Subject Chemistry

Paper No and Title 1; ORGANIC CHEMISTRY- I (Nature of Bonding and Stereochemistry) Module No and 22; Optical Purity Title Module Tag CHE_P1_M22

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

TABLE OF CONTENTS

1. Learning Outcomes 2. Introduction 3. Optical Purity and its Determination

3.1 Criteria of Specific Rotation for Calculating the Optical Purity

3.2 Other Methods of Determining Optical Purity

3.2.1 The Enzymatic Method

3.2.2 Isotopic Dilution Method

3.2.3 Correlative Method

4. Summary

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

1. Learning Outcomes

After studying this module, you shall be able to

 Know about the term optical purity and its meaning.  Understand the criteria for optical purity.  Learn how to calculate optical purity or enantiomeric excess.  Analyse the various techniques used to find optical purity of a mixture.  Study some problems related to optical purity.

2. Introduction

By optical purity of a partially resolved material is meant the excess of one enantiomer in the material expressed as a percentage of the total. In a dl pair, there is no excess enantiomer and the optical purity is zero. In a completely resolved material, the excess enantiomer is equal in weight to the total material and the optical purity is 100%. In the previous module, we have discussed at length about the various methods of resolving a mixture completely to obtain pure enantiomers. It is often desirable to find out whether a given resolution method has gone to completion, i.e., whether the enantiomer obtained is really 100% pure. In the present module, we shall take up all aspects related to optical purity in detail and also give an insight to solving problems based on the same.

3. Optical Purity and its Determination

Optical purity is defined as the ratio of the observed optical rotation of a sample which consists of a mixture of enantiomers to the optical rotation of one pure enantiomer. Several simple criteria of optical purity have been developed. Taking an example, a crystalline enantiomer is often considered optically pure when its melting point and rotation are unchanged by further crystallization. However, this criteria of calculating or getting an idea of the optical purity fails when the racemic modification forms a solid solution, since in that case even a partially resolved enantiomer may not change in

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

either rotation or melting point by further recrystallization. A resolution is often deemed complete when the diastereomeric salt employed doesnot change in rotation upon further crystallization and when once both enantiomers are obtained in a state of equal purity (i.e., with equal and opposite specific rotation).

3.1 Criteria of Specific Rotation for Calculating the Optical Purity Optical rotation is the usual and most useful means of monitoring enantiomeric purity of chiral molecules. Therefore, we need to know what variables influence the magnitude of optical rotation. The measured rotation, α, of a chiral substance varies with the concentration of the solution (or the density of a pure liquid) and on the distance through which the light travels. This is to be expected because the magnitude of α will depends on the number as well as the kind of molecules the light encounters. Another important variable is the wavelength of the incident light, which always must be specified even though the sodium D line (589.3 nm) commonly is used. To a lesser extent, α varies with the temperature and with the solvent (if used), which also should be specified. The optical rotation of a chiral substance usually is reported as a specific rotation [α], which is expressed by the equations.

Frequently, molecular rotation, [M], is used in preference to specific rotation and is related to specific rotation by equation

in which M is the molecular weight of the compound. Expressed in this form, optical rotations of different compounds are directly comparable on a molecular rather than a weight basis.

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

If a solution contains only one enantiomer, the maximum rotation is observed. The observed rotation is proportional to the amount of each enantiomer present.

Fig. 1: Calculation of enatiomeric excess ( e e )

Example 1: If a sample contains eight moles of the excess enantiomer and two moles of the other enantiomer, the enantiomeric excess is ee = (0.8 - 0.2) · 100 % = 60 %. If a sample contains nine moles of the excess enantiomer and six moles of the other enantiomer the enantiomeric excess is ee = (9 / 15 - 6 / 15) · 100 % = (0.6 - 0.4) · 100 % = 20 %. The enantiomeric excess of a racemate, a 1:1 mixture of two enantiomers, is (0.5 - 0.5) · 100 % = 0.

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

In a solution of a chemically (not enantiomerically) pure compound, the values of optical purity and enantiomeric excess are identical. If the solution does not contain any other compound (except for the solvent) and the specific rotation of the pure enantiomer is known, the enantiomeric excess may therefore be determined by measuring the optical rotation of a solution of a two-enantiomer mixture. In order for the optical purity and the enantiomeric excess to be calculated, the specific rotation of the pure enantiomer must first be noted.

Now we shall consider a few more examples which shall clear the concept of optical purity to a greater extent.

Consider that (S)-2-bromobutane has a specific rotation of +23.1o and (R)-2-bromobutane has a specific rotation of -23.1o

Question 1: Determine the optical purity of a racemic mixture.

Answer 1: The specific rotation, [α], of the racemate is expected to be 0, since the effect of one enantiomer cancel's the other out, molecule for molecule.

