Activity, optical

Optical activity was first understood with respect to naturally occurring tartaric acid crystals by Pasteur in 1848. At this stage, the puzzle was that tartaric acid crystals were optically active, while the chemically identical racemic acid was not. The eventual results of the study revealed that racemic acid crystallised to give two morphologically different crystals, which were mirror images of each other, that is, they existed as a left-handed and right-handed pair. Each of these crystal types was identical to tartaric acid in every way except that crystals of one hand would rotate the plane of polarised light one way, just as ordinary tartaric acid, 

Optical activity arises from a dissymmetric stmcture of matter. Before we discuss the origin of optical activity in detail, we recall the equations of nature of light. 

Johann Joseph Loschmidt, born Mar. 15, 1821, in Putschirn (Pocerny), Czech Republic, died Jul. 8, 1895, in Vienna. 

Albert Ladenburg, born Jul. 2, 1842, in Mannheim, Germany, died Aug. 15, 1911, in Breslau, now Poland. 

Jacobus Henricus van t Hoff, born Aug. 30, 1852, in Rotterdam, died Mar. 1, 1911, in Berlin-Steglitz. 

The electric displacement field is related to electric field by D = E, and the magnetic flux density is related to the magnetic field by B = e is the electrical permittivity, which is related to the dielectric constant and p. is the magnetic permeability. 

Optical activity is reported as specific rotation, [a], calculated as shown in equation 2.1. 

W)mberg, H. Hekkert, G. L. Houbiers, J. P. M. Bosch, H. W. /. Am. Chem. Soc. 1%5,87,2635. Such a structure may be termed cryptochiral Mislow, K. Bickart, P. hr. J. Chem.1976/77,1 5,1. Precursors to 81 were chiral structures with significant optical activity, so failure to observe optical activity with 81 was not due to racemization or low optical purity. See also Wynberg, H. Hulshof, L. A. Tetrahedron 1974,30,1775. 

For solutions it is necessary to specify the solvent, since solvent-solute interactions can affect not only the magnitude of optical activity, but perhaps the direction of the rotation as well. ° For example, the specific rotation of (-)-a-methylbenzylamine was found to be -31.86° in benzene and -52.29° in Specific rotations are usually reported in an abbreviated format. The specific rotation of cholesterol is given as [a]D-31.5° (c = 2 in ether) [a]D°-39.5° (c = 2 in chloroform). Note that in this format, the concentration of a solution is usually taken to mean grams per 100 mL. ° It is also possible to define a molecular rotation (O) when molecular weight is known, as shown in equation 2.2. Calculating molecular rotation makes it easier to determine the effect of the same chromophore in different molecules. 

Our discussion to this point has assumed that we can obtain pure enantiomers. In many cases we can obtain one pure enantiomer from a natural source, but often we find that enantiomeric species are formed as a racemate—an equimolar mixture of the two enantiomers. Racemates (frequently termed racemic mixtures) are denoted with the prefixes ( )-, rac-, RS, or SR. We may try to resolve a racemate (separate it into enantiomers) by any of a variety of chemical or biological means. If we are nevertheless unable to obtain one pure enantiomer, we may be forced to use a mixture in which there is more of one enantiomer than its mirror image. In such cases we would like to know the optical purity of the sample, which is defined as the percentage of [a] of the pure enantiomer exhibited by the mixture. For example, the specific rotation of (+ )-glyceraldehyde is +14°. A mixture of 95% (+ )-glyceraldehyde and 5% (-)-glyceraldehyde is said to be 90% optically pure because the rotation of the sample is 12.6°, which is 90% of 

While specific rotation is ordinarily reported only as degrees, it is helpful to carry units through calculations to ensure that correct path length and concentration units are used. Fischer, A. T. Compton, R. N. Pagni, R. M. /. Phys. Chem. A 2006, 110, 7067. 

Optical activity is a phenomenon when the transparent material rotates the polarization direction of light transversing through the material. As proposed first by Fresnel in 1825, optical activity arises from circular double refraction. 

