Organic Chemistry

Selected sections Ch 26, 27 + Ch 11

The chemistry of life and living
things

The chemistry of carbon compounds

See corrections to slides 22, 137 – in red boxes Chem 2

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Evolution of the field Why is organic chemistry important?

• To understand how we interact with

– other organisms (food & nutrients, infections),
– our environment (aromas, pollutants),
– drugs, and
– ourselves (metabolism, growth, immunity,
cancer)

• To understand how things are made, what

they're made of, and how they react with
each other
Chem 3 Chem 4
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Organic Chemistry Components Organic Compounds

1) Structure: The connectivity and 3-D
nature of compounds
2) Theory: Structure and reactivity in
terms of atoms and the electrons
that bind them together
• Why give carbon its own field?
– 98% of all known chemicals are organic
• Inorganic chemistry = the chemistry of
everything else

3) Synthesis: How to design and make • Nearly all pharmaceuticals are organic
new molecules

Chem 5 Chem 6
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 Alkanes
• Hydrocarbons – the simplest organic
compounds (CnH2n+2)

Alkanes • Saturated (all bonding electrons used to

make single bonds)
• Methane (various representations):

Section 26-1, 26-2 Chem 8

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Ethane (C2H6) Propane (C3H8)

Wedged line: bond is coming forward out of the plane

Dashed line: bond is going backward behind the plane
Straight line: bond (and attached group) is in the plane
Chem 9 Chem 10
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How to Draw Organic Molecules Advice and hints

1. Draw molecules in a Zig-Zag shape versus linear structures
vs CH3CH2CH2CH2CH2CH3 • Be neat – messy structures lead to mistakes

2. Assume there are H atoms attached to each carbon in a

Zig-Zag structure, giving valences of 4
• Count your carbon atoms!
H H
H OH
OH • Count the substituents on carbon atoms
H
H H H (including implied H atoms)
3. For reactions, draw out the functional groups in detail and
include lone pairs (electrons)
• In this course, there are never more than four
O bonds to carbon
OH
Chem 11 Chem 12
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 Concept Check: Skeletal/Structural Isomerism

Skeletal or structural isomers have:

- The same molecular formula but different
connectivity.
Structural Diversity
- Different physical properties.

Isomers, cycloalkanes
Concept check:
Draw all structural isomers of C5H12

Section 26-1, 26-3 Chem 14

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Concept Check: Solution Conformations of alkanes

H H H H H Newman Projections
H C C C C C H
H H H H H pentane

H
H C H
H H H
H C C C C H
H H H H
2-methylbutane
H
or methylbutane
H C H Lower E
H H
H C C C H
H H
H C H 2,2-dimethylpropane or
H dimethylpropane Chem 15 Chem 16
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Conformations of alkanes Conformation versus configuration

H atoms in ethane's eclipsed conformation appear to be far
apart, but in reality, they are in contact with each other • Conformation: arrangement of atoms in a molecule that
can be changed by simple rotation of single bonds,
without breaking any bonds.

eclipsed

• Configuration: the permanent geometry of a molecule

resulting from the spatial arrangement of its bonds.
– Must break bonds to change configuration.
staggered

versus

Chem 17 Chem 18
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Conformations of ‘disubstituted ethane’ Eclipsed Conformations
H H
Eclipsed
R'
Anti R Gauche
conformation H H HR R' R HR
conformations
Staggered H H R'
H H H H H H
R' H H
R R R
H H H R' R' H Highest E

H H H H H H
H • All eclipsed conformations have higher energy than all
R' H
staggered conformations.
Lowest E

Chem 19 Chem 20
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Conformations and Potential Energies Conformations and Potential Energies

(Ethane) (Butane)

CH3

Chem 21 Chem 22
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iClicker Question #1 Ring Structures: Cycloalkanes

Which conformation has the highest (least CnH2n
favourable) energy? Assume R, R’ is
methyl.
R R RH
H R' H H
(a) (b) (c) H
H H H H H H
R'
H R'

R R'
R H
R'
(d) H (e)
H H H
H H H
Chem 23 Chem 24
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Molecules are not always flat: Cyclohexane Boat conformation movie

Boat Chair
Chem 25 Chem 26
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Chair conformation movie Axial vs. equatorial substituents.

