ORGANIC REACTION

TYPES
CHAPTER 2
Kinds of Organic Reactions
2
4 general types:
A. Additions
B. Eliminations
C. Substitutions
D. Rearrangements

Kinds of Organic Reactions
3
A. Additions
Two reactants add together to form a single product without
side products.
Kinds of Organic Reactions
4
B. Elimination
Single reactant splits into 2 products with side product
water or HBr
Kinds of Organic Reactions
5
C. Substitution
Two reactants exchange parts to give two new
products.

Kinds of Organic Reactions
6
D. Rearrangement
single reactant rearranges the bond and atoms to
yield an isomeric product.
How Organic Reactions Occur: Mechanisms
7
Reaction mechanism describe in detail everything that
occurs during chemical reaction, which bonds are broken
or formed, and in what order, the relative rates of steps
involved.
All chemical reactions involve bond-breaking and bond-
making.

Steps in Mechanisms
8
We classify the types of steps in a sequence
A step involves either the formation or breaking of a
covalent bond
Steps can occur in individually or in combination with
other steps
When several steps occur at the same time they are said
to be concerted

Types of Steps in Reaction Mechanisms
Symmetrical- homolytic Unsymmetrical- heterolytic
9
Bond breaking (radical)
1 bonding electron
stays with each product


Bond-making (radical)
1 bonding electron is
donated by each
reactant
Bond-breaking (polar)
2 bonding electrons
stays with 1 product.


Bond-making (polar) 2
bonding electrons are
donated by 1 reactant
Indicating Steps in Mechanisms
10
Curved arrows indicate breaking and
forming of bonds
Arrowheads with a half head (fish-
hook) indicate homolytic and
homogenic steps (called radical
processes)
Arrowheads with a complete head
indicate heterolytic and heterogenic
steps (called polar processes)
Radical Reactions
11
Not as common as polar
reactions
Radicals react to complete
electron octet of valence shell
A radical can break a bond in
another molecule and
abstract a partner with an
electron, giving substitution in
the original molecule
A radical can add to an
alkene to give a new radical,
causing an addition reaction
Steps in Radical Substitution
12
Three types of steps
Initiation homolytic formation of two reactive species with
unpaired electrons
Example formation of Cl atoms form Cl
2
and light



Propagation reaction with molecule to generate radical
Example - reaction of chlorine atom with methane to give
HCl and CH
3
.





Steps in Radical Substitution
13

Termination combination of two radicals to form a stable
product: CH
3
.
+ CH
3
.
CH
3
CH
3

Polar Reactions
14
Involve species with electron pairs in their orbitals.
More common reaction in organic chemistry.
Occur because of the electrical attraction between positive and
negative centers most organic compounds are electrically neutral,
bonds in functional group are polar.
This causes a partial negative charge on an atom and a
compensating partial positive charge on an adjacent atom
The more electronegative atom has the greater electron density such
as O, F, N, Cl more electronegative than carbon carbon atom has
partial positive charge (+)
Metal with lesser electronegativity carbon atom has partial
negative charge (-)

15
Polarizability
16
Polarization is a change in electron distribution as a
response to change in electronic nature of the
surroundings
Polarizability is the tendency to undergo polarization
Polar reactions occur between regions of high electron
density and regions of low electron density
Generalized Polar Reactions
17
Nucleophile: nucleus
loving
Negatively polarised
Electron-rich atom
Donate pair of electrons to
electron poor atom
Neutral or negatively
charged
Example: NH
4
+
, H
2
O, OH
-
,
Cl
-
Electrophile: electron-
loving
Positively polarised
Electron-poor atom
Accepting a pair of
electrons from electron rich
atom
Neutral or positively
charged
Example: acids, alkyl
halides, carbonyl
compounds
18
19
An Example of a Polar Reaction: Addition of
HBr to Ethylene
20
HBr adds to the part of C-C double bond
The bond is electron-rich, allowing it to function as a
nucleophile
H-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile
Mechanism of Addition of HBr to Ethylene
21
HBr electrophile is attacked
by electrons of ethylene
(nucleophile) to form a
carbocation intermediate and
bromide ion
Bromide adds to the positive
center of the carbocation,
which is an electrophile,
forming a C-Br bond
The result is that ethylene and
HBr combine to form
bromoethane
All polar reactions occur by
combination of an electron-
rich site of a nucleophile and
an electron-deficient site of an
electrophile
Using Curved Arrows in Polar Reaction
Mechanisms
22
Curved arrows are a way to keep track of changes in
bonding in polar reaction
The arrows track electron movement
Electrons always move in pairs
Charges change during the reaction
One curved arrow corresponds to one step in a reaction
mechanism
Rules for Using Curved Arrows
23
The arrow goes from the nucleophilic reaction site to the
electrophilic reaction site





