Download Stereochemistry and Stereoisomers Revisited

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Appendix D
Stereochemistry and
Stereoisomers Revisited
D.1 Introduction to Isomers
Compounds with identical molecular formulas but different structures are called
isomers. Many types of isomers exist, and several of them are discussed throughout
this text. Constitutional isomers differ from one another in configuration; that is,
they differ in terms of which atoms are bonded to one another. Constitutional or
structural isomers can be interconverted only by breaking bonds within the molecule and forming new bonds. Functional group isomers are molecules having the
same molecular formula but different functional groups. For instance, alcohols and
ethers having the same number of carbon atoms are functional group isomers,
such as:
CH3CH2CH2OH
CH3CH2OCH3
1-Propanol (C3H8O)
Ethylmethyl ether (C3H8O)
Similarly, carboxylic acids and esters having the same number of carbon atoms are
also functional group isomers, as are aldehydes and ketones. Geometric isomers,
also called cis-trans isomers, differ from one another in the placement of substituents on a double bond or ring.
Stereoisomers are the major focus of this appendix. By definition, stereoisomers
are molecules that have the same structural formulas but differ in the arrangement
of the atoms in space. Stereoisomers may be distinguished from one another by their
different optical properties. They rotate plane-polarized light in different directions.
D.2 Rotation of Plane-Polarized Light
White light is a form of electromagnetic (EM) radiation and thus consists of waves
in motion. In fact, white light is made up of many different wavelengths (colors) of
light. The light waves vibrate in all directions, or planes, but are always perpendicular to the direction of the light beam (refer to Figure 17.5a and b). Special light
sources, such as sodium or mercury lamps, and filters can be used to produce
monochromatic light, light consisting of only a single wavelength.
When monochromatic light is passed through a polarizing material, such as a
polaroid lens, only light waves in one plane can pass through; all others are filtered out. The light that emerges from the lens is called plane-polarized light. Polaroid lenses, like those found in polaroid sunglasses, consist of parallel arrays of
crystals that can be imagined to look like the slats of Venetian blinds. When light
interacts with this material, the emerging light beam is plane-polarized by the regular crystalline structure.
Applying these principles, scientists have developed an instrument called a
polarimeter that is used to measure the optical activity of molecules. Specifically, the
polarimeter measures the ability of a compound to change the angle of the plane
of plane-polarized light (refer to Figure 17.5c).
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The monochromatic light source of a polarimeter is generally a sodium lamp.
The light waves are directed through a polarizer, and the emerging plane-polarized
light passes through the sample. Finally, the light passes through an analyzer. If the
plane of the light is not altered by the sample, the compound is optically inactive.
However, if the plane of light is rotated either clockwise or counterclockwise, the
sample is optically active.
The angle and direction of rotation are determined by rotating the analyzer,
which is attached to a round dial graduated in degrees. First, the zero point is determined by passing light through the polarimeter without the sample present.
The position that allows the maximum amount of light to pass through is the zero
point. Next, the sample is placed in the polarimeter, and the analyzer is again rotated to allow the maximum amount of light to pass through. The angle of rotation,
or optical rotation, is the difference between the zero point and the new angle obtained with the sample in place.
The observed angles of rotation are proportional to the number of optically active molecules in the sample that interact with light. Thus optical rotation is proportional to the concentration of the sample and to the length of the sample tube,
because both affect the total number of molecules in the light path. To compare
values from different laboratories that use different concentrations and apparatus,
a standard reference, the specific rotation, was developed. Chemists have defined
specific rotation [], as the amount of rotation produced by 1.00 g of substance in
1.00 mL of solution and in a sample tube 1.00 decimeter (dm) in length. Because rotation is also a function of the temperature, the wavelength of monochromatic
light, and the solvent used (if any), these experimental variables must also be reported. The following equation is used to calculate and express specific rotation:
[]tD [obs]
lc
in which
[] specific rotation
[obs] observed rotation
l sample tube length (dm)
c concentration of sample (expressed as g/mL)
t temperature (C)
D the most intense line of the Na spectrum (589.3 nm)
D.3 The Relationship between Molecular
Structure and Optical Activity
As noted in Section 17.3 of the text, some optically active compounds rotate planepolarized light clockwise. These are said to be dextrorotatory and are designated by
a plus sign () before the specific rotation value. Substances that rotate planepolarized light counterclockwise are called levorotatory and are designated by a minus sign () before the specific rotation value.
