Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

An Operationally Simple and Efficient Synthesis of 7-Benzylidene-substitutedphenyl- 3,3a,4,5,6,7-hexahydro-2H-indazole by Grinding Method

Author(s): Santosh Raut*, Bharat Dhotre , Atul Tidke and Mohammad Arif Pathan

Volume 17, Issue 4, 2020

Page: [313 - 321] Pages: 9

DOI: 10.2174/1570179417666200406142118

Price: $65

Abstract

Background: An eco-friendly, operationally simple and efficient reaction is shown between various 2,6-bis-(substituted-benzylidene)-cyclohexanones and differently substituted hydrazine in the presence of acetic acid.

Methods: The reaction between various 2,6-bis-(substituted-benzylidene)-cyclohexanones and differently substituted hydrazine in the presence of acetic acid afforded 7-Benzylidene-substituted-phenyl-3,3a,4,5,6,7- hexahydro-2H-indazole in 74 to 92 % yield in short reaction time using the grindstone technique.

Results and Discussion: The notable advantages of this method include mild synthetic conditions, weak acid catalysis, and non-hazardous solvent which make this method environmentally safer.

Conclusion: In conclusion, we have developed an efficient, simple and eco-friendly method for the synthesis of 7-Benzylidene-substituted-phenyl-3,3a,4,5,6,7-hexahydro-2H-indazole by grinding technique. The notable benefits of this method are waste minimization, no organic solvent required, simple procedure, easy work-up, and clean reaction profile.

Keywords: Acetic acid, hydrazine, grindstone chemistry, 2H-indazoles, 2, 6-Bis-(substituted-benzylidene)-cyclohexanone, eco-friendly.

