Download lecture 2 - alcohols-ethers

Alcohols and Ethers-2
Dr AKM Shafiqul Islam
School of Bioprocess Engineering
University Malaysia Perlis (UniMAP)
Substitution Reactions of Alcohols
Alcohols are not reactive in nucleophilic substitution
or elimination reactions since hydroxide is a strong base,
poor leaving group.
R OH
Nu
R
OH
X
X
R+
Nu
no reaction in
either case
SN1
+
R
HOSN2
+
strong
base
HOpoor leaving
group
Substitution Reactions of Alcohols
The situation improves under acid conditions. We
change the leaving group to water, a neutral group.
R
OH
H+
R
O
H
NuNu R
+
H
neutral
O
H
neutral
H
- H2O
R+
NuNu R
Electrophiles
Molecules that contain atoms with empty
orbital, which can accommodate electrons.
Typically, these are positively charged.
Examples:
H
CH3CH2
BF3
Boron has only 6 valence electrons.
BF3 is a Lewis acid.
Nucleophiles
Molecules that contain atoms with lone pairs, which
can donate electrons. Often these are negatively
charged. Almost all the time they contain elements
from groups 15–17 of the periodic table, since those
have lone pairs.
Examples:
HO
Cl
CH3NH2
H2O
SN1 reaction
► The
SN1 reaction is a substitution reaction in
organic chemistry. "SN" stands for nucleophilic
substitution and the "1" represents the fact that
the rate-determining step is unimolecular.
► It
involves a carbocation intermediate and is
commonly seen in reactions of secondary or
tertiary alkyl halides or, under strongly acidic
conditions, with secondary or tertiary alcohols.
SN2 reaction
►
The SN2 reaction (known as bimolecular
substitution nucleophilic) is a type of nucleophilic
substitution, where a lone pair from a nucleophilic
attacks an electron deficient electrophilic center and
bonds to it, expelling another group called a leaving
group. Thus the incoming group replaces the leaving
group in one step.
►
Since two reacting species are involved in the slow, ratedetermining step of the reaction, this leads to the name
bimolecular nucleophilic substitution, or SN2.
►
The somewhat more transparently named analog to SN2
among inorganic chemists is the interchange
mechanism.
Nucleophilic Substitution
R
X
substrate
+
:Nu
nucleophile
chloride
bromide
iodide
hydroxide
water
alkoxides
alcohols
cyanide
amines
sulfides
acetylides
carbanions
carboxylates
R
Nu
product
+
.. _
:X:
..
leaving group
chloride
bromide
iodide
water
alcohols
sulfonates
amines
Examples
HI
+ H2O
I
HO

iodocyclohexane
cyclohexanol
HCl
OH

1-propanol
Cl + H O
2
1-chloropropane
Mechanism of Substitution
► Secondary
and tertiary alcohols
undergo SN1 reaction.
H3C
H3C
H3C
H Br
OH
tert-butanol
carbocation
O
H
CH2
CH3
H3C
H
H3C
H3C
H3C
CH3
H3C
Br-
CH3
HBr
Br
tert-butyl chloride
- H2O
Mechanism of Substitution
► Primary
alcohols undergo SN2 reaction. Primary
carbocations are too unstable to be formed.
H
Br
O H
OH
1-butanol
H
Br
- H2O
O H
H
Attack from back-side
Br
1-bromobutane
► Elimination
Elimination
of water, dehydration, is
commonly obtained using sulfuric acid
(H2SO4) as a catalyst.
H3C
OH
CH3
H2SO4

H3CHC CHCH3 + H2O
 The acid is mandatory to convert the poor
leaving group OH– into a good leaving group
H2O.
Elimination
► First
step is protonation of the hydroxyl
group.
H
H3C
OH
H2SO4
CH3

H3C
O H
CH3
Loss of water leads to a carbocation.
H
H3C
O H - H2O
CH3
H3C
CH3
Elimination
a base removes a proton b to the
carbocation
center.
H3C
► Second,
b
H H
H3CHC CHCH3

CH3
+
H2SO4
OSO3H
Notice that this reaction is an E1 reaction.
•Rate-determining step is the formation of the
carbocation.
Elimination
► In
case we have a choice between several
b-hydrogens, the most stable alkene is
formed preferentially.
CH3
H3PO4 H3C
CH3CHCH2CH3
OH

