Organic Reactions
A detailed study of the following:
Dehydration Synthesis
Addition
Free Radical Reactions
Substitution (SN1 & SN2)
Elimination (E1 & E2)
Dehydration Synthesis
• A reaction involving the formation of a single
product through the formation & removal of
water.
• These reactions usually involve reactions
between an alcohol and something else.
What can be made using this process?
•
•
•
•
Alcohol + alcohol  Ether*
Alcohol + acid  Ester*
Alcohol + ammonia  Amine
Alcohol + Acid  Amide
• * These are discussed further
Dehydration of Alcohols to form Ethers
• Simple, symmetrical ethers can be formed from the
intermolecular acid-catalyzed dehydration of 1° (or
methyl) alcohols (a “substitution reaction”)
• 2° and 3° alcohols can’t be used because they eliminate
(intramolecular dehydration) to form alkenes
OH
H3O+
+
OH
+
O
heat
H2O
•Unsymmetrical ethers can’t be made this way because a mixture of products
results:
+
OH
+
CH3-OH
H3O
heat
+
O
+
O
O
Mechanism of Formation of Ethers from Alcohols
• First, an alcohol is protonated by H3O+
• Next, H2O is displaced by another alcohol (substitution)
• Finally, a proton is removed by H2O to form the product
H
OH
H
O
+
+
O
H
H
O
H
H
H
H
OH
O
O
+
O
+
H
H
H
H
H
O
H
+
H
H
O
O
+
O
H
H
Combustion of alkanes
• Alkanes are unreactive as a family because of the strong C–C and
C–H bonds as well as them being nonpolar compounds. At room
temperature alkanes do not react with acids, bases, or strong
oxidizing agents.
• Alkanes do undergo combustion in air (making them good fuels):
2C2H6(g) + 7O2(g)  4CO2(g) + 6H2O(l)
H = –2855 kJ
• Complete combustion produced carbon dioxide and water while
incomplete may produces a combination of carbon monoxide,
carbon and water in addition to carbon dioxide. Carbon dioxide
contributes to global warming while carbon monoxide is toxic;
hemoglobin binds to carbon monoxide in preference to oxygen
causing suffocation and even death.
Products of combustion
Complete combustion produces:
carbon dioxide
water vapour
while incomplete may produces a combination of :
carbon monoxide
carbon
water vapour
carbon dioxide.
Carbon dioxide contributes to global warming.
Carbon monoxide is toxic; hemoglobin binds to carbon monoxide in
preference to oxygen causing suffocation and even death.
Alkane Substitution Reaction
• In the presence of light alkanes undergo substitution reaction with
halogens.
RH + Br2  RBr + HBr
• In a substitution reaction, one atom of a molecule is removed and replaced
or substituted by another atom or group of atoms.
• Mechanism of subtitution reaction involves free radicals.
Free Radical Substitution reaction
UV
CH3CH 2CH 2CH 2CH 2CH3  Br2 
 CH3CH 2CH 2CH 2CH 2CH 2 Br  HBr
1-bromohexane
For a reaction between an alkane and bromine to occur, C-H and Br-Br bonds
must break.
The C-H bond is stronger than Br-Br bond
Therefore, the reaction proceeds by first the breakage of Br-Br bond, which is
brought about by UV light.
Br-Br bond can be broken in one of two ways.
Br2 
 2Br .
UV
or
UV

Br2 
 Br :  Br

Free Radical Substitution reaction
When the bond is broken, either
•the bond pair can be equally shared between the two atoms producing two
bromine atoms (called free radicals), or
•The bond pair goes with one atom producing a positive and a negatively
charged ions of bromine.
The first type of bond breakage producing free radicals is referred to as a homolytic
fission and the second heterolytic fission.
•Homolytic fission because the bond pairs are equally distributed, or particles
that are the same in every way is produced.
•homolytic fission of the halogen takes place.
In the next step, the free radical removes a hydrogen atom from the alkane forming
hydrogen bromine and a free radical of the alkane.
CH3CH2CH2CH2CH2CH2-H + Br•  CH3CH2CH2CH2CH2CH2• + HBr
Free Radical Substitution reaction
•
The free radical goes on to react with a molecule of chlorine and regenerate another
chlorine free radical.
CH3CH2CH2CH2CH2CH2• + Br2  CH3CH2CH2CH2CH2CH2Br + Br•
And so on.
