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A one-pot, three-component synthesis of new pyrano[2,3-h]coumarin derivatives
Tetrahedron Letters 53 (2012) 1445–1446
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A one-pot, three-component synthesis of new pyrano[2,3-h]coumarin derivatives Bahador Karami ⇑, Saeed Khodabakhshi, Khalil Eskandari Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran
a r t i c l e
i n f o
Article history: Received 25 July 2011 Revised 16 December 2011 Accepted 6 January 2012 Available online 13 January 2012
a b s t r a c t The reaction between 5,7-dihydroxy-4-substituted coumarin, malononitrile, and aromatic aldehydes in the presence of a catalytic amount of K2CO3 as a basic catalyst leads to new pyrano[2,3-h]coumarin derivatives in good to excellent yields. Ó 2012 Elsevier Ltd. All rights reserved.
Keywords: 5,7-Dihydroxy-4-methylcoumarin Malononitrile Aromatic aldehyde Pyrano[2,3-h]coumarin
The synthesis of pyrano[2,3-c]coumarin derivatives via multicomponent reactions (MCRs) has attracted significant interest because of their biological and pharmacological activities.1–3 Also, MCRs have drawn special attention due to the advent of high-throughput screening techniques that have enabled rapid identification of potential new medicines among large collections of organic compounds.4,5 It should be mentioned that three-component reactions have emerged as useful methods because the combination of three components to generate new products in a single step is extremely economical. A broad spectrum of biological activity has been reported for coumarin derivatives.6 Dihydropyran rings fused with a coumarin nucleus are important as they are valuable synthons for the synthesis of pharmacological agents.7,8 Pyrano[2,3-h]benzopyran has been used as the key intermediate for the synthesis of urea and thiourea derivatives, thioxo-imidazolidinedione, dithioxodiazetidine and Schiff’s bases.9 Firstly, we decided to prepare 5,7-dihydroxy-4-substituted coumarin 3 via the ZrOCl28H2O/SiO2-catalyzed Pechmann condensation of phloroglucinol (1) with b-ketoester 2 under thermal and solvent-free conditions (Scheme 1).10,11 Subsequently, the multicomponent reaction of 3, malononitrile (4) and suitable aromatic aldehydes 5 in the presence of a catalytic amount of K2CO3 in refluxing methanol gave a range of new dihydropyrans fused with a coumarin nucleus 6 (pyrano[2,3-h]coumarin) (Scheme 2, Table 1). The structures of the products were deduced from their IR, 1H NMR, and 13C NMR spectral data.12
⇑ Corresponding author. Tel.: +98 7412223048; fax: +98 7412242167. E-mail address: [email protected] (B. Karami). 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2012.01.024
The 1H NMR spectrum of 6a exhibited five sharp singlets identified as methyl (d = 2.55), methine (d = 4.61), a methine ortho to the OH group (d = 5.80), an olefinic C–H of the coumarin ring (d = 6.10), and NH2 (d = 6.88) protons. Two multiplets (d = 7.13– 7.18) and (d = 7.23–7.27) corresponded to the protons of the phenyl group. The proton decoupled 13C NMR spectrum of 6a showed 18 distinct resonances in agreement with the proposed structure. In another investigation, and in order to optimize the procedure, we performed the reaction in two steps involving the synthesis of arylmethylene 7 through the Knoevenagel condensation of 4 and 5 under solvent-free grinding conditions, and then treatment of arylmethylene 7 with 5,7-dihydroxy-4-substituted coumarin 3 to afford product 6a. Although, the reaction of arylmethylene 7 with 3 occurred in a shorter reaction time (about 25 min) compared to the three-component reaction (about 40 min), it required
OH
HO
OH R1
OH ZrOCl2.8H2O/SiO2 (10 mol%)
1 + O
solvent-free, 90 oC
O 2
1
O 3
OR
R
HO
2 R1: CH 3, CH2Cl, Ph R2: CH 3, CH3CH2 Scheme 1.
O
1446
B. Karami et al. / Tetrahedron Letters 53 (2012) 1445–1446
OH R1
O Ar
H
K2CO3 (10 mol%)
