Optical activity achiral molecules

Mixtures of enantiomers in equal proportions are racemic mixtures, which are not optically active. A molecule that has a superimposable mirror image is said to be achiral. 

The origin of optical activity in molecules often reduces to the question of how the molecule acquires the electronic properties expected of a chiral object when it is formed from an achiral object. Most often an achiral molecule becomes chiral by chemical substitution. In coordination compounds, chirality commonly arises by the assembly of achiral units. So it is natural to develop ideas on the origins of chiral spectroscopic properties from the interactions of chirally disposed, but intrinsically achiral, units. Where this approach, an example of the independent systems model, can be used, it has obvious economic benefits. Exceptions will occur with strongly interacting subunits, e.g., twisted metal-metal-bonded systems, and in these cases the system must be treated as a whole—as an intrinsically chiral chromophore. ... 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

Since chirality is a property of a molecule as a whole, the specific juxtaposition of two or more stereogenic centers in a molecule may result in an achiral molecule. For example, there are three stereoisomers of tartaric acid (2,3-dihydroxybutanedioic acid). Two of these are chiral and optically active but the third is not. 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achiral enol or enolate ion. The 5/) -hybridized carbon that is the chirality center in the starting ketone becomes 5/) -hybridized in the enol or enolate. Careful kinetic studies have established that the rate of loss of optical activity of 5cc-butyl phenyl ketone is equal to its rate of hydrogen-deuterium exchange, its rate of bromination, and its rate of iodina-tion. In each case, the rate-detennining step is conversion of the starting ketone to the enol or enolate anion. 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

In general, it may be said that enantiomers have identical properties in a symmetrical environment, but their properties may differ in an unsymmetrical environment. Besides the important differences previously noted, enantiomers may react at different rates with achiral molecules if an optically active catalyst is present they may have different solubilities in an optically active solvent., they may have different indexes of refraction or absorption spectra when examined with circularly polarized light, and so on. In most cases these differences are too small to be useful and are often too small to be measured. 

This situation changed dramatically in 1996 with the discovery of strong electro-optic (EO) activity in smectics composed of bent-core, bowshaped, or banana-shaped achiral molecules.4 Since then, the banana-phases exhibited by such compounds have been shown to possess a rich supermolecular stereochemistry, with examples of both macroscopic racemates and conglomerates represented. Indeed, the chiral banana phases formed from achiral or racemic compounds represent the first known bulk fluid conglomerates, identified 150 years after the discovery of their organic crystalline counterparts by Pasteur. A brief introduction to LCs as supermolecular self-assemblies, and in particular SmC ferroelectric and SmCA antiferroelectric LCs, followed by a snapshot of the rapidly evolving banana-phase stereochemistry story, is presented here. 

There are two possible approaches for the preparation of optically active products by chemical transformation of optically inactive starting materials kinetic resolution and asymmetric synthesis [44,87], For both types of reactions there is one principle in order to make an optically active compound we need another optically active compound. A kinetic resolution depends on the fact that two enantiomers of a racemate react at different rates with a chiral reagent or catalyst. Accordingly, an asymmetric synthesis involves the creation of an asymmetric center that occurs by chiral discrimination of equivalent groups in an achiral starting material. This can be done either by enan-tioselective (which involves the reaction of a prochiral molecule with a chiral substance) or diastereoselective (which involves the preferential formation of a single diastereomer by the creation of a new asymmetric center in a chiral molecule) synthesis. 

The inactivity in the molecule is due to the fact that it is perfectly symmetric as shown by the dotted line, the upper half exactly coinciding with the lower half. Therefore, molecular asymmetry and not the presence of asymmetric carbon atoms is responsible for optical activity. Since the term asymmetric has been found to be inadequate, now the term chirality has been introduced. The word chiral (the Greek word cheir means hand pronounced kiral) signifies, the property of Handedness . An object that in not superimposable upon its mirror image is chiral and this mirror-image relationship is the same as left hand has with the right. If an object and its mirror image can be made to coincide in space, they are said to be achiral. 

Rychnovsky et al. considered the formation of achiral conformers from chiral molecules and trapping the prochiral radical with a hydrogen atom donor based on memory of chirality (Scheme 12) [41], The photo-decarboxylation of optically active tetrahydropyran 40 leads to an intermediate 43, which now does not contain a stereocenter. If the intermediate 43 can be trapped by some hydrogen atom source before ring inversion takes place, then an optically active product 41 will be formed. This is an example of conformational memory effect in a radical reaction. It was reported that the radical inversion barrier is low (< 0.5 kcal/mol) while the energy for chair flip 43 44 is higher (5 to... 

We can see why a compound with chiral centres should end up optically inactive by looking again at the eclipsed conformer. The molecule itself has a plane of symmetry, and because of this symmetry the optical activity conferred by one chiral centre is equal and opposite to that conferred by the other and, therefore, is cancelled out. It has the characteristics of a racemic mixture, but as an intramolecular phenomenon. A meso compound is defined as one that has chiral centres but is itself achiral. Note that numbering is a problem in tartaric acid because of the symmetry, and that positions 2 and 3 depend on which carboxyl is numbered as C-1. It can be seen that (2R,3S) could easily have been (3R,2S) if we had numbered from the other end, a warning sign that there is something unusual about this isomer. 

Until now I have discussed the methods of synthesis of optically active polymers from chiral monomers. As is well known in organic chemistry, it is also possible to produce chiral molecules with one preferred configuration by reaction of achiral molecules in the presence of some chiral influence. These reactions are known as asymmetric syntheses (36, 323-325) when an unsatuiated compound is involved, the term enantioface-differenriating reaction is often used (281). 

Asymmetric synthesis is a term first used in 1894 by E. Fischer and defined4 in 1904 by W. Markwald as a reaction which produces optically active substances from symmetrically constituted compounds with the intermediate use of optically active materials but with the exclusion of all analytical processes . A modem definition was proposed 5) by Morrison and Mosher An asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereosiomeric products (enantiomeric or diastereomeric) are formed in unequal amounts. This is to say, an asymmetric synthesis is a process which converts a prochiral6) unit into a chiral unit so that unequal amounts of stereoisomeric products result . When a prochiral molecule... 

Problem 5.23 Answer True or False to each of the following statements and explain your choice. ( ) There are two broad classes of stereoisomers, (b) Achiral molecules cannot possess chiral centers, (c) A reaction catalyzed by an enzyme always gives an optically active product, (d) Racemization of an enantiomer must result in the breaking of at least one bond to the chiral center, (e) An attempted resolution can distinguish a racemate from a meso compound. <... 

Structures 1 and 2 are enantiomers, and both are optically active. In structures 3 and 4, there is a plane of symmetry, i.e., there is a mirror image within a single molecule. Such a structure is called a meso structure. Structures 3 and 4 are superimposable, and essentially are the same compound. Hence, we have a meso-tartaric acid and it is achiral (since it has a plane of symmetry, and it is superimposable on its mirror image). Meso-tartaric acid is optically inactive. Therefore, for tartaric acid, we have (-f), (—) and meio-tartaric acid. 

Cyclic compounds Depending on the type of substitution on a ring, the molecule can be chiral (optically active) or achiral (optically inactive). For example, 1,2-dichlorocyclohexane can exists as meso compounds (optically inactive) and enantiomers (optically active). If the two groups attached to the ring are different, i.e. no plane of symmetry, there will be four isomers. 

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