04 - Stereochemistry Part 1 3

STEREOCHEMISTRY
CHEM 40 Basic Organic Chemistry

isomers
same formula, different structures
Structural isomers
different bonding arrangement
stereoisomers
same bonding arrangement conformers
enantiomers same compound with different
non-superimposable mirror rotations about single bonds
images
Geometric isomers
different orientations of groups
around double bonds
Isomer Types
CHEM 40 | Basic Organic Chemistry | AJAMagsino
concerned with the 3D structure of organic compounds
concept of “handedness” in chemistry
consider the structure of lactic 3-D/Dash-wedge representation

acid: around the chiral center:
BACK
IN-PLANE
lacks 3D perspective
FRONT
Stereochemistry
FLYING-WEDGE REPRESENTATION
3D representation
upward
H downward
H
*
C *
HO COOH H3 C C COOH
CH3 OH
horizontal bonds - upward
vertical bonds - downward
Stereochemical Representation
FISCHER PROJECTION
3D representation in 2D paper
intersection of two lines indicate

a chiral carbon atom (carbon
atom with 4 non-equivalent
groups attached to it)
Draw the following molecules in
PRACTICE! flying wedge representation and Fischer projection:
Cl
H3C CHO
HO
Br CH2CH3
Convert the following Fischer projections to 3-D
PRACTICE! representations:
Cl
HO CH3
CHO
Br
H CH3
CH2CH3
FISCHER PROJECTION RESTRICTIONS
The formula may not be rotated by 90o or 270o,

only 180o is permissible.
COOH o
180 CH3 90o H
H2N H H NH2 HOOC CH3
CH3 COOH NH2
The formula may not be taken out of the plane of
the paper, i.e. rotation of the whole projection
about the x- or y-axis is not allowed, only at the z-
axis. CH
COOH CH3 3
o
180o 180
H2N H H NH2 H2N H
z-axis
CH3 COOH y-axis COOH
COOH CH3 CH3

o o
180 180
H2N C H H C NH2 H2N C H
z-axis y-axis
CH3 COOH COOH
It is allowed to keep one group fixed and rotate
the other three clockwise or counterclockwise.
Hold -COOH
COOH COOH COOH COOH
H2N H H3C NH2 H CH3 H2N H
CH3 H NH2 CH3
property of non-superimposability
of a molecule with its mirror image
VIDEO ON CHIRALITY: https://www.khanacademy.org/test-prep/mcat/chemical-

processes/stereochemistry/v/chiral-achiral-jay
Chirality
Determine if the following compounds are
PRACTICE! superimposable with their mirror images:
CH3 CH3 CH3
rotate by 180o
H Br Br H along the z-axis H Br
H Br Br H (rotation around H Br
the y-axis is not SUPERIMPOSABLE
CH3 CH3 permissible) CH3 ACHIRAL!
CH3 CH3 CH3
rotate by 180o
H Br Br H Br H
along the z-axis
Br H H Br (rotation around H Br
the y-axis is not NONSUPERIMPOSABLE
permissible) CH3 CHIRAL!
CH3 CH3
Chirality
CHIRAL MOLECULE
a molecule that is not superimposable with its mirror image
Properties:
presence of chiral center(s) or stereocenter AND absence of
plane of symmetry
optical activity – the ability of a substance to rotate the
plane polarized-light
Chirality
CHIRAL MOLECULE
presence of CHIRAL CENTER/ STEREOGENIC CENTER
CHIRAL CENTER – an atom with non-equivalent groups attached

