1

Stereochemistry and Optical Activity

Building Bridges to Knowledge

Photo of the Yangpu Suspension Bridge in Shanghai, China.

Light possesses the property of a wave, and it vibrates at right angles to the direction in which it is traveling. Light vibrates in an infinite number of planes. This can be illustrated by Diagram 7.1.

2

Diagram 7.1: ordinary lights vibrating in an infinite number of planes

Plane Polarized Light

Plane-polarized light is light that vibrates in one plane, Diagram 7.2.

Diagram 7.2 plane-polarized light

Ordinary light can be converted into plane polarized light by passing it through a lens made of polaroid material or through pieces of calcite (a crystalline form of CaCO

3), Nicol prism.

http://en.wikipedia.org/wiki/Nicol_prism

3

An optically active substance is a substance that rotates plane polarized-light. When polarized light vibrating in one plane is passed through an optically active substance, the plane polarized light comes out vibrating in another plane, and a polarimeter is used to detect the degree of rotation of the plane polarized light.

The polarimeter consists of a light source; two lenses (polaroid or Nicol prism); and, between the lenses, a tube to hold the optically active substance. The first lens polarizes the light, then the resulting plane polarized light is passed through the optically active substance and finally a second lens functions as an analyzer. The observer viewing the plane polarized light can detect the number of degrees the polarized light rotated- either to the left or right of its original propagation. This is illustrated in Diagram 7.3.

4

Diagram 7.3: plane polarized light rotated after passing through an optically active substance

If a substance is not optically active, then it does not affect plane-polarized light. On the other hand, if a substance is optically active, it would rotate plane-polarized light by a specified number of degrees either to the right or to the left. If the optically active substance rotates plane-polarized light to the right, then it is dextrorotatory, and the number of degrees of rotation is indicated with a plus, +, sign. This substance is said to rotate plane polarized light clockwise. If the optically active substance rotates plane polarized light to the left, then it is levorotatory, and the number of

5

degrees of rotation is indicated with a minus, -, sign. This substance is said to rotate plane polarized light counterclockwise.

One possible identifying mark of an optically active substance is a chiral atom. A chiral atom has four (4) different groups or ligands attached to a central atom. For example lactic acid has two stereoisomers, compounds I and II. Compounds I and II have four different groups around their central carbon atoms:

These two compounds cannot be superimposed on each other where all the atoms would have the same spatial relationship. They both possess the same identical physical properties except one rotates plane polarized light clockwise, i.e., it is dextrorotatory, and the other rotates plane polarized light counterclockwise, i.e., it is levorotatory. Compound II is extracted from muscle tissue, and it is dextrorotatory. Since compound II rotates plane polarized light to the left, (+)-lactic acid is a more descriptive nomenclature for dextrorotatory lactic acid.

Compound I rotates plane polarized light counterclockwise; therefore, it is referred to as (-)-lactic acid.

Compounds III, 2-methyj-1-butanol, and IV, 2-methyl-1-butanol,

6

have four (4) different groups about their central carbon atoms. A carbon atom surrounded by four different groups is referred to as a chiral carbon atom or a chiral center. Though compounds III and IV have the same chemical and physical properties, they rotate plane polarized light differently. One rotates plane polarized light clockwise, and the other rotates plane polarized light counterclockwise.

Compound III is levorotatory, and is referred to as (-)-2-methyl-1-butanol. Compound IV is dextrorotatory, and is indicated as (+)-2-methyl-1-butanol

Specific Rotation

The number of degrees that plane polarized light is rotated depends on the number of molecules of the optically active substance that comes into contact with plane polarized light that passes through the sample tube. Light will encounter twice as many molecules of the optically active substance in a sample tube that is 0.20 m long compared to a sample tube that is 0.10 m long. Consequently, the rotation of plane polarized light passing through a 0.20 m sample

7

tube containing a specified concentration of an optically active substance would be twice the rotation of plane polarized light passing through a 0.10 m sample tube containing the same concentration of optically active substance. Also, light will encounter twice as many molecules in a solution in a 0.20 m sample tube containing 2.00 x 10-2 kg/L compared to 1.00 x 10-2 kg/L.

