1

Chapter 5
Isomers
Constitutional Isomers
Stereoisomers
Cis/Trans
R/S
Enantiomers
Diastereomers
Chiral
Achiral
Stereocenter
Meso
Mirror image
Superimposable/Nonsuperimposable
Racemic/Racemate
Stereocenter
Plane of symmetry
Configuration
Enantioselective
Enzymes/Hydrolysis/Lipase

Stereochemistry
Chirality/Chiral/Enantiomers/Diastereomers/ Achiral
OH

Constitutional vs. Stereoisomers

OH

Constitutional isomers b/c OH is on different carbons in each molecule.

Different Connectivity.
1
OH 1

OH

S
2

Stereoisomers b/c all the connectivity is the same, it is just orientation that is
different. Specifically, these are enantiomers.

Biological chiralitylimonene, carvone, thalomid

Stereogenic center vs chirality
Historyvant Hoff, Le Belthe tetrahedral; PasteurStereochemistry
Meso compoundsplane of symmetry
1 stereocenter can only be a pair of enantiomers
2 or more stereocenters is needed for diastereomers
2 stereoisomers that are mirror images of each other and nonsuperposableenantiomers
2 molecules that are mirror images of each other and superposablesame molecule
2 stereoisomers that are not mirror images of each otherdiastereomers
enantiomers

OH HO
Br
1 Br

same molecule

H
Br

mirror

1
Cl

mirror
S

S
OH

HO Cl

not mirror images, diastereomers

3
3

2
3

Br

Br

OH HO

Br

R/S nomenclatureCahn, Ingold, Prelog

All 4 atoms attached to a stereocenter are assigned a priority from 1-4(a-d) based
on atomic number. The highest priority(largest atomic number) is assigned 1(a)
the lowest priority is assigned 4(d).
If 2 isotopes of the same element are attached the heavier isotope gets the
higher priority.
If 2 identical elements are on same stereocenter then you go to the next
carbon for each. You keep going out one carbon till you get to a
difference. Priority is then determined based on size of different groups.
Double bonds count twice. Triple bonds count three times.
Now rotate the lowest priority away from you. Follow 1 to 2 to 3(a to b to c). If
you go in a clockwise manner to go from 1 to 2 to 3(a to b to c), then the
enatiomer is R(rectus). If you go counterclockwise then the enantiomer is
S(sinister).

A
1Br

H
Br

Cl

OH
Br

S 1

H HO

Br

3
S

Br

Br

Cl

3
H Br H3CO Cl

OCH3

R
d

1
Br

Br

d
2

H OH

H OH

HO

3
R

O
HH

H 3CO Cl

OCH3 HO H

Br

HO
Br

Br

1 Br

2
2

D
3

OH
H
OH

Br

Label the stereocenters R or S in the following

HS Br

OH

H Br

Cl

CH3

Cl

Cl
Br

HO CCl 3

H
Br

H
HO

Cl

HO

CH3

Br

Br
OH

Br

H Br

OH

Cl

F
Br

Cl

Br

OH

OCH3

Et

HO

Cl
Br

OH

OH

KEY
3

OH

1
HS

Br

R
Cl
Br

2 Cl

CH3

3
HO

1
S

C Cl 3

1
R
2

Cl

CH3

Br

4
3H O

Br

R
1

4
H

Br

Br

OH

Br

Cl

2
R

3 R

2
HO

1 R

Br

2
H

S
3

3
2
1

2
S

OH

R 1

3
OH

Br

1
H

Br

HO

O CH 3

Et

1
OH

Cl

Cl

1 Cl

R
1

Br

OH

Properties of enantiomers
R/S have the same physical properties(bp/mp/solubility/IR/rate of reaction) because they
share the same environment. Most of the physical properties are based on
environment(intermolecular forces).
The have different properties with other chiral environments such as plane-polarized
light. Enantiomers rotate plane polarized light in the opposite direction but by the same
amount.
Single enantiomers are considered to be optically active. R/S mixtures are racemic.
Polarimeterlight is first passed through a polarizer which allows only one band of light
through. Then the light passes through the chiral environment of the enantiomer. Finally
the light lands on the detector. By where it lands on the 360
degree detector the amount of deflection is calculated.
If the light is rotated clockwise, the value will be (+). This is called Dextrorotatory
(dexterright).
If the light is rotated counterclockwise, the value will be (-). This is called Levorotatory
(laevusleft).
The degree of rotation is given the term specific rotation, .
[]25 D