For example, in the liquid crystal, cholesteryl 2-2-ethoxy-ethoxy ethyl carbonate (CEEC), at A = 650 nm the ORP = 285°/mm, which from (5.60) gives that I n, - ni I = 1.03 x 10 . This shows that optical rotation is an extremely sensitive way to measure circular double refraction. 

Typically, ORP decreases with increasing wavelength. For example, in quartz ORP varies between 17 and 49, in AgGaS2 between 430 and 950 (in units of degree/mm), and in the liquid crystal cholesteryl oleyl carbonate it varies between 167 and 4167. 

The phenomenon of optical activity was discovered by the French physicist Jean-Baptiste Biot in 1815. 

Sample tube with solution of optically Angle of active substance rotation 

Plane-polarized light oscillates in only one plane 

To be optically active, the sample must contain a chiral substance and one enantiomer must be present in excess of the other. A substance that does not rotate the plane of polarized light is said to be optically inactive. All achiral substances are optically inactive. 

What causes optical rotation The plane of polarization of a light wave undergoes a minute rotation when it encounters a chiral molecule. Enantiomeric forms of a chiral molecule cause a rotation of the plane of polarization in exactly equal amounts but in opposite directions. A solution containing equal quantities of enantiomers therefore exhibits no net rotation because all the tiny increments of clockwise rotation produced by molecules of one handedness are canceled by an equal number of increments of counterclockwise rotation produced by molecules of the opposite handedness. 

The first example of optical activity in a compound of the type RxRsCHD was reported in 19 9 by Aleirander and Pinfcus (71). They measured a specific rotation for 2,3-dideutero-trans-menthane of = -0.09°, They could not, however, establish 

In the same year Eliel ( 2) reported the synthesis of ethylbenzene with one deuterium in the a TOsition. The optical activity of this compound ([o] = -0.30°) clearly derives from 

Anderson, Colonna, and Stirling (jj) have recently reported (r)-dibenzyl-sulfoxide. In this compound the optical activity ([oJaao =+0-Tl) originates from having two carbon isotopes bonded to sulfur. 

There have also appeared very recently the studies of Kokke and Oosterhoff (78,22) These authors have prepared (lR)-[2- 0]-Q -fenchocamphoronequlnone and (ir)-[1-D]-o-fenchocamphoronequlnone. In these molecules thes sole source of asymmetry was either an in the a-diketone function, or a single deuterium atom at a bridgehead. The circular dichroism spectra of these two compounds in the visible are remarkably different. 

Herzberg, G., Atomic Spectra and Atomic Structure, Dover Publications, New York, 19lj-lj-. 

The pronounced influence of the phenyl group on optical activity led Fredga and Palm to initiate an investigation on the optical activity of thiophene derivatives, in order to use this physical property for the elucidation of the aromatic character of thiophene. 2-(27) and 3-Thenylsuccinic acid (28), 2- (29) and 3-thienyl-succinic acid (30), 2- (31) and 3-thienylglycolic acid (32), 2-(33) and 3-a-methoxythienylacetie acid (34), -phenyl 2-thienyl-glycolic acid (35), -(2-thienyl)-y5-phenylpropionic acid (36), a-phenyl- -(2-thienyl) propionic acid (37), a,/ -di (2-thienyl)propionic acid (38) have been resolved into antipodes with the help of optically active bases. 

Fredga-, K, Aejmeleaus, and B. Tollander, Arkiv Kemi 3, 331 (1951). K. Pettersson, Arkiv Kemi 7, 279 (1954). 

The quasi racemate method proved very useful for the steric correlation of these compounds with the corresponding benzene deriva- 

In addition, the steric configuration can be obtained by Raney nickel desulfurization to optically active aliphatic acids of known con-figuration. 2 2 Combined with the quasi racemate method this 

Rotation Values for Thienylsubstituted Carboxylic Acids in Ethanol 

There is considerable scope for further work on the topic of molecular chirality. There is a clear definition of how to relate optical rotation to degree of chirality in terms of molecular symmetry. The ultimate aim is a theoretical framework for the quantitative interpretation of optical rotary dispersion and circular dichroism of chiral materials. The importance of this pursuit is almost self-evident. 