5
3 +
O
MeOH, reflux 20-180 min
H2N
N
N
O
O
Ar CN
4
6 Scheme 2.
Table 1 Synthesis of new pyrano[2,3-h]coumarins in the presence of K2CO3 under reflux in methanol Product
Ar
R1
Yielda (%)
Mp (°C)
6a 6b 6c 6d 6e 6f 6g
C6H5 4-Cl-C6H4 3-O2N-C6H4 3-Br-C6H4 4-Me-C6H4 2,4-Cl2-C6H3 4-MeO-C6H4
CH3 CH3 CH3 CH3 CH3 CH3 CH3
95 98 95 93 90 95 93
255–256 242–244 293–295 295–296 225–226 322–324 265–266
CH3
88
250–252
CH3 CH3 CH3 CH3 Ph CH2Cl
80 90 95 80 87 78
208–210 303–305 320–322 245–247 243–245 308–310
S
6h
3-Cl-C6H4 2-MeO-C6H4 2-Cl-C6H4 4-O2N-C6H4 2-Cl-C6H4 2-Cl-C6H4
6i 6j 6k 6l 6m 6n a
Isolated yield.
more effort. Therefore, we decided to perform these reactions by employing the one-pot procedure. A mechanistic rationale for the formation of 6 is suggested in Scheme 3. The reaction is thought to take place in three steps. It is reasonable to assume that the initial event involves the generation of arylmethylene 7 via Knoevenagel condensation of the aldehyde and malononitrile. In the next step, adduct 8 results from a Michael type addition of C-8 of 3 to arylmethylene 7 and subsequent cyclization of intermediate 8 gives pyrano[2,3-h]coumarin 6. It should be mentioned that our efforts on the synthesis of pyrano[2,3-h]coumarin derivatives using aliphatic aldehydes were
R1
OH
H
R1
OH
Step 2 O
3
O
O
HN
O C
HO Ar
Ar
B
B
N
N
B
8
N
7
O
Step 3 -H2 O
R1
OH
Step 1 O Ar
CN H
5
O
+ CN 4
O
H 2N
Ar CN
B-: HCO 3- and OH Scheme 3.
6
O
unsuccessful. The problem with alkyl aldehydes is likely to be because they can undergo enolization. In summary, the reaction between 5,7-dihydroxy-4-substituted coumarin, various aromatic aldehydes, and malononitrile in the presence of K2CO3 provides a simple one-pot entry for the synthesis of pyrano[2,3-h]coumarins of potential synthetic and pharmaceutical interest. This method has advantages such as the use of an inexpensive and commercially available basic catalyst (K2CO3), high yields of products, short reaction times, and a simple workup procedure. It is worthwhile to note that the presence of transformable functionalities in the products makes them potentially valuable for further synthetic manipulations. Acknowledgments The authors gratefully acknowledge partial support of this work by Yasouj University, Iran. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2012.01.024. References and notes 1. Burgard, A.; Lang, H. J.; Gerlach, U. Tetrahedron 1999, 55, 7555. 2. (a) Na, J. E.; Lee, K. Y.; Seo, J.; Kim, J. N. Tetrahedron Lett. 2005, 46, 4505; (b) Evans, J. M.; Fake, C. S.; Hamilton, T. C.; Poyser, R. H.; Showell, G. A. J. Med. Chem. 1984, 27, 1127. 3. Evans, J. M.; Fake, C. S.; Hamilton, T. C.; Poyser, R. H.; Watts, E. A. J. Med. Chem. 1983, 26, 1582. 4. (a) Ivachtchenko, A. V.; Ivanenkov, Ya. A.; Kysil, V. M.; Krasavin, M. Y.; Ilyin, A. P. Russ. Chem. Rev. 2010, 79, 787; (b) Shaabani, A.; Rahmati, A.; Rezayan, A. H.; Khavasi, H. R. J. Iran Chem. Soc. 2001, 8, 24. 