You are on page 1of 102

ORGANIC REACTION

TYPES
CHAPTER 2

Kinds of Organic Reactions


In general, we look at what occurs and try to learn
how it happens.
Common patterns describe the changes.
4 general types:

A.
B.

C.
D.

Additions two molecules combine


Eliminations one molecule splits into two
Substitutions parts from two molecules exchange
Rearrangements a molecule undergoes changes in the
way its atoms are connected

Kinds of Organic Reactions


A.

Addition
Two reactants add together to form a single product
without side products.

Kinds of Organic Reactions


B.

Elimination
Single reactant splits into 2 products with side product
water or HBr.

Kinds of Organic Reactions


Elimination is the opposite of addition .

Kinds of Organic Reactions


C.

Substitution
Two reactants exchange parts to give two new products.

Kinds of Organic Reactions


D.

Rearrangement
Single reactant rearranges the bond and atoms to
yield an isomeric product.

Exercises
Classify the following reactions as addition, elimination,
substitution or rearrangement.
1)

2)

3)

4)
8

How Organic Reactions Occur: Mechanisms


In an organic reaction, we see the transformation that has
occurred. The mechanism describes the steps behind the
changes that we can observe.
Reactions occur in defined steps that lead from reactant to
product.
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 bondmaking.

Steps in Mechanisms

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.

10

Types of Steps in Reaction Mechanisms


Bond formation or breakage can be symmetrical or
unsymetrical.
Symmetrical- homolytic
Bond breaking (radical) 1
bonding electron stays with
each product

Bond-making (radical) 1
bonding electron is donated
by each reactant

11

Unsymmetrical- heterolytic
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

12

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)

Bond breaking forms particles called reaction


intermediates.

13

Common Reaction Intermediates


Formed by Breaking a Covalent Bond

14

Radical Reactions

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.

15

A radical can add to an alkene to give a new radical, causing an


addition reaction .

Steps in Radical Substitution

Three types of steps:

Initiation
- Radicals are formed.
- Light supplies the energy to split a molecule.

Propagation
- A radical reacts with molecule to generate another radical.
- Free radical species are constantly generated throughout
the reaction.

Termination
- Combination of any two radicals to form stable product.

16

Steps in Radical Substitution

Example:

Initiation

Propagation

17

formation of Cl radicals form Cl2 and light

reaction of chlorine radical with methane to give HCl and CH3


methyl radical reacts with Cl2 to generate the product and Cl

Steps in Radical Substitution

Termination

18

reaction of any two radicals

Polar Reactions

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.

Molecules can contain local unsymmetrical electron


distributions due to differences in electronegativities.

This causes a partial negative charge on an atom and a


compensating partial positive charge on an adjacent atom.
19

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 (-).

20

21

22

Polarizability

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.
In the halogen family, for example, polarizability increases in
the order F < Cl < Br < I.

F atom is the lowest because their electrons are very tightly held;
they are close to the nucleus.
I atom is the highest since their valence electrons are far from
nucleus.

Atoms with unshared pairs are generally more polarizable than


those with only bonding pairs.
23

Generalized Polar Reactions

Nucleophile: nucleus loving

24

Negatively polarized
Electron-rich species
Donate pair of electrons to
electron poor atom
Neutral or negatively charged
Example: NH4+ , H2O, OH, Cl

Electrophile: electron loving

Positively polarized
Electron-poor species
Accepting a pair of electrons
from electron rich atom
Neutral or positively charged
Example: acids, alkyl halides,
carbonyl compounds

Generalized Polar Reactions


In general, electrons flow from nucleophile to electrophiles.

25

26

Exercises

Answers:

27

An Example of a Polar Reaction: Addition


of HBr to Ethylene

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.

28

Mechanism of Addition of HBr to


Ethylene

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.

29

30

Using Curved Arrows in Polar Reaction


Mechanisms

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.
The arrow goes from the nucleophilic reaction site to the
electrophilic reaction site.

31

Rules for Using Curved Arrows

The nucleophilic site can be neutral or negatively charged.

