Generic placeholder image

Mini-Reviews in Organic Chemistry

Author(s): Mahmoud N. M. Yousif*

DOI: 10.2174/1570193X18666210224153249

DownloadDownload PDF Flyer Cite As
Recent Advances in Chemistry and Biological Activity of 2,6-Diphenyl Piperidines

Page: [125 - 135] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

The review discusses different methods for the preparation of 2,6-diphenyl-piperidin-4-one derivatives. 2,6-Diphenyl-piperidin-4-one is prepared from aromatic aldehyde and acetone in ammonium acetate. Reaction of 1-phenylsulfinylpropan-2-one or 1-(4-chlorophenylsulfinyl)propan-2-one, aromatic aldehyde and ammonium acetate gives a series of 2,6-diaryl-2,3-dihydro-1H-pyridin-4-one 6a,b. 4-Phenyl-2-amino-1,3-butadienes reacts with N-allyl benzaldimine through Diels-Alder reaction to afford 2,6-diphenyl-4-piperidinone derivative 7. Also, reactions of 2,6-diphenyl-piperdin-4-one are discussed. The reactions of the latter compounds can be on nitrogen atom or carbonyl function group or methylene group adjacent to the carbonyl group. In addition, different applications of 2,6-diphenylpiperidin- 4-one are summarized.

Keywords: 2, 6-Diphenyl-piperidin-4-one, piperidine, biological activity, conformations, synthesis, applications