Problems associated with the quantum-mechanical definition of molecular shape do not diminish the importance of molecular conformation as a chemically meaningful concept. To find the balanced perspective it is necessary to know that the same wave function that describes an isolated molecule, also describes the chemically equivalent molecule, closely confined. The distinction arises from different sets of boundary conditions. The spherically symmetrical solutions of the free molecule are no longer physically acceptable solutions for the confined molecule. 

The simplest illustration of this argument is provided by a free particle in linear motion, correctly described by a wave function (T6.2.1) that satisfies the equation 

Since there are no restrictions on the value of k the energy spectrum is continuous. When the particle is confined to the line segment 0 x L, new boundary conditions, / (0) = tp(L) — 0 come into play and these require 

Draw stereochemical formulas for all the possible stereoisomers of the following compounds. Label pairs of enantiomers, and meso comounds. Tell which isomers, if separated from all other stereoisomers, will be optically active. 

Stereoisomers may be defined as isomers that are different from each other only in the way the atoms are oriented in space. Non-superimposable mirror-image stereoisomers are referred to as enantiomers. 

These two models are not superimposable. Although two substituent groups may coincide as they are twisted and turned, the other two do not. When molecules are not superimposable on their own mirror images, they are chiral. 

A compound whose molecules are chiral can exist as enantiomers a compound whose molecules are without chirality (achiral) cannot exist as enantiomers. Enantiomers have identical physical and chemical properties, except for the direction of rotation of the plane of polarized light and the reaction with optically active reagents. Because enantiomers can rotate the plane of polarized light, they are called optically active substances. Stereoisomers that are not mirror images of each other are called diastereomers, A meso compound is defined as one whose molecules are superimposable on their mirror images, even though they contain 

In solving this problem, we need to draw the compounds and look for possible configurations that would give rise to enantiomers, diastereomers, or meso compounds. One method of drawing the compound is to use a cross in which the intersection marks the location of the chiral carbon and the four groups attached to the carbon are at the ends of the cross. 

Biot made the remarkable observation that, when a beam of planr-polarized light passes through a solution of certain organic molecules such as sugar or camphor, the plane of polarization is rotated. Not all organic substances exhibit this property, but those that do are said to be optically active. 

FIGURE 5.5 Schematic representation of a polarimeter. Plane-polarized light passes through a solution of optically active molecules, which rotate the plane of polarization. 

The extent of rotation observed in a polarimetry experiment depends on the number of optically active molecules encountered by the light beam. This number, in turn, depends on sample concentration and sample pathlength. If the concentration of sample is doubled, the observed rotation doubles. If the concentration is kept constant but the length of the sample tube is doubled, the observed rotation is doubled. It also happens that the angle of rotation depends on the wavelength of the light used. 

To express optical rotations in a meaningful way so that comparisons can be made, we have to choose standard conditions. The specific rotation, [ajp, of a compound is defined as the observed rotation when light of 589.6 nanometer (nm 1 nm = 10 m) wavelength is used with a sample pathlength 1 of 1 decimeter (dm 1 dm = 10 cm) and a sample concentration c of 1 g/cm. (Light of 589.6 nm, the so-called sodium D line, is the yellow light emitted from common sodium lamps.) 

When optical rotation data are expressed in this standard way, the specific rotation, [ajp, is a physical constant characteristic of a given optically active compound. For example, (-f)-lactic acid has [o ]d = +3.82, and (-)-lactic acid has [a]p = -3.82. That is, the two enantiomers rotate plane-polarized light to exactly the same extent but in opposite directions. Note that the units of specific rotation are [(deg cm )/g] but that values are usually expressed without the units. Some additional examples are listed in Table 5.1. 

Polymers with a single kind of chiral monomeric unit are always optically active, that is, they rotate the plane of polarized light. In general, the effect of end groups disappears for degrees of polymerization above about 10-20 thus, the measured optical activity of high-molar-mass polymers results from that of the chiral monomeric units. An example of this consists of poly(L-a-amino acids) in the coiled state, for example, in dichloroacetic acid. 

This chiral influence is superimposed on that of the helix in the case of helical polymers from chiral monomeric units, since the helix is also chiral. Thus, a reinforced effect is observed, which makes the study of polymer dimensions in solution through measurement of optical activity remarkably interesting. 

