SN2 – Substitution, Nucleophilic, Bimolecular

H3C CH3 CH3

H C OTs Nu C OTs Nu H
H H H H
Nu
Transition State

Rate = k [CH3CH2OTs] [ Nu- ] ---------Bimolecular

Backside Nucleophilic Attack – Inversion in Configuration

H3C CH3 CH3
H C Br HO C Br HO H
C6H13 H C6H13 C6H13
HO
S-(+)-2-Octanol
R-(-)-2-Bromooctane Transition State
Optically Active
Enantiomericaly Pure
Concerted Mechanism
Inversion of Stereochemistry
 SN1 – Substitution, Nucleophilic, Unimolecular
(CH3)3CCl + 2 H2O (CH3)3COH + 2 H3O+ + Cl -

Slow Step (RDS)

 
CH3 CH2
H3C C Cl + Cl
CH3 H3C CH3
                              
Aided by polar Solvent Stable 3o Carbocation
ions are stabilized via solvation

CH2 Fast Step CH3

Professor George Olah H3C C O H
Nobel Prize 1994 H3C CH3 CH3 H
O H
Carbocation is sp2-planar H
- H+
more stable Front or Backside Attack
R H H CH3
R C > R C > R C
R R H H3C C O H
R groups are electron releasing CH3
- delocalise the positive charge tert-Butyl alcohol
 CH2CH3
H3CH2CH2C - HBr HO C CH3
H3C C Br CH2CH2CH3
H3CH2C
H3CH2CH2C +
S-3-Bromo-3-methylhexane H3C C OH
H3CH2C
1:1 Mixture of R- and S-3-Methyl-3-hexanol

The Carbocation intermediate is

attacked by water from either side by
the same rate
STEREOCHEMISTRY
Isomers are different compounds that have the same molecular formula
Structural isomers are isomers that differ because their atoms are
connected in a different order

CH3OCH3 ---- dimethyl ether and

CH3CH2OH ---- ethanol

Stereoisomers differ only in the arrangement of

their atoms in space
Geometric Isomers

Cl H Cl H
C2H2Cl2
Cl H H Cl
cis-1,2-Dichloroethene trans-1,2-Dichloroethene
 Enantiomers are stereoisomers whose molecules are
nonsuperimposable mirror images of one another
Objects that are superimposable on their
mirror images are said to be achiral

Involves a tetrahedral sp3 atom H

CH3 C CH2 CH3
OH
Chiral Centre
2-Butanol
CH3 CH3
HO H H OH Interchanging any two groups at a chiral
C C
centre (stereocentre) that bears four
CH2 CH2 different groups converts one enantiomer
CH3 CH3 into another
 Nobel Prize 2001

Professor William Knowles

 
Professor Ryoji Noyori
Professor K. Barry Sharpless

                              

For synthesis of optically active compounds – asymmetric synthesis

SN2
H3C CH3 CH3
H C Br HO C Br HO H
C6H13 H C6H13 C6H13
HO
S-(+)-2-Octanol
R-(-)-2-Bromooctane Transition State

Inversion of Stereochemistry
 One structure can be superimposed on another

CH3 CH3 If any of the groups

H C OH HO C H attached to the
tetrahedral atom are
CH3 CH3 the same, the centre
is achiral.
2-Propanol

The ultimate way to test for Screwdriver is achiral

molecular chirality is to construct Socks are achiral
models of the molecule and its
Golf club is chiral
mirror image and then determine
Gloves are chiral
whether they are superimposable

A molecule will not be chiral if it possess a

centre or plane of Symmetry
 Properties of Enantiomers
Enantiomers have identical melting points and boiling points
Enantiomers have identical solubilities in solvents
Enantiomers have identical spectra and refractive index
Enantiomers interact, and react with achiral molecules in the
same manner
Enantiomers interact and react with other
chiral molecules at different rates
Enantiomers rotate plane-polarised light by
equal amounts but in opposite directions
Chiral molecules are
optically active Plane-polarised light

Oscillation of electrical field of ordinary light

occurs in all possible directions
Polarimeter is a devise used to measure the effect of plane-
polarised light on an optically active compound
 No Correlation between the direction of rotation of plane
polarised light and the absolute configuration of a molecule
Clockwise Rotation (+) – dextrorotatory
Anti-Clockwise Rotation (-) – levorotatory

Same Configuration

CH3 CH3
H2 C H2C
C H C H
HO Cl
CH2CH3 CH2CH3

(R)-(+)-2-Methyl-1-butanol (R)-(-)-1-Chloro-2-methylbutanol

An equimolar mixture of two enantiomers is called a Racemic Mixture

It is Optically Inactive
O O

H
H

S-(+)-Carvone R-(-)-Carvone

Principle component of Principle component

Caraway seed oil and of Spearmint oil and
responsible for the responsible for the
characteristic odour characteristic odour

Receptor Sites in the Nose are Chiral

STEREOISOMERISM
AND CHIRALITY

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 Enantiomers
• Isomers that are non-superimposable
mirror-images

W W

C C
X Y Y X
Z Z

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Locating a Stereocenter (Chiral
Carbon)
O

*
CH3 CH C OH

OH
Lactic acid

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 Locating a Stereocenter

Br

CH3 CH2 CH2 CH2 CH2 C* CH2 CH2 CH2 CH3

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Locating a Stereocenter
O

CH3
*
H

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Locating a Stereocenter
H CH3
no stereocenter

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Locating a Stereocenter
CH3

Cl

no stereocenter

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Coniine: The Compound that
Killed Socrates
H

N CH2 CH3
* CH2

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Is there a stereocenter?
HO C CH

Nope!