Graphical Abstract

[1]
Yousif, M.N.M.; El-Gazzar, A.B.A.; El-Enany, M.M. Synthesis and biological evaluation of pyrido(2,3-d)pyrimidines. Mini Rev. Org. Chem., 2021, 18(1), 43-54.
[http://dx.doi.org/10.2174/1570193X17999200511010402”]
[2]
Yousif, M.N.M.; El-Gazzar, A.B.A.; Fayed, A.A.; El-Manawaty, M.A.; Yousif, N.M. Synthesis and cytotoxic evaluation of novel chromenes, and chromene(2,3-d)pyrimidines. J. Appl. Pharm. Sci., 2020, 10(12), 35-43.
[3]
Yousif, M.N.M.; Soliman, H.A.; Said, M.M.; Hassan, N.A.; Abdel-Megeid, F.M.E. Synthesis and biological activity of triacetonamine. Russ. J. Gen. Chem., 2020, 90(3), 460-469.
[http://dx.doi.org/10.1134/S1070363220030202]
[4]
Fayed, A.A.; Bahashwan, S.A.; Yousif, M.N.M.; Yousif, N.M.; Gad, F.A. Synthesis and anti-inflammatory activity of some new pyrimidinothienocinnoline derivatives. Russ. J. Gen. Chem., 2019, 89(9), 1887-1895.
[http://dx.doi.org/10.1134/S1070363219090251]
[5]
Yousif, M.N.M.; Nassar, I.F.; Yousif, N.M.; Awad, H.M.; El-Sayed, W.A. Synthesis and anticancer activity of new substituted piperidone compounds and their derived pyrimidine, thiazole and triazole glycoside derivatives. Russ. J. Gen. Chem., 2019, 89(8), 1673-1682.
[http://dx.doi.org/10.1134/S1070363219080218]
[6]
Fayed, A.A.; Yousif, M.N.M.; Abdelgawad, T.T.; Amr, A.E.; Yousif, N.M.; Gad, F.A. Synthesis and antimicrobial activity of novel polycyclic thienopyridazine derivatives. Chem. Heterocycl. Compd., 2019, 55(8), 773-778.
[http://dx.doi.org/10.1007/s10593-019-02534-1]
[7]
Nemr, M.T.M.; Yousif, M.N.M.; Barciszewski, J. Interaction of small molecules with polynucleotide repeats and frameshift site RNA. Arch. Pharm. (Weinheim), 2019, 352(8)e1900062
[http://dx.doi.org/10.1002/ardp.201900062] [PMID: 31169327]
[8]
Yousif, M.N.M.; Fayed, A.A.; Yousif, N.M. Synthesis and reactions of N-hydroxy-triacetonamine derivatives. Egypt. J. Chem., 2019, 62(8), 1759-1766.
[9]
Fayed, A.A.; Bahashwan, S.A.; Yousif, M.N.M.; El Shafey, H.M.; Amr, A.E.; Yousif, N.M.; Shadid, K.A. Synthesis and antiproliferative activity of some newly synthesized pyrazolo-pyridine derivatives. Russ. J. Gen. Chem., 2019, 89(6), 1209-1217.
[http://dx.doi.org/10.1134/S1070363219060173]
[10]
Yousif, M.N.M.; Hussein, H.A.R.; Yousif, N.M.; El-Manawaty, M.A.; El-Sayed, W.A. Synthesis and cytotoxic activity of novel 2-phenylindole linked imidazolothiazole, thiazolo-s-triazine and imidazolyl-sugar systems. J. Appl. Pharm. Sci., 2019, 9(1), 6-14.
[http://dx.doi.org/10.7324/JAPS.2019.90102]
[11]
Yousif, M.N.M.; Fayed, A.A.; Yousif, N.M. Reactions of triacetonamine Part II, synthesis of novel pyrazolo(4,3-c)pyridine derivatives, and 2-(piperidin-4-ylidene)hydrazinecarbothioamide derivatives derived from 2,2,6,6-tetramethyl-piperidin-4-one for in vitro anticancer evaluation. Pharma Chem., 2018, 10(8), 105-109.
[12]
Yousif, M.N.M.; El-Sayed, W.A.; Abbas, H.S.; Awad, H.M.; Yousif, N.M. Anticancer activity of new substituted pyrimidines, their thioglycosides and thiazolopyrimidine derivatives. J. Appl. Pharm. Sci., 2017, 7(11), 21-32.
[13]
Soliman, H.A.; Yousif, M.N.M.; Said, M.M.; Hassan, N.A.; Ali, M.M.; Awad, H.M.; Abdel-Megeid, F.M.E. Synthesis of novel 1,6-naphthyridines, pyrano[3,2-c]pyridines and pyrido[4,3-d]pyrimi-dines derived from 2,2,6,6-tetramethylpiperidin-4-one for in vitro anticancer and antioxidant evaluation. Pharma Chem., 2014, 6(3), 394-410.