Cyclohexane Conformations

Boat Chair

Chem 27 Equatorial H atoms are pink, axial H atoms are blue Chem 28
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Ring Strain in Cycloalkanes

Naming

propane cyclopropane

• Bond angles (at C atoms) 109.5o • Bond angles (at C atoms) 60o
• H-atoms are eclipsed

Chem 29
Section 26-1
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 Naming Naming Practice
• Name the following compounds
• Chemistry is a visual science: Structures
are key to understanding reactivity and
physical properties
3-methylhexane 3-ethyl-2,4-dimethylheptane
not not
• Systematic nomenclature: IUPAC rules 2-ethylpentane 3-isopropyl-4-methylheptane
(assumed knowledge)
IUPAC: International Union of Pure and Applied Chemistry

See the supplementary information and podcast about 3-ethyl-5-methylheptane

naming in Avenue for more information not
Chem 31 Chem 32
1AA3 5-ethyl-3-methylheptane 1AA3

Names of common compounds Common compounds (continued)

O
O Benzene
Acetone Acetic acid
OH

O O
Acetaldehyde Ethyl acetate Toluene
H OCH2CH3

O OH
Formic acid Ether CH3CH2OCH2CH3 Phenol
H OH

The acetyl group is

not a “functional O N
Pyridine
group”; it is a Acetyl group H3C
commonly seen
Chem 33 Chem 34
structural motif. 1AA3 1AA3

Some Common Alkyl Substituents (Table 26.1)

More alkyl names
n-butyl
R

sec-butyl
R

R isobutyl

R tert-butyl
Chem 35 Chem 36
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 Substituents Diagnostic iClicker Question
What is the name of this compound?
Vinyl groups R O

Allyl groups O
R
R (a) sec-butyl acetate
Phenyl groups (b) butyl methyl carboxylic acid
(c) ethyl butanoate
O
Example: Allyl acetate (d) isobutyl acetate
O
(e) n-butyl acetate
Chem 37 Chem 38
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Take-Home Practice

C8H18(l) + O 2(g) ?
Reactions of Alkanes
1) What are the products of the reaction at 298K?
2) Write a balanced chemical equation
3) Predict the signs of ΔH, ΔS and ΔG
4) What type of reaction is shown?

Section 26-2 Chem 40

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Take-Home Practice: Solution Halogenation

X2
CH4 CH3X + HX + CH3-CH3
25
C8H18(l) + O2(g) → 8 CO2(g) + 9 H2O(l) Light or heat
2

ΔH° = -5.48 × 103 kJ mol−1 (exothermic!)

ΔSo is negative (note H2O is in liquid form at 298K)

ΔGo = ΔH°-TΔSo, ΔGo should be negative (ΔH° is large)

Reaction type: Combustion, redox

Chem 41 Chem 42
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 Halogenation
Δ or hν
Initiation: Cl-Cl → 2 Cl·

Propagation: H3C-H + Cl· → H3C· + HCl

H3C· + Cl2 → H3C-Cl + Cl· Bonding in alkanes

Termination: Cl· + Cl· → Cl-Cl

H3C· + Cl· → H3C-Cl Hybridization

H3C· + H3C· → H3C-CH3

Applicable also for F2 (often explosive), Br2 (slow),

but not I2 (no reaction) Chem 43 Section 11-3
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Review: Electronic Structure and Bonding Review: Principal Energy Levels

The following section, up to "Review: p-orbitals", is

assumed knowledge and will not be discussed in class. • Electrons are confined to shells defined by the
principal quantum number (n)
The Atom: A dense nucleus surrounded by
a much larger extranuclear space • n = 1, 2, 3 …

• Each shell can contain 2n2 electrons

• The lower the value of n, the lower the energy of

the shell (nearest to the nucleus)
Chem 45 Chem 46
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Review: Orbitals Review: Electron Configuration

• Shells are divided into sub-shells s, p, d, f

Three principles/rules are used to
• p, d, and f orbitals are further divided up
determine the electron configuration:
based on their spatial orientation

Shell Orbitals in that shell Aufbau Principle

n=1 1s Pauli Exclusion Principle
n=2 2s, 2px, 2py, 2pz Hund’s rule

n=3 3s, 3px, 3py, 3pz, + 5 3d

Chem 47 Chem 48
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 Review: Orbitals (subshells) Review: s-orbitals

• Each type of orbital (s, p, d, f) has a Spherical:

distinct shape

• The shape represents the probability of

finding an electron (quantum mechanics)

• Organic chemists are interested in shells

1, 2, and sometimes 3
Chem 49 Chem 50
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Review: p-orbitals Example: Carbon

1s22s22p2
3 of them: px, py, pz

The outer most electrons of atoms (valence

electrons) govern the chemical and physical
properties

Chem 51 Chem 52
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p-Orbital Shapes Methane - CH4

• The p-orbitals in carbon are at 90o to each • Problem: the shape of methane is
other tetrahedral (AX4)

• Bond angles are 109.5o not 90o

• Atoms bonding to a carbon atom should

therefore be situated at 90o to each other…?

