Journal of the Chinese Chemical Society, 2009, 56, 43-46

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Communication

Oxidative Aromatization of 1,3,5-Trisubstituted 4,5-Dihydro-1H-pyrazoles Efficiently by Tetrabromine-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane Complex, Br4-TATCD, as a Novel Reagent both under Microwave Irradiation and at Room Temperature
Davood Azarifar* and Kaveh Khosravi
Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Zip Code 65178, Iran

Oxidation of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles to the corresponding pyrazoles has been achieved by utilizing tetrabromine-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane complex, Br4-TATCD, in glacial acetic acid under microwave irradiation and conventional thermal condition at room temperature with excellent yields. Keywords: Tetrabromine-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane complex; Br4-TATCD; 1,3,5-Trisubstituted 2-pyrazolines; Pyrazoles; Microwave.

INTRODUCTION Many five-membered heterocycles including pyra1 zoles are considered as important class of heterocyclic compounds possessing interesting biological,2 and pharmacological properties as anti-inflammatory,3 anti-cancer,4 anti-bacterial,5 anti-viral,6 anti-diabetic,7 anti-microbial,8 and anti-fungal agents.9 Some pyrazoles possess fluorescence characteristics,10 display agrochemical properties11 (i.e., herbicidal and soil fungicidal activity) and have applications as pesticides and insecticides. 12 Pyrazolines obtained by cyclization of chalcones with arylhydrazines,13 can be easily oxidized to pyrazoles. A variety of oxidizing agents have been previously reported to convert pyrazolines to pyrazoles including Zr(NO3)4,14 carbon-activated oxygen,15 Pd/C/AcOH,16 Co(II)/O2,17 iodobenzenediacetate,18 Pb(OAc)4,19 MnO2,20 KMnO4,21 Ag(NO3)2,22 HgO,23 N-hydroxyphthalimide (NHPI) 24 and I 2O 5/KBr. 25 Many, however, impose certain disadvantages such as longer reaction times, low yields of products and toxicity due to the presence of some metallic ions embodied in these reagents. Such limitations necessitate further demand to develop other environmentally benign and easily accessible reagents for conversion of 2-pyrazolines to pyrazoles. the presence of some metallic ions embodied in these reagents. Such limitations necessitate further demand to develop other environmentally benign and easily accessible reagents for conversion of 2-pyrazolines to pyrazoles.

RESULTS AND DISCUSSION As part of our ongoing efforts to search for more robust protocols for aromatization of various heterocycles including pyrazolines,26 we have successfully examined in this article the application of Br4-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane complex, (Br4-TATCD), in glacial acetic acid as a new and efficient system for aromatization of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles (1a-q) to the corresponding pyrazoles (2a-q) (Scheme I). The reactions were conducted under microwave irradiation as well as stirring at room temperature.
Scheme I

Br 4-1,3,5,7-tetrazatricyclo[3.3.1.1 3,7]decane complex is a non-hygroscopic solid which is quite stable to air, moisture and light at room temperature and has been previously used for oxidation of alcohols to carbonyls.27 This complex can be easily prepared by slow addition of bromine to a stirred solution of 1,3,5,7-tetrazatricyclo[3.3.1.1 3,7]decane in chloroform. It is also interesting to know that the conversion of pyrazolines to pyrazoles by

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Br4-TATCD does not require any promoter in these reactions. According to the experimental results shown in Table 1, more efficient conversion of 2-pyrazolines occurs under microwave irradiation in AcOH to yield the corresponding pyrazoles in shorter reaction times and higher yields (95-100%) when compared with the results obtained under conventional thermal condition at room temperature (6585%). In conclusion, we have developed a new and mild procedure for oxidation of 2-pyrazolines to 2-pyrazoles utilizing Br4-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane complex as a highly efficient, inexpensive, ecologically safe and easily recoverable reagent which acts both under microwave irradiation and conventional thermal condition at room temperature. EXPERIMENTAL IR spectra were recorded using a Shimadzu 435-U-04 spectrophotometer (KBr pellets) and NMR spectra were obtained using 200 and 90 MHz JEOL FT NMR spectrometers. Microwave-assisted reactions were conducted in a commercial Black & Decker model MX30PG1000 watt

microwave oven. 4,5-Dihydro-1H-pyrazoles were all prepared according to our previously reported procedure. 13 Br4-TATCD complex was prepared as reported.27 2-Pyrazoles were characterized on the basis of their melting points and IR, 1H NMR, and 13C NMR spectral analysis and compared with the reported data.14,26 Preparation of Br4-TATCD complex To a magnetically stirred solution of 1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane (TATCD) (8.5 g, 60 mmoles) in chloroform (100 mL) was added dropwise a solution of bromine (20.0 g, 125 mmoles) in chloroform (100 mL) at rt. A yellow solid appeared as the bromine was taken up. The resulting mixture was further stirred for 30 min and then filtered to obtain almost pure yellow solid. Yield: 25.5 g (92%), decomp. 170-175 C. The active bromine content of this complex was found to be 1.5 moles Br2 per one mole of the complex as determined by thiosulfate titration.27 Oxidation of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles with Br4-TATCD complex: General Procedure To a magnetically stirred suspension of Br4-TATCD complex (0.092 g, 0.2 mmol) in glacial acetic acid (10 mL), was added 2-pyrazoline (1a-q) (0.1 mmol). The resulting

Table 1. Oxidative aromatization of 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazoles (1a-q) with tetrabromine-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane complex, Br4-TATCD, in AcOH under both microwave irradiation and thermal conditions at rta Substrate Productb 1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k 1l 1m 1n 1o 1p 1q
a b

