Binyamin Feibush

Interaction between asymmetric solutes and solvents. Diamides derived from L-valine as stationary phases in gas-liquid partition chromatography.

The resolution of enantiomers of (+/-)-a-amino acid derivatives on optically active diamides derived from L-valine, R1CONHCH[CH(CH3)2]CONHR2, as gas chromatographic stationary phases was studied. The effects of the structure of R1 and R2 in the stationary phases, the structure of the racemic a-amino acid derivatives, temperature, etc., on the separation factors are reported. In the light of these and related results, a more probable mechanism of resolution is presented.

Separation of enantiomers on packed columns containing optically active diamide phases

Chromatography of fourteen protein amino acids has been studied on 2-4- m long packed columns containing chiral diamide phases. Twelve of the thirteen optically active compounds examined could be resolved, with R greater than or equal to 1 in many instances. Two of the phases, N-docosanoyl-L-valine tert.-butylamide and N-lauroyl-L-valine 2-methyl-2-hepatadecylamide, can be employed at temperatures as high as 190 degrees and 180 degrees, respectively, without losing their efficiency, even after prolonged use. The problem of peak overlap in the analysis of mixtures of different amino acids was examined and partially solved.

Novel, highly deactivated reversed-phase for basic compounds

Abstract Silica has proven invaluable as a support material for reversed-phase high-performance liquid chromatography. However, contributions of residual acidic silanols lead to poor chromatography of basic compounds. This paper demonstrates the utility of a new, highly deactivated silica-based reversed-phase packing material for the study of a series of weak and strong organic bases. Correlation between retention times on the column and octanol-water partition coefficients at pH 7.0 is demonstrated. Also shown are the results of further experiments in which we investigated the retention characteristics of basic, acidic and neutral compounds by the new deactivated phase.

N-acyl derivatives of chiral amines as novel, readily prepared phases for the separation of optical isomers by gas chromatography

Abstract The results reported demonstrate that it suffices for a chiral stationary phase to contain an amide group and an asymmetric carbon atom, attached to the nitrogen atom [RCONHCH(CH3)R′], in order to show selectivity in its interaction with the enantiomers of amides such as N-trifluoroacetylamines, N-trifluoroacetylamino acid esters and α-methyl- and α-phenylcarboxylic acid amides. The best efficiency is obtained when R′ is aromatic, particularly α-naphthyl, as in N-lauroyl-S-α-(1-naphthyl)ethylamine. The highest resolution factors were found for aromatic solutes, such as N-trifluoroacetyl-α-phenylethylamine and α-phenylbutyric acid amides, which could be resolved readily on packed columns. The enantiomers of α-branched carboxylic acids were separated for the first time by gas chromatography. Based on the packing arrangement in the crystalline form of the N-acetyl homologue of N-lauroyl-S-α-(1-naphthyl)ethylamine, a mechanism for the resolution is proposed. It is assumed that the mode of association found in the solid state is at least partially retained in the melt through a network of hydrogen bonds. The mechanism proposed is developed with particular reference to the aromatic solute-solvent systems. It is suggested that the solute is intercalated (“sandwiched”) between two solvent molecules. Arguments, based on X-ray data, are given to explain the selectivity observed.

Hydrophilic shielding of hydrophobic, cation- and anion-exchange phases for separation of small analytes: direct injection of biological fluids onto high-performance liquid chromatographic columns

Shielded hydrophobic phases (SHPs) have an external hydrophilic network that prevents larger protein molecules from interacting with hydrophobic zones. Smaller analytes are not sterically hindered from interacting with the hydrophobic zones and are retained. This mechanism allows the separation of the proteins from the analytes of interest. SHPs have been shown to be useful for the direct-injection analysis of drugs in biological fluids. In this paper, two kinds of shielded phases are discussed: bonded micellar phases and embedded polymeric phases. For some compounds of interest, the hydrophobic retention and selectivity is insufficient to obtain the desired resolution. To increase selectivity without affecting protein exclusion, shielded phases were prepared with ion-exchange groups added to the hydrophobic zones. Such modified phases with cation-exchange and anion-exchange capabilities were examined for additional selectivities. Usage of these additional selectivities will be demonstrated to achieve better analysis and resolution for basic, acidic, and neutral compounds.