5. (a) Nair, V.; Babu, B. P.; Varghese, V.; Sinu, C. R.; Paul, R. R.; Anabha, E. R.; Suresh, E. Tetrahedron Lett. 2009, 50, 3716; (b) Yavari, I.; Djahaniani, H.; Nasiri, F. Tetrahedron 2003, 59, 9409. 6. (a) Murray, R. D. H.; Mendey, J.; Brown, S. A. The Natural Coumarins; Wiley: New York, 1982; (b) Murakami, A.; Gao, G.; Omura, M.; Yano, M.; Ito, C.; Furukawa, H.; Takahashi, D.; Koshimizu, K.; Ohigashi, H. Bioorg. Med. Chem. Lett. 2000, 10, 59; (c) Xie, L.; Takeuchi, Y.; Cosentino, L. M.; McPhail, A. T.; Lee, K.-H. J. Med. Chem. 2001, 44, 664. 7. (a) El-Agrody, A. M.; Abd El-Latif, M. S.; El-Hadi, N. A.; Fakery, A. H.; Bedair, A. H. Molecules 2001, 6, 15; (b) El-Agrody, A. M.; Abd El-Latif, M. S.; Fakery, A. H.; Bedair, A. H. J. Chem. Res. 2000, 26. 8. Shaker, R. M. Pharmazie 1996, 51, 148. 9. Nofal, Z. M.; Fahmy, H. H.; Kamel, M. M.; Sarhan, A. I.; Maghraby, A. S. Egypt. J. Chem. 2004, 47, 345. 10. General procedure for the synthesis of 5,7-dihydroxy-4-substituted coumarins 3. b-Ketoester 2 (1 mmol) was added to a mixture of phloroglucinol (1) (1 mmol) and ZrOCl28H2O/SiO2 (0.27 g, 10 mol %) in a screw-cap vial. The mixture was stirred in a preheated oil bath (90 °C). After completion of the reaction, the resulting solid product was suspended in H2O (20 ml), filtered and recrystallized from hot EtOH to give the pure product 3. 11. Karami, B.; Kiani, M. Catal. Commun. 2011, 14, 62. 12. Typical procedure for the synthesis of 6a: To a stirred solution of benzaldehyde (0.106 g, 1 mmol), malononitrile (4) (0.066 mmol), and 5,7-dihydroxy-4methylcoumarin 3 (0.192 g, 1 mmol) in MeOH (10 mL), was added K2CO3 (0.014 g, 0.1 mol). The mixture was stirred under reflux for 40 min. The reaction progress was monitored by TLC (hexane/AcOEt, 1:1). After completion of the reaction, the mixture was filtered and evaporated and the residue recrystallized from EtOH to afford pure 6a (0.33 g, 95%) as a light yellow solid, mp 255–256 °C; 1H NMR (DMSO-d6, 400 MHz): d = 7.27–7.23 (m, 2H), 7.18– 7.13 (m, 3H), 6.88 (s, 2H), 6.10 (s, 1H), 5.80 (s, 1H), 4.61 (s, 1H), 2.55 (s, 3H); 13C NMR (DMSO-d6, 100 MHz): d = 163.69, 160.10, 160.05, 155.26, 153.51, 147.59, 145.81, 128.16, 127.01, 126.19, 120.53, 109.70, 107.89, 98.92, 98.57, 57.68, 36.31, 23.97; IR (KBr) v: 3460, 3390, 2191, 1652, 1617, 1399 cm 1. Anal. Calcd for C20H14N2O4: C, 69.36; H, 4.07; N, 8.09. Found: C, 69.50; H, 3.92; N, 7.95; MS (m/z): 346.1 [M]+. Compound 6m: Pale yellow solid; mp 243–245 °C; 1H NMR (DMSO-d6, 400 MHz): d = 11.16 (s, 1H), 7.52 (s, 5H), 7.39 (d, 1H, J = 7.2 Hz), 7.23 (t, 2H, J = 6.8 Hz), 7.00 (d, 1H, J = 6.8 Hz), 6.56 (s, 1H), 6.07 (s, 1H), 5.14 (s, 1H), 4.98 (s, 2H); 13C NMR (DMSO-d6, 100 MHz): d = 159.62, 158.84, 158.26, 155.22, 154.30, 147.00, 142.41, 139.74, 132.42, 130.55, 129.78, 128.77, 128.68, 128.32, 128.12, 127.83, 119.25, 112.87, 107.91, 100.92, 99.16, 57.79, 33.96; IR (KBr) v: 3219, 2192, 1649, 1618, 1385, 1157, 833; Anal. Calcd for C25H15ClN2O4: C, 67.80; H, 3.41; N, 6.33. Found: C, 67.45; H, 3.59; N, 6.22; MS (m/z): 443.1 [M+H]+.
