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 RO-
a)
-
CH3OH + Li+N- CH3O + HN pKa = 40

pKa = 15.5

-
b) CH3OH + Li+-CH2CH2CH2CH3 CH3O + CH3CH2CH2CH3
pKa = 15.5 pKa = 50

c) CH3OH + K +H- CH3O - + H2

pKa = 15.5 pKa = 38

2) 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) Uses of Alkoxides
a) Strong base for E2 reactions
b) Ether synthesis by SN2 reactions (stay tuned!)

B. 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
+ H
ROH R O R+ + H2O
H

3) Synthesis of Haloalkanes from Alcohols

HBr H Br-
ROH R O RBr + H2O
H
a) Only I- and Br- are nucleophilic enough to work
b) 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 S N1 substitution

OH HBr OH2 SN 1 Br- Br

c) If there is not nucleophile or have high Temperature, you get E1

OH HBr OH2 -H2O E1

d) Dehydration = loss of an H2O molecule

Use non-nucleophilic acid = H2SO4, H3PO4
OH OH2
Catalytic
H
H2SO4 -H2O
o
+ 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
H OH H Br Br H
HBr + + H2O
0 oC
H H H
normal product rearranged
product

2) How does the rearrangement occur?

a) Carbocation intermediate rearranges
b) Hydrogen and an electron moves = hydride shift

H OH + H OH2 H H Br
H Br
-
3) Mechanism -H2O

H H H H
secondary normal product
carbocation
hydride
a) H:- and + trade places shift
b) Very fast (faster than SN1/E1) Br
- Br H
tertiary H
if new C+ more stable carbon
(more stable) H H
rearranged
product
4) Orbital Picture of the Hydride Shift Mechanism

5) Primary ROH/RX won’t form carbocations, so don’t do Hydride Shift

6) Secondary and Tertiary ROH give mixture of products with nucleophile
 6) Mixture of E1 Products are also observed at high Temp., no nucleophile

H OH H OH2 H H
H2SO4
-H2O
+
o
130 C
H H H H OH2 H H
secondary normal products
carbocation
hydride
shift

H H
tertiary H
carbon +

(more stable) OH2 H

H
H rearranged products
B. Alkyl Shifts
1) If the carbocation doesn’t have a H- positioned to shift, an alkyl group can
move = Alkyl Shift
Me OH Me OH2 Me Me Br
H+ -H2O Br-
Me Me Me Me Me Me Me

Me H Me H Me H Me H
secondary normal product
carbocation Alkyl
shift

Me Br- Br Me
tertiary
carbon Me Me Me Me rearranged
product
(more stable) Me H Me H
 2) 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

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 Br
H+ -
Br
Me CH2 OH Me CH2 OH2 Me CH2 Me Me CH2 Me
Me Me Me 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 O
2) HO P OH HO P OR Phosphate Ester
Inorganic Ester
O O
 B. Synthesis of Organic Esters O O
Subject of chapters 19 and 20 R C OH + R'OH R C OR'

C. 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 + H3PO 3
Et2O
OH Br

4) Mechanism

-Br SN 2 2 more reactions

RCH2OH + PBr3 RCH2 O PBr2 RCH2Br + HOPBr2
H

5) Reaction also works to make iodoalkanes with PI3

6) Chlorination of an alcohol requires thionyl chloride = SOCl 2
NEt3
RCH2OH + SOCl2 RCH2Cl + SO2 + HCl
 7) Mechanism
-Cl + -
RCH2OH + SOCl2 RCH2O SOCl + H + Cl RCH2Cl + SO 2 + HNEt3
NEt3

8) Amine works as a base to remove H+ from reaction

D. Alkyl Sulfonates in Substitution Reactions

1) Preparation of Alkyl Sulfonates (good leaving groups)
O N O -
NH Cl
RCH2OH + CH3 S Cl + RCH2O S CH3 +
O O
Sulfonyl Chloride pyridine

2) Substitution reactions take advantage of the good sulfonate leaving group

O O
O I
I- + S CH3 SN2 + -O S CH3
O O

O
Nu
R OH R O S R' R Nu
O