Amides diastereomeric compounds

There are few differences between the separation in gas chromatography [14-16] and the separation in liquid chromatography (LC), because it is assumed that the differential solvation of the diastereomeric compounds during the LC separation does not play a very important role [17], Helmchen et al. [18] explained the separation of diastereomeric amides using LC with a silica gel stationary phase under normal-phase conditions. In order to explain their separation, the authors made some assumptions ... 

Tcible 6.24. chemical shifts of Z, E diastereomeric amides (neat compounds)... 

The [2 + 2] cycloaddition reaction of A -benzyl-l,4-dihydropyridine 34b with acrylonitrile, followed by catalytic reduction gave two pairs of diastereoisomeric amides 36 and 37 with a low diastereomeric excess, probably due to the large distance between the asymmetric center and the site of acrylonitrile attack. Compounds 36 and 37 were resolved into the four individual diastereoisomers (ca 5% for compound 36 and 15% for 37) [97JCR(M)321], Irradiation of 1,4-dibenzyl-1,4,5,6-tetrahydropyridine 38 in the presence of 29 gave two stereoisomers. 

For this reaction, CALB catalyzes the amidation between a racemic P-hydroxyester and racemic amines, leading to the corresponding amide with very high enantiomeric and diastereomeric excesses. Besides, the remaining ester and amine are recovered from the reaction media, also showing good enantiomeric excesses. By this method, three enantioenriched interesting compounds are obtained from an easy one-step reaction. 

Thus Pasteur noted that the amide of (-) malic acid forms molecular compounds of different properties with the enantiomeric amides of tartaric acid. With amide of (+) tartaric acid large transparent crystals are formed whose solubility is 18% at 20°C, while with the amide of (-) tartaric acid, thin needles are formed with solubility almost two times higher. Free malic and tartaric acids also form diastereomeric molecular compounds. 

One of the main principles for chiral separation used in modern capillary GC is the bonding of the optically active compounds via hydrogen bridges to a stationary-phase material. Feibush and Gil-Av [8] suggested a rapid and reversible formation of association complexes between carbonyl and amide functions of selector and selectand. The formation of diastereomeric associates yields complexes of different stability, depending on the relative configuration. The introduction of dipeptide and diamide phases leads... 

Moreover, it is possible to lead these compounds into the diastereomeric esters or amides using of optically active acid anhydrides. In this case, the diastereomers with a covalent bond need not always necessarily be a crystalline compound because there are still some other methods left to separate these diastereomers, such as thin layer chromatography, high-performance liquid chromatography, etc. 

This reaction can be also performed asymmetrically, when it is applied to a, 3-unsaturated amide derivatives bearing a chiral auxiliary [299]. Among several common auxiliaries, the frans-2,5-dinaphthylpyrrolidine unit proved to be optimal, giving a-hydroxy amides in 62-87% yield and diastereomeric ratios ranging from 78 22 up to 97 3 for the compound with (R)-configuration. 

The unpurified a-amino esters obtained after the two first steps were acylated with (+)-MTPA chloride (MTPA = a-methoxy-a-(trifluoromethyl)phenylacetic acid) to afford the (+)-MTPA amides 41. In the case of R = CH2Ph, the final compound 41 was found to be identical to the (+)-MTPA amide derived from L-phenylalanine. The (2S) configuration was correlated for 41 and capillary GC analysis proved that the diastereomeric ratio (2S) (2R) was > 200 1. 

Glycosyl imines from aliphatic aldehydes are sensitive to anomerization. However, the anomerization can be avoided by conducting the reactions at lower temperatures (-78 °C). Recrystallization of the crude products (methanol/water for aliphatic, heptane for aromatic compounds) gave the diastereomerically pure D-amino acid amides (Table 4.3). 

Resolving Reagent for Carboxylic Acids and Other Types of Compounds. A large number of carboxylic acids have been resolved via their diastereomeric salts with (S)- or (7 )-a-methylbenzylamine (1). The ready availability of both enantiomers of (1) guarantees access to both enantiomers of the desired acid. Compounds (2)-(6) are representative examples of acids obtained in high enantiomeric purity. " Alternatively, racemic carboxylic acids have been resolved by covalent derivatization with (1) and separation of the resulting diastereomeric amides by physical means such as chromatography (eq 1) or fractional crystallization (eq 2). ... 

Racemic compounds other than carboxylic acids have also been resolved by reaction with enantiomerically pure (1) and separation of the corresponding diastereomeric mixtures by physical methods. For example, reaction of a racemic p-substituted 7-butyrolactone with (1) yields a mixture of hydroxy amides, which can be separated by fractional recrystallization and chromatography (eq 3). Amide hydrolysis regenerates the chiral hydroxy acids, which spontaneously cyclize to produce the chiral lactones. 

Many chiral derivatization reactions were used and the compounds examined are mostly amphetamines, /3-blocking agents, amino adds, and anti-inflammatory drugs. Silica gel and, to a lesser extent, silanized silica were used as stationary phases. The Rf values obtained for the diastereomeric pairs were not usually very high (0.04 -0.07), with the exception of amino alcohol and amino acid diastereomers obtained with Marphey s reagent, a derivative of L-alanine amide (0.06 - 0.22). 

The unsaturated acid, a compound that could not be prepared readily by asymmetric induction, seemed a good candidate for resolution. In fact, this acid was resolved by fractional crystallization of diastereomeric amides (Figure 10), and then the pure diastereomers were cleaved by means described above. 

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