Synthesis of 4-Chloro-2,5-Dimethoxyphenethylamine (2C-C)

Synthesis of 4-Chloro-2,5-Dimethoxyphenethylamine (2C-C)

2,5-Dimethoxyphenylethylamine (1.81g, 10 mmol) was dissolved in 20ml glacial acetic acid in a 50ml beaker equipped with magnetic stirring and a thermometer, and placed in an ice-bath. Sulfuryl chloride (2.0g, 1.20ml, 15 mmol) was added dropwise1 to the solution over 30 minutes, the whole time keeping the temperature of the solution between 15-20°C2. When the addition was finished, the ice-bath was removed, and the solution allowed to warm up to room temperature (25°C) and stirred for another 90 minutes, the temperature being monitored occasionally so that it didn’t exceed 30°C. A too high reaction temperature causes partial dichlorination of the substrate, a temperature of 40°C during the addition invariably causes side reactions.

When the mixture had reacted for a total of 2 hours, 20ml of dry diethyl ether was added, and the solution stirred at room temperature for another 30 minutes, followed by filtration of the precipitated 4-Chloro-2,5-Dimethoxyphenethylamine Hydrochloride and washing with 15ml of dry ether, and air drying to give 0.54g of a white powder. The mother liquor was diluted with an equal amount of dry ether and allowed to stand overnight in the fridge, giving a second crop of 0.74g 2C-C.HCl. The combined crops weighed 1.28g (51% yield) which were and dissolved in a boiling mixture of 50ml acetonitrile and 5ml methanol, which after cooling somewhat was diluted with 30ml dry ether and placed in the fridge to fully crystallize to give 0.67g (27% yield) of pure 4-Chloro-2,5-Dimethoxyphenethylamine (2C-C) Hydrochloride after filtration, washing with 10ml ether and air drying. The recrystallization was very wasteful, and a different solvent system should have been used. Reference [1] suggests methanol/ether.

Notes:

1. Sulfuryl Chloride is poisonous, and its vapors dissociate into Cl2 and SO2 gas. Use only in a well ventilated area, and preferably chill the bottle before use, as to minimize evaporation.
2. If the reaction mixture is chilled too much, the acetic acid will solidify, so try to keep the temperature between 15-20°C and not below.

References

[1] Tetrahedron Letters 42, 3247-3249 (2001)