Preparation Of 2-(N-substituted) Amino Benzyl Alcohols And Their Application In The Synthesis Of 3,1-benzoxazines

Because 3,1-benzoxazines having a wide range of biological activity, the synthesis of these compounds have received much attention. 2-Aminobenzyl alcohol compounds are very important raw materials, especially, they can serve as important intermediates in the synthesis of 3,1-benzoxazoles. Therefore, the study of the synthesis of 2-(N-substituted amino) benzyl alcohols and their application in the synthesis of 3,1-benzoxazoles is very significant.In this paper, using of(2-aminobenzyl) alcohol as raw material, via the N-alkylation, a series of 2-(N-substituted amino) benzyl alcohols 13 a, 19a~19c and 19e~19h were prepared.New 1-benzyl-2-aryl-3,1-benzoxazines 20a~20c were synthesized by using 2-(N-substituted amino) benzyl alcohols as the main raw material. Meanwhile, the fungicidal activity of20a~20c were preliminary investigated.(1) 2-(Benzylamino) phenyl methanol 13 a was synthesized by using N- alkylation reaction of 2-aminobenzyl alcohol with benzyl bromide, and the reaction conditions was optimized. Firstly, using single-factor method to investigate the reaction conditions and obtained the main factors affecting the reaction. Then, by orthogonal experiment won the primary and secondary factors affecting reaction: material ratio > reaction temperature >reaction time > amount of alkali, and the optimal reaction conditions was determined: reactant material ratio of n(14): n(15) = 1 : 1.2; reaction temperature 45 ℃; reaction time 9.5 h;K2CO3 as acid binding agent and its using amount 1.6 eq. The yield of compound 13 a was enhanced to 80.5% under the optimized conditions, which was increased by nearly 30%compared with the non-optimized.(2) Using 2-aminobenzyl alcohol and 2-bromoacetyl aromatic amines as starting material a series of 2-(2-hydroxyphenyl) acetyl aromatic amines were synthesized in 64.5% to 79.5%yield. The results show that the electron donating ability of substituent group on the benzene ring is stronger, higher yield obtained.(3) By reduction reaction of 2-(2-hydroxymethylphenyl) acetyl aromatic amines with LiAlH4 a series of new 2-(arylamino ethylamino) benzyl alcohols were synthesized. The effect of the amount of LiAlH4 on the reaction was mainly explored.(4) Reactions of 2-(benzylamino) benzyl alcohol 13 a with nitrobenzeneformaldehyde gave 1-benzyl-2-aryl-3,1-benzoxazine 20 a, 20 b and 20 c. The effect of the type of catalyst and the using amount, reaction time, temperature and reactant ratio on the reaction yield was investigated, and obtained optimal reaction conditions: the ratio of reactants of 2-2-(N-benzylamino) benzyl alcohol to aryl aldehydes 1 : 1.2, reaction time 5 h, reactiontemperature 90 ℃, 15% TMSCl.(5) The structures of all the products were analyzed and characterized by IR, 1H NMR and 13 C NMR, etc.(6) The fungicidal activity of 1-benzyl-2-aryl-3,1-benzoxazines was priliminarily evaluated and the tested compounds exhibited certain activity.