[14]
El-Gazzar, A.R.; El-Enany, M.M.; Mahmoud, M.N. Synthesis, analgesic, anti-inflammatory, and antimicrobial activity of some novel pyrimido[4,5-b]quinolin-4-ones. Bioorg. Med. Chem., 2008, 16(6), 3261-3273.
[http://dx.doi.org/10.1016/j.bmc.2007.12.012] [PMID: 18158248]
[15]
Kumar, S.K. sridharbabu, G.; Naresh, B. microwave mediated synthesis of some diaryl piperidine-4one derivatives. Int. J. Biol. Pharm. Res., 2012, 3(1), 48-50.
[16]
Kanagarajan, V.; Sureshkumar, P.; Gopalakrishnan, M. Strange formation of N-hydroxy-3,3-dimethyl-2,6-diarylpiperidin-4-one and its oxime derivative--synthesis, stereochemistry, antibacterial and antifungal activity. Eur. Rev. Med. Pharmacol. Sci., 2010, 14(7), 597-604.
[PMID: 20707249]
[17]
Aridoss, G.; Amirthaganesan, S.; Kumar, N.A.; Kim, J.T.; Lim, K.T.; Kabilan, S.; Jeong, Y.T. A facile synthesis, antibacterial, and antitubercular studies of some piperidin-4-one and tetra-hydropyridine derivatives. Bioorg. Med. Chem. Lett., 2008, 18(24), 6542-6548.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.045] [PMID: 18952418]
[18]
Doss, M.A.; Savithiri, S.; Vembu, S.; Rajarajan, G.; Thanikachalam, V. Synthesis, spectral characterization, of some 3-alkyl-2,6-di(naphthalene-1-yl)piperidin-4-one and oxime deriva-tives and their screening for antimicrobial properities. Can. Chem. Trans., 2015, 3(3), 261-274.
[19]
Jebaraj, J.W.; Gopalakrishnan, M.; Baskar, G. Synthesis and conformational analysis of some 3-alkyl-2,6-diarylpiperidin-4-one semicarbazone. Asian J. Chem., 2008, 20(7), 5282-5288.
[20]
Rani, S.; Sharma, B.K. Kinetic study of oxidation of 2,6-diphenyl-piperidin-4-one and 3-methyl 2,6-diphenyl-piperdin-4-one by manganese (IV) ion. IJETMS, 2017, 6(1), 36-40.
[21]
Arulraj, R.; Sivakumar, S.; Thiruvalluvar, A.; Manimekakai, A. t-3-benzyl-r-2,c-6-diphenylpiperidin-4-one. IUCrData 1, 2016.x160188
[22]
Rajaraman, D.; Sundararajan, G.; Krishnasamy, K. Synthesis, biological evaluation and docking studies of some novel (E)-(4-(2-(benzo[d]thiazol-2-yl)hydrazono)methyl-2,6-diphenylpiperidin-1-yl)(phenyl)methanone derivatives. Int. Lett. Chem. Phys. Astronom., 2015, 60, 35-46.
[23]
Osmani, R.A.; Jadhav, R.L.; Magdum, C.S.; Bhossale, R.R.; Harkare, B.R.; Ghodake, P.P. Synthesis and evaluation of novel furfurylidene derivatives of 2,6-diphenyl piperidin-4-one as antifungal agent. Am. J. Adv. Drug Deliv., 2013, 1(5), 724-733.
[24]
Xavier, G.T.; Thirumalairaj, B.; Jaganathan, M. Effect of piperidin-4-ones on the corrosion inhibition of mild steel in 1N H2SO4. Int. J. Corros., 2015, 2015, 1-15.
[http://dx.doi.org/10.1155/2015/410120]
[25]
Savitha, N.D.; Perumal, S. A facile four-component tandem protocol for the synthesis of novel 2,6-diaryl-2,3-dihydro-1H-pyridin-4-ones. Tetrahedron Lett., 2007, 48, 5627-5629.
[http://dx.doi.org/10.1016/j.tetlet.2007.06.024]
[26]
Garcia, A-B.; Valdes, C.; Cabal, M-P. An imino-Diels-Alder route to meso-2,6-disubstituted-4-piperidones. Tetrahedron Lett., 2004, 45, 4357-4360.
[http://dx.doi.org/10.1016/j.tetlet.2004.03.195]
[27]
Sheeja, N.; Baskar, G.; Veeramalini, J.B.V. Ellucidation of cyclic voltammetric behavior of N-hydroxy-3-isopropyl-2,6-difuryl-piperidin-4-one semicarbazone and thiosemicarbazone and the antibacterial study of the products. Int. Res. J. Pharm., 2017, 8(7), 66-72.
