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KI catalyzed one-pot synthesis of quinazolin-4(3H)-ones
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Chinese Chemical Letters 19 (2008) 1403–1406 www.elsevier.com/locate/cclet
Clean heterocyclic synthesis in water: I2/KI catalyzed one-pot synthesis of quinazolin-4(3H)-ones Mehdi Bakavoli *, Ali Shiri, Zahra Ebrahimpour, Mohammad Rahimizadeh Department of Chemistry, School of Sciences, Ferdowsi University, Mashhad 91775-1436, Iran Received 21 May 2008
Abstract Oxidative cyclocondensation of o-aminobenzamide with various aldehydes in water using I2/KI as catalyst and oxidizing agent is carried out giving the corresponding quinazolin-4(3H)-ones 3a–n in good to excellent yields. # 2008 Mehdi Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Iodine; Quinazolinone; Cyclocondensation
Environmental and economic pressures have been forcing the chemical community to search for more efficient ways of performing chemical transformations [1]. In this context, extraordinary attention has been paid to organic reactions in water in the past decade and research and development in this area are still increasing exponentially [2]. Water as a solvent is not only inexpensive and environmentally benign, but also gives completely new reactivity. Many of organic reactions carried out in aqueous media occur quickly with excellent yields. Reactions previously thought to be impossible to conduct in water are truly realized today. Quinazolin-4(3H)-ones are an important class of fused heterocycles with an array of biological activities such as inhibition of humane erythrocyte purine nucleoside phosphorylase [3] and poly(ADP-ribose) polymerase [4], treatment of diabetes and obesity [5], antagonist [6], anti-tumor [7], anti-inflammatory [8], insecticidal and antimicrobial activity [9]. They are also important building-blocks in total synthesis of natural products [10] and are the constituents of some isolated naturally occurring alkaloids [11]. Quinazolin-4(3H)-one derivatives were previously prepared by thermolysis of 3-arylideneamine-1,2,3-benzotriazine4-ones in paraffin oil at 300 8C [12] or condensation of aryl, alkyl and heteroaryl aldehydes in refluxing ethanol in the presence of CuCl2[13], but these methods are suffering from high-temperature reaction, low yield, long-reaction time as well as not being environmentally green. As part of our interests in the synthesis of quinazolinones [14] and due to the present awareness of applying environmentally benign strategies in organic synthesis, in this communication we report the I2/KI mediated oxidative cyclocondensation of o-amminobenzamide with various aldehydes for preparation of quinazolin-4(3H)-ones in ethanol–water (method A) or boiling water (method B). Initially, a solution of I2/KI was prepared by dissolving specified molecular iodine in a saturated aqueous solution of potassium iodide. We were delighted to find that exposure of o-aminobenzamide with aromatic aldehydes on stirring
* Corresponding author. E-mail address: [email protected] (M. Bakavoli). 1001-8417/$ – see front matter # 2008 Mehdi Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.07.016
1404
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
Scheme 1.