Copolymers consisting of alternatively arranged monomeric units of opposite chirality are optically inactive as a result of the configuration itself. They can, however, produce helices of a specific direction of turn in certain solvents, such that this preferential conformation produces an optical activity. Poly(L-alt-D-leucine), which produces what is known as a tt helix in benzene, is an example of this. 

A similar effect sometimes occurs with copolymers of chiral and nonchiral monomeric units, whereby their optical activity is higher than the additivity rule allows. The nonchiral monomeric units are obviously drawn into helical conformations by the helical sequences of the chiral monomeric units. 

In contrast, polymers from nonchiral monomeric units are not optically active, even when their chains adopt a helical conformation. Since their molecules are enantiomeric to each other, left-handed and right-handed helices occur with equal probability, and the optical activity of the polymer is zero. 

For a finite group of atoms the criterion for enantiomorphism is the absence of an axis of rotatory inversion. An axis n implies a centre of symmetry if n is odd, it introduces planes of symmetry if k is a multiple of 2 but not of 4, and if k is a multiple of 4 the system can be brought into coincidence with its mirror image. Of the simplest axes of these three types, T is synonymous with a centreof symmetry, and 2 with a plane of symmetry. Since axes of rotatory inversion 4 are likely to occur very rarely in molecules, we may for practical purposes take as the criterion for enantiomorphism and for optical activity in a finite molecule or complex ion the absence of a centre or plane of symmetry. 

One isomer of the tetramethyl-sp/ro-bipyrrolidinium cation provides an example of a molecule with 4 symmetry. Each methyl group can project either above or below the plane of the ring to which it is attached, and the two rings lie in perpendicular planes. There are accordingly four forms of this molecule, which may be shown diagrammatically as set out below. The molecules are viewed along the direction of the dotted line and the thick lines indicate the rings  

All four forms have been prepared, the meso transitrans-form being inactive having 4 symmetry. 

The relation between optical activity and enantiomorphism is not quite so simple for a crystal. Of the thirty-two crystal classes eleven are enantiomorphic  

A particular crystal having the symmetry of one of these classes is either left- or right-handed, and if suitable faces happen to develop when the crystal grows hand-sorting may be possible. Optical activity is also theoretically possible in four of the non-enantiomorphic classes  

PROBLEMS For each compound below, determine the configuration of every stereocenter. Then draw the enantiomer of each compound below (the COOH group is a carboxylic acid group). 

The rotation of plane polarized hght (either -I- or -) is not a man-made convention. It is a physical effect that is measured in the lab. It is impossible to predict whether a compound will be -l- or - without actually going into the lab and trying. If a stereocenter is R, this does not mean that the compound will be +. It could just as easily be. In fact, whether a compound is -l- or - will depend on temperature. So a compound can be + at one temperature and - at another temperature. But clearly, temperature has nothing to do with R and S. So, don t confuse R/S with +/-. They are totally independent and unrelated concepts. 

You will never be expected to look at a compound that you have never seen and then predict in which direction it will rotate plane-polarized light (nnless you know how the enantiomer rotates plane-polarized light, becanse enantiomers have opposite effects). Bnt yon will be expected to assign confignrations (R and S) for stereocenters in componnds that you have never seen. 

Mechanisms are your key to success in this course. If you can master the mechanisms, you will do very well in this class. If you don t master mechanisms, you will do poorly in this class. What are mechanisms and why are they so important  

When two compounds react with each other to form new and different products, we try to understand how the reaction occurred. Every reaction involves the flow of electron density—electrons move to break bonds and form new bonds. Mechanisms illustrate how the electrons move during a reaction. The flow of electrons is shown with curved arrows for example. 

Biot made the remarkable observation that when a beam of plane-polarized light passes through a solution of certain organic molecules, such as sugar or 

Jean-Baptiste Biot (1774-1862) was born in Paris, France, and was educated there at the Ecole Polytechnique. In 1800. he was appointed professor of mathematical physics atthe College de France. His work on determining the optica rotation of naturally occurring molecules included an experiment on turpentine, which caught fire and nearly burned down the church building he was using for his experiments. 

