Download 4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen

Reaction of Alcohols with Hydrogen Halides
4.7
Preparation of Alkyl Halides from
Alcohols and Hydrogen Halides
ROH +
HX → RX
RX + HOH
Hydrogen halide reactivity
HF
HCl
HBr
HI
ROH + HX → RX + H2O
least reactive
Preparation of Alkyl Halides
Reaction of Alcohols with Hydrogen Halides
ROH +
HX → RX
RX + HOH
most reactive
25°
25°C
(CH3)3COH + HCl
HCl
78-88%
Alcohol reactivity
CH3OH
Methanol
RCH2OH
Primary
R2CHO
CHOH
Secondary
OH + HBr
R3COH
Tertiary
80-100°
80-100°C
Br + H2O
73%
CH3(CH2)5CH2OH + HBr
HBr
least reactive
(CH3)3CCl + H2O
120°
120°C
CH3(CH2)5CH2Br + H2O
most reactive
87-90%
Preparation of Alkyl Halides
Question 5
A mixture of sodium bromide and sulfuric
acid may be used in place of HBr.
CH3CH2CH2CH2OH
NaBr
NaBr
H2SO4
heat
CH3CH2CH2CH2Br
What is the product of the reaction of 2methylcyclohexanol with HBr?
HBr?
A)
B)
C)
D)
70-83%
Question 6
What product will be isolated from the reaction
of 2-pentanol with HBr?
HBr?
A)
B)
C)
D)
4.8
Mechanism of the Reaction of
Alcohols with Hydrogen Halides
About mechanisms
A mechanism describes how reactants are
converted to products.
About mechanisms
For the reaction:
(CH3)3COH + HCl
25°
25°C
(CH3)3CCl + H2O
Mechanisms are often written as a series of
chemical equations showing the elementary steps.
tert-Butyl
tert-Butyl alcohol
An elementary step is a reaction that proceeds
by way of a single transition state.
the generally accepted mechanism involves
three elementary steps.
Mechanisms can be shown likely to be correct,
but cannot be proven correct.
Step 1 is a Brø
Brønsted acid-base reaction.
Like proton transfer
from a strong acid to
water, proton transfer
..
..
: from a strong acid to
O : + H Cl:
Cl
..
an alcohol is normally
H
very fast.
fast.
fast, bimolecular
Step 1: Proton Transfer
(CH3)3C
H
+
(CH3)3C O :
+
H
terttert-Butyloxonium ion
.. –
: Cl:
..
tert-Butyl
tert-Butyl chloride
Step 1: Proton Transfer
(CH3)3C
..
O: + H
..
:
Cl:
Cl
..
H
Two molecules react
in this elementary
step; therefore it is
bimolecular.
bimolecular.
fast, bimolecular
H
+
(CH3)3C O :
+
H
terttert-Butyloxonium ion
.. –
: Cl:
..
Potential Energy Diagram for Step 1
Step 1: Proton Transfer
(CH3)3C
..
O: + H
..
:
Cl:
Cl
..
δ+
(CH3)3CO
H
Potential
energy
fast, bimolecular
H
+
(CH3)3C O :
+
.. –
: Cl:
..
H
terttert-Butyloxonium ion
Species formed in
this step (tert
(tert-butyloxonium ion) is
an intermediate in
the overall reaction.
δ−
H
Cl
H
(CH3)3COH + H—
H—Cl
+
(CH3)3CO
H
Reaction coordinate
Step 2: Carbocation Formation
Dissociation of the
alkyloxonium ion involves
H
bond-breaking, without
+
any bond-making to
(CH3)3C O :
compensate for it. It
H
has a high activation
energy and is slow.
slow.
slow, unimolecular
Step 2: Carbocation Formation
A single molecule
reacts in this step;
therefore, it is
unimolecular.
unimolecular.
H
+
(CH3)3C O :
H
slow, unimolecular
H
+
(CH3)3C
+
H
+
(CH3)3C
: O:
tert-Butyl
tert-Butyl cation
H
Step 2: Carbocation Formation
+
(CH3)3C
(CH3)3C
Potential
energy
+
tert-Butyl
tert-Butyl cation
: O:
H
H
+
(CH3)3CO
H
O δ+
H
+
(CH3)3C + H2O
slow, unimolecular
H
: O:
Potential Energy Diagram for Step 2
δ+
H
+
tert-Butyl
tert-Butyl cation
H
+
(CH3)3C O :
The product of this
step is a carbocation.
It is an intermediate
in the overall process.
H + Cl –
H
H
Reaction coordinate
Carbocation
R
+
C
Figure 4.8 Structure of tert-Butyl
tert-Butyl Cation
R
CH3
R
The key intermediate in reaction of secondary
and tertiary alcohols with hydrogen halides is
a carbocation.
A carbocation is a cation in which carbon has
6 valence electrons and a positive charge.
Step 3: Carbocation Capture
+
(CH3)3C
(CH3)3C
tert-Butyl
tert-Butyl chloride
+
C
CH3
Positively charged carbon is sp2 hybridized.
All four carbons lie in same plane.
Unhybridized p orbital is perpendicular to
plane of four carbons.
Step 3: Carbocation Capture
Bond formation between
the positively charged
.. –
:
carbocation and the
+ : Cl:
Cl
..
negatively charged
chloride ion is fast.
fast.
fast, bimolecular
..
Cl:
Cl
.. :
H3C
Two species are
involved in this step.
Therefore, this step
is bimolecular.
bimolecular.
+
(CH3)3C
.. –
: Cl:
:
Cl
..