The specific rotation is the number of degrees of rotation of plane polarized light observed if a 1.00 decimeter (dm) tube is used and the optically active compound has a concentration of 1.00 g/mL

Where D is the D line of Na at 5.893 x 10-7 m

The specific rotation is as much of a physical constant as the melting point.

http://en.wikipedia.org/wiki/Specific_rotation

α[ ]D20oC = αobserved

length of the tube in decimeters x concentration in g/mL

8

Enantiomers

While doing some work on salts of tartaric acid, Louis Pasteur discovered that optically inactive sodium ammonium tartrate (a mixture of compounds V and VI) exists as a mixture of two different kinds of crystals that are mirror images of each other. Pasteur physically separated the mixture. When he had accomplished this meticulous task, he discovered that the mixture of compounds V and VI was optically inactive; however, after carefully separating compound V from compound VI and dissolving them in water, each compound exhibited optical activity. One rotated plane polarized light clockwise and the other rotated plane polarized light counterclockwise.

Pasteur proposed the existence of a new type of isomer whose structures differ only in being mirror images of one another, and whose properties differ in the direction each rotates plane polarized light. These compounds are identified as enantiomers. Compounds I and II are enantiomers, compounds III and IV are enantiomers, and compounds V and VI are also enantiomers. Enantiomers are non-superimposable compounds that are mirror images of each other. It is impossible to superpose one isomer on

9

the other without breaking bonds. Compounds 1-IV possess one chiral center, and compound V and VI possess two chiral centers.

Molecules possessing at least one chiral center are capable of existing as enantiomers. Chiral centers are also described as asymmetrical carbon atoms. Molecules that can exist as enantiomers are described as chiral molecules, and molecules that cannot exist as enantiomers are described as achiral molecules. However, a chiral center is not a criterion for the molecule existing as enantiomers, because the primary property of optical activity is the ability of the isomers to be non-superimposable or dissymmetric.

Molecules with carbon atoms containing three different groups have mirror images, but their mirror images are superimposable; therefore, they are identical since they can be superimposed atom for atom on one another.

Many common objects possess an enantiomeric relationship. For example, shoes, a helix, gloves, human hands, and right and left handed screws.

Properties of Enantiomers

Enantiomers have identical physical properties such as boiling point, melting point, spectrum, refractive index, solubility, and specific gravity. Enantiomers cannot be separated by conventional techniques such as distillation, chromatography or crystallization since their physical properties are identical. Special separation

10

techniques must be employed to separate enantiomers into their mirror image components. Enantiomers also have the same chemical properties, and they react identically with reagents that are not themselves enantiomeric. The reactivity of enantiomers differs with enantiomeric reagents. These reaction differences are used to separate enantiomers into their mirror image components.

An equal mixture of the levorotatory isomer and the dextrorotatory isomer will not rotate plane polarized light. Each enantiomer would cancel the rotation of the other. When the enantiomers exist in equal proportion, the mixture is referred to as a racemic modification. The dextrorotatory compound is designate with a “+” sign and the levorotatory compound is designated with a “-“sign; therefore, the racemic modification is designated as “±” or dl. If there is no designation before the name of the chiral compound, the compound is assumed to be a racemic modification.

Practically all the naturally occurring chiral molecules exist as only one of the enantiomers. Nature rarely produces racemic modifications. The opposite occurs in the laboratory where syntheses of molecules that are chiral generally produce a racemic modification.

The physiological properties of enantiomers can differ. There are multiple examples where one enantiomer has a pronounced physiological activity while its mirror image is devoid of such activity. The difference in physiological activity can be attributed to a difference in reactivity of enantiomeric pairs toward biochemical compounds such as enantiomeric enzymes and proteins. Also the

11

difference in physiological activity can be attributed to the difference in the products formed when enantiomers react with other enantiomers. Later we will see that this factor is the basis for separating enantiomers.

Compounds VII and VIII, have chiral carbon atoms indicated by asterisks; therefore, they exist as enantiomers.

Both enantiomers, with identical physical properties, are known in nature. Compounds VII and VIII are known as carvone. Compound VIII, β-carvone, isolated from spearmint, has the odor of spearmint. Compound VII, α-carvone, isolated from caraway seeds, has the odor of caraway seeds. These distinct odors are anticipated since the odor receptors in the nose are chiral, and are able to distinguish between the two enantiomers. http://www.leffingwell.com/chirality/carvotanacetone.htm gives another perspectives of compounds VII and VIII.