32

Rules for Using Curved Arrows

The electrophilic site can be neutral or positively charged

The octet rule must be followed

33

Organic Reaction Types:


Nucleophilic Substitutions and Eliminations

Alkyl Halides React with Nucleophiles


and Bases

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.

35

Why this Chapter?

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?

36

The Discovery of Nucleophilic


Substitution Reactions

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.

37

Reaction of (-)-malic acid with PCl5 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

38

Significance of the Walden Inversion

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.

39

Nucleophilic Substitution Reactions

In this type of reaction, a nucleophile, a species with an


unshared electron pair, reacts with an alkyl halide by
replacing the halogen substituent.
A substitution reaction takes places and the halogen
substituent, called the leaving group, departs as a halide ion.
Because the substitution reaction is initiated by a nucleophile,
it is called a nucleophilic substitution reaction.
Example:
Nucleophile

40

Alkyl halide
(substrate)

Product

Halide ion

Mechanisms of Nucleophilic Substitution

In a nucleophilic substitution:

But what is the order of bond making and bond breaking?


In theory, there are three possibilities.

41

Bond making and bond breaking occur at the same time


Bond breaking occurs before bond making
Bond making occurs before bond breaking

Mechanisms of Nucleophilic Substitution

Bond Making and Bond Breaking Occur at The Same Time

42

In this scenario, the mechanism is comprised of one step.


In such a bimolecular reaction, the rate depends upon the
concentration of both reactants.
The rate equation is second order.

Mechanisms of Nucleophilic Substitution

Bond Breaking Occurs Before Bond Making

43

In this scenario, the mechanism has two steps and a


carbocation is formed as an intermediate.
Because the first step is rate-determining, the rate depends on
the concentration of RX only.
The rate equation is first order.

Mechanisms of Nucleophilic Substitution

Bond Making Occurs Before Bond Breaking

44

This mechanism has an inherent problem.


The intermediate generated in the first step has 10 electrons
around carbon, violating the octet rule.
Because two other mechanistic possibilities do not violate a
fundamental rule, this last possibility can be disregarded.

Kinetics of Nucleophilic Substitution

The study of rates of reactions is called kinetics.


Rate (V) is change in concentration with time.
Rates decrease as concentrations decrease but the rate
constant does not.
Rate units: [concentration]/time such as molL-1/s.
The rate law is a result of the mechanism.
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.

45

The SN2 Reaction

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)

46

SN2 Process

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.

47

SN2 Transition State

The transition state of an SN2 reaction has a planar


arrangement of the carbon atom and the remaining three
groups.

48

Stereochemistry of The SN2 Reaction

All SN2 reactions proceed with backside attack of the nucleophile,


resulting in inversion of configuration at a stereogenic center.

49

Reactant and Transition State Energy


Levels Affect Rate
Higher reactant energy
level (red curve) = faster
reaction (smaller G).

Higher transition state


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

50

Factors Influencing The Rate of SN2


Reactions

There are 4 factors that influence the rate of SN2


reactions:
The substrate (alkyl halide) structure.
The nucleophile
The leaving group
The solvent

51

Characteristics of SN2 Reaction

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)

52

Steric Effects on SN2 Reactions

The carbon atom in (a) bromomethane is readily accessible


resulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane
(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2methylpropane (tertiary) are successively more hindered, resulting in
successively slower SN2 reactions.
53

Steric Effects on SN2 Reactions

The higher the Ea, the slower the reaction rate. Thus, any factor that
increases Ea decreases the reaction rate.
Two Energy Diagrams Depicting The Effect of Steric Hindrance in SN2 Reactions

54

Order of Reactivity in SN2

The more alkyl groups connected to the reacting carbon, the


slower the reaction.

55

Order of Reactivity in SN2

Methyl and 1 alkyl halides undergo SN2 reactions with ease.


2 Alkyl halides react more slowly.
3 Alkyl halides do not undergo SN2 reactions.
This order of reactivity can be explained by steric effects. Steric
hindrance caused by bulky R groups makes nucleophilic attack from
the backside more difficult, slowing the reaction rate.
56

The Nucleophile

Neutral or negatively charged species.