Interactive to learn the relationship between observed optical rotation and concentration for optically active compounds. 

We have seen how stereochemical relationships can be designated and distinguished. Now let us see how tire stereochemistry influences the chemical and/or physical properties of molecules. 

When both enantiomers are present in solution, die observed rotation will reflect tile enantiomeric composition of the mixture. If equal amounts of enantiomers are present, the solution will not exhibit optical activity, because for each molecule that rotates light in one direction there will be another molecule that rotates light in the opposite direction and the net rotation is zero. Such a mixture is called a racemic mixture and is indicated by ( ). Thus ( )-2-butanol is an equal mixture of the R and S enantiomers of 2-butanol. In the liquid state, racemic mixtures have the same physical properties as the individual enantiomers. 

If one enantiomer is present in excess over the other, then the solution will have a net rotation corresponding in sign (+ or —) to that of the more abundant enantiomer. The composition of the mixture is denoted by the optical purity or the percent enantiomeric excess (ee%). The enantiomeric excess is defined as ee = % major enantiomer — % minor enantiomer and is a measure of the optical purity of the sample. Values range from 100% (pure enantiomer, ee = 100% — 0%) to 0% (racemic mixture or ee = 50% — 50%). A sample which has an optical purity of 92% is thus a mixture of 96% of one enantiomer and 4% of the other enantiomer. 

When optical rotation data are expressed in this standard way, the specific rotation, [alQ, is a physical constant characteristic of a given optically active 

Mirror-image molecules have nearly identical physical properties. Compare the following properties of (f )-2-bromobutane and (5)-2-bromobutane. 

Differences in enantiomers become apparent in their interactions with other chiral molecules, such as enzymes. Still, we need a simple method to distinguish between enantiomers and measure their purity in the laboratory. Polarimetry is a common method used to distinguish between enantiomers, based on their ability to rotate the plane of polarized light in opposite directions. For example, the two enantiomers of thyroid hormone are shown below. The (S) enantiomer has a powerful effect on the metabolic rate of all the cells in the body. The (/ ) enantiomer is useless. In the laboratory, we distinguish between the enantiomers by observing that the active one rotates the plane of polarized light to the left 

Most of what we see is unpolarized light, vibrating randomly in all directions. Plane-polarized light is composed of waves that vibrate in only one plane. Although there are other types of polarized light, the term usually refers to plane-polarized light. 

When light passes first through one polarizing filter and then through another, the amount of light emerging depends on the relationship between the axes of the two 

Function of a polarizing filter. The waves of plane-polarized light vibrate primarily in a single plane. 

Which of the following molecules are chiral Identify the chirality center(s) in each. 

Alanine, an amino acid found in proteins, is chiral. Draw the two enantiomers of alanine using the standard convention of solid, wedged, and dashed lines. 

Identify the chirality centers in the following molecules (green = Cl, yellow-green = F)  

An enantiomer that rotates the plane of light in a clockwise sense as the viewer faces the light source is dextrorotatory (dexter, Latin, right), and the compound is (arbitrarily) referred to as the (+) enantiomer. Consequently, the other enantiomer, which will effect counterclockwise rotation, is levorotatory (laevus, Latin, left) and called the (-) enantiomer. 

This special interaction with hght is called optical activity, and enantiomers are frequently called optical isomers. 

When light travels through a molecule, the electrons around the nuclei and in the various bonds interact with the electric field of the light beam. If a beam of plane-polarized light is passed through a chiral substance, the electric field interacts differently with, say, the left and right halves of the molecule. This interaction results in a rotation of the plane of polarization, called optical rotation the sample giving rise to it is referred to as optically active. 

Note The presence of chiral molecules in a substance does not mean that the sample will necessarily exhibit optical activity. The material must contain an excess of one enantiomer of at least one chiral compound over the other for observation of optical activity to be possible. 

A = wavelength of incident fight for a sodium vapor lamp, which is commonly used for this purpose, the yellow D emission fine (usually indicated simply by D) has A = 589 nm. a = observed optical rotation in degrees 

Although enantiomers have identical chemical properties in achiral environments, they differ in one important physical property Enantiomers behave differently toward plane-polari2ed light. This difference allows us to distinguish a chiral molecule from its enantiomer in the laboratory. 