Chirality is not an exclusive property of carbon compounds. Certain nitrogen, phosphorus and silicon compounds also possess chirality. For example, the

12

phosphorus compounds IX and X are enantiomers. The silicon containing compounds XI and XII are enantiomers.

Compounds IX and X are nonsuperimposable mirror images, and compounds XI and XII are nonsuperimposable mirror images. For further clarification of the nonsuperimposability of these molecules, try building models of their mirror images and attempt to overlap them atom for atom.

Nitrogen compounds interconvert to their enantiomers by an inexplicable process identified as the “umbrella effect;” therefore, canceling the nonsuperimposability of the enantiomers (the criterion for optical activity).

13

Absolute Configuration

The (-) or (+) before the name of the enantiomer only specifies the direction of rotation of plane polarized light. It has nothing to do with the configuration of the enantiomer (i.e., it does not indicate the arrangement of the atoms in the molecule). How, then, do we specify one enantiomer as opposed to its mirror image? The left hand and the right hand are distinguished from one another by simply referring to the right hand as the right hand, and the left hand as the left hand. Enantiomers cannot be distinguished in such a simple manner. They are distinguished by designating their chiral centers as R (Rectus, Latin for right) and S (Sinister, Latin for left). An R designation means that when the atom of fourth priority is hidden behind the chiral center the remaining three attached atoms are arranged in a clockwise manner moving from the first priority atom to the third priority atom. An S designation means that when the atom of fourth priority is hidden behind the chiral center the remaining three attached atoms are arranged in a counterclockwise manner moving from the first priority atom to the third priority atom. The rules for specifying absolute configuration follow the Cahn-Ingold-Prelog priority rules.

(1) Assign priority to the four atoms attached to the chiral carbon

14

atom on the basis of their atomic numbers. The atom with the highest atomic number attached to the chiral center is given the first priority. For example, let’s consider an enantiomer of compound XIII, 1-bromoethanol

Br, atomic number 35, would have the first priority

O, atomic number 8, would have the second priority

C, atomic number 6, would have the third priority

H, atomic number 1, would have the fourth priority

(2) The molecule is rotated so that the fourth priority atom is placed behind the chiral center. The remaining three atoms are identified as positioned from the first priority atom to the third priority atom in a clockwise arrangement or a counterclockwise arrangement.

For example, the chiral center in compound XIII has an “R” designation as a consequence of following the above rules.

15

On the other hand, if the enantiomer had the atoms attached as in compound XIV

And the molecule is rotated so that the fourth priority atom is placed behind the chiral center. The remaining three atoms would have the following arrangement:

Therefore, the chiral center in compound XIV would have an “S”

16

designation as a consequence of following the above rules.

(3) The “R” configuration is specified when the atoms are arranged from first priority to third priority in a clockwise manner.

(4) The “S” configuration is specified when the atoms are arranged from first priority to third priority in a counterclockwise manner.

By observing these rules, both the configuration and the direction of rotation of plane polarized light of the enantiomer can be specified. Remember that the rotation of plane polarized light can only be determined by using a polarimeter. Also, the R and S configurations do not determine if a compound is levorotatory or dextrorotatory. A compound can be S and dextrorotatory, or R and levorotatory, or S and levorotatory, or R and dextrorotatory.

The enantiomers of 2-chlorobutane, compounds XV and XVI, have the following structures:

Measurements with a polarimeter showed that compound XV with the S designation at the chiral center is dextrorotatory, and that

17

compound XVI with the R designation at the chiral center is levorotatory. Therefore, the IUPAC name for compound XV is S-(+)-2-chlorobutane and the IUPAC name for compound XVI is R-(-)-2-chlorobutane.

If two or more of the atoms attached to the chiral center are identical as in compound XVII, 2-bromobutane, then the following rules apply.

(1) If two or more atoms are attached to the chiral center are identical, then go to the next atom attached to the identical atom. This process is continued until an atom of higher priority has been established. Also, a triple bond attached to a chiral center would have priority over a double bond, because in establishing priorities a double bond would be envisioned as (a), and a triple bond would be envisioned as (b).