Reaction increases coordination at nucleophile.
Neutral nucleophile acquires positive charge.
Anionic nucleophile becomes neutral.

57

Relative Reactivity of Nucleophiles

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.

58

The Leaving Group

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.

59

Poor Leaving Groups

If a group is very basic or very small, it is prevents reaction.


Alkyl fluorides, alcohols, ethers, and amines do not typically undergo
SN2 reactions.

60

The Solvent

Solvents that can donate hydrogen bonds (-OH or NH) slow SN2
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.

61

The SN1 Reaction

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 SN1 reaction occurs in two distinct steps while SN2
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.

62

Rate-Limiting Step

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).
63

SN1 Energy Diagram

Rate-determining/ rate-limiting step is formation of


carbocation.
First order process

64

Stereochemistry of SN1 Reaction

The planar intermediate leads to loss of chirality.


A free carbocation is achiral.
Product is racemic or has some inversion.

65

SN1 in Reality

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 SN2 is also occurring is unlikely.

66

Effects of Ion Pair Formation

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.

67

Characteristics of the SN1 Reaction


Substrate
Tertiary alkyl halide is most reactive by this mechanism.

68

Controlled by stability of carbocation.


Hammond postulate, "Any factor that stabilizes a highenergy intermediate stabilizes transition state leading to that
intermediate.

Allylic and Benzylic Halides

Allylic and benzylic intermediates stabilized by delocalization of


charge.
Primary allylic and benzylic are also more reactive in the
SN2 mechanism.

69

Effect of Leaving Group on SN1

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
H2O, which is still less reactive than halide.
p-Toluensulfonate (TosO-) is excellent leaving group.

70

Nucleophiles in SN1

Since nucleophilic addition occurs after formation of


carbocation, reaction rate is not normally affected by
nature or concentration of nucleophile.

71

Solvent in SN1

Stabilizing carbocation
also stabilizes associated
transition state and
controls rate.

Solvent effects in the SN1


reaction are due largely
to stabilization or
destabilization of the
transition state.

72

Polar Solvents Promote Ionization

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

73

Exercises

74

Biological Substitution Reactions

SN1 and SN2 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.

75

Summary: SN2 versus SN1

SN2

SN1

76

Factors in Predicting SN1 vs SN2 Mechanisms

Four factors are relevant in predicting whether a given reaction is


likely to proceed by an SN1 or an SN2 mechanism.

S N1

S N2

77

Substrate

Nucleophile

Leaving Group

Solvent

3o > 2o

Nucleophilic
strength not
important

Good LG
important to
form C+

Enhanced by
more polar
solvent

CH3 > 1o > 2o

Needs a strong
nucleophile

Not as important
but enhances
reaction

Enhanced by
less polar
solvent

Predicting SN1 vs SN2 Mechanisms:


The Substrate

The most important is the structure of the alkyl halide (substrate).

78

Predicting SN1 vs SN2 Mechanisms:


The Nucleophile

The strong nucleophile favors an SN2 mechanism.

The weak nucleophile favors an SN1 mechanism.

79

Predicting SN1 vs SN2 Mechanisms:


The Leaving Group

A better leaving group increases the rate of both SN1 and SN2
reactions.

80

Predicting SN1 vs SN2 Mechanisms:


The Solvent

The nature of the solvent is the fourth factor.

Polar protic solvents like H2O and ROH favor SN1


reactions because the ionic intermediates (both
cations and anions) are stabilized by solvation.

Polar aprotic solvents favor SN2 reactions because


nucleophiles are not well solvated, and therefore, are
more nucleophilic.

