Manufacturing Process
A mixture of 3-methylphenylacetonitrile and dry ethanol was cooled in an ice-
bath and dry hydrogen chloride was passed. The mixture was allowed to stand
at room temperature for 3 days and then treated portionwise, with vigorous
shaking and occasional cooling, with a saturated solution of ammonia in dry
ethanol. Addition was continued until a smell of ammonia persisted. The
mixture was allowed to stand at room temperature for 2 days and then
filtered. The fitltrate was treated with a saturated aqueous solution of 1.1
equivalents of sodium p-toluene-sulfonate and diluted with water. The
crystalline precipitate was removed and 3-methylphenylacetamidine p-
toluenesulphonate (recrystallised from ethanol) was obtained.
A mixture of methyl phenolate and anhydrous potassium carbonate in dry
ethyl methyl ketone was stirred and heated to reflux, during the dropwise
addition of a solution of 2-chloropropionitrile in dry ethyl methyl ketone
containing finely-powdered potassium iodide. The addition took 20 min.
Stirring and heating were continued for a total of 2 h after which the mixture
was cooled, poured into water and extracted with ether. The combined ether
extract was washed several times with 2 N sodium hydroxide to remove
phenol, dried over anhydrous sodium sulfate, and evaporated. The residue
was distilled under water-pump vacuum to give pure 2-(3-methoxy-phenoxy)-
propionitrile, boiling point 152-154°C/13 mm.
A solution of 2-(3-methoxy-phenoxy)-propionitrile in dry ether was added
dropwise to a stirred suspension of lithium aluminium hydride in dry ether.
The mixture was then heated to reflux for 3 h, cooled and treated cautiously
(vigorous stirring) with water, then with 15% aqueous sodium hydroxide and
finally with water. The mixture was stirred for 20 min and filtered. The filtrate
was dried over anhydrous potassium carbonate and evaporated. The residue
was distilled under water-pump vacuum to give pure 2-(3-methoxy-phenoxy)-
propylamine, boiling point 148-152°C/13 mm.
2-(3-Methoxy-phenoxy)-propylamine was added to a suspension of 3-
methylphenylacetamidine ρ-toluenesulphonate in absolute ethanol. The
mixture was heated to reflux for 4 h by which time the initially vigorous
evolution or ammonia had practically ceased. The resulting solution was
cooled somewhat and diluted with ether to give an oil which rapidly
crystallised on scratching. The solid was filtered and recrystallised from a
mixture of ethanol and water to give N-[2-(3-methoxyphenoxy)-propyl]-3-
methylbenzeneethanimidamide ρ-toluenesulphonate, melting point 93-96°C
(crystallized from water).
