Enantiomeric fractional distillation

The enantiomeric menthols have identical physical properties (apart from their specific rotation), but the racemates differ from the optically active forms in, for example, their melting points. Although the differences between the boiling points of the stereoisomers are small, the racemates can be separated by fractional distillation. Boiling points (in °C at 101.3 kPa) are as follows ... 

To purify the 5ec-butyl chloride obtained by chlorination of n-butane, we would carry out a fractional distillation. But since the enantiomeric jcc-butyl chlorides have exactly the same boiling point, they cannot be separated, and are collected in the same distillation fraction. If recrystallization is attempted, there can again be no separation since their solubilities in every (optically inactive) solvent are identical. It is easy to see. then, that whenever a racemic modification is formed n a reaction, we will isolate (by ordinary methods) a racemic modification. 

The CATHy catalysts are best used below 40 °C, above this temperature we have observed signs of decomposition. In the I PA system, preventing the back-re-action depends on how efficiently acetone is distilled. Normally this would be best done at around 80 °C, the boiling point of isopropanol, but an optimal performance of the catalyst requires ambient temperature or less, and reduced pressure. Whilst acetone can be fractionally distilled, it is simpler to distil the mixture with isopropanol and to maintain constant volume by continuously charging with fresh solvent. In the TEAF system the reaction is normally operated at ambient temperature. Operating at lower temperatures can improve the enantiomeric excess slightly but gives lower rates, for example with 4-fluoroacetophenone the results described in Tab. 3 were achieved. 

At the end of the reaction the autoclave was cooled and depressurised. Conversion to aldehydes and the regioselectivity of the reaction (2-phenylpro-panal/3-phenylpropanal) were determined without evaporation of the solvent. The reaction mixture was fractionally distilled under reduced pressure to give a mixture of regioisomers of aldehydes. The enantiomeric excess was determined... 

Enantiomeric Separation by Inclusion Complexation in Suspension Media and by Fractional Distillation... 

In this section, one-pot preparations of optically active compounds by a combination of solid-state reaction and enantioselective inclusion complexation in a water suspension medium are described. In order to establish the suspension procedure as a general enantiomeric separation method, enantiomeric separations of various compounds by complexation in hexane and water suspension media were studied. Furthermore, by combining enantioselective inclusion complexation with a chiral host in the solid state with distillation, a fascinating enantiomeric separation method by fractional distillation was established. 

A mixture of (+) and (—) isomers in equal proportion is known as a racemic mixture. A racemic mixture is optically inactive, as expected. Sometimes, a racemic mixture exhibits different physical and chemical properties than any other isomer. The separation of a racemic mixture into its enantiomeric components ((+) and (—) forms) is called resolution. Since the (+) and (—) forms have the same physical and chemical properties, they cannot be separated by ordinary methods such as fractional crystallization and fractional distillation. The use of enzymes and chromatography has enabled the separation of some isomers. 

Preparative Uses of MTPA Derivatives. Resolution of racemic compounds on a preparative scale is always a challenging endeavor. Conversion of the enantiomeric mixture into a mixture of diastereomers, each with unique physical properties, makes it possible to separate the components by a variety of physical methods, such as fractional recrystallization, distillation, or chromatography. One of the earliest uses of MTPA was the resolution of racemic alcohols via the separation of diastereomeric MTPA esters by preparative gas-liquid chromatography, followed by alcohol regeneration with Lithium Aluminum Hydride (eq 2). More frequently, diastereomeric MTPA esters have been separated by high performance liquid chromatography (HPLC), followed by al-... 

For workup the reaction mixture is cooled to 0 C, 50 mL of CH3OH are added, and the mixture is refluxed for 2 h. The solvent is evaporated, and the viscous residue treated with 15 mL of 20 % aq HCI at 0 "C and shaken with 30 mL of El20. The ethereal layer is washed with 15 mL of water and discarded. The combined aqueous phases are rendered alkaline at 0 °C by addition of 15 mL of aq KOH. The amine fraction which separates on the surface is extracted with 50 and then 30 mL of Et20. The combined ethereal extracts arc dried with anhyd MgSO,. After evaporation of the solvent the product is distilled in vacuo using a microdistillation apparatus. The enantiomeric composition is determined by GLC analysis (fused silica Chirasil-t.-Val column). 

CCI4), [a] p (-) and (+) 10.0" (neat). The most likely impurity is the free acid due to hydrolysis and should be checked by IR. If free from acid, then distil, taking care to keep moisture out of the apparatus. Otherwise add SOCI2 and reflux for 5 hours and distil it. Note that shorter reflux times result in a higher boiling fraction (b 130-155"/lmm) which has been identified as the anhydride. [Dale et al. J Org Chem 34 2543 1969, for enantiomeric purity see Dale Mosher Chem Soc 97 512 1973.]... 

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