Studies On Tandem Aza-wittig Reaction And The Synthesis,Biological Activities Of Bistriazole Compounds

Chemists have expressed great concern about N-heterocycles because of their good biological activities,such as broad-spectrum,efficient and low toxicity.The study of N-heterocycles chemistry have found a great deal of compounds with good prospects in pesticide、fungicide、herbicide、anti-Virus、anti-inflammatory and anti-tumor drugs.Some of them have been used as pesticide and medicine,the research on the synthesis and evaluate their biological activities of new N-heterocycle compounds is very active.aza-Wittig reaction are widely used in the synthesis of nitrogen-containing heterocyclic compounds because of their mild reaction conditions,the easily accessible starting materials,the wide range of substrates and the high yields,etc.In this paper,some novel heterocyclic compounds were synthesized by tandem aza-Wittig reactions,and the properties of these compounds were studied preliminarily.At the same time,the new bistriazole derivatives were synthesized by using click reaction as the key step,and their biological activities were studied.Some compounds showed good bactericidal activity.The details are as follows:1.This paper reviewed the recent progress of aza-Wittig reaction,Ugi reaction and their application in heterocyclic synthesis.Meanwhile,a brief introduction of the triazole fungicides was given.2.We have developed a facile synthesis of 2-alkylthio-pyrimidin-4(3H)-ones(S-DABOs)11-16 by a new sequential aza-Wittig/intramolecular cyclization/S-alkylation/isomerization reaction,starting from the Baylis-Hillman adducts.Due to the easily accessible and versatile starting material,this method has the advantage in the synthesis of many biologically and pharmaceutically active S-DABOs derivatives.Meanwhile,S-DABOs 11-16 were characterized by standard spectroscopic techniques and were tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that compounds 11-161 exhibited notable bactericidal activity of up to 77%against Uromyces viciae-fabae at 100 ppm,respectively;Ⅱ-16r exhibited notable insecticidal activity of up to 99%against Plutella xylostella at 500 ppm.3.An efficient preparation of 1,4-benzodiazepin-3-ones Ⅲ-9 and 3,4-dihydroquinazolines Ⅲ-12 starting from 2-azidobenzylamines,aldehyde,carboxylic acid/keto acid and isocyanide by Ugi 4CR/aza-Wittig sequence is provided.This method has the potential in synthetic and medicinal chemistry.1,4-Benzodiazepin-3-ones Ⅲ-9 and 3,4-dihydroquinazolines Ⅲ-12 were characterized by standard spectroscopic techniques and were tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that Ⅲ-9a,Ⅲ-9c,Ⅲ-12g exhibited notable insecticidal activity of up to 66%,60%and 83%against Plutella xylostella at 500 ppm.4.3,4-Dihydroquinazolines were prepared regioselectively by a Ugi/Staudinger/aza-Wittig sequence starting from the functionalized 2-azidobenzylisocyanides,secondary amines,aldehyde,carboxylic acid.The method was adapted to the synthesis of various multisubstituted 3,4-dihydroquinazolines in one-pot fashion under mild reaction condition,which makes it useful in synthetic and medicinal chemistry.3,4-Dihydroquinazolines Ⅳ-14 were characterized by standard spectroscopic techniques and were tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that Ⅳ-14e exhibited notable insecticidal activity of up to 76%against Aphid species at 1000 ppm.5.We have developed a new method for preparation of 1,2,4,5-tetrasubstituted imidazoles by sequential Staudinger/aza-Wittig/Ag(Ⅰ)-catalyzed cyclization/isomerization starting from the easily accessible propargylazide derivatives.The method was adapted to the synthesis of various polysubstituted imidazoles in one-pot fashion under mild reaction condition,which makes it useful in synthetic and medicinal chemistry.Imidazoles Ⅴ-9 were characterized by standard spectroscopic techniques and were tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that these compounds no significant inhibition activity.6.Ⅵ-7 was prepared via azidation and NBS bromination starting from p-aminotoluene,then the target compounds Ⅵ-11 were prepared via sequential nucleophilic substitution,click reaction and reduction reactions using Ⅵ-7.Compounds Ⅵ-11 were characterized by standard spectroscopic techniques and tested for bactericide on Penicillium digitatum,Fusarium graminearum,Magnaporthe grisea and Fusarium oxysporum by gradient test.The experimental results show that compoundsⅥ-11 with R2 as tertiary butyl group show higher bioactivity than the commercial triadimefon.Some of compounds Ⅵ-11 even show comparable or higher activity as compared to diniconazole.The experimental results show that Ⅵ-11b,Ⅵ-11e,Ⅵ-11f,Ⅵ-11i,Ⅵ-111,Ⅵ-11n,Ⅵ-11o notable bactericidal activity of up to 100%against Magnaporthe grisea at 50ppm;Ⅵ-11a,Ⅵ-11b,Ⅵ-11c exhibited notable bactericidal activity of up to 83%,100%,100%against Penicilium digitatum at 50ppm;Ⅵ-11a,Ⅵ-11b,Ⅵ-111 exhibited notable bactericidal activity of up to 80%,89%,84%against Fusarium graminearum at 50ppm.These compounds possessing novel structure,which have not been reported in the literature and have the potential as novel pesticide precursor compounds.