Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of Some New 1, 3, 4-Oxadiazole, Pyrazole, and Pyrimidine Bearing Thienopyrazole Moieties

Author(s): Mohamed Ahmed Elian Sophy* and Mohamed Ahmed Mahmoud Abdel Reheim

Volume 17, Issue 8, 2020

Page: [661 - 670] Pages: 10

DOI: 10.2174/1570179417999200730215318

Price: $65

Abstract

Aim and Objective: According to the literature survey, pyrazole is a unique template that is associated with several biological activities. This article highlighted the research work of many researchers reported in the literature for synthesis and different pharmacological activities of the pyrazole nucleus. In the present work, pyrazol- 3-one 1 was reacted with cyanoacetic acid hydrazide and elemental sulfur to afford the corresponding thieno[3,2-c]pyrazol-6-carbohydrazide 3 derivatives. The latter compound reacted with some electrophilic reagents such as DMF-DMA, triethylorthoformate, arylidenemalononitriles and chalcones under neat conditions to give substituted oxadiazole and pyrazole, respectively. The treatment of compound 3 with active methylene reagents such as acetylacetone, diethylmalonate, ethyl acetoacetate and ethyl cyanoacetate under suitable conditions afforded pyrazole derivatives 10, 11, 13, and 15, respectively. Novel pyrazolothienopyrimidine 27 and 30 were prepared from precursor 26 with carbon disulfide and triethylorthoformate, respectively. The chemical structures of the newly synthesized compounds were established by elemental and spectral analyses including IR, and 1HNMR in addition to 13C-NMR and mass spectra.

Materials and Methods: A novel substituted pyrazole, pyrimidine and pyrazolothienopyrimidine were obtained via Gewald synthesis of thiophene and fused thiophene and Mannich reactions of 5-amino-3-phenyl-1Hthieno[ 3,2-c]pyrazole-6-carbohydrazide.

Results and Discussion: A series of some newly azoles and azines were prepared via reaction of thieno[3,2- c]pyrazol-6-carbohydrazide derivative 3 as starting material with some electrophilic and nucleophilic reagents. The structures of target compounds were established by elemental analyses and spectral data.

Conclusion: Pyrazole is a unique template that is associated with several biological activities. This article highlighted the research work of many researchers reported in the literature for synthesis and different pharmacological activities of the pyrazole nucleus. In the current investigation, we have developed new and efficient methods for the synthesis of thieno[3,2-c]pyrazol-6-carbohydrazide derivatives. In addition, we have explored the preparative potential of these substances as intermediates for the synthesis of substituted pyrazoles and fused pyrazoles 10-30, respectively.

Keywords: Synthesis, thienopyrazole, oxadiazole, pyrazole, pyrimidine, pyrazolothienopyrimidine.

