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Synthesis and characterization of novel calix[6]phyrin derivatives
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Chinese Chemical Letters 19 (2008) 1199–1201 www.elsevier.com/locate/cclet
Synthesis and characterization of novel calix[6]phyrin derivatives Wei Chen, Tian Jun Liu * Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin 300192, China Received 23 April 2008
Abstract Three novel calix[6]phyrin derivatives have been synthesized by reaction of corresponding tripyrrane with aromatic aldehyde. The reaction condition was optimized and the structures of these compounds have been characterized by NMR and MS. # 2008 Tian Jun Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Calix[6]phyrin; Synthesis; Effect of catalysts
The development of synthetic receptors and chemosensors for anions has attracted much attention in recent years as the fundamental role of anions in biological and chemical processes has become increasingly understood [1,2]. Many new types of receptor has been designed, such as calyx[4]arene [3], cyclophane [4], porphyrin [5], etc. Recently, a new hybrid of porphyrin and calix[n]arene type compounds calix[6]phyrin has been synthesized by Sessler and coworkers, they isolated a 5,5-10,10-20,20,25,25-octamethylcalix[6]phyrin [6], which has a deep cavity structure, acts as an anion receptor both in solution and in the solid state. This fascinating characteristics of this nonplanar porphyrin species aroused our interest. Nonplanar macrocyclic compounds possesses reflexible conformation, and its periphery structure exert a large influence on its properties and transient state, which displays difference in its recognition abilities as well as its synthetic yields. In order to study periphery structure effect on calix[6]phyrin properties such as molecular recognition mechanism, as well as its synthetic generality, here a series of calix[6]phyrin with different substituents have been synthesized. Additionally, because of low yield of the synthetic macrocyclic porphyrin, an effective synthetic method for this kind of compounds is a challenge in organic methodology, so the effect of nature and concentration of the catalyst on the yield of the resultant product was emphasized here. 1. Experimental In the experiment, all reagents are commercially available and purified by standard methods prior to use. 1H NMR spectra were measured on a Mercur Plus-400 at 300 MHz spectrometer at 298 K in CdCl3. High-resolution mass spectra were obtained on a Ionspec FT-MS 7.0T mass spectrometer. UV–vis spectra were recorded on a 384plus molecular spectrophotometer in spectrophotometric grade acetonitrile. The tripyrranes 1a–d were prepared according to the literature procedures [6,7]. * Corresponding author. E-mail address: [email protected] (T.J. Liu). 1001-8417/$ – see front matter # 2008 Tian Jun Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.06.055
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W. Chen, T.J. Liu / Chinese Chemical Letters 19 (2008) 1199–1201
Scheme 1.
The procedure for the synthesis of compounds 2a–d [6]: a solution of tripyrrane 1 (2.3 mmol) in dry dichloromethane (100 ml) was degassed by bubbling with argon for 10 min. Pentafluorobenzaldehyde (2.5 mmol) was then added and the reaction mixture was stirred under argon for 10–12 h. DDQ (2.3 mmol) was simply added to the solution then stirred for another 2 h. The solvent was purified crudely by chromatography on a basic alumina column eluted with dichloromethane. The collected pink solution was evaporated under reduced pressure. The residue was purified through silica gel chromatography using hexane–dichloromethane mixture(2:1 v/v) as eluent gave the products 2. And importantly, 0.2 equiv. acid catalyst is necessary in the synthesis of 2c and 2d. The structures of 2a–d were confirmed by 1H NMR and QFT-ESI, and 2b–d were new compounds [8] (Scheme 1). 