Chapter 7

Alkyl
y Halide
Organic
g Chemistry,
y, Third Edition
Janice Gorzynski Smith
U i
University
i off Hawai’i
H i’i

Prepared by Layne A. Morsch

The University of Illinois - Springfield

Modified and Used for Basic Org Chem Lecture

by V.P. Hoven, as of August 2012

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
 Types of Alkyl Halides

• Alkyl halides are organic molecules containing a

halogen atom bonded to an sp3 hybridized carbon atom.
• Alkyl halides are classified as primary (1 (1°)), secondary
(2°), or tertiary (3°), depending on the number of carbons
bonded to the carbon with the halogen g atom.
• The halogen atom in halides is often denoted by the
symbol “X”.
X .

2
3
 Other Types of Alkyl Halides
• Vinyl halides have a halogen atom (X) bonded to a C–C double
bond.
• Aryl halides have a halogen atom bonded to a benzene ring.
• Allylic halides have X bonded to the carbon atom adjacent to a
C-C double bond.
• Benzylic halides have X bonded to the carbon atom adjacent
to a benzene ring.

4
Naming Alkyl Halides

5
 Common Names of Alkyl Halides
• Common names are often used for simple alkyl halides.
To assign a common name:
• Name all the carbon atoms of the molecule as a single
alkyl group.
• Name the halogen bonded to the alkyl group.
• C
Combine
bi the
th names off the
th alkyl
lk l group and
d halide,
h lid
separating the words with a space.

6
 Polarity of Alkyl Halides

• Alkyl halides are weak polar molecules.

• They exhibit dipole-dipole
dipole dipole interactions because of their polar
C–X bond.
• Since the rest of the molecule contains only C–C
C C and C–H
C H
bonds, they are incapable of intermolecular hydrogen
bonding.

7
Physical Properties of Alkyl Halides

8
Simple Alkyl Halides

9
Common Alkyl Halides

10
 The Polar Carbon–Halogen Bond
• The electronegative halogen atom in alkyl halides creates a
polar C–X bond,, making
p g the carbon atom electron deficient.
• This electron deficient carbon is a key site in the reactivity of
alkyl halides.

Electrostatic potential maps

11
Reaction Types

12
Substitution Reactions

13
 Nucleophiles

• Nucleophiles are Lewis bases that can be negatively charged

or neutral.
g
• Negatively y charged
g nucleophiles
p like HO¯ and HS¯ are used
as salts with Li+, Na+, or K+ counterions to balance the charge.
• Since the identity of the counterion is usually inconsequential,
i is
it i often
f omitted
i d from
f the
h chemical
h i l equation.
i

14
 Neutral Nucleophiles
• When a neutral nucleophile is used, the substitution product
bears a positive charge.

• The substitution product’s positive charge is usually

caused by a proton bonded to O or N.
• That proton is readily lost from this in a BrØnsted–Lowry
acid–base reaction, forming a neutral product.

15
• Th
The substitution
b tit ti product’s
d t’ positive
iti charge
h i usually
is ll
caused by a proton bonded to O or N that is readily lost
from this in a BrØnsted–Lowry y acid–base reaction,,
forming a neutral product.

16
 Drawing Products of Nucleophilic
S b tit ti Reactions
Substitution R ti

• The overall effect of any nucleophilic substitution is the

replacement
p of the leaving
gggroup
p by
y the nucleophile.
p

• To draw any nucleophilic substitution product:

• Find the sp3 hybridized carbon with the leaving group.
• Identify the nucleophile, the species with a lone pair or π
bond.
• Substitute the nucleophile for the leaving group and
assign charges (if necessary) to any atom that is involved
in bond breaking or bond formation.

17
 The Leaving Group
• In a nucleophilic substitution reaction of R–X, the C–X bond is
heterolytically
y y cleaved, and the leaving g g
group departs with the
electron pair in that bond, forming X:¯.
• The more stable the leaving group X:¯, the better able it is to
accept an electron pair.
pair

• For example,
example H2O is a better leaving group than HO¯ because
H2O is a weaker base.
18
 Trends in Leaving Group Ability

• The weaker the base, the better the leaving group.