to it
ex. sp3 hybridized C attached to 4 different groups
A A
ü
C
vs. C
D C
B B
C C
NOTE: a molecule can have more than one chiral center
Chirality
Determine the number of chiral centers in the
PRACTICE! following compounds:
1. HOH2C-CHOH-CHO
2. HOOC-CHOH-CHOH-COOH
3. HO-CHOH-CHOH-CHOH-CHOH-CHO
4. H2N-CHOH-COOH
5. H3CCH2CH2CH3
CHIRAL MOLECULE
maximum number of stereoisomers = 2n max # of
where n = no. of chiral centers stereosiomers = 2n
1. HOH2C-CHOH-CHO 21 = 2
2. HOOC-CHOH-CHOH-COOH 22 = 4
3. HO-CHOH-CHOH-CHOH-CHOH-CHO 23 = 8
4. H2N-CHOH-COOH 21 = 2
5. H3CCH2CH2CH3 20 = 1
Chirality
CHIRAL MOLECULE
presence of plane of symmetry
symmetric asymmetric
ACHIRAL CHIRAL
Chirality
Determine whether the following compounds
PRACTICE! contains a plane of symmetry or not:
CH3
H Br
H Br
CH3
Chirality
Determine if the following compounds are chiral or
PRACTICE! achiral:
ACHIRAL ACHIRAL
ACHIRAL CHIRAL
Chirality
CHIRAL CENTERS OTHER THAN CARBON
Quadrivalent chiral atoms

H O16
C S
H O18 N
Tervalent chiral atoms

H
N P C S
www.rowland.harvard.edu
X Z X Z
Y H O
Y
Chirality
Identify the chiral centers in…
PRACTICE!
ephedrine
Chirality
PRACTICE!
aspartame
Chirality
PRACTICE!
H H
HO cholesterol
Chirality
CHIRALITY
CHEAT SHEET
Chirality
Applications and Importance of Stereoisomers
R – rectus L. ‘right’
if the first three high
priority groups rotate in a
clockwise
1 H2N
2
COOH
H
4
CH3 3
R
S
S – sinister L. ‘left’ 2
if the first three high COOH
priority groups rotate in a 3 H3C NH2 1

counterclockwise
H
4
Absolute Configurations
Cahn-Ingold-Prelog Rules
RULE 1: Look at the two atoms directly attached to the chiral center
and rank according to atomic number
3
COOH
1 Br NH2 2
H
4
RULE 2: If a decision can’t be reached by ranking the first atoms in the

substituent, look at the second, third, or fourth atoms away until the
first difference is found.
VS. ü
VS. ü
RULE 3: Multiple-bonded atoms are equivalent to the same number

of single-bonded atoms.
ex. –CH2OH VS. –CHO ü
Determine the sequence of priority in the following
PRACTICE! compounds:
2 1
COOH COOH
3 H3C NH2 1 3 H3C CHO 2
H H
4 4
ASSIGNING ABSOLUTE CONFIGURATIONS
STEP 1: Assign priorities from 1 to 4 to each group bonded to the
stereogenic center.
COOH
3 H3C NH2 1
H
4
STEP 2: Orient the molecule with the lowest priority group at the back
(broken wedge or top or bottom in the Fischer projection) then
visualize the relative positions of the remaining three groups (priorities
1, 2, and 3).
S
assign a configuration R if the first 2
three high priority groups rotate COOH
in a clockwise
assign a configuration S if the first 3 H3C NH2 1
three high priority groups rotate H

in a counterclockwise 4
EXAMPLE
1 • assign priority numbers

4 • rotate the structure to position H
(last priority) at the back. Hold –
2 CH3 and rotate the remaining
3 groups in a clockwise manner
H 4
2
S
1
HOOC C OH (S)-lactic acid
3 CH3
EXAMPLE
1
4
2
3 • clockwise => R
• but H is not at the
back, hence S
• Or without positioning the configuration
last priority (H) at the back,
determine if the top 3
priority is clockwise or
counterclockwise, then take
the opposite of the
configuration
Determine the absolute configuration of the
PRACTICE! following compounds and draw the structure of the
other enantiomer:
NH2
A.
S HOOC
H
C
CH3 R
B. Br
R H 3C
C
CN S
OH
Determine the absolute configuration of the
PRACTICE! following compounds and draw the structure of the
other enantiomer:
C. CH3
S Cl
H R
D. H
S H3CO
C
CH2OH
COOH
R
Multiple Stereocenters
2
COOH
R COOH
consider this
4 as one group
H OH 1 H OH 3
3 HO H 4
HO H
consider this as 1
one group
COOH COOH
2 R
(2R, 3R)-Tartaric Acid
Enantiomers Diastereomers
non-superimposable mirror images not related as mirror images
have identical physical and chemical exists in stereoisomers with more
properties (color, MP, BP, solubility, etc.) than one chiral centers
differ in their rotation of plane-polarized have different physical properties,