« Previous
Graphical Abstract
[1]
Vidyacharan, S.; Sagar, A.; Chaitra, N.C.; Sharada, D.S. A facile synthesis of 2H-indazoles under neat conditions and further transformation into aza-γ-carboline alkaloid analogues in a tandem one-pot fashion. RSC Advances, 2014, 4, 34232.
[http://dx.doi.org/10.1039/C4RA06838F]
[2]
Hassankhani, A.; Mosaddegh, E.; Ebrahimipour, E.Y. Tungstosilicic acid as an efficient catalyst for the one-pot multicomponent synthesis of triazolo[1,2-a]indazole-1,3,8-trione derivatives under solvent-free conditions. Arab. J. Chem., 2011, 9, S936.
[http://dx.doi.org/10.1016/j.arabjc.2011.10.003]
[3]
Zangade, S.; Mokle, S.; Vibhute, A.; Vibhute, Y. An efficient and operationally simple synthesis of some new Chalcones by using Grinding Technique. Chem. Sci. J., 2011, 13, 1.
[http://dx.doi.org/10.4172/2150-3494.1000011]
[4]
Senthilkumar, G.; Neelakandan, K.; Manikandan, H. A convenient, green, solvent free synthesis and characterization of novel fluoro chalcones under grind-stone chemistry. Der Chemica Sinica, 2014, 5(2), 106-113.
[5]
Friscić, T.; Trask, A.V.; Jones, W.; Motherwell, W.D.S. Screening for inclusion compounds and systematic construction of three-component solids by liquid-assisted grinding. Angew. Chem. Int. Ed. Engl., 2006, 45(45), 7546-7550.
[http://dx.doi.org/10.1002/anie.200603235] [PMID: 17051633]
[6]
Piste, B. P. Synthesis of Chalcones by grindstone chemistry as an intermediate in Organic Synthesis. Int. j. curr. Sci., 2014, 13, E 62-66.
[7]
Cyr, P.; Régnier, S.; Bechara, W.S.; Charette, A.B. Rapid access to 3-aminoindazoles from tertiary amides. Org. Lett., 2015, 17(14), 3386-3389.
[http://dx.doi.org/10.1021/acs.orglett.5b00765] [PMID: 26154712]
[8]
Conrad, W.E.; Rodriguez, K.X.; Nguyen, H.H.; Fettinger, J.C.; Haddadin, M.J.; Kurth, M.J. A one-pot-three-step route to triazolotriazepinoindazolones from oxazolino-2H-indazoles. Org. Lett., 2012, 14(15), 3870-3873.
[http://dx.doi.org/10.1021/ol3015804] [PMID: 22823414]
[9]
Prasad, A.N.; Srinivas, R.; Reddy, B.M. CuII–hydrotalcite catalyzed one-pot three component synthesis of 2H-indazoles by consecutive condensation, C–N and N–N bond formations. Catal. Sci. Technol., 2013, 3, 654-658.
[http://dx.doi.org/10.1039/C2CY20590D]
[10]
Laleu, B.; Lautens, M. Synthesis of annulated 2H-indazoles and 1,2,3- and 1,2,4-triazoles via a one-pot palladium-catalyzed alkylation/direct arylation reaction. J. Org. Chem., 2008, 73(22), 9164-9167.
[http://dx.doi.org/10.1021/jo8017236] [PMID: 18947186]
[11]
Soltani Rad, M. N. Ultrasound promoted mild and facile one-pot, three component synthesis of 2H-indazoles by consecutive condensation, CN and NN bond formations catalysed by copper-doped silica cuprous sulphate (CDSCS) as an efficient heterogeneous nano-catalyst Ultrason. Sonochem, 2017, 34, 865.
[http://dx.doi.org/10.1016/j.ultsonch.2016.07.026]
[12]
Meenatchi, V.; Muthu, K.; Rajasekar, M.; Meenakshisundaram, S. Synthesis, spectral, thermal, optical and theoretical studies of (2E,6E)-2-benzylidene-6-(4-methoxybenzylidene)cyclohexanone. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2014, 120, 72-76.
[http://dx.doi.org/10.1016/j.saa.2013.10.003] [PMID: 24177872]
[13]
