Studies On The Synthesis And Fungicidal Activity Of 1-amidyl-2-aryl-2,4-dihydro-3,1-benzoxazines

Developing of high efficiency, environmentally friendly and low toxicity of “green” pesticides has recieved more and more attention. In recent years, 3,1-benzoxazine compounds have found wide application in the research and dicovery of new drugs because 3,1-benzoxazines have a wide range of biological activity, such as fungicidal, insecticidal, anti-tumor and plant growth regulating activity, etc.This paper mainly designed and synthesized a novel class of 1- amidyl-2-aryl-2,4-dihy dro-3,1-benzoxazines. The fungicidal activity of the prepared compounds were also preliminarily investigated. The structures of 30 target compounds were characterized by 1HNMR, 13 CNMR and IR.(1) Reactions of bromoacetyl bromide and substituted amines in the presence of triethylamine gave N-substituted-2- bromoacetyl amides 32a?32j in 89.4% ?97.0 % yields. And it was found that the yield of the nitrogen atom connected with benzene ring was higher than that of the nitrogen connected with alkyl group.(2) N-substituted 2-(2-hydroxymethylphenylamino) acetamides 33a?33j were synthes-ized by N-alkylation of 2-aminobenzyl alcohol with N-substituted-2- bromoacetyl amides. It was studied the effects of the type and the loading of the base, solvent, reaction time, reaction temperature and the reactant ratio on the yield of the reaction, and obtained an optimum conditions: solvent DMF(v):THF(v)= 1: 2, potassium carbonate as base, n(N-substituted 2-bromo-acetamide): n(2-aminobenzyl alcohol): n(potassium carbonate) = 1.0: 1.2: 1.4, the reaction time 12 h, temperature 65 ℃. Under these conditions, the yield of compound 33 a increased from 36.1% to 70.3%. Under the same condition, compound 33b?33j were also synthesized in 58.6%?76.4% yields.(3) 30 New 1-amidyl-2-aryl-2,4-dihydro-3,1-benzoxazines 30a?31d were synthesized by reactions of compounds 33a?33j with nitrobenzaldehydes in the presence of catalyst. It was investigated the effect of the type and the loading of catalyst, reaction time and the reactant ratio on the yield of the reaction, and got optimum conditions : reaction time 10 h, temperature 65 ℃, BF3·OEt2(20 mol%) as catalyst, n(33) : n(nitrobenzaldehyde) = 1 : 1.5, THF as solvent. Under these conditions, target compounds 30a?31d were synthesized in 38.7%?80.4% yields. The results also showed that the yields of the compounds had closely related to the position of the nitro group on the benzene ring at 2-position of the benzoxazine ring in the order of meta > para > ortho.(4) The fungicidal activity of intermidates 33a?33e and the target compounds 30a?31d were evaluated. The results showed that the fungicidal activity of the target compounds was higher than that of intermediates, which indicated that the benzoxazine ring was the principle activity group. The target compounds showed the highest activity against Sclerotinia sclerotiorum, the inhibitory activity of compound 30 p is 71.9%, and 68.1% for compounds 30 v and 31 d. Secondly, compound 30 i displayed 60.1% activity against rice blast fungus, and 51.7% activity for compound 30 a.