Abstract
(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone 2 has been synthesized through condensation of 3-acetyl-6-chloro-1H-cinnolin-4-one 1 with isonicotinic acid hydrazide (INH) in absolute ethanol. The structure of the title compound 2 was established on the basis of IR, 1H-NMR, 13C-NMR and mass spectral data.
Cinnoline is a benzfused pyridazine containing two nitrogen atoms at 1,2-position and it is categorized under benzfused diazines class of heterocyclic compounds. Literature shows several compounds containing a cinnoline moiety with a wide spectrum of pharmacological activities, like antimicrobial, anti-inflammatory, anticancer, antimalarial and antipsychotic etc. [1,2,3,4,5]. As a part of research on benzfused heterocyclic compounds [6], we report here the synthesis of (8-chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone 2.
The 1H-NMR spectrum of the compound 1 showed two singlets: one for the methyl group at 2.60 ppm and another for the cinnoline-NH proton at 13.90 ppm which is D2O exchangeable. The characteristic peak of the cinnoline-NH proton disappeared and the singlet of the methyl group shifts to 2.34 ppm in the 1H-NMR spectrum of compound 2. Furthermore, in the 13C-NMR spectrum of compound 2 the peaks due to carbonyl carbons were missing. The fact was also supported by the mass spectrum of compound 2 which showed an (M + 2) peak at m/z 326. The values are completely in agreement with the structure assigned. Starting material 3-acetyl-6-chloro-1H-cinnolin-4-one (1) was synthesized based on a literature method [7].
Synthesis of (8-chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone 2
To a solution of 1 (1.0 g, 0.005 mol) in absolute EtOH (40 mL) isonicotinic acid hydrazide (0.68 g, 0.005 mol) and conc. H2SO4 (0.4 mL) were added. The reaction mixture was refluxed for 6 h, then the excess ethanol was distilled off and the mixture was allowed to cool to room temperature. The resulting product was poured into 150 mL of cold H2O. The precipitate was filtered, air dried and recrystallised from methanol. The purity of compound 2 was checked by TLC, using benzene/acetone (8:2) as mobile phase and iodine (I2) as visualizing agent.
Yield 84%; mp 162 °C; pale yellow amorphous solid.
IR (KBr) cm-1: 2921 (C-H), 1690 (C=O), 1623 (C=N), 1524 (C=C), 756 (C-Cl).
1H-NMR (300 MHz, CDCl3): δ (ppm) 2.34 (s, 3H, -CH3), 7.39 (unresolved broad singlet, 3H, cinnoline-H), 7.51 (d, 2H, pyridine-H, J = 8.8 Hz), 7.80 (d, 2H, pyridine-H, J = 8.4 Hz).
13C-NMR (75 MHz, CDCl3): δ 12.9 (CH3), 123.4, 128.8, 130.9, 132.4, 133.2, 138.4, 140.8, 144.3, 149.2, 151.7, 189.8 (C=O).
FAB-MS m/z: 324.09 (M+), 326.09 (M + 2).
Anal. Calcd for C16H10ClN5O: C, 59.36, H, 3.11, N, 21.63; Found: C, 59.53, H, 3.09, N, 21.71.
Supplementary materials
Supplementary File 1Supplementary File 2Supplementary File 3Acknowledgements
One of the authors (R.K.) expresses sincere thanks to the University Grant Commission (UGC), New Delhi, India, for the award of Rajiv Gandhi National Fellowship (RGNF). The authors are also thankful to Central Drug Research Institute (CDRI), Lucknow, India for recording spectral data.
References
- Narayana, B.; Vijayaraj, K.K.; Ashalatha, B.V.; Kumari, S.N. Antibacterial and antifungal studies on some new acetylcinnolines and cinnolinyl thiazole derivatives. Indian J. Chem. 2006, 45B, 1704–1709. [Google Scholar] [CrossRef]
- Schatz, F.; Wagner-Jauregg, T. Synthesis of substituted 1, 2-malonyl-1,2-dihydrocinnolin (1,3-Dioxo-2,3-dihydro-1H-pyrazolo[1,2-a]cinnoline) with anti-inflammatory properties. Helv. Chim. Acta 1968, 51, 1919–1931. [Google Scholar] [CrossRef] [PubMed]
- Barraja, P.; Diana, P.; Lauria, A.; Passannanti, A.; Almerico, A.M.; Minnei, C.; Longu, S.; Congiu, D.; Musiu, C.; La Colla, P. Indolo[3,2-c]cinnolines with antiproliferative, antifungal, and antibacterial activity. Bioorg. Med. Chem. 1999, 7, 1591–1596. [Google Scholar] [CrossRef]
- Keneford, J.R.; Simpson, J.C.E. Synthetic antimalarials. Part XX. cinnolines. Part XIII. Synthesis and antimalarial action of 4-aminoalkylaminocinnolines. J. Chem. Soc. 1947, 917–920. [Google Scholar] [CrossRef]
- Alvarado, M.; Barcelo, M.; Carro, L.; Masaguer, C.F.; Ravina, E. Synthesis and biological evaluation of new quinazoline and cinnoline derivatives as potential atypical antipsychotics. Chem. Biodivers. 2006, 3, 106–117. [Google Scholar] [CrossRef] [PubMed]
- Kumar, S.; Bawa, S.; Drabu, S. N-[(2-chloro-6-mthylquinolin-3-yl)methyl]aniline. Molbank 2009, 2009, M618. [Google Scholar] [CrossRef]
- Vingkar, S.L.; Bobade, A.S.; Khadse, B.G. Synthesis and antimicrobial activity of 3-2(alkyl/aryl,4-substituted thiozolo)-6-fluorocinnoline-4-ones. Indian J. Chem. 1993, 32B, 1281–1284. [Google Scholar]
© 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an Open Access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).