« Previous Next »
Graphical Abstract

[1]
Rabie, S.T.; Abdelhalim, M.M.; Mohamed, N.R. Synthesis of some novel pyrazole derivatives as potent antimicrobial agents. OCAIJ, 2013, 9(10), 414-424.
[2]
El Sekily, M.A.; Mancy, S.H.; Hamada, N.M.M. Synthesis, characterization, and antimicrobial activity of pyrazole-3-yl pyrimidine, pyrazole and pyran derivatives. Int. J. Curr. Res., 2019, 11(7), 5563-5570.
[3]
Rani, V.E.; Ravindranath, L.K. Synthesis, characterization and antimicrobial evaluation of novel mannich bases containing pyrazole-5-one phosphonates. J. Pharm. Pharm. Sci., 2016.
[http://dx.doi.org/10.2174/1874844901603010049]
[4]
Akula, G.; Chandrul, K.K.; Dvrn, B. Synthesis, characterization and antimicrobial activity of some novel 3,4-disubstituted pyrazole derivaitves. Asian J of Pharm Clin Res, 2020, 13(1), 129-133.
[5]
Bildirici, I.; Cetin, A.; Menges, N.; Alan, Y. Synthesis and SAR studies of pyrazole-3-carboxamides and 3-carbonyl thioureides including chiral moiety: novel candidates as antibacterial agents. J. Serb. Chem. Soc., 2018, 83(7-8), 795-807.
[http://dx.doi.org/10.2298/JSC170313029B]
[6]
Soylem, E.A.; Assy, M.G.; Morsi, G.M. Michael cyclization of polarized systems: synthesis and in vitro anti-diabetic evalution of some novel pyrimidine, pyridine, pyrazole and pyrazolo[3,4-b]pyridine derivatives. Croat. Chem. Acta, 2017, 90(3), 461-469.
[http://dx.doi.org/10.5562/cca3122]
[7]
Anandarajagopal, K.; Anbu Jeba Sunilson, J. IIIavarasu, A.; Thangavelpandian, N.; Kalirajan, R. Antiepileptic and antimicrobial activites of novel 1-(unsubstituted/substituted)-3,5-dimethyl-1H-pyrazole derivatives. Int. J. Chemtech Res., 2010, 2(1), 45-49.
[8]
Bansal, S.; Bala, M.; Suthar, S.K.; Choudhary, S.; Bhattacharya, S.; Bhardwaj, V.; Singla, S.; Joseph, A. Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity. Eur. J. Med. Chem., 2014, 80, 167-174.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.045] [PMID: 24780593]
[9]
El-Moghazy, S.M.; Barsoum, F.F.; Abdel-Rahman, H.M.; Marzouk, A.A. Synthesis and anti-inflammatory activity of some pyrazole derivatives. Med. Chem. Res., 2012, 21, 1722-1733.
[http://dx.doi.org/10.1007/s00044-011-9691-4]
[10]
Zheng, L.W.; Wu, L.L.; Zhao, B.X.; Dong, W.L.; Miao, J.Y. Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells. Bioorg. Med. Chem., 2009, 17(5), 1957-1962.
[http://dx.doi.org/10.1016/j.bmc.2009.01.037] [PMID: 19217789]
[11]
Xia, Y.; Dong, Z.W.; Zhao, B.X.; Ge, X.; Meng, N.; Shin, D.S.; Miao, J.Y. Synthesis and structure-activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide derivatives as potential agents against A549 lung cancer cells. Bioorg. Med. Chem., 2007, 15(22), 6893-6899.
[http://dx.doi.org/10.1016/j.bmc.2007.08.021] [PMID: 17804244]
[12]
Lian, S.; Su, H.; Zhao, B.X.; Liu, W.Y.; Zheng, L.W.; Miao, J.Y. Synthesis and discovery as anti cancer of autophagy in A549 lung cancer cells. Bioorg. Med. Chem., 2009, 17, 7085-7092.
[http://dx.doi.org/10.1016/j.bmc.2009.09.004] [PMID: 19773174]
[13]
Pathak, R.B.; Chovatia, P.T.; Parekh, H.H. Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorg. Med. Chem. Lett., 2012, 22(15), 5129-5133.
[http://dx.doi.org/10.1016/j.bmcl.2012.05.063] [PMID: 22695129]
[14]
Pathak, V.; Maurya, H.K.; Sharma, S.; Srivastava, K.K.; Gupta, A. Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents. Bioorg. Med. Chem. Lett., 2014, 24(13), 2892-2896.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.094] [PMID: 24835631]
[15]
Shih, S.R.; Chu, T.Y.; Reddy, G.R.; Tseng, S.N.; Chen, H.L.; Tang, W.F.; Wu, M.S.; Yeh, J.Y.; Chao, Y.S.; Hsu, J.T.; Hsieh, H.P.; Horng, J.T. Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. J. Biomed. Sci., 2010, 17(13), 13.