19
Good Leaving Groups

20
 Poor Leaving Groups
• Conjugate bases of weaker acids are poorer leaving groups.

21
 Nucleophiles and Bases
• Nucleophiles and bases are structurally similar: both have a
lone pair or a π bond.
• They differ in what they attack.
• Bases attack protons.
p
• Nucleophiles attack other electron-deficient atoms
(usually carbons).

22
 Nucleophiles versus Bases

• Although nucleophilicity and basicity are interrelated,

they are fundamentally different.
different
• Basicity is a measure of how readily an atom donates its
electron pair to a proton. It is characterized by an
equilibrium constant, Ka in an acid–base reaction, making
it a thermodynamic property.

• Nucleophilicity is a measure of how readily an atom

d
donates
t its
it electron
l t pair
i to
t other
th atoms.
t It is
i characterized
h t i d
by a rate constant, k, making it a kinetic property.

23
 Nucleophilicity Parallels Basicity
Nucleophilicity parallels basicity in three instances:
1. For two nucleophiles with the same nucleophilic atom, the
stronger base is the stronger nucleophile.
• The relative nucleophilicity of HO¯ and CH3COO¯, is
determined by comparing the pKa values of their conjugate
acids (H2O = 15.7
15 7 and CH3COOH = 4.8).4 8)
• HO¯ is a stronger base and stronger nucleophile than
CH3COO¯.
2. A negatively charged nucleophile is always a stronger
nucleophile than its conjugate acid.
• HO HO¯ is a stronger base and stronger nucleophile than H2O.O
3. Right-to-left across a row of the periodic table, nucleophilicity
increases as basicity increases:

24
 Steric Effects on Nucleophile Strength
• Nucleophilicity does not parallel basicity when steric
hindrance becomes important.
• Steric hindrance is a decrease in reactivity resulting from
the presence of bulky groups at the site of a reaction.
• Steric
St i hindrance
hi d d
decreases nucleophilicity
l hili it but
b t nott basicity.
b i it
• Sterically hindered bases that are poor nucleophiles are
called nonnucleophilic bases.
bases

25
 Solvent Effects on Nucleophilicity
• Most organic reactions are performed in a liquid solvent
capable of dissolving the reactants, at least to some extent.

• Since substitution reactions involve ppolar starting

g materials,
polar solvents are used to dissolve them.

• There are two type of polar solvents: protic and aprotic.

• Nucleophilicity
N l hili it can be
b affected
ff t d by
b the
th nature
t off the
th solvent.
l t

26
 Solvation by Polar Protic Solvents
• Polar protic solvents solvate both cations and anions well.
• If the salt NaBr is used as a source of the nucleophile Br¯ in H2O:
• The Na+ cations are solvated by ion-dipole interactions with
H2O molecules.
• The Br¯ anions are solvated by strong hydrogen bonding
interactions.

27
 Nucleophilicity in Polar Protic Solvents
• Smaller, more electronegative anions are solvated more
strongly, effectively shielding them from reaction.
• In
I polar
l proticti solvents,
l t nucleophilicity
l hili it increases
i down
d a
column of the periodic table as the size of the anion
increases.
• This is the opposite of basicity.

28
 Polar Aprotic Solvents
• Polar aprotic solvents also exhibit dipole–dipole interactions,
but they have no OO–H
H or N–H
N H bonds.
• They are incapable of hydrogen bonding.

29
 Nucleophilicity in Polar Aprotic Solvents
• Polar aprotic solvents solvate cations by ion–dipole
interactions.
• Anions are not well solvated because the solvent cannot
hydrogen bond to them.
• These
Th anions
i are said
id to
t be
b “naked”
“ k d” and d therefore,
th f more
reactive.

30
 Nucleophilicity versus Basicity in Polar
A
Aprotic
ti Solvents
S l t
• In polar aprotic solvents
solvents, nucleophilicity parallels basicity
basicity, and
the stronger base is the stronger nucleophile.
• Because basicity y decreases as size increases down a column,
nucleophilicity decreases as well.

