Ch. 5 Textbook
5.1 Optical activity
Light is polarized when it passes through a Nicol prism or polaroid. The passed light is in a certain oscillating plane. The polarized light (polarized by the first Polaroid) passes through the second polaroid when the it is placed in parallel with the first one, but the polarized light completely disappear when the second polaroid is placed perpendicular to the first one (Fig. 5.1).
Figure 5.1 The direction of polaroid and polarized light
Some compounds can rotate the plane of polarized light to a certain amount. This phenomenon is referred to as optical activity, and compounds with such ability is named an optical active substance. Optically active substances exist as a pair ((+) and (-) forms) of enantiomers. If one of the enantiomers rotates the polarized plane clockwise, the other enantiomer rotates the same amount but to the reverse direction. Clockwise rotation is "dextrorotatory", while the counterclockwise rotation is "levorotatory". For dextrorotatory, symbols d or (+), and for levorotatory, symbols l or (-) are frequently used (Fig. 5.2).
Figure 5.2 Rotation of polarized plane by an optically active compound
The magnitude of rotation depends not only the type of compound, but also the concentration of the solution, the length of light path, the solvent, the wavelength of the light employed, and he temperature. The specific rotation ([a]) is defined for a given compound as the rotation (ｰ) induced by 1 g/ml solution 10 cm long under a specified condition (the temperature, wavelength of the light used, the solvent) as shown below. where λ is the wavelength of the light and t is the temperature.
5.2 Chirality
Molecules which form a pair of enantiomers are necessarily chiral. A chiral molecule is related to its own mirror image in the way that your left hand is related to your right hand. All chiral molecules have at least one of the three kinds of chiral centers, the center of chirality, the axis of chirality or the plane of chirality. Molecules without any chiral center are achiral. There are many chiral substances around you, and you will find that the chirality quite often plays a definite role in relation to the property or function of the substance. Hands, gloves, and screws are familiar examples. The representative molecule with a center of chirality is a methane derivative, a sp3 hybridized carbon atom with four different ligands which can be represented as CXYZW (X ≠Y ≠ Z ≠ W). This type of carbon atom is referred to as asymmetric carbon atom. Asymmetric carbon atoms are sometimes indicated by * as superscript in the chemical formula.
▶go to S5.4 Types of chirality
5.3 Racemates and optical resolution
The two compounds forming a pair of enantiomers have the same physical (e.g., melting point) and chemical (e.g., acidity) properties except optical rotation and reactivity to chiral reagents. A 1 : 1 mixture of enantiomeric pair is named racemateand designated as (±) or dl. Racemates are optically inactive because the effect of one enantiomer is cancelled by the effect of other enantiomer. The chemical property of solution of racemates is identical with that of an enantiomer although sometimes properties of a racemate and an enantiomer may vary in the solid state.
Separation of racemates into their component enantiomer is named optical resolution. There are three methods of resolution.
1) physical resolution: manual separation when enantiomers crystallize in different crystal forms.
2) chemical resolution: separation by conventional chemical separating methods of the diastereomer (Ch. 6) obtained by the reaction with chiral reagents.
3) biological resolution: use of a specific enzyme which selectively consumes one of the enantiomers.
▶go to S5.5 Racemates and optical resolution
A good example of chemical resolution is that of lactic acid CH3CH(OH)COOH. Since lactic acid is a carboxylic acid, the chiral reagent of choice is a base which may form a crystalline salt with lactic acid. An alkaloid, (-)-brucine, is often employed. (-)-Brucine is a natural product.
The two salts are stereoisomers, or rather diastereomers. In principle these are separable by usual chemical method such as recrystallization from an appropriate solvent. For optical active carboxylic acid, an optical active base can be employed to prepare diastereomers. When the racemates belong to a different type of compounds, a different type of chiral reagent should be chosen. In Table 5.1, a variety of resolution reagents are listed.