[http://dx.doi.org/10.1186/1423-0127-17-13] [PMID: 20178582]
[16]
Chimenti, F.; Fioravanti, R.; Bolasco, A.; Manna, F.; Chimenti, P.; Secci, D.; Befani, O.; Turini, P.; Ortuso, F.; Alcaro, S. Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors. J. Med. Chem., 2007, 50(3), 425-428.
[http://dx.doi.org/10.1021/jm060868l] [PMID: 17266193]
[17]
Sahar, A.A.; Samir, M.A.; Ahmed, M.S.; Shahenda, M.; Heba, T.; Naglaa, M.A.A. Design, Synthesis, molecular modelling and biological evalution of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors. J. Enzyme. Med. Chem., 2020, 35(1), 847-863.
[18]
Rashed, A.E.; Abdelmegid, M.; Sharmoukh, A.H.; Abdelmegeid, F.M.E. The chemistry of pyrazolopyrimidines and their applications. OCAIJ, 2014, 10(6), 224-250.
[19]
Faidallah, H.M.; Rostom, S.A.F.; Al-Saadi, M.S. Synthesis and biological evaluation of some new substituted fused pyrazole ring systems as possible anticancer and antimicrobial agents. JKAU:Sci, 2010, 22(1), 177-191.
[http://dx.doi.org/10.4197/Sci.22-1.12]
[20]
El-arab, E.E. Synthesis and cytotoxixty of novel pyrazole derivaitves derived from 3-methyl-1-phenyl-1H-pyrazole-5(4H)-one. Egypt. J. Chem., 2015, 58(6), 741-753.
[http://dx.doi.org/10.21608/ejchem.2015.1017]
[21]
Darwish, E.S.; Mahmoud, F.F.; Altalbawy, F.M.A. Synthesis and antimicrobial evalution of some new pyrazole, fused pyrazolo[1,5-a]-pyrimidine and pyrazolo[1,5-d]pyrimido[4,5-d][1,2,3]triazine derivatives. Asian J. Chem., 2012, 24(7), 2997-3002.
[22]
Darbholkar, V.V.; Ansari, F.Y. Synthesis and characterization of selected fused isoxazole and pyrazole derivatives and their antimicrobial activity. J. Serb. Chem. Soc., 2009, 74(11), 1219-1228.
[http://dx.doi.org/10.2298/JSC0911219D]
[23]
Abdelhafiz, I.S. abdel Reheim, M. A. M.; Baker, S. M.; Ramiz, M. M. Enaminone in heterocyclic synthesis: Synthesis of new pyrazolopyrazole, pyrazolothienooxazine and pyrazolothienopyridine derivatives. J. Chem. Soc. Pak., 2014, 36(6), 1133-1143.
[24]
Ramiz, M.M.M.; Abdel Hafiz, I.S.; Abdel Reheim, M.A.M.; Gaber, H.M. Pyrazolones as building blocks in heterocyclic synthesis: synthesis of new pyrazolopyran, pyrazolopyridazine and pyrazole derivatives of expected antifungicidal activity. J. Chin. Chem. Soc. (Taipei), 2012, 59, 72-80.
[http://dx.doi.org/10.1002/jccs.201100194]
[25]
Sayed, A. E.; Zaki, R. M.; El-Dean, A. M. K. The biological activity of new thieno[2,3-c]pyrazole compounds as anti-oxidants against toxicity of 4- nonylphenol in clarias gariepinus Toxocology reports, 2015, 2, 1145-1453.
[26]
Vaghasiya, S.J.; Dodiya, D.K.; Trivedi, A.R.; Shah, V.H. Synthesis and biological screening of some novel pyrazolo[3′,4′:4,5]thieno[2,3-d]pyrimidin-8-ones via a Gewald reaction. ARKIVOC, 2008, xii, 1-8.
[27]
Zaki, R.M.; El-Dean, A.M.K.; Radwan, S.M.; Saber, A.F. A convenient synthesis, Reactions and biological activity of some new 6H-pyrazolo[4′,3′:4,5]thieno[3,2-d]triazine compounds as antibacterial, anti-fungal and anti- inflammatory agents. J. Braz. Chem. Soc., 2018, 29(12), 2482-2495.
[http://dx.doi.org/10.21577/0103-5053.20180127]
[28]
Mohareb, R.M.; Abbas, N.S.; Ibrahim, R.A. New approaches for the synthesis of thiophene derivatives with anti-tumor activities. Acta Chim. Slov., 2013, 60(3), 583-594.
[PMID: 24169713]
[29]
Deeb, A.; Kotb, M.; El-Abbasy, M. Pyridazine derivatives and related compounds, Part 12: synthesis of some pyridazino[4′,3′:4,5]thieno[3,2-d]-1,2,3-triazines. Phosphorus Sulfur Silicon Relat. Elem., 2005, 180, 591-599.
[http://dx.doi.org/10.1080/104265090517398]
[30]
