الفهرس 
Synthesis of Five Membered Rings with threeOnly 14 pages are availabe for public view
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Abstract
The utility of activated nitriles in synthesis of a wide variety of heterocyclic systems encourage us to synthesis pyrimidine derivatives from relatively simple starting materials. The title compound 3 was prepared by reaction of 2-(4-methoxybenzylidene)malononitrile 1 with s-benzyl-thioronium chloride 2 in refluxing ethanolic sodium hydroxide. (Scheme 1)
Hydrazinolysis of 3 afforded the sulfur free compound which identified as 4-amino-2-hydrazinyl-6-(4-methoxyphenyl)pyrimidine-5-carbonitrile 4. (Scheme 1)
Recently, it has been reported that the hydrazino pyrimidines can be considered as key starting materials for the synthesis of diverse nitrogen bridgehead compounds. This prompted us to reinvestigate the proclivity of compound 4 with electrophilic reagents such as, pentane-2,4-dione, acetic anhydride, furoyl chloride, phthalic anhyd- ride, ethyl chloroformate, carbon disulphide, 2-(3,4-dimeth- oxybenzylidene)malononitrile, p-nitrobenzaldehyde , phenyl isothiocyanate and diethyl oxalate with the aim of preparing new pyrimidine derivatives which might have chemothera- peutic and biological evaluation. Thus, treatment of the 2-hydrazino derivative 4 with pentane-2,4-dione in refluxing ethanol afforded 4-amino-2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(4-methoxyphenyl)pyrimidine-5-carbonitrile 5. (Scheme 1)
Acetylation of compound 4 using freshly distilled acetic anhydride yielded the acetylated product 6 (Scheme 1). Furthermore, treatment of 4 with ethyl chloroformate yielded ethyl N-pyrimidin-2-yl carbazate derivative 7 (Scheme 1). Compound 4 was treated with carbon disulphide in ethanolic potassium hydroxide to yield 7-amino-5-(4-methoxyphenyl)-3-thioxo-2,3-dihydro-[1,2,4]-triazolo[4,3-a]pyrimidine-6-carbonitrile 8 (Scheme 1).
7-Amino-3-(3,4-dimethoxyphenyl)-5-(4-methoxyphe- enyl)-[1,2,4]triazolo[4,3-a]pyrimidine-6-carbonitrile 10 was obtained in fairly good yield upon treatment of compound 4 with 2-(3,4-dimethoxybenzylidene)malononitrile 9 in boiling ethanol in the presence of few DROPs of acetic acid (Scheme 1).
Refluxing the hydrazino derivative 4 with p-nitro-benzaldehyde in ethanol afforded (E)-2-(2-(4-nitrobenzyli- dene)hydrazinyl)-4-amino-6-(4-methoxyphenyl)pyramidine-5-carbonitrile 13 (Scheme 2). On the other hand, treatment of 4 with furoyl chloride afforded the monoacylated product 15. (Scheme 2)
In the context, it was claimed that the reaction of the hydrazino pyrimidine derivative with phenyl isothiocyanate in refluxing pyridine resulted in the formation of 1,2,4-triazolopyrimidinthione or thiourea derivatives. Herein, when compound 4 was refluxed with the same reagent in boiling pyridine afforded 7-amino-5-(4-methoxyphenyl)-3-(phenylamino)-[1,2,4]triazolo[4,3-a]pyramidine-6-carbonit-rile 16. (Scheme 2)
However, the reaction of 4 with phthalic anhydride in refluxing acetic acid gave the phthalimide derivative 19. (Scheme 2)
Treatment of 4 with diethyl oxalate in refluxing n-butanol in the presence of acetic acid afforded the mono acetylated product 20 which confirmed by refluxing 4 with acetic acid in n-butanol to yield the same product 20. (Scheme 2)
Reaction of (E)-2-cyano-3-(4-nitrophenyl)acrylamide 21 with 6-amino-2-thioxo-2,3-dihyDROPyrimidin-4(1H)-one 22 in boiling ethanol in the presence of piperidine yielded a mixture of pyrimidine derivative 23 (13%) and pyrido[2,3-d] pyrimidine derivative 24 (56.6%). (Scheme 3)
In contrast, similar treatment of (E)-ethyl 2-cyano-3-(3,4-dimethoxyphenyl)acrylate 26 with 6-amino-2-thioxo-2,3-dihyDROPyrimidin-4(1H)-one 22 in refluxing ethanol in the presence of piperidine yielded 5-(3,4-dimethoxyphenyl)-4-oxo-7-(piperidin-1-yl)-2-thioxo-1,2,3,4-tetrahyDROPyrido [2,3-d]pyrimidine-6-carbonitrile 27. (Scheme 3)
N-Amino-2-pyridones have proved to be useful synthetic intermediates. We report herein one step synthesis of N-amino-2-pyridone 31 besides diazepinone 32 from reaction of 21 with 2-cyanoacetohydrazide 30. (Scheme 3)
Beside the analytical and spectral data the structure 31 was got a further chemical support by the reaction with carbon disulphide to give 1,2,4-triazolo[1,5-a]pyridine derivative 33. (Scheme3)
Furthermore, treatment of 21 with 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetonitrile 34 in boiling ethanol in the presence of catalytic amount of piperidine afforded (E)-2-(5-(4-nitrobenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)acet- onitrile 35 as the sole product (62.8%) (Scheme 3). The structure 35 was chemically supported by identity with an authentic sample resulted from the condensation of 34 with p-nitrobenzaldehyde. (Scheme 3)
All the structures were identified by microanalysis and spectral data included IR, MS and 1H-NMR spectra.