2. Discussion and conclusion The macrocyclic compounds synthesis is sensitive to the substrate structure and the catalyst used [9,10]. We have carefully studied the effect of nature and concentration of the catalyst on the yield of the resultant product. To understand the role of the catalyst in the condensation reaction, we have carried out the reaction under the following categories: (a) without the use of catalyst and (b) use different catalyst, for example, trifluoroacetic acid (TFA) and paratoluenesulphonic acid (TsOH). The results of these studies are tabulated in Table 1, almost in each case the yields is less 10%. It is known that the condensation reaction between pyrrole derivatives and electron with-drawing Table 1 The effect of nature and concentration of the catalyst on the yield of the resultant product Entry
Product
Condition
Yield (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
2a 2b 2c 2d 2a 2b 2c 2d 2a 2a 2a 2b 2c 2d
0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TFA 0.2 equiv. TFA 0.2 equiv. TFA 0.2 equiv. TFA 1.0 equiv. TFA 2.0 equiv. TFA No catalyst No catalyst No catalyst No catalyst
8.3 8 6.5 7.9 6.7 7.2 5 7.6 2.3 1.5 9.3 10 No reaction No reaction
W. Chen, T.J. Liu / Chinese Chemical Letters 19 (2008) 1199–1201
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aldehydes gives the corresponding corrole in the absence of any catalyst [11,12], we were able to isolate 2a and 2b, while 2c and 2d were not formed under the same condition because of the stereo-factor and lower reactivity. The tripyrrane 1 is unstable in the presence of acid, so in the presence of 0.2 equiv. catalyst either TsOH or TFA in our cases, 2a and 2b have a lower yield due to the acidolysis of tripyrrane. And in condition of higher molar ratio of acid catalyst, for example 1 or 2 equiv., the yield of the desired product decreased acutely, yields are less than 3%. As for the structure of catalysts used, the results above showed that in the same molar ratio TsOH and TFA showed less difference in the product yields. Future work will be directed towards synthesizing other calix[n]phyrin derivatives and investigating their recognition ability as receptor of anions, cations as well as neutral molecules. Acknowledgments Financial support from National Basic Research Program of China (No. 2006CB705703-2) and National Natural Science Foundation of China (No. 50573092) is acknowledged. References [1] [2] [3] [4] [5] [6] [7] [8]
[9] [10] [11] [12]
C. Suksai, T. Tuntulani, Chem. Soc. Rev. 32 (2003) 192. R. Martı´nez-Ma´n˜ez, F. Sanceno´n, Chem. Rev. 103 (11) (2003) 4419. B. Tomapatanaget, T. Tuntulani, et al. Org. Lett. 5 (9) (2003) 1539. M.C. Rotger, J.F. Gonza´lez, et al. J. Org. Chem. 59 (16) (1994) 4501. T. Mizutani, K. Wada, et al. J. Am. Chem. Soc. 121 (49) (1999) 11425. C. Bucher, R.S. Zimmerman, et al. J. Am. Chem. Soc. 123 (9) (2001) 2099. J.W. Ka, C.H. Lee, Tetrahedron Lett. 41 (2000) 4609. 5,5-10,10-20,20-25,25-Octamethylcalix[6]phyrin (2a): 1H NMR (CdCl3 (ppm)): 1.66 (bs, H2O), 1.69 (s, 24H, –CH3), 5.30 (s, 2H, CH2Cl2), 5.96 (d, 4H), J = 2.4 Hz, (H), 6.11 (d, 4H), J = 4.5 Hz, (H), 6.21 (d, 4H), J = 3.9 Hz, (H), 7.87 (bs, NH), 12.35 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 436 (2.3); QFT-ESI: m/z 915.3222 (M+H) + (calcd. for C50H40F10N6+H+915.3228). 5-10-20-25-Tetraethyl-5-10-20-25tetramethylcalix[6]phyrin (2b): 1H NMR (CdCl3 (ppm)): 0.86 (t, 12H, J = 7 Hz, –CH3), 1.26 (s, 12H, –CH3), 1.65 (bs, H2O), 1.707–1.764 (m, 8H, –CH2–), 5.30 (s, 2H, CH2Cl2), 5.96 (d, 4H, J = 2.1Hz, (H), 6.12 (d, 4H, J = 4.2 Hz, (H), 6.21 (d,4H, J = 4.5 Hz, (H), 7.67 (bs, NH), 12.31 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 436 (2.4); QFT-ESI: m/z 971.3848 (M+H) + (calcd. for C54H48F10N6+H+971.3853). 