D refers to the light source. D = D line of Na(589.6 nm)

R/S has no relation to (+/-). R can be (+) in some molecules and (-) in others.
Racemic mixtures give 0o reading. The R and S forms cancel each other out.
Pure R will give one reading(+30 for ex.). Pure S will give opposite reading(-30).
Mixtures of R/S will give readings from +30 to 30 depending on concentrations of R
and S.
100% R give +30. 50% R/50% S gives 0. 100% S gives 30.
Racemic mixtures(50/50) can be referred to as R/S 2-butanol or (+/-) 2-butanol.
In most journals, scientific, medical and pharmaceutical, the %ee(enantiomeric excess) is a
vital statistic when referring to a reaction. You will see entries such asThe reaction was
carried out under typical conditions to give a 78 % yield an enantiomeric excess of 98%.

% ee = [(moles of excess enantiomer moles of other enantiomer)/total moles] x 100.

OR

%ee = (observed specific rotation/specific rotation of pure enantiomer) x 100

Enantiomeric excessif ee = 50 % that means 50% is racemic and the other 50% is pure
enatiomer(50 + of 50 = 75). Therefore 50 % ee means 75% of one enatiomer
and 25 % of the other enantiomer.
A. Given the ee
If a molecule is in the R form at 90%ee, what is the % of R and S? 90%ee means 90%
pure R and 10%(100-90) a mixture of R and S; therefore it is 95% R(90% + of 10%)
and 5% S ( of 10%)
82%ee S means 91% S(82 + of 18) and 9% R( of 18).
71%ee R means 85.5% R(71 + of 29) and 14.5 S( of 29)
B. Given the %
If a molecule is 20% R and 80% S, what is the ee?

ee = 80 20 = 60 % ee

If a molecule is 43% R and 57% S, what is the ee?

ee = 57 43 = 14 % ee

C. Given the optical rotation.

If the specific rotation of a molecule with R designation is + 45 and a mixture of R/S of
that molecule gives an observed rotation of + 25, what is the % R, % S and the ee?
ee = observed/specific x 100; ee = 25/45 x 100 = 56% ee; since it is 56% ee, that
means 56% R, and 44% R/S mixture; therefore, R = 78%(56 + of 44) and S =
22%( of 44)
If the specific rotation of a molecule with R designation is + 45 and a mixture of R/S of
that molecule gives an observed rotation of - 25, what is the % R, % S and the ee?
ee = observed/specific x 100; ee = 25/45 x 100 = 56% ee; since it is 56% ee, that
means 56% S, and 44% R/S mixture; therefore, S = 78%(56 + of 44) and R =
22%( of 44)

Since the observed rotation is the opposite sign of the specific rotation that means
that the major isomer is the opposite of the specific rotation isomer. IE since +45 =
R, then 25 is predominately S.

Most reactions yield a racemic form of the final product. If a reaction yields one enantiomer
in excess of the other the reactions is called enantioselective. These are highly desirable. In
biochemistry, you will study many enantioselective reactions driven by enzymes.
Chiral Drugsmany drugs are chiral. In their chirality it is often one of the 2 enantiomers
that does all the work, while the other is inert or even toxic.
Ibuprofen, Methyldopa, Penicillamine, FDA, pharmaceuticals, Glaxo Prilosec/Nexium
Diastereomerschiral molecules with more than one stereocenter.
2N = number of stereoisomers possible(where N = # of stereocenters).
A molecule with 2 stereocenters(22 = 4) would have 4 possible stereoisomers(A, B, C
and D). A and B are enantiomers of each other. C and D are enantiomers of each
other(because they are mirror images). A and C, A and D, B and C, B and D are
diastereomers of each other because they are not mirror images.
Diastereomers have different physical properties from each other. I.E. A and B melt at
same temperature. C and D melt at same temperature. But the A/B temperature is
different from the C/D temperature.
Many times the true amount of stereoisomers is less than the maximum. This is due to
meso compounds(which are achiral).
Meso comopunds have a plane of symmetry which destroys chirality.
If A had a plane of symmetry it would be meso. Therefore B would be meso and
actually A and B would be the same thing. Therefore C and D would be enantiomers
of each other and they would both be diastereomers of A/B, where A/B is the same.
CH 3

CH 3

CH 3

OH H O

OH H O

HO

CH 3

CH 3

CH 3
OH
H

HO

OH

CH 3

CH 3

Fischer projections are often used to look for meso. Fischers are also often used in
carbohydrate che mistry. In Fischer projections the compound can be rotated in the
plane of the paper but it can NOT be flipped.
Nomenclature of diastereomers is the same as for enantiomers. Each stereocenter is
given a R/S designation.

