Studies On The Synthesis And Fungicidal Activity Of 2-Aryl-3-Amidyl-1,3-Benzoxazines

Fungicides play an important role in agricultural production and crop protection.Creating and developping novel structure, high efficiency, low toxicity and environmental friendly new fungicides are of great significance to healthy and stable development of national economy.This paper designed and synthesized a series of novel 2-aryl-3-amidyl-1,3-benzoxazine compounds, and studied the fungicidal activity of these compounds. In the presence of catalyst, N-substitued-2-(2-hydroxy benzylamine)acetamide(III-1 ~ III-11) reacted with aromatic aldehydes gave new2-aryl-3-amidyl-1,3-benzoxazine compounds(I-1 ~ I-33). All the structures of synthesized compounds were characterized by 1H NMR, 13 C NMR and IR.(1) Catalyzed by La(OTf)3, reaction of 2-(hydroxybenzyl)aminoacetate and benzylamine in toluene under reflux fournished the intermediate N-benzyl-2-(2-hydroxy-benzylamino) acetamides. It was studied the catalyst dosage,reaction temperature, reaction time and material ratio of reactants on the reaction yields, and obtained the suitable reaction conditions: the catalyst dosage is 5.0mol %, the reaction temperature 80 ℃, the reaction time 24 h,n(2-hydroxybenzylamino acetate):n(benzylamine)=1:1.2. Under these conditions,compounds III-1~III-6 were synthesize in yields of 54.4~68.7%.(2) N-alkylation reaction of N-aryl-2-bromoacetamide with2-hydroxybenzylamine gave N-aryl-2-(2-hydroxy-benzylamino) acetamide, and the reaction conditions were explored. The optimized reaction conditions were obtained,Na2CO3(150 mol %), temperature 65 ℃, solvent DMF/THF(v/v=1/1),n(2-bromoacetamide):n(o-hydroxybenzylamine)=1:1.2, the reaction time 3 h. Under the optimized reaction conditions, the intermediate N-aryl-2-(2-hydroxy-benzylamino) acetamide III-7 ~ III-11, were synthesized in yields of61.2 ~ 71.1%. The yields of unsubstituent phenyl linked with N atoms of amiddy is higher than those of the substituent benzyl with substituent, and according to the order of hydrogen>methyl>methoxy. And when methyl or methoxyl on the benzene ring, the yield is closely related to their position in the benzene ring following the order of para>ortho position.(3) In the presence of catalyst, reactions of N-substituted-2-(2-hydroxybenzylamino) acetamides with substituted aromatic aldehydes gave a seires of new 2-aryl-3-amidyl-1,3-benzoxazine compounds. It was mainly studied the effect of the kind and the amount of catalyst, reaction temperature,reaction time, the ratio of the reactants and solvent on the reaction yields, and obtained the optimized reaction conditions: La(OTf)3(5.0 mol %) as catalyst, the reaction temperature 80 ℃, reaction time 3 h, n(2-(2-hydroxybenzylamino)acetamide):n(aldehyde)=1:1.1, solvent(CHCl3)/(cyclohexane)(v: v =1:1). Under these conditions, target compounds I-1~I-33 were synthesized in yields of52.7~93.1%. The experimental results show that the yields of the compound were close to the substituents and their position on the benzene ring.(1)In most cases, the yields were close to the position of nitro group on the benzene ring at 2-position of the benzoxazine ring in the order of para>ortho>meta.(2)Amidyl N atom connected with benzyl gave higher yield than those with aryl group, and substituent on the benzyl ring had effect on reaction yield following the order of methoxy>methyl>hydrogen, and also following the order of para>ortho>meta. This is the first time to use La(OTf)3 as catalyst to synthesize substituted1,3-benzoxazines, and the experiment results show that it was an efficient catalyst.(4) The fungicidal activity of the synthesized intermediates and target compounds were tested. The results showed that the intermediate III had good fungicidal activity for all the test fungi. Compounds III-4 and III-6 showed 100%activity against Sclerotonia sclerotiorum. The inhibition activity of compounds III-4and III-6 against Phytophythora capsici were 100%. For Magnaporthe oryzae, III-4and III-6 inhibition rates were 100% and 94.4%, respectively. The inhibition activity of compound III-6 against Botrytis cinerea was 100%. Thus, the compounds III-4and III-6 showed a broad spectrum of fungicidal activity, moreover the inhibitory activity of III-4 against Sclerotonia sclerotiorum was better than that of chlorothalonil.The target product 2-aryl-3-amidyl-1,3-benzoxazine I showed a certain amount of inhibitory activity against six kinds of fungi. The inhibition activity against Phytophythora capsici of compounds I-19 was 81.0%, 70.0% for I-10, 66.7% for I-22, and 58.1 for I-28. The inhibition activity against Sclerotonia sclerotiorum of I-31 was 73.1%. The inhibition activity against Rhizoctorzia solani of compounds I-21 was 56.1, and 53.7 for I-30.