Transcript Organic Chemistry

Organic
Chemistry
William H. Brown
Christopher S. Foote
Brent L. Iverson
3-1
Stereoisomerism
and Chirality
Chapter 3
3-2
Isomers
 Isomers:
different compounds with the same
molecular formula
 Constitutional isomers: isomers with a different
connectivity
 Stereoisomers: isomers with the same
connectivity but a different orientation of their
atoms in space
3-3
Chirality
 Chiral:
from the Greek, cheir, hand
• an object that is not superposable on its mirror image
 Achiral:
an object that lacks chirality; one that
lacks handedness
• an achiral object has at least one element of symmetry
• plane of symmetry: an imaginary plane passing
through an object dividing it so that one half is the
mirror image of the other half
• center of symmetry: a point so situated that identical
components are located on opposite sides and
equidistant from that point along the axis passing
through it
3-4
Elements of Symmetry
 Symmetry
in objects
3-5
Elements of Symmetry
 Plane
of symmetry (cont’d)
mirror
plane
HO
OH
3-6
Chiral Center
 The
most common (but not the only) cause of
chirality in organic molecules is a tetrahedral
atom, most commonly carbon, bonded to four
different groups
 A carbon with four different groups bonded to it
is called a chiral center
• all chiral centers are stereocenters, but not all
stereocenters are chiral centers (see Figure 3.5)
 Enantiomers:
stereoisomers that are
nonsuperposable mirror images
• refers to the relationship between pairs of objects
3-7
Enantiomers
 2-Butanol
• has one chiral center
• here are four different representations for one
enantiomer
OH
C H
H3 C
CH2 CH3
(1)
H
H3 C
OH
C
CH2 CH3
(2)
H OH
OH
(3)
(4)
• using (4) as a model, here are two different
representations for the enantiomer of (4)
OH
(4)
OH
OH
representations for the
enantiomer of (4)
3-8
Enantiomers
 The
enantiomers of lactic acid
• drawn in two different representations
O
OH
HO
O
C
C
C
C
H
CH3
OH
HO
O
O
OH
OH
H
CH3
HO
OH
3-9
Enantiomers
 2-Chlorobutane
Cl
CH3 CHCH2 CH3
H Cl
Cl H
3-10
Enantiomers
 3-Chlorocyclohexene
Cl
Cl
3-11
Enantiomers
A
nitrogen chiral center
+
+
N
H3 C
N
CH2 CH3
CH3 CH2 CH3
A pair of enantiomers
3-12
R,S Convention
 Priority
rules
1. Each atom bonded to the chiral center is assigned a
priority based on atomic number; the higher the
atomic number, the higher the priority
(1)
(6)
-H
-CH3
(7)
-N H2
(8)
(16)
(17)
- OH
- SH
- Cl
(35)
(53)
- Br
-I
Increasing priority
2. If priority cannot be assigned per the atoms bonded to
the chiral center, look to the next set of atoms; priority
is assigned at the first point of difference
(1)
- CH 2 -H
(6)
- CH 2 -CH 3
(7)
- CH 2 -NH2
(8)
- CH 2 -OH
Increasing priority
3-13
R,S Convention
3. Atoms participating in a double or triple bond are
considered to be bonded to an equivalent
number of similar atoms by single bonds
-CH=CH2
O
-CH
is treated as
is treated as
C
C
-CH-CH2
O C
C
O
H
C CH
is treated as
C C
C C H
C C
3-14
Naming Chiral Centers
1. Locate the chiral center, identify its four substituents, and assign
priority from 1 (highest) to 4 (lowest) to each substituent
2. Orient the molecule so that the group of lowest priority (4) is
directed away from you
3. Read the three groups projecting toward you in order from
highest (1) to lowest priority (3)
4. If the groups are read clockwise, the configuration is R; if they are
read counterclockwise, the configuration is S
H Cl
(S)-2-Chlorobutane
S
2
1
3
3-15
Naming Chiral Centers
• (R)-3-Chlorocyclohexene
Cl
3
1
H
2
R
• (R)-Mevalonic acid
1
1 4
HO CH3 O
HO
3
2
R
OH
3
2
3-16
Enantiomers & Diastereomers
a molecule with 1 chiral center, 21 = 2
stereoisomers are possible
 For a molecule with 2 chiral centers, a maximum
of 22 = 4 stereoisomers are possible
