Optical methods rotatory dispersion

Besides the physicochemical studies on solution chemistry, investigations for chemical reactions in solution were extensively developed in the latter half of the 20th century. Studies on chemical reactions in solution were, in principle, closely related to Werner s synthetic works of coordination compounds, and thus, these studies were carried out mostly by coordination chemists rather than physical chemists. Accumulation of knowledge on chemical reactions through studies on synthetic and decomposition reactions led to construction of more reasonable scheme for chemical reactions in solution. Spectrophotometric and optical rotatory dispersive methods, which had been employed in the structural investigations for inert complexes in solution, became important techniques in studies of solution chemistry including reactions of labile complexes. 

Two valuable methods for characterizing organic compounds by optical rotation have been developed (1) the monochromatic-rotation predictions of WhilTen and Brewster, and (2) the optical rotatory dispersion methods of Djerassi. As Eliel has pointed out, these methods are complementary, as optical rotatory dispersion is mainly useful for compounds chromophoric in the near ultraviolet, and rotation predictions are principally of use for saturated compounds. 

Chiroptical techniques allow optical distinction between chiral molecules. In the ORD (optical rotatory dispersion) method the optical rotation is recorded as a function of the wavelength. In the CD (circular dichroism) method the difference in molar absorptivity between left and right circularly polarized light is measured as a function of the wavelength. The ORD curve of (-) humulone in methanol is displayed in Fig. 4. 

The optical rotatory dispersion curves of steroidal ketones permit a distinction to be made between the conformations, and assignment of configuration is possible without resorting to chemical methods (see, e.g. ref. 36) which are often tedious. The axial halo ketone rule and, in the more general form, the octant rule summarize this principle and have revealed examples inconsistent with the theory of invariable axial attack in ketone bromination. 2-Methyl-3-ketones have been subjected to a particularly detailed analysis. There are a considerable number of examples where the products isolated from kinetically controlled brominations have the equatorial orientation. These results have been interpreted in terms of direct equatorial attack rather than initial formation of the axial boat form. 

Other methods have also been used, including optical rotatory dispersion, circular dichroism (CD), and asymmetric synthesis (see p. 147). 

If two different three-dimensional arrangements in space of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are called conformationsIf they are not interconvertible, they are called configurations Configurations represent isomers that can be separated, as previously discussed in this chapter. Conformations represent conformers, which are rapidly interconvertible and are thus nonseparable. The terms conformational isomer and rotamer are sometimes used instead of conformer . A number of methods have been used to determine conformations. These include X-ray and electron diffraction, IR, Raman, UV, NMR, and microwave spectra, photoelectron spectroscopy, supersonic molecular jet spectroscopy, and optical rotatory dispersion (ORD) and CD measurements. Some of these methods are useful only for solids. It must be kept in mind that the conformation of a molecule in the solid state is not necessarily the same as in solution. Conformations can be calculated by a method called molecular mechanics (p. 178). 

In addition to chemical correlations discussed above, several physical methods are now available for the determination of the relative and absolute configurations of chiral sulfur compounds. Among these, NMR, infrared (IR), optical rotatory dispersion (ORD), circular dichroism (CD), and X-ray analysis are the most important. Sections III-B-1 to III-B-5 outline applications of these techniques for establishing the chirality around the sulfur atom. 

A number of methods have been used for determining Kg values cation selective electrodes, pH-metric methods, conductimetry, calorimetry, temperature-jump relaxation measurements, membrane conductance measurements, nuclear magnetic resonance, optical rotatory dispersion. The results listed in Tables 7—10 have been obtained by various methods and at different ionic strengths so they may not always be strictly comparable. However, the corrections are probably small and the experimental accuracy is generally the same or very similar within a certain ligand type. 

The inherent difficulty in analyzing enantiomers arises from the well-known fact that apart from their chiroptical characteristics, optical isomers have identical physical and chemical properties in an achiral environment (assuming ideal conditions). Therefore, methods of distinguishing enantiomers must rely on either their chiroptical properties (optical rotation, optical rotatory dispersion, circular dichroism), or must employ a chiral environment via diastereomer formation or interaction. Recently, it has become increasingly clear that such diastereomeric relationships may already exist in nonracemic mixtures of enantiomers via self-association in the absence of a chiral auxiliary (see Section 3.1.4.7.). 

Optical Rotatory Dispersion, Circular Dichroism, and Magnetic Circular Dichroism , R. B. Homer, in Physical Methods in Heterocyclic Chemistry , ed. A. R. Katritzky, Academic Press, New York, 1971, vol. 3, pp. 397-423. 

With heating from 5 to 45°C, thermal changes in conformation in the major /3-casein are observed by spectral methods (Garnier 1966). From measurements of the optical density at 286 nm and of the specific optical rotation at 436 nm, a rapidly reversible endothermic transition (AH 30 kcal/mole) with a half-transition temperature of 23-24°C is observed. The optical rotatory dispersion data suggest a decrease in the poly-L-proline II structure (12 to 5%) and a slight increase in a-helix (11 to 16%) with increasing temperature. This transition probably occurs prior to association, since it is rapid, and the carboxyacyl derivative of the monomer, which does not polymerize with increasing temperature, also demonstrates the optical rotatory disperson thermal transition. 

The term chiroptical basically refers to spectroscopic methods which afford values with opposite signs for the two enantiomers of a chiral compound [77]. Measurement of optical rotatory dispersion (ORD) and circular dichroism (CD) number among the most important chiroptical methods. 

Most measurements of the optical rotation are carried out at a single frequency, usually corresponding to the sodium D-line. However, studies of the variation of the optical rotation with the frequency of the incident light are also known, and are referred to as optical rotatory dispersion (ORD) [7], Historically, this was an important method for the determination of excitation energies in chiral molecules, but was later superseded by CD. We note that the calculation of ORD through regions of electronic absorption requires special care [27,28],... 

The interaction of polarized light with chiral compounds is of great interest since chiroptical techniques are extremely useful as methods of characterization. It is equally true that although most scientists are aware that enantiomerically rich solutions will rotate the plane of linearly polarized light, the origins of this effect are not as simple as might be imagined. In this first article, the phenomena of polarimetry and optical rotatory dispersion will be discussed. A subsequent note will concern the related phenomenon of circular dichroism. 

Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra (71PMH(3)397) are very sensitive to the spatial disposition of the atoms in a molecule, and conformational changes may yield rather dramatic changes in the appearance of a CD or ORD spectrum of a chiral molecule. The analysis of the temperature dependence of the CD spectrum may give information on populations and free energy differences. Except for nucleosides, the use of the chiroptical method in conformational analysis is rather limited, which may be accounted for by the complexity of the theory for optical activity. 

The elucidation and confirmation of structure should include physical and chemical information derived from applicable analyses, such as (a) elemental analysis (b) functional group analysis using spectroscopic methods (i.e., mass spectrometry, nuclear magnetic resonance) (c) molecular weight determinations (d) degradation studies (e) complex formation determinations (f) chromatographic studies methods using HPLC, GC, TLC, GLC (h) infrared spectroscopy (j) ultraviolet spectroscopy (k) stereochemistry and (1) others, such as optical rotatory dispersion (ORD) or X-ray diffraction. 

Gillard, R. D. Optical Rotatory Dispersion and Circular Dichroism. In Physical Methods in Advanced Inorganic Chemistry, p. 167 edited by H. A. O, Hill and P. Day. London Interscience, 1968. 

---