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Journal of the Chilean Chemical Society

versión On-line ISSN 0717-9707

J. Chil. Chem. Soc. v.54 n.1 Concepción  2009

http://dx.doi.org/10.4067/S0717-97072009000100005 

J. Chil. Chem. Soc, 54, N° 1 (2009); págs: 20-22

 

A NEW METHOD TO SYNTHESIZE 3,5-DIARYLPYRAZOL DERIVATIVES

 

XIANQIANG HUANG, JIANMIN DOU1, DACHENG LI1 DAQI WANG

Department of Chemistry & Chemical Engineering, Liaocheng University Liaocheng, 252059, China. e-mail: hxqqxh2008@163.com


ABSTRACT

Twelve 3, 5-diarylpyrazoles have been synthesized by microwave-assisted condensation reaction in a short and concise manner using various aromatic aldehydes and aromatic ketones as starting materials. The corresponding products were obtained in good yields (87-96%). All products were identified by MS, 1H NMR, 13C NMR and elemental analysis. The advantages of this novel protocol include the excellent yield, operational simplicity, short time and the avoidance of the use of expensive catalysts.

Keywords: 2,4, 6-Triarylpyrylium salts, 3,5-Diarylpyrazoles, Microwave irradiation.


INTRODUCTION

Pyrazoles are important nitrogen-containing five-membered heterocyclic compounds1-3 and numerous compounds containing pyrazole have been shown to exhibit anr1Hyperglycemic, analgesic, anti-inflammatory, antipyretic, antibacterial activity4. Moreover, metal complexation to the pyrazole heterocycle could offer a straightforward way to couple the effect of a metal bound to one heterocyclic nitrogen with the ability of the N-H to dónate a protón or hydrogen bond5. Thus, continuous efforts have been devoted to the development of more general and versatile synthetic methodologies to this class of compounds6-7.

Meanwhile, high-speed synthesis under microwave irradiation conditions has attracted a considerable amount of attention8-9, and some important reviews in the study of microwave assisted organic synthesis have been published10, the scope of applications is very extended and concerns a wide spectrum of organic synthesis procedures including, for instance, heterocyclic, organometallic, radio photo and combinatorial chemistries11-12.

In recent years, Wang et al have developed a general synthesis of 2,4,6-triarylpyridiums, which were important oxygen-containing building blocks and their use in heterocyclic preparations (e.g., pyridines, thiophenes, furans and diazepines) has been extensively described13-14.

In continuation of our efforts to develop novel synthetic routes for carbon-carbon and carbon-heteroatom bond formations and heterocycles using 2,4,6-triarylpyridiums as starting materials, we have been interested in developing new, more efficient, and synthetically useful reactions for the synthesis of biologically active molecules via microwave acceleration Thus, the aún of this work is to demónstrate the advantages obtained by the use of microwave irradiation for the synthesis of 3,5-diarylpyrazoles.

EXPERIMENTAL

1H NMR spectra (200MHz) were recorded using a Bruker AC-E 200 MHz , 400 MHz spectrometer in CDCL3, CD3COCD3, DMSO-d6 with TMS as an infernal standard. Mass spectra measurements were performed on a QP-1000A GC-MS spectrometer by El ionization at 70 eV. Purification of products was performed via flash chromatography with 200-400 mesh silica gel [petroleum ether (bp 60-90 °C)-EtOAc, 5:1]. The chemicals were obtained from commercial sources.

General experimental procedure

We prepared a series of pyrylium salts in the absence of solvent under microwave irradiation. Then, 1,3,5-triphenyl-2-pentene-l,5-diketone were prepared by the reaction of pyrylium salts with NaOAc. Next, 1,3,5-triphenyl-2-pentene-1,5-diketone (O.lmmol) was added in an open flask, followed by the addition of hydrazine hydrate (1mmol) and acetic acid (1.2 mi). Then the mixture was irradiated in microwave (375W) in an open flask for 5min. After the reaction was completed, the reaction mixture was left to room temperature, then water was added obtaining a white precipítate, the solid was isolated by flltration and washed with water. The product was purified by recrystallization once or twice from dilute ethanol or by flash chromatography with 200-400 mesh silica gel [petroleum ether (bp 60-90 °C)-EtOAc, 5:1]. The reactions are shown in Scheme 1 and the results are summarized in Table 1



Taking the reaction of l,3,5-triphenyl-2-pentene-l,5-diketone with hydrazine hydrate as an example, we investigated the effect of the power and time of microwave irradiation. The results are summarized in the Table 2 and Table 3. The results shown that the title compounds can rapidly be obtained in 375W power for 5 min.