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A one-pot, three-component synthesis of new pyrano[2,3-h]coumarin derivatives Bahador Karami ⇑, Saeed Khodabakhshi, Khalil Eskandari Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran
a r t i c l e
i n f o
Article history: Received 25 July 2011 Revised 16 December 2011 Accepted 6 January 2012 Available online 13 January 2012
a b s t r a c t The reaction between 5,7-dihydroxy-4-substituted coumarin, malononitrile, and aromatic aldehydes in the presence of a catalytic amount of K2CO3 as a basic catalyst leads to new pyrano[2,3-h]coumarin derivatives in good to excellent yields. Ó 2012 Elsevier Ltd. All rights reserved.
Keywords: 5,7-Dihydroxy-4-methylcoumarin Malononitrile Aromatic aldehyde Pyrano[2,3-h]coumarin
The synthesis of pyrano[2,3-c]coumarin derivatives via multicomponent reactions (MCRs) has attracted significant interest because of their biological and pharmacological activities.1–3 Also, MCRs have drawn special attention due to the advent of high-throughput screening techniques that have enabled rapid identification of potential new medicines among large collections of organic compounds.4,5 It should be mentioned that three-component reactions have emerged as useful methods because the combination of three components to generate new products in a single step is extremely economical. A broad spectrum of biological activity has been reported for coumarin derivatives.6 Dihydropyran rings fused with a coumarin nucleus are important as they are valuable synthons for the synthesis of pharmacological agents.7,8 Pyrano[2,3-h]benzopyran has been used as the key intermediate for the synthesis of urea and thiourea derivatives, thioxo-imidazolidinedione, dithioxodiazetidine and Schiff’s bases.9 Firstly, we decided to prepare 5,7-dihydroxy-4-substituted coumarin 3 via the ZrOCl28H2O/SiO2-catalyzed Pechmann condensation of phloroglucinol (1) with b-ketoester 2 under thermal and solvent-free conditions (Scheme 1).10,11 Subsequently, the multicomponent reaction of 3, malononitrile (4) and suitable aromatic aldehydes 5 in the presence of a catalytic amount of K2CO3 in refluxing methanol gave a range of new dihydropyrans fused with a coumarin nucleus 6 (pyrano[2,3-h]coumarin) (Scheme 2, Table 1). The structures of the products were deduced from their IR, 1H NMR, and 13C NMR spectral data.12
⇑ Corresponding author. Tel.: +98 7412223048; fax: +98 7412242167. E-mail address: [email protected] (B. Karami). 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2012.01.024
The 1H NMR spectrum of 6a exhibited five sharp singlets identified as methyl (d = 2.55), methine (d = 4.61), a methine ortho to the OH group (d = 5.80), an olefinic C–H of the coumarin ring (d = 6.10), and NH2 (d = 6.88) protons. Two multiplets (d = 7.13– 7.18) and (d = 7.23–7.27) corresponded to the protons of the phenyl group. The proton decoupled 13C NMR spectrum of 6a showed 18 distinct resonances in agreement with the proposed structure. In another investigation, and in order to optimize the procedure, we performed the reaction in two steps involving the synthesis of arylmethylene 7 through the Knoevenagel condensation of 4 and 5 under solvent-free grinding conditions, and then treatment of arylmethylene 7 with 5,7-dihydroxy-4-substituted coumarin 3 to afford product 6a. Although, the reaction of arylmethylene 7 with 3 occurred in a shorter reaction time (about 25 min) compared to the three-component reaction (about 40 min), it required
OH
HO
OH R1
OH ZrOCl2.8H2O/SiO2 (10 mol%)
1 + O
solvent-free, 90 oC
O 2
1
O 3
OR
R
HO
2 R1: CH 3, CH2Cl, Ph R2: CH 3, CH3CH2 Scheme 1.
O
1446
B. Karami et al. / Tetrahedron Letters 53 (2012) 1445–1446
OH R1
O Ar
H
K2CO3 (10 mol%)
