Chemical And Enzymatic Preparation Of Chiral1-(4-Chlorophenyl) Ethylamine And Synthesis Of Chiral Pesticides

In this paper, we used the material of1-(4-chlorophenyl) acetophenone to synthesize the1-(4-chlorophenyl) ethylamine, and took it as the substrate of enzymatic resolution. After a series of operation of separation and purification, we finally got the S-1-(4-chlorophenyl) ethylamine, and then successfully synthesized a chiral compound with it, named S-N-1-(4-chlorophenyl) ethyl-2-(5,7-dimethyl-[1,2,4]-triazolo [1,5-a] pyrimidine-thio) acetamide (code:ZJ-2725), which is a novel and effective herbicide.Firstly, we discussed some synthetic methods of chloroaniline, and finded the most effective synthetic method of l-(4-chlorophenyl) ethylamine—R. Leuckart Reaction. After optimizing and comparing these processes, we obtained the optimal synthesis conditions:reaction time was1.5hours, reaction temperature was165℃, raw material parachloroacetophenone:ammonium formate was1mol:5mol, parachloroacetophenone:concentrated hydrochloric acid was lmol:1.5mol, petroleum ether as the extractant. In this condition, product yield was from70%to78%, and the purity was from90%to98%. The synthetic product detected by HPLC, NMR and IR. At last, we identified this synthetic product is1-(4-chlorophenyl) ethylamine.Secondly, based on the catalytic resolution by lipase in organic phase of Rac-1-(4-chlorophenyl) ethylamine, we found the best system for enzymatic resolution:lipase Novozym435as the enzyme of reaction, MTBE as the reaction solvent and methyl2-tetrahydrofuroate as acylating agent. Optimal catalytic conditions is solvent MTBE10mL, Rac-1-(4-chlorophenyl) ethylamine50uL, acylating agent methyl2-tetrahydrofuroate110uL, Novozym43520mg, reaction temperature was40℃, shaking speed was200rpm and reaction time was20hours.Under the optimal conditions, the value of e.e.s%was more than99%, the conversion rate was54%, the value of E was about70. The reuse of enzyme was greater than24times, when the value of e.e.s%was90%.Then, by chemical methods of separation on lipase catalytic reaction, we successfully isolated R-2-tetrahydrofuran-N-(1-(4-chlorophenyl) ethyl) formamide and S-1-(4-chlorophenyl) ethylamine. Besides, we obtained the S-1-(4-chlorophenyl) ethylamine1.98g, e.e.s%was97.4%.Followed by amidation, S-chloroaniline was been converted to S-2-chlorine-N-(1-(4-chlorophenyl) ethyl) acetamide. After this reaction, we got some S-acetamide, weight about1.62g and the purity was91.8%by test of HPLC. Finally, we used the synthetic route of ZJ-2725, which was found by other scientists, and triumphantly got the new chiral herbicide—S-N-1-(4-chlorophenyl) ethyl-2-(5,7-dimethyl-[1,2,4]-triazolo [1,5-a] pyrimidine-thio) acetamide1.44g, purity was94.5%, the optical rotation was-0.025degree.