2
Geometrical cis-trans and E-/Z-isomers Such isomers contain double bonds, which cannot rotate They can also arise from ring structures, wherein the rotation of bonds is greatly restricted
Nomenclature Rules CIP (Cahn-Ingold-Prelog): - ranking all substituents according to atomic number - in case of identical atoms go to the next / adjacent atom 4
Cis isomers
Trans isomers
The same groups are
The same groups are
on the same side of
on opposite sides of the
the C=C bond
C=C bond
Chapter 4
Cis but-2-ene
trans but-2-ene
Geometric isomerism
H
H C=C
H
does not exist in symmetrical alkenes
CH2CH3
But-1-ene
because one C has two identical groups attached
Cis-trans isomers are not mirror images, so these are diastereomers. H
H
CH3 C C
C C H3C
H
CH3
cis-2-butene
H3C H trans-2-butene
DiastereomerďźšIsomers that are non superimposable, not mirror images. 8
The E-Z convention for Cis-Trans Isomers
Br
Br C
CH3
CH3
Br
C
C
H
H
H
C C
C
H
Br
C
C
H
CH3
Br
Br H3C
C
CH3
Br
Br CH3 H
cis-1,2-dimethyl-3,3-dibromocyclopropane
H3C H
C C
H C CH3
trans-1,2-dimethyl-3,3-dibromocyclopropane
Different compounds- different properties.
Conformation (Rotation of C-C Single Bonds) Conformations are different arrangements of atoms that are interconverted by rotation about single bonds. Different conformations also are called conformational isomers or conformers:
12
Conformations of Alkanes: Rotation of C-C Single Bonds
13
Newman projection How to Draw a Newman Projection: Step 1. Look directly down the C—C bond (end-on), and draw a circle with a dot in the center to represent the carbons of the C—C bond.
14
Step 2. Draw the bonds on the front C as three lines meeting at the center of the circle. Draw the bonds on the back C as three lines coming out of the edge of the circle.
Step 3. Add the atoms on each bond.
15
16
• In the eclipsed conformation, the C—H bonds on one carbon are directly aligned with the C—H bonds on the adjacent carbon. • In the staggered conformation, the C—H bonds on one carbon bisect the H—C—H bond angle on the adjacent carbon. • The staggered conformations are more stable than the eclipsed conformations. • Electron-electron repulsion between bonds in the eclipsed conformation increases its energy compared with the staggered conformation.
17
• An energy minimum and maximum occur every 60° as the conformation changes from staggered to eclipsed. Conformations that are neither staggered nor eclipsed are intermediate in energy. • Butane and higher molecular weight alkanes have several C—C bonds, all capable of rotation. It takes six 60° rotations to return to the original conformation.
18
A staggered conformation with two larger groups 180째 from each other is called anti. A staggered conformation with two larger groups 60째 from each other is called gauche. The staggered conformations are lower in energy than the eclipsed conformations. Steric strain is an increase in energy resulting when atoms are forced too close to one another. Gauche conformations are generally higher in energy than anti conformations because of steric strain.
19
Conformations of Butane: Rotation of C2-C3 Single Bond
20
Drawing Cyclohexane
Numbering Cyclohexane
Start anywhere and number consecutive carbons.
hold red bonds in a plane, flip this carbon above the plane. flip the other carbon below the plane you get the other chair conformation.
How to draw the two conformations of
a substituted
cyclohexane: • The two conformations of cyclohexane are different, so they are not equally stable. • Larger axial substituents create unfavorable 1,3-diaxial interactions. • In methylcyclohexane, each unfavorable H,CH3 interaction destabilizes the conformation by 0.9 kcal/mol, so Conformation 2 is 1.8 kcal/mol less stable than Conformation 1.
Substituted Cyclohexane • The larger the substituent on the six-membered ring, the higher the percentage of the conformation containing the equatorial substituent. • With a very large substituent like tert-butyl [(CH3)3C-], essentially none of the conformation containing an axial tert-butyl group is present at room temperature, so the ring is essentially anchored in a single conformation having an equatorial tert-butyl group.
5
up
up 6
down
up 1
up
2
3
down down
up
4 down
4
up
up
up
up
up
down down
5
6 down
down up
1
2 3
down
down
down down
Each carbon has two groups (up and down) cis: When the two groups are on the same side, either both on up bonds or both on down bonds.
trans: When the two groups on opposite sides, one up and one down.
up
trans-1,4-dimethylcyclohexane
The two conformations have one methyl up and one methyl down. Conformations 1 and 2 are not equally stable because conformation 2 has both larger CH3 groups in the equatorial position, it is lower in energy.
cis-1,4-dimethylcyclohexane
The two conformations have the two methyl groups drawn up Both conformations have one methyl group axial and one equatorial, making them equally stable.
Optical isomerism Chirality
Chapter 4
Chiral objects don’t have a plane of symmetry. symmetry
Objects with a plane of symmetry are achiral.
Problem 2.2: chiral objects achiral (non chiral) objects • screw, scissors nail, knife • glove, shoe, jacket sock, pullover • your hand, foot, ear, nose, yourself
32
Configuration Isomers: Isomers with One Chirality Center
A chirality center arises when four
different
substituents
are bonded to a carbon.
33
Two
enantiomers
nonsuperimposable images of each other
are mirror (as
right and left hand).