CH3C CH2CH3

Br

H

XVII

18

Therefore, the priority around the chiral center of compound XVI would be indicated in the following manner:

Therefore, the ethyl (CH3CH2) group would have priority over the methyl (CH3) group. In the case of the ethyl group, the next atom attached to the carbon atom (attached to the chiral center) is another carbon atom. In the case of the methyl group, the next atom attached to the carbon (attached to the chiral center) is a hydrogen atom. In compound XVII, the priority is Br > CH3CH2 >

19

CH3 > H, and the absolute configurations of the enantiomers of compound XVII would be:

In considering the enantiomers of compound XVIII, 3-methylhexane, the propyl group would have the first priority, the ethyl group the second priority, and the methyl group the third priority.

Compounds Containing Two or More Chiral Centers

The maximum number of stereoisomers possible for compounds

CH2CH3H3C

H

CH3CH2

H

CH3

CH2CH2CH3CH3CH2CH2

R-3-methylhexane S-3-methylhexane

XVIII

20

containing two or more chiral centers is given by 2n , where n is the number of chiral centers. If two or more of the chiral centers are identical, i.e., contain the same substituents, then the number of stereoisomers decreases. Compound XIX, 2,3-dichlorbutane, has two chiral centers that are identical.

The enantiomers of compound XIX can be written in the following manner:

C CCH3 CH3

Cl Cl

H H

XIX

21

A and B are different, and this difference can be determined by rotating A and B about the C2 – C3 sigma bond until the methyl groups are eclipsed.

22

Rotation about the C2-C3 sigma bond in A results in eclipsing the methyl groups, the hydrogen atoms and the chlorine atoms. The methyl groups are eclipsed when they are rotated about the C2 and C3 sigma bond in B . Therefore, A and B must be different isomers.

Configurations A and B have mirror images. Let’s see if their mirror

23

images are superimposable. The mirror image of A, A’, is

The mirror image of B, B’, is

A and A’ are superimposable. Simply rotate A’ 180o about the y axis as illustrated in Diagram 6.4 and A will be generated.

24

Therefore A and A’ are identical. In addition, the eclipsed conformation of A has a plane of symmetry and the staggered conformation of A has a point of symmetry.

25

Stereoisomer A does not have a nonsuperimposable mirror image and is, therefore, not optically active-this is the meso isomer. Carbon atoms 2 and 3 of stereoisomers A have opposite configurations; consequently, there is an internal cancellation of rotation of plane polarized light; therefore, the meso compound can be thought of as an internal racemic modification.

Stereoisomer B has a nonsuperimposable mirror image and can therefore exist as an enantiomeric pair. The enantiomers of B will rotate plane of polarized light an equal number of degrees to the right or the left. Nevertheless, the enantiomers of B have identical physical properties and chemical properties except in reactions with other enantiomers.

The meso compound A has physical and chemical properties different from those of the enantiomers of B. This is expected since A and B are not mirror images.

The meso compound can be thought of as the RS stereoisomer

26

where there is an internal cancellation making the compound optically inactive. The enantiomers of B can be considered as the RR and SS stereoisomers, and one stereoisomer rotates plane- polarized light to the right and the other rotates plane-polarized light to the left.

Diastereoisomers

In review, there are three stereoisomers of compound XIX.

The enantiomers of B and B’, the RR and SS compounds, and the meso, RS, compound. A and B and A and B’ are diastereoisomers. B and B’ are enantiomers.

C CCH3 CH3

Cl Cl

H H

XIX

27

A is a stereoisomer, but not a mirror image of B or B’. A is a diastereoisomer, a stereoisomer that is not a mirror image, of B or B’.

Another example of diastereoisomers is the isomers of compound XX, 1,2-dichlorocyclobutane.

XX

28

Cyclobutane is shown here to be a rigid square geometric structure. In reality, this is not the case, because the cyclobutane ring is slightly puckered.

