Synthesis And Biological Activities Of Novel Triazolopyrimidine Derivatives

Triazolopyrimidine derivatives have been found to show widespread biological activities, many of which have been developed as fungicide, herbicide, medicine and functional material. In order to optimize the fungicidal and herbicidal lead compounds discovered previously by our research group, 216 novel 1, 2, 4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized, whose structures were characterized by NMR, MS spectrum and elemental analysis. The crystal structures of six representative compounds were determined by X-ray refraction analysis. In addition, a novel base-catalytic hydrazinolysis ring-opening reaction of triazolopyrimidines was discovered, and the effects of substituent, pH value and amount of hydrazine hydrate on the ring-opening reaction were studied systematically. And we propose a mechanism for ring opening reaction of triazolopyrimidines. Further, a one-pot three component Biginelli reaction for the synthesis of triazolopyrimidine was designed based on the principle of isoelectronic substitution. Bioassay indicated that most of compounds did not exhibit good fungicidal activities, however, some target compounds displayed promising herbicidal activities and ALS-inhibiting activities. The further crop safety experiment indicated the representative compounds displayed excellent selectivity between crop and weeds, which showed the potential value of these compounds for further study. What the paper studied may be summarized as follows:1 216 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized, whose structures were characterized by NMR, MS spectrum and elemental analysis. The crystal structures of six representative compounds were determined by X-ray refraction analysis.2, A novel base-catalytic hydrazinolysis ring-opening reaction of triazolopyrimidines was discovered, and the effects of substituent, pH value and amount of hydrazine hydrate on the ring-opening reaction were studied systematically. And we propose a mechanism for ring opening reaction of triazolopyrimidines.3,A one-pot three component Biginelli reaction for the synthesis of triazolopyrimidine was designed based on the principle of isoelectronic substitution. We optimized solvent and catalyst of the ring opening reaction, found ethanol was the best solvent. Finally, we obtained moderate yield and better regionselectivity under microwave irradiation (with temperature 150℃and reaction time 30 min), The structures of product were characterized by NMR, MS spectrum, elemental analysis and X-ray diffraction. We deduce the possible reaction mechanism.4,Bioassay indicated that most of compounds did not exhibit good fungicidal activities, however, some target compounds displayed promising herbicidal activities and ALS-inhibiting activities. The further crop safety experiment indicated the representative compounds displayed excellent selectivity between crop and weeds, which showed the potential value of these compounds for further study. Key words: lead compound, 1, 2, 4-triazolo[1,5-a]pyrimidine, microwave assisted organic synthesis, hydrazinolysis ring-opening reaction, Biginelli reaction, fungicidal activity, herbicidal activity.