SCALE-UP OF THE NITRATION OF 1-ACETYL-3,4-DICHLORO-1,2-(ETHYLENEDIOXY)BENZENE USING NITRIC-ACID TRIFLUOROACETIC-ACID

The process development of the nitration of 3-acetyl-4,5-dichloro-1,2- (ethylenedioxy)benzene (1) to 3 yl-4,5-dichloro-1,2-(ethylenedioxy)-6- nitrobenzene (2) led to two potential scaleup processes. The two nitra tion processes were a solids addition to nitric acid and nitric acid a ddition to a trifluoroacetic acid solution. The detailed hazards safet y evaluation of the two processes was carried out using abuse studies, CHETAH calculations, the reactive system screening tool, accelerating rate calorimetry, and differential scanning calorimetry, The nitric a cid addition to a trifluoroacetic acid solution process was chosen bec ause of the better safety profile, This process was successfully scale d up in a pharmaceutical pilot plant.