From the tables, we found the optimum condition of the reaction: the time of MWI is 5~7min, the power of MWI is 375W.

Spectral data for compounds

3,5-diphenyl-1H-pyrazole

White crystals, mp 199-201°C (lit.[15] 199°C), >H NMR (200MHz, CDCl3) δ = 7.75-7.69 (m, 5H), 7.45-7.24 (m, 5H), 6.84 (s, 1H), 13C NMR (100MHz, CDCl3) δ = 148.75, 130.99, 128.90, 128.42, 125.66, 100.22; MS (m/e, %): 220 (M+, 80.38), 191 (M+-N-NH, 13.87), 77 (C6H5, 32.16); Anal Calcd for C15H12N2: C, 81.79; H, 5.49; N, 12.72; Found: C, 81.88; H, 5.163; N, 12.92.

S-phenyl-3-p-tolyl-1H-pyrazole

White crystals, mp 179-181°C(lit.[16] 183-184°C) 1H NMR (200MHz, CD3COCD3) δ = 12.59 (b,1H), 8.01-7.36 (m, 9H), 7.19 (s, 1H), 2.47 (s, 3H); 13C NMR (100MHz, CDCl3) δ = 149.19, 148.06, 138.28, 129.56, 128.82, 128.23,125.64,125.52,99.86,21.28; MS (m/e, %): 234 (M+, 100), 205(M+-N-NH, 6.15), 91 (C15H12N2 17.58), 77 (C6H5 62.10); Anal Calcd for C16H14N2:C, 82.02; H, 6.024; N, 11.95; Found: C, 81.81; H, 5.833; N, 12.04.

3-(4-chlorophenyl)-5-phenyl-1H-pyrazole

White crystals, mp 218-220°C (lit.[17] 217°C); 1H NMR (200MHz, CDCl3) δ = 7.68-7.41 (m, 9H), 6.83 (s, 1H); 13C NMR (100MHz, CD3COCD3) δ = 149.19, 148.06, 138.28, 129.66, 128.84, 127.70, 126.12, 100.52; MS (m/e, %): 256 (M++2, 34.86), 254 (M+, 100), 225(M+-N-NH, 9.43), 111 (ClC6H5, 48.48), 77 (C6H5, 38.64); Anal Calcd for C15H11ClN2: C.70.73; H, 4.35; N, 10.99; Found: C, 70.67; H, 4.28; N, 11.08.

3-(4-bromophenyl)-5-phenyl-1H-pyrazole

White crystals, mp 217-218°C (lit.[17] 215°C); 1H NMR (200MHz, CDCl3) δ = 7.66-7.35 (m, 9H), 6.77 (s, 1H), MS (m/e, %): 300 (M++2,93.68), 298 (M+, 100), 269(M+-N-NH, 7.14), 77 (C6H5,16.49).

3-phenyl-5-p-tolyl-1H-pyrazole

White crystals, mp 180-182°C(lit[16] 183-184°C); 1H NMR (200MHz, CD3COCD3) δ = 12.54 (b,1H), 7.97-7.28 (m, 9H), 7.14 (s, 1H), 2.42 (s, 3H); 13C NMR (100MHz, CDCl3) δ = 149.08, 148.35, 138.22, 131.39, 129.53, 128.80, 128.19, 128.09, 125.65, 125.53, 99.84, 21.26; MS (m/e, %): 234 (M+, 100), 205(M+-N-NH, 6.15), 91 (C6H5CH2, 17.58), 77 (C6H5, 62.10); Anal Calcd for C16H14N2: C, 82.02; H, 6.024; N, 11.95; Found: C, 81.72; H, 5.627; N, 12.44.

3,5-dip-tolyl-1H-pyrazole

White crystals, mp 237-238°C; 1H NMR (200MHz, CD3COCD3) δ = 12.39 (b,1H), 7.78-7.23 (m, 8H), 7.02 (s, 1H), 2.389 (s, 6H); 13C (100MHz, CDCl3) δ = 150.31, 148.73, 138.50, 129.56, 127.90, 125.68, 99.82, 21.29; MS (m/e, %): 248 (M+, 100), 233 (M+-CH3, 2.35), 219(M+-N-NH, 3.71), 91 (C6H5CH2,5.01), 77 (C6H5,9.64); Anal Calcd for C17H16N2: C, 82.22; H, 11.28; N: 6.49; Found: C, 81.88; H, 10.60; N, 6.06.

