Synthesis Of N-ethyl-(3,4-methylenedioxy) Aniline

N-ethyl-(3,4-methylenedioxy)aniline(namely N-ethyl MDA), is an industrial chemical with a wide variety of applications, which can be used as intermediates in the preparation of quinazolinone and quilazolinthione derivatives having antibacterial properties. As an intermediates of medicine which are useful for treating CNS-system, cardiovascular system, and gastrointestinal disorders. There is no internal literature about the preparation of N-ethyl MDA at present, and only two process routes were reported in foreign articles. The first route only have two synthetic steps: bromination of 1,3-benzodioxole(MDO) to afford the intermediate 4-bromo-1,2-methylenedioxybenzene, then reaction of this intermediate with aqueous ethylamine to afford the product of N-ethyl MDA. However, there are several disadvantages to the above synthesis. The aminolysis step demands a lot of CuSO4 as catalyst , together with the high temperature and pressure conditions, and then the product is not easy to acquire in above conditions, so the route is not suitable for use in industry. The second route involving a three-step synthesis: nitration of MDO to produce the 1,2-methylnedioxy-4--nitrobenzene-(MDNB),-subsequent reduction of MDNB with hydrogen and a suitable catalyst to produce 3,4-methylenedioxyaniline(MDA), and ethylation of MDA to produce N-ethyl MDA. This route only acquires simple reaction conditions and easy to be industrialized. But, the key data of this route can not be found in relative articles, so it's urgent for us to research and develop the key data of this process route. In this paper, with MDO synthesized from catechol as starting material, the three-step process to prepare N-ethyl MDA was studied, which was nitration, hydrogenation, reductive alkylation. At the same time, the optimal process conditions and methods of TLC for tailing reductive alkylation course were also presented. The product was confirmed by m.p. measure, element analysis, IR, MS and GC. During the nitration of MDO, the paper discussed the mechanism of nitration and the rule of orientation, while the effect of HNO3 dosage, reaction temperature, reaction time on the yield of MDNB was studied. The optimal reaction conditions are as follows: v(MDO):v(23%HNO3)=1:6; the dropping time of MDO is 40～50min, and at this time the temperature of dilute HNO3 is 60～70 ℃; the reaction is continued for 2h at 90℃after completion of adding MDO. After finished the reaction, the surplus hazardous nitric acid can be recycled and used in next time. Under these conditions the yield can reach 97%. In the low-pressure catalytic hydrogenation of MDNB, Raney nickel was selected for the catalyst of this reaction, and the catalytic impact of high active Raney nickel which were prepared by different methods was compared, then the methods of preparation of high active Raney nickel was confirmed. The effect of catalyst's dosage and active stability, ethanol dosage, reaction temperature, hydrogenation pressure and stir velocity on the hydrogenation time of MDNB were investigated, and then the optimal process parameters were given: w(Raney nickel):w(ethanol):w(MDNB)=0.15: 6:1; the reaction temperature is 40℃; the hydrogenation pressure is 0.45～0.50MPa; the stir velocity is 450r/min.In this way the yield of 3,4-methylenedioxyaniline is up to 97%, purity 98%. As for the reductive alkylation process of MDA, the paper selected Raney nickel as the catalyst of the reaction, and compared the effect of Raney nickel with different activities of hydrogenation on the reductive alkylation reaction, altered the activity of the selected Raney nickel by loading Cu and confirmed the amount of copper was 2.5～3.0 percent of the mass of Raney nickel. The effect of catalyst's dosage, ethanol dosage and reaction temperature on the reductive alkylation of MDAwere examined by the orthogonal experiment, and then the catalyst dosage and times of catalyst reuse were investigated by the experiment of single factor. Finally, the optimal process parameters are as follow: w(Raney nickel):w(MDA):w(ethanol)= 0.2:1:6; the reaction temperature is 80℃; the stir velocity is 250r/min; GC or TLC control the time of reaction. Under these conditions the yield of designed product is 87.6%, purity is 90%.