34
Drawing Enantiomers Perspective Formulas:
35
Naming Enantiomers: The R,S System Cahn, Ingold, Prelog sequence rules: The atom attached to the chiral center with the highest atomic number = 1, next = 2, etc. If the four atoms attached to the chiral center are not all different, the sequence is determined at the first point of difference. The multiply bonded atom as an equivalent number of singly bonded atoms (For example, the C of a C=O is considered to be bonded to two O atoms)
Rotate the number 4 group away from you and observe the sequence 1 3 for the remaining groups. If going from 1
2
If going from 1
2
2
3 is clockwise, then the configuration is R (rectus). 3 is anti-clockwise, then the configuration is S (sinister).
Examples of assigning priorities to stereogenic centers
1
4 2
3
(S)-2-bromobutane
37
1
2 3 R
2
1 3 S
Orienting the lowest priority group in back
R
If group of lowest priority is not bonded by a hatched wedge, switch a pair of groups so that the group of lowest priority is bonded by the hatched wedge: Any one exchange of groups around a stereocenter produces the other stereoisomer Any even number of exchange of groups around a stereocenter produces the original configuration
In drawing arrow from 1 to 2, you can draw past the group of lowest priority (4), but never draw past the group of priority (3):
Optical Rotation
[α ] = Τ λ
α lxc
T = temperature [°C] λ = wavelength [nm] α = measured rotation [°] l = path length [dm] c = concentration [g/mL]
[α ]Tλ = specific rotation 41
Optical Rotation and Absolute Configuration In general there is no relationship between the R or S configuration of an enantiomer and the direction it rotates polarized light. This must be determined by experiment: CH3
CH3 H
H OH
COOH
(S)-(+)-lactic acid
OH
COO-Na+
(S)-(–)-sodium lactate
42
Racemic mixture (racemate) A mixture of equal amounts of two enantiomers is called a racemic mixture (racemate) A racemic mixture is denoted by the prefix (Âą) or dl indicating an equal (1:1) mixture of dextro and levo isomers Also the prefix rac- (or racem-) or the symbols RS and SR are used A racemate is optically inactive, meaning that there is no net rotation of plane-polarized light. Although the two enantiomers rotate planepolarized light in opposite directions, the rotations cancel because they are present in equal amounts.
Chapter 4
R and S configuration Indicate whether the structure has R or S configuration: 2 CH(CH3)2
4
C
CH3
3 CH2CH3
switch CH3 and CH3CH2
CH2Br 1
R 44
Drawing Enantiomers Fischer Projections: vertical bonds horizontal bonds
substituents directed away from the observer substituents dircted toward the observer
46
Fischer Guidelines 1. Fischer formulas may only be rotated 180o in the plane of the paper 2. Any even number of exchange of groups around a stereocenter produces the original configuration 3. Any one exchange of groups around a stereocenter produces the other stereoisomer (R
S, S
R)
4. If manipulation outlined in 2 or 3 allows one Fischer projection to superimpose on another, they are the same steroisomer
Fischer projections
transform molecule to eclipsed conformation in order to construct Fischer projection
The R,S System in case of Fischer projection If the group of lowest priority is on a vertical line, just draw the curve according to decreasing priority. Clockwise
- configuration is R.
Counterclockwise - configuration is S.
(S)-2-bromobutane 50
If the group of lowest priority is on a horizontal line, just draw the curve according to decreasing priority. Clockwise
- configuration is S.
Counterclockwise - configuration is R.
(R)-2-bromobutane 51
Naming Enantiomers: The R,S System Working
with
Fischer
Projections, a rotation of 90째 or a horizontal flip will switch
(R)-2-bromobutane (S)-2-bromobutane
chirality.
(R)-2-bromobutane (S)-2-bromobutane Rotation
of
a
Fischer
projection by 180째in the plane of the paper does not switch the chirality.
(R)-2-bromobutane (R)-2-bromobutane 52
In each case, assign the correct configuration ( R or S) ? To simplify the problem, we convert the three dimension structure into Fisher projection, as follow:
4
2
4 3
1
1
3
4
2
S 1
1 2
3
1
2 4
1
3
3
4
S
4
2 4
3 1
2
4
2 1
3
1
4
4
3
2
4
4
R 1
3
1
2
3
3
1
4
3
R
2
4
4
2
2 4
3
3
2
1
S
2 2
1
2
3
1
4
2
2 1
3
R
3 1
4
1 3
1
2
3
2
3 1 4
4
4 1 2
3
4
1
3
2
4
2
1
3
2
1
R 3
4
1
1 3 2
2 3 4
4 4
2
1
1
2
3 4
3
R 3
1
4
4 3 2
S
2 3 1
2
1
4
2 4
1
2
3
4 3
1
Compounds with more than one chiral center
Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
chiral
chiral
enantiomers
meso-compound
CH3 H
OH
H
OH CH3 2R,3S
2R,3S
achiral
meso forms have a plane of symmetry and/or a center of symmetry The top half of the molecule is mirror image of the bottom half
Other Examples
meso-compound – a compound that has chiral centers but is not chiral (optically inactive).
Erythro and Threo They are diastereomers with two adjacent chiral Carbons, without symmetric ends
Threo isomer
Erythro isomer They have two similar substituents
They have two similar substituents on the opposite side
on the same side
CH2CH3
X CH2CH3
X H
H
R R
H
H
R
Br
e.g. H
R H
e.g.
Br
H
H
Br
Br
Y Y erythro X#Y
CH3
CH3 threo erythro-2,3-dibromopentane
threo-2,3-dibromopentane
X#Y
61
Example 2: 2,3-dichloropentane
Conversion of Newman into sawhrose and Fisher projection
Chapter 4
Conversion of Perspective into Fisher projection D
A B A
C
D
B
C
F
E
E F
E
F
C
B
D
Top left view
A
bottom right view