Nakhjiri, M.; Safavi, M.; Alipour, E.; Emami, S.; Atash, A.F.; Jafari-Zavareh, M.; Ardestani, S.K.; Khoshneviszadeh, M.; Foroumadi, A.; Shafiee, A. Asymmetrical 2,6-bis(benzylidene)cyclohexanones: Synthesis, cytotoxic activity and QSAR study. Eur. J. Med. Chem., 2012, 50, 113-123.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.045] [PMID: 22341788]
[14]
Nakhai, A.; Bergman, J. Synthesis of hydrogenated indazole derivatives starting with α,β-unsaturated ketones and hydrazine derivatives. Tetrahedron, 2009, 65, 2298-2306.
[http://dx.doi.org/10.1016/j.tet.2009.01.041]
[15]
Shinde, S.S.; Deshmukh, S.U.; Pawar, R.P.; Marathe, R.P. Silica Sulfuric Acid : An efficient catalyst for the synthesis of substituted indazoles Der Chemica Sinica, 2010, 2, 29-34.http://www.imedpub.com/articles/silicasulfuric-acid--an-efficient-catalyst-for-the-synthesis-ofsubstitutedindazoles.pdf
[16]
Nordmann, J.; Eierhoff, S.; Denißen, M.; Mayer, B.; Müller, T.J.J. Two-Step Synthesis of Blue Luminescent (Pyrrol-3-yl)-1H-(aza)indazoles Based on a Three-Component Coupling-Cyclocondensation Sequence. Eur. J. Org. Chem., 2015, 2015(23), 5128-5142.
[http://dx.doi.org/10.1002/ejoc.201500575]
[17]
Sun, F.; Feng, X.; Zhao, X.; Huang, Z.; Shi, D.Q. An efficient synthesis of 2H-indazoles via reductive cyclization of 2-nitrobenzylamines induced by low-valent titanium reagent. Tetrahedron, 2012, 20, 3851-3855.
[http://dx.doi.org/10.1016/j.tet.2012.03.043]
[18]
Lebedev, A.Y.; Khartulyari, A.S.; Voskoboynikov, A.Z. Synthesis of 1-aryl-1H-indazoles via palladium-catalyzed intramolecular amination of aryl halides. J. Org. Chem., 2005, 70(2), 596-602.
[http://dx.doi.org/10.1021/jo048671t] [PMID: 15651807]
[19]
Bae, Y.K.; Cho, C.S. Copper(I) salt/PEG-400 catalysis in one-pot direct synthesis of 1-aryl-1H-indazoles from 2-bromobenzaldehydes and arylhydrazines. Appl. Organomet. Chem., 2013, 27(4), 224-227.
[http://dx.doi.org/10.1002/aoc.2956]
[20]
Thomé, I.; Besson, C.; Kleine, T.; Bolm, C. Base-catalyzed synthesis of substituted indazoles under mild, transition-metal-free conditions. Angew. Chem. Int. Ed. Engl., 2013, 52(29), 7509-7513.
[http://dx.doi.org/10.1002/anie.201300917] [PMID: 23740864]
[21]
Zhou, P.; Malamas, M.; Robichaud, A.J. An efficient synthesis of 2-amino-4-(4-fluoro-3-(2-fluoropyridin-3-yl)phenyl)-4-(4-methoxy-3-methylphenyl)-1-methyl-1H-imidazol-5(4H)-one, a potent BACE1 inhibitor. ARKIVOC, 2010, (vi), 84-88.
[http://dx.doi.org/10.3998/ark.5550190.0011.609]
[22]
Folkes, A.J.; Ahmadi, K.; Alderton, W.K.; Alix, S.; Baker, S.J.; Box, G.; Chuckowree, I.S.; Clarke, P.A.; Depledge, P.; Eccles, S.A.; Friedman, L.S.; Hayes, A.; Hancox, T.C.; Kugendradas, A.; Lensun, L.; Moore, P.; Olivero, A.G.; Pang, J.; Patel, S.; Pergl-Wilson, G.H.; Raynaud, F.I.; Robson, A.; Saghir, N.; Salphati, L.; Sohal, S.; Ultsch, M.H.; Valenti, M.; Wallweber, H.J.; Wan, N.C.; Wiesmann, C.; Workman, P.; Zhyvoloup, A.; Zvelebil, M.J.; Shuttleworth, S.J. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J. Med. Chem., 2008, 51(18), 5522-5532.
[http://dx.doi.org/10.1021/jm800295d] [PMID: 18754654]
[23]
Slade, D.J.; Pelz, N.F.; Bodnar, W.; Lampe, J.W.; Watson, P.S. Indazoles: regioselective protection and subsequent amine coupling reactions. J. Org. Chem., 2009, 74(16), 6331-6334.
