ORD curves

Figure A Diagrammatic representation of the Cotton effect (actually po-sitivc Cotton effect. The negative effect oceur.s when the CD curve. shows a minimum and the ORD curve is the reverse of the above).

The behaviours of CD and ORD curves in the vicinity of an absorption band are collectively known as the Cotton effect after the French physicist A. Colton who discovered them in 189S. Their importance in the present context is that molecules with the same absolute conhguration will exhibit the same Cotton effect for the same d-d absorption and, if the configuration of one compound is known, that of closeiy similar ones can be established by comparison. 

The character of ORD curves depends on the structure, configuration and conformation of optically active substances and also on the nature of choromophores present and their position relative to asymmetric centre. In many cases the curves depend on solvent and temperature. This is why spectropolarimetry becomes an important physico-chemical method (for investigating organic compounds). By introducing an optically active radial into organic compounds that do not possess optical activity, it is possible to extend the range of investigation by spectropolarimetric methods. 

The focus of the earlier chapter was a brief outline of the sources of chiral amino compounds, application of Brewster s rules for the assignment of the absolute configurations to a few chiral amines, a discussion of the ORD and CD in the visible (380-780 nm) and near-ultraviolet (200-380 nm) spectral regions of chiral amino compounds and some of their derivatives, and how the observed Cotton effects (CEs) in their ORD curves and CD spectra relate to their conformational preferences and absolute configurations. 

The ORD curves and ECD spectra of a number of chiral methyl-substituted cyclic amines, aziridine, azetidine, pyrrolidine and piperidine, and their A-mcthyl, A-halo and A-cyano derivatives, and of (5 )-l-azabicyclo[3.1.0]hexane [(5 )-115] were measured96. 

Between 1926 and 1962, numerous ORD curves of optically active sulfoxides were described in the literature for the visible and ultraviolet (UV) regions. However, down to about 250 nm all compounds investigated showed plain curves with [0] increasing toward shorter wavelengths, and this limited their diagnostic value for the determination of the absolute configuration of these compounds. 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

The ORD and CD curves of chiral sulfinamides derived from aromatic sulfinic acids show a strong Cotton effect centered at 240 to 256 nm (83). The position of this Cotton effect, its dependence on the solvent used, and the amplitude reveal a complete analogy with that observed in alkyl aryl sulfoxides and aromatic menthyl sulfin-ates. Thus, the positive sign of the Cotton effect observed in the ORD curves of dextrorotatory sulfinamides is indicative of the (5)-configuration around sulfur in these compounds. 

The influence of the solvent on chiroptical properties of synthetic polymers is dramatically illustrated in the case of poly (propylene oxide). Price and Osgan had already shown, in their first article, that this polymer presents optical activity of opposite sign when dissolved in CHCI3 or in benzene (78). The hypothesis of a conformational transition similar to the helix-coil transition of polypeptides was rejected because the optical activity varies linearly with the content of the two components in the mixture of solvents. Chiellini observed that the ORD curves in several solvents show a maximum around 235 nm, which should not be attributed to a Cotton effect and which was interpreted by a two-term Drude equation. He emphasized the influence of solvation on the position of the conformational equilibrium (383). In turn, Furakawa, as the result of an investigation in 35 different solvents, focused on the polarizability change of methyl and methylene groups in the polymer due to the formation of a contact complex with aromatic solvents (384). 

A contemporaneous study on the same subject utilized a chemical correlation method where (—)-A-benzylargemonine chloride, obtained by sequential optical resolution and quatemization of ( )-7V-methylpavine (5), underwent a multistep degradative process to furnish (-)-A,A-dimethyl-di-H-propyl aspartate. Comparison of this final product with L-aspartic acid of known chirality led to the absolute configuration of (—)-5 (115,158). (—)-Eschscholtzine (9) was assigned the same absolute configuration by correlation of its ORD curve and optical rotation with those of (—)-argemonine (775). 

A successful application of the aromatic chirality method (6) has led to the determination of the absolute configuration of (-)-amurensine (24), thus establishing the absolute configuration of the isopavine bases as shown in expression 24a 161). This result was later verified by the correlation of optical rotations and ORD curves of (—)-argemonine (5) and (—)-amurensinine (25) 67,70,160) as well as of their first-step Hofmann degradation products 160). 

The Kronig-Kramers relation is of fundamental importance for optics and for physics in general13). Here, these equations do not seem practical because of the integration of the wavelength from 0 to oo. However, these are very useful for calculating the molar ellipticity magnitude from the observed ORD curve 14). 

