Sciencemadness Discussion Board

Selecting chiral acids for resolution of amines.

Mark Van Adium - 29-4-2013 at 08:28

Is this just done by trial and error? Is there anything I can do to improve my yields?

I've not attempted it yet but have some d-tartaric acid which I want to give it a go with. One amine is similar to amphetamine, for which there is a published procedure, but the other is an arylcyclohexamine and I'm concerned that it won't be effective?

zed - 1-5-2013 at 12:59

Well, you could just experiment. Or, you could go to the library. Where you will search, and you try to find out what has worked for others.

Slick "Pharma" chemists with big budgets and lots of helpers, have spent years figuring these things out. Why re-invent the wheel?

Mark Van Adium - 2-5-2013 at 10:07

It looks like it's actually more challenging and less rational than I thought.

1999 Molecular Chirality Award Winner; Kazuhiko Saigo Ph.D.
Quote:

Usually we choose a suitable resolving agent by trial-and-error, because there is no criterion for selecting a suitable resolving agent at present. Actually, the study on the optical resolution by the diastereomeric salt formation is strongly target oriented; when one researcher want to resolve this racemic amine, the researcher prepare many kinds of salts with enantiopure acids and choose the best one.
A shame. I did have a go, and the arylcyclohexamine and the cathinone that were tried both precipitated very quickly once tartaric acid was added. They are evaporating now and I am trying to hunt down a set of 3D specs to make a polarimeter but having read that I don't hold so much hope.

[Edited on 2-5-2013 by Mark Van Adium]

aliced25 - 12-5-2013 at 02:04

I know the isoquinolines used for making dextromethorphan are resolved using Naproxen, a chiral acid available in most chemists/drugstores.

paw_20 - 14-5-2013 at 10:45

I think naproxen is usually sold as the sodium salt (not that that's much of a problem). I remember a college ochem experiment that involved extracting naproxen from aleve, the outer blue coating comes off fairly readily by stirring a few minutes in methanol.

Mush - 8-5-2015 at 14:02

Twenty Years of Naproxen Technology
Peter J. Harrington * and Eric Lodewijk
Syntex Group Technology Center, 2075 North 55th Street, Boulder, Colorado 80301
Org. Process Res. Dev., 1997, 1 (1), pp 72–76
DOI: 10.1021/op960009e

Optical Resolving Agents
http://www.tcichemicals.com/eshop/en/us/category_index/00204...

My favorite OTC D-Aspartic Acid.

A neutral amino acid complex and a method for optical resolution of a dl-amino acid
EP 0132373 B1

Example 3
Eight grams of DL-phenylalanine and 1.2 g of sulfuric acid were suspended in 100 ml of water at 40°C. Ten grams of N - carbobenzoxy - D - aspartic acid was added to the solution over five hours, while this solution was continuously stirred. The resulting crystal was separated, washed with 10 ml of water and dried to give 5.2 g of a D - phenylalanine N - carbobenzoxy - D - aspartic acid. Analysis revealed that the optical purity of the D-phenylalanine was 98%.


Addition salts of N-acyl aspartic acid and alpha-arylalkylamines and process for the optical resolution of alpha-arylalkylamines
EP 0845455 B1

Journal of Oleo Science
Vol. 64 (2015) No. 1 p. 75-90

Chemistry and Organic Synthesis
Preparation of Optically Pure δ-Lactones Using Diastereomeric Resolution with Amino Acid as Resolving Agent

Yasutaka Shimotori1), Masayuki Hoshi1), Syota Seki2), Takeshi Osanai2), Hayato Okabe2), Yoshitaka Ikeda2), Tetsuo Miyakoshi2)

Indian Journal of Chemistry
Vol. 48B, September 2009, pp. 1261-1273
Simple and convenient methods for synthesis, resolu
tion and application of
aminonaphthols



Attachment: Naproxen Harrington, Peter J.pdf (319kB)
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[Edited on 8-5-2015 by Mush]

Attachment: IJCB 48B(09) 1261-1273.pdf (158kB)
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smaerd - 10-5-2015 at 03:53

There's a pretty big thread here about making polarimeters - http://www.sciencemadness.org/talk/viewthread.php?tid=18597

Templar - 15-5-2015 at 08:02

There was another derivative of tartaric acid that was suitable as well. Supposedly it gave quicker resolution of the d/l amphetamine molecules as solubility difference between the two was greater.

However, it wasn't OTC and quite specialist.

Using D-tartaric and building a rough idea of solubilities of the d/l dextro tartaric salts using a polarimeter would help. Base + tartaric -> wash ppt with cold water-> check optical activity of the filtrate solution -> repeat process

Industrially speaking, i dont think amphetamine is very expensive to make, but that special derivative of tartaric might be, so the chosen big pharma method may just be to use d-tartaric.

Chemosynthesis - 15-5-2015 at 08:20

See US2833823

Loptr - 15-5-2015 at 09:34

I am not quite sure what is up with the site at this time, but at one time it was a nice little read with a few procedures, with one of them being a racemic resolution of Praziquantel and Praziquanamine using dibenzoyl tartaric acid.

http://www.ourexperiment.org/racres_pzq/1279

http://www.ourexperiment.org/search?q=dibenzoyl+tartaric+aci...