+
fast, bimolecular
(CH3)3C
tert-Butyl
tert-Butyl chloride
δ+
(CH3)3C
+
–
C+
Cl
CH3
Lewis acid
Lewis base
Electrophile
Nucleophile
The carbocation is
an electrophile.
electrophile.
Chloride ion is a
nucleophile.
nucleophile.
..
Cl:
Cl
.. :
Potential Energy Diagram for Step 3
Step 3: Carbocation Capture
H3C CH3
This is a Lewis acidLewis base reaction.
The carbocation is the
Lewis acid; chloride
ion is the Lewis base.
H3C CH3
C Cl
Cl
δ−
Potential
energy
+
(CH3)3C + Cl–
H 3C
(CH3)3C—Cl
Reaction coordinate
Question 7
Question 8
What is the rate-determining step in the reaction
of cyclobutanol with HCl?
HCl?
The species shown below represents _____ of
the reaction between isopropyl alcohol and
hydrogen bromide.
A) protonation of the OH group
A) the alkyloxonium ion intermediate
B) the transition step of the bimolecular
proton transfer
C) the transition state of the attack of the
nucleophile on the carbocation
D) the transition state of the unimolecular
dissociation
B) attack of the bromide on the carbocation
C) simultaneous formation of the C-Br bond
and the breaking of the C-OH bond
D) carbocation formation
Potential Energy Diagram - Overall
4.9
Potential Energy Diagrams for
Multistep Reactions:
The SN1 Mechanism
The potential energy diagram for a
multistep mechanism is simply a collection of the
potential energy diagrams for the individual
steps.
Consider the three-step mechanism for the
reaction of tert-butyl
tert-butyl alcohol with HCl.
(CH3)3COH + HCl
carbocation
formation
(CH3)3CCl + H2O
carbocation
formation
carbocation
capture
(CH 33)33C
R+
25°
25°C
δ+
O
H
δ–
Cl
carbocation
capture
R+
H
proton
transfer
ROH
proton
transfer
+
ROH2
ROH
RX
+
ROH2
RX
carbocation
formation
H
δ+
(CH 33)33C
O
carbocation
formation
carbocation
capture
carbocation
capture
δ+
δ+
R+
H
(CH 33)33C
R+
proton
transfer
proton
transfer
ROH
+
ROH2
ROH
RX
Mechanistic Notation
+
ROH2
RX
Mechanistic Notation
The mechanism just described is an
example of an SN1 process.
The molecularity of the rate-determining step
defines the molecularity of the overall reaction.
SN1 stands for substitution-nucleophilicunimolecular.
unimolecular.
δδ++
(CH
(CH33))33C
C
The molecularity of the rate-determining
step defines the molecularity of the
overall reaction.
H
H
O
O
δδ++
H
H
Rate-determining step is unimolecular
dissociation of alkyloxonium ion.
Activation energy for formation of tertiary
carbocation is less than that for formation of
secondary carbocation.
Question 9
Select the most stable carbocation.
carbocation.
δ+
R3C
δ+
H
O ••
A)
B)
C)
D)
H
R3C
H
+ •
O•
H
Eact
+
R3C + •• O ••
H
H
δ–
Cl
Preparation of Alkyl Halides
25°
25°C
(CH3)3COH + HCl
4.12
Reaction of Primary Alcohols with
Hydrogen Halides.
The SN2 Mechanism
(CH3)3CCl + H2O
78-88%
OH + HBr
80-100°
80-100°C
Br + H2O
73%
120°
120°C
CH3(CH2)5CH2OH + HBr
CH3(CH2)5CH2Br + H2O
87-90%
Preparation of Alkyl Halides
Primary carbocations are too high in energy to
allow S N1 mechanism. Yet, primary alcohols
are converted to alkyl halides.
Primary alcohols react by a mechanism called
SN2 (substitution-nucleophilic-bimolecular).
CH3(CH2)5CH2OH + HBr
120°
120°C
The SN2 Mechanism
Two-step mechanism for conversion of alcohols
to alkyl halides:
(1) proton transfer to alcohol to form
alkyloxonium ion
(2) bimolecular displacement of water
(water is the “leaving group”
group”) by the halide
which is the “nucleophile”
nucleophile”
CH3(CH2)5CH2Br + H2O
87-90%
Example
CH3(CH2)5CH2OH + HBr
120°
120°C
CH3(CH2)5CH2Br + H2O
Mechanism
Step 1:
Proton transfer from HBr to 1-heptanol
CH3(CH2)5CH2
Mechanism
Step 2:
Reaction of alkyloxonium ion with bromide
ion.
H
.. –
+
+ CH3(CH2)5CH2 O :
: Br:
Br
.. :
..
:
Br
..
..
O: + H
H
H
fast, bimolecular
H
+
CH3(CH2)5CH2 O :
slow, bimolecular
+
.. –
: Br:
..
H
H
CH3(CH2)5CH2
Heptyloxonium ion
+
1-Bromoheptane
:O:
H
δ+
δ–
Br
..
Br:
Br
.. :
CH2
OH2
Question 11
CH3(CH2)4CH2
Which of the following is the least able to serve
as a nucleophile in a chemical reaction?
A) BrB) OH-
proton
transfer
C) NH3
ROH
+
ROH2
D) CH3+
RX
Reagents for ROH to RX
Thionyl chloride
SOCl2 + ROH → RCl + HCl + SO 2
Examples
CH3CH(CH2)5CH3
SOCl
SOCl2
K2CO3
Cl
OH
(81%)
Phosphorus tribromide
PBr 3 + 3ROH → 3RBr + H 3PO 3
Also: Phosphorus trichloride
CH3CH(CH2)5CH3
(pyridine often used instead of K2CO3)
(CH3)2CHCH 2OH
PBr3
(CH3)2CHCH 2Br
(55-60%)