Sciencemadness Discussion Board - Removing HCl from L-histidine methyl ester dihydrochloride

Removing HCl from L-histidine methyl ester dihydrochloride

ZidaneTribal - 22-3-2019 at 11:24

I need the free base of L-histidine methyl ester dihydrochloride. I dissolved it in a saturated K2CO3 solution and extracted it with CH2Cl2, CHCl3 and EtOAc but no product was found in the organic phase. What am I doing wrong?

Metacelsus - 23-3-2019 at 05:00

Histidine is quite polar, even when not protonated. At high pH the carboxylate form will dominate. I would try carefully adjusting the pH to the isoelectric point (7.5), then doing multiple extractions into chloroform.

It might also be possible to form the free base in situ for the next step. What is your downstream application?

ZidaneTribal - 23-3-2019 at 12:42

Quote: Originally posted by Metacelsus

Histidine is quite polar, even when not protonated. At high pH the carboxylate form will dominate. I would try carefully adjusting the pH to the isoelectric point (7.5), then doing multiple extractions into chloroform.

It might also be possible to form the free base in situ for the next step. What is your downstream application?

I need it to react with methacryloyl acid in organic solvent. Should I just put it in dichlormethane and add triethylamine, then add methacryloyl chloride? Could be a good alternative.

Based on this paper: B. Garipcan, A. Denizli, Macromolecular Bioscience 2002, 2, 135-144.

[Edited on 23-3-2019 by ZidaneTribal]

Cactuar - 24-3-2019 at 01:12

Quote: Originally posted by ZidaneTribal

That's how I would have done it. Keep base in excess to quench formed HCl as the free amine would be protonated and the imidazole would be alkylated instead. Also keep temperature low to lower the imidazoles reactivity.