Question

What would happen if you attempted to separate a racemic mixture of (±)-Ibuprofen with a mixture of (±)-a-methylbenzylamine? Would it be possible to perform the resolution of (+)-Ibuprofen with (±)- a-methylbenzylamine? Explain.

Answer 1

Separating a racemic mixture of (±)-Ibuprofen with another racemic mixture is ineffective; however, using enantiomerically pure (±)-α-methylbenzylamine could resolve (+)-Ibuprofen as it forms separable diastereomeric salts.

Step-by-step explanation:

If you attempt to separate a racemic mixture of (±)-Ibuprofen using a mixture of (±)-α-methylbenzylamine, you would not achieve resolution of the ibuprofen because both the ibuprofen and the α-methylbenzylamine would be racemic, leading to four possible combinations — which are not readily separable. However, it would be possible to perform the resolution of (+)-Ibuprofen if you use enantiomerically pure (−)-α-methylbenzylamine or (+)-α-methylbenzylamine. By doing this, diastereomeric salts are formed between the (+)-Ibuprofen and the (−)-α-methylbenzylamine or vice versa, which then have different physical properties and can be separated.

There are primarily two methods of racemate resolution: Enzymatic resolution and Diastereomeric resolution. In diastereomeric resolution, the racemate reacts with a specific enantiomerically pure reagent to form diastereomers, which have different properties and are thus separable. After separating the diastereomers, the original enantiomers can be recovered through a reverse reaction.

Answer 2

Separating a racemic mixture of (±)-Ibuprofen with (±)-a-methylbenzylamine would not be effective. Resolution of (+)-Ibuprofen requires reaction with a single-enantiomer reagent to produce and separate diastereomers.

Step-by-step explanation:

If you attempted to separate a racemic mixture of (±)-Ibuprofen with a mixture of (±)-a-methylbenzylamine, it would not be an effective method for resolution because both reagents are racemic, containing equal amounts of left- and right-handed enantiomers. Thus, no preferential formation of one type of diastereomer would occur, leading to an ineffective separation.

To perform the resolution of (+)-Ibuprofen, you need to react it with a single-enantiomer reagent such as (−)-a-methylbenzylamine. The reaction would produce diastereomers, which are separable due to their differing physical and chemical properties. Once separated, a reverse reaction or another suitable method could be used to retrieve the pure (+)-Ibuprofen.

Biological systems often exhibit a high degree of stereospecificity, reacting favorably with only one stereoisomer of a drug, making the resolution of enantiomers very important for pharmaceutical applications. Two common approaches to resolving racemates are enzymatic resolution and diastereomeric resolution. The former involves the stereospecific cleaving of a compound by an enzyme, while the latter entails the formation of diastereomers by reaction with a chiral agent, followed by separation of the diastereomers and restoration of the original enantiomers.