Amines derivatization

Many times an analyte must be derivatized to improve detection. When this derivatization takes place is incredibly important, especially in regards to chiral separations. Papers cited in this chapter employ both precolumn and postcolumn derivatization. Since postcolumn derivatization takes place after the enantiomeric separation it does not change the way the analyte separates on the chiral stationary phase. This prevents the need for development of a new chiral separation method for the derivatized analyte. A chiral analyte that has been derivatized before the enantiomeric separation may not interact with the chiral stationary phase in the same manner as the underivatized analyte. This change in interactions can cause a decrease or increase in the enantioselectivity. A decrease in enantioselectivity can result when precolumn derivatization modifies the same functional groups that contribute to enantioselectivity. For example, chiral crown ethers can no longer separate amino acids that have a derivatized amine group because the protonated primary amine is... 

An easily accessible DA CSP derived from L-A-(2-naphthyl)valine (80) was used to separate appropriately derivatized amines, amino alcohols and thiols, derivatization consisting of N-, O- and 5-acylation with 3,5-dinitrobenzoyl chloride or 3,5-dinitrophenyl... 

Fig. 26 Reversed-phase liquid chromatographic separation of GITC-derivatized amines. 1 = R,R-pseudoephedrine, 2 = 5,5-pseudoephedrine, 3-R,5-ephedrine, 4 = 5, R-ephed-rine, 5 = 5-methamphetamine, 6 = R-methamphetamine. (From Ref...

Amino group protection. Title reagent 1 is proposed to derivatize amines for their protection. Mild conditions are needed to cleave the derived carbamates. ... 

Chloroformates have been widely used to derivatize amines because the derivatives are easily made, even in buffered aqueous solution, and have useful chromatographic properties, especially volatility. The derivatization reactions were studied by Ahnfeldt and Hartvig, who found the trichloroethyl chloroformate an order of magnitude more reactive than alkyl chloroformates. The reactions went faster with the secondary amine studied [148]. Methyl chloroformate was used to derivatize adrenaline and noradrenaline in plasma (1 ml) buffered at pH 7.4. Methyl chloroformate (20 fd) was added and the mixture was stirred for 30 seconds. After 5 minutes the product was extracted into methylene chloride, the extract was evaporated to dryness and the residue was silylated for analysis by gas chromatography [149]. A very similar procedure was developed by Japanese workers around the same time, using ethyl chloroformate to derivatize both amino and hydroxyl groups [150]. 

Chromatography Pirkle and Simmons [93] separated the derivatized amines by HPLC on a silica column with 0.5% 2-propanol in hexane as mobile phase. 

This reaction can be extended further to include other functionalized organozinc reagents. The products are derivatized amines as shown below (Table 2). 

Table 2 Preparation of derivatized amines using trimethylsilyldiethylamine and functionalized organozinc reagents...

Axially chiral carboxylic acids such as [2] and [3] can be used to prepare diastereoisomers of secondary alcohols. The NMR spectra of the diastereoisomers show enantiomeric resolution and it is possible to assign absolute configurations. Monocyclic, chiral carboxylic acid compounds such as tetrahydro-5-oxo-2-furancarboxylic acid and 2,2-diphenylcyclo-propane-carboxylic acid have been used to derivatize secondary alcohols for the purpose of enantiomeric resolution. Similarly, bicyclic derivatizing agents such as camphanic acid, camphanic acid chloride, or camphor sulfonyl chloride have been used to derivatize amines or alcohols to their respective amides or esters for the purpose of enantiomeric resolution. 

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