Because this reaction, once initiated, can keep itself going is referred to as a chain reaction.
The reaction can conducted with any halogen and the mechanism would be the same.
Not only that, more than one hydrogen can be substituted.
UV
CH3CH 2CH 2CH 2CH 2CH3  2Br2 
 CH3CH 2CH 2CH 2CH 2CHBr2  2HBr
1,1
dibromohexane
Mechanism of chlorination of methane
CHAIN REACTION
1. Initiation
..
: Cl
..
..
Cl :
..
light
2
..
: Cl .
..
a free radical
“dissociation”
R
E
P
E
A
T
I
N
G
S
T
E
P
S
2. Chain Propagation (first step)
+
CH3 H
..
: Cl .
..
H
..
Cl :
..
+
. CH3
methyl radical
“hydrogen abstraction”
3. Chain Propagation (second step)
. CH3
+
..
: Cl
..
..
Cl :
..
CH3
..
Cl :
..
+
..
: Cl .
..
feeds back into
step two
Mechanism of chlorination of methane
4. Termination Steps
..
2 : Cl .
..
CH3.
..
: Cl .
..
+
+
. CH
3
. CH
3
“recombinations”
..
: Cl
..
..
Cl :
..
CH3CH3
..
: Cl CH3
..
These steps stop
the chain reaction
Reactions of Alkenes: Addition Reactions
Hydrogenation of Alkenes – addition of H-H (H2) to the
π-bond of alkenes to afford an alkane. The reaction must be
catalyzed by metals such as Pd, Pt, Rh, and Ni.
H
H
H
C
+
C
Pd/C
H
H
EtOH
H
H
C-C π-bond
= 243 KJ/mol
H-H
= 435 KJ/mol
H
C
C
H
H
H
H°hydrogenation = -136 KJ/mol
H
C-H
= 2 x -410 KJ/mol
= -142 KJ/mol
• The catalysts is not soluble in the reaction media, thus this
process is referred to as a heterogenous catalysis.
• The catalyst assists in breaking the -bond of the alkene and
the H-H -bond.
• The reaction takes places on the surface of the catalyst. Thus,
the rate of the reaction is proportional to the surface area
of the catalyst.
14
14
• Carbon-carbon -bond of alkenes and alkynes can be reduced
to the corresponding saturated C-C bond. Other -bond bond
such as C=O (carbonyl) and CN are not easily reduced by
catalytic hydrogenation. The C=C bonds of aryl rings are not
easily reduced.
O
O
H2, PtO2
ethanol
O
C5H11
OH
H2, Pd/C
CH3(CH2)16CO2H
Linoleic Acid (unsaturated fatty acid)
Steric Acid (saturated fatty acid)
O
O
OCH3
H2, Pd/C
OCH3
ethanol
C
H2, Pd/C
N
C
N
ethanol
15
15
Heats of Hydrogenation -an be used to measure relative stability
of isomeric alkenes
H
H3C
H
CH3
cis-2-butene
H°combustion : -2710 KJ/mol
H
H3C
H
H2, Pd
CH3
cis-2-butene
H
H3C
CH3
H
trans-2-butene
trans isomer is ~3 KJ/mol
more stable than the
cis isomer
-2707 KJ/mol
H2, Pd
H
CH3
CH3CH2CH2CH3
H3C
H
trans-2-butene
H°hydrogenation: -119 KJ/mol
-115 KJ/mo
trans isomer is ~4 KJ/mol more stable than the cis isomer
The greater release
of heat, the less
stable the reactant.
16
16
Heats of Hydrogenation of Some Alkenes
Alkene
H2C=CH2
H
H
H3C
H
monosubstituted
H
H° (KJ/mol)
136
125 - 126
H
117 - 119
H3C
CH3
H
CH3
disubstituted
H3C
H3C
H
114 - 115
H
116 - 117
H3C
H
H3C
H
H3C
CH3
H3C
CH3
H3C
CH3
trisubstituted
tetrasubstituted
112
110
17
17
Electrophilic Addition of Hydrogen Halides to Alkenes
C-C -bond: H°= 368 KJ/mol
C-C -bond: H°= 243 KJ/mol
-bond of an alkene can
act as a nucleophile!!