or refluxing in equimolar aqueous solution of I2/KI offered the 2-arylquinazolin-4(3H)-ones 3a–n in good to excellent isolated yields (Scheme 1). To assess the catalytic effect of I2/KI system, the typical reaction of o-aminobezamide with benzaldehyde was attempted in the absence of I2/KI catalyst at room temperature and also at reflux temperature, but only the starting materials were recovered. It can be assumed that in the I2/KI catalytic system, molecular iodine acts as a mild Lewis acid and oxidant and KI as a solublizing agent of molecular iodine in water. On the other hand water as the reaction media is mostly suitable because the products are practically insoluble in water and the work-up process can be much simplified. The reaction was performed in two methods. In method (A), reactants were first dissolved in minimum ethanol (ca. 1 mL) in order to make the mixture homogeneous then, the I2/KI aqueous solution was added and stirred at room temperature for desired times indicated in Table 1. Progress of the reaction was monitored by TLC. In method (B), the reaction was only conducted in I2/KI aqueous solution at reflux conditions. The products from both procedures were isolated in a practically pure form by simple Bu¨chner filtration of the final aqueous mixture. The structures of these compounds were established by comparing their physical and spectral data with those of their authentic samples (Table 1). From the data in Table 1 it can be concluded that the presence of the electron-withdrawing substituents on the aromatic ring like entry 3c, 3d, and 3e can increase the reaction rate and as the result the reaction times are shortened and the yields are increased while the electron donating substituents have the diverse effect. It should be pointed out here that in method (A), except 2-hydroxy-3-methoxybenzaldehyde, 4-hydroxy-3-methoxy-benzaldehyde and 1naphthaldehyde all other aldehydes we have examined were able to react at room temperature, and in general, yields from method (A) are higher compared with that of method (B). But the reactions in method (B) showed an attractive feature from the viewpoint of environmental benign. In conclusion we report here a one-pot procedure with moderate to high yields. The mildness, green, short reaction time, easy work-up and being applied for large-scale reactions are the superiorities of these two protocols for the synthesis of quinazolin-4(3H)-ones 3a–n through I2/KI catalyzed heterocyclization of o-aminobenzamide with different aldehydes. 1. Experimental General procedure for preparation of quinazolin-4(3H)-ones 3a–n. Method (A). o-Amminobenzamide (1 mmol, 0.136 g) and various substituted aromatic aldehydes (1 mmol) were added to ethanol (1 mL). The mixture was stirred for 5 min before the 0.1 mol/L aqueous solution of iodine/potassium iodide (10 mL) was added to this mixture. The mixture was stirred at room temperature except for compounds 3l, 3m and 3n which were refluxed for 15 min. The completion of the reaction was monitored by TLC using chloroform: methanol (8:2) as eluent. The resultant solid was filtered and washed with sodium thiosulphate solution 5% and hot water, respectively. The solid was pure enough but further purification can be achieved by recrystallization from ethanol. Method (B). To a mixture of o-amminobenzamide (1 mmol, 0.136 g) and various substituted aromatic aldehydes (1 mmol), an aqueous solution of iodine/potassium iodide (10 mL, 0.1 mol/L) was added. The mixture was refluxed for the indicated time (Table 1). The precipitant was filtered and washed with sodium thiosulphate solution 5% and hot water, respectively. The solid was pure enough but further purification can be achieved by recrystallization from ethanol. 2-(2-Hydroxy-3-methoxyphenyl)quinazolin-4(3H)-one (3l). 1H NMR (100 MHz, DMSO-d6, d ppm): 3.8 (s, 3H, CH3), 6.9–7.2 (m, 2H, Ar), 7.4–7.8 (m, 4H, Ar), 8.2 (d, 1H, J = 7.4 Hz, Ar), 12.5 (s, 1H, –NH), 14.1(s, 1H, –OH); IR (n, cm 1) 3405, 3220, 1650, 1100; EIMS: m/z 268. Anal. calcd. for C15H12N2O3: C, 67.16; H, 4.51; N, 10.44; found: C, 67.02; H, 4.39; N, 10.13.
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
1405
Table 1 Synthesis of quinazolinones 3a–n via I2/KI oxidative cyclization of o-aminobenzamide with various aromatic aldehydes. Entry
Ar
Time (min) Ethanol:water
Yield (%) Ethanol:water
water
30
95
90
235–237 [12]
35 b
45
97
75
241–243 [12]
3c
15 b
30
97
88
305–307 [12]
3d
20 b
60
95
80
315–316 [15a]
3e
20 b
30
89
75
363–264 [15b]
3f
25 b
45
98
78
351–353 [15b]
3g
30 b
60
85
81
208–210 [12]
3h
45 b
60
89
76
209–211 [12]
3i
30 b
60
84
77
248–249 [12]
3j
30 b
90
97
87
295–298 [7]
3k
30 b
90
84
79
254–257 [15a]
3l
15 c
120
88
71
293–295
3m
15 c
120
84
73
269–272 [15a]
3n
15 c
120
90
75
289–292 [15b]
3a
20
b
3b
a
Isolated yield, bat room temperature, creflux conditions.