Cyclic compounds
Cyclopentane(the 2 substituents must be the same)

1,2 disubstituted

Planes of symmetry
no plane of symmetry

cis is meso

H3C

trans is a pair of enantiomers

H3C

H3C

H3C

cis and trans are diastereomers

trans

cis
diastereomers

enantiomers

same

1,3 disubstituted

Planes of symmetry

no plane of symmetry

cis is meso
trans is a pair of enantiomers
cis and trans are diastereomers
trans

diastereomers
cis

enantiomers

same

If the substituents are different then 1,2 cis and 1,3 cis are pairs of enantiomers instead of the
same. 1,2 trans and 1,3 trans are still pairs of enantiomers and still diastereomers of the cis.
no plane of symm etry
Br

Cl

Br

no pla ne of symm etry

Cl

Br

diastereom ers
cis

e nantiomers

Cl

Cl

trans
e nantiomers

Br

10

Cyclohexane(the 2 substitue nts must be the same)

1,2 disubstituted
cis is a pair of rapidly intraconverting enantiomers(mimics meso)
they are considered conformational isomers
trans if a pair of enantiomers
cis and trans are diastereomers of each other
1,3 disubstituted
cis is meso
trans if a pair of enantiomers
cis and trans are diastereomers of each other
1,4 disubstituted
cis is meso
trans is meso
cis and trans are diastereomers of each other

cis

cis
cis

cis

cis

trans

all have planes of symmetry

If the substituents are different then 1,2 cis, 1,3 cis, 1,4 cis and 1,4 trans are pairs of
enantiomers instead of the same. 1,2 trans and 1,3 trans are still pairs of enantiomers and still
diastereomers of the cis.

11

Chemical Reactions
One of the goals of orga nic chemist is to create enantioselective reactions so that pure
chemicals can be obtained. One way to do this is to create a pure isomer and then
keep it unchanged.
Retention of Configurationif a chemical reactions proceeds without breaking the
bonds of the stereocenter it is said to have retention of configuration
When a reaction proceed through retention of configuration, the R/S designation and
the optical rotation may stay the same or it may change.
Inversion of Configurationif a reaction proceeds through the stereocenter it can
quite often invert the stereochemistry of the stereocenter.
Racemizationmost often if a reaction proceeds through the stereocenter it will
racemize the mixture
Absolute/Relative Configurations
Absolutethe stereochemistry is known for all stereocenters.
Relativethe stereochemistry of all stereocenters is relative to the original
stereocenter which is unknown.
See the glyceraldehyde example
Resolution
Pasteurby crystallization of diastereomers
1848separation of (+/-) tartaric acid. Led to the field of stereochemistry.
Modernby separation of diastereomers based on different physical properties which
could include mp, crystallization, solubility. Chromatography is most often
used(HPLC). Enzymes are very useful also.
Stereocenters other than carbon
4-bonded atoms such as Si, Ge, N and S can be stereocenters.
Chiral molecules that dont have stereocenters
Allene b/c of out of plane double bonds has chirality(build a model).

12

A. Given the ee
If a molecule is in the R form at 90%ee, what is the % of R and S?
90%ee means 90% pure R and 10%(100-90) a mixture of R and S;
therefore it is 95% R(90% + of 10%) and 5% S ( of 10%)
Other examples:
82%ee S means 91% S(82 + of 18) and 9% R( of 18).
71%ee R means 85.5% R(71 + of 29) and 14.5 S( of 29)

B. Given the %
If a molecule is 20% R and 80% S, what is the ee?

ee = 80 20 = 60 % ee

If a molecule is 43% R and 57% S, what is the ee?

