SUMMARY of answers sent directly to me. Thanks to all. A. Simon ______________________________________________ My original question: Dear ORGLISTers, I want to resolve a racemic mixture of a carboxylic acid derivative. Do you know any non-enzymatic method ? If I use an enzymatic method would you predict better results with amides or esters ? TIA, Albert Simon ______________________________________________ My second question: Thanks to all that answered my question suggesting the reaction of the acid with a chiral base and separation of the resulting distereoisomeric salts by crystalisation. (Or amidation with a chiral amine and separation of the resulting diastereoisomers.) However I had a different approach in mind. I meant an enantiospecific reaction that would hydrolyse one of the enantiomers faster than the other. Any suggestion ? I will summarize the answers I get. Thanks to all ! A. Simon __________________________________________ My third question: >From the answers I got it seems that there is no enantiospecific hydrolysis (non-enzymatic) of esters or amides available. Is it true ? It should be a useful reaction. Don't you agree ? A. Simon __________________________________________ Answers: 1. > Albert > > If you can lay your hands on a copy of Enzymes in Organic Synthesis by Wong > & Whitesides (Tetrahedron Organic Chemistry Series Vol 12, Pergamon 1994) > there are many examples of the use of enzymes to hydrolyse racemic esters. > Probably Pig liver esterase is the most readily available. > > Costa _____ 2. It is difficult to make a reaction that does not yield a chiral center a stereospecific one. Any chirality of an ester or amide is already established, and is not changed during hydrolysis to the alcohol/amine and acid. Therefore one would have to have a reagent that selectively picked only one stereoisomer out of solution and only hydrolyzed THAT one. Anything that could do that would be at least as complicated as an enzyme, and harder to make (since one could not trick some bug to churn it out for you). Good luck. You could trans-esterify with a chirally pure alcohol, and separate the two diastereomers, by crystallization or distillation or chromatography, then hydrolyze the ester to yield your desired product, I would imagine. Dr. John Chubb _____ 3. Perhaps you would get better answers to your question if you described it in more detail. Give a specific example, where is the chiral center in relation to the carbonyl carbon? If it is further away the next carbon, it is unlikely any non-enzymatic method would have appreciably different rate constants for hydrolysis, don't you think. Also, what are the substituents of the chiral carbon? There is more possibility for different rate constants if the substituents are say, -H and -OH than for -H and -F since intramolecular hydrogen bonding in the hydrolysis activated complex could (conceivably) be stereospecific. I am less hopeful about purely steric effects inducing stereospecificity, at least for acid-catalyzed hydrolysis. You wrote: >It should be a useful reaction. Don't you agree ? Not unless the resolution was substantial, unless, again, you have something specific in mind. is this thinking at all useful you? Gerald Morine _____ 4. Maybe many of you would be interested in the article: Angew. Chem. Int. Ed. Engl. 1997, 36, 2731 Nonenzymatic Kinetic Resolution of Secondary Alcohols by Peter Somfai And also, I suggest to follow reports of G.C.Fu, who is now keen on the kinetic resolution by using chiral DMAP-defivatives. (I think the most recent result appeard on JACS 99, 2637). Mitsuhiko FUJIWHARA, Ph.D. ------------------------------------------------------ Get the Latest News at CNN Interactive: http://CNN.com __________________ ORGLIST - Organic Chemistry Mailing List Website and Archive: http://www.orglist.net/ List coordinator: Joao Aires de Sousa (jas@mail.fct.unl.pt)