Azoniaallene salts as versatile building blocks in the synthesis of antibacterial and antifungal heterocyclic compounds

El-Sayed H. El-Tammany, Atef A. Hamed, Salah Z. A. Sowellim, Ahmed S. Radwan

Department of Chemistry, Faculty of Science, Menofia University, Shebin El-Koom, Egypt.
Department of Chemistry, Faculty of Science, University of Suez Canal, Ismailia, Egypt;.

DOI: 10.4236/ns.2012.412130                

Abstract

Substituted 2-azoniaallene salts 1 are strong bifunctional electrophiles, undergo cyclization reactions furnish many series of heterocyclic compounds, where reacted with p-tolyl urea, phenyl thiourea and thiosemicarbazone derivatives to afford triazinium salts, and converted to corresponding free bases 3, 5, 7 under treatment with Na₂CO₃. While triazole derivatives 8 and 9 were obtained by the reaction 2-azoniaallene salts 1 with benzohydrazide and phenyl hydrazine, respectively. Benzoxazinium salts 10 and 11 were acquired when asymmetric 2-azoniaallene salt reacted in (1:1) ratio with p-cresol and 3-methyl-1-phenyl-5-pyrazolone, respectively. The reaction of 2-azoniaallene salt with malononitrile furnished the primidinium salt 12 which underwent neutralization with Na₂CO₃ followed by heterocyclization with hydrazine hydrate afforded the bicyclic compound 3-aminopyrazolo[3,4-d]pyrimidine 14, which is highly reactive for nucleophilic addition to phenyl isothiocyanate to furnish thiourea derivative 15. Moreover, 14 undergo condensation with aldehydes to give imine derivatives 16a,b. All free base compounds were screened for their antimicrobial activities.

Keywords

Azoniaallene Salts; Triazines; Triazoles; Pyrazolo[3, 4-d]primidines; Antimicrobial Activity

