1. Chapter 8: Alcohols R OH
O
HH
O
CH3CH3
δ+
O
HCH3
δ+ δ+ δ+ δ+δ+
δ--
δ-- δ--
Water Alcohol Ether

2. 1. Find the longest chain containing the –OH
function: alkane  alkanol. Note: This may not be
the longest chain in the molecule!
2. Number such as to give HO-C lowest #
3. Other rules same as in alkanes
4,4-Dimethyl-1-nonanol 5-Bromo-3-propyl-
2-heptanol
OH
OH
Br
1
2
3456789
12
345
6
Names
7

3. OH
OH
CH3
HO
Cyclohexanol
Cis-3-methyl-
cyclohexanol
1-Ethylcyclo-
pentanol
-OH as a substituent is called hydroxy
-OR is alkoxy: Ethers R-O-R’, alkoxyalkanes
RCH2OH RCHOH
R’
RCOH
R’
R’’
Primary Secondary Tertiary alcohol
Cyclic alcohols are called cycloalkanols:
Defined as C1,
# is not part of name
1
1
3

4. Structure
O can be thought of as sp3-hybridized,
“tetrahedral”, i.e. bent, not linear.
DHº (O H) = 119 kcal mol-1
HH3C
O

5. Most striking: Relatively high melting and
boiling points, and water solubility. Why?

6. Hydrogen Bonding
O
R
H
H O
Rδ-
δ-
δ+
δ+
5 kcalmol-1
Extensive network:
Methanol
tetramer
Water
hexamer
Increases inter-
molecular interactions.
Allows for solvation by
water.

7. Hydrophobic-Hydrophilic
R OH
Water solubility: Decreases with size of R
R is hydrophobic; –OH is hydrophilic

8. ROH + H2O RO- + H3O+ pKa’s
H2O
CH3OH
CH3CH2OH
(CH3)2CHOH
15.7
15.5
15.9
17.1
(CH3)3COH
ClCH2CH2OH
CF3CH2OH
CF3CH2CH2OH
18
14.3
12.4
15.4
Steric
effect
“Inductive”
electronic
effect.
Tapers off
with distance.
K Sterics
and
solvation
Acidity

9. Alkoxides RO
CH3OH + Na NH2 CH3O Na + NH3
CH3CH2OH + Na OH CH3CH2O Na + H2O
K ~ 1
pKa 15.5 35
K
15.9 15.7
+ - +-
+-+-
K
K = 1019.5
Preparation:
When CH3CH2OH is solvent, equilibrium is displaced
to the right.

10. Lone e-pairs can be protonated.
Molecules which are both acids
and bases are called amphoteric.
H
H
R-O-H + H2SO4 R-O + HSO4
Oxonium ion pKa ~ -3
Compare R NH2 + H R NH3
Ammonium ion pKa ~10
Alcohols are also basic:
+ -
+ +

11. Synthesis of Alcohols R-OH
1. R-X R-OH Review: SN
By SN2: Rprim-X
I OH
OH
OHI
Problem: β-Branching  E2 ( OH = base)
-
-
-

12. By SN1: Rsec X, Rtert X
OH
H-OH
+
Br
Cl OH
Minimize
at low T
HBr
H-OH
HCl +
Problem: E1

13. Solution for E2 problem: Use a relatively
nonbasic, “masked” OH–equivalent
CH3 C
O
O
Acetate (for Rprim, branched, or
Rsec)
Br + O CCH3
O
O CCH3
O
SN2 H2O, OH
OH
+ CH3CO, removed in aqueous work up
O “Ester”
Hydrolysis
-

14. Preview: Ester Hydrolysis (Chapter 20)

15. 2. Reduction of Aldehydes and
Ketones .
O
R C R’
O
R C H
C
O
C
O
C
O
δ
+2e reduction
-2e oxidation C
O
C
HO H 2e + 2H equals H2. There are
two practical ways to add H2:
a. as such, or b. as H-, then H+.-2H+
+2H+
+
δ+
+
Redox relationship:

16. Na+H:- + BH3 Na+BH4
- Sodium borohydride
sp2 sp3
Li+H- + AlH3 Li+AlH4
- Lithium aluminum
hydride (LAH)
Ketones Rsec-OH
Aldehydes Rprim-OH
red
red
ox
ox
What are
the
reagents?
Reduction
Hydrogenation is possible, but is cumbersome: Needs H2
pressure and catalysts (e.g., Pd, Pt).
Better: Use reagent that is equivalent to H:-, but not as
basic, such as “complex” hydrides, prepared simply by:

17. NaBH4 is less reactive, more selective:
Na+BH4 4H2 + NaB(OH)4
Li+ AlH4 4H2 + LiAl(OH)4
RX + LiAlH4 R-H
H-OH
H-OH -
-
These reagents are still somewhat basic and will
undergo hydrolysis. Reactivity differs greatly.
-
-
LiAlH4 (but not NaBH4) will reduce even halides:
slow, OK to use in CH3OH
But:
violent, needs aprotic
solvents (ethers)

18. Nucleophilicity: Attack at
C
O
O HHO
O Li+H3AlO H HO H
NaBH4, CH3OH
LiAlH4
ether
H+, H2O
work up-
Electrophilic
carbonyl carbon
Hydride
The resulting alkoxide is protonated by
alcohol solvent or on aqueous work up
The aqueous work-up step is normally not shown in eqns.
H H H

19. NaBH4: Termolecular, concerted
Simultaneous addition of H- and H+
CH3O H H BH3 C
H O H
LiAlH4: Stepwise delivery of, first, H:-,
then, H+ (work-up)
C
O
CH3O BH3+
Mechanisms

20. CrVI reagents CrIII
Typically, use Na2Cr2O7
or CrO3 in H2O, H2SO4
Cr
O
OH
O
HO
Chromic acid
+3e
Oxidation
OH
+ Na2Cr2O7
O
H2SO4
H2O
Good for Rsec-OH
Example:
Best for secondary alcohols giving ketones. Primary
alcohols are overoxidized in aqueous medium.

21. PyridinePyridinium chlorochromate : “PCC”
OH OH
O
H
O
Mechanism: via intermediate chromate ester
NH
+
RCH2OH HO Cr OH
O
O
R CH O Cr OH
H O
O
RCH +
O
CrOH
O
O
goes on to CrIII
N
PCC
HOH
VI
IV
Rprim–OH: Use CrO3Cl
-
Avoids overoxidation with aqueous Cr reagents.
E2

22. 3. Alcohols from Organometallics: R:- M+
Hexane
or etherR-X + Li RLi + LiX
R-X + Mg R-Mg-X
O
O
O
Ether
needed
“Grignard reagent”
“RMgX”
MeLi MeMgBr
Alkyllithium

24. Reverse Polarization RX RM
RM are basic and nucleophilic
MgBr D
Mg D2O
Basicity
Br
Hydrolysis:

25. Not strong enough for R – M+ + R’X R-R’
(obviously, since they are made from RX).
But:
O
R M O M
R
δ-
δ- δ+
δ+
+-
RM as Nucleophiles
+
Works with ketones, aldehydes,
even formaldehyde, CH2=O
H2O
O H
R

26. O
+ CH3MgBr
HO CH3
H2O
tert
+ Li
HO HO
H
MgBr OH
CH2 O +
Formaldehyde
prim
sec
Ketones:
Aldehydes:
Grignard

27. Retrosynthetic Analysis
Work Backwards! Break up into
even pieces!

28. Make
Synthetic Planning:
• Know your reactions, forward and backward (vocabulary)
• Know your mechanisms, forward and backward (grammar)
HO
O
Li
from starting materials
4 carbons or less
O
H
Li
HHO
+
+
Example:

29. Roadmaps

31. Problem:
Which retrosynthesis is best: a, b, or c?

32. Ethanol
Beverage
Chemical, Fuel

33. Abuse
Cyrrhosis

34. Initial dose causes euphoria, but alcohol is
a general, CNS active, depressant drug.

36. Absorption: 20% stomach, 80% gastrointestinal.
Food slows it, but what is in, stays in……
Distribution through the body and brain is fast.
Intravenous can be lethal: Sudden depression of
the respiratory system, brain centers.
Excretion: Lungs Alcoholic breath; 5% in
urine.
Metabolism: Zero order in ROH! Linear with
time; 10 mL/h (cocktail/hour); by oxidation:
CH3CH2OH CH3CH CO2
Poisonous
Second step is prevented by
antabuse (disulfiram):
N S
S N
S
S
O
Enzyme Enzyme

37. Effect misconceptions:
1. Not a stimulant
2. Doesn’t warm you
3. Doesn’t help your sleep
4. Not an aphrodisiac