H3C
CH3 H2C
CH +
H3C
84 %
CH2
CH3
16 %
Elimination
► As
a result of the E1 mechanism, the ease
of dehydration follows the order:
R
H
R
R
OH
>
H
OH
>
R
H
R
R
OH
 That directly reflects the stability of the
intermediate carbocations.
R
R
R
H
R
>
H
R
>
R
H
Elimination
► Primary
alcohols undergo dehydration by an E2
pathway.
► First, however, we generate the good leaving
H
group.
+
OH
H
O H
The subsequent steps, removal of water and
deprotonation, take place simultaneously.
OSO3H
H
H3C
CH
H
O H
H3C
CH2
► The
Substitution of Ethers
behavior of ethers is comparable to
alcohols.
 pKa of the leaving group is comparable.
H OCH3
H OH
pKa
15.7
15.5
Activation by acid allows substitution.
H
R O R'
R O R' + HI
R
I
+
R'
OH

Substitution of Ethers
► The
mechanism involves first a protonation
H
step.
R O R' + HI
R O R'
The subsequent steps are determined by the
stability of the intermediates.
• Stable carbocation  SN1
• Unstable carbocation  SN2
Substitution of Ethers
► Examples
CH3
H3C
CH3 H
H+ IH3C
OCH3
CH3
OCH3
CH3
stable carbocation
CH3
H3C
SN1
CH3
I
H3C
CH3 attack of nucleophile
I
CH3
Substitution of Ethers
H3C
H+ IOCH3
H3C
H
OCH3
SN2
Primary carbocations are unstable;
thus, reaction proceeds via SN2.
H3C
H
O CH3
SN2
H3C
OH
+ CH3I
I
Reaction takes place on the less hindered of the
two alkyl groups.
Ethers
► Only
hydrogen halides react with ethers
► Ethers commonly used as solvents
► Often used solvents are:
O
O
tetrahydrofuran
THF
O
O
tetrahydropyran
1,4-dioxan
CH3CH2OCH2CH3
diethyl ether
"ether"
CH3OCH2CH2OCH3
dimethoxyethane
DME
Epoxides
►A
special group of ethers are epoxides.
► Here the oxygen is incorporated into a threeO
membered ring.
H2C CH2
 We name epoxides commonly by using the name
of the parent alkene followed by oxide.
O
H2C CH
CH3
propylene oxide
O
H2C CH2
ethylene oxide
Epoxides
► Alternatively
we can use the name of the
parent alkane
an
“epoxy”
prefix
O
O with
CH
3
H2C C
CH3
1,2-epoxy-2-methylpropane
H2C CH CH
3
CH2
1,2-epoxybutane
Formation of epoxides can be accomplished
by a reaction of a peracid with an alkene
O
+ RCOOH
R
O
O
+
R
RCOH
Epoxides
► Reaction
with hydrogen halides proceeds as
with other ethers.
H
O
H2C CH2 + HBr
O
H2C CH2
ethylene oxide
Br
HO
Br
Epoxides
► Reaction
with water and alcohols can be
accomplished via acid catalysis.
H
O
H2C CH2 + H+
O
H2C CH2
ethylene oxide
OR
HO
HO R
Epoxides
► For unsymmetrical epoxides we have to inspect
the individual steps in the reaction more
carefully.
H
acidic conditions
H+
O
H3C
O
CH3
CH3OH
O
OH
H3C
H3C
H
O
CH3O
H3C
O
H3C
OCH3
H+
O
H3C
basic conditions
We obtain different results depending on the
reaction conditions used.
OCH3
► Acidic
Epoxides
conditions:
 First step is the formation of an oxonium
species.
H
O
H+
H3C
O
H3C
• Attack of the nucleophile can take place
at two positions.
H
O
H3C
Epoxides
►
For the process of breaking the C-O bond of the epoxide
we have to assume that the oxygen is keeping the bonding
electrons, thus creating a partial positive charge on the
neighboring carbon.
H
+
H
O
+
+ secondary
O
tertiary
+
carbocation
carbocation
H3C
H3C
 Now we have carbocation-type carbons that can
be distinguished via their stability.
Epoxides
► Reaction
H
O
proceeds at the tertiary center
H
+
+
+
H3C
H
H
O +
+
CH3OH
CH3
H3C
OH
- H+
O
H3C
CH3
O
CH3
CH3
O
H3C
OH
OH
Epoxides
► Under
basic reaction conditions the situation
changes.
 First we generate an alcoholate anion
 Attack takes place on the less hindered side.
base
CH3OH
CH3O
O
CH3
Epoxides
► Finally,
the reaction is completed by taking
up a proton.
CH3O
CH3O
O
CH3
CH3
CH3O
O
O H
CH3
H+
Epoxides
► Ring
opening of epoxides is an important
reaction in organic chemistry. A wide variety
of nucleophiles can be used for this
reaction.
OH
O
+
(CH3)2NH
H3C
H3C CH2
N
CH2 CH3
CH3
CH3CH2CH2CH2-Li+
O
OH
+
H3C CH2
H3C CH2 CH2
H2C
CH2 CH3