Hydrogen bonding steric conditions

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

The brush-type (Pirkle-type) CSPs have been used predominantly under normal phase conditions in LC. The chiral selector typically incorporates tt-acidic and/or n-basic functionality, and the chiral interactions between the analyte and the CSP include dipole-dipole interactions, n-n interactions, hydrogen bonding, and steric hindrance. The concept of reciprocity has been used to facilitate the rational design of chiral selectors having the desired selectivity [45]. 

Theoretically, the problem has been attacked by various approaches and on different levels. Simple derivations are connected with the theory of extrathermodynamic relationships and consider a single and simple mechanism of interaction to be a sufficient condition (2, 120). Alternative simple derivations depend on a plurality of mechanisms (4, 121, 122) or a complex mechanism of so called cooperative processes (113), or a particular form of temperature dependence (123). Fundamental studies in the framework of statistical mechanics have been done by Riietschi (96), Ritchie and Sager (124), and Thorn (125). Theories of more limited range of application have been advanced for heterogeneous catalysis (4, 5, 46-48, 122) and for solution enthalpies and entropies (126). However, most theories are concerned with reactions in the condensed phase (6, 127) and assume the controlling factors to be solvent effects (13, 21, 56, 109, 116, 128-130), hydrogen bonding (131), steric (13, 116, 132) and electrostatic (37, 133) effects, and the tunnel effect (4,... 

FIGURE 1.10 Comparison of enantiomer separations of DNB-Leu on quinine (QN) based and 0-9-(terf-butylcarbamoyl)quinine (tBuCQN) based CSPs. 1, ionic interaction 2, jt-7T-interaction 3, hydrogen bonding 4, steric interaction. Experimental conditions Eluent, methanol-0.1 M ammonium acetate (80 20 v/v) (pHa = 6.0) flowrate, 1 mLmin temperature, 25°C column dimension, 150 x 4 mm ID detection, UV 250 nm. Selector loadings, 0.37 and 0.30 mmol g l for QN- and tBuCQN-based CSPs, respectively. (Reproduced from A. Mandl et ah, J. Chromatogr. A, 858 1 (1999). With permission.)... 

Preference for the ds/irons-peptide bond in N-acylprolines, a condition for the stereochemistry of peptides and proteins, is governed mostly by steric factors due to substituents on C , by short-range electrostatic effects, and by intramolecular hydrogen bonding. 

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