[28]
Pandey, P.; Chawia, P. Synthesis, characterization and biological activity of novel 2,6-disubstituted piperidin-4-one derivatives. Int. J. Pharm. Chem. Biol. Sci., 2012, 2(3), 305-309.
[29]
Vardanyan, R. Piperidine Based Drug Discovery; Elsevier: Amsterdam, 2017.
[30]
Hassner, A. Synthesis of heterocycles via cycloaddition; Springer Nature: Basingstoke, 2008.
[31]
Davis, F.A.; Xu, H.; Zhang, J. Asymmetric synthesis of ring functionalized trans-2,6-disubstituted piperidines from N-sulfinyl δ-amino β-keto phosphonates. total synthesis of (-)-myrtine. J. Org. Chem., 2007, 72(6), 2046-2052.
[http://dx.doi.org/10.1021/jo062365t] [PMID: 17305397]
[32]
Venkateswaramoorthi, R.; Krishnasamy, K. synthesis spectral characterization antimicrobial studies of some 3-substituted piperidine-4-one derivatives. Int. J. Recent Sci. Res., 2013, 4(1), 45-49.
[33]
Senthil, A.; Kumar, P.S. Synthesis spectral characterization antimicrobial studies of some 3-substituted piperidine-4-one derivatives. Int. J. Recent Sci. Res., 2011, 4(1), 45-49.
[34]
Noller, C.R.; Baliah, V. The preparation of some piperidine derivatives by the Mannich reaction. J. Am. Chem. Soc., 1948, 70(11), 3853-3855.
[http://dx.doi.org/10.1021/ja01191a092] [PMID: 18121891]
[35]
Baliah, V.; Ekambaram, A.; Govindarajan, T.S. Condensation of acetone with aldehydes and ammonia. Curr. Sci., 1954, 23, 264.
[36]
Baliah, V.; Govindarajan, T.S. Synthesis of some 4-piperidone derivative. Curr. Sci., 1954, 23, 91-92.
[37]
Baliah, V.; Ekambaram, A.J. Studies on conformation I: Preparation and stereochemistry of some 4-piperidinols. Ind. Chem. Soc., 1955, 33, 274.
[38]
Manimekalai, A.; Jayabarathi, J.; Rufina, L.; Mahendran, R. stereochemical studies of some t-3-methyl-r-2,c-6-diphenyl-piperidin-4-one azine derivatives. Indian J. Chem., 2003, 42B(9), 2074-2079.
[39]
Rao, H.S.P.; Poonguzhali, E. Synthesis and stereochemistry of cis-2,6-diphenyl-1-alkylpiperidines. Tetrahedron Lett., 2015, 56, 6190-6193.
[http://dx.doi.org/10.1016/j.tetlet.2015.09.085]
[40]
Salgado, M.M.; Manchado, A.; Nieto, C.T.; Diez, D.; Garrido, N.M. Asymetric synthesis of 2,3,6-trisubstituted piperidines via baylis-hillman adducts and lithium amide through domino reaction. Synlett, 2019, 30. [A-E.].
[41]
Lahosa, A.; Yus, M.; Foubelo, F. Enantiodivergent approach to the synthesis of cis-2,6-disubstituted piperidin-4-ones. J. Org. Chem., 2019, 84(11), 7331-7341.
[http://dx.doi.org/10.1021/acs.joc.9b01008] [PMID: 31063684]
[42]
Baliah, V.; Rangarajan, T. Preparation of tetrahydro-1:4-thiazine 1:1-dioxides. J. Chem. Soc., 1954, 3068-3070
[http://dx.doi.org/10.1039/jr9540003068]
[43]
Baliah, V.; Rangarajan, T. Preparation of substituted thiamorpho-line 1,1-dioxides. J. Org. Chem., 1961, 26, 969-970.
[http://dx.doi.org/10.1021/jo01062a621]
[44]
Thiel, M.; Deissner, I. Über die gemeinsame Einwirkung von elementarem Schwefel und gasförmigem ammoniak auf ketone, XXI.: Synthese und verhalten einiger 2.6‐Diphenyl‐piperidone‐(4). Justus Liebigs Ann. Chem., 1959, 622, 98-106.
[http://dx.doi.org/10.1002/jlac.19596220116]
[45]
Azerbaev, I.N.; Omarov, T.T.; Gubasheva, A.S.; Al’mukhanova, K.A.; Baisalbaeva, S.A. Synthese unsymmetrischer heterocyclischer diaetylen-glykole; Vestn. Akad. Nauk Kaz, 1975, p. 47.