81

Results of SN1 vs SN2 Mechanisms


Kinetics:
SN1
SN2

rate = k[RX]
rate = k[RX][Nu:]

Stereochemistry:
SN1
both inversion and retention (racemic)
SN2
inversion only
Rearrangements:
SN1
rearrangements common
SN2
rearrangements not possible
82

Exercises

83

Exercises

84

Exercise

85

Elimination Reactions of Alkyl Halides

A widely used method for synthesizing alkenes is the elimination of HX


from adjacent atoms of an alkyl halide.
When the elements of a hydrogen halide are eliminated from a haloalkane
in this way, the reaction is often called dehydrohalogenation:

A hydrogen atom attached to the carbon atom is called a hydrogen


atom.
Since the hydrogen atom that is eliminated in dehydrohalogenation is
from the b carbon atom, these reactions are often called
eliminations.
86

Elimination Reactions of Alkyl Halides

There are two idealized mechanisms for -elimination


reactions, E1 and E2.
E1 mechanism: at one extreme, breaking of the R-Lv
bond to give a carbocation is complete before
reaction with base to break the C-H bond.

only R-Lv is involved in the rate-determining step (as in SN1)

E2 mechanism: at the other extreme, breaking of the


R-Lv and C-H bonds is concerted (same time).

87

both R-Lv and base are involved in the rate-determining step


(as in SN2)

Mechanisms of Elimination Reactions:


E1 and E2

E1 Reaction (Unimolecular Elimination)

X- leaves first to generate a carbocation

E2 Reaction (Bimolecular Elimination)

88

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

E2 Reaction Mechanisms

E2 = Elimination, Bimolecular (2nd order). Rate = k [RX] [Nu:-]


E2 reactions occur when a 2 or 3 alkyl halide is treated with a
strong base such as OH-, OR-, NH2-, H-, etc.

89

Elimination Reactions of Alkyl Halides:


Zaitsevs Rule

Elimination is an alternative pathway to substitution.


Opposite of addition.
Generates an alkene.
Can compete with substitution and decrease yield, especially
for SN1 processes.

90

Zaitsevs Rule for Elimination Reactions

In the elimination of HX from an alkyl halide, the more highly


substituted alkene product predominates.

91

The E2 Reaction and the Deuterium


Isotope Effect

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.

92

Geometry of Elimination E2

Antiperiplanar allows orbital overlap and minimizes steric


interactions.

93

E2 Stereochemistry

Overlap of the developing orbital in the transition state


requires periplanar geometry, anti arrangement.

94

Predicting Product

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.

95

The E2 Reaction and Cyclohexane


Formation

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.

96

E1 Reaction Mechanisms

Just as SN2 reactions are analogous to E2 reactions, so SN1 reactions


have an analog, E1 reaction.

E1 = Elimination, unimolecular (1st order); Rate = k [RX]


Slow step

97

Fast step

E1 Reaction Mechanisms

E1 eliminations, like SN1 substitutions, begin with unimolecular


dissociation, but the dissociation is followed by loss of a proton
from the -carbon (attached to the C+) rather than by substitution.
E1 & SN1 normally occur in competition, whenever an alkyl halide is
treated in a protic solvent with a nonbasic, poor nucleophile.
As with E2 reactions, E1 reactions also produce the more highly
substituted alkene (Zaitsevs rule). However, unlike E2 reactions
where no C+ is produced, C+ rearrangements can occur in E1
reactions.
Example:

98

Comparing E1 and E2

Strong base is needed for E2 but not for E1.


E2 is stereospecifc, E1 is not.
E1 gives Zaitsev orientation.

99

A Comparison of E1 and E2
major product
E2
syn
H

Anti-Zaitsev

NaOEt
Br

CH3

EtOH /

stereospecific
anti

H
CH3
EtOH /

E1

anti

E1 doesnt require
anti-coplanarity
100

CH3

Zaitsev
not
stereospecific

Correlation of Structure & Reactivity for


SN1, SN2, E1, E2
Halide
Type

SN1

SN2

E1

E2

Does not
occur

Highly
favored

Does not
occur

R2CHX
(secondary)

Can occur
with benzylic
and allylic
halides

Occurs in
competition
with E2
reaction

Can occur
with benzylic
and allylic
halides

Favored when
strong bases
are used

R3CX
(tertiary)

Favored in
hydroxylic
solvents

Does not
occur

Occurs in
competition
with SN2
reaction

Favored when
bases are
used

RCH2X
(primary)

101

Occurs when
strong bases
are used

Mechanism Review:
Substitution vs Elimination

102