5-10-2025-Tetramethyl-5-10-20-25-tetraphenylcalix[6]phyrin (2c):1H NMR (CdCl3 (ppm)): 1.41 (s, 24H, –CH3), 1.66 (bs, H2O), 5.30 (s, 2H, CH2Cl2), 5.95 (d, 4H), J = 2.7 Hz, (H), 6.15 (d, 4H), J = 5.1 Hz, (H), 6.21 (d, 4H), J = 4.5 Hz, (H), 7.25 (s, 20H, –Ar), 7.91 (bs, NH), 12.23 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 446 (2.2); QFT-ESI: m/z 1163.3867 (M+H) + (calcd. for C70H48F10N6+H+1163.3853). 5-10-2025-Tetracyclohexylcalix[6]phyrin (2d): 1H NMR (CdCl3 (ppm)): 1.39–1.49 (m, 24H, –CH2–CH2–CH2–), 1.66 (bs, H2O), 2.04 (t, 16H, J = 9 Hz, C–CH2–), 5.30 (s, 2H, CH2Cl2), 5.97 (d, 4H), J = 2.4 Hz, (H), 6.13 (d, 4H), J = 4.2 Hz, (H), 6.22 (d, 4H), J = 3.9 Hz, (H), 7.83 (bs, NH), 12.34 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 460 (3.0); QFT-ESI: m/z 1075.4483 (M+H) + (calcd. for C62H56F10N6+H+1075.4480). S.J. Narayanan, B. Sridevi, et al. J. Am. Chem. Soc. 121 (39) (1999) 9053. D. Gryko, J.S. Lindsey, J. Org. Chem. 65 (7) (2000) 2249. Z. Gross, N. Galili, I. Saltsman, Angew. Chem. Int. Ed. 38 (10) (1999) 1427. D.T. Gryko, Chem. Commun. (2000) 2243.
Chinese Chemical Letters 19 (2008) 1199–1201 www.elsevier.com/locate/cclet
Synthesis and characterization of novel calix[6]phyrin derivatives Wei Chen, Tian Jun Liu * Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin 300192, China Received 23 April 2008
Abstract Three novel calix[6]phyrin derivatives have been synthesized by reaction of corresponding tripyrrane with aromatic aldehyde. The reaction condition was optimized and the structures of these compounds have been characterized by NMR and MS. # 2008 Tian Jun Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Calix[6]phyrin; Synthesis; Effect of catalysts
The development of synthetic receptors and chemosensors for anions has attracted much attention in recent years as the fundamental role of anions in biological and chemical processes has become increasingly understood [1,2]. Many new types of receptor has been designed, such as calyx[4]arene [3], cyclophane [4], porphyrin [5], etc. Recently, a new hybrid of porphyrin and calix[n]arene type compounds calix[6]phyrin has been synthesized by Sessler and coworkers, they isolated a 5,5-10,10-20,20,25,25-octamethylcalix[6]phyrin [6], which has a deep cavity structure, acts as an anion receptor both in solution and in the solid state. This fascinating characteristics of this nonplanar porphyrin species aroused our interest. Nonplanar macrocyclic compounds possesses reflexible conformation, and its periphery structure exert a large influence on its properties and transient state, which displays difference in its recognition abilities as well as its synthetic yields. In order to study periphery structure effect on calix[6]phyrin properties such as molecular recognition mechanism, as well as its synthetic generality, here a series of calix[6]phyrin with different substituents have been synthesized. Additionally, because of low yield of the synthetic macrocyclic porphyrin, an effective synthetic method for this kind of compounds is a challenge in organic methodology, so the effect of nature and concentration of the catalyst on the yield of the resultant product was emphasized here. 1. Experimental In the experiment, all reagents are commercially available and purified by standard methods prior to use. 1H NMR spectra were measured on a Mercur Plus-400 at 300 MHz spectrometer at 298 K in CdCl3. High-resolution mass spectra were obtained on a Ionspec FT-MS 7.0T mass spectrometer. UV–vis spectra were recorded on a 384plus molecular spectrophotometer in spectrophotometric grade acetonitrile. The tripyrranes 1a–d were prepared according to the literature procedures [6,7]. * Corresponding author. E-mail address: [email protected] (T.J. Liu). 1001-8417/$ – see front matter # 2008 Tian Jun Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.06.055
1200
W. Chen, T.J. Liu / Chinese Chemical Letters 19 (2008) 1199–1201
Scheme 1.