Optical purity, % = 100 [α]mixture / [α]pure sample = 100 (0) / +23.1o = 0%

Question 2: Determine the enantiomeric excess of the racemic mixture.

Answer 2: You would expect [R] = [S] = 50%.

ee % = 100 ([R]-[S]) / ([R]+[S]) = 100 (50-50) / (50+50) = 0%

Question 3: Which isomer is dominant and what is the optical purity of a mixture, of (R)- and (S)-2-bromobutane, whose specific rotation was found to be -9.2o?

Answer 3: The negative sign tells indicates that the R enantiomer is the dominant one.

Optical purity, % = 100 [α]mixture / [α]pure sample = 100 (-9.2) / -23.1o = 40% this indicates a 40% excess of R over S!

Question 4: What is the percent composition of the mixture?

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

Answer 4: The 60% leftover, which is optically inactive, must be equal amounts of both (R)- and (S)-bromobutane. The excess 40% is all R so there is a total of 70% (R) and 30% (S).

3.2 Other Methods of Determining Optical Purity

There are three other ways of determining optical purity namely an enzymatic method, an isotope dilution method, and a method of relating a compound of unknown optical purity to another one whose purity is known. The basic principles of these methods are briefly outlined below.

3.2.1 The Enzymatic Method

The enzymatic method depends on the fact that many enzymes are highly selective for one enantiomer of a dl pair. If one incubates a supposedly pure preparation of the other compound with such an enzyme, reaction (which must be detectable by suitable means) would indicate the presence of some of the wrong antipode, owing to incomplete resolution or racemization following complete resolution, whereas the absence of reaction would indicate purity. This method is applicable to those cases where the enzyme action is possible on the substrates.

3.2.2 Isotopic Dilution Method

In this method, the supposedly pure enantiomer [for example the (-) isomer] is mixed with some labelled (radioactively or otherwise) racemic material in solution, and the racemic material is then reisolated (usually by crystallization).

Since in solution the racemic material is split up into (+) and (-) molecules, the labelled (-) molecules get comingled with the molecule of the enantiomer whose optical purity is determined, but the molecules of the (+) isomer do not. One can thus calculate a dilution factor, knowing the weight of the original active material and the weight of the added labelled racemic material, and can thus predict how active the recovered labelled racemic material should be. The predicted activity is then compared with the experimental one. If the

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

experimental activity is less than that predicted, it indicates that there was some residual (unlabelled) racemic material in the supposedly pure enantiomer.

ab C± = aCο (2)()BaRaR Where,

Cο is the activity of the added racemic material,

C± is the activity of the recovered material, A is the weight of the added racemic material B is the weight of the resolved material (whose purity is to be tested) admixed with a R is the weight of racemate (if any) in the amount of B

By solving, the above equation for R, knowing all the other quantities from experiment, one may calculate the amount of racemic contaminant and hence the optical purity will be BR 100 % B 3.2.3 Correlative Method

If we assume that the optical purity of a compound Cabde is known. The minimum purity of

another compound Cabdf may be determined if Cabdf can be converted chemically to Cabde.

Cabdf will be atleast as pure optically as the Cabde prepared from it.

This can better understood with the following illustrative example: 25 The highest known rotation of α-phenethyl chloride, C6H5CHClCH3, is αD (neat, 1 dm) 109°. When dextrorotatory material of this rotation is allowed to react with allylsodium and

the resulting 4-phenylpentane, CH3CH2CH2CH(C6H5)CH3, one obtains material of rotation 25 αD – 12.96° (neat, 1 dm). Since the known rotation of optically pure 2-phenylpentane, 25 established in other ways, is αD – 14.91°, the optical purity of the hydrocarbon obtained from the chloride is 12.96/14.91*100 or 86.9%. The minimum optical purity of chloride of 25 αD 109° is therefore also 86.9%, and it follows that the maximum possible rotation of α- phenethyl chloride is 109*100/86.9, or 125.4°.

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity

4. Summary

 Optical purity is defined as the ratio of the observed optical rotation of a sample which consists of a mixture of enantiomers to the optical rotation of one pure enantiomer. Several simple criteria of optical purity have been developed.

 Optical rotation is the usual and most useful means of monitoring enantiomeric purity of chiral molecules.

 The measured rotation, α, of a chiral substance varies with the concentration of the solution (or the density of a pure liquid) and on the distance through which the light travels.

 The observed rotation is proportional to the amount of each enantiomer present in a mixture.

 There are three other ways determining optical purity (at least within specifiable experimental limits); an enzymatic method, an isotope dilution method, and a method of relating a compound of unknown optical purity to another one whose purity is known.

CHEMISTRY PAPER No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) MODULE No. 22: Optical Purity