Chiral solute–solvent systems. Selective interaction between N-dodecanoyl-L-valine amides and N-trifluoroacetyl esters of the enantiomers of 2-aminoalkan-1-ols and α-, β-, and γ-amino-acids

Optically active 2-aminoalkan-1-ols in the form of their O-acyl-N-trifluoroacetyl derivatives have been resolved by g.l.c. with N-dodecanoyl-L-valine 6-undecylamide (1) as the stationary phase. A bulky O-acyl group substantially facilitates resolution. Resolutions of the N-trifluoroacetyl-esters of α-, β-, and γ-amino-acids on diamide phases are also reported. The order of emergence of the derivatives of the 2-aminoalkan-1-ols and the γ-amino-acids is D after the L-isomer, i.e., the reverse of that found for the α-amino-acids.The mechanism of resolution is discussed on the basis of association complexes involving the formation of two hydrogen bonds between the solutes and the solvent.

Assignment of the configuration of optical isomers by gas chromatography by the use of asymmetric stationary phases. Absolute configuration of 2-amino-3-methylbutane and 2-amino-4-methylpentane

The relationship, found previously, correlating the configuration and order of emergence of enantiomeric 2-N-trifluoroacetylaminoalkanes on carbonylbis-(N-L-valine isopropyl ester) has been confirmed for 2-amino-3-methylbutane (I) and 2-amino-4-methylpentane (II) by unambiguous synthesis of the L(R)-isomers. Confusion of assignment due to the effect of polar solvents on the sign of rotation of aminoalkanes has been cleared up for compounds (I) and (II). The findings of Brewster and his co-workers which correlate the sign of rotation [(–)–L(R)] have been shown to be correct, provided data referring to the neat liquid are considered, as specified by the authors. Cyclization of 2-aminoalkan-1-ols to aziridines, followed by hydrogenolysis, has been shown to lead to amines of known configuration (R : S 80 : 20) from the corresponding α-amino-acids.

Differential gas–liquid chromatographic behaviour in diastereoisomeric systems. Part III. Symmetrically substituted dichiral ethers, alkoxysiloxanes, and disiloxanes

G.l.c. resolution of diastereomers containing an asymmetric silicon atom as alkoxysiloxane was studied and compared with that of similar compounds of the ether and of the disiloxane series. The resolution factors of some diastereomers containing an asymmetric silicon atom are ca. 1·04 and complete separation is achieved on an efficient capillary column coated with Apiezon L.

Differential gas–liquid chromatographic behaviour in diastereoisomeric systems. Part II. Assignment of diastereomer configuration in 2,3-dipentylbutanes and 2,4-dipentylpentanes

During the preparation of the ditoluene-p-sulphonates of 2,3-dipentylbutane-1,4-diols and 2,4-dipentylpentane-1,5-diols, two competing reactions occurred; the ditoluene-p-sulphonylation and the formation of the appropriate cyclic ethers. Each of the meso-isomers produce a mixture of meso-ditoluene-p-sulphonyl derivative and the cis-cyclic ethers while the (±)-isomers from a mixture of the (±)-ditoluene-p-sulphonyl derivatives and the trans-cyclic ethers. As a result of a difference in the activation energy of formation, the cis- and trans-isomers of each cyclic compound are obtained in unequal amounts with the trans in majority; thus the corresponding ditoluene-p-sulphonyl products are obtained proportionally unbalanced with the (±)-form in minority. The ditoluene-p-sulphonyl derivatives are quantitatively reduced to the corresponding hydrocarbons and after chromatography, help to determine the relative retention times and volatilities of the meso-(±) and cis–trans pairs in the 3,4-dipentyltetrahydrofurans, 3,5-dipentyltetrahydropyrans, 2,3-dipentylbutanes, and 2,4-dipentylpentanes.

Differential gas–liquid chromatographic behaviour in diastereoisomeric systems. Part I. Symmetrically substituted dichiral hydrocarbons and ester precursors

Dichiral molecules are defined as those with two asymmetric centres. In the present work, the differential g.l.c. behaviour of diastereomers of 2,3-dipentylbutanes and 2,4-dipentylpentanes, wherein the pentyl groups were selected from various isomeric C5H11 moieties and cyclopentyl, have been examined. Also obtained were comparable results for synthetic precursors to these compounds, the respective diethyl αα′-dipentylsuccinates and αα′-dipentylglutarates, the diacetates of 2,3-dipentylbutane-1,4-diols and 2,4-dipentylpentane-1,5-diols, and for by-product 3,4-dipentyltetrahydrofurans and 3,5-dipentyltetrahydropyrans. The experimental data provide information on configuration of the diastereomers, the effect of substituent bulk, the influence of distance between chiral centres, and the role of polar dipole–dipole interactions versus steric effects.