Chapter 9 Alcohol Reactions
I.
Reactions of Alcohols with Acids and Bases
A.
Preparations of Alkoxides
1) To deprotonate an alcohol, Base more basic than ROa)
CH3OH + Li+N-
CH3O
-
pKa = 40
+ HN
pKa = 15.5
b)
CH3OH + Li+-CH2CH2CH2CH3
CH3O
-
+ CH3CH2CH2CH3
pKa = 50
pKa = 15.5
c)
2)
CH3OH + K+HpKa = 15.5
CH3O- + H2
pKa = 38
Alkali Metal Reductions give Alkoxides
a) 2 H2O + Na (Li, K, Cs)
2 Na+OH- + H2 (Violent!)
b) 2 ROH + Na
2 Na+OR- + H2
c) Reactivity: MeOH > primary > secondary > tertiary
Electron donating R groups destabilize RO- anion
3)
B.
Uses of Alkoxides
a) Strong base for E2 reactions
b) Ether synthesis by SN2 reactions (stay tuned!)
Protonation of Alcohols form a better Leaving Group
1) X- + ROH
RX + OH- (OH- is a poor leaving group)
2) Strong acid converts OH- leaving group to H2O (good leaving group)
H
+
ROH
H
+
R
R O
+ H2O
H
3)
Synthesis of Haloalkanes from Alcohols
ROH
HBr
H
R O
Br-
RBr + H2O
H
a)
b)
Only I- and Br- are nucleophilic enough to work
Works best for primary alcohols
4)
Reaction of Secondary and Tertiary ROH with H+
a) Secondary and Tertiary alcohols easily lose water to from carbocations
b) If the acid contains a good nucleophile, you get SN1 substitution
OH
c)
OH2
Br-
SN1
Br
If there is not nucleophile or have high Temperature, you get E1
OH
d)
HBr
HBr
OH2
-H2O
E1
Dehydration = loss of an H2O molecule
Use non-nucleophilic acid = H2SO4, H3PO4
OH
OH2
H2SO4
o
-H2O
H
Catalytic
+
+ H
130 C
e)
As usual, Tertiary ROH only does SN1, E1 while Secondary ROH
can do SN2, SN1, or E1 in a strong acid
II.
Carbocation Rearrangement
A.
Hydride Shift
1) Sometimes we get mixtures of products from 2o and 3o ROH reactions
HBr
0 oC
3)
+ H2O
+
H
normal product
H
2)
Br H
H Br
H OH
H
rearranged
product
How does the rearrangement occur?
a) Carbocation intermediate rearranges
b) Hydrogen and an electron moves = hydride shift
Mechanism
H OH
H
a)
b)
+
H
H OH2
H
H:- and + trade places
Very fast (faster than SN1/E1)
if new C+ more stable
-H2O
H
secondary
carbocation
tertiary
carbon
(more stable)
-
H
Br
Br
H
normal product
H
hydride
shift
H
H
Br-
Br H
H
rearranged
product
4)
Orbital Picture of the Hydride Shift Mechanism
5)
6)
Primary ROH/RX won’t form carbocations, so don’t do Hydride Shift
Secondary and Tertiary ROH give mixture of products with nucleophile
6)
H OH
Mixture of E1 Products are also observed at high Temp., no nucleophile
H2SO4
H OH2
H
H
-H2O
+
o
130 C
H
H
secondary
carbocation
Me
Me H
H
OH2
H
H
rearranged products
Alkyl Shifts
1) If the carbocation doesn’t have a H- positioned to shift, an alkyl group can
move = Alkyl Shift
Me OH2
H+
Me
H
+
H
Me OH
H
hydride
shift
H
tertiary
carbon
(more stable)
B.
H
normal products
H H OH2
Me
Me H
-H2O
Me
Br-
Me
Me
Br-
Me
Me
Me H
Me
Me
Me H
normal product
Me H
secondary
carbocation
Alkyl
shift
tertiary
carbon Me
(more stable)
Me Br
Br Me
Me
Me H
Me rearranged
product
2)
C.
Concerted Hydride and Alkyl Shifts in Primary Alcohols
1) Primary alcohol will not form a carbocation, but sometimes rearranged
products are observed anyway
2) Only observed with much heat and much time
3) Concerted mechanism explains how
Me
Me
Hydride and Alkyl Shifts occur at about the same rate
a) Very fast if rearranged carbocation is more stable
b) Formation of tertiary carbocation is faster than secondary
Me
+
H
CH2 OH
Me
CH2 OH2
Me
Me
Me
CH2
Me
Br
Me
III. Ester Formation from Alcohols
A.
Esters are derivatives of organic and inorganic acids
O
O
1)
R C OH
R C OR' Carboxylate Ester
Organic Ester
O
2)
HO
P OH
O
Br
-
O
HO
P OR Phosphate Ester
Inorganic Ester
O
Me
CH2
Me
Me
B.
C.
Synthesis of Organic Esters
Subject of chapters 19 and 20
O
R C OH
O
+
R'OH
R C OR'
Synthesis of Haloalkanes from Alcohols involves Inorganic Esters
1) R—OH + HBr
R+
multiple products
2) Use Inorganic Reagent to make the water leaving group
3) 1o or 2o ROH + PBr3
1o or 2o RBr + H3PO3
PBr3
3
3
+ H3PO3
Et2O
Br
OH
4)
Mechanism
RCH2OH + PBr3
-Br
SN2
RCH2
O
PBr2
RCH2Br + HOPBr2
H
5)
6)
Reaction also works to make iodoalkanes with PI3
Chlorination of an alcohol requires thionyl chloride = SOCl2
RCH2OH + SOCl2
NEt3
RCH2Cl + SO2 + HCl
2 more reactions
7)
Mechanism
RCH2OH + SOCl2
8)
D.
-Cl
RCH2O
+
SOCl + H
-
+ Cl
NEt3
RCH2Cl + SO2 + HNEt3
Amine works as a base to remove H+ from reaction
Alkyl Sulfonates in Substitution Reactions
1) Preparation of Alkyl Sulfonates (good leaving groups)
O
RCH2OH + CH3
S
Cl +
O
Sulfonyl Chloride
2)
I- +
O
N
RCH2O
S
NH
CH3
-
Cl
+
O
pyridine
Substitution reactions take advantage of the good sulfonate leaving group
O
O
O
I
+ -O S CH3
S CH3 SN2
O
O
O
R OH
R O
S
O
R'
Nu
R Nu