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A minor chemical use for many of the commoner alkaloids is the resolution of racemic compounds (often acids) into their optically active enantiomorphs. 

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

In complexes of chelates there are a number of types of isomerism which may occur. In a tris(ethylenediamine) octahedral complex two optically active isomers occur (often denoted A and A). 

A molecule is chiral if it cannot be superimposed on its mirror image (or if it does not possess an alternating axis of symmetry) and would exhibit optical activity, i.e. lead to the rotation of the plane of polarization of polarized light. Lactic acid, which has the structure (2 mirror images) shown exhibits molecular chirality. In this the central carbon atom is said to be chiral but strictly it is the environment which is chiral. 

In certain crystals, e.g. in quartz, there is chirality in the crystal structure. Molecular chirality is possible in compounds which have no chiral carbon atoms and yet possess non-superimposable mirror image structures. Restricted rotation about the C=C = C bonds in an allene abC = C = Cba causes chirality and the existence of two optically active forms (i)... 

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

C3H6O4, HO OCHCOHj-CH OH. An un-crystallizable syrup it occurs in optically active forms. Prepared by oxidation of glycerin with nitric acid. 

The most important menthadiene, an optically active monocyclic terpene found in chenopo-dium oil. Used in the manufacture of p-cymene. 

These reactions follow first-order kinetics and proceed with racemisalion if the reaction site is an optically active centre. For alkyl halides nucleophilic substitution proceeds easily primary halides favour Sn2 mechanisms and tertiary halides favour S 1 mechanisms. Aryl halides undergo nucleophilic substitution with difficulty and sometimes involve aryne intermediates. 

Pfeiffer effect The change in rotation of a solution of an optically active substance on the addition of a racemic mixture of an asymmetric compound. 

An optically active, secondary terpene alcohol. ( —)-Piperilol is found in various eucalyptus oils and (-l-) piperitol in the oil from a species of Andropogon. A somewhat viscous oil of pleasant smell. It yields piperitone on oxidation with chromic acid. 

Isovaleric acid, Me2CHCH2COOH, is a colourless liquid with the unpleasant odour of valerian, b.p. 177 "C. Occurs in the roots of valerian and angelica together with an optically active form of methylethylethanoic acid. Prepared by oxidation of isoamyl alcohol. A mixture of acids similar to that obtained from valerian roots is prepared by oxidation of fusel oil. 

In the absence of special syimnetry, the phase mle requires a minimum of tliree components for a tricritical point to occur. Synnnetrical tricritical points do have such syimnetry, but it is easiest to illustrate such phenomena with a tme ternary system with the necessary syimnetry. A ternary system comprised of a pair of enantiomers (optically active d- and /-isomers) together with a third optically inert substance could satisfy this condition. While liquid-liquid phase separation between enantiomers has not yet been found, ternary phase diagrams like those shown in figure A2.5.30 can be imagined in these diagrams there is a necessary syimnetry around a horizontal axis that represents equal amounts of the two enantiomers. 

Plenary 7(5. N I Koroteev et al, e-mail address Koroteev nik.phys.iusu.su (CARS/CSRS, CAHRS, BioCARS). A survey of the many applications of what we call the Class II spectroscopies from third order and beyond. 2D and 3D Raman imaging. Coherence as stored infonuation, quantum infonuation (the qubit ). Uses tenus CARS/CSRS regardless of order. BioCARS is fourtli order in optically active solutions. 

Barron L D, Hecht L, Bell A F and WIson G 1996 Raman optical activity an incisive probe of chirality and biomolecular structure and dynamics ICORS 96 XVth Int. Conf. on Raman Spectroscopy ed S A Asher and P B Stein (New York Wley) pp 1212-15... 

Hecht L and Barron L D 1996 Raman optical activity Modern Techniques in Raman Spectroscopy ed J J Laserna (New York Wley) pp 265-342... 

Koroteev N I 1996 Optical rectification, circular photogalvanic effect and five-wave mixing in optically active solutions Proc. SPIE 2796 227-38... 

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