Synthesis and Biological Activity of Some New Thienopyrimidine Derivatives
Osama Farouk Mohamed Ibrahim;
Abstract
Thienopyrimidines are well known biologically active compounds. In view of the significant biological activities of these compounds, it was considered of interest to synthesize some new condensed and isolated heterocycles containing thienopyrimidine moiety as potential antimicrobial agents using 3-amino-2-methyl-5,6,7,8-tetrahydro[1]benzothieno [2,3-d]pyrimidin-4(3H)-one (1a) and 3-amino-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one (1b) as starting materials for their preparation.
Reaction of 3-amino-2-methyl-5,6,7,8-tetrahydro[1] benzothieno[2,3-d]pyrimidin-4(3H)-one (1a) with POCl3/ DMF under Vilsmeier-Haack reaction condition afforded 10-oxo-4,6,7,8,9,10-hexahydropyrazolo[1,5-a][1]benzothieno [2,3-d]pyrimidine-3-carbaldehyde (2), which condensed with malononitrile to give arylidene malononitrile derivative 3. The latter compound, in turn, underwent cyclization with thiourea to yield thioxopyrimidine derivative 4, which could also be obtained directly by reaction of compound 2 with malononitrile and thiourea in basic medium.
Further, treatment of formyl derivative 2 with ethyl acetoacetate and acetylacetone in presence of thiourea afforded the corresponding thioxopyrimidine derivatives 5 and 6. Similarly, treatment of compound 2 with dimedone and ethyl cyanoacetate in presence of thiourea yielded quinazoline derivative 7 and mercaptopyrimidine derivative 8, respectively.
Furthermore, hydrazinolysis of compound 2 with hydrazine hydrate gave hydrazone derivative 9, which on treatment with phenyl isothiocyanate afforded N-phenyl thiosemi-carbazone derivative 10, which underwent heterocyclization with oxalyl chloride to yield thioxoimidazoline derivative 11. Also, cyclocondensation of compound 2 with semicarbazide hydrochloride afforded 1,2,4-triazole derivative 12. In addition, condensation of compound 2 with thiosemi-carbazide in refluxing glacial acetic acid for 5 hrs gave 5-thioxo-1,2,4-triazole derivative 13, while thiosemicarbazone derivative 14 was obtained under the same reaction on refluxing for 3 hrs.
Similarly, condensation of formyl derivative 2 with thiocarbohydrazide gave the corresponding arylidenethio-carbohydrazide 15, which is a convenient intermediate for synthesis of 1,2,4-triazole deivatives 16-18 through cyclization with benzoyl chloride, acetic anhydride and carbon disulfide, respectively.
On the other hand, compound 15 was used for construction of some new Schiff’s bases bearing 1,2,4-triazine moiety 19-21 through its heterocyclization with chloroacetyl chloride, oxalyl chloride and sodium pyruvate, respectively.
Moreover, compound 15 reacted with 2-cyano-3,3-bis(methylthio)acrylonitrile to produce pyrazole o-amino-nitrile derivative 22, which on treatment with carbon disulfide afforded 4,6-dithioxopyrazolopyrimidine derivative 23. Also, acylation of compound 22 with acetic anhydride yielded pyrazole o-acetamidonitrile derivative 24, which, in turn, underwent cyclization by refluxing in pyridine to give pyrazolopyrimidine derivative 25. The latter compound could also be obtained directly by reaction of compound 22 with acetic anhydride in pyridine. In addition, interaction of compound 22 with formamide and phenyl isothiocyanate yielded the respective pyrazolopyrimidine derivatives 26 and 27.
Reaction of 3-amino-2-methyl-5,6,7,8-tetrahydro[1] benzothieno[2,3-d]pyrimidin-4(3H)-one (1a) with POCl3/ DMF under Vilsmeier-Haack reaction condition afforded 10-oxo-4,6,7,8,9,10-hexahydropyrazolo[1,5-a][1]benzothieno [2,3-d]pyrimidine-3-carbaldehyde (2), which condensed with malononitrile to give arylidene malononitrile derivative 3. The latter compound, in turn, underwent cyclization with thiourea to yield thioxopyrimidine derivative 4, which could also be obtained directly by reaction of compound 2 with malononitrile and thiourea in basic medium.
Further, treatment of formyl derivative 2 with ethyl acetoacetate and acetylacetone in presence of thiourea afforded the corresponding thioxopyrimidine derivatives 5 and 6. Similarly, treatment of compound 2 with dimedone and ethyl cyanoacetate in presence of thiourea yielded quinazoline derivative 7 and mercaptopyrimidine derivative 8, respectively.
Furthermore, hydrazinolysis of compound 2 with hydrazine hydrate gave hydrazone derivative 9, which on treatment with phenyl isothiocyanate afforded N-phenyl thiosemi-carbazone derivative 10, which underwent heterocyclization with oxalyl chloride to yield thioxoimidazoline derivative 11. Also, cyclocondensation of compound 2 with semicarbazide hydrochloride afforded 1,2,4-triazole derivative 12. In addition, condensation of compound 2 with thiosemi-carbazide in refluxing glacial acetic acid for 5 hrs gave 5-thioxo-1,2,4-triazole derivative 13, while thiosemicarbazone derivative 14 was obtained under the same reaction on refluxing for 3 hrs.
Similarly, condensation of formyl derivative 2 with thiocarbohydrazide gave the corresponding arylidenethio-carbohydrazide 15, which is a convenient intermediate for synthesis of 1,2,4-triazole deivatives 16-18 through cyclization with benzoyl chloride, acetic anhydride and carbon disulfide, respectively.
On the other hand, compound 15 was used for construction of some new Schiff’s bases bearing 1,2,4-triazine moiety 19-21 through its heterocyclization with chloroacetyl chloride, oxalyl chloride and sodium pyruvate, respectively.
Moreover, compound 15 reacted with 2-cyano-3,3-bis(methylthio)acrylonitrile to produce pyrazole o-amino-nitrile derivative 22, which on treatment with carbon disulfide afforded 4,6-dithioxopyrazolopyrimidine derivative 23. Also, acylation of compound 22 with acetic anhydride yielded pyrazole o-acetamidonitrile derivative 24, which, in turn, underwent cyclization by refluxing in pyridine to give pyrazolopyrimidine derivative 25. The latter compound could also be obtained directly by reaction of compound 22 with acetic anhydride in pyridine. In addition, interaction of compound 22 with formamide and phenyl isothiocyanate yielded the respective pyrazolopyrimidine derivatives 26 and 27.
Other data
| Title | Synthesis and Biological Activity of Some New Thienopyrimidine Derivatives | Other Titles | "تخليق بعض مشتقات الثيينوبيريميدين الجديدة ودراسة الفاعلية البيولوجية لها" | Authors | Osama Farouk Mohamed Ibrahim | Issue Date | 2015 |
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