The procedure for the synthesis of compounds 2a–d [6]: a solution of tripyrrane 1 (2.3 mmol) in dry dichloromethane (100 ml) was degassed by bubbling with argon for 10 min. Pentafluorobenzaldehyde (2.5 mmol) was then added and the reaction mixture was stirred under argon for 10–12 h. DDQ (2.3 mmol) was simply added to the solution then stirred for another 2 h. The solvent was purified crudely by chromatography on a basic alumina column eluted with dichloromethane. The collected pink solution was evaporated under reduced pressure. The residue was purified through silica gel chromatography using hexane–dichloromethane mixture(2:1 v/v) as eluent gave the products 2. And importantly, 0.2 equiv. acid catalyst is necessary in the synthesis of 2c and 2d. The structures of 2a–d were confirmed by 1H NMR and QFT-ESI, and 2b–d were new compounds [8] (Scheme 1). 2. Discussion and conclusion The macrocyclic compounds synthesis is sensitive to the substrate structure and the catalyst used [9,10]. We have carefully studied the effect of nature and concentration of the catalyst on the yield of the resultant product. To understand the role of the catalyst in the condensation reaction, we have carried out the reaction under the following categories: (a) without the use of catalyst and (b) use different catalyst, for example, trifluoroacetic acid (TFA) and paratoluenesulphonic acid (TsOH). The results of these studies are tabulated in Table 1, almost in each case the yields is less 10%. It is known that the condensation reaction between pyrrole derivatives and electron with-drawing Table 1 The effect of nature and concentration of the catalyst on the yield of the resultant product Entry
Product
Condition
Yield (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
2a 2b 2c 2d 2a 2b 2c 2d 2a 2a 2a 2b 2c 2d
0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TsOH 0.2 equiv. TFA 0.2 equiv. TFA 0.2 equiv. TFA 0.2 equiv. TFA 1.0 equiv. TFA 2.0 equiv. TFA No catalyst No catalyst No catalyst No catalyst
8.3 8 6.5 7.9 6.7 7.2 5 7.6 2.3 1.5 9.3 10 No reaction No reaction
W. Chen, T.J. Liu / Chinese Chemical Letters 19 (2008) 1199–1201
1201
aldehydes gives the corresponding corrole in the absence of any catalyst [11,12], we were able to isolate 2a and 2b, while 2c and 2d were not formed under the same condition because of the stereo-factor and lower reactivity. The tripyrrane 1 is unstable in the presence of acid, so in the presence of 0.2 equiv. catalyst either TsOH or TFA in our cases, 2a and 2b have a lower yield due to the acidolysis of tripyrrane. And in condition of higher molar ratio of acid catalyst, for example 1 or 2 equiv., the yield of the desired product decreased acutely, yields are less than 3%. As for the structure of catalysts used, the results above showed that in the same molar ratio TsOH and