ee = 57 43 = 14 % ee

C. Given the optical rotation.

If the specific rotation of a molecule with R designation is + 45 and a mixture of R/S of that molecule gives
an observed rotation of + 25, what is the % R, % S and the ee?
ee = observed/specific x 100; ee = 25/45 x 100 = 56% ee;
since it is 56% ee, that means 56% R, and 44% R/S mixture;
therefore, R = 78%(56 + of 44) and S = 22%( of 44)
If the specific rotation of a molecule with R designation is + 45 and a mixture of R/S of that molecule gives
an observed rotation of - 25, what is the % R, % S and the ee?
ee = observed/specific x 100; ee = 25/45 x 100 = 56% ee;
since it is 56% ee, that means 56% S, and 44% R/S mixture;
therefore, S = 78%(56 + of 44) and R = 22%( of 44)
Since the observed rotation is the opposite sign of the specific rotation that means that the major
isomer is the opposite of the specific rotation isomer. IE since +45 = R, then 25 is predominately S.

13

1. What is the % R and S of the following?

88 %ee R

25 % ee S

42 % ee R

91 % ee R

68 % ee S

2. What is the % ee for the following?

90 % R 10 % S 40 % R 60 % S 70 % R 30 % S

85 % R 15 % S 74 % R 26 % S

3. If the observed rotation is +35 and the pure R rotates at +43, what is the % ee, % R and % S?
4. If the % ee = 50%R and pure S rotates at 20, what is the observed rotation?
5. (2S, 3R, 4R, 5S)-2,3,4,5-tetrachlorononane is made in the lab using stereospecific reactions. What is the
stereochemistry of the enantiomer of that molecule? What is the stereochemistry of one of the diastereomers?
How many possible stereoisomers are there for this molecule?
6. Four stereoisomers of dibromopentane are isolated. RR
RR has the same bp as

SS has the same solubility as

RS

SR

SS

RS has a different bp from

7. In the following pairs, label them as the same molecule, enantiomers or diastereomers.

a . _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _

Br
OH
Br

H 3C

Br

HO

CH

HO

b . _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ __
3

H
H

Cl

c . _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _
HO
Br

H 3C

Cl

Br

Br

d. _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _
H 3C H 2 C

C H3

H3C

C H2C H3

( 2 R , 3 R ) - 2 , 3 - d ic h lo r o p e n t a n e a n d
e . _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _
( 2 S , 3 R ) - 2 , 3 - d ic h l o r o p e n ta n e
HO
H
C H 2O H

C H2O H

H
HO

f. _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ __

14

1. What is the % R and S of the following?

88 %ee Rthis means 88% R and 12%(R/S mix) therefore 88% R and (6% R/6%S) or 94% R and 6% S
25 % ee Sthis means 25% S and 75%(R/S mix) therefore 25% S and (37.5% R/37.5%S) or 62.5% S and 37.5% R
42 % ee Rthis means 42% R and 58%(R/S mix) therefore 42% R and (29% R/29%S) or 71% R and 29% S
91 % ee Rthis means 91% R and 9%(R/S mix) therefore 91% R and (4.5% R/4.5%S) or 95.5% R and 4.5% S
68 % ee Sthis means 68% S and 32%(R/S mix) therefore 68% S and (16% R/16%S) or 84% R and 16% S
2. What is the % ee for the following?
90 % R 10 % S90-10 = 80% ee R

40 % R 60 % S60-40 = 20% ee S

70 % R 3 % S70-30 = 40% ee R

85 % R 15 % S85-15 = 70% ee R

74 % R 26 % S74-26 = 48% ee R
3. If the observed rotation is +35 and the pure R rotates at +43, what is the % ee, % R and % S?
% ee = obs/sp x 100 = 35/43 x 100 = 81% ee R
81 % ee Rthis means 81% R and 19%(R/S mix) therefore 81% R and (9.5% R/9.5%S) or
90.5% R and 9.5% S
4. If the % ee = 50%R and pure S rotates at 20, what is the observed rotation?
Pure S = -20 then R = +20
% ee = obs/sp x 100; 50 = x/+20 x 100; 50 = 100x/20; (50)(20) = 100 x; 1000 = 100 x;
x = 10, therefore the observed rotation is +10
5. (2S, 3R, 4R, 5S)-2,3,4,5-tetrachlorononane is made in the lab using stereospecific reactions. What is the
stereochemistry of the enantiomer of that molecule? What is the stereochemistry of one of the diastereomers?
How many possible stereoisomers are there for this molecule?
Enantiomer