Compounds C and C’ are non-superimposable mirror images; therefore, they are enantiomers. Compound D does not have a non-superimposable mirror image; therefore, it does not have an enantiomer. However, D has an isomeric relationship with C and C’. D is a stereoisomer that is not a mirror image of C and C’; therefore, D is a diastereoisomer of C and C’. In summary, C and C’ are enantiomers; C and D are diastereoisomers; and C’ and D are diastereoisomers.

29

Compounds Containing Two Non-Identical Chiral Centers

Recall that the maximum number of stereoisomers possible for a compound containing n number of chiral centers is 2n. For a compound with two non-identical chiral centers, the maximum number of stereoisomers is 22 = 4. Using 2-chloro-3-bromobutane as an example, the configuration for the four (4) expected stereoisomers and their relationship to each other are illustrated is Figure 7.1.

Figure 7.1: the enantiomers and diastereoisomers of 2-chloro-3-bromobutane

Figure 7.2 is the staggered arrangement of E, E’, F, and F’, the isomers of 2-chloro-3-bromobutane.

30

Figure 7.2: staggered conformations of the stereoisomers of 2-chloro-3-bromebutane

Figure 7.2 shows that E and E’ are enantiomers; F and F’ are enantiomers; E’ and F are diastereoisomers; E and F are diastereoisomers; E and F’ are diastereoisomers. There are two sets of enantiomers and three sets of diastereoisomers.

The number of stereoisomers possible for a compound containing four non-identical chiral centers would be 16 (24) different stereoisomers. For example, compound XXI, would have sixteen different stereoisomers.

31

Try drawing the sixteen stereoisomers of compound XXI.

Symmetry, a Better Method for Determining Chirality

A chiral center conveys chirality to molecules; however, often it is not clear that a molecule is chiral. This is especially true for some cyclic compounds. A molecule can be chiral, but yet does not possess a chiral center. There are three elements that should be looked for to ascertain if a molecule is non-chiral or achiral. Molecules are achiral if they possess a plane of symmetry; a point of symmetry; or a rotating axis of symmetry.

C

C

C

C

C

C

H

H

H

H

H

H

H

O

OH

OH

OH

OH

OH

XXI

32

Plane of Symmetry

If a molecule has a plane of symmetry, it is achiral, and the molecule is non-dissymmetric. A plane of symmetry is an imagined mirror that bisects the molecule in a way that half of the bisected molecule is the mirror reflection of the other half. For example, as indicated in Figure 6.3, a plane of symmetry can be drawn through compound XXII, dichloromethanol; compound XXIII, 1,2-dichloro-1,2-dibromoethane; compound XXIV, 1,2-dichlorocyclopropane; compound XXV, 1,2-dichlorocycbutane; compound XXVI, 1,2-dichloro-1,2-dibromoethene; and compound XXVII, trichloromethane.

C

OH

Cl

Cl

H

XXII

C

C

Br

Br Cl

Cl

H

H

XXIII

33

Compounds XXI – XXVI are achiral; therefore, they are superimposable on their mirror images and optically inactive.

Compound XXVIII, 3-bromo-1-chloro-1-phenylallene does not have a plane of symmetry; consequently, the molecule is chiral. This molecule is chiral even though it does not have a chiral center.

Cl

H H

HH

Cl

XXIV

Cl Cl

H H

XXV

C

C

Br

BrCl

Cl

XXVI

Cl

Cl

C H

Cl

XXVII

34

Often it is necessary to construct models of the molecule before chirality can be established. Nevertheless, with experience and practice, one is able to visualize the chirality of molecules on paper. The important factor is that if a plane, point, or rotating axis of symmetry is established, then the molecule is achiral- if not, then the molecule is chiral.

Let’s use the plane of symmetry model to ascertain if compound XXIX, chloroallene; compound XXX, 1,1-dibromoallene; and compound XXXI, 1-chloro-1,2-butadiene are chiral or achiral.

C C C

H

ClBrC C C

Br

H

Cl

XXVIII

C C C

H

ClC C C

HCl H

H

XXIX

H H

35

Compound XXIX has a plane of symmetry; therefore, it has a superimposable mirror image.

C C C

H

Br

C C C

Br

H

H H

XXX

BrBr

C C C

H

ClC C C

HCl H

HCH3

XXXI

CH3

36

These two compounds overlap atom for atom and p orbitals with p orbitals, and there is a plane of symmetry in the molecule. Consequently the molecule is achiral.