CH3

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Serine: one of the essential
amino acids
O
*
H2N CH C OH

CH2

OH

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Carvone: mirror-image isomers
have different flavors and odors!
O

CH3

CH3 *
C

CH2

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Muscone: the sex attractant of
the musk deer
O

*
CH3

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 Cholesterol: how many
stereocenters can you find?
CH3

CH3
*CH CH2
CH2
CH2
CH3
* * CH
CH3
CH3
* * *
*
HO

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Crystals of Sodium Ammonium
Tartrate

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 Optical Isomerism
• Difference in the way that isomers interact
with polarized light
– Differences arise from molecular symmetry
properties
– this is another type of stereoisomerism.

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 Ordinary Light
(showing magnetic and electric field vectors)

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Double Refraction

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The “Picket Fence Analogy”

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Optical Activity

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The Polarimeter

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 Specific Rotation

t 
[
 cl

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 Configuration

• Arrangement in space of atoms or groups

around the chiral part of the molecule

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Specification of Configuration

1
2 2 1
C
C
4 4
3 3

R S
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 Specification of Configuration
• SEQUENCE RULE 1: If the four atoms
attached to the chiral carbon are all
different, priority depends on atomic
number, with the atom of higher atomic
number receiving the higher priority.
• COROLLARY: If two atoms are isotopes
of the same element, the heavier isotope is
assigned the higher priority
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 I I

C C
F F
Cl Br Br Cl

R S

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 Specification of Configuration
• SEQUENCE RULE 2: If the relative
priority of two groups cannot be decided by
Rule 1, it shall be determined by a similar
comparison of the next atoms in the groups
(and so on, if necessary), working outward
in ranks from the chiral carbon.
– hydrogen atoms are ignored when the atoms
within a rank are compared to each other.

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 Specification of Configuration
SEQUENCE RULE 3: A doubly-bonded atom A is treated as if there
were two C-A single bonds.

A A (C)
Priorities in the expanded representations are assigned on the basis of
Rule
C2. C

(A)

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 REMEMBER!!!
The atoms shown in parentheses (the
duplicate representations) do not exist!

They are written only for purposes of

assigning priorities.

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 More...
A triply-bonded atom A is treated as if there
were three C-A bonds, as in:
(A) (C)

C A C A

(A) (C)

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 Corollary of Rule 3
• If no other distinction can be made, a real
atom outranks a “fictional” atom.

• NOTE CAREFULLY: This exception is

used only as a last resort!

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 3-Chloro-2-butanol

CH3 CH3 CH3 CH3

H C OH HO C H HO C H H C OH

H C Cl Cl C H H C Cl Cl C H

CH3 CH3 CH3 CH3

enantiomers enantiomers

diastereomers
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 Diastereomers
• Non-mirror-image stereoisomers
• Differ in configuration about some, but not
all, chiral atoms

– have different physical properties

– can be separated by ordinary physical methods
– differ in (R)/(S) sequence

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How Many Stereoisomers Are
Possible?

number of stereoisomers = 2n,

where n = number of chiral atoms

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 2,3-Dichlorobutane

CH3 CH3 CH3 CH3

H C Cl Cl C H Cl C H H C Cl

H C Cl Cl C H H C Cl Cl C H

CH3 CH3 CH3 CH3

enantiomers
meso

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 Is there a NO
stereocenter? ACHIRAL

YES
OPTICALLY
STEREOISOMERS INACTIVE
mirror-image non-mirror-image

ENANTIOMERS DIASTEREOMERS
“always” no plane of plane of
symmetry symmetry
OPTICALLY
n = 1 ACTIVE meso
n = 2 or more
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 Glyceraldehyde
(an aldotriose)

H H O
O
C C

H C OH HO C H

CH2 OH CH2 OH

(+) (-)

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 The Aldotetroses
H H
O O
C C

H OH HO H
Erythrose
H OH HO H

CH2OH CH2OH
(-) (+)

H H
O O
C C

HO H H OH
Threose
H OH HO H

CH2OH CH2OH
(-) (+)

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 The Aldopentoses
CHO CHO CHO CHO

H OH HO H HO H H OH

H OH HO H H OH HO H

H OH HO H H OH HO H

CH2OH CH2OH CH2OH CH2OH

(-) (+) (-) (+)
Ribose Arabinose

CHO CHO CHO CHO

H OH HO H HO H H OH

HO H H OH HO H H OH

H OH HO H H OH HO H

CH2OH CH2OH CH2OH CH2OH

(+) (-) (-) (+)
Xylose Lyxose

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 The Aldohexoses
CHO CHO CHO CHO
H OH HO H H OH HO H
H OH H OH HO H HO H
H OH H OH H OH H OH
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH
(+)-Allose (+)-Altrose (+)-Glucose (+)-Mannose

CHO CHO CHO CHO

H OH HO H H OH HO H
H OH H OH HO H HO H
HO H HO H HO H HO H
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH
(-)-Gulose (-)-Idose (+)-Galactose (+)-Talose

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The Aldohexoses (the other half)
CHO CHO CHO CHO
HO H H OH HO H H OH
HO H HO H H OH H OH
HO H HO H HO H HO H
HO H HO H HO H HO H
CH2OH CH2OH CH2OH CH2OH
(-)-Allose (-)-Altrose (-)-Glucose (-)-Mannose

CHO CHO CHO CHO

HO H H OH HO H H OH
HO H HO H H OH H OH
H OH H OH H OH H OH
HO H HO H HO H HO H
CH2OH CH2OH CH2OH CH2OH
(+)-Gulose (+)-Idose (-)-Galactose (-)-Talose

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WWU Chemistry