water
mp (8C)
1406
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
References [1] N. Hall, Science 32 (1994) 266. [2] (a) C.J. Li, L. Chen, Chem. Soc. Rev. 35 (2006) 68; (b) Y. Gu, C. Ogawa, J. Kobayashi, Y. Mori, S. Kobayashi, Angew. Chem. Eng. Ed. 45 (2006) 7217; (c) C.J. Li, T.H. Chan, Comprehensive Organic Reactions in Aqueous Media, 2nd ed., Wiley, 2007; (d) H.C. Hailes, Org. Process Res. Dev. 11 (2007) 114; (e) D. Dallinger, C.O. Kappe, Chem. Rev. 107 (2007) 2546. [3] R.O. Dempcy, E.B. Skibo, Biochemistry 30 (1991) 8480. [4] K. Hattori, Y. Kido, H. Yamamoto, J. Ishida, A. Iwashita, K. Mihara, Bioorg. Med. Chem. Lett. 17 (2007) 5577. [5] J. Rudolph, W.P. Esler, S. O’Connor, P.D.G. Coish, P.L. Wickens, M. Brands, D.E. Bierer, B.T. Bloomquist, G. Bondar, L. Chen, C. Chuang, T.H. Claus, Z. Fathi, W. Fu, U.R. Khire, J.A. Kristie, X. Liu, D.B. Lowe, A.C. McClure, M. Michels, A.A. Ortiz, P.D. Ramsden, R.W. Schoenleber, T.E. Shelekhin, A. Vakalopoulos, W. Tang, W. Lei, L. Yi, S.J. Gardell, J.N. Livingston, L.J. Sweet, W.H. Bullock, J. Med. Chem. 50 (2007) 5202. [6] J.K. Padia, M. Field, J. Hinton, K. Meecham, J. Pablo, R. Pinnock, B.D. Roth, L. Singh, N. Suman-Chauhan, B.K. Trivedi, L. Webdale, J. Med. Chem. 41 (1998) 1042. [7] Y. Xia, Z. Yang, M. Hour, S. Kuo, P. Xia, K.F. Bastow, Y. Nakanishi, P. Nampoothiri, T. Hackl, E. Hamel, K. Lee, Bioorg. Med. Chem. Lett. 11 (2001) 1193. [8] M.R. Yadav, S.T. Shirude, A. Parmar, R. Balaraman, R. Giridhar, Chem. Heterocycl. Compd. Engl. Transl. (2006) 1198. [9] T. Singh, S. Sharma, V.K. Srivastava, A. Kumar, Indian J. Chem. B: Org. Med. Chem. 45 (2006) 2558. [10] J. Liu, Curr. Org. Syn. 4 (2007) 223. [11] S.B. Mhaske, N.P. Argade, Tetrahedron 62 (2006) 9787. [12] T.McC. Paterson, R.K. Smalley, H. Suschitzky, Synthesis (1975) 187. [13] R.J. Abdel-Jalil, W. Vo¨lter, M. Saeed, Tetrahedron Lett. 45 (2004) 3475. [14] (a) M. Rahimizadeh, Z. Tavallai, M. Bakavoli, Indian J. Chem. 43B (2004) 679; (b) M. Bakavoli, O. Sabzevari, M. Rahimizadeh, Chin. Chem. Lett. 18 (2007) 533; (c) M. Bakavoli, O. Sabsevari, M. Rahimizadeh, Chin. Chem. Lett. 18 (2007) 1466. [15] (a) T.A. Kilroe Smith, H. Stephen, Tetrahedron 1 (1957) 38; (b) J.J. Naleway, C.M.J. Fox, D. Robinhold, E. Terpetschnig, N.A. Olson, R.P. Haugland, Tetrahedron Lett. 35 (1994) 8569.
