Racemization
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص459-460
2025-06-04
488
Any stereogenic centre next to a carbonyl group is precarious because enolization will destroy it. It would be foolish to try and make optically active β-keto esters whose only stereogenic centre was between the two carbonyl groups. Although the keto-ester is chiral, the enol is flat and cannot be chiral. The two forms are in rapid equilibrium so all optical activity would quickly be lost.
Compounds with one carbonyl group next to the stereogenic centre can be made but care still needs to be taken. The α amino acids, the component parts of proteins, are like this. They are perfectly stable and do not racemize in aqueous acid or base. In base they exist as carboxylate anions that do not enolize, as explained above. Enolization in acid is prevented by the –NH3 + group, which inhibits the protonation of the carbonyl group necessary for enol formation. Amino acids can be converted into their N-acetyl derivatives with acetic anhydride. These N-acetyl amides can be racemized on recrystallization from hot acetic acid, no doubt by enolization. The amino group is no longer basic, and is not protonated in acid, so protonation on the carbonyl group and hence enolization is now possible.
You may think it a crazy idea to want to racemize an amino acid. Supposing, however, that you are preparing a pure (S)-amino acid from a racemate by resolution. Half your material ends up as the wrong (R)-enantiomer and you don’t want just to throw it away. If you racemize it you can put it back into the next resolution and convert half of it into the (S)-acid. Then you can racemize what remains and so on.
Racemization in vivo Some compounds may be racemized inside the human body. Bacterial cell walls are built partly from ‘unnatural’ (R)-amino-acids, which humans can’t digest. But we can use enzymes to racemize them. There is an important group of analgesic (pain-killing) drugs, such as ibuprofen, based on the aryl-propionic acid structure. Ibuprofen can be bought over the counter in chemists’ shops as Nurofen. Only the (S)-enantiomer of ibupro fen is an effective painkiller but the compound is administered as the racemate. The body does the rest, racemizing the compound by enolizing it.
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