Objective

To synthesize the methyl ester of L-tryptophan using thionyl chloride and metanol

UCExp248-i.png



Procedure

To L-tryptophan (10.2115g, 50mmol) dissolved in dry methanol (140mL), thionyl chloride (5mL, 68.5mmol) was added drop wise while stirring the mixture at room temperature. After a 10min wait, the temperature was raised, until the mixture started to reflux. This was continued for the next 18h (Ref 1).

Results

HNMR
L-tryptophan
UCExp248-1A (L-tryptophanmethyl ester hydrochloride)

Conclusion

L-tryptophanmethyl ester hydrochloride was successfully synthesized in 86.2% yield.

Log

2009-09-06
14:30 Weighed out L-tryptophan (50mmol, 10.212g) in to a three neck 500mL round bottom flask with a reflux condenser and a addition funnel attached to it. Placed a stir bar in it and set the flask on a hot/stir plate. The condenser was connected to cold water supply.
15:00 Added methanol (140mL, dry) to it while stirring the mix..The acid did not dissolve in methanol (maybe very little)
15:15 Measured out thionyl chloride (60mmol, 5mL) in to the addition funnel.
15:30 Started adding thionyl chloride drop wise in to the methanol/acid solution...No heating at this time..
15:45 Completed addition of thionyl chloride
15:47 Turned on the heating coil on the hot plate.
16:00 Started refluxing methanol...adjusted it to 1-2 drop a sec..temp at 69-70C
2009-09-07
11:00 Turned off heating.
11:30 Evaporated some of the methanol by boiling the reaction mixture in a beaker (1000mL) on hot plate.
12:00 Poured out the remaining solution in to a clean 100mL rb flask and set it on a roto-vap connected to house-vac.
12:15 Almost all of the solvent had evaporated from the beaker leaving a white powdery solid in it. It had however not completely dried out and appeared like a paste. Removed the beaker from the hot plate and left it in the hood to cool down to room temp.
12:30 Covered the beaker with a parafilm and pierced the film several times to make hole in it.
12:35 Placed the covered beaker in to a desiccator connected to a high vac and turned on the vacuum pump.
14:20 Obtained UCExp248-1A (10.973g, 86.2%).
15:50 Obtained HNMR of a sample UCExp248-1A by dissolving approximately 100mg in 700uL DMSO-d6.

Reference

  1. Synthesis of enantiomerically pure β-amino-α-methylene-γ-butyrolactones by way of ozonolysis of aromatic α-amino acids; Torsten Hvidt, Walter A. Szarek, and David B. Maclean Pages 779-782CAN. J. CHEM.Vol 66 1988 p779-782 (Link)