Chinese Chemical Letters 19 (2008) 1403–1406 www.elsevier.com/locate/cclet
Clean heterocyclic synthesis in water: I2/KI catalyzed one-pot synthesis of quinazolin-4(3H)-ones Mehdi Bakavoli *, Ali Shiri, Zahra Ebrahimpour, Mohammad Rahimizadeh Department of Chemistry, School of Sciences, Ferdowsi University, Mashhad 91775-1436, Iran Received 21 May 2008
Abstract Oxidative cyclocondensation of o-aminobenzamide with various aldehydes in water using I2/KI as catalyst and oxidizing agent is carried out giving the corresponding quinazolin-4(3H)-ones 3a–n in good to excellent yields. # 2008 Mehdi Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Iodine; Quinazolinone; Cyclocondensation
Environmental and economic pressures have been forcing the chemical community to search for more efficient ways of performing chemical transformations [1]. In this context, extraordinary attention has been paid to organic reactions in water in the past decade and research and development in this area are still increasing exponentially [2]. Water as a solvent is not only inexpensive and environmentally benign, but also gives completely new reactivity. Many of organic reactions carried out in aqueous media occur quickly with excellent yields. Reactions previously thought to be impossible to conduct in water are truly realized today. Quinazolin-4(3H)-ones are an important class of fused heterocycles with an array of biological activities such as inhibition of humane erythrocyte purine nucleoside phosphorylase [3] and poly(ADP-ribose) polymerase [4], treatment of diabetes and obesity [5], antagonist [6], anti-tumor [7], anti-inflammatory [8], insecticidal and antimicrobial activity [9]. They are also important building-blocks in total synthesis of natural products [10] and are the constituents of some isolated naturally occurring alkaloids [11]. Quinazolin-4(3H)-one derivatives were previously prepared by thermolysis of 3-arylideneamine-1,2,3-benzotriazine4-ones in paraffin oil at 300 8C [12] or condensation of aryl, alkyl and heteroaryl aldehydes in refluxing ethanol in the presence of CuCl2[13], but these methods are suffering from high-temperature reaction, low yield, long-reaction time as well as not being environmentally green. As part of our interests in the synthesis of quinazolinones [14] and due to the present awareness of applying environmentally benign strategies in organic synthesis, in this communication we report the I2/KI mediated oxidative cyclocondensation of o-amminobenzamide with various aldehydes for preparation of quinazolin-4(3H)-ones in ethanol–water (method A) or boiling water (method B). Initially, a solution of I2/KI was prepared by dissolving specified molecular iodine in a saturated aqueous solution of potassium iodide. We were delighted to find that exposure of o-aminobenzamide with aromatic aldehydes on stirring
* Corresponding author. E-mail address: [email protected] (M. Bakavoli). 1001-8417/$ – see front matter # 2008 Mehdi Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.07.016
1404
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
Scheme 1.
