Chiroptical properties determination

Methyl-3-(2-methylphenyl)quinazoline-4(3H)-thione (471), the sulfur analogue of MQ, and 2-methyl-3-(2-aminophenyl)quinazoline-4(3H)-thione (472) were baseline separated into enantiomers on various chiral supports opening a way to barrier and chiroptical property determinations. Figure 27 reports the excellent baseline separation obtained on a Chiralpak AD column. Polarimetry indicates the sign of the optical rotation of the first and second eluted enantiomer in the mobile phase (llUPl). 

On the other hand, optically active telluroxides have not been isolated until recently, although it has been surmised that they are key intermediates in asymmetric synthesis.3,4 In 1997, optically active telluroxides 3, stabilized by bulky substituents toward racemization, were isolated for the first time by liquid chromatography on optically active columns.13,14 The stereochemistry was determined by comparing their chiroptical properties with those of chiral selenoxides with known absolute configurations. The stability of the chiral telluroxides toward racemization was found to be lower than that of the corresponding selenoxides, and the racemization mechanism that involved formation of the achiral hydrate by reaction of water was also clarified. Telluroxides 4 and 5, which were thermodynamically stabilized by nitrogen-tellurium interactions, were also optically resolved and their absolute configurations and stability were studied (Scheme 2).12,14... 

It has been shown that CD measurement is a proper tool to determine the absolute configuration of the C-3 stereo center in corynantheine and yohimbine alkaloids (300). The chiroptical properties of stereoisomeric yohimbanes and 17-ketoyohimbanes also have been studied. Cotton effects due to aromatic and ketone absorptions have been considered in terms of the appropriate sector and... 

Their isolation by flash chromatography on silica gel was comparatively easy. The CD spectra of related pairs of diastereomers whose addition pattern represent pairs of enantiomers, reveal pronounced Cotton effects and mirror image behavior. It is the chiral arrangement of the conjugated Jt-electron system within the fullerene core that predominantly determines the chiroptical properties. Adducts with a C2-... 

At least for 14 the usual methods for determining the enantiomeric purity (especially NMR-methods) failed. From 14 and 15 several optically active derivatives were prepared 40 441 and their chiroptical properties [especially the circular dichroism (CD) spectra of derivatives of 14]40) recorded. 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

The chiralities of two [2.2]metacyclophanes were determined in 1973 and 1981 X-ray structure of a (—)-meta-bromobenzoate derived from levorotatory l-oxo[2.2]-metacyclophane (61) (via the equatorial-positioned alcohol) confirmed the chirality (5) for (—)-6I as had been deduced also from chiroptical properties 10S). 

Slightly distorted chair conformations have also been assigned to the e-caprolactones (3) and (4) on the basis of their chiroptical properties (67JA5649). Both variable temperature NMR and racemization methods have been used to determine the rate of conformational interchange in dihydrodibenz[c, e]oxepins (5). Barriers were found to be in the range 38-71 kJ mol-1 for a single ortho R substituent (5 R = H) increasing to 117-146 kJ mol-1 for two ortho substituents (5, R, R H). 

Investigations of the chiroptical properties of 9-halogen derivatives of 6-methyltetrahydro-4//-pyrido[ 1,2-a]pyrimidin-4-ones 28 (X and X1 = Cl, Br) established that the sign of the most characteristic CD bands is determined by the axial halogen atom in position 9 to the inherently achiral pyrimidinone chromophore (87JHC393). 

TDDFT computation of chiroptical properties, like computations of other molecular properties, is determined by how well the electronic structure of the molecules of interest is described. In Sect. 2.3 it was emphasized that the one-particle basis set, and the approximations for the XC potential and the XC response kernel, are the major factors that determine the quality of the electronic structure, and response calculations. 

Fig. 15 A selection of molecules for which the absolute configuration has been determined with the help of measurements and computations of chiroptical properties. Part I...

The chiroptical properties of molecules are of substantial interest in chemistry and biochemistry and become important tools for the determination of the absolute configuration and conformation of molecular systems. In particular, the circular dichroism [1] is a quantitative measure of the difference in absorption coefficient for left and right circular polarized light ... 

A racemic mixture of three-layered [3.3]paracyclophane (45) was resolved into two enantiomers by chiral HPLC (on a Daicel OD column), and their absolute configuration was determined by a comparison of the experimental CD spectrum with the theoretical one at the TD-DFT-B3-LYP/TZVP level [55]. A simple model, composed of two p-xylenes and durene (the side chains were modeled again by methyl groups), was used to explain the origin of the chiroptical properties of the three-layered cyclophane system. Due to the flexibility of the [3.3]paracyclophanes, the solvent effects on the conformer distribution and thus on the chiroptical properties were significant (Fig. 10). 

Usually, the chiroptical properties of highly cross-linked polymers cannot be measured. The asymmetry of the empty cavities can be deduced from their excellent racemate resolution ability, but under special conditions it can also be directly detected by optical activity measurements [41]. For this, the polymer is suspended in a solvent that has the same refractive index as the polymer, a technique which was developed for other types of insoluble polymers. The values of molar optical rotation thus determined are shown in Table 4.3. 

Because of its computational simplicity and other obvious qualities the random-phase approximation has been used in many calculations. Reviews of RPA calculations include one on chiroptical properties by Hansen and Bouman (1980), one on the equation-of-motion formulation of RPA (McCurdy et al, 1977) and my own review of the literature through 1977 (Oddershede, 1978, Appendix B). Ab initio molecular RPA calculations in the intervening period are reviewed in Table I. Coupled Hartree-Fock calculations have not been included in the table. Only calculations which require diagonalization of both A -I- B and A — B and thus may give frequency-dependent response properties and excitation spectra are included. In CHF we only need to evaluate either (A -I- B) or (A — B) Mn order to determine the (static) response properties. 

Accordingly, enantioselective synthesis of a pheromone with known absolute configuration was the only realistic method to determine its absolute configuration and supply a sample in an amount sufficient for its biological evaluation. Of course, it was also possible to compare the chiroptical properties of the synthetic pheromone with those of the naturally occurring ones. These biological and physical comparisons of the natural pheromone with those of its synthetic enantiomers were the only way to determine the absolute configuration of a pheromone. 

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