3-(4-cblorophenyl)-5-p-tolyl-1H-pyrazole

White crystals, mp 236-237°C; 1H NMR (200MHz, CD3COCD3) δ = 12.70 (b, 1H), 8.06-7.43 (m, 8H), 7.23 (s, 1H), 2.49 (s, 3H); 3C NMR (100MHz, DMSO-d6) δ =149.23,148.54,137.34,132.07,131.68,129.43,128.78,127.05, 126.75, 125.03, 120.63, 99.52, 20.83; MS (m/e, %): 270(M++2, 31.66), 268 (M+, 100), 233(M+-C1,5.47), 111 (ClC6H5, 5.70), 77 (C6H5, 38.64); Anal Calcd for C16H13ClN2: C, 71.50; H, 4.88; N, 10.42; Found: C, 71.34; H, 4.63; N,

3-(4-bromopbenyl)-5-p-tolyl-1H-pyrazole

White crystals, mp 244-245°C; 1H NMR (200MHz, CDCl3) δ = 7.63-7.57 (m, 8H), 6.79 (s, 1H), 2.40 (s, 3H); 3C NMR (100MHz - d6) δ=149.07, 148.14,137.35,132.07,131.69,129.44,128.79,127.06,126.75,125.04,99.53, 20.83; MS (m/e, %): 314 (M++2,100), 312 (M+, 95.06), 283 (M+-N-NH, 2.61), 233(M+-Br, 9.26); Anal Calcd for C16H13BrN2: C, 61.39; H, 4.18; N, 8.94; Found: C, 61.30; H, 4.14; N, 8.93.

5-(4-chlorophenyl)-3-phenyl-1H-pyrazole

White crystals, mp 216-218°C ( lit[17] 217°C); 1H NMR (200MHz, CD3COCD3) δ = 12.65 (b, 1H), 7.97-7.36 (m, 9H), 7.19 (s, 1H); 3C NMR (100MHz, DMSO-d6) δ =149.12, 148.64, 132.16, 128.88, 128.83, 127.97, 126.78, 125.11, 99.90; MS (m/e, %): 256 (M++2, 27.99), 254 (M+, 100), 225(M+-N-NH, 7.43), 111 (ClC6H5, 4.82), 77 (C6H5, 43.21); Anal Calcd for C15H11ClN2: C.70.73; H, 4.35; N, 10.99; Found: C, 70.60; H, 4.244; N, 11.17.

5-(4-chlorophenyl)-3-p-tolyl-1H-pyrazole

White crystals, mp 236-237°C; 1H NMR (200MHz, CD3COCD3) δ =12.29 (s, 1H), 7.68-7.02 (m, 8H), 6.84 (s, 1H), 2.37 (s, 3H); 13C NMR (100MHz, DMSO-d6) δ = 149.23, 148.62,132.07, 129.44, 128.79, 126.75, 125.03, 99.53, 20.83; MS (m/e, %): 270 (M++2,35.21), 268 (M+, 100), 239 (M+-N-NH, 4.27), 111 (ClC6H5, 23.03), 77 (C6H5, 34.45); Anal Calcd for C16H13ClN2: C, 71.50; H, 4.88; N ,10.42; Found: C.71.40; H, 4.67; N: 10.58.

3,5-bis(4-chlorophenyl)-1H-pyrazole

White crystals, mp 248-249°C; 1H NMR (200MHz, CDCl3) δ = 7.67-7.38 (m, 8H), 6.80 (s, 1H);13C NMR (100MHz, DMSO-d6) δ = 149.67, 148.58, 132.34, 128.89, 126.79, 100.23; MS (m/e, %): 290 (M++2, 68.23), 288 (M+, 100), 259 (M+-N-NH, 3.46), 111 (ClC6H5, 8.63); Anal Calcd for C16H13ClN2: C, 62.30; H, 3.48; N ,9.69; Found: C,62.47; H, 3.223; N: 9.771.

3-(4-bromophenyl)-5-(4-chlorophenyl)-1H-pyrazole

White crystals, mp 248-250°C; 1H NMR (200MHz, CDCl3) δ = 7.63-7.28 (m, 8H), 6.82 (s, 1H); MS (m/e, %): 334 (M++2, 100), 332 (M+, 76.43),305 (M+-N-NH, 3.55), 111 (ClC6H5, 8.21); Anal Calcd for C16H13ClN2: C, 54.00; H, 3.02; N ,8.39; Found: C,53.80; H, 2.807; N: 8.692.

