β-Oxo Anilides in Heterocyclic Synthesis: Novel Synthesis of Substituted Pyridazinones, Pyridine, Pyrimidines and Pyrazolotriazines

Abdel Haleem Mostafa Hussein^*, Mohamed Sayed Abdel Aal El-Gaby, Ahmed Abdel Hameed Abd El-Maged, Ahmed Mohmed El-Sharief, Yousry Ahmed Ammar

Chemistry Department, Faculty of Science, Al-Azhar University, Assiut, Egypt.

DOI: 10.4236/oalib.1101439                

Abstract

Diazotization and coupling of acetoacetanilide derivative 1 with aromatic amines afforded the arylhydrazones 2a,b. Arylhydrazones 2a,b were treated with (DMF-DMA) to yield the pyridazine derivatives 3a,b in good yield. Pyridazinone was treated with hydrazine hydrate to yield 4a,b. Reaction of 2a with hydroxylamine hydrochloride afforded the oxime derivative 5. Similarly, the reaction of acetoacetanilide 1 with hydroxylamine hydrochloride gave 3-hydroxyimino-N-p-tolyl-butyramide 8 not the pyrazolone 9. The reaction of anilide 4 with aromatic aldehydes yielded 10a,b. Also, when anilide 4 was reacted with a mixture of aromatic aldehydes, urea or thiourea afforded the pyrimidines 11a,b. The reaction of anilide 1 with active methylene reagents was also investigated. So, 1 was reacted with malononitrile to give the pyridone derivative 12. Similarly, anilide 1 was reacted with cyanoacetamide under the same reaction conditions to yield 4-methyl-2-oxo-6-p-tolylamino-1,2-dihydro-pyridine-3-carbonitrile 13 in quantitative yield. The reaction of 1 with ylidenemalononitrile depends on structure of substituent. Thus, reaction of 1 with benzylidenemalononitrile or naphthylidenemalononitrile afforded 14a,b, while that with p-anisidine-malononitrile afforded 15. Coupling 1 with diazotized 16 - 18 afforded 19 - 21 respectively. Condensing 1 and aminopyrazoles 22a,b afforded the acyclic adduct 23a,b rather than the pyrazolopyrimidine 24a,b.

Keywords

Heterocyclic Synthesis

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	G’Hussein, A.M. (1997) Studies with Polyfunctionally Substituted Heteroaromatics: A Facile Route for the Synthesis of Polyfunctionally Substituted N-Aminopyridines, 1,2,4-Triazolo[1,5-a]pyridines and Isoquinolines. Heteroatom Chemistry, 8, 1. http://dx.doi.org/10.1002/(SICI)1098-1071(1997)8:1<1::AID-HC1>3.0.CO;2-J
[2]	Hussein, A.M. (1999) Afinidad, 484, 377.
[3]	Elghandour. A.H.H., Hussein, A.M., Elnagdi, M.H. and Metwally, S.A. (1992) Polyfunctionally Substituted Heterocycles: Synthesis of New Polyfunctionally Substituted Phthalazines, Thieno[3,4-d]pyridazines and Pyrido[3,4-c]pyridazines. Journal für Praktische Chemie, 334, 723. http://dx.doi.org/10.1002/prac.19923340816
[4]	Elnagdi, M.H., Elghandour, A.H.H., Harb, A.A., Hussein, A.M. and Metwally, S.A. (1992) Heterocycles, 38, 739.
[5]	Hussein, A.M., Atalla, A.A. and Kamal El-Dean, A.M. (1995) Die Pharmazie, 50, 788.
[6]	Hussein, A.M. (1998) Z. Naturforsch, 53b, 1.
[7]	Hidehiro, T., Kensuke, A. and Koichi, T. (2004) Chem. Abs., 140, 254977.
[8]	Hossbach, R., Lettabu, H., Nuhu, P., Schneider, R., Stenger, P. and Stiebitz, B. (1991) Pharmazie, 46, 412-415.
[9]	Gelbard, G., Lin, J. and Roques, N. (1992) Reductions with NADH Models. 3. The High Reactivity of Hantzsch Amides. Journal of Organic Chemistry, 57, 1789-1793. http://dx.doi.org/10.1021/jo00032a035
[10]	Sadanandam, Y.S., Shetty, M.M. and Diwan, P.V. (1992) Synthesis and Biological Evaluation of New 3,4-Dihydro-6-methyl-5-N-methyl-carbamoyl-4-(substituted phenyl)-2(1H)pyrimidinones and Pyrimidinethiones. European Journal of Medicinal Chemistry, 27, 87-92. http://dx.doi.org/10.1016/0223-5234(92)90066-A
[11]	Kaupp, G., Metwally, M.A., Fathy, A.A. and Abdel Latif, E. (2003) Quantitative Gas-Solid Diazotization of 3-Aminopyrazolo[3,4-b]pyridine Derivatives and Azo Dye Syntheses by Means of Solid-Solid Reactions. European Journal of Organic Chemistry, 8, 1545-1551. http://dx.doi.org/10.1002/ejoc.200390213
[12]	Ibrahim, M.K.A. (1989) Pakistan Journal of Scientific and Industrial Research, 32, 301-305.
[13]	Abu Elmaati, T.M. and El-Taweel, F.M.A. (2002) Journal of the Chinese Chemical Society, 49, 1045-1050.