Abdel Reheim, M.A.M.; Baker, S.M. Synthesis, characterization and in vitro antimicrobial activity of novel fused pyrazolo[3,4-c]pyridazine, pyrazolo[3,4-d]pyrimidine, thieno[3,2-c]pyrazole and pyrazolo[3′,4′:4,5]thieno[2,3-d]pyrimidine derivatives. Chem. Cent. J., 2017, 11(1), 112.
[http://dx.doi.org/10.1186/s13065-017-0339-4] [PMID: 29098473]
[31]
Hafez, H.N.; El-Gazzar, A.B.A. Design and synthesis of 3-pyrazolyl-thiophene, thieno[2,3-d]pyrimidines as new bioactive and pharmacological activities. Bioorg. Med. Chem. Lett., 2008, 18(19), 5222-5227.
[http://dx.doi.org/10.1016/j.bmcl.2008.08.071] [PMID: 18783947]
[32]
Nagesh, H.K.; Padmashali, B.; Sandeep, C.; Yuvaraj, T.C.M.; Siddesh, M.B.; Mallikarjuna, S.M. Synthesis and antimicrobial activity of benzothiophene substituted coumarins, pyrimidines and pyrazole as new scaffold. Int. J. Pharm. Sci. Rev. Res., 2014, 28(2), 6-10.
[33]
Arief, M.M.M.; Aly, A.A.; Khalili, A.A.; Mohamed, H.I. Utility of 4-(isatin-3-ylidenamino)benzohydrazide in the synthesis of bioactive N-heterocyclic compounds. J. Chem. Pharm. Res., 2014, 6(2), 327-335.
[34]
Yassin, F.A. Novel pyrazolyl pyridazine derivatives likely to possess anti-inflammatory activity. J. Microbiol. Antimicrob., 2010, 2(7), 93-99.
[35]
Gaafar, A.M.; Aly, A.S.; Abu-zied, K.H.M.; Gabal, S.H.A. El-B. Shaban, M. Novel one-pot synthesis of thiazolo[3,2-a]pyrimidin-5-one as a key compound for poly nuclear heterocycles. Egypt. J. Chem., 2016, 59(3), 305-319.
[http://dx.doi.org/10.21608/ejchem.2016.1052]
[36]
Barot, V.M.; Rathod, B.G. Syntheis of novel pyrazole derivatives as potential anti microbial agent. Asian J. Biomed. Pharm., 2013, 1(3), 80-85.
[37]
Lee, C.H.; Cho, H.I.; Lee, K.J. Indolyl-1,3,4-oxadiazole derivatives were prepared as reversible. Bull. Korean Chem. Soc., 2001, 22(10), 1153-1155.
[38]
Lee, L.; Robb, L.M.; Lee, M.; Davis, R.; Mackay, H.; Chavda, S.; Babu, B.; O’Brien, E.L.; Risinger, A.L.; Mooberry, S.L.; Lee, M. Design, synthesis, and biological evaluations of 2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoline analogs of combretastatin-A4. J. Med. Chem., 2010, 53(1), 325-334.
[http://dx.doi.org/10.1021/jm901268n] [PMID: 19894742]
[39]
Daidone, G.; Raffa, D.; Plescia, F.; Maggio, B.; Roccaro, A. Synthesis of pyrazole-4-carbohydrazide derivatives of pharmaceutical interest. ARKIVOC, 2002, xi, 227-235.
[40]
Sudha, B.N.; Sridhar, C.; Girija, V.; Reddy, Y.S.R.; Sreevidya, O.; Lavanya, S.; Jyothi, V.A.; Nagesh, V.; Sent, S.; Chakraborty, R. Synthesis, chatacterisation and anthelmintic activity of 3-(4-acetyl-5-phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one derivatives. Indian J. Chem., 2013, 52B, 422-427.
[41]
Radwan, S.H.M.; El-Dean, A.M.K. Synthesis of pyridazothienothiazine and pyrimidothienopyridazines. Phosphorus Sulfur Silicon Relat. Elem., 2000, 164, 299-313.
[http://dx.doi.org/10.1080/10426500008045255]
[42]
de Oliveira, C.S.; Lira, B.F.; dos Santos Falcão-Silva, V.; Siqueira, J.P., Jr; Barbosa-Filho, J.M.; de Athayde-Filho, P.F. Synthesis, molecular properties prediction, and anti-staphylococcal activity of N-acylhydrazones and new 1,3,4-oxadiazole derivatives. Molecules, 2012, 17(5), 5095-5107.
[http://dx.doi.org/10.3390/molecules17055095] [PMID: 22555298]
[43]
Siddiqui, N.J.; Idrees, M.; Khati, N.T.; Dhonde, M.G. Synthesis and antimicrobial activities of some new pyrazoles, oxadiazoles and isoxazole bearing benzofuran moiety. S. Afr. J. Chem., 2013, 66, 248-253.
[44]
Koparir, M.; Cetin, A.; Cansiz, A. 5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-furan-2yl-4H [1,2,4] triazole-3-thiol and their thiol-thione tautomerism. Molecules, 2005, 10(2), 475-480.
[http://dx.doi.org/10.3390/10020475] [PMID: 18007318]

Rights & Permissions Print Cite
Article Metrics
31
© 2024 Bentham Science Publishers | Privacy Policy