[46]
Baltableiah, V.; Gopalakrishnan, V.; Jeyaraman, R. Synthesis of 2n,4n-bis(o-hydroxyphenylmethylene)-2,3-dialkyl-2,3-dihydro-4h-1-benzopyran-2,4-diamines. Indian J. Chem., 1978, 16B, 1065.
[47]
Manimekalai, A.; Anusuya, J.; Jayabharathi, J. Synthesis and conformational analysis of some cyanomethylene derivatives of piperidines. J. Struct. Chem., 2008, 49(3), 448-458.
[http://dx.doi.org/10.1007/s10947-008-0062-z]
[48]
Balachandravinayagam, E.; Natarajan, M.; Ganesan, S. Synthesis spectral characterization and antioxidant activities of 3-methyl-2,6-diphenyl-1,3-dihydrospiro(benzo(D)imidazole-2,4-piperidine). Int. J. Pharm. Chem. Biol. Sci., 2014, 4(3), 620-627.
[49]
Jayalakshmi, N.; Nanjundan, S. Synthesis, characterization and pharmacological studies of selenadiazole and hydrazine derivatives of 2,6-diphenyl-4-piperidone. Int. J. Chem. Sciences, 2008, 6(3), 1177-1188.
[50]
Rajalakshmi, S.; Srinivasan, S.; Aruna, S.; Girija, R. Synthesis and characterization of some new substituted piperidine derivatives. Int. J. Sci. Res. (Ahmedabad), 2014, 3(10), 82-84.
[51]
Singh, H.P.; Gupta, S.D.; Moorthy, N.S.H.N. Synthesis, characterization, biological evaluation and in silico study of some novel bid-piperidine derivatives. Int. J. Pharm. Tech. Res., 2009, 1(2), 282-287.
[52]
Padmavathi, V.; Reddy, T.V.R.; Reddy, K.A.; Padmaja, A.; Reddy, D.B. A study on the reactivity of 1,3-dimethyl-2,6-diphenyl-4-piperidone: synthesis of some novel heterocycles. Indian J. Chem., 2005, 44B, 2527-2531.
[53]
Thirunarayanan, G.; Lakshmanan, K. Bioactive 3-methyl-2,6-diarylpiperidin-4-one, oxime and its copper (II) complex. World Sci. News, 2019, 123, 124-140.
[54]
Amala, S.; Rajarajan, G.; Dhineshkumar, E.; Doss, M.A.; Thanikachalam, V.; Selvanayagam, S.; Sridhar, B. The synthesis of 3-ethyl-5-methyl-2,6-diarylpiperidin-4-one-1-ium picrates and their spectral, XRD and theoretical studies. New J. Chem., 2019, 43, 11003-11014.
[http://dx.doi.org/10.1039/C9NJ01631G]
[55]
Alkhafaji, D.S.M.S.; Fenjan, A.M.; Mohammad, A. Synthesis and spectroscopic, studies of some new piperidin-4-one derivatives. J. Al-Nahrain Univ., 2018, 21(2), 64-72.
[http://dx.doi.org/10.22401/JNUS.21.2.10]
[56]
Krishnan, K.G.; Sivakumar, R.; Thanikachalam, V. Synthesis structural characterization and antimicrobial evaluation of some novel piperidin-4-one oxime ester. J. Serb. Chem. Soc., 2015, 80(9), 1101-1111.
[http://dx.doi.org/10.2298/JSC141113037K]
[57]
Jadhav, R.L.; Magdum, C.S. Cytotoxic and antifungal activity of arylidene derivatives of 2,6-diphenyl piperidin-4-one. J. Pharm. Res., 2011, 4(9), 3093-3095.
[58]
Dineshkumar, J.; Parthiban, P. Impact on NMR by ortho substitution of 2,6-bis(polymethoxyphenyl)piperidin-4-ones. J. Chem. Pharm. Sci., 2018, 11(1), 17-24.
[59]
Mubarak, M.S.; Sirajudheen, P.; Shebin, K.S.M.; Muhasina, M.; Rishana, T. Synthesis characterization and antimicrobial activity of N-nitroso-2,6-diphenylpiperidin-4-one semicarbazone. J. Appl. Chem., 2015, 8(6), 1-6.
[60]
Revathi, R.; Venkatesha Perumal R,; Pai, K.S.; Arunkumar, G.; Sriram D.; Kini, S.G. Design, development, drug-likeness, and molecular docking studies of novel piperidin-4-imine derivatives as antitubercular agents. Drug Des. DeveL. Ther. 2015, 9, 3779-3787.
[PMID: 26229439]