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