Compounds, optically active

The melting-points of the dextto and laevo forms of any optically active compound may, as in this case, be virtually identical with that of the racemic fomi in many compounds however there is a marked difference in melting-point, and often in solubility, between the (-)-) and ( -) forms on one hand and the ( ) form on the other. 

Specific Rotation. Optical rotation is caused by individual molecules of the optically active compound. The amount of rotation depends upon how many molecules the light beam encounters in passing through the tube. When allowances are made for the length of the tube that contains the sample and the sample concentration, it is found that the amount of rotation, as well as its direction, is a characteristic of each individual optically active compound. 

Chiral nematic Hquid crystals are sometimes referred to as spontaneously twisted nematics, and hence a special case of the nematic phase. The essential requirement for the chiral nematic stmcture is a chiral center that acts to bias the director of the Hquid crystal with a spontaneous cumulative twist. An ordinary nematic Hquid crystal can be converted into a chiral nematic by adding an optically active compound (4). In many cases the inverse of the pitch is directiy proportional to the molar concentration of the optically active compound. Racemic mixtures (1 1 mixtures of both isomers) of optically active mesogens form nematic rather than chiral nematic phases. Because of their twist encumbrance, chiral nematic Hquid crystals generally are more viscous than nematics (6). 

R. A. Sheldon, Chirotechnology Industrial Synthesis of Optically Active Compounds, Marcel Dekker, Inc., New York, 1993. 

Double Polarization. The Clerget double polarization method is a procedure that attempts to account for the presence of interfering optically active compounds. Two polarizations are obtained a direct polarization, followed by acid hydrolysis and a second polarization. The rotation of substances other than sucrose remains constant, and the change in polarization is the result of inversion (hydrolysis) of the sucrose. 

The resolution of optically active compounds by gas chromatography with chiral phases is a well-established procedure, and the separation of Al-perfluoto-acetylated ammo acid ester enantiomers m 1967 was the first successful application of enantioselective gas-liquid chromatography [39] Ammo acids have been resolved as their A -trifluoroacetyl esters on chiral diamide phases such as N-lauroyl-L-valineferf-butylamideorAl-docosanoyl-L-valme /ez-r-butylamide [40,41,... 

V. M. L. Wood, Crystal science techniques in the manufacture of chiral compounds in Chirality and Industry II. Developments in the Manufacture and applications of optically active compounds, A. N. Collins, G. N. Sheldrake, J. Crosby (Eds.), John Wiley Sons, New York (1997) Chapter 7. 

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

A polarimeter. The sample lube contains an optically active compound. The analyzing filter has been tuned clockwise to restore the light field and measure the rotation caused by the sample. 

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. 

Measurement of the optical rotation of optically active compounds. Polarimetric measurements can likewise be used as a method of identifying pure substances, and can also be employed for quantitative purposes. 

Catalytic kinetic resolution can be the method of choice for the preparation of enantioenriched materials, particularly when the racemate is inexpensive and readily available and direct asymmetric routes to the optically active compounds are lacking. However, several other criteria-induding catalyst selectivity, efficiency, and cost, stoichiometric reagent cost, waste generation, volumetric throughput, ease of product isolation, scalability, and the existence of viable alternatives from the chiral pool (or classical resolution)-must be taken into consideration as well... 

In general, yields of (/ )-acyloins and (2S,3/ )-diols, respectively, are low due to the formation of several byproducts (mainly reduction products of the substrate). Nevertheless, the optically active compounds thus obtained are extremely useful intermediates for the synthesis of many natural products51. 

This type of procedure is referred to as a kinetic resolution since the enantiomers of the racemic substrate exhibit different rates of reaction with the optically active compound, i.e. the diastereomeric transition states that arise from differences in e.g. non-bonded interactions have different free energies. Horeau and Nouaille (1966) estimate that a rate difference corresponding to A AG of the order of 0 2 cal mol at 25°C could in principle be revealed by this method. 

Trialkylsilyl radicals are known to be strongly bent out of the plane (cr-type structure 5). The pyramidal structure of trialkylsilyl radicals (RaSi ) was first indicated by chirality studies on optically active compounds containing... 

Optically active compounds may be classified into several categories. 

Once again, one reaction and only one must be an inversion, but which7" It may also be noticed [illustrated by the use of thionyl chloride on (+)-malic acid and treatment of the product with KOH] that it is possible to convert an optically active compound into its enantiomer." ... 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

The synthesis of the first optically active compound is illustrated in Eq. (16) it was obtained with retention (>85%) of configuration about silicon 223). 

Example The discarded (-) phenylethylamine (3) from the resolution on page T 95 can be used to make other optically active compounds. 

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