It was the experimental work of Louis Pasteur that first revealed a relationship
between structure and optical activity. However, it was not until 1874 that the
Dutch chemist van’t Hoff and the French chemist LeBel independently came up
with a basis for the observed optical activity: tetrahedral carbon atoms bonded to
four different atoms or groups of atoms.
In Section 11.2 we saw that a carbon atom involved in four single bonds has
tetrahedral geometry. If the carbon atom is bonded to two identical substituents and
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Mirror
b
a
a
c
c
b
b
b
c
c
Superimposable mirror
images
two nonidentical substituents, the resulting molecule is symmetrical (Figure D.1). In
other words, a plane of symmetry can be drawn through this molecule. Furthermore, this molecule is superimposable on its mirror image. (Prove this to yourself by
building the molecules with molecular models or toothpicks and gumdrops.)
Compare the structure in Figure D.1 with that shown in Figure 17.3 of the text.
In that molecule the tetrahedral carbon is bonded to four nonidentical groups. The
resulting molecule is asymmetric. No plane of symmetry can be drawn through the
molecule, nor can the molecule be superimposed on its mirror image. (Build the
molecules to demonstrate these characteristics.)
As discussed in Section 17.3, the analogy can be made between these mirrorimage molecules and your left and right hands. Your hands are, indeed, mirror images of one another; you cannot draw a plane of symmetry through your hand,
nor can you superimpose your left and right hands on one another.
A molecule that cannot be superimposed on its mirror image is said to be
chiral. When a carbon atom is bonded to four different atoms or groups of atoms,
it is called a chiral carbon. Two stereoisomers that are nonsuperimposable mirror
images of one another are a pair of enantiomers. As mentioned in Section 17.3, the
chemical and physical properties of enantiomers are identical, with the exception
that they rotate plane-polarized light to the same degree but in opposite directions.
This is exactly the phenomenon that Pasteur observed with the mirror-image crystals of tartaric acid salts.
Refer to Figure 17.4 in the text for the structures of the enantiomers of glyceraldehyde. Note that when you are comparing two structures to determine whether
two molecules are enantiomers, you may rotate the structures as much as 180°, but
you may never “flip” the structure out of the plane of the page. Always remember:
If you are in doubt about the three-dimensional structure of a molecule, build it
with a molecular model kit. This is particularly useful as you begin your study of
organic chemistry, and it will help you in your future study of biochemistry.
D.4 Racemic Mixtures
When Louis Pasteur measured the specific rotation of the mixture of left- and
right-handed tartaric acid salt crystals, he observed that it was optically inactive.
The reason was that the mixture contained equal amounts of the () enantiomer
and the () enantiomer. A mixture of equal amounts of a pair of enantiomers is
called a racemic mixture, or simply a racemate. The prefix () is used to designate a
racemic mixture. Consider the following situation:
Figure D.1
A pair of superimposable mirror images.
These molecules have an internal plane
of symmetry that can be drawn through
atoms a—C—c.
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50% () tartrate
50% () tartrate
[]D20 4.7
[]D20 4.7
() tartrate
[]D20 0
50% () enantiomer 50% () enantiomer racemic mixture
In this situation the specific rotation is zero because the rotation caused by one
enantiomer is canceled by the opposite rotation caused by the mirror-image
enantiomer.
D.5 Diastereomers
So far, we have looked only at molecules containing a single carbon. In this case
only two enantiomers are possible. However, it is quite common to find molecules
with two or more chiral carbons. For a molecule of n chiral carbons the maximum
possible number of different configurations is 2n. Note that this formula predicts the
maximum number of configurations. As we will see, there may actually be fewer.
EXAMPLE
D.1
Drawing Stereoisomers for Compounds with More Than One Chiral Carbon
Draw all the possible stereoisomers of 2,3,4-trichlorobutanal.
Solution
1. There are two chiral carbons in this molecule, C-2 and C-3. Thus there
are 22 or 4 possible stereoisomers.
2. There are two possible configurations for each of the chiral carbons (Cl
on the left or on the right). Begin by drawing an isomer with both Cl
atoms on the right (a). Now draw the mirror image (b). You have now
generated the first pair of enantiomers, (a) and (b).
CHO
A
HOCOCl
A
HOCOCl
A
CH2Cl
CHO
A
ClOCOH
A
ClOCOH
A
CH2Cl
(a)
(b)
Enantiomers
3. Next, change the location of one of the two Cl atoms bonded to a chiral
carbon to produce another possible isomer (c). Finally, draw the mirror
image of (c) to produce the second set of enantiomers, (c) and (d).
