Enantiomeric purity analysis amines

An interesting feature of this study is the enantiomeric purity analysis of the products. By converting the amine functionality of the pyrrolidine to a 3,5-dinitrobenzamide, the substrate can be analyzed by chiral HPLC. To date, the 3,5-dinitrobenzamide of 2-substituted pyrrolidines that the submitters have prepared have beer baseline-resolved by the Pirkle S-N1 N-Naphthylleucine column. This approach obviates the need for MPTA-derivativization which has been previously employed in enantiomeric purity determinations.3 5... 

Sl-a-Phenylethylaminc (2a 94% ee) and (.S)-2-heptylamine (2b 82% ec) were synthesized from enantiomerically pure nitrones 1 a and 1 b (33-39% overall yield). The enantiomeric purity of the amines was determined by HPLC analysis of their 3,5-dinitrobenzamidines on a D-naphthyl alanine column,... 

Amines. In a manner similar to alcohols, the enantiomeric purity of primary and secondary amines can be assayed by H NMR analysis of their MTPA amides. The technique has been particularly useful for amino acid derivatives, e.g. (13), (14), and (15). ... 

Other Compounds. In theory, any chiral compound with a reactive functional group can be derivatized with (5)- or (R)-MTPA in order to assess its enantiomeric purity. An example is the derivatization of cyclic carbamates, followed by H NMR analysis (eq 1). Similarly, axially chiral biaryls bearing amine or alcohol substituents, e.g. (16) and (17), have been analyzed via the corresponding MPTA derivatives. ... 

Analysis of the enantiomeric ratios of several p-blocking drugs (l-aryloxy-3-isopropylamino-2-propanol derivatives) is carried out by HPLC with UV or fluorescence detection after derivatization with (R)-NEI or (i )-(+)-l-(l-phenyl)ethyl isocyanate (in a reversed-phase system), or (S)-NEI (on silica gel) only the amine function of the drugs reacts with the NEI the hydroxy group does not. Similar schemes for HPLC determination of enantiomeric purity of tetrahydrofolate derivatives and of fluoxetine are also reported. 

Several boron-containing species have been used as chiral NMR derivatizing agents for the analysis of primary amines or diols. " Most noteworthy among these is 2-for-mylphenylboronic acid 61, which is commercially available. Reaction of 61 with an amine and diol forms a borate-imine as shown in Scheme 50.1. The reaction can be run using an enantiomerically pure amine such as PEA to determine the enantiomeric purity of the diol, or using an enantiomerically pure diol such as BINOL to determine the enantiomeric purity of the amine.The system has been used to determine the enantiomeric purity of amines with remote chiral centers such as l-amino-4-5 ec-butylbenzene and the methyl ester of 2-methyl-5-aminopentanoic acid. 

When one needs to determine the optical purity of a compound that is not amenable to salt formation (i.e., not a carboxylic acid or amine), analysis by NMR becomes slightly more difficult. It is frequently necessary to determine the enantiomeric excesses of chiral secondary alcohols, for example. In these cases, derivatization of the alcohol through covalent attachment of an optically pure auxiliary provides the mixture of diastereomers for analysis. This requires reacting a (usually small, a few milligrams) sample of sample alcohol with the optically pure derivatizing agent. Sometimes, purification of the products is necessary. In the example shown below, a chiral secondary alcohol is reacted with (5)-2-methoxyphenylacetic acid [(5)-MPA] using dicyclohexylcarbodiimide (DCC) to form diastereomeric esters. After workup, the NMR spectrum of product mixture is acquired, and the res-... 

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