31
Common Nucleophiles

32
Bond Breaking and Making in Nucleophilic
S b tit ti Mechanisms
Substitution M h i

• But what is the order of bond making and bond

breaking?
• In
I theory,
th th
there are three
th possibilities.
ibiliti
• Bond making and breaking occur at the same time.
• Bond breaking occurs first.
• Bond making occurs first.

33
 Nucleophilic Substitution Mechanisms—
C
Concerted
t d
1. Bond making and bond breaking occur at the same
1
time.

• Th
The mechanism
h i i comprised
is i d off one step.
t
• In such a bimolecular reaction, the rate depends upon the
concentration of both reactants.
reactants
• The rate equation is second order.

34
 Nucleophilic Substitution Mechanisms—
B d Breaking
Bond B ki Fi Firstt
2. Bond breaking
g occurs before bond making.
g

• The mechanism has two steps and a carbocation is formed as

an intermediate.
p is rate-determining.
• The first step g
• The rate depends on the concentration of RX only.
• The rate equation is first order.

35
 Nucleophilic Substitution Mechanisms—
B d Making
Bond M ki First
Fi t
3 Bond making occurs before bond breaking.
3. breaking

• 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 p possibilities do not violate a
fundamental rule, this last possibility can be disregarded.
36
 Kinetics and Mechanisms
Consider reaction 1 below:

• Kinetic data show that the rate of reaction 1 depends on the

concentration of both reactants, which suggests a bimolecular
reaction with a one-step
one step mechanism.
• This is an example of an SN2 (substitution nucleophilic
bimolecular) mechanism.

37
Consider reaction 2 below:

• Kinetic data show that the rate of reaction 2 depends on the

concentration of only the alkyl halide.
• This suggests a two-step mechanism in which the rate-
determining step involves the alkyl halide only.
only
• This is an example of an SN1 (substitution nucleophilic
unimolecular) mechanism.
38
 SN2 Reaction Mechanism

• The mechanism of an SN2 reaction would be drawn as

follows.
follows
• Curved arrow notation is used to show the flow of
electrons.
electrons

39
Energy Diagrams for SN2 Reactions

40
 Transition States of SN2 Reactions
• The transition state always has partial bonds to the nucleophile
and the leaving group.
• There can also be partial charges on the nucleophile and/or
leaving group.

41
 Inversion in SN2 Reactions
• The bond to the nucleophile in the product is always on the
opposite side relative to the bond of the leaving group in the
starting
t ti material.
t i l
• This is called backside attack.
• This results in inversion of configuration at a stereogenic center.
center

42
 Substrate Reactivity in SN2 Reactions

• As the number of R groups on the carbon with the leaving

group increases,
increases the rate of an SN2 reaction decreases.
decreases

• Methyl and 1 1° alkyl halides undergo SN2 reactions with ease.

ease
• 2° Alkyl halides react more slowly.
• 3
3° Alkyl halides do not undergo SN2 reactions due to steric
effects.
• Bulky R groups near the reaction site make nucleophilic
attack from the backside more difficult, slowing the reaction
rate. 43
 Steric Effects in SN2 Reactions

Electrostatic potential maps illustrate the effects of steric

hi d
hindrance aroundd the
th carbon
b b
bearing
i th leaving
the l i group in
i
a series of alkyl halides.

44
 Energy Diagrams for SN2 Reactions
• The higher the Ea, the slower the reaction rate.
• Thus, any factor that increases Ea decreases the reaction rate.

45
 Effect of Sterics on Rate of SN2 Reactions
• Increasing the number of R groups on the carbon with the
leaving group increases crowding in the transition state,
thereby decreasing the reaction rate.
• The SN2 reaction is fastest with unhindered halides.

46
Characteristics of the SN2 Mechanism

47
 SN1 Reaction Mechanism

• Key features of the SN1 mechanism are that it has two steps,
and carbocations are formed as reactive intermediates.
48
Energy Diagrams for SN1 Reactions

49
 Stereochemistry of SN1 Reactions

To understand the stereochemistry of the SN1 reaction, we

must examine the geometry of the carbocation intermediate.
intermediate

50
 Racemization in SN1 Reactions
• Loss of the leaving group in Step [1] generates a planar
carbocation that is achiral. In Step [2], attack of the nucleophile
can occur on either
ith side
id to
t afford
ff d two
t products
d t which
hi h are a pair
i
of enantiomers.
• Because there is no p preference for nucleophilic
p attack from
either direction, an equal amount of the two enantiomers is
formed—a racemic mixture. This process is called racemization.