2R, 3S, 4S, 5R

Possible isomers 2N = 24 = 16
Diastereomer

2R, 3R, 4R, 5S

2S, 3S, 4R, 5S

2S, 3R, 4S, 5S

2S, 3R, 4R, 5R

2S, 3S, 4S, 5R

2R, 3R, 4S, 5R

2R, 3S, 4R, 5R

2R, 3S, 4S, 5S

2R, 3S, 4R, 5S

2R, 3R, 4S, 5S

2R, 3R, 4R, 5R

2S, 3R, 4S, 5R

2S, 3S, 4R, 5R

2S, 3S, 4S, 5S

15

6. Four stereoisomers of dibromopentane are isolated. Fill in the blanks using the 4 isomers below.
RR

RS

SR

RR has the same bp as

SS

SS has the same solubility as

RR

RS has a different bp from

SR

SS

7. In the following pairs, label them as the same molecule, enantiomers or diastereomers.

a. E NA NT IO M E RS

1,2 tra ns

1,2 trans
H

1
R
OH
Br

H 3C

Br

2
HO

2
1 Br

HO

b. SAM E

C H3

S
HO

2
1 Br

H 3C

Cl

1
1

Br

d. EN AN T IO M E RS

H 3 CH 2 C

C H3

H3 C

CH 2 CH 3

c. D IA ST E R EO M E RS

Br

Cl

(2R ,3R )-2,3- dichlor opentane a nd

e. DI AST ER E OM ER S
(2S,3R )- 2,3-dichloropentane

HO

H
C H 2 OH

2
C H 2 OH

HO

f. E NA NT IO M E RS

16

a. ___________________

b. ___________________

Cl
Br

c. ___________________

Cl
Br

Br

H3C

H3C

OH

OH

Br

d. ____________________
C2H5

C2H5

Br

e. ____________________
HO
Br

CH3

HO
H3C

f. ____________________

2R, 3R, 4S

2S, 3S, 4S

2R, 3R, 4S, 5R, 6S

2S, 3S, 4R, 5S, 6R

g. ____________________

17

a.

Diastereomers

b.

Same

c.

Enantiomers

Cl
Br
Cl
Br

Br

H3C

H3C

OH

C2H5

OH

Br

C2H5

Br

e. SAME

HO
Br

d. Diastereomers

CH3

HO
H3C

3
f. Diastereomers

2R, 3R, 4S

2S, 3S, 4S

2R, 3R, 4S, 5R, 6S

2S, 3S, 4R, 5S, 6R

g. Enantiomers

18

Br

Br

H
H

Br

Cl

Cl

Cl

I
Br

Cl

Cl

Cl

Br

Br

Br

H3C

Cl

I
F

Br

(2R, 3R, 4S, 5R)

(2S, 3S, 4R, 5S)

Cl

19

SAME
ENANTIOMERS
H

Br

Br

SAME

Br

Cl

Cl

Cl

I
Br

Br

H3C

Cl

DIASTEREOMERS

H
Br

DIFFERENT CMPDS
Cl

Cl

ENANTIOMERS
Br

Cl

I
F

Br

(2R, 3R, 4S, 5R)

(2S, 3S, 4R, 5S)

Cl

DIASTEREOMERS
H

ENANTIOMERS

20

OH

Br

OH

HO CH2 CH3

H 3C H

H3C OH

Br

OH

OH

E N AN T IO M ER S

D IA S T E R E O M E R S

Br

HO CH2CH3

H 3C H

H3C OH

DIASTEREOMERS
Br

SAME MOLECULE

SAME MOLECULE

21

Homework, Chapter 5

Name:

Label the priority of the four groups connected to the stereocenter and then determine if
the stereochemistry is R or S.

OH

F Br

Br

Cl

Cl

HO

Br

H
Cl

H3CO SH

Br

Br

OH
H

SCH3

22

Homework, Chapter 5

KEY

Label the priority of the four groups connected to the stereocenter and then determine if
the stereochemistry is R or S.

3
OH

Cl

Br
H

Cl

H3CO SH

2,3,3-trimethylpentane

1
1

O 2

Br

1R

Br

2
3

A2
B

C
H

1 Br H

Cl

HO

F Br 1

3
H3CS

OH