CHO
A
HOCOCl
A
ClOCOH
A
CH2Cl
CHO
A
ClOCOH
A
HOCOCl
A
CH2Cl
(c)
(d)
Enantiomers
4. By this systematic procedure we have drawn the four possible isomers
of 2,3,4-trichlorobutanal.
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In Example D.1, structures (a) and (b) are clearly enantiomers, as are (c) and
(d). But how do we describe the relationship between structure (a) and (c) or any
of the pairs of stereoisomers that are not enantiomers? The term diastereomers is
used to describe a pair of stereoisomers that are not enantiomers.
Although enantiomers differ from one another only in the direction of rotation
of plane-polarized light, diastereomers are different in their chemical and physical
properties.
D.6 Meso Compounds
As mentioned previously, the maximum number of configurations for a molecule
with two chiral carbons is 22, or 4. However, if each of the two chiral carbons is
bonded to the same four nonidentical groups, fewer than four stereoisomers exist.
The example of tartaric acid, studied by Pasteur, helps to explain this phenomenon.
Drawing Stereoisomers of Compounds with More Than One Chiral Carbon
Draw all the possible stereoisomers of tartaric acid, HOOC—CHOH—
CHOH—COOH.
Solution
1. Proceeding as in Example D.1, you will generate the following four
structures:
COOH
A
HOCOOH
A
HOCOOH
A
COOH
COOH
A
HOOCOH
A
HOOCOH
A
COOH
COOH
A
HOCOOH
A
HOOCOH
A
COOH
COOH
A
HOOCOH
A
HOCOOH
A
COOH
(b)
(c)
(d)
(a)
Identical
Enantiomers
2. Careful examination of pair (c) and (d) reveals that these molecules are
nonsuperimposable mirror images. Thus they are enantiomers.
3. Similar inspection of structures (a) and (b) reveals that, although they
are mirror images, they are identical. Structure (b) can simply be rotated
180 to produce structure (a); therefore they are identical.
Note that if you draw a line between chiral carbon-2 and chiral carbon-3 of
structure (a) or (b) in Example D.2, the top half of the molecule is the mirror image
of the bottom half. There is a plane of symmetry within the molecule:
COOH
A
HOCOOH
A
HOCOOH
A
.
COOH
As a result, structure (a) is optically inactive. Even though there are two chiral carbons, the rotation of plane-polarized light by chiral carbon-2 is canceled by the opposite rotation of plane-polarized light caused by chiral carbon-3. This molecule is
achiral and is termed meso-tartaric acid. Any compound with an internal plane of
EXAMPLE
D.2
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symmetry (i.e., that can be superimposed on its mirror image) is optically inactive
and is termed a meso-compound.
D.7 Assignment of Absolute Configuration:
The (R) and (S) System
Absolute configuration is the actual arrangement of the four groups around a chiral carbon atom. The (R) and (S) System indicates the absolute configuration for any
chiral carbon. In this system, (R) stands for a right-handed configuration (Latin,
rectus), and (S) stands for a left-handed configuration (Latin, sinister).
To assign an (R) or (S) configuration to a chiral carbon, the following set of
rules is used:
1. Priority rank the atoms or groups of atoms attached to the chiral carbon
according to the sequence rules listed in Table D.1.
2. Draw the molecule with the lowest priority group projecting to the rear.
3. Draw a circular arrow from the group of highest priority to the group with
the next highest priority.
4. If the arrow points in a clockwise direction (right), the configuration of the
chiral carbon is (R); if the arrow points counterclockwise (left), it is (S).
Table D.1
Sequence Rules for Order of Priority
Rule
Example
1. For atoms, those with the highest atomic number
are given the highest priority.
2. If two isotopes of an element are present, the
isotope of higher mass is given the higher priority.
3. If two atoms are identical, the atomic numbers
of the next atoms are used to assign priority.
F < Cl < Br < I
4. Atoms attached by double or triple bonds are
assigned single bond equivalences. Every
double-bonded atom is duplicated, and every
triple-bonded atom is triplicated.
1H
< 2H < 3H
H Cl H
A A A
HOCOCOCOBr
A A A
H H H
Higher
priority
because
of Br
O
O
B
A
ROCOR 88n ROCOR
A
OOC
N
C
A
D
ROCqN 88n ROCON
G
A
C
N