Cyclization And Sulfoxide Reaction Of Aminotetrazole And The Antifungal Activities Of Sulfoxytetrazole Derivatives

Nitrogen-containing heterocyclic compounds as an important branch of heterocyclic compounds are widely found in natural products and drug molecules.Such compounds often exhibit anti-inflammatory,anti-allergic,antibacterial or other biological activities.Hence,they are extensively applied in agriculture,biochemistry,pharmacology,dyesand fine chemistry.At present,many commercially available products with bioactivities such as ultra-efficient herbicides,fungicides,insecticides,have been proved to contain N-heterocyclic structures,which is the core of the biological activity unit.Among them,the compounds containing pyrazole,triazole and tetrazole skeletons always exhibit good biological activities.For a representative commercial variety,herbicide Thiadrova Phthalamine was developed by Bayer Company in United States.On the other hand,sulfoxide compounds are also important skeletons in antifungal pesticides.However,limited studies have been reported on the construction of novel biologically active molecules with tetrazolium and sulfoxide structural units up to now.In this thesis,cyclization of amino tetrazolium with alkyne under metal-free condtion and direct sulfoxide reaction of amino tetrazolium with dimethyl sulfoxide are studied in detail to build novel compounds.Furthermore,the antifungal activity research of sulfoxide tetrazole derivatives was carried out.Specifically,three aspects are included as follows:(1)In the presence of tert-butyl nitrite,[4+2]cycloaddition reaction was achieved in acetone with 5-aminotetrazole and alkyne compounds,affording tetrazol[1,5-a]quinoline derivatives efficiently.Based on the control experimental study it was found that,the reaction underwent a free radical mechanism,and the free radicals were produced by the synergistic action of diazonium salt with t-butyl nitrite.This reaction is highlighted in the metal-free condition with no additives,as well as its high efficiency and good regional selectivity.With this method,27 new compounds were synthesized and single crystal structure was obtained for p-methyltetrazole[1,5-a]quinoline,which confirmed the high regional selectivity of the reaction.(2)A new method for the synthesis of methyl sulfoxide tetrazolium derivatives at room temperature was developed using dimethyl sulfoxide and 5-aminotetrazole derivatives as starting materials.It was the first time to realize the structure of sulfoxide tetrazole skeleton with dimethyl sulfoxide as the methyl sulfoxide source without transition metal or additives.The operation is simple and the yield is high.Considering a number of controlled experiments,the mechanism showed a similar initiation process of free radicals compared with the results in the first part.The difference lied in the participation oftetrazole free radicals in the cleavage of S-Me bonds.With this method,24 new compounds were successfully synthesized.(3)The effects of several sulfoxide tetrazolium compounds on the sterilization of four common agricultural plant diseases were studied.10 kinds of representative methyl sulfoxide aryltetrazole compounds were evaluated in vitro for their antifungal activity against Botrytis cinerea,Altemariasolani,Rhizoctoniasolani,Alternariamali,respectively.Some of the designed compounds exhibited potential activity in the primary assays.3-3w gave the lowest EC50 of 1.3701 ?g/mL,exhibiting obivious activity against Rhizoctoniasolani,which was better than that of the control drug pyridinamide.The EC50 value of compound 3-3k was 2.5439 ?g/mL for Botrytis cinerea,demonstrating a comparable result of pyridinamide(0.5096 ?g/mL).