Studies On The Synthesis And Fungicidal Activity Of Substituted-1,3-Benzoxazines

In recent years, the heterocyclic compounds have already become one of hot point ofnew pesticide discovery research due to their wide range of biological activity.1,3-benzoxazines is a kind of hexa-heterocyclic compounds containing nitrogen and oxygenatoms, which exhibit a broad biological activity such as anticancer, antitumour, bactericidaland fungicidal. This class of compounds has a broad foreground in the field of drugresearches. This paper mainly studies on the synthesis and bioactivity of substituted1,3-benzoxazines. Three categories of substituted1,3-benzoxazines3,6(8)-disubstituted-1,3-benzoxazines,2,3-disubstituted-1,3-benzoxazines and2,3,6(8)-trisubsti-tuted-1,3-benzoxazines were synthesized by Mannich reaction or reactions ofo-arylaminomethyl phenols with substituted benzaldehydes. Their structures werecharacterized by IR,1H NMR and13C NMR, and some of them were chareacterized by MS.⑴12Kinds of novel3,6(8)-disubstituted-1,3-benzoxazines44were synthesized in46-73%yields by Mannich reactions of substituted anilines, paraformaldehyde andsubstituted phenols in the absent of catalyst and refluxing anhydrous ethanol. The resultsshowed substituted phenols and anilines with electron-releasing group on the benzene ringgave higher yields than those with electron-withdrawing ones.⑵Schiff bases resulted from reactions of substituted amines with salicylaldehyde, werereduced by NaBH4in anhydrous ethanol giving5kinds o-aminomethyl phenols50.13Kindsof novel2,3-disubstituted-1,3-benzoxazines45were synthesized by reactions ofo-aminomethyl phenols with aromatic aldehydes in the presence of TMSCl. The effect of thesorts of catalyst, the amount of catalyst, reaction time on the yield of the reaction wereinvestigated affording an optimized conditions:20mol%TMSCl, reaction time5h, reactiontemperature85℃, in which the reactions gave the products in50-74%yields. Alkyl groupsat3-position of the benzoxazine ring connected with the nitrogen atom gave higher yieldsthan aryl groups. Electron-releasing groups on the benzene ring connected with the nitrogenatom gave higher yields than electron-withdrawing ones. Groups on the benzene ring at2-position of benzoxazine ring have effect on the yields of the compounds in the order of-NO2>-F>-Cl.⑶6Kinds of2–arylaminomethyl-4-methyl phenols51were synthesized by Mannichreactions of substituted phenols, paraformaldehyde and substituted anilines at roomtemperature.10Kinds of2,3-diaryl-6-methyl-1,3-benzoxazines46a1-46a10were prepared in59-72%yields by reaction of2–arylaminomethyl-4-methyl phenols with nitrobenzaldehydes in the presence of TMSCl (20mol%). Electron-releasing groups on thebenzene ring connected with the nitrogen atom at3-position of the benzoxazine ring gavehigher yields than electron-withdrawing ones. Different position of the nitro group on thebenzene ring at2-position of the benzoxazine ring has effect on the yields of the products inthe order of ortho> para> meta.⑷We employed “one-pot reaction” to prepare14kinds of o-arylaminomethyl phenolsby reactions of substituted salicylaldehydes with substituted amines (aromatic amines,aminoacid esters,2-aminothiadiazoles), and22kinds of2,3,6(8)-trisubstituted-1,3-benzoxaz-ines46a11-46a32were synthsized in38-80%yields by reactions of o-arylaminomethylphenols with substituted benzaldehydes. The results showed that benzoxazine ring withelectron-releasing groups at6(8)-position gave higher yields than those withelectron-withdrawing ones. Benzoxazine ring with thiadiazolyl at3-position gave the lowestyield. Different position of the nitro group on the benzene ring at2-position of thebenzoxazine ring has effect on the yields of the products in the order of ortho, para> meta.⑸The fungicidal activity of novel substituted-1,3-benzoxazines were assayed, and theresults showed three categories of compounds exhibited good fungicidal activity againstSclerotonia sclerotiorum as shown by86.1%activity of compound44l. The fungicidalactivity against Sclerotonia sclerotiorum of these compounds has the following order:3,6,(8)-disubstituted-1,3-benzoxazines>2,3,6(8)-trisubstituted-1,3-benzoxazines>2,3-disub-stitutd-1,3-benzoxazines. As for3,6,(8)-disubstituted-1,3-benzoxazines, benzoxazine ringwith electron-withdrawing groups has higher inhibitory activity than those withelectron-releasing ones. As for2,3-disubstitutd-1,3-benzoxazines, N-aryl substitutedcompounds exhibit higher activity than N-alkyl substituted ones, moreover, benzene ringconnected with nitrogen with electron-withdrawing groups shows higher activity than thosewith electron-releasing ones. As for2,3,6(8)-trisubstituted-1,3-benzoxazines, substituent on3-position of the benzoxazine ring connected with the nitrogen atom shows fungicidalactivity in the order of thiadiazolyl <alkyl <aryl.