CHEM1030: Lecture 7

CHEM1030: Organic Chemistry

Dr Michelle Spencer

Rm 3.2.15

[email protected]

UNIT 7: Isomerism and Stereochemistry

…. continued

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CHEM1030: Lecture 7

Chiral Centres in Rings

• identifying chiral centres in molecules with rings can sometimes be difficult

HO H
COOH - differences in these 2 chains is obvious

these are not - carbons immediately adjacent to chiral centre are clearly different
the same
- chiral because of differences 2 carbons away from chiral centre
because these
are different

• in a ring we may see 2 groups attached which are technically the same (e.g. both
methylenes: –CH2–) but if groups to which they are in turn attached are different, then first
groups are as well
HO H

these are not the same

because these are different

Chiral Centres in Rings

• all these have chiral centres, as indicated

OH OH OH

* * *
Br * * CH3
Br
Br Br

CH3 OH
OH
H * *
* * *
*
* *
H H
HO
estradiol

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CHEM1030: Lecture 7

Fischer Projection Formulas

• developed originally for describing structures of carbohydrates
• carbon chain is written vertically, with most oxidised C at top, and most
reduced C at bottom CHO
glyceraldehyde
H * OH (a three-carbon
carbohydrate)
CH2OH

- horizontal lines in formula show groups that project above plane of paper toward viewer
- vertical lines show groups that project below plane of paper away from the viewer
CHO CHO
H OH H OH
CH2OH CH2OH

There are 4 rules for handling Fischer diagrams:

• rotating whole diagram 180° gives same configuration
• rotating whole diagram 90° gives opposite configuration
• interchanging any 2 groups while leaving other 2 unchanged gives opposite configuration
• keeping 1 group in same position and rotating other 3 gives same configuration

Compounds with >1 Chiral Centre

• compounds that contain ≥2 chiral centres can exist as >2 optical isomers
• maximum number is 2n (n = number of chiral carbons)
OH
an aldotetrose (a four carbon sugar)
* *
HOCH2CHCHCHO 2 chiral carbons, hence
22 = 4 isomers
OH

• There are 2 chiral centres, and hence 4 optical isomers

CHO CHO
H OH HO H pair
of
H OH HO H enantiomers
CH2OH CH2OH
• 2 pairs of enantiomers:
I II
a) I and II are (+) and (–)
CHO CHO
(another) b) III and IV are (–) and (+)
H OH HO H pair
HO H H OH of
enantiomers
CH2OH CH2OH
III IV

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CHEM1030: Lecture 7

Compounds with >1 Chiral Centre

• each compound has 2 optical isomers that are not mirror images
• are diastereomers (I is the diastereomer of III, etc.)
• Diastereomers are stereoisomers that are not mirror images
• have same configuration at 1 asymmetric centre, and different configuration at 2nd centre
• diastereomers are physically different molecules, and have different physical and chemical
properties, such as solubility and melting point

pair of enantiomers pair of diastereomers

CHO CHO CHO

H OH HO H H OH
H OH HO H HO H
CH2OH CH2OH CH2OH

another pair of diastereomers

Meso Compounds
• some molecules have special symmetry properties which reduce number of optical isomers
• hence there are fewer than would be predicted by the 2n rule

* *
HOOC CH CH COOH
tartaric acid
OH OH

This compound has 2 chiral centres, and hence 4 stereoisomers would be predicted:
COOH COOH
H OH HO H non-superimposable
a pair of
HO H H OH enantiomers
COOH COOH
A B

COOH COOH
H OH HO H superimposable
plane of
symetry ≡ therefore identical -
H OH HO H a meso compound
COOH COOH
C D

• structure which contains ≥2 chiral carbons but is superimposable on its mirror image is called
a meso compound
• said to be an optical isomer, even though it has no effect on plane polarised light

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CHEM1030: Lecture 7

Meso Compounds

http://www.youtube.com/watch?v=bzYsE_hnC9g

• physical properties of the three optical isomers of tartaric acid are:

Isomer m.p. α]25
[α
(+)–tartaric acid 170°C +12° * *
HOOC CH CH COOH
tartaric acid
(–)–tartaric acid 170°C -12° OH OH
meso–tartaric acid 146°C 0°

• meso-tartaric acid is optically inactive because one half of molecule is mirror image of other
• hence, any rotation caused by one half of the molecule is counteracted by other half

Chiral Compounds in Biological Systems

• many organic compounds in body contain ≥1 chiral carbons, so ≥2 stereoisomers are possible
• however, it is often found that in nature only 1 of the possible stereoisomers is ever found

Example: cholesterol
- has 8 chiral carbons, so that there are potentially 256 (28) stereoisomers of this compound
- of these, only 1 is found in nature, no matter what organism is being considered

*
* *
cholesterol
* * (a steroid)
8 chiral centres
* *

HO *

• some exceptions:
Example: D-glucose and D-galactose (which are diastereomers), are found in nature, and both
the (+) and (–) forms of lactic acid (enantiomers) are found in different organisms
• however, where several isomers are possible, usually only one is made by a given organism

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CHEM1030: Lecture 7

Chiral Compounds in Biological Systems

Why?
• to do with their reactions
• as a general rule, 1 enantiomer fits into active site of enzymes to allow reaction to proceed,
whereas other enantiomer does not
• in other cases, molecules bind to protein receptors to produce a biological effect, and for
most compounds, only one stereoisomer will have desired effect

(R)-limonene (S)-limonene
orange fragrance lemon fragrance

Chiral Compounds in Biological Systems

O O

(S)-carvone (R)-carvone
spearmint caraway

O
LSD

HN * N hallucinogenic properties depend

on the configuration of this carbon
N
CH3

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CHEM1030: Lecture 7

Chiral Compounds in Biological Systems

H COOH H CH3

CH3 COOH

O O
S-Naproxen R-Naproxen
anti-inflammatory drug liver toxin

OH OH
H H H H
N N
N N
H H H H
HO HO

S,S-Ethambutol R,R-Ethambutol
tuberculostatic causes blindness

COOH COOH
HS HS
H NH2 H NH2

S-Penicillamine R-Penicillamine
antiarthritic causes blindness

Summary
Isomers
Different compounds with the same molecular formula

Structural Isomers Stereoisomers Isomers

Different atom-atom commectivity Same atom-atom commectivity

Structural Isomers

Functional Isomers Positional Isomers

Different functional groups Same functional groups,
different attachment positions
Skeletal Isomers
CH3CH2CH2CH2OH Same functional groups,
different carbon skeletons
and CH3CH2CH2CH2OH

CH3CH2OCH2CH3 and
CH3CH2CH2CH2OH
CH3CH2CHCH3
and
OH
CH3
CHCH2OH
CH3

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CHEM1030: Lecture 7

Summary
Isomers
Different compounds with the same molecular formula

Structural Isomers Stereoisomers Isomers

Different atom-atom commectivity Same atom-atom commectivity

Stereoisomers

Geometric Isomers Diastereomers

Caused by lack of free rotation Parts of molecule are mirror images,
around bonds but not all
Optical Isomers
H3C CH3 (Enantiomers) OH OH
Molecules are non-identical H3C H3C
C C C Cl C Cl
mirror images and
H H
H H C Cl Cl C
and H3C CH3
Br Br
H3C H C and C
H3C Cl Cl CH3
C C Br Br
H CH3

Summary
Structural and Stereo Isomers
• Skeletal isomers- same formula but different carbon skeleton
• Positional isomers- carbon skeleton and functional groups are same but functional groups
occupy different positions on carbon chain
• Functional group isomers- compounds with same formula but different functional groups
• Tautomers- structural isomers that readily interconvert (tautomerization)
• Geometrical isomers- cis-trans
• Optical isomers- pair of enantiomers that plane of polarised light (look for chiral centre)

- enantiomers: stereoisomers that are mirror images of each other that are non-superposable
- diastereomers: steroisomers that are not mirror images (has 2 or more chiral centres)
- meso compound: compound with 2 or more chiral centres with plane of symmetry through
centre of molecule

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CHEM1030: Lecture 7

UNIT 8: Overview of Chemical Reactions

Outline for Unit 8:

OVERVIEW OF CHEMICAL REACTIONS

Introduction:
We will come across seven important types of reaction in the study of organic chemistry: addition,
reduction, oxidation, elimination, substitution, hydrolysis and rearrangement.