 For a molecule with n chiral centers, a maximum
of 2n stereoisomers are possible
 For
3-17
Enantiomers & Diastereomers
 2,3,4-Trihydroxybutanal
• two chiral centers
• 22 = 4 stereoisomers exist; two pairs of enantiomers
CHO
CHO
H
C
OH HO
C
H
H
C
OH HO
C
H
CH2 OH
CH2 OH
A pair of enantiomers
(Erythreose)
CHO
CHO
H
C
OH HO
C
H
HO
C
H
C
OH
CH2 OH
H
CH2 OH
A pair of enantiomers
(Threose)
 Diastereomers:
• stereoisomers that are not mirror images
• refers to the relationship among two or more objects
3-18
Enantiomers & Diastereomers
 2,3-Dihydroxybutanedioic
acid (tartaric acid)
• two chiral centers; 2n = 4, but only three stereoisomers
exist
COOH
COOH
H
C
OH HO
C
H
H
C
OH HO
C
H
COOH
COOH
A meso compound
(plane of symmetry)
 Meso
COOH
COOH
H
C
OH HO
C
H
HO
C
H
C
OH
COOH
H
COOH
A pair of enantiomers
compound: an achiral compound
possessing two or more chiral centers that also
3-19
has chiral isomers
Enantiomers & Diastereomers
 2-Methylcyclopentanol
CH 3 OH
HO H 3 C
H
H
H
H
cis-2-Methylcyclopentanol
(a pair of enantiomers)
CH3 H
diastereomers
H H3 C
H
OH
H
HO
trans-2-Methylcyclopentanol
(a pair of enantiomers)
3-20
Enantiomers & Diastereomers
 1,2-Cyclopentanediol
OH HO
H
OH HO
H
H
H
cis-1,2-Cyclopentanediol
(a meso compound)
OH
H
H
diastereomers
HO
OH H
H HO
trans-1,2-Cyclopentanediol
(a pair of enantiomers)
3-21
Enantiomers & Diastereomers
 cis-3-Methylcyclohexanol
H3 C
OH HO
CH3
3-22
Enantiomers & Diastereomers
 trans-3-Methylcyclohexanol
H3 C
CH3
OH
HO
3-23
Isomers
rotation about
single bonds
Compounds with the
same molecular formula
same
connectivity
different
connectivity
Cis,Trans
(E,Z) Isomers
(can be called
diastereomers)
rotation
restricted
Constitutional
Isomers
Stereoisomers
stereoisomers
but no chiral centers
Conformations
Conformational
Isomers
with chiral centers
m ore than
one chiral center
achiral
Meso
Compounds
Atropisomers
one chiral center
chiral
not mirror
images
Diastereomers
mirror
images
Enantiomers
Enantiomers
3-24
Properties of Stereoisomers
 Enantiomers
have identical physical and
chemical properties in achiral environments
 Diastereomers are different compounds and have
different physical and chemical properties
• meso tartaric acid, for example, has different physical
and chemical properties from its enantiomers (see
Table 3.1)
3-25
Plane-Polarized Light
 Ordinary
light: light vibrating in all planes
perpendicular to its direction of propagation
 Plane-polarized light: light vibrating only in
parallel planes
 Optically active: refers to a compound that
rotates the plane of plane-polarized light
3-26
Plane-Polarized Light
• plane-polarized light is the vector sum of left and right
circularly polarized light
• circularly polarized light reacts one way with an R
chiral center, and the opposite way with its enantiomer
• the result of interaction of plane-polarized light with a
chiral compound is rotation of the plane of polarization
3-27
Plane-Polarized Light
 Polarimeter:
a device for measuring the extent of
rotation of plane-polarized light
3-28
Optical Activity
• observed rotation: the number of degrees, , through
which a compound rotates the plane of polarized light
• dextrorotatory (+): refers to a compound that rotates
the plane of polarized light to the right
• levorotatory (-): refers to a compound that rotates of
the plane of polarized light to the left
• specific rotation: observed rotation when a pure
sample is placed in a tube 1.0 dm in length and
concentration in g/mL (density); for a solution,
concentration is expressed in g/ 100 mL
COOH
C
H
H3 C
OH
(S)-(+)-Lactic acid
21
[] D = +2.6°
COOH
H C
CH3
HO
(R)-(-)-Lactatic acid
21
[] D = -2.6°
3-29
Optical Purity
 Optical
purity: a way of describing the
composition of a mixture of enantiomers
Percent optical purity =
[]sample