Electrophilic addition reaction
H
H
Br
C C
H
+
H-Br
H
nucleophile
H
H
C C
H
H
H
electrophile
Bonds broken
C=C -bond 243 KJ/mol
H–Br
366 KJ/mol
Bonds formed
H3C-H2C–H -410 KJ/mol
H3C-H2C–Br -283 KJ/mol
calc. H° = -84 KJ/mol
expt. H°= -84 KJ/mol
18
18
Reactivity of HX correlates with acidity:
HF << HCl < HBr < HI fastest
Regioselectivity of Hydrogen Halide Addition:
H
Markovnikov's Rule
Br H
H-Br
C
H
slowest
R
R
R
C
H
R
C
R
C
C
H
C
R
R C C H
H H
H
H-Br
H
H-Br
Br H
R C C H
R H
Br H
R C C R
R H
+
+
+
H Br
R C C H
H H
none of this
H Br
R C C H
R H
none of this
H Br
R C C R
R H
none of this
H
R
C
C
R'
H
H-Br
Br H
R C C R
H H
+
H Br
R C C R'
H H
Both products observed
For the electrophilic addition of HX across a C=C bond, the H (of
HX) will add to the carbon of the double bond with the most H’s
(the least substitutent carbon) and the X will add to the carbon of
19
19
the double bond that has the most alkyl groups.
Mechanism of electrophilic addition of HX to alkenes
Regioselectivity determined by Markovnikov’s rule –
which can be explained by comparing the stability of the
intermediate carbocations
20
20
For the electrophilic addition of HX to an unsymmetrically
substituted alkene:
• The more highly substituted carbocation intermediate is
formed.
• More highly substituted carbocations are more stable than
less substituted carbocations. (hyperconjugation)
• The more highly substituted carbocation is formed faster
than the less substituted carbocation. Once formed, the
more highly substituted carbocation goes on to the final
product more rapidly as well.
21
21
Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes - In reactions involving
carbocation intermediates, the carbocation may sometimes rearrange if a
more stable carbocation can be formed by the rearrangement. These involve hydride and
methyl shifts.
H
C
H3C
C
H3C
Cl
H
H-Cl
C
H
C
H3C
H3C
H
H
H
H
C
C
H
H
+
H
~ 50%
expected product
H
C
H3C
C
H3C
Cl
CH3
H
C
H
H-Cl
H3C
C
C
Cl
H
H3C
H
C
C
CH3
H
H
H
H
~ 50%
H
C
H3C
C
H3C
H3C
H
+
C
H3C
H3C
H
H
C
C
Cl
H
H
Note that the shifting atom or group moves with its electron pair.
A MORE STABLE CARBOCATION IS FORMED. 22
22
Free-radical Addition of HBr to Alkenes
H3CH2C
H3CH2C
R
R
R
H
H
C
H
C
H
C
R
C
R
C
R
C
C
H
C
H
H
H-Br
Br H
H3CH2C C C H
H H
H
H-Br
Br H
H3CH2C C C H
H H
peroxides
(RO-OR)
H-Br
C
H
C
H
C
R
C
R'
H
ROOR
(peroxides)
H
H-Br
ROOR
H
H-Br
ROOR
H
H-Br
ROOR
+
+
H Br
H3CH2C C C H
H H
none of this
H Br
H3CH2C C C H
H H
Polar mechanism
(Markovnikov addition)
Radical mechanism
(Anti-Markovnikov addition)
none of this
Br H
R C C H
H H
none of this
Br H
R C C H
R H
none of this
Br H
R C C R
R H
none of this
Br H
R C C R
H H
+
+
H Br
R C C H
H H
H Br
R C C H
R H
+
H Br
R C C R
R H
+
H Br
R C C R'
H H
Both products observed
The regiochemistry of
HBr addition is reversed
in the presence of
peroxides.
Peroxides are radical
initiators - change in
mechanism
23
23
The regiochemistry of free radical addition of H-Br to alkenes
reflects the stability of the radical intermediate.
H
H
R C•
R C•
H
Primary (1°)
R
R C•
R
<
Secondary (2°)
R
<
Tertiary (3°)
24
Acid-Catalyzed Hydration of Alkenes
The addition of water (H-OH) across the -bond of an alkene to give an alcohol; opposite
of dehydration
H3C
C
H3C
CH2
H2SO4, H2O
H3C
H3C
H3C
C
OH
This addition reaction follows Markovnikov’s rule The more
highly substituted alcohol is the product and is derived from
The most stable carbocation intermediate.