R1 Ph Ph Ph Ph Ph Ph 4-MeC6H4 4-MeC6H4 4-MeOC6H4 4-MeOC6H4 2-Naphthyl 2-Naphthyl 2-Naphthyl 2-Naphthyl 2-Thienyl 3-Thienyl 2-Thienyl

R2 Ph 4-ClC6H4 3-ClC6H4 4-BrC6H4 4-Me2NC6H4 4-NO2C6H4 4-i-PrC6H4 2-Furyl Ph 2-ClC6H4 Ph 4-i-PrC6H4 2-ClC6H4 4-NO2C6H4 4-ClC6H4 4-Me2NC6H4 C6H5CH=CH

Time (h) 4.5 (0.4) 4 (0.35) 3.8 (0.3) 5 (0.42) 3.8 (0.4) 5.5 (0.45) 5.2 (0.4) 4 (0.3) 3.5 (0.25) 4 (0.3) 6 (0.5) 4.5 (0.45) 5 (0.5) 6 (0.4) 4.2 (0.38) 3.5 (0.4) 4.3 (0.32)

Yield (%)c 84 (97) 80 (100) 85 (99) 82 (98) 84 (100) 80 (95) 78 (96) 86 (98) 65 (95) 78 (96) 68 (96) 80 (98) 86 (100) 84 (96) 75 (98) 82 (98) 80 (98)

mp (C) Found 138-140 112-114 92-94 127-129 70-72 140-142 59-61 90-92 75-77 67-69 96-98 87-89 66-68 92-94 133-135 118-120 68-70 Reported14,26 139-140 114-115 93-95 126-128 68-71 142-143 57-59 93-95 77-79 66-68 67-70 135-138 120-123 71-73

2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 2k 2l 2m 2n 2o 2p 2q

The reaction data obtained under microwave irradiation are given in parentheses. All the isolated products were characterized on the basis of their physical properties and IR, 1HNMR and 13C-NMR spectral analysis and by direct comparison with authentic materials. c Isolated yields.

Aromatization of 4,5-Dihydro-1H-pyrazoles

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reaction mixture was stirred at rt for an appropriate time as given in Table 1. After the complete conversion of the substrate in 3.5-6 hours (Table 1) as monitored by TLC using acetone/n-hexane (4:1), the reaction mixture was quenched with aqueous sodium bicarbonate solution (5%) and extracted with ethyl ether (10 mL). Then organic layer was dried over anhydrous sodium sulphate and concentrated to leave the crude products (2a-q) which were purified by recrystallization from ethanol (96%) to afford the pure products in 78-98% yield (Table 1). In a separate set of experiments, these reactions were all repeated under microwave irradiation condition in an alumina bath using a MX30PG microwave oven (900 Watt). The results for the known compounds are collected in Table 1. The characterization data obtained for the compounds 2k, 2l and 2n are provided below. 3-(2-Naphthyl)-1,5-diphenylpyrazole (2k) mp 96-98 C; 1H-NMR (90 MHz, CDCl3, d): 7.268.53 (18H, m, Ar-H); 13C-NMR (22.5 MHz, CDCl3, d): 95.44 (C4 pyrazole), 121.21 (C5 pyrazole), 126.06, 128.26, 128.41, 130.16, 131.99, 135.99, 138.80, 142.08, 150.08 (C=N Pyrazol); IR (KBr): 3055, 1594, 1492, 1357, 1324, 1127, 1072, 967, 859, 822, 759, 697 cm-1; Anal. Calcd for C25H18N2: C, 86.70; H, 5.20; N, 8.10. Found C, 86.52; H, 5.15; N, 8.30. 5-(4-Isopropylphenyl)-3-(2-naphtyl)-1-phenylpyrazole (2l) mp 87-89 C; 1H-NMR (90 MHz, CDCl3, d): 1.26 (6H, d, CH(Me)2), 2.95 (1H, m, CH), 6.93-8.50 (17H, m, Ar-H); 13C-NMR: (22.5 MHz, CDCl3, d): 23.83, 33.85, 105.29 (C4 pyrazole), 124.25 (C5 pyrazole), 125.41, 126.58, 128.70, 131.99, 140.41, 144.70, 149.16, 151.89 (C=N); IR (KBr): 3049, 2954, 2925, 2856, 1588, 1493, 1400, 1370, 1325, 1270, 1173, 1149, 1099, 1070, 1011, 968, 937, 893, 858, 827, 796, 749, 616, 599 cm-1; Anal. Calcd for C28H24N2: C, 86.80; H, 6.18; N, 7.22. Found C, 86.48; H, 5.95; N, 7.18. 3-(2-Naphtyl)-5-(4-nitrophenyl)-1-phenylpyrazole (2n) mp 92-94 C; 1H-NMR (90 MHz, CDCl3, d): 7.068.54 (17H, m, Ar-H); 13C-NMR: (22.5 MHz, CDCl3, d): 105.61 (C4 pyrazole), 124.16 (C5 pyrazole), 124.88, 125.44, 126.00, 126.29, 124.20, 125.06, 125.72, 126.80, 127.27, 127.79, 128.38, 128.65, 129.11, 130.02, 133.40, 133.68, 134.51, 140.00, 143.44, 152.12 (C=N); IR (KBr): 3058, 1600, 1520, 1494, 1345, 1288, 1210, 1186, 1150, 1123, 1015, 969, 899, 857, 923, 755, 697, 618 cm-1; Anal. Calcd for C25H17N3O2: C, 76.73; H, 4.35; N, 10.74. Found

C, 76.68; H, 4.32; N, 10.50. ACKNOWLEDGMENT The University of Bu-Ali Sina, Hamadan, Iran, supported this work. Received August 15, 2008. REFERENCES
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