Crystallization coupling with chromatography

We will first describe briefly the main experimental techniques coupled with electrochemical methods Infrared Reflectance Spectroscopy (IRS), Electrochemical Quartz Crystal Microbalance (EQCM), Differential Electrochemical Mass Spectrometry (DEMS), Chemical Radiotracers and High Performance Liquid Chromatography (HPLC). 

For achiral molecules that, when coupling with a chiral molecule (mostly alkaloids, such as brucine, cinchonidine, and sparteine), form a pair of diastereomers with different physical properties that can be separated by the methods of fractional crystallization, column chromatography, etc., resulting in the enantiomeric resolution. No actual mechanism is necessary for this reaction. 

C Racemic mixture Resolution - Crysullization (spontaneous resolution) - Chiral chromatography Crystallization (spontaneous resolution) coupled with an in situ fast racemization - Separation via diasteieomers - Kinetic resolution with or without creation of new chiral units - Asymmetric Transformation - Deracemization... 

In the synthesis of 29 [78], axially chiral precursor was obtained via biaryl coupling between benzodithiophenes with chiral oxazoline [derived from (S)-valinol] as an auxiliary, e.g. Stille cross-coupling of 25 and 26 provided bis(benzodithio-phene) 27 in 68% yield with 49% de (Fig. 15.10). Although the diastereomers were not separable by silica gel column chromatography, crystallization of diastereomers from hexane-ethyl acetate gave crystals with an S-axial configuration. 

Direct alkylation of 5-substituted tetrazoles is often the best method of obtaining simple 2,5-disubstituted tetrazoles. The 1,5-isomers, which are formed as competitive side products, are usually separated with ease by fractional crystallization or better by column chromatography on alumina or silica gel which gives excellent separations of most tetrazole isomers (8UCR(S)174). Another convenient synthesis of 2,5-disubstituted tetrazoles (241) is the formazan method (Scheme 31). By coupling aldehyde arylsulfonylhydrazones (240) with diazonium salts in basic solutions, compounds (241) may be obtained directly in yields of up to 78% (76BCJ1920). 

Tetra-p-tolylsilane, prepared via Wurtz-coupling of 4-bromotoluene and SiCU, was brominated with NBS according to a procedure described by Drefahl [13] yielding a mixture of the three- and four-fold benzylic bromides la, lb which can be separated by repeated crystallization from acetone. A more convenient way is to convert the crude mixture in a Michaelis-Arbusow reaction to the phosphonates 2a, 2b and to separate these via chromatography (SiOa/ethyl acetate/ethanol). A second Wohl-Ziegler bromination/Michaelis-Arbusow sequence allows one to transform 2a into the tetrahedral 2b in moderate yield. 

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