SYNTHESIS OF RESOLUTION OF (±)-𝜶-METHYLBENZYLAMINE [(±)-1-Phenylethylamine]

(—)-𝜶-MethylbenzyIamine:

• Add 450 ml of methanol to 31.5g (0.21 mol) of (+)-tartaric acid in a 1-litre conical flask and heat the mixture almost to boiling on a water bath. 

• Then add cautiously with swirling 24.2g (0.20 mol) of (+)-𝜶-methylbenzylamine; too rapid an addition may cause the mixture to boil over. 

• Allow the mixture to cool to room temperature and then to stand for 24 hours to allow slow separation of the (-)-amine-(+)-hydrogen tartrate as prismatic crystals (1). 

• Filter off the product (17.9g); concentrate the filtrate to 225 ml under reduced pressure on a rotary evaporator and allow it to stand at room temperature for 24 hours to obtain a second crop. The total yield of the (-)-amine-(+)-hydrogen tartrate is about 21g (77%).

• Shake the total product with 90 ml of water in a 250-ml separating funnel and basify the mixture by cautiously adding 50 per cent aqueous sodium hydroxide. 

• Extract out the liberated amine with three 40 ml portions of ether, dry the extract over anhydrous sodium sulphate, filter and concentrate to about 25 ml using a rotary evaporator. 

• Remove the remainder of the ether in a distillation apparatus and fractionally distil the residue at atmospheric pressure (2), collecting the (-)-𝜶-methylbenzylamine as a fraction of b.p. 184-186 °C; the yield is about 5g (53%). 

• Measure the optical rotation of the neat liquid and calculate the specific rotation. 

• Pure (-)-𝜶-methylbenzylamine has d₄²² 0.950, [𝜶]ᴅ²² -40.3° (neat); [𝜶]ᴅ²º -31.5° (c 3.2 in EtOH).

(+)-𝜶-Methy!benzyIamine:

• This enantiomer may be recovered using the following procedure. 

• Evaporate the methanolic filtrate from the isolation of the (-)-amine salt to dryness using a rotary evaporator. 

• Convert the residual salt to the free amine by treatment with sodium hydroxide solution followed by ether extraction as described above. 

• Do not distil the recovered amine but remove the last traces of ether completely by warming under reduced pressure. 

• Weigh the resulting product (x g), measure its optical rotation and calculate the specific rotation. 

• The ratio of this value to that of pure ( + )-amine is the optical purity of the sample; the weight of ( + )-amine in the sample in excess of that present in the racemic modification is given by:

• For each gram of excess (+)-amine present add firstly 10.0 ml of rectified spirit, bring to the boil and then add, for each gram, a hot solution of 0.44g of 98 per cent sulphuric acid (1.03 times the theoretical amount) in 21.5 ml of rectified spirit. 

• Allow the solution to cool slowly to room temperature, filter off the crystalline (+)-amine sulphate and wash it with cold rectified spirit.

• The yield is about 1g of sulphate per gram of (+)-amine (71%). 

• Liberate the free (+)-amine from the sulphate as described for the (-)-amine from the tartrate, but use 4 ml of water and 0.5 ml of 50 per cent aqueous sodium hydroxide for each gram of sulphate. The yield of (+)-amine, b.p. 184—186°C, is 60 per cent of theory; its optical purity is 95 per cent.

Notes to keep in mind:

1. If fine needles separate, the mixture should be warmed until they redissolve, and the solution allowed to cool. The solution should be seeded with the prismatic crystals if these are available.

2. The free amine rapidly absorbs carbon dioxide. It is therefore essential to protect the distillation apparatus from the atmosphere with a guard-tube filled with soda-lime. As the product tends to foam excessively during distillation, the apparatus used should be larger than is customary for the volume of liquid to be distilled.