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Alcohols
Biological Activity
Nomenclature
Preparation
Reactions
Some Alcohols
CH3CH2OH
HO
OH
OH
CHCH2NH2
CHCHNHCH3
CH3
ethanol
HO
adrenaline (epinephrine)
OH
H
HOCH2CHCH2OH
glycerol
H
HO
H
cholesterol
pseudephedrine
Alcohols are Found in Many
Natural Products
HO
N CH3
O
H
HO
Morphine
most abundant of opium's alkaloids
Paralytic Shellfish Poisoning
NH2
O
O
H
HN
A possible chemical warfare agent
H
N
N
NH
N
roughly 1000 times more toxic
than saran gas or cyanide
N H
OH
The toxin blocks entry of sodium
OH required by cells to make "action potentials"
Saxitoxin (STX)
LD 50 = 2 g/kg
OH
O
O
OH
OH
HO
OH
O
H2N
OH
OH
OH
OH
HO
PALYTOXIN
LD 50 = 0.15 g/kg
OH
OH
OH
OH
OH
OH
O
HO
O
N
N
H
H
HO
OH
OH
OH
OH
OH
O
OH
OH
OH
OH
HO
OH
O
O
O
OH
HO
OH
OH
OH
OH
HO
OH
OH
OH
OH
OH
Ethanol: the Beverage
Ethanol is a central nervous system depressant
- depresses brain areas responsible for judgement
(thus the illusion of stimulation)
alcohol dehydrogenase
CH 3CH 2OH
ethanol
NAD
+
O
CH 3CH + NADH + H
acetaldehyde
LD 50 = 1.9 g/Kg
NAD
enz.
+
CH 3CO 2H + NADH + H
acetic acid
+
+
Methanol: Not a Beverage
CH3OH
methanol
ADH
NAD
+
O
+
+
NADH
+
H
HCH
formaldehyde
LD 50 = 0.07 g/Kg
Alcohol Nomenclature
OH
3
3-heptanol
6
2
5
5-methyl-6-hepten-2-ol OH
2
OH
1
1
3
CH3
CH3
3,3-dimethylcyclohexanol
OH
CH3
5
CH3
5,5-dimethylcyclohex-2-enol
Nomenclature
OH
OH
(E) 3-methyl-3-penten-2-ol
(S) 2-hexanol
OH
OH
trans 3-isopropylcyclopentanol
H
OH
(R) 2-butyl-1,4-butanediol
(R) 2-butylbutane-1,4-diol
Oxidation levels of
oxygen- halogen- and nitrogencontaining molecules
CH2=CH2
CH3CH3
[O]
CH3CH2OH
HC
[O]
CH
CH3CH=O
[O]
CH3CO2H
CH3CH2Cl
CH 3CHCl2
CH3CCl3
CH3CH2NH2
CH3CH=NH
CH3CN
Oxidation
Reduction
Acidity of Alcohols
• Due to the electronegativity of the O atoms,
alcohols are slightly acidic (pKa 16-18).
• The anion dervived by the deprotonation of an
alcohol is the alkoxide.
• Alcohols also react with Na/K (same as water
does) to give the alkoxide.
CH3CH2OH + Na
CH3CH2O Na + 1/2 H2
Withdrawing Groups Enhance
Acidity
F
H
F C OH
F
>
more acidic
alcohol
CH3OH
CH3CH2OH
CF3CH2OH
(CH3)3COH
(CF3)3COH
Why?
F C OH
H
H
>
H C OH
H
less acidic
pKa
15.54
16.00
12.43
18.00
5.4
Withdrawing Groups Enhance
Acidity
CF3
CF3
CF3
C OH + NaHCO3
CF3
CF3
alcohol
CH3OH
CH3CH2OH
CF3CH2OH
(CH3)3COH
(CF3)3COH
C O Na + H2CO3
CF3
pKa
15.54
16.00
12.43
18.00
5.4
A similar case for phenols
Physical Properties
b.p. oC
D
sol. in H2O
CH3CH2CH3
-42
0.08
i
CH3OCH3
-25
1.3
ss
CH3CH2OH
78
1.7
vs
Intermolecular H-Bonding
 
O H
H
H
 
O H
 
O H
O
associated liquid
intermolecular H bonding
O H
H
H
O
Preparation of Alcohols
•
•
•
•
Reduction of ketones and aldehydes
Reduction of esters and carboxylic acids
Hydration of Alkenes
Nucleophilic addition
– Grignard reaction
– Acetylide addition
• Substitution
• Epoxide opening
NaBH4 Reduction
O
R
1) NaBH4, ethanol
+
R'
2) H3O
H
H
OH
R
R'
+
H3O
H
R
O
R'
Some Examples
O
OH
1) NaBH 4, ether
2) H3O
O
CH
+
"
CH2OH
Two Alcohol Products Form in Lab
O
H
axial approach
NaBH4
(CH3)3C
H
O Na
(CH3)3C
trans
O Na
O
NaBH4
(CH3)3C
H
(CH3)3C
H
equatorial approach
cis
LiAlH4 Reduction
a Stronger Reducing Agent
OH
O
1) LiAlH 4, THF
+
2) H3O
LiAlH 4 will reduce:
o
ketones to 2 alcohols
o
aldehydes to 1 alcohols
o
carboxylic acids and esters to 1 alcohols
LiAlH4 is a much stronger
reducing agent
1) LiAlH 4
O
OH
+
2) H3O
+ CH3OH
O
1) NaBH4
+
2) H3O
no reaction
NaBH4 is More Selective
O
O
1) NaBH4
OH
OH
+
2) H3O
O
OH
OH
1) LiAlH 4
+
2) H3O
OH
Oxymercuration Hydration
Markovnikov
1) Hg(OAc) 2 in
THF/H2O
2) NaBH4
OH
H
Hydroboration Hydration
Anti-Markovnikov
3
1) BH3-THF
2) H2O2, NaOH
H OH
3
Base Catalyzed Ring-Opening
of Epoxides
Acid Catalyzed Ring-Opening
Aqueous and in Alcohol
Nucleophilic addition to Carbonyl
Compounds
Acetylides

O

H
O

C
CH3
CH3CH2C

CH3
CH3
CH3CH2C
C
CH3
C
C
H3O
+
OH
CH3
CH3CH2C
C
C
CH3
Organometallic Chemistry
Grignard Reaction
CH3
Br + Mg
"CH3 MgBr "
excellent nucleophile
very strong base
 
CH3 MgBr
Grignard Reagent
Grignard Reagents React With
Ketones to form tertiary alcohols
O
CH3
1) CH3MgBr in ether
2) H3O
HO
+ MgBrOH
+
o
a 3 alcohol
H3O
MgBrO
CH3
CH3
+
Grignard Reagents React With
Aldehydes to form secondary alcohols
O

 
MgBr
in ether
1)
H
OH
+
2) H3O
H
Grignard Reagents React With
Formaldehyde to form primary
alcohols
CH2CH2O MgBr
CH2CH2OH
H3O
+
O

C 
H
H
formaldehyde
CH2 MgBr
CH2Br
Mg, ether, 
Grignard Reagents react (twice) with
Esters