.Q. Shi, J.X. Wang, L.C. Rong, Q.Y. Zhuang, S.J. Tu, H.W. Hu, J. Chem. Res. Synop. (2003) 671; (c) D.Q. Shi, L.C. Rong, J.X. Wang, Q.Y. Zhuang, X.S. Wang, H.W. Hu, Tetrahedron Lett. 44 (2003) 3199; (d) D.Q. Shi, C.L. Shi, J.X. Wang, L.C. Rong, Q.Y. Zhuang, X.S. Wang, J. Heterocyclic Chem. 40 (2005) 173; (e) G.P. Cai, X.L. Xu, Z.F. Li, W.P. Weber, P. Lu, J. Heterocyclic Chem. 39 (2002) 1271.
538
J.X. Chen et al. / Chinese Chemical Letters 18 (2007) 536–538
[5] H. Asakawa, M. Matano, Chem. Pharm. Bull. 27 (1979) 1287. [6] (a) W.K. Su, B.B. Yang, Aust. J. Chem. 55 (2002) 695; (b) W.K. Su, B.B. Yang, J. Chem. Res. Synop. (2002) 604. [7] S. Kobayashi, M. Sugiura, H. Kitagawa, W.L. Lam, Chem. Rev. 102 (2002) 2227. [8] (a) W.K. Su, J.J. Li, Z.G. Zheng, Y.C. Shen, Tetrahedron Lett. 46 (2005) 6037; (b) W.K. Su, Z. Hong, W.G. Shan, X.X. Zhang, Eur. J. Org. Chem. 2 (2006) 723; (c) J.X. Chen, H.Y. Wu, Z.G. Zheng, C. Jin, X.X. Zhang, W.K. Su, Tetrahedron Lett. 47 (2006) 5383; (d) J.X. Chen, H.Y. Wu, C. Jin, X.X. Zhang, Y.Y. Xie, W.K. Su, Green Chem. 8 (2006) 330. [9] Selected data of 3f: 1H NMR (400 MHz, DMSO-d6 d ppm): 2.29 (s, 3H), 5.74 (s, 1H), 6.77 (d, 1H, J = 8.4 Hz), 7.19 (d, 2H, J = 8.0 Hz), 7.26– 7.31 (m, 2H), 7.19 (d, 2H, J = 8.0 Hz), 7.54 (d, 1H, J = 2.4 Hz), 8.44 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 20.7, 66.2, 116.1, 116.4, 120.7, 126.8, 128.9, 129.2, 133.0, 137.9, 142.7, 146.6, 162.5; MS (EI) m/z (%): 273 ([M + 2]+, 32), 271 (M+, 95), 181 (100), 183 (25), 154 (34); elemental analysis Calcd. for C15H13ClN2O: C, 66.06; H, 4.80; found: C 66.01; H 4.88; 3g: 1H NMR (400 MHz, DMSO-d6 d ppm): 5.84 (s, 1H), 6.80 (d, 1H, J = 8.4 Hz), 7.22–7.31 (m, 3H), 7.35 (s, 1H), 7.54–7.57 (m, 3H), 8.51 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 65.9, 115.2 (d, 2JCF = 21.2 Hz), 116.1, 116.5, 121.0, 126.5, 129.1 (d, 3JCF = 8.3 Hz), 133.2, 137.4, 146.6, 162.2 (d, 1JCF = 243.4 Hz), 162.5; MS (EI) m/z (%): 278 ([M + 2]+, 5), 276 (M+, 15), 181 (100), 183 (25), 154 (30); elemental analysis Calcd. for C14H10ClFN2O: C, 60.77; H, 3.64; found: C 60.82; H 3.69; 3h: 1H NMR (400 MHz, DMSO-d6 d ppm): 6.01 (s, 1H), 6.85 (d, 1H, J = 8.8 Hz), 7.32 (dd, 1H, J = 2.4, 8.8 Hz), 7.58 (m, 2 H), 7.77 (d, 2H, J = 8.8 Hz), 8.29 (d, 2H, J = 8.8 Hz), 8.76 (s, 1H); 13C NMR (100 MHz, DMSO-d6 d ppm): 65.2, 116.0, 116.6, 121.2, 123.7, 126.5, 128.0, 133.4, 146.0, 147.5, 148.9, 162.2; MS (EI) m/z (%): 305 ([M + 2]+, 10), 303 (M+, 31), 181 (100), 183 (31), 154 (39); elemental analysis Calcd. for C14H10ClN3O3: C, 55.37; H, 3.32; found: C 55.32; H 3.25.