My PhD dissertation - Institut Fresnel
My PhD dissertation - Institut Fresnel
My PhD dissertation - Institut Fresnel
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4.2.2 Racemate Resolution of 6,6’-Dibromobiphenyl-2,2’-dicarboxylic<br />
Acid<br />
46<br />
The most reliable procedure to resolve chiral carboxylic acids is the fractional<br />
crystallization of a diastereomeric salt which can be easily obtained by treatment of<br />
the racemic acid mixture with an enantiomer of a chiral amine such as alkaloids, amino<br />
acids, terpene derivatives, etc.<br />
methylbenzylamine<br />
[5] . A first attempt was made with (S)-(-)-α-<br />
[ ] 188 . Its low molecular weight constitutes an advantage for large<br />
scale racemate resolution. Moreover, this chiral amine is commercially available in<br />
both enantiomeric forms. Unfortunately, crystallization of the resulting diastereomeric<br />
salt happened to be very slow and had to be repeated several times to give<br />
enantiomerically pure products.<br />
In view to the results reported by K. Mislow et al.<br />
[ ] 189 and R. Adams et al.<br />
[ 190 ]<br />
, commercial alkaloids were used. The brucine dihydrate salt was prepared and its<br />
crystallization attempted in various solvents. Unfortunately, both diastereomeric salts<br />
co-crystallized. Quinine monohydrate finally proved to be a better choice.<br />
Crystallization of its biphenol salt in ethanol followed by hydrolysis finally allowed<br />
separation both atropisomers in good yield (42% and 39%).<br />
Br COOH<br />
Br COOH<br />
rac-31<br />
O<br />
HO<br />
H<br />
H<br />
N<br />
(Quinine)<br />
Ethanol<br />
reflux<br />
N<br />
H<br />
Precipitate<br />
Mother liquors<br />
Br<br />
Br<br />
COO Quinine, H<br />
COOH<br />
Br COO Quinine, H<br />
Br COOH<br />
10% aq. HCl Br<br />
Br<br />
COOH<br />
COOH<br />
(P)-(-)-37, 42%<br />
10% aq. HCl<br />
Br COOH<br />
Br COOH<br />
(M)-(+)-37, 39%