McMurryVIII
As a result of this part of the course you should be able to: BrownII reference:
reference:

See Lecture Notes page xv

Problems:
McMurryVIII Ch. 6, problems 1, 20

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CHEM1030: Lecture 7

Overview of Chemical Reactions

During this semester we will come across eight important types of reactions:

1) Addition
2) Reduction
3) Oxidation
4) Substitution
5) Elimination
6) Hydrolysis
7) Condensation
8) Rearrangement

Tutorial Questions
Classify the following reactions as addition, substitution or elimination:

Cl HO– OH
(i) + Cl– substitution

(ii) Cl + HCl elimination

Br
Br2
(iii)
addition
Br
Cl NH3 NH2
(iv) + HCl substitution

HCl Cl
(v) addition

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CHEM1030: Lecture 7

Overview of Chemical Reactions

During this semester we will come across eight important types of reactions:

1) Addition
- addition of a small molecule across a double or triple bond:

Br Cl
Br2 HCl

Br

Example:
- addition of H2O across a double bond is very important in biological systems
OH
H2O

Overview of Chemical Reactions

2) Reduction
- addition of hydrogen across a double or triple bond (special case of an addition; symbol [H]):

O OH

H2 H2
Pt Pt

NO2 H2 NH2
Pt

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CHEM1030: Lecture 7

Overview of Chemical Reactions

3) Oxidation
- addition of oxygen across a double or triple bond; symbol [O]

OH
KMnO4

OH

- or an increase in the number of bonds between oxygen and a carbon, nitrogen or sulphur
O O
CH2OH C C
[O] H [O] OH

alcohol aldehyde acid

one C–O bond two C–O bonds three C–O bonds

NH2 NO2
KMnO4

Overview of Chemical Reactions

Example:
thioethers can be oxidised to sulphoxides or sulphones:

O O
[O] [O]
S S S
O
thioether sulphoxide sulphone

O
S S
[O]

N Cl N Cl
CH2 CH2CH2N(CH3)2 CH2 CH2CH2N(CH3)2
chlorpromazine chlorpromazine sulphoxide

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CHEM1030: Lecture 7

Overview of Chemical Reactions

4) Substitution
- replacement of one atom or group with another:

CH2Br CH2OH
HO–
+ Br–

Overview of Chemical Reactions

5) Elimination

- elimination of a small molecule to form a double or triple bond (opposite of addition):

Br
HO–
+ HBr
(base
catalyst)

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Overview of Chemical Reactions

6) Hydrolysis
- breaking of a bond (lysis) in the presence of water
• most commonly seen in the cleavage (breaking) of ester and amide bonds:
O O
H2O
+
O OH HO

O O
H2O
+ H
N OH N
H
H

Two functional groups react giving a new functional group with the loss of a small molecule
O O
C C
CH3 OH + CH3OH CH3 OCH3 + H2O
acid alcohol ester water

O O
C C
CH3 Cl + NH3 CH3 NH2 + HCl
acid chloride ammonia amide hydrogen chloride

Overview of Chemical Reactions

7) Condensation
- removal of water

6,7) Hydrolysis vs Condensation

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Overview of Chemical Reactions

8) Rearrangement

- reaction generates an isomer, and again the number of bonds normally does not change

Example:
- conversion of double bond of sunscreen octyl methoxycinnamate from cis- to more stable
(but inactive) trans- configuration with time

O H O H
O
H
O H O n-octyl
n-octyl O

cis trans

Overview of Chemical Reactions

Classify the following reactions as oxidation or reduction:

OH O
KMnO4 oxidation
(i)

O
KMnO4 oxidation
(ii)
OH OH

H2/Pt
(iii)
reduction

O OH
LiAlH4 reduction
(iv)

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