or refluxing in equimolar aqueous solution of I2/KI offered the 2-arylquinazolin-4(3H)-ones 3a–n in good to excellent isolated yields (Scheme 1). To assess the catalytic effect of I2/KI system, the typical reaction of o-aminobezamide with benzaldehyde was attempted in the absence of I2/KI catalyst at room temperature and also at reflux temperature, but only the starting materials were recovered. It can be assumed that in the I2/KI catalytic system, molecular iodine acts as a mild Lewis acid and oxidant and KI as a solublizing agent of molecular iodine in water. On the other hand water as the reaction media is mostly suitable because the products are practically insoluble in water and the work-up process can be much simplified. The reaction was performed in two methods. In method (A), reactants were first dissolved in minimum ethanol (ca. 1 mL) in order to make the mixture homogeneous then, the I2/KI aqueous solution was added and stirred at room temperature for desired times indicated in Table 1. Progress of the reaction was monitored by TLC. In method (B), the reaction was only conducted in I2/KI aqueous solution at reflux conditions. The products from both procedures were isolated in a practically pure form by simple Bu¨chner filtration of the final aqueous mixture. The structures of these compounds were established by comparing their physical and spectral data with those of their authentic samples (Table 1). From the data in Table 1 it can be concluded that the presence of the electron-withdrawing substituents on the aromatic ring like entry 3c, 3d, and 3e can increase the reaction rate and as the result the reaction times are shortened and the yields are increased while the electron donating substituents have the diverse effect. It should be pointed out here that in method (A), except 2-hydroxy-3-methoxybenzaldehyde, 4-hydroxy-3-methoxy-benzaldehyde and 1naphthaldehyde all other aldehydes we have examined were able to react at room temperature, and in general, yields from method (A) are higher compared with that of method (B). But the reactions in method (B) showed an attractive feature from the viewpoint of environmental benign. In conclusion we report here a one-pot procedure with moderate to high yields. The mildness, green, short reaction time, easy work-up and being applied for large-scale reactions are the superiorities of these two protocols for the synthesis of quinazolin-4(3H)-ones 3a–n through I2/KI catalyzed heterocyclization of o-aminobenzamide with different aldehydes. 1. Experimental General procedure for preparation of quinazolin-4(3H)-ones 3a–n. Method (A). o-Amminobenzamide (1 mmol, 0.136 g) and various substituted aromatic aldehydes (1 mmol) were added to ethanol (1 mL). The mixture was stirred for 5 min before the 0.1 mol/L aqueous solution of iodine/potassium iodide (10 mL) was added to this mixture. The mixture was stirred at room temperature except for compounds 3l, 3m and 3n which were refluxed for 15 min. The completion of the reaction was monitored by TLC using chloroform: methanol (8:2) as eluent. The resultant solid was filtered and washed with sodium thiosulphate solution 5% and hot water, respectively. The solid was pure enough but further purification can be achieved by recrystallization from ethanol. Method (B). To a mixture of o-amminobenzamide (1 mmol, 0.136 g) and various substituted aromatic aldehydes (1 mmol), an aqueous solution of iodine/potassium iodide (10 mL, 0.1 mol/L) was added. The mixture was refluxed for the indicated time (Table 1). The precipitant was filtered and washed with sodium thiosulphate solution 5% and hot water, respectively. The solid was pure enough but further purification can be achieved by recrystallization from ethanol. 2-(2-Hydroxy-3-methoxyphenyl)quinazolin-4(3H)-one (3l). 1H NMR (100 MHz, DMSO-d6, d ppm): 3.8 (s, 3H, CH3), 6.9–7.2 (m, 2H, Ar), 7.4–7.8 (m, 4H, Ar), 8.2 (d, 1H, J = 7.4 Hz, Ar), 12.5 (s, 1H, –NH), 14.1(s, 1H, –OH); IR (n, cm 1) 3405, 3220, 1650, 1100; EIMS: m/z 268. Anal. calcd. for C15H12N2O3: C, 67.16; H, 4.51; N, 10.44; found: C, 67.02; H, 4.39; N, 10.13.
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
1405
Table 1 Synthesis of quinazolinones 3a–n via I2/KI oxidative cyclization of o-aminobenzamide with various aromatic aldehydes. Entry
Ar
Time (min) Ethanol:water
Yield (%) Ethanol:water
water
30
95
90
235–237 [12]
35 b
45
97
75
241–243 [12]
3c
15 b
30
97
88
305–307 [12]
3d
20 b
60
95
80
315–316 [15a]
3e
20 b
30
89
75
363–264 [15b]
3f
25 b
45
98
78
351–353 [15b]
3g
30 b
60
85
81
208–210 [12]
3h
45 b
60
89
76
209–211 [12]
3i
30 b
60
84
77
248–249 [12]
3j
30 b
90
97
87
295–298 [7]
3k
30 b
90
84
79
254–257 [15a]
3l
15 c
120
88
71
293–295
3m
15 c
120
84
73
269–272 [15a]
3n
15 c
120
90
75
289–292 [15b]
3a
20
b
3b
a
Isolated yield, bat room temperature, creflux conditions.