Compound XXX has a plane of symmetry; therefore, its mirror image is superimposable.

These two compounds overlap atom for atom and p orbitals with p orbitals, and, analogous to compound XXIX, there is a plane of symmetry in the molecule. Consequently the molecule is achiral.

Compound XXXI does not have a plane of symmetry; therefore, its mirror image is non superimposable.

Cl

H

H

H

C C C

37

These two compounds cannot overlap atom for atom and p orbitals with p orbitals, and, there is not a plane of symmetry in the molecule. Consequently, the molecule is chiral and can exist as enantiomers.

Compounds XXIX and XXX are achiral, and compound XXXI is chiral. Compounds XXIX and XXX are achiral, because they have planes of symmetry; however, compound XXXI is chiral, because there is no plane of symmetry, point or symmetry or rotating axis of symmetry.

Resolution of Racemic Modifications

When a racemic modification reacts with an optically active resolving agent, two compounds of different physical properties are produced. These two compounds have diastereomeric relationships to one another; therefore, they can be separated using techniques like crystallization, chromatography, etc. Once the diastereoisomers are separated, the pure enantiomer can be generated – usually by hydrolysis.

Following is a general schema for resolving enantiomers:

1. (+) E + (-) E + 2 (+) R (+) E (+)-R + (-) E (+) R

Cl

C C CHCl

H CH3

CCCH

HH3C

38

racemic modification resolution agent diastereoisomers (different physical properties)

2. (+) E (+)-R (+) E + (+) R

pure enantiomer

3. (-) E (+)-R (-) E + (+) R

pure enantiomer

The choice of a resolution agent is dictated by the structure of the racemic modification. The resolving agent must react with the racemic modification, producing diastereoisomers that can be hydrolyzed (or under some other kind of separation reaction) to give the pure enantiomers and the original resolving agent. After separating and hydrolyzing the diastereoisomers, there is generally little or no problem in separating the resolving agent from the enantiomer.

If the racemic mixture is an amine, usually the resolving agent is an optically active acid. The reaction of the acid and the amine results in two diastereomeric amine salts. The salts can then be separated and the pure enantiomers regenerated by hydrolysis.

The following equations illustrate the resolution of racemic 2-aminobutane into optically pure levorotatory and dextrorotatory enantiomers.

39

(2S)-2-aminobutane (2R)-2-aminobutane R (+) Lactic A The Racemic Modification The Resolving Agent

S R

R R

SR and RR represent a racemic mixture (also referred to as a racemic modification) of the diastereoisomeric salts. Diastereoisomers can be physically separate, and the enantiomers isolated or resolved. When the diastereoisomers are physically separated, they can be treated with sodium hydroxide to regenerate

40

the separated pure enantiomers

The S enantiomer

The R enantiomer

If the enantiomers were acids, then the racemic acids could be resolved with an optically active base. The series of reactions

41

would be similar to the previous discussion except the resolving agent would be an acid.

Loss of optical Activity

Whenever a bond to a chiral atom is broken, the optical activity of the compound is either partially or totally destroyed. For example, the free radical chlorination of 1-chloro-3-methylpentane will result in the formation of a compound that will be a racemic modification. This observation can be rationalized by examining the mechanistic pathway for the conversion of 1-chloro-3-methylpentane to 1,3-dichloro-2-methylpentane.

1.

2. Step two is a propagation step that leads to two possible isomers, i.e., attack of a chlorine radical on the right of the flat radical and attack of a chlorine radical on the left of the flat radical.

42

(3R)-1,3-dichloro-2-methylpentane

(3S)-1,3-dichloro-2-methylpentane

Other dichloroisomers are possible in this free radical chlorination reaction in addition to (3R)-1,3-dichloro-2-methylpentane and (3S)-1,3-dichloro-2-methylpentane. However, this discussion focused on disrupting the chiral center in 1-chloro-3-methylpentane with the generation of 1,3-dichloro-2-methylpentane.

When 1,3-dichloro-2-methylpentane is produced, the chlorine radical abstracts the tertiary hydrogen atom on the chiral carbon. Once the tertiary hydrogen has been abstracted, a flat tertiary alkyl radical is generated, and the chiral center is destroyed. The flat tertiary alkyl radical is attacked by chlorine in a propagation step. The chlorine can attack either side of the flat radical to generate a racemic modification.

