Dutch Resolution

Kellogg RM, Kaptein B, Vries TR (2007) Dutch Resolution of Racemates and the Roles of Solid Solution Formation and Nucleation Inhibition. 269 159-197 Kessler H, see Weide T (2007) 272 1-50... 

FIGURE 7.5 Dutch Resolution of D,L-f/meo-(4-methylthiophenyl)serine amide with P-(-)-mix. 

Selection of Racemates Resolved by the Dutch Resolution (DR) Approach ee and Mix (Ratio after One Recrystallization)... 

FIGURE 7.8 Dutch Resolution of (R,S)-jt>-hydroxyphenylglycine with (+)-camphor-10-sulfonic acid and (R,S) or (R)-phenylglycine as a family member. 

FIGURE 7.9 Dutch Resolution of (R,5)-alaninol with (R)-mandelic acid using (R)-, or (5)-2-amino-l-butanol as a family member. 

Even more interesting is the addition of the (.S )-cnantiomcr of 2-amino-1-butanol, which itself forms a salt with (R)-mandelic acid. This salt has almost inhnite solubility. With this additive, the resolution of alaninol with (W)-mandelic acid results in the crystallization of an almost diastereoiso-merically pure salt, without incorporation of 2-amino-l-butanol. On use of this method enantiopure (R)-alaninol can be obtained after an additional recrystallization, without the need to separate the alaninol from the 2-amino-l-butanol. We call this procedure reverse Dutch Resolution, to indicate that the family mix remains in solution. Most likely in this case stereoselective nucleation inhibition plays a role by suppressing the nucleation of the (.S )-alaninol-(A )-mandclic acid diastereoisomer. 

In this context, chemists at DSM have made interesting observations. They could demonstrate better yields and selectivities for the crystallisation of substance families, rather than pure substances (Dutch Resolution). [65-69]... 

The purity (de) of the diastereoisomer can be improved using a mixture of structurally related resolving agents. It is often referred as "Dutch resolution" in the literature.ii... 

Brasile MLG, Gelens E, Vries T, Kaptein B, Kellogg R. Structural aspects of nucleation inhibitors for diastereomeric resolutions and the relationship to Dutch resolution. Angew. chem. Int. Ed. 2008 47 1287-1290. 

Kellogg RM, Kaptein B, Vries TR. Dutch resolution of racemates and the roles of sohd solution formation and nucleation inhibition. Top. Curr. Chem. 2007 269 159-197. 

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