[]pure enantio mer
x 100
 Enantiomeric
excess: the difference between the
percentage of two enantiomers in a mixture
[R] - [S]
x 100 = %R - %S
Enantiomeric excess (ee) =
[R] + [S]
• optical purity is numerically equal to enantiomeric
excess, but is experimentally determined
3-30
Enantiomeric Excess
Example: a commercial synthesis of naproxen, a
nonsteroidal anti-inflammatory drug (NSAID), gives the S
enantiomer in 97% ee
CH3
COOH
H3 CO
(S)-Naproxen
Calculate the percentages of the R and S enantiomers in
this mixture
3-31
Resolution
 Racemic
mixture: an equimolar mixture of two
enantiomers
• because a racemic mixture contains equal numbers of
dextrorotatory and levorotatory molecules, its specific
rotation is zero
 Resolution:
the separation of a racemic mixture
into its enantiomers
3-32
Resolution
 One
means of resolution is to convert the pair of
enantiomers into two diastereomers
• diastereomers are different compounds and have
different physical properties
A
common reaction for chemical resolution is
salt formation
+
:B
RCOOH
(R,S)-Carboxylic (R)-Base
acid
-
+
RCOO HB
(R,R)-Salt + (S,R)-Salt)
• after separation of the diastereomers, the
enantiomerically pure acids are recovered
3-33
Resolution
• racemic acids can be resolved using commercially
available chiral bases such as 1-phenylethanamine
NH2
NH2
(S)-1-Phenylethanamine
(R)-1-Phenylethanamine
• racemic bases can be resolved using chiral acids such
as
OH O
HO
H3 C CH3
O
OH
HO
OH
HOOC
COOH
CH3
O
OH
O
OH
(2R,3R)-(+)-Tartaric acid (S)-(-)-Malic acid (1S,3R)-(+)-Camphoric acid
3-34
3-35
Resolution
 Enzymes
as resolving agents
O
OEt
EtO
CH3
H3 C
H3 CO
+
O
OCH3
Ethyl ester of (S)-naproxen
1. esterase
NaOH, H2 O
2 . HCl, H2 O
O
Ethyl ester of (R)-naproxen
(not affected by the esterase)
OH
CH3
H3 CO
(S)-Naproxen
3-36
Amino Acids
• the 20 most common amino acids have a central
carbon, called an -carbon, bonded to an NH2 group
and a COOH group
• in 19 of the 20, the -carbon is a chiral center
• 18 of the 19 -carbons have the R configuration, one
has the S configuration
• in the D,L system, all have the L configuration
• at neutral pH, an amino acid exists as an internal salt
• in this structural formula, the symbol R = a side chain
side chain
O
H3 N
-
O
R
Ionized or zwitterion
form of an amino acid
3-37
Proteins
• proteins are long chains of amino acids covalently
bonded by amide bonds formed between the carboxyl
group of one amino acid and the amino group of
another amino acid
R
O
H
N
H3 N
O
R
R
N
H
O
H
N
n
O
OR
for most proteins, n= 10-750
3-38
Chirality in the Biological World
 Except
for inorganic salts and a few lowmolecular-weight organic substances, the
molecules of living systems are chiral
 Although these molecules can exist as a number
of stereoisomers, generally only one is produced
and used in a given biological system
 It’s a chiral world!
3-39
Chirality in the Biological World
 Consider
chymotrypsin, a protein-digesting
enzyme in the digestive system of animals
• chymotrypsin contains 251 chiral centers
• the maximum number of stereoisomers possible is 2251
• there are only 238 stars in our galaxy!
3-40
Chirality in the Biological World
 Enzymes
are like hands in a handshake
• the substrate fits into a binding site on the enzyme
surface
• a left-handed molecule will only fit into a left-handed
binding site and
• a right-handed molecule will only fit into a righthanded binding site
• enantiomers have different physiological properties
because of the handedness of their interactions with
other chiral molecules in living systems
3-41
Chirality in the Biological World
• a schematic diagram of an enzyme surface capable of
binding with (R)-glyceraldehyde but not with (S)glyceraldehyde
3-42
Stereoisomerism
and Chirality
End Chapter 3
3-43