51
Racemization in SN1 Reactions

52
 Substrate Reactivity in SN1 Reactions
• The rate of an SN1 reaction is affected by the type of alkyl halide
involved.

• This trend is exactly opposite to that observed in SN2 reactions.

53
 Carbocation Stability

• The effect of the type of alkyl halide on SN1 reaction rates

can be explained by considering carbocation stability.
stability
• Carbocations are classified as primary (1°), secondary (2°),
or tertiary
y ((3°),
), based on the number of R g
groups
p bonded to
the charged carbon atom.
• As the number of R groups increases, carbocation stability
increases.

54
Inductive Effects and Carbocation Stability

• The order of carbocation stability can be rationalized

through inductive effects and hyperconjugation which occur
by the pull of electron density through σ bonds caused by
electronegativity
g y differences between atoms.
• Alkyl groups are electron donor groups that stabilize a
positive charge because they contain several σ bonds, each
containing
t i i electron
l t d
density.
it
• As a result, alkyl groups are more polarizable than a
hydrogen atom,
atom and better able to donate electron density.
density
• In general, the more alkyl groups attached to a carbon with a
positive charge, the more stable the cation will be.

55
Carbocation Stability

56
Hyperconjugation and Carbocation Stability
• The order of carbocation stability is also a consequence of
hyperconjugation.
• Hyperconjugation is the spreading out of charge by the
overlap of an empty p orbital with an adjacent σ bond.
• This overlap delocalizes the positive charge on the
carbocation over a larger volume, thus stabilizing it.
• For example: (CH3)2CH+ can be stabilized by hyperconjugation
but CH3+ cannot .

57
Characteristics of the SN1 Mechanism

58
Predicting the Mechanism of Nucleophilic
S b tit ti
Substitutions Reactions
R ti

• F
Four factors
f t are relevant
l t in
i predicting
di ti whether
h th a
given reaction is likely to proceed by an SN1 or an SN2
mechanism:

• The alkyl halide—CH3X,

X RCH2X,
X R2CHX,
CHX or R3CX

• The nucleophile—strong
nucleophile strong or weak

• The leaving group—good

group good or poor

• The solvent—protic
solvent protic or aprotic
59
 Nature of the Alkyl Halide
• The most important factor is the identity of the alkyl halide.

60
 Effect of the Nucleophile
• Strong nucleophiles (which usually bear a negative charge)
present in high concentrations favor SN2 reactions.
• Weak nucleophiles, such as H2O and ROH favor SN1 reactions
by decreasing the rate of any competing SN2 reaction.
• Consider what happens when the 2° alkyl halide A,A which can
react by either mechanism, is treated with either the strong
nucleophile
p HO¯ or the weak nucleophile
p H2O.

61
 Predicting SN1 or an SN2 Nucleophile

• The strong nucleophile favors an SN2 mechanism.

62
• The weak nucleophile favors an SN1 mechanism.

63
 Effect of Leaving Groups
• A better leaving group increases the rate of both SN1 and SN2
reactions.

64
 Effect of Solvent

• Polar protic solvents like H2O and ROH favor SN1

reactions
ti b
because th ionic
the i i intermediates
i t di t (both
(b th cations
ti
and anions) are stabilized by solvation.

• Polar aprotic solvents favor SN2 reactions because

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

65
Predicting SN1 or an SN2—Summary

66
 Vinyl and Aryl Halides
• SN1 or SN2 reactions occur on sp3 hybridized carbons.
• Vinyl and aryl halides,
halides which have a halogen attached to a
sp2 hybridized carbon, do not undergo SN1 or SN2 reactions.
• Heterolysis of the C–X bond would form a highly unstable
vinyl or aryl cation.

67
Organic Synthesis Using Alkyl Halides

68