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hamed, A., Jochims, J.C. and Przybylski, M. (1989) 2- Azoniaallene salts from the reaction of chlorocarbenium salts with N-silylimines. Synthesis, 5, 400-402. doi:10.1055/s-1989-27267
[2]	Samuel, B. and Wade, A.K. (1968) Dialkylideneammonium cation analogous to an allene. Journal of the Chemical Society, 1081.
[3]	Hamed, A. (2005) Some reactions of 3-chloroisoindolium salts with nucleophiles: access to isoindole derivatives and ellipticine analogues as potential antiviral agents. Journal of Chemical Research, 3, 54-58.
[4]	Hamed, A., Müller, E., Al-Talib, M. and Jochims, J.C. (1987) On the reactions of α-chlorocarbenium ions with ammonium thiocyanate and potassium cyanate. Synthesis, 8, 745-748. doi:10.1055/s-1987-28073
[5]	Voges, A., Hamed, A., El-Badry, A.A., Ismail A.H. and Jochims, J.C. (1995) On the reaction of α-chloro carbenium ions with sulfinylamines. Synthesis, 3, 253-260. doi:10.1055/s-1995-3902
[6]	Peterson, P.E., Clifford, P.R. and Slame, F.J. (1970) Reactions of tetramethylenehalonium ions. Journal of the American Chemical Society, 92, 2840-2844. doi:10.1021/ja00712a039
[7]	Wei, M.J., Fang, D.C. and Liu, R.Z. (2004) Theoretical studies on cycloaddition reactions between 1-aza-2-azoniaallene Cations and Isocyanates. European Journal of Organic Chemistry, 2004, 4070-4076. doi:10.1002/ejoc.200400343
[8]	Padwa, A. and Pearson, W.H. (2002) Chemistry toward heterocycles and natural products. John Wily & Sons. Inc., Hoboken, 817-899.
[9]	Li, G.Y., Chen, J., Yu, W.Y., Hong, W. and Che, C.M. (2003) Stereoselective synthesis of functionalized pyrrolidines by ruthenium porphyrin-catalyzed decomposition of α-diazo esters and cascade azomethine ylide formation/1,3-dipolar cycloaddition reactions. Organic Letters, 5, 2153-2156. doi:10.1021/ol034614v
[10]	Rajaian, E., Monajjemi, M. and Gholami, M.R. (2002) Ab initio calculation of thermodynamicand kinetic quantities for 1,3-dipolar cycloadditions of benzonitrile oxide with various dipolarophiles. Journal of Chemical Research, 6, 279-281. doi:10.3184/030823402103171979
[11]	Wirchun, G.W., Hitzler, G.M., Jochims, J.C. and Groth U. (2002) On alkylidene amidosulfenyl chlorides and 1-thia2-azoniaallene salts. Helvetica Chimica Acta, 85, 2627- 2635. doi:10.1002/1522-2675(200209)85:9<2627::AID-HLCA2627>3.0.CO;2-H
[12]	Al-Soud, Y.A. (2008) Synthesis, structure, and in vitro anti-HIV activity of new pyrazole, 1,2,4-thiadiazole, and 1,2,4-triazole derivatives. Phophorus, Sulfur, and Silicon, 183, 2621-2636. doi:10.1080/10426500801968003
[13]	Leey, H.H., Cain, B.F., Denny, J.S., Bnckleron, J.S. and Clark, G.R. (1989) Synthesis and characterization of masked aminopyrazolecarboxylic acid synthons. Journal of Organic Chemistry, 54, 428-431. doi:10.1021/jo00263a032
[14]	Claramut, R.M. and Elguero, J. (1991) The chemistry of pyrazolidinones. A review. Organic Preparations and Procedures International, 23, 273-320. doi:10.1080/00304949109458208
[15]	Dogan, H.N., Duran, A., Rollas, S., Sener, G., Uysal, M.K. and Gülen, D. (2002) Synthesis of new 2,5-disubstituted1,3,4-thiadiazoles and preliminary evaluation of anticonvulsant and antimicrobial activities. Bioorganic & Medicinal Chemistry, 10, 2893-2898. doi:10.1016/S0968-0896(02)00143-8
[16]	Mamolo, M.G., Vio, L. and Banfi, E. (1996) Synthesis and antimicrobial activity of some 2,5-disubstituted 1,3,4- thiadiazole derivatives. Il Farmaco, 51, 71-74.
[17]	Schenone, S., Brullo, C., Bruno, O., Bondavalli, F., Ranise, A., Filippelli, W., Rinaldi, B., Capuano, A. and Falcone, G. (2006) New 1,3,4-thiadiazole derivatives endowed with analgesic and anti-inflammatory activities. Bioorganic & Medicinal Chemistry, 14, 1698.
[18]	Palaska, E., Sahin, G., Kelecin, P., Durlu, N.T. and Altinok, G. (2002) Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones. Il Farmaco, 57, 101-107. doi:10.1016/S0014-827X(01)01176-4
[19]	Naito, Y., Akahoshi, F., Takeda, S., Okada, T., Kajii, M., Nishimura, H., Sugiura, M., Fukaya, C. and Kagitani, Y. (1996) Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia. Journal of Medicinal Chemistry, 39, 3019. doi:10.1021/jm9507993
[20]	Clercq, E.D. (2004) Antiviral drugs in current clinical use. Journal of Clinical Virology, 30, 115-133. doi:10.1016/j.jcv.2004.02.009
[21]	Jenkins, S.M., Wadsworth, H.J., Bromidge, S., Orlek, B.S., Wyman, P.A. and Riley, G.J. (1992) Substituent variation in azabicyclic triazoleand tetrazole-based muscarinic receptor ligands. Journal of Medicinal Chemistry, 35, 2392-2406. doi:10.1021/jm00091a007
[22]	Al-Soud, Y.A., Al-Dweri, M.N. and Al-Masoudi, N.A. (2004) Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives. Il Farmaco, 59, 775-783. doi:10.1016/j.farmac.2004.05.006
[23]	El-Gazzar, A.B., Hegab, M.I. and Hassan, N.A. (2002) One-pot synthesis of N-nucleosides via 1,3-dipolar cycloaddition of 1-aza-2-azoniaallene salts to 2,3,4,6-tetraO-acetyl-β-D-glucopyranosyl isothiocyanate. Sulfur Letters, 25, 61-71. doi:10.1080/02786110213978
[24]	Hassan, N.A. (2007) Syntheses of acyclic C-glycosidic derivatives of 1,2,4-triazoles by cycloadditions of 1- aza-2-azoniaallene salts to D-glucononitrile-2,3,4,5,6-pentaacetate. Journal of Heterocyclic Chemistry, 44, 933-936. doi:10.1002/jhet.5570440432
[25]	Schmidt, U. and Schwochau, M. (1967) Syntheses with trimethylsilyl esters of acetoacetate and malonate. A new way to diacylmethanes and diacylacetates. Monatshefte für Chemie, 98, 1492-1511. doi:10.1007/BF00909019