43

Problems

Stereochemistry

1. A measured mass of an optically active compound is dissolved in

an aprotic solvent making a total volume of 50.0 mL. When this

solution is placed in a 10.0 cm polarimeter tube, the observed

rotation is +2.79o. If the specific rotation is +93o g-1 dm-1 mL,

calculate the mass of the optically active sample in the polarimeter

tube.

2. Specify the absolute configuration of the chiral centers, if any, in

the following compounds. Indicate whether the compound is

optically active.

a.

b.

C

Br

CH2CH3H3C

H

CC CCH3

CH3H

H

44

c.

d.

e.

f.

CC CCH3

CH3H

H

CH3

H

O

Br

BrH

H

45

g.

h.

i.

CH3 HCH2CH3

N

..

C

C

C

CH2OH

H

H

OH

OH

O

H

C

C

H

H

CH2CH3

CH2CH3

Br

Br

46

j.

3. Show how differences in the solubility of diastereomeric salts

may be used to resolve optically active alcohols, ROH.

Hint:

4. In the following reaction, determine if the chiral center in the

reactants has been disrupted in synthesizing the products:

C

H

CH2CH3

CH2CH2CH3CH3

C

C

O

O

O

+ ROH

C

C

O

OH

OR

O

phthalic anhydride an acid-ester

47

(a)

(b)

(c)

(d)

CCH3 COOH

H

OH

+ ROHH+

CH3 C

H

OH

COOR + H2O

C

CH3

COOH

H

+

CH3

C

H

+CNCH3CH2 H2O HCl2 + NH4ClCH3CH2

C

CH3

H

+

CH3

C

H

+CH3CH2 CH3CH2Br NaOH OH NaBr

+ C CH2CH3

CH3

H

ClAlCl3

C

H

CH2CH3

CH3HCl+

48

5. The specific rotation of an optically active dextrorotatory

compound is +56o. Calculate the percentage composition of a

mixture of enantiomers of this compound whose rotation is -22o.

6. Which of the following structures are superimposable on their

enantiomers?

(a)

(b)

CH3

CH3

Br

Br

H

H

CH3

CH3

HH

49

(c)

(d)

(e)

C

C

CH3

CH3

OH

OH

H

H

OH3C

H

..+

NCH3CH2

CH3

CH2CO2CH3

H

+ Cl-

50

(f)

(g)

7. Calculate the number of stereoisomers possible for the following

compound:

8. Using chemical equations, suggest a pathway for resolving the

following enantiomers:

Cl Cl

H H

Br

Br

H

H

SHO

HO

H

H

HH

H

OHCH3H3CCH2

51

9. Determine which compounds are nonsuperimposable

(dissymmetric) on their mirror images:

a.

b.

C

CH3

CH3CH2

H

N

H

CH3

C

CH3

CH2CH3

H3C

H

H

N

C C CCl

Cl

H H

CH3

H3C

52

c.

d.

e.

C

C

COOH

COOH

OH

OH

H

H

C C CH

H

Cl

H

53

10. A compound with the molecular formula of C7H

16 was found to be

optically active. When C7H

16 is treated with Br

2 and light, the resulting

monobrominated mixture is optically inactive, but resolvable.

(a) Suggest structures for C7H16and the resulting

monobrominated product.

(b) Write a mechanism for the conversion of the optically active

C7H16 to the optically inactive monobrominated mixture.

11. Anisatin, C15H20O8, is a poisonous compound found in the

Shikimi plant. Anisatin has eight chiral centers. Following is the

molecular structure of anisatin.

A three-dimensional model for anisatin can be represented by

Figure 1.

O

O

H

HO

OHO

HO OOH

54

Figure 1

Rotating the three-dimensional model of anisatin down and to the

left would generate the following structure for anisatin.

A three-dimensional model for this structure may be represented by

Figure 2.

O

OHHO

O

HO

O

O

OHH

55

Figure 2

Identify the eight chiral carbon atoms in anisatin, and determine the

R/S notation (the absolute configuration) at each chiral center.