Studies On Synthesis And Properties Of Novel Biological Activity Of Thienopyrimidine Derivatives

Thienopyrimidine derivatives have been found to show widespread biological activities, such as, some of them have been used as fungicide, herbicide, pesticide and medicine. In this paper, we studied the synthesis of novel thienopyrimidine derivatives and benzothienopyrimidine derivatives via aza-Wittig reaction. The condition for cyclization was researched. The spectral properties and biological activities of some compounds were also researched and some of them were found to show good fungicidal activities. More than one hundred and forty unreported compounds in four series and some other triazole derivatives were synthesized, it can be summarized as bellows:1. A general novel synthetic method to Symmetrically or unsymmetrically 2,3,6,7- substituted thieno[2,3-d:5,4-d']dipyrimidine-4,5(3H,6H)-diones and 2-substituted benzothieno[3,2-d] pyrimidin-4(3H)-dione by utilizing aza-Wittig reaction was proposed firstly. This synthetic method has the advantage of easily accessible starting material, mild condition and good yields. The condition of the reaction and the spectral properties of the products were studied.2. The cyclization of carbodiimides 2 and 6 with phenol or alcohol was studied and the results showed that the cyclization of carbodiimides 2 and 6 with phenol in the presence of solid potassium at room temperature to 40℃, the cyclization of carbodiimides 2 and 6 with alcohol should in the presence of RONa.3. The reaction of carbodiimide 14 with chiral amino alcohol was studies firstly, a facile synthetic methods for 2-substituted benzothieno[3,2-d]pyrimidin-4(3H)-one with high ee value, but reacted with chiral amino esters got the racemic product benzothieno[3,2-d]imidazol[1,2-a]pyrimidin-2,5 (1H, 3H)-diones, which boarded the utilization of aza-Wittig in organic synthesis.4. The reaction of carbodiimide 14 with various neucleophiles was investigated. The selectivity of cyclization of the carbodiimide 14 with NH₃, RNH₂, R₂NH and NH₂NH₂ were studied, some of the gualidene-type intermediates were isolated and the possible mechanism was suggested.5. Benzothieno[3,2-d]imidazol[1,2-a]pyrimidin-2,5(1H, 3H)-diones were synthesized from consecutived aza-Wittig reaction. And the results showed that at ambient temperature the gualidene-type intermediates 26 cyclization automaticly to form a five-member ring at the absence of RONa, then condensed to form a six-member ring in the presence of RONa.6. Seven triazole derivatives were synthesized, the spectral properties and its fungicidal activities were studied. 7. The biological activities of partial new compounds mentioned were studied. The results showed that 2,3,6,7-substituted thieno[2,3-d:5,4-d']dipyrimidine-4,5(3H , 6H)-diones exhibited of partial fungicidal in 50ppm. The best of them were 4c and 8d which exhibited 87% and 89% inhibition of Penicilium digitatum . And benzothieno[3,2-d]imidazol[1,2-a]pyrimidin-2,5(1H, 3H)-diones or benzothieno[3,2-d][1,2,4]triazol[1,5-a]pyrimidin-10(3H)-one only exhibited moderate inhibition. Compound 23 did not exhibit obvious inhibition of Rhizoctonia solani,Gibberella zeae,Botrytis cinereapers,Dothiorella gregaria,Fusarium oxysporium and Colletotrichum gossypii.