Originator
Ecolid Chloride,Ciba,US,1956
Manufacturing Process
50 parts by weight of 3,4,5,6-tetrachlorophthalic anhydride is added with
stirring and cooling to 30 parts by volume of 2-dimethylaminoethyl amine.
The mixture is heated at 170°C for 4 minutes and the oily residue then
dissolved in 200 parts by volume of hot ethanol. On cooling, N-(2'-
dimethylaminoethyl)-3,4,5,6-tetrachlorophthalimide separates. It crystallizes
from ethanol and melts at 184°-186°C.
6 parts by weight of N-(2'-dimethylaminoethyl)-3,4,5,6-tetrachlorophthalimide
is extracted continuously with 300 parts by volume of dry ether in which have
been dissolved 3.1 parts by weight of lithium aluminum hydride. After 48
hours the excess lithium aluminum hydride is destroyed by cautious addition
of 9 parts by volume of ethyl acetate while stirring. There is then added in
succession with stirring 3 parts by volume of water, 6 parts by volume of 15%
aqueous sodium hydroxide and 9 parts by volume of water. The granular
precipitate of lithium and aluminum salts are filtered and washed with ether.
The ether is distilled off, yielding the crude, oily 4,5,6,7-tetrachloro-2-(2'-
dimethylaminoethyl)-isoindoline. The above base is dissolved in 25 parts by
volume of 90% ethanol and refluxed 2 hours with 6 parts by volume of methyl
iodide. 4,5,6,7-tetrachloro-2-(2'-dimethylaminoethyl)-isoindoline dimethiodide
separates during the reaction. It is collected by filtration and recrystallized
from a mixture of ethanol and water; MP 244°-246°C.
4,5,6,7-tetrachloro-2-(2'-dimethylaminoethyl)-isoindoline dimethochloride is
prepared by shaking an aqueous solution of the dimethiodide with an excess
of freshly prepared silver chloride and evaporating to dryness the aqueous
solution after removal of the silver salts. 4,5,6,7-tetrachloro-2-(2'-
dimethylaminoethyl)-isoindoline dimethochloride is recrystallized from ethanolethylacetate; MP 276°-280°C.