water
mp (8C)
1406
M. Bakavoli et al. / Chinese Chemical Letters 19 (2008) 1403–1406
References [1] N. Hall, Science 32 (1994) 266. [2] (a) C.J. Li, L. Chen, Chem. Soc. Rev. 35 (2006) 68; (b) Y. Gu, C. Ogawa, J. Kobayashi, Y. Mori, S. Kobayashi, Angew. Chem. Eng. Ed. 45 (2006) 7217; (c) C.J. Li, T.H. Chan, Comprehensive Organic Reactions in Aqueous Media, 2nd ed., Wiley, 2007; (d) H.C. Hailes, Org. Process Res. Dev. 11 (2007) 114; (e) D. Dallinger, C.O. Kappe, Chem. Rev. 107 (2007) 2546. [3] R.O. Dempcy, E.B. Skibo, Biochemistry 30 (1991) 8480. [4] K. Hattori, Y. Kido, H. Yamamoto, J. Ishida, A. Iwashita, K. Mihara, Bioorg. Med. Chem. Lett. 17 (2007) 5577. [5] J. Rudolph, W.P. Esler, S. O’Connor, P.D.G. Coish, P.L. Wickens, M. Brands, D.E. Bierer, B.T. Bloomquist, G. Bondar, L. Chen, C. Chuang, T.H. Claus, Z. Fathi, W. Fu, U.R. Khire, J.A. Kristie, X. Liu, D.B. Lowe, A.C. McClure, M. Michels, A.A. Ortiz, P.D. Ramsden, R.W. Schoenleber, T.E. Shelekhin, A. Vakalopoulos, W. Tang, W. Lei, L. Yi, S.J. Gardell, J.N. Livingston, L.J. Sweet, W.H. Bullock, J. Med. Chem. 50 (2007) 5202. [6] J.K. Padia, M. Field, J. Hinton, K. Meecham, J. Pablo, R. Pinnock, B.D. Roth, L. Singh, N. Suman-Chauhan, B.K. Trivedi, L. Webdale, J. Med. Chem. 41 (1998) 1042. [7] Y. Xia, Z. Yang, M. Hour, S. Kuo, P. Xia, K.F. Bastow, Y. Nakanishi, P. Nampoothiri, T. Hackl, E. Hamel, K. Lee, Bioorg. Med. Chem. Lett. 11 (2001) 1193. [8] M.R. Yadav, S.T. Shirude, A. Parmar, R. Balaraman, R. Giridhar, Chem. Heterocycl. Compd. Engl. Transl. (2006) 1198. [9] T. Singh, S. Sharma, V.K. Srivastava, A. Kumar, Indian J. Chem. B: Org. Med. Chem. 45 (2006) 2558. [10] J. Liu, Curr. Org. Syn. 4 (2007) 223. [11] S.B. Mhaske, N.P. Argade, Tetrahedron 62 (2006) 9787. [12] T.McC. Paterson, R.K. Smalley, H. Suschitzky, Synthesis (1975) 187. [13] R.J. Abdel-Jalil, W. Vo¨lter, M. Saeed, Tetrahedron Lett. 45 (2004) 3475. [14] (a) M. Rahimizadeh, Z. Tavallai, M. Bakavoli, Indian J. Chem. 43B (2004) 679; (b) M. Bakavoli, O. Sabzevari, M. Rahimizadeh, Chin. Chem. Lett. 18 (2007) 533; (c) M. Bakavoli, O. Sabsevari, M. Rahimizadeh, Chin. Chem. Lett. 18 (2007) 1466. [15] (a) T.A. Kilroe Smith, H. Stephen, Tetrahedron 1 (1957) 38; (b) J.J. Naleway, C.M.J. Fox, D. Robinhold, E. Terpetschnig, N.A. Olson, R.P. Haugland, Tetrahedron Lett. 35 (1994) 8569.