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[5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone

Department of Pharmaceutical Chemistry, RITS, 4th Mile Stone, Hisar Road, Sirsa-125055, India
*
Author to whom correspondence should be addressed.
Molbank 2011, 2011(1), M714; https://doi.org/10.3390/M714
Submission received: 13 December 2010 / Accepted: 4 January 2011 / Published: 11 January 2011

Abstract

:
A novel pyrazoline derivative 2 was synthesized by reaction of an α,β-unsaturated ketone 1 with isonicotinic acid hydrazide (INH) in glacial acetic acid. The structure of the title compound 2 was established on basis of IR, 1H-NMR, 13C-NMR and mass spectral data.

Graphical Abstract

1. Introduction

Pyrazoline derivatives are electron-rich nitrogen heterocycles which play an important role due to their diverse biological activities [1]. They have been found to possess antimicrobial, antidiabetic, antidepressant, anticancer, hypotensive, antiamoebic, anti-inflammatory and antitubercular activity [2,3,4,5,6,7,8,9,10]. As a part of our research programme on pyrazoline derivatives [11], we report herein the synthesis of [5-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone (2).

2. Results & Discussion

The title compound 2 was prepared by reaction of 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one (1) and isonicotinic acid hydrazide in glacial acetic acid (Scheme 1). The 1H-NMR spectrum of compound 2 displayed three characteristic signals due to diasterotopic protons (HA, HB and HX). The HA proton which is cis to HX resonates upfield at δ 3.21 (center) as doublet of doublets (dd, J = 17.55 and 4.50 Hz), while the HB proton which is trans to HX resonates downfield at 3.71 (dd, J = 17.40 and 11.70 Hz). The HX proton which is vicinal to two methylene protons (HA and HB) is also observed as double doublet at a δ value of 6.08 (dd, J = 11.55 and 4.80 Hz). The aromatic protons are observed at the expected chemical shift and integral values. The 5-H proton of pyrazole is observed as a singlet at 8.76 ppm apparently due to deshielding caused by the pyrazoline ring.
The cyclization of chalcone 1 into pyrazoline derivative 2 was further supported by 13C-NMR of prototype compound in which C4 and C5 carbon resonate at δ 41.49 and 53.62, respectively, while the peaks due to carbonyl carbon (C=O) are observed at 167.82 ppm. These values are in close agreement with reported values of carbon C4 and C5 in pyrazolines [12]. DEPT-135 is an important tool of 13C-NMR spectroscopy in which only primary, secondary and tertiary carbons that have an attached proton give signals, but the phase of signals is different, depending on whether the number of attached hydrogens is an odd or even number. Signals arising from CH or CH3 groups will give positive peaks, while signals arising from CH2 groups will give negative (inverse) peaks. Here, the DEPT-135 spectrum gives positive peaks at δ 53.62 due to CH of pyrazoline (i.e., C5) and a negative (inverse) peak at 41.49 due to CH2 of pyrazoline (C4), respectively. The combination of 1H-NMR, 13C-NMR and DEPT-135 provides strong evidence in support of the structure assigned to this pyrazoline derivative. The MS (ESI) spectrum of compound 2 exhibits an M+1 peak at m/z = 470. The value is in complete agreement with the structure assigned. Starting material 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one 1 was synthesized based on a literature method [13].
Scheme 1. Synthetic route to the title compound 2.
Scheme 1. Synthetic route to the title compound 2.
Molbank 2011 m714 sch001

3. Experimental

The melting point was determined in an open-end capillary tube on a digital melting point apparatus and is uncorrected. Infrared (IR) and proton nuclear magnetic resonance (1H-NMR) spectra were recorded on a Nicolet 380 FT-IR (KBr) and a Bruker DRX-300 instrument, respectively. Chemical shifts are expressed in parts per million (ppm) relative to tetramethylsilane as an internal standard. The elemental analysis (C/N) was performed on a Vario EL III CHNS analyzer using sulphanilic acid as a standard. The ESI-MS spectrum was recorded on a Waters Micromass Q-TOF Micro. The homogeneity of the compounds was monitored by ascending thin-layer chromatography (TLC), visualized by iodine vapour.

Synthesis of [5-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone (2)

A solution of chalcone 1 (0.0025 mol) and INH (0.0031 mol) in glacial acetic acid (6 mL) was refluxed for 38 h. The reaction mixture was poured into crushed ice to give the crude product which was filtered and washed first with ethyl acetate (to remove any traces of chalcone) and then with hot water (to remove excess of hydrazide), followed by recrystallization from ethanol.
Yield: 78%; mp: 224–226 °C; buff cream amorphous solid.
IR (KBr) cm−1: 2,921 (C-H), 2,847 (C-H), 1,638 (C=O), 1,613 (C=N), 1,556 (C=C).
1H-NMR (300 MHz, CDCl3): δ (ppm) 8.76 (s, IH, C5 pyrazole), 7.83–7.76 (m, 5H, Ar-H), 7.70–7.60 (m, 4H, Ar-H), 7.46–7.37 (m, 9H, Ar-H), 6.08 (dd, 1H, HX, J = 11.55, 4.80 Hz), 3.71 (dd, 1H, HB, J = 17.40, 11.70 Hz), 3.21 (dd, 1H, HA, J = 17.55, 4.50 Hz).
13C-NMR (75 MHz, CDCl3): δ 41.49 (CH2), 53.62 (CH), 118.26, 119.15, 125.79, 126.66, 126.85, 128.31, 128.50, 128.71, 128.82, 129.38, 130.91, 133.17, 134.61, 139.78, 140.93, 149.84, 150.10, 151.8, 167.82.
DEPT-135: 41.49 (negative peak, CH2), 53.62 (positive peak, CH).
Anal. Calcd for C30H23N5O: C, 76.74; H, 4.94; N, 14.92. Found: C, 76.41; H, 4.59; N, 14.31. ESI-MS: m/z = 470 (M+1)+.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgments

Authors express sincere thanks to the management of RITS, Sirsa for providing the necessary facility for the project.

References

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MDPI and ACS Style

Kaushik, D.; Nagpal, U.; Verma, T.; Madan, K. [5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone. Molbank 2011, 2011, M714. https://doi.org/10.3390/M714

AMA Style

Kaushik D, Nagpal U, Verma T, Madan K. [5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone. Molbank. 2011; 2011(1):M714. https://doi.org/10.3390/M714

Chicago/Turabian Style

Kaushik, Darpan, Upasana Nagpal, Tarawanti Verma, and Kapish Madan. 2011. "[5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone" Molbank 2011, no. 1: M714. https://doi.org/10.3390/M714

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