light (same magnitude different direction) similar but not identical chemical
properties and different optical
activities
Stereoisomers
the ability of a substance to rotate the plane polarized-light
Optical Activity
the ability of a substance to rotate the plane polarized-light
Dextrorotatory (d) or (+):

rotates light in a clockwise direction
Levorotatory (l) or (-):
rotates light in a counterclockwise direction
S R IMPORTANT!
Optical activity is not the same
with the absolute configuration!
(+) – lactic acid (-) – lactic acid
S–(+)–lactic acid R–(-)–lactic acid
Optical Activity
ENANTIOMERS AND DIASTEREOMERS
non-superimposable not related as mirror images
mirror images
CH3 CH3 CH3
H Br H Br Br H
H Br Br H H Br
CH3 CH3 CH3
I II III
II and III are a pair of enantiomers

I and II, I and III are diastereomers
Stereoisomers
Which of the following are related as diastereomers?
PRACTICE!
as enantiomers?
enantiomers: a-d and b-c
diastereomers: a-b, a-c

b-d, c-d
Stereoisomers
RACEMIC MIXTURES/RACEMATE
a solution of equal amounts of enantiomers, i.e. 1:1 ratio of (+)
and (-) isomer
optically inactive
the two enantiomers rotate plane-polarized light to an equal
extent but in opposite directions, the rotations cancel, and no
rotation is observed
50% (+)-lactic acid and 50% (-)-lactic acid
Stereoisomers
MESO COMPOUND
a molecule with chiral centers but is achiral because it has a
plane of symmetry
optically inactive
common feature is the presence of identical set of substituents

CH3 COOH
H Br H OH
H Br H OH
CH3 COOH
Stereoisomers
Which of the following compounds will have a meso
PRACTICE!
stereoisomer?
CH2OH COOH
CH2OH
H F HO H
F H
F H
H OH
H F
OH
HO H
H F
F H Cl CH2CH3
HO H
F H
CH2OH HO Cl
COOH
CH2OH
CH2CH3
Chirality
Draw all the possible stereoisomers of tartaric acid
PRACTICE! and identify which are related as enantiomers and
diastereomers
COOH
H OH
HO H
COOH
Chirality
FLAVORS AND AROMA
S-(+)-carvone R-(-)-carvone

BIOCHEMICAL PROPERTIES
S-ibuprofen R-ibuprofen

BIOCHEMICAL PROPERTIES
O O
HS HS
OH OH
NH2 NH2
R-penicillamine S-penicillamine
antiarthritic drug mutagen


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STEREOCHEMISTRY

CHEM 40 Basic Organic Chemistry

consider the structure of lactic 3-D/Dash-wedge representation

intersection of two lines indicate

The formula may not be rotated by 90o or 270o,

H2N H H NH2 HOOC CH3

CH3 COOH NH2

COOH CH3 CH3

COOH COOH COOH COOH

H2N H H3C NH2 H CH3 H2N H

CH3 H NH2 CH3

VIDEO ON CHIRALITY: https://www.khanacademy.org/test-prep/mcat/chemical-

CH3 CH3 CH3

CHIRAL CENTER – an atom with non-equivalent groups attached

NOTE: a molecule can have more than one chiral center

Quadrivalent chiral atoms

Tervalent chiral atoms

priority groups rotate in a 3 H3C NH2 1

RULE 2: If a decision can’t be reached by ranking the first atoms in the

RULE 3: Multiple-bonded atoms are equivalent to the same number

3 H3C NH2 1 3 H3C CHO 2

three high priority groups rotate H

1 • assign priority numbers

differ in their rotation of plane-polarized have different physical properties,

Dextrorotatory (d) or (+):

CH3 CH3 CH3

II and III are a pair of enantiomers

enantiomers: a-d and b-c

diastereomers: a-b, a-c

50% (+)-lactic acid and 50% (-)-lactic acid

common feature is the presence of identical set of substituents

Applications and Importance of Stereoisomers

Applications and Importance of Stereoisomers

Applications and Importance of Stereoisomers

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