Reactions works best for the preparation of 3° alcohols
25
p. 91a
Mechanism for this reaction is the reverse of the acid-catalyzed dehydration
of alcohols:
27
6.11: Thermodynamics of Addition-Elimination Equlibria
H3C
H2SO4
C
CH2
H3C
C
H3C
H3C
+ H2O
H3C
Bonds broken
C=C -bond 243 KJ/mol
H–OH
497 KJ/mol
OH
Bonds formed
H3C-H2C–H -410 KJ/mol
(H3C)3C–OH -380 KJ/mol
calc. H° = -50 KJ/mol
G° = -5.4 KJ/mol H° = -52.7 KJ/mol
S° = -0.16 KJ/mol
How is the position of the equilibrium controlled?
Le Chatelier’s Principle - an equilibrium will adjusts to any stress
The hydration-dehydration equilibria is pushed toward hydration (alcohol) by adding water
and toward alkene (dehydration) by removing water.
28
The acid catalyzed hydration is not a good or general method for
the hydration of an alkene.
Oxymercuration: a general (2-step) method for the Markovnokov
hydration of alkenes
H
H
C
C4H9
H
1) Hg(OAc)2, H2O
C
H
Hg(OAc)
C
H H
O
C
H3C
C
C4H9
H
Ac= acetate =
OH
O
2) NaBH4
OH
C
C4H9
H
C
H H
NaBH4 reduces the C-Hg
bond to a C-H bond
29
Addition of Halogens to Alkenes
X2 = Cl2 and Br2
X2
X
X
(vicinal dihalide)
C C
C C
alkene
1,2-dihalide
Stereochemistry of Halogen Addition - 1,2-dibromide has the anti stereochemistry
Br
Br
+
+
Br2
Br
Br
not observed
CH3
Br
Br2
H
CH3
Br
30
Substitution Reaction with Halides
(1)
bromomethane
If concentration of (1) is
doubled, the rate of the
reaction is doubled.
If concentration of (2) is
doubled, the rate of the
reaction is doubled.
(2)
methanol
If concentration of (1) and
(2) is doubled, the rate of
the reaction quadruples.
Substitution Reaction with Halides
(1)
(2)
bromomethane
methanol
Rate law:
rate = k [bromoethane][OH-]
this reaction is an example of a SN2 reaction.
S stands for substitution
N stands for nucleophilic
2 stands for bimolecular
Mechanism of SN2 Reactions
Alkyl halide
The rate of reaction depends on the
concentrations of both reactants.
When the hydrogens of bromomethane
are replaced with methyl groups the
reaction rate slow down.
The reaction of an alkyl halide in which
the halogen is bonded to an asymetric
center leads to the formation of only
one stereoisomer
Relative rate
1200
40
1
≈0
Mechanism of SN2 Reactions
Hughes and Ingold proposed the following mechanism:
Transition state
Increasing the concentration of either of the
reactant makes their collision more probable.
Mechanism of SN2 Reactions
Steric effect
Energy
activation
energy: G2
activation
energy: G1
reaction coordinate
reaction coordinate
Inversion of configuration
(R)-2-bromobutane
(S)-2-butanol
Factor Affecting SN2 Reactions
The leaving group
-
HO
HO
HO
HO
relative rates of reaction
+ RCH2I
RCH2OH + I
+ RCH2Br
RCH2OH + Br
+ RCH2Cl
RCH2OH + Cl
+ RCH2F
RCH2OH + F
pKa HX
30 000
10 000
200
1
-10
-9
-7
3.2
The nucleophile
In general, for halogen substitution the
strongest the base the better the
nucleophile.
pKa
Nuclephilicity
SN2 Reactions With Alkyl Halides
an alcohol
a thiol
an ether
a thioether
an amine
an alkyne
a nitrile
Substitution Reactions With Halides
1-bromo-1,1-dimethylethane
1,1-dimethylethanol
Rate law:
If concentration of (1) is
doubled, the rate of the
reaction is doubled.
If concentration of (2) is
doubled, the rate of the
reaction is not doubled.
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a SN1
reaction.
S stands for substitution
N stands for nucleophilic
1 stands for unimolecular
Mechanism of SN1 Reactions
Alkyl halide
Relative rate
The rate of reaction depends on the
concentrations of the alkyl halide only.