5
3 +
O
MeOH, reflux 20-180 min
H2N
N
N
O
O
Ar CN
4
6 Scheme 2.
Table 1 Synthesis of new pyrano[2,3-h]coumarins in the presence of K2CO3 under reflux in methanol Product
Ar
R1
Yielda (%)
Mp (°C)
6a 6b 6c 6d 6e 6f 6g
C6H5 4-Cl-C6H4 3-O2N-C6H4 3-Br-C6H4 4-Me-C6H4 2,4-Cl2-C6H3 4-MeO-C6H4
CH3 CH3 CH3 CH3 CH3 CH3 CH3
95 98 95 93 90 95 93
255–256 242–244 293–295 295–296 225–226 322–324 265–266
CH3
88
250–252
CH3 CH3 CH3 CH3 Ph CH2Cl
80 90 95 80 87 78
208–210 303–305 320–322 245–247 243–245 308–310
S
6h
3-Cl-C6H4 2-MeO-C6H4 2-Cl-C6H4 4-O2N-C6H4 2-Cl-C6H4 2-Cl-C6H4
6i 6j 6k 6l 6m 6n a
Isolated yield.
more effort. Therefore, we decided to perform these reactions by employing the one-pot procedure. A mechanistic rationale for the formation of 6 is suggested in Scheme 3. The reaction is thought to take place in three steps. It is reasonable to assume that the initial event involves the generation of arylmethylene 7 via Knoevenagel condensation of the aldehyde and malononitrile. In the next step, adduct 8 results from a Michael type addition of C-8 of 3 to arylmethylene 7 and subsequent cyclization of intermediate 8 gives pyrano[2,3-h]coumarin 6. It should be mentioned that our efforts on the synthesis of pyrano[2,3-h]coumarin derivatives using aliphatic aldehydes were
R1
OH
H
R1
OH
Step 2 O
3
O
O
HN
O C
HO Ar
Ar
B
B
N
N
B
8
N
7
O
Step 3 -H2 O
R1
OH
Step 1 O Ar
CN H
5
O
+ CN 4
O
H 2N
Ar CN
B-: HCO 3- and OH Scheme 3.
6
O
unsuccessful. The problem with alkyl aldehydes is likely to be because they can undergo enolization. In summary, the reaction between 5,7-dihydroxy-4-substituted coumarin, various aromatic aldehydes, and malononitrile in the presence of K2CO3 provides a simple one-pot entry for the synthesis of pyrano[2,3-h]coumarins of potential synthetic and pharmaceutical interest. This method has advantages such as the use of an inexpensive and commercially available basic catalyst (K2CO3), high yields of products, short reaction times, and a simple workup procedure. It is worthwhile to note that the presence of transformable functionalities in the products makes them potentially valuable for further synthetic manipulations. Acknowledgments The authors gratefully acknowledge partial support of this work by Yasouj University, Iran. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2012.01.024. References and notes 1. Burgard, A.; Lang, H. J.; Gerlach, U. Tetrahedron 1999, 55, 7555. 2. (a) Na, J. E.; Lee, K. Y.; Seo, J.; Kim, J. N. Tetrahedron Lett. 2005, 46, 4505; (b) Evans, J. M.; Fake, C. S.; Hamilton, T. C.; Poyser, R. H.; Showell, G. A. J. Med. Chem. 1984, 27, 1127. 3. Evans, J. M.; Fake, C. S.; Hamilton, T. C.; Poyser, R. H.; Watts, E. A. J. Med. Chem. 1983, 26, 1582. 4. (a) Ivachtchenko, A. V.; Ivanenkov, Ya. A.; Kysil, V. M.; Krasavin, M. Y.; Ilyin, A. P. Russ. Chem. Rev. 2010, 79, 787; (b) Shaabani, A.; Rahmati, A.; Rezayan, A. H.; Khavasi, H. R. J. Iran Chem. Soc. 2001, 8, 24. 