TFA showed less difference in the product yields. Future work will be directed towards synthesizing other calix[n]phyrin derivatives and investigating their recognition ability as receptor of anions, cations as well as neutral molecules. Acknowledgments Financial support from National Basic Research Program of China (No. 2006CB705703-2) and National Natural Science Foundation of China (No. 50573092) is acknowledged. References [1] [2] [3] [4] [5] [6] [7] [8]
[9] [10] [11] [12]
C. Suksai, T. Tuntulani, Chem. Soc. Rev. 32 (2003) 192. R. Martı´nez-Ma´n˜ez, F. Sanceno´n, Chem. Rev. 103 (11) (2003) 4419. B. Tomapatanaget, T. Tuntulani, et al. Org. Lett. 5 (9) (2003) 1539. M.C. Rotger, J.F. Gonza´lez, et al. J. Org. Chem. 59 (16) (1994) 4501. T. Mizutani, K. Wada, et al. J. Am. Chem. Soc. 121 (49) (1999) 11425. C. Bucher, R.S. Zimmerman, et al. J. Am. Chem. Soc. 123 (9) (2001) 2099. J.W. Ka, C.H. Lee, Tetrahedron Lett. 41 (2000) 4609. 5,5-10,10-20,20-25,25-Octamethylcalix[6]phyrin (2a): 1H NMR (CdCl3 (ppm)): 1.66 (bs, H2O), 1.69 (s, 24H, –CH3), 5.30 (s, 2H, CH2Cl2), 5.96 (d, 4H), J = 2.4 Hz, (H), 6.11 (d, 4H), J = 4.5 Hz, (H), 6.21 (d, 4H), J = 3.9 Hz, (H), 7.87 (bs, NH), 12.35 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 436 (2.3); QFT-ESI: m/z 915.3222 (M+H) + (calcd. for C50H40F10N6+H+915.3228). 5-10-20-25-Tetraethyl-5-10-20-25tetramethylcalix[6]phyrin (2b): 1H NMR (CdCl3 (ppm)): 0.86 (t, 12H, J = 7 Hz, –CH3), 1.26 (s, 12H, –CH3), 1.65 (bs, H2O), 1.707–1.764 (m, 8H, –CH2–), 5.30 (s, 2H, CH2Cl2), 5.96 (d, 4H, J = 2.1Hz, (H), 6.12 (d, 4H, J = 4.2 Hz, (H), 6.21 (d,4H, J = 4.5 Hz, (H), 7.67 (bs, NH), 12.31 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 436 (2.4); QFT-ESI: m/z 971.3848 (M+H) + (calcd. for C54H48F10N6+H+971.3853). 5-10-2025-Tetramethyl-5-10-20-25-tetraphenylcalix[6]phyrin (2c):1H NMR (CdCl3 (ppm)): 1.41 (s, 24H, –CH3), 1.66 (bs, H2O), 5.30 (s, 2H, CH2Cl2), 5.95 (d, 4H), J = 2.7 Hz, (H), 6.15 (d, 4H), J = 5.1 Hz, (H), 6.21 (d, 4H), J = 4.5 Hz, (H), 7.25 (s, 20H, –Ar), 7.91 (bs, NH), 12.23 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 446 (2.2); QFT-ESI: m/z 1163.3867 (M+H) + (calcd. for C70H48F10N6+H+1163.3853). 5-10-2025-Tetracyclohexylcalix[6]phyrin (2d): 1H NMR (CdCl3 (ppm)): 1.39–1.49 (m, 24H, –CH2–CH2–CH2–), 1.66 (bs, H2O), 2.04 (t, 16H, J = 9 Hz, C–CH2–), 5.30 (s, 2H, CH2Cl2), 5.97 (d, 4H), J = 2.4 Hz, (H), 6.13 (d, 4H), J = 4.2 Hz, (H), 6.22 (d, 4H), J = 3.9 Hz, (H), 7.83 (bs, NH), 12.34 (bs, NH); UV–vis (CH3CN): (max (10 4 nm)): 460 (3.0); QFT-ESI: m/z 1075.4483 (M+H) + (calcd. for C62H56F10N6+H+1075.4480). S.J. Narayanan, B. Sridevi, et al. J. Am. Chem. Soc. 121 (39) (1999) 9053. D. Gryko, J.S. Lindsey, J. Org. Chem. 65 (7) (2000) 2249. Z. Gross, N. Galili, I. Saltsman, Angew. Chem. Int. Ed. 38 (10) (1999) 1427. D.T. Gryko, Chem. Commun. (2000) 2243.