[http://dx.doi.org/10.1021/jo9006656] [PMID: 19618957]
[24]
Lokhande, P.D.; Hasanzadeh, K.; Khaledi, H.; Hapipah, M.A.H.M. Aromatization and halogenation of 3,3a,4,5-Tetrahydro-3-aryl-2- phenyl-2benzo[g]indazole using I2/DMSO, CuCl2/DMSO, and N-Bromosuccinimide. J. heterocyclic. Chem, 2012, 49, 1398-1406.
[25]
Rajanarendar, E.; Reddy, A.S.R.; Shaik, F.P. A simplified Cadogan’s approach to synthesis of new isoxazolyl indazoles. Indian J. Chem. - Sect. B Org. Med. Chem., 2008, 12, 1591-1596.http://nopr.niscair.res.in/handle/123456789/2267
[26]
Wang, C.D.; Liu, R.S. Silver-catalyzed [3+2]-cycloaddition of benzynes with diazocarbonyl species via a postulated (1H-indazol-1-yl)silver intermediate. Org. Biomol. Chem., 2012, 10(45), 8948-8952.
[http://dx.doi.org/10.1039/c2ob26760h] [PMID: 23076121]
[27]
Sagar, A.; Babu, V.N.; Sharada, D.S. Silica gel promoted environment-friendly synthesis of α-amino amidines and regioselective transformation of α-amino amidines into amidino substituted indazoles. RSC Advances, 2015, 37, 29066-29071.
[http://dx.doi.org/10.1039/C5RA02491A]
[28]
Yu, D.G.; Suri, M.; Glorius, F. Rh(III)/Cu(II)-cocatalyzed synthesis of 1Hindazoles through C-H amidation and N-N bond formation. J. Am. Chem. Soc., 2013, 135(24), 8802-8805.
[http://dx.doi.org/10.1021/ja4033555] [PMID: 23711098]
[29]
Fang, Y.; Wu, C.; Larock, R.C.; Shi, F. Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes. J. Org. Chem., 2011, 76(21), 8840-8851.
[http://dx.doi.org/10.1021/jo201605v] [PMID: 21970468]
[30]
Lefebvre, V.; Cailly, T.; Fabis, F.; Rault, S. Two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles. J. Org. Chem., 2010, 75(8), 2730-2732.
[http://dx.doi.org/10.1021/jo100243c] [PMID: 20232925]
[31]
Li, P.; Zhao, J.; Wu, C.; Larock, R.C.; Shi, F. Synthesis of 3-substituted indazoles from arynes and N-tosylhydrazones. Org. Lett., 2011, 13(13), 3340-3343.
[http://dx.doi.org/10.1021/ol201086g] [PMID: 21630698]
[32]
Muralikrishna, S.; Rao, P.J.; Reddy, P.R. Synthesis and screening of some novel 1-((5-phenyl-1,3,4- oxadiazol-2-yl)methyl)-3-((piperazin-1-yl)methyl)-1Hindazole. Biomed. J. Sci. Tech. Res., 2017, 1(7), 4-8.
[33]
Teixeira, F.C.; Antunes, I.F.; Curto, M.J.M.; Neves, M.; Teixeirac, A.P.S. Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: Synthesis and characterization. ARKIVOC, 2009, (11), 69-84.
[http://dx.doi.org/10.3998/ark.5550190.0010.b07]
[34]
Gorja, D.R.; Kumar, K.S.; Dulla, B.B.; Mukkanti, K.; Pala, M. Pd/C-mediated alkynylation of indazoles: Synthesis and pharmacological evaluation of mono and dialkynyl-substituted indazoles. J. Heterocycl. Chem., 2014, 51, 374-382.
[http://dx.doi.org/10.1002/jhet.1602]
[35]
May, J.A.; Dantanarayana, A.P.; Zinke, P.W.; McLaughlin, M.A.; Sharif, N.A. 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. J. Med. Chem., 2006, 49(1), 318-328.
[http://dx.doi.org/10.1021/jm050663x] [PMID: 16392816]
[36]
Gogireddya, S.; Kalle, A.M.; Dubey, P.K.; Reddy, A.V. Design, synthesis and characterization of 1H-pyridin-4-yl-3,5-disubstituted indazoles and their AKT inhibition activity. J. Chem. Sci., 2014, 126(4), 1055-1062.
[http://dx.doi.org/10.1007/s12039-014-0644-6]
[37]