5. (a) Nair, V.; Babu, B. P.; Varghese, V.; Sinu, C. R.; Paul, R. R.; Anabha, E. R.; Suresh, E. Tetrahedron Lett. 2009, 50, 3716; (b) Yavari, I.; Djahaniani, H.; Nasiri, F. Tetrahedron 2003, 59, 9409. 6. (a) Murray, R. D. H.; Mendey, J.; Brown, S. A. The Natural Coumarins; Wiley: New York, 1982; (b) Murakami, A.; Gao, G.; Omura, M.; Yano, M.; Ito, C.; Furukawa, H.; Takahashi, D.; Koshimizu, K.; Ohigashi, H. Bioorg. Med. Chem. Lett. 2000, 10, 59; (c) Xie, L.; Takeuchi, Y.; Cosentino, L. M.; McPhail, A. T.; Lee, K.-H. J. Med. Chem. 2001, 44, 664. 7. (a) El-Agrody, A. M.; Abd El-Latif, M. S.; El-Hadi, N. A.; Fakery, A. H.; Bedair, A. H. Molecules 2001, 6, 15; (b) El-Agrody, A. M.; Abd El-Latif, M. S.; Fakery, A. H.; Bedair, A. H. J. Chem. Res. 2000, 26. 8. Shaker, R. M. Pharmazie 1996, 51, 148. 9. Nofal, Z. M.; Fahmy, H. H.; Kamel, M. M.; Sarhan, A. I.; Maghraby, A. S. Egypt. J. Chem. 2004, 47, 345. 10. General procedure for the synthesis of 5,7-dihydroxy-4-substituted coumarins 3. b-Ketoester 2 (1 mmol) was added to a mixture of phloroglucinol (1) (1 mmol) and ZrOCl28H2O/SiO2 (0.27 g, 10 mol %) in a screw-cap vial. The mixture was stirred in a preheated oil bath (90 °C). After completion of the reaction, the resulting solid product was suspended in H2O (20 ml), filtered and recrystallized from hot EtOH to give the pure product 3. 11. Karami, B.; Kiani, M. Catal. Commun. 2011, 14, 62. 12. Typical procedure for the synthesis of 6a: To a stirred solution of benzaldehyde (0.106 g, 1 mmol), malononitrile (4) (0.066 mmol), and 5,7-dihydroxy-4methylcoumarin 3 (0.192 g, 1 mmol) in MeOH (10 mL), was added K2CO3 (0.014 g, 0.1 mol). The mixture was stirred under reflux for 40 min. The reaction progress was monitored by TLC (hexane/AcOEt, 1:1). After completion of the reaction, the mixture was filtered and evaporated and the residue recrystallized from EtOH to afford pure 6a (0.33 g, 95%) as a light yellow solid, mp 255–256 °C; 1H NMR (DMSO-d6, 400 MHz): d = 7.27–7.23 (m, 2H), 7.18– 7.13 (m, 3H), 6.88 (s, 2H), 6.10 (s, 1H), 5.80 (s, 1H), 4.61 (s, 1H), 2.55 (s, 3H); 13C NMR (DMSO-d6, 100 MHz): d = 163.69, 160.10, 160.05, 155.26, 153.51, 147.59, 145.81, 128.16, 127.01, 126.19, 120.53, 109.70, 107.89, 98.92, 98.57, 57.68, 36.31, 23.97; IR (KBr) v: 3460, 3390, 2191, 1652, 1617, 1399 cm 1. Anal. Calcd for C20H14N2O4: C, 69.36; H, 4.07; N, 8.09. Found: C, 69.50; H, 3.92; N, 7.95; MS (m/z): 346.1 [M]+. Compound 6m: Pale yellow solid; mp 243–245 °C; 1H NMR (DMSO-d6, 400 MHz): d = 11.16 (s, 1H), 7.52 (s, 5H), 7.39 (d, 1H, J = 7.2 Hz), 7.23 (t, 2H, J = 6.8 Hz), 7.00 (d, 1H, J = 6.8 Hz), 6.56 (s, 1H), 6.07 (s, 1H), 5.14 (s, 1H), 4.98 (s, 2H); 13C NMR (DMSO-d6, 100 MHz): d = 159.62, 158.84, 158.26, 155.22, 154.30, 147.00, 142.41, 139.74, 132.42, 130.55, 129.78, 128.77, 128.68, 128.32, 128.12, 127.83, 119.25, 112.87, 107.91, 100.92, 99.16, 57.79, 33.96; IR (KBr) v: 3219, 2192, 1649, 1618, 1385, 1157, 833; Anal. Calcd for C25H15ClN2O4: C, 67.80; H, 3.41; N, 6.33. Found: C, 67.45; H, 3.59; N, 6.22; MS (m/z): 443.1 [M+H]+.