CONCLUSIONS

In summary, a benign, simple, versatile routes to 3, 5-diarylpyrazoles in high yield have been demonstrated. In order to investigate the microwave energy transfer system both mineral supports and a polar paste system were surveyed. We have found that acetic acid is a good catalyst in a new, microwave assisted method for the produets synthesis. On the other hand, the most significant result remains on using a polar paste system. The excellent product yields and simple washing with water and fíltration make this methodology as an alternative platform under the umbrella of environmentally green and safe processes. In general, these approaches lead to a clean, efficient and economical technology (green chemistry); safety is largely increased, work-up is considerably simplified, cost is reduced. The extensión of this type of reaction is aetually under progress.

ACKNOWLEDGEMENTS

This work was flnancially supported by the Natural Science Foundation of China (No. 20671048) and the the National Natural Science Foundation of Liaocheng University (No. X051040).

 

REFERENCES

J. Elguero, P. Goya, N. Jagerovic, A. M. S. Silva, Targets Heterocycl. Syst. 6,52, (2002).        [ Links ]

S. W. Djuric, N. Y. BaMaung, A. Basha, H. Liu, J. R. Luly, D. J. Madar, R. J. Sciotti, N. P. Tu, F. L.Wagenaar, P. E. Wiedman, X. Zhou, S. Bailaron, J. Bauch, Y.- W. Chen, X. G. Chiou, T. Fey, D. Gauvin, E. Gubbins, G. C. Hsieh, K. C. Marsch, K. W. Mollison, M. Pong, T. K. Shaughnessy, M. P. Sheets, M. Smith, J. M.Trevillyan, U. Warrior, C. D. Wegner, G. W.Carter, J. Med. Chem. 43, 2975, (2000).        [ Links ]

M. A. P. Martins, W. Cunico, C. M. P. Pereira, A. F. C. Flores, H. G. Bonacorso, N. Zanatta, Curr. Org. Synth. 1, 391, (2004),        [ Links ]

S. G. Kücükgüzel, S. Rollas, H. Erdeniz, M. Kiraz, A. C. Ekinci, A. Vidin, Prog. Drug Res. 35, 761, (2000).        [ Links ]

(a) Y. R. Huang, J. A. Katzenellenbogen, Org. Lett. 2,2833,(2000).         [ Links ] (b) X. J. Wang, J. Tan, K. Grozinger, R. Betageri, T. Kirrane, J. R. Proundfoot, Tetrahedron Lett. 41, 5321, (2000).        [ Links ]

M. C. Bagley, M. C. Lubinu, C. Mason, Synlett. 704, (2007).         [ Links ]

A. P. M. Marcos, B. Paulo, M. Pablo, B. Sergio, M. Sidnei, Z. Nilo, G. B. Helio, F. C. F. Alex, J. Braz. Chem. Soc. 17,408, (2006).        [ Links ]

G. W. Kabalka, M. Al-Masum, Org. Lett. 8, 11, (2006).        [ Links ]

M.Shanmugasundaram, A. L. Aguirre, M. Leyva, B. Quan, L. E. Martínez, Tetrahedron Lett. 48, 7698, (2007).        [ Links ]

(a) D. Adam, Nature, 421, 571, (2003),         [ Links ] (b). C. O. Kapper, Angew. Chem. Int. Ed. 43, 6250, (2004).        [ Links ]

Z. Ni, R. I. Masel, J. Am. Chem. Soc. 128, 12394, (2006).        [ Links ]

E. F. DiMauro, J. M. Kennedy, J. Org. Chem. 72, 1013, (2007).        [ Links ]

J.-X. Wang , X. N. Shi, X. Q. Men, L. B.Zhao, Synth. Commun. 33, 2849, (2003).        [ Links ]

X. Q. Huang, H. X. Li, J.-X. Wang , X. F. Jia, Chin. Chem. Lett. 16, 607, (2005).        [ Links ]

A. T. Balaban, Tetrahedron, 26, 739, (1970).        [ Links ]

F. S. Al-Hajjar, S. S. Sabri, J. Heterocyclic Chem. 23, 727, (1986).        [ Links ]

T. C. Sharma, H. Patel, M. M. Bokadia, Iridian J. Chem. 11, 703, (1973).        [ Links ]

 

(Received 26 February 2008 - Accepted 22 July 2008)