The Research On Synthesis Of Lamotrigine And Its Intermediates

Lamotigine is a new and specific antiepileptic. They used by our nation are all imports from Britain. Because the product of Lamotigine is close to the patent term (the year of 2002), and the synthetical route of the product in the patent is long and in low yield, it is very necessary for us to bring the whole synthetical route of Lamotrigine to success and to exploit an economical and practical synthetical route of it's intermediates. This will bring us a goodish economical and social foreground.2,3-Dichlorotoluene which is not reported at home has been synthesized by routeâ… in the thesis from o-toluidine which is cheap and easily gained. Moreover, each step get further studied and optimized. It will bring economical benefit and good prospect in total yield of 25.8% and purity of 99.1% .Three new processes for the preparation of 2,3-dichlorobenzoic acid are provided in the thesis, which are not reported at home and abroad.(1) With nitric acid as oxidant, 2,3-dichlorobenzoic acid has been successfully synthesized from 2,3-dichlorotoluene in the autoclave and in yield of 84.3%. (2) 2,3-Dichlorobenzoic acid has been synthesized by hydrolyzing 2,3-dchlorobenzonitrile with sulfuric acid, and which has been synthesized from 2,3-dichloroaniline by diazo and Sandmeyer reaction. The total yield is 58% upwards. (3) 2,3-Dichlorobenzoic acid has been synthesized by oxidating 2,3-dichlorobenzaldehyde with potassium permanganate as oxidant, and which has been synthesized from 2,3-dichloroaniline by diazo and Meerwein reaction. The total yield is 37%. In the thesis, the synthetical route of Lamotrigine from 2,3-Dichlorobenzoic acid has been brought to success. And the yield of the step of synthesizing 2,3-dichlorobenzoyl chloride has been improved from 85% to 91% upwards by prolonging the reaction time.