Chem 53 Chem 54
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 Hybridization sp3 Hybridization (section 11-3)

• Comes from the word hybrid which

means something is of mixed origin or
composition

• Hybrid orbitals arise by combination of 1s22s22p2 4 sp3 hybrid orbitals

atomic orbitals within an atom Ground state
4 atomic orbitals

Chem 55 Chem 56
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sp3 Hybridization sp3 Hybridization

The number of hybrid orbitals is equal to

the number of combining atomic orbitals

Combine one 2s orbital and three 2p

orbitals Æ four sp3 orbitals

Chem 57 Chem 58
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Bonding-methane iClicker Question #2

How many σ-bonds are there in this
Overlap of sp3 orbitals from carbon and 1s- molecule?
orbitals from hydrogen H H
H
End-on (or end-to-end) overlap H
produces sigma (σ) bonds. H H
109.5o

End-on overlap of sp3-orbitals (a) 1

also produces σ-bonds. (b) 2
(c) 7
(d) 14
Chem 59 Chem 60
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 Take-Home Practice Question
How many sp3-sp3 σ-bonds are there in this
molecule?
Moving beyond alkanes:
Functional Groups

(a) 1
(b) 2
(c) 7
(d) 14
Chem 61
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Sample Problem Sample Problem: Solution

Carboxylic Acid Ester

CO2H
O
H CO2H
N O
H2N OMe H
N
H2N OMe
O
O
Arene
Amine
What functional groups do you see? Amide

Chem 63 Chem 64
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Table 26.2 Table 26.2

O O O O
carboxylic acid
Chem 65 anhydride R O R H3 C O CH3 Chem 66
p. 1154 * Not a functional group 1AA3 1AA3
 Table 26.2 Organic Compounds: Medicines
EtO N
Me2N O
N N
S
N O O
NH
N
O

Arene = any Tamoxifen Viagra

hydrocarbon
containing an
aromatic group H OH OH O
N
(e.g. a benzene- N OH
like ring) O

You must be able to recognize these functional groups

Chem 67
Lipitor Chem 68
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Organic Compounds: Drugs Organic Compounds: Industrial Chemicals

Indigo dye
CH3 OH
CH3 HN O (blue jeans)
CH3

HN O NH
N
H

Stanozolol CO2H
O
H
N Aspartame
H2 N OMe
O

Chem 69 Chem 70
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Organic Compounds: Natural Products Diagnostic iClicker Question

Which functional group is not found in this
O O
molecule? NH2
N

O Cocaine
HO
O

N
(a) alkene H

N
(b) amine
HO Quinine
(c) amide
MeO
(d) phenol
N Chem 71 Chem 72
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 Alkenes (CnH2n)

Alkenes

Section 26-5 Chem 74

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Multiple Covalent Bonds sp2 Hybrid Orbitals (section 11-4)

• Ethylene has a double bond in its Lewis

structure Combine one 2s orbital + two 2p orbitals Æ
three sp2 orbitals (+ one 2p orbital left over)
• VSEPR says trigonal planar shape at C

Hybrid orbital lobes pointing in the direction

of an equilateral triangle: bond angles =120o

sp2 hybridization

Chem 75 Chem 76
p. 461 1AA3 1AA3

sp2 Hybrid Orbitals sp2 Hybrid Orbitals

• The extra p-orbital can be used to form a
π-bond
• π-bonds are covalent bonds that form by
the sideways overlap of parallel p-orbitals

eclipsed p-orbitals staggered p-orbitals

π-bond no π-bond
Chem 77 Chem 78
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 Ethene Recall: Conformations of alkanes

Rotation around C-C single bonds leads

to different conformations.
Section 11-4 Overlap above and below plane of Chem 79 Chem 80
atoms gives one π bond (in total). 1AA3 1AA3