≈0*
When the methyl groups of 1-bromo1,1-dimethylethane are replaced with
hydrogens the reaction rate slow down.
≈0*
The reaction of an alkyl halide in which
the halogen is bonded to an asymetric
center leads to the formation of two
stereoisomers
12
1 200 000
* a small rate is actually observed as a result of a SN2
Mechanism of SN1 Reactions
nucleophile attacks the
carbocation
slow
C-Br bond breaks
fast
Proton dissociation
Mechanism of SN1 Reactions
Rate determining step
G
Carbocation
intermediate
R++ X+
R-OH2
R-OH
Mechanism of SN1 Reactions
Inverted
configuration relative
the alkyl halide
Same configuration
as the alkyl halide
Factor Affecting SN1 reaction
Two factors affect the rate of a SN1 reaction:
• The ease with which the leaving group dissociate from the carbon
• The stability of the carbocation
The more the substituted the
carbocation is, the more
stable it is and therefore the
easier it is to form.
As in the case of SN2, the
weaker base is the leaving
group, the less tightly it is
bonded to the carbon and the
easier it is to break the bond
The reactivity of the
nucleophile has no effect on
the rate of a SN1 reaction
Comparison SN1 – SN2
SN1
SN2
A two-step mechanism
A one-step mechanism
A unimolecular rate-determining step
A bimolecular rate-determining step
Products have both retained and inverted
configuration relative to the reactant
Product has inverted configuration
relative to the reactant
Reactivity order:
3o > 2o > 1o > methyl
Reactivity order:
methyl > 1o > 2o > 3o
Elimination Reactions
1-bromo-1,1-dimethylethane
2-methylpropene
Rate law:
rate = k [1-bromo-1,1-dimethylethane][OH-]
this reaction is an example of a E2 reaction.
E stands for elimination
2 stands for bimolecular
The E2 Reaction
A proton is
removed
Br- is eliminated
The mechanism shows that an E2
reaction is a one-step reaction
Elimination Reactions
1-bromo-1,1-dimethylethane
2-methylpropene
Rate law:
If concentration of (1) is
doubled, the rate of the
reaction is doubled.
rate = k [1-bromo-1,1-dimethylethane]
If concentration of (2) is
doubled, the rate of the
reaction is not doubled.
this reaction is an example of a E1
reaction.
E stands for elimination
1 stands for unimolecular
The E1 Reaction
The base
removes a proton
The alkyl halide
dissociate, forming a
carbocation
The mechanism shows that an E1
reaction is a two-step reaction
Products of Elimination Reaction
30%
2-bromobutane
50%
80%
2-butene
20%
1-butene
The most stable alkene is the
major product of the reaction
for both E1 and E2 reaction
For both E1 and E2 reactions, tertiary alkyl halides
are the most reactive and primary alkyl halides
are the least reactive
The greater the number of
alkyl substituent the more
stable is the alkene
Competition Between
SN2/E2 and SN1/E1
SN1
SN2
E1
E2
rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] + k2[alkyl halide][base]
• SN2 and E2 are favoured by a high concentration of a good
nucleophile/strong base
• SN1 and E1 are favoured by a poor nucleophile/weak base, because a
poor nucleophile/weak base disfavours SN2 and E2 reactions
Competition Between
Substitution and Elimination
• SN2/E2 conditions:
In a SN2 reaction: 1o > 2o > 3o
In a E2 reaction: 3o > 2o > 1o
10%
90%
75%
25%
100%
Competition Between
Substitution and Elimination
• SN1/E1 conditions:
All alkyl halides that react under SN1/E1 conditions will give
both substitution and elimination products (≈50%/50%)
Summary of Elimination & Substitution
Reactions
• Alkyl halides undergo two kinds of nucleophilic subtitutions:
SN1 and SN2, and two kinds of elimination: E1 and E2.
• SN2 and E2 are bimolecular one-step reactions
• SN1 and E1 are unimolecular two step reactions
• SN1 lead to a mixture of stereoisomers
• SN2 inverts the configuration od an asymmetric carbon
• The major product of a elimination is the most stable alkene
• SN2 are E2 are favoured by strong nucleophile/strong base
• SN2 reactions are favoured by primary alkyl halides
• E2 reactions are favoured by tertiary alkyl halides