Sequential Ugi/(Catalytic Aza-)wittig Reaction And The Synthesis Of Biologically Active Heterocyclic Compounds

Ugi,aza-Wittig and 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 the above reactions,and the properties of these compounds were studied preliminarily.At the same time,the new triazole 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 new progresses of the Multi-Component Reactions,and mainly introduced the recent progress of Ugi reaction,aza-Wittig reaction,Wittig reaction and their application in heterocyclic synthesis.Meanwhile,a brief introduction of the triazole fungicides was given.2.An efficient preparation of multisubstituted benzimidazoles ?-4 and quinoxalin-2(1H)-ones?-7 starts with 2-azidobenzenamines,aldehyde,carboxylic acid/keto acid and isocyanide by Ugi 4CR/aza-Wittig sequence.Benzimidazoles ?-4 and quinoxalin-2(1H)-ones ?-7 were characterized by standard spectroscopic techniques and tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that compounds ?-7k,?-7n and ?-7o exhibited notable bactericidal activity of up to 66%?84%?84%against Zymoseptoria tritici at 100 ppm,respectively;?-7j exhibited notable herbicidal activity of up to 99%against Arabidopsis thaliana at 10 ppm;?-40??-7k??-7o exhibited notable insecticidal activity of up to 99%against Plutella xylostella at 500 ppm;?-7k exhibited notable insecticidal activity of up to 99%against Aphid species at 500 ppm.3.The synthesis of quinoxalin ?-6 starts with 2-azidobenzenamines and a-bromoacetophenone by SN/aza-Wittig sequence.Quinoxalin ?-6 were characterized by standard spectroscopic techniques and tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that Compounds ?-6a,?-6c and ?-6d exhibited notable bactericidal activity of up to 99%against Botryotinia fuckeliana,Pythium dissimile and Zymoseptoria tritici,and Zymoseptoria tritici at 20 ppm,respectively.4.Indole derivatives ?-3 was prepared via a phosphoric acid-catalyzed Ugi 3CR reaction and intramolecular witting reaction using the functionalized isocyanide-substituted phosphonium salts?-1,aldehyde and amine.Indole derivatives ?-3 were characterized by standard spectroscopic techniques and tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that compounds ?-3f and ?-3h exhibited notable bactericidal activity of up to 99%against Gibberella zeae at 20 ppm;IV-3i and IV-3j exhibited notable bactericidal activity of up to 66%against Uromyces viciae-fabae at 100 ppm.5.The synthesis of benzimidazoles V-4 starts with 2-acyl azide aniline,carboxylic acid,aldehyde and isocyanide by Ugi 4CR/Catalytic aza-Wittig sequence in one pot.Benzimidazoles V-4 were characterized by standard spectroscopic techniques and tested for herbicidal,fungicidal and insecticidal activities.The experimental results show that compounds V-4f and V-4i exhibited notable antibiotic activity of up to 99%against Plutella xylostella at 500 ppm.6.1,2,3-Triazole VI-2 was prepared via click reaction using p-tolyacetylene and alkyl azide.Then,the target compounds VI-6 were prepared via NBS bromination,nucleophilic substitution and reduction reactions using 1,2,3-Triazole ?-2.Compounds ?-6 were characterized by standard spectroscopic techniques and tested for bactericide on Penicillium digitatum,Fusarium graminearum,Magnaporthe grisea and Fusarium oxysporum by gradient test.At the same time,fungicidal and insecticidal activities were tested.The experimental results show that compounds VI-6 with R2 as tertiary butyl group show higher bioactivity than the commercial triadimefon.Some of compounds VI-6 even show comparable or higher activity as compared to diniconazole.These compounds possessing novel structure,which have not beeen reported in the literature and have the potential as novel pesticide precursor compounds.