Alkenes have restricted rotation cis versus trans fatty acids: impact of geometry

Geometric Isomers

Restricted rotation leads to different configurations. cis-9-octadecenoic acid trans-9-octadecenoic acid

Rotation requires breaking a pi bond to change configuration. (Oleic acid) (Elaidic acid)

Chem 81 Chem 82
p. 1176 cis trans 1AA3 1AA3

Take-Home Practice Take-Home Practice: Solution

O
Which of these two fatty acids has the
higher melting point and why? RO
HO

O Linoleic acid mp = -5oC

HO
RO Less efficient packing because of kink in chain geometry, therefore
weaker intermolecular forces and lower melting point.

O
O
RO
HO
RO
HO Stearic acid mp = 70oC
Straight chain allows more efficient packing, therefore stronger
Chem 83
intermolecular forces and higher melting point. Chem 84
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 The E,Z System of Nomenclature Assigning E and Z

• Need a new system:

Higher priority Æ
higher atomic number

Look first at atoms directly bonded to double bond.

Look at next set of atoms until a difference in priority is found.

Z isomer E isomer
Assign the Br
High priority groups on High priority groups on molecule
same side opposite sides as E or Z. Cl
Chem 85 Chem 86
p. 1178 1AA3 1AA3

E/Z Take-Home Practice: iClicker Question #3

Label these tamoxifen isomers as E or Z: Which of these molecules has/have a Z configuration?
Me2N O
Me2N O
Cl
Cl Cl
Cl
(i) (ii) (iii)
Z E (A) i
(B) ii
Why is this important?
(C) iii
Tamoxifen (Z-isomer, left) is used to treat hormone
(D) i, ii
dependent breast cancer.
(E) none
The E-isomer (right) can promote cancer growth.
Chem 87 Chem 88
1AA3 1AA3

Organic Compounds: Biological Take-Home Practice

Which is the cis (or Z) double bond in 11-
cis-retinal?
(b)
11-cis-retinal (d)
(c)
(a)
H O
(e)
H O
(d) is the cis (or Z) double bond. We can use the term cis
here because there is only one non-H substituent on each
Chem 89 carbon atom of that double bond. Chem 90
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 Chemical Reactions
• Charge attraction draws molecules together

• In organic chemistry, there is often not a full

Reactions involving cation reacting with an anion
alkenes
• It is more common to have a charged reagent be
attracted to an organic compound that has a
dipole

• The reagent does not necessarily need to be

charged: Lone electron pairs would also be
attracted to a dipole
Section 27-5 Chem 92
p. 1209 1AA3

Chemical Reactions Chemical Reactions

• The majority of reactions in organic

• In most organic reactions the orbitals of
chemistry involve the flow of electrons
the nucleophile and electrophile are
from one molecule to another
directional Æ therefore the two orbitals
• nucleophile (nucleus loving) = electron must be correctly aligned for a reaction to
donor = Lewis base occur

• electrophile (electron loving) = electron

acceptor = Lewis acid

p. 1211 Chem
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93 Chem
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94

Mechanism Mechanism (continued)

• The flow of electrons between a nucleophile and
electrophile can be represented by a double- • The arrow tail starts at the source of the moving
barbed curly arrow electrons and the arrow head indicates its final
destination

NH3 E+
NH3 E+
• The result of the movement is to form a bond
between an electrophile and a nucleophile

H
+
NH3 E+ H N E
H
Chem 95 Chem 96
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 Addition Reactions Explanation of Markovnikov’s rule
ANTI addition (Br atoms Br -
+
add to opposite faces of
alkene)
X H
H Br 2o carbocation - less stable
δ+
δ-

Br - +
Not observed 3o carbocation - more stable

Markovnikov’s rule: the H atom ends up attached to that

H
carbon atom of the double bond that has the most
hydrogen atoms to start with. Br

p. 1240-1241
Chem
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97
haloalkane product Chem
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98

Curly arrows Carbocation stability

• One curly arrow represents electrons moving from the Stability:
alkene π-bond to the proton of HBr, forming a C-H bond.

H3C+ < < <

H Br
δ+
δ-
• The next arrow shows that the bond between H and Br methyl < 1° < 2° < 3°
breaks, with the electron pair going to Br (Br− is formed).

Chem 99 Chem 100

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Carbocation stability iClicker Question #4

H
Electronic: H H
What is the expected product, according to Markovnikov's
C rule?
• Alkyl substituents are electron HI
donating compared with H. H
+
H
C C

• Donating electrons to an electron H H

H H
deficient (positively charged) centre
stabilizes it. H
(a) (b) I
I I
+
H H
I
(c) I (d)
= a permanent electric dipole
δ+ δ-
Chem 101 Chem 102
1AA3 1AA3
 Hydration Reaction Hydration also follows Markovnikov's rule
H
H3O+
+ H2O
HO

+
H H H
O O
H H
• Addition (forward reaction) is favoured in dilute acid
• Elimination (reverse reaction) is favoured in concentrated acid H
H
(conc. H2SO4), heat
H O+
HO
H

H3O+
O H
103 104
p. 1242
Chem
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H Chem
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Reduction of Alkenes Polymerization of Alkenes

Hydrogenation • Monomer Polymer
H
H H H
n
catalyst
C2H4, ethylene polyethylene

• Production of polymer chain follows chain reaction

mechanisms
Catalyst: typically a group 10 metal (Pd, Pt or Ni)
• Initiation often starts with an organic peroxide (R-O-O-R)
SYN addition (H atoms add to same face of alkene) which dissociates by heat into 2 R-O• radicals. These
react with a monomer to complete the initiation.
Chem 105 Chem 106
p. 1240 1AA3 p. 1250-1252 1AA3

Chain Mechanism Examples of Polymers

• Initiation:
R-O-O-R Æ R-O• + •O-R
Name Monomer Polymer Uses
R-O + CH2=CH2 Æ R-O-CH2CH2•
•

• Propagation:
R-O-CH2CH2• + CH2=CH2 Æ R-O-[CH2CH2]2•
R-O-[CH2CH2]n + CH2=CH2 Æ R-O-[CH2CH2]n+1•
•

etc. (chain continues to grow in 2C units)

• Termination:
R-O-[CH2CH2]m• + R-O-[CH2CH2]n• Æ R-O-[CH2CH2]m+nOR
Chem 107 Chem 108
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 Alkynes

Alkynes

According to VSEPR, alkynes are linear

Section 26-5 Chem 110

p. 1175 1AA3

sp Hybrid Orbitals sp Hybrid Orbitals

• Combine one 2s orbital + one 2p orbital Æ

two sp orbitals (+ two 2p orbitals left over)

sp hybridization

Section 11-4, p. 462 Chem 111 Chem 112

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Acetylene: Orbitals

• Acetylene, C2H2, has a triple bond.

• Linear at carbon
Reactions of Alkynes

Chem 113
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 Reduction of Alkenes and Alkynes
H
H H H
Recall: The Carbonyl Group:
catalyst ketones and aldehydes
Similarly:
Pd/C
CH3CH2C CCH3 + 2 H2 CH3CH2CH2CH2CH3

Et CH3
Lindlar's catalyst
CH3CH2C CCH3 + H2
excess
H H
Cis (Z) isomer only!
Chem 115 Section 26-7
p. 1240 1AA3

Examples Structure and Polarity

CH3OH
O O O
Ketones O
H3C 121o 121o 118o 124o 122o 122o
O
O H 118o
H H 118o
CH3 H3C 116o CH3
Acetone Methyl ethyl ketone (MEK) Testosterone

Aldehydes O O AX3 trigonal O δ-

O planar geometry
δ+
H H (sp2-hybridized
H H at C) R R
Formaldehyde Benzaldehyde Cinnamaldehyde
Chem 117 Chem 118
p. 1184 1AA3 1AA3

Primary, Secondary & Tertiary Alcohols

R CH2 OH Primary (1o)

Synthesis and reactions of

aldehydes and ketones R CH OH Secondary (2o)
R'

R''
R C OH Tertiary (3o)

R'
Section 26-7 Chem 120
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 Oxidation of ROH yields Carbonyls Oxidizing Agents
• Primary alcohol Æ aldehyde Æ carboxylic acid • Oxidation: Addition of an O or removal of (a molecule of)
O O hydrogen
[O] [O]
OH H OH
• Agents: commonly metals in high oxidation states
• Secondary alcohol Æ ketone (transfer of 2 to 4 electrons)
e.g., MnO4-, Cr2O72- (KMnO4, K2Cr2O7)
OH O [O] = Oxidizing
[O]
agent
• Usually done in acid or base to facilitate electron transfer

• Tertiary alcohol Æ no reaction • Pyridinium chlorochromate (PCC in CH2Cl2)

– a C-C bond would have to break in order for oxidation to occur – Specific for oxidizing 1o alcohols to aldehydes
Will also oxidize secondary alcohol to ketone
p. 1185
Chem
1AA3
121
(does one oxidation step only) Chem
1AA3
122

iClicker Question #5 Addition Reactions to the Carbonyl Group

What is the expected product of oxidation of Reduction: NaBH4 is a source of H- (hydride)
2-pentanol?
O 1. NaBH4
(a) dimethyl ketone H OH
2. H3O+
(b) 2-pentanone aldehyde 1o alcohol
(c) pentanoic acid
(d) none of the above O 1. NaBH4 OH

2. H3O+
ketone 2o alcohol

Chem 123 Chem 124

1AA3 p. 1185 1AA3

Grignard Reagent Mechanism of Grignard Addition

Formation of a Mg
Grignard R X R MgX
Et2O
reagent: R MgX O MgX
X = Cl, Br or I O
R

Mg δ-
Example: H H
Cl MgCl O
Et2O δ+ H

H
Magnesium is very electropositive:
O
ÆCarbon in Grignard reagent gains partial negative charge + H2O
R
ÆThis carbon now acts as nucleophile + MgX+

Chem 125 Chem 126

(p. 1264, Q78) 1AA3 1AA3
 Mechanism of Grignard Addition C-C bond formation: Addition of a Grignard
The carbanion of Grignard reagent is a Lewis base (in the
extreme view it has a C with a lone pair of electrons and a O 1. CH3MgBr, Et2O OH
negative charge).
H 2. H3O+ H
This carbanion donates an electron pair to the slightly positive aldehyde 2o alcohol
(δ+) carbon atom of a carbonyl group (such as those in
aldehydes, ketones, or carbon dioxide). This C atom is a Lewis
acid (electron deficient). MgCl , Et2O OH
O 1.
This forces the π bond between carbon and oxygen to break;
the π bond electrons end up as a lone pair on O. 2. H3O+
This results in the formation of a C-C bond, and a negatively ketone
charged O atom. 3o alcohol
Addition of acid produces a neutral functional group (alcohol, or
carboxylic acid if you started from CO2).
Chem 127 Chem 128
1AA3 1AA3

Examples

Synthesis and Reactions of

Carboxylic Acids and
Derivatives

Section 26-7 Chem 130

p. 1187 1AA3

Carboxylic Acid: Structure

Carboxylic Acid
Reactivity and Synthesis

Chem 131 Section 26-7

1AA3
 Carboxylic acids Preparation of Esters
Weak acids: O
O H+
O O + CH3CH2OH + H2O
+ H2O + H3O+ Ka = 1.4x10−5 OH OCH2CH3
OH O-
O O
+
+ H2O
NaOH + + H
Na + 3O
H2O
OH O- • Fischer Esterification
• Acid catalyst

Derivatives: • Condensation reaction

O O O O O

R Cl R O R R O R R NHR
Acid chloride Anhydride Ester Amide

Chem
1AA3
133
p. 1188 Chem
1AA3
134

Hydrolysis of Esters Synthesis of RCOOH

O H+ O • Oxidation of 1° alcohol or aldehyde – seen
+ CH3CH2OH
+ H2O
OCH2CH3 OH
• Addition of Grignard to CO2, with acid work-up
• Reverse of previous reaction
• Also requires acid catalyst
1. CO2
R MgX R CO2H
• Use excess water, heat 2. H3O+

O=C=O

Chem 135 Chem 136

1AA3 1AA3

Challenging Naming Practice

• Draw the following compounds

Substitution Reactions and

E-7-methylocta-3,6-dienoic acid O OH Cl
Mechanisms
O

Cl
propyl 4,5-dichloro-3-hydroxyhexanoate

cis-3-chlorocyclohexanal Chem 137 Section 27-2

1AA3
 Substitution Reactions at sp3 Hybridized Carbon SN2 Mechanism

Charged nucleophiles S = substitution; N = nucleophilic, 2 = bimolecular

Neutral nucleophiles
Rate = k[OH-][CH3Cl]

p. 1212
Chem
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139
p. 1213 Chem
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140

iClicker Question #6 SN2 Mechanism

What are the nucleophile and the electrophile in this reaction? δ- δ-

Na+OCH3- + CH3Br CH3OCH3 + NaBr

Nucleophile Electrophile
(a) −OCH
3 Br−
(b) −OCH
3 CH3Br
(c) CH3Br −OCH
3

(d) Na+ CH3Br

Chem 141 Chem 142
1AA3 p. 1216 1AA3

SN2: Inversion of Configuration SN1 Mechanism (unimolecular)

SN2 shows only inversion

SN1 can show mixture of inversion and retention of

p. 1216 stereochemistry because of carbocation in Step 1
Chem 143 Chem 144
1AA3 1AA3
 SN1 Mechanism SN1 versus SN2
• The mechanism depends on many factors, but as
a general rule:

• 1o electrophile = SN2
slow

t – less stable carbocation intermediate, less steric

fas
Rate = k [(CH3)3CBr]
t hindrance to nucleophilic attack
fas
• 2o electrophile = ?
– hard to predict (you will see this next year)

• 3o electrophile = SN1
– more stable carbocation intermediate, more steric
hindrance to nucleophilic attack
Chem 145 Chem 146
1AA3 1AA3

Carbocation stability Carbocation stability

H
Stability: 2. Electronic: H H
H3C+ < < <
C
• Alkyl substituents are electron
methyl < 1° < 2° < 3° donating compared with H. H
+
H
C C

Two ways for alkyl substituents to increase cation stability: • Donating electrons to an electron H H
H H
deficient (positively charged) centre
1. Steric: Br - stabilizes it. H
Br
H3C CH3
H3C H3C +
H3C CH3 H H

The cationic carbon atom rehybridizes from sp3 to sp2,

relieving the steric clash between substituents = a permanent electric dipole
δ+ δ-
Chem 147 Chem 148
1AA3 1AA3

iClicker Question #7
Rank the likelihood of the following compounds to
undergo SN2 nucleophilic substitutions:

Cl

Cl
Cl Synthesis

i ii iii

(a) i ≈ iii < ii

(b) i ≈ ii < iii
(c) i < ii > iii
(d) ii ≈ i > iii Section 27-9: Refer to the Chem 1AA3
Chem 149 synthesis chart, posted in Avenue
1AA3
 Synthesis Practice Question : Synthesis
1) Functional group interconversion
– e.g., Converting an aldehyde to an alcohol Fill in the missing reagents:
O
O OH
H OH

2) Carbon-carbon bond forming reactions

– e.g., Grignard reaction
1. CO2
R MgX R CO2H
2. H3O+
Chem 151 Chem 152
1AA3 1AA3

Practice Question: Solution Take-Home Practice #1

What are conditions i and ii? i
OH
O 1. NaBH4 OH O
conc. H2SO4, Δ
2. H3O+ ii

i ii
(a) H2 / Pt KMnO4
(b) PCC 10% H2SO4
(c) (1) NaBH4, (2) H3O+ KMnO4
(d) (1) NaBH4 , (2) H3 O+ PCC
Chem 153 Chem 154
1AA3 1AA3

Take-Home Practice #2 Take-Home Practice #3

What are conditions i and ii? i What are conditions i and ii?
OH
i ii

Cl
ii
i ii
i ii
(a) PCC Cl2
(a) 10% H2SO4 conc. H2SO4
(b) H2/Pd-C HCl
(b) PCC 10% H2SO4
(c) H2/Pd-C Cl2
(c) 10% H2SO4 H2/Pd-C
(d) conc. H2SO4 10% H2SO4 (d) conc. H2SO4 HCl
Chem 155 Chem 156
1AA3 1AA3
Medical Application: Molecular Imaging Synthesis of 18F-FDG

• The half-life of 18F is 109.8 minutes

– it must be produced in a cyclotron and immediately used
– the synthesis of 18F-FDG must be fast and reliable.

O OAc
OAc O S CF3 18F-, CH3CN O
OO AcO
AcO 2,2,2-Krypt AcO OAc
AcO OAc F
PET scans SN2 reaction Note the inversion!
Mannose triflate tetraacetate
F is equatorial, but triflate
H CH2OH OH group was axial, therefore
H
O HCl inversion has occurred.
HO O
HO OH 18F-fluorodeoxyglucose
H2 O HO
HO OH
F H F
H H Ester Hydrolysis
Chem 157 Chem 158
1AA3 1AA3