The nucleophilic site can be neutral or negatively
charged


24
The electrophilic site can be neutral or positively
charged




The octet rule must be followed

Organic reaction types:
Nucleophilic Substitutions and Eliminations
Alkyl Halides React with Nucleophiles and
Bases
26
Alkyl halides are polarized at the carbon-halide bond,
making the carbon electrophilic
Nucleophiles will replace the halide in C-X bonds of many
alkyl halides(reaction as Lewis base)
Nucleophiles that are Brnsted bases produce
elimination
Why this Chapter?
27
Nucleophilic substitution, base induced elimination
are among most widely occurring and versatile
reaction types in organic chemistry
Reactions will be examined closely to see:
- How they occur
- What their characteristics are
- How they can be used
The Discovery of Nucleophilic
Substitution Reactions
28
In 1896, Walden showed that (-)-malic acid could be
converted to (+)-malic acid by a series of chemical steps
with achiral reagents
This established that optical rotation was directly related
to chirality and that it changes with chemical alteration
Reaction of (-)-malic acid with PCl
5
gives (+)-chlorosuccinic
acid
Further reaction with wet silver oxide gives (+)-malic acid
The reaction series starting with (+) malic acid gives (-) acid
Reactions of the Walden Inversion
29
Significance of the Walden Inversion
30
The reactions alter the array at the chirality center
The reactions involve substitution at that center
Therefore, nucleophilic substitution can invert the
configuration at a chirality center
The presence of carboxyl groups in malic acid led to
some dispute as to the nature of the reactions in
Waldens cycle
The S
N
2 Reaction
31
Reaction is with inversion at reacting center
Follows second order reaction kinetics
Ingold nomenclature to describe characteristic step:
S=substitution
N (subscript) = nucleophilic
2 = both nucleophile and substrate in characteristic
step (bimolecular)

Kinetics of Nucleophilic Substitution
32
Rate (V) is change in concentration with time
Depends on concentration(s), temperature, inherent
nature of reaction (barrier on energy surface)
A rate law describes relationship between the
concentration of reactants and conversion to products
A rate constant (k) is the proportionality factor between
concentration and rate

Second order
process
Reaction Kinetics
33
The study of rates of reactions is called kinetics
Rates decrease as concentrations decrease but the rate
constant does not
Rate units: [concentration]/time such as L/(mol x s)
The rate law is a result of the mechanism
The order of a reaction is sum of the exponents of the
concentrations in the rate law the example is second
order
S
N
2 Process
34
The reaction involves a transition state in which both
reactants are together
Single step without intermediates when nucleophile react
with alkyl halide or tosylate (substrate) from the opposite
direction of the leaving group.
S
N
2 Transition State
35
The transition state of an S
N
2 reaction has a planar
arrangement of the carbon atom and the remaining three
groups
Reactant and Transition State Energy Levels
Affect Rate
36
Higher reactant energy
level (red curve) = faster
reaction (smaller G

).
Higher transition state
energy level (red curve) =
slower reaction (larger G

).
Characteristics of the S
N
2 Reaction
37
Sensitive to steric effects
Methyl halides are most reactive
Primary are next most reactive
Secondary might react
Tertiary are unreactive by this path
No reaction at C=C (vinyl halides)
Steric Effects on S
N
2 Reactions
38
The carbon atom in (a) bromomethane is readily accessible
resulting in a fast S
N
2 reaction. The carbon atoms in (b) bromoethane
(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-
methylpropane (tertiary) are successively more hindered, resulting in
successively slower S
N
2 reactions.
Order of Reactivity in S
N
2
39
The more alkyl groups connected to the reacting carbon,
the slower the reaction
The Nucleophile
40
Neutral or negatively charged species
Reaction increases coordination at nucleophile
Neutral nucleophile acquires positive charge
Anionic nucleophile becomes neutral
Relative Reactivity of Nucleophiles
41
Depends on reaction and
conditions
More basic nucleophiles
react faster
Better nucleophiles are
lower in a column of the
periodic table
Anions are usually more
reactive than neutrals
The Leaving Group
42
A good leaving group reduces the barrier to a reaction
Stable anions that are weak bases are usually excellent
leaving groups and can delocalize charge
Poor Leaving Groups
43
If a group is very basic or very small, it prevents reaction