Similar curves are obtained with other synthetic polypeptides, and in most cases they are reasonably independent of the nature of the amino acid side chains. In synthetic polypeptides and proteins the observed Cotton effects do not arise from isolated chromophores but are composite curves resulting from several transitions assigned to the amide bonds in the 200-m/x region. The a-helical curve, for example, results from three optically active absorption bands. One around 222 m/ arises from an n — 7T transition of nonbonding electrons, and the other two at 208 and 191 m/ji are attributed to w — tt transitions parallel and perpendicular to the axis of the helix. These transitions of the a-helix and the resulting Cotton effects characteristic of the a-helix are at present of great interest in interpreting ORD curves of membranes. 

Circular dichroism arises from the same optically active transitions responsible for the Cotton effects observed in ORD curves, but unlike ORD it is an absorption, not a dispersion, phenomenon. Hence, the CD effect is restricted to the region of the transition and can be interpreted more straightforwardly. Both ORD and CD can best be understood if one imagines the incident plane-polarized beam resolved into two in-phase circularly polarized beams whose vectors rotate in opposite directions. A difference in index of refraction between the left and right circularly polarized beams results in rotation of the transmitted plane polarized beam while differential absorption of the two circularly polarized beams results in depolarization of the transmitted beam, so that an incident plane-polarized beam whose frequency is within that of an optically active absorption band becomes both rotated and elliptically polarized upon passage through the sample. This depolarization effect is CD, and the measured parameter is (et — er), the difference in extinction coefficient between the left and right circularly polarized beams. The data is usually recorded as the specific ellipticity, defined as ... 

Optical rotatory dispersion involves measuring the variation of optical rotation with wavelength. There is an abrupt reversal of rotation in the vicinity of an absorp- tion band. If the complex is initially levorotatory (Fig. 12.25a), the ORD curve fells to a minimum, rises rapidly to a maximum, and then slowly falls. If the complex was initially dextrorotatory, the effect is reversed with the ORD curve rising first to a ... 

Fig. 12.25 The Cotton effect (a) positive Cotton effect (b) negative Cotton effect. The absorption band is not shown it would be a positive Gaussian curve centered on Am, but o scale. The dashed line represents the ORD curve (and relates to the refractive index scale on left. The solid line represents the CD curve ( ( — scale on right). The maximum absorption, zero values of DRD. and maxima and minima of CD values occur at The...

After decarboxylation, enolization in the alternative mode would cause racemization. However, this reasoning does not explain why 199 was racemized. The racemic a-aminoketones were eventually resolved via their bromocamphorsulfonates. Optically pure (—)-indolizidin-l-one (196) was reduced with lithium aluminum hydride to the alcohol, tosylated, and again reduced to (+)-indolizidine [Eq. (28)]. Since indolizidine obtained from R-pipecolic acid [Eq. (29)] was levorotatory, it followed that the absolute configuration of the original ketone was S.254 The optical rotatory dispersion (ORD) curve of the S(-)-ketone showed a strong negative Cotton effect as predicted by the octant rule. 

Automatic spectropolarimeters are available for the measurement of optical rotation as a function of wavelength (in the region 180-700 nm), enabling optical rotatory dispersion (ORD) curves to be recorded. Models are also available (e.g. Japan Spectroscopic Co. Ltd) for the measurement of circular dichroism (CD) curves in the wavelength region of 180-1000 nm, and 700-2000 nm. Authoritative accounts of the value of ORD and CD data in studies on the structure... 

However, if the dependence of the angle of rotation a upon the wavelength is measured in the region of the absorption band of the optically active substance under investigation, then superposition of an S-shaped component on the normal ORD curve is observed in this region. Circular dichroism effects are responsible for this anomalous ORD curve. 

Latifine (594) is a new phenolic base isomeric with cheiylline (595) that has been isolated from Crinum latifolium L. (227). The (S) configuration at C-4 of 594 was deduced from an observed negative Cotton effect in the ORD curve of 594 and 595, and this assignment was confirmed by an X-ray analysis of the N-bromobenzamide derivative of 594. 

The method was indeed useful for inter- and intra-system identifications among alkaloids of several groups for example, the ORD and CD curves of maritidine (277) could be compared in shape and intensity with those of vittatine (284) and haemanthamine (318) although the suggestions of a a configuration for the C-3 hydroxy group, as deduced from the amplitude of the ORD curve at 250m, proved to be incorrect (43, 44). 

Oxidation of 172 with chromium trioxide in pyridine gave the monoketone 176, whereas oxidation of spiradine F under the same conditions afforded the hydroxylactam 177. Catalytic hydrogenation of compound 176 afforded the a-ketol 178. The latter was treated with sodium methoxide in benzene to give an enolated a-diketone (179), which definitely fixed the position of the hydroxyl group at C-6 in spiradine G. Comparison of an ORD curve of compound 178 with that of 5a-cholestane-6-one established the indicated absolute configuration for these alkaloids. It is worth noting that these alkaloids bear many structural similarities to the earlier mentioned alkaloid ajaconine. 

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