Table 5.1 List of resolution reagents
| Racemate | resolution reagent |
| carboxylic acid | brucine, strychnine, ephedrine, cinchonine |
| base (amine) | camphor-10-sulfonic acid, tartaric acid, malic acid |
| alcohol | phthalic acid, succinic acid (via half ester) |
| aldehyde, ketone | mentylsemicarbazide, mentylhydrazine |
5.4 Fischer Projection
Several methods have been introduced to visualize the configuration of the asymmetric carbon atom. We have already learned the flying-wedge drawing. Tetrahedral drawing is another method which was often used in the past. The four corners of a tetrahedron are used to indicate the four ligands. The dashed line represents the hidden edge behind the tetrahedron. Most frequently used is, however, Fischer’s projection formula (hereafter simply Fischer projection). A chiral compound CXYZW is drawn by several methods. According to the convention of Fischer projection, the asymmetric carbon atom lies on the surface of the paper, and horizontal bonds are taken, as coming toward you and vertical bonds as retreating from you. In other word, Fischer projection 7 and 8 are equivalent to the flying-wedge drawings 3 and 4, respectively.
▶go to S5.6 Rules of Fischer projection
5.5 Relative configuration
As mentioned before, lactic acid in muscle is dextrorotatory, i.e., (+)-lactic acid. This can be determined by experiment. However, based on this experimental fact, will it be possible to decide which configuration, 17 or 18, (+)-lactic acid has? It is impossible unless one can see the molecule! The pioneers of stereochemistry built up a logical system of relative configuration by making a few simple hypothesis. The system of relative configuration can be summarized as below.
1) Of the enantiomer pair ofglyceraldehydes HOCH2C*H(OH)CHO, the dextrorotatory isomer is assigned to have the configuration 21, and the levorotatory isomer the configuration 22. (Note that there was no experimental support for this assignment)
2) Compound which can be derived from either 21 or 22 without changing the configuration of the asymmetric carbon atom belong toD- and L-series, respectively. 3) The stereochemistry of a chiral compound is named by a combination of two terms, one (D or L) defines the relative configuration, and the other (+ or -) indicates the experimentally determined rotation.
▶go to S5.7 Relative configuration
5.6 Absolute configuration一R ，S 一convention
the system of relative configuration is a self-consistent system except the arbitrary assumption give one of the enantiomer of glyceraldehyde a certain configuration. In practice, the system was effective and a very important field of organic chemistry, i.e., sugar chemistry, and natural product chemistry in general, was constructed on it. Chemists were, however, anxious to know the fact: what configuration has D(+)-glyceraldehyde? Is it really 21, or 22 instead? In 1951, Bijvoet et al. successfully determined the true configuration, i.e., absolute configuration, of a chiral molecule rubidium sodium salt of tartaric acid by abnormal scattering of X-ray. Very fortunately, the absolute configuration did coincide with the relative configuration. The hypothesis was correct! Today the absolute configuration of many compounds has been decided.
There were several difficulties in practicing the relative configuration when a variety of chiral compounds were treated. Sometimes it was impossible to relate a complex molecule to glyceraldehyde. Under such a circumstance, a new stereochemical nomenclature, R, S nomenclature, was proposed. The idea was that the system should be general and be related to the sequence rule which is the ground of systematic nomenclature. The essence of R, S nomenclature is as follows. For each center of symmetry (compounds with many centers should be considered), 1) The priority of four ligands is decided by the sequence rule. 2) An alphabet is assigned to each ligand according to the decreasing order of priority; L > M > S > s 3) We suppose looking down the bond from the asymmetric carbon atom toward the ligand of lowest priority (s). The other three ligands (L, M and S) will face you. Connect these three ligands with an arrow running from highest to lowest priority (L > M > S). 4) If this arrow runs clockwise, the enantiomer is called R (Latin, rectus (meaning right)). If it runs counterclockwise, the enantiomer is called S (Latin, sinister (meaning left)). 5) The label (R ) or (S) is added to the name.
▶go to S5.9 How to decide the configuration by R, S nomenclature