Alkyl fluorides, alcohols, ethers, and amines do not
typically undergo S
N
2 reactions.
The Solvent
44
Solvents that can donate hydrogen bonds (-OH or NH)
slow S
N
2 reactions by associating with reactants
Energy is required to break interactions between reactant
and solvent
Polar aprotic solvents (no NH, OH, SH) form weaker
interactions with substrate and permit faster reaction
The S
N
1 Reaction
45
Tertiary alkyl halides react rapidly in protic solvents by a
mechanism that involves departure of the leaving group
prior to addition of the nucleophile
Called an S
N
1 reaction occurs in two distinct steps
while S
N
2 occurs with both events in same step
If nucleophile is present in reasonable concentration (or it
is the solvent), then ionization is the slowest step
Rate-Limiting Step
46
The overall rate of a
reaction is controlled by
the rate of the slowest
step
The rate depends on the
concentration of the
species and the rate
constant of the step
The highest energy
transition state point on
the diagram is that for the
rate determining step
(which is not always the
highest barrier)
S
N
1 Energy Diagram
47
Rate-determining/ rate-limiting step is formation of
carbocation
First order
process
Stereochemistry of S
N
1 Reaction
48
The planar intermediate leads to loss of chirality
A free carbocation is achiral
Product is racemic or has some inversion
S
N
1 in Reality
49
Carbocation is biased to react on side opposite leaving
group
Suggests reaction occurs with carbocation loosely
associated with leaving group during nucleophilic
addition
Alternative that S
N
2 is also occurring is unlikely
Effects of Ion Pair Formation
50
If leaving group remains associated, then product has
more inversion than retention
Product is only partially racemic with more inversion than
retention
Associated carbocation and leaving group is an ion pair
Characteristics of the S
N
1 Reaction
51
Substrate
Tertiary alkyl halide is most reactive by this
mechanism
Controlled by stability of carbocation
Hammond postulate, "Any factor that stabilizes
a high-energy intermediate stabilizes transition
state leading to that intermediate
Allylic and Benzylic Halides
52
Allylic and benzylic intermediates stabilized by
delocalization of charge
Primary allylic and benzylic are also more reactive in
the S
N
2 mechanism
Effect of Leaving Group on S
N
1
53
Critically dependent on leaving group
Reactivity: the larger halides ions are better leaving
groups
In acid, OH of an alcohol is protonated and leaving group
is H
2
O, which is still less reactive than halide
p-Toluensulfonate (TosO
-
) is excellent leaving group
Nucleophiles in S
N
1
54
Since nucleophilic addition occurs after formation of
carbocation, reaction rate is not normally affected by
nature or concentration of nucleophile
Solvent in S
N
1
55
Stabilizing carbocation
also stabilizes associated
transition state and
controls rate
Solvent effects in the S
N
1
reaction are due largely to
stabilization or
destabilization of the
transition state
Polar Solvents Promote Ionization
56
Polar, protic and unreactive Lewis base solvents facilitate
formation of R
+

Solvent polarity is measured as dielectric polarization
(P)
Nonpolar solvents have low P
Polar solvents have high P values
57
Biological Substitution Reactions
58
S
N
1 and S
N
2 reactions are well known in biological
chemistry
Unlike what happens in the laboratory, substrate in
biological substitutions is often organodiphosphate
rather than an alkyl halide



Elimination Reactions of Alkyl Halides: Zaitsevs
Rule
59
Elimination is an alternative pathway to substitution
Opposite of addition
Generates an alkene
Can compete with substitution and decrease yield,
especially for S
N
1 processes
Zaitsevs Rule for Elimination Reactions
60
In the elimination of HX from an alkyl halide, the more
highly substituted alkene product predominates

Mechanisms of Elimination Reactions
61
E1: X
-
leaves first to
generate a carbocation
a base abstracts a
proton from the
carbocation




E2: Concerted transfer
of a proton to a base
and departure of
leaving group

The E2 Reaction and the Deuterium Isotope
Effect
62
A proton is transferred to base as leaving group begins to
depart
Transition state combines leaving of X and transfer of H
Product alkene forms stereospecifically
Geometry of Elimination E2
63
Antiperiplanar allows orbital overlap and minimizes steric
interactions
E2 Stereochemistry
64
Overlap of the developing orbital in the transition state
requires periplanar geometry, anti arrangement
Predicting Product
65
E2 is stereospecific
Meso-1,2-dibromo-1,2-diphenylethane with base gives
cis 1,2-diphenyl
RR or SS 1,2-dibromo-1,2-diphenylethane gives trans
1,2-diphenyl
The E2 Reaction and Cyclohexane
Formation
66
Abstracted proton and leaving group should align
trans-diaxial to be anti periplanar (app) in
approaching transition state
Equatorial groups are not in proper alignment
The E1and S
N
1Reactions
67
Competes with S
N
1 and E1 at 3 centers
V = k [RX], same as S
N
1
Comparing E1 and E2
68
Strong base is needed for E2 but not for E1
E2 is stereospecifc, E1 is not
E1 gives Zaitsev orientation
E1cB Reaction
69
Takes place through a carbanion intermediate



Biological Elimination Reactions
70
All three elimination reactions occur in biological
pathways
E1cB very common
Typical example occurs during biosynthesis of fats
when 3-hydroxybutyryl thioester is dehydrated to
corresponding thioester



Summary of Reactivity: S
N
1, S
N
2,
E1,E1cB, E2
71
Alkyl halides undergo different reactions in
competition, depending on the reacting molecule
and the conditions
Based on patterns, we can predict likely
outcomes
72