Dutch Resolution

Dutch Resolution is the term given to the use of mixtures of resolving agents in classical resolutions. These ‘mixtures’ have to meet certain criteria, however. They must be members of the same ‘family’, that is to say they must resemble each other structurally and must be stereochemically homogeneous. In general three family members are used in a Dutch Resolution. Such resolutions, chiefly of acids and bases, proceed rapidly and diastereomeric excesses in the precipitated salts are usually high. These salts almost always contain a mixture of the family of resolving agents.

Success rates, defined for the moment as the chance of obtaining solid salts with significant diastereomeric excesses, were significantly higher, 90–95%, than the 20–30% estimated for classical resolutions. Since the initial discovery of Dutch Resolution in 1996 more than 1000 resolutions of racemic acids and bases have been carried out for clients. Dutch Resolution has been used on a regular basis in the screening of these resolutions. The overall success rate for achieving resolution is greater than 95%. The technique of Dutch Resolution has obviously played a large role in this success.

We find Dutch Resolution extremely useful for small scale resolutions, but because mixtures are involved, we would ordinarily look for a single resolving agent for larger scale separations. Once crystals are available, the search for a single resolving agent becomes far easier.

In further refinements Syncom has discovered that nucleation inhibition and solid solution formation both play a role in Dutch Resolution. Syncom is specialized in development of selective nucleation inhibitors to improve resolutions.

Syncom achieves successful resolution of racemates rapidly by means of diastereomeric salt formation very often aided by the Dutch Resolution variant.