Kim, O.S.; Jang, J.H.; Kim, H.T.; Han, S.J.; Tsui, G.C.; Joo, J.M. Synthesis of fluorescent indazoles by palladium-catalyzed benzannulation of pyrazoles with alkynes. Org. Lett., 2017, 19(6), 1450-1453.
[http://dx.doi.org/10.1021/acs.orglett.7b00410] [PMID: 28271896]
[38]
Miloudi, A.; El Abed, D.; Boyer, G. Phenylation of aminoindazole derivatives. Arab. J. Chem., 2017, 10(8), 1184-1187.
[http://dx.doi.org/10.1016/j.arabjc.2014.08.003]
[39]
Saikia, A.K.; Unnava, R.; Indukuri, K.; Sarkar, S. Regioselective one-pot, three-component synthesis of substituted 2H-indazoles from 2-nitroarylaldehyde, alkyne and amine catalyzed by the CuBr/Zn(OTf)2system. RSC Advances, 2014, 4(98), 55296-55299.
[http://dx.doi.org/10.1039/C4RA10093J]
[40]
Veerareddy, A.; Gogireddy, S.; Dubey, P.K. Regioselective synthesis of 1-substituted indazole-3-carboxylic acids. J. Heterocycl. Chem., 2014, 51, 1311-1321.
[http://dx.doi.org/10.1002/jhet.1717]
[41]
Guan, Z.; Namyslo, J.C.; Drafz, M.H.; Nieger, M.; Schmidt, A.; Schmidt, A. Dimerisation, rhodium complex formation and rearrangements of Nheterocyclic carbenes of indazoles. Beilstein J. Org. Chem., 2014, 10, 832-840.
[http://dx.doi.org/10.3762/bjoc.10.79] [PMID: 24778738]
[42]
Han, S.; Shin, Y.; Sharma, S.; Mishra, N.K.; Park, J.; Kim, M.; Kim, M.; Jang, J.; Kim, I.S. Rh(III)-catalyzed oxidative coupling of 1,2-disubstituted arylhydrazines and olefins: a new strategy for 2,3-dihydro-1H-indazoles. Org. Lett., 2014, 16(9), 2494-2497.
[http://dx.doi.org/10.1021/ol500865j] [PMID: 24754303]
[43]
Chen, J.; Chen, P.; Song, C.; Zhu, J. Rhodium(III)-catalyzed N-nitroso-directed C-H addition to ethyl 2-oxoacetate for cycloaddition/fragmentation synthesis of indazoles. Chemistry, 2014, 20(44), 14245-14249.
[http://dx.doi.org/10.1002/chem.201404506] [PMID: 25224915]
[44]
Hangirgekar, S.P. Montmorillonite K-10 catalysed synthesis of 1-aryl-3- alkyl substituted indazoles. J. Chem. Bio. Phy. Sci. Sec. A., 2012, 2(4), 1676-1680.
[45]
Yu, J.; Lim, J.W.; Kim, S.Y.; Kim, J.; Kim, J.N. An efficient transition-metal-free synthesis of 1H-indazoles from arylhydrazones with montmorillonite K-10 under O2 atmosphere. Tetrahedron Lett., 2015, 56(11), 1432-1436.
[http://dx.doi.org/10.1016/j.tetlet.2015.01.183]
[46]
Wasi, A.; Bhupendra, B.K.; Gupta, A.K.; Intodia, K. Ecofriendly synthesis of some bioactive pyrazoline and isoxazoline derivatives from α, β-unsaturated cyclohexanone. Int. J. Chem. Sci., 2013, 11(4), 1621-1635.
[47]
Deokate, M.D.; Joshi, R.S.; Gaikwad, S.V.; Lokhande, P.D. Synthesis of 2,6- dibenzylidenecyclohexanone and e-7-benzylidene-3-phenyl-3,3a,4,5,6,7-hexahydro-2H-indazole. JETIR, 2017, 4(6), 25-29.
[48]
Mahdavinia, G.H.; Mirzazadeh, M. Zahed Karimi-Jaber. A mild, simple, and efficient approach to the synthesis of some novel 7-benzylidene-2,3-diphenyl-3,3a,4,5,6,7-hexahydro-2H-indazole derivatives. Green Chem. Lett. Rev., 2014, 8, 13-15.
[http://dx.doi.org/10.1080/17518253.2014.976280]
[49]
Amoozadeha, A.; Tabriziana, E.; Salehia, M.; Kubickib, M.; Rahmania, S.; Shamsia, T.; Bitarafa, M. Catalyst-free synthesis of (7E)-7-benzylidene-3,3a,4,5,6,7-hexahydro-2,3-diphenyl-2H-indazole derivatives in PEG-400 as a green and reusable solvent. J. Chem. Res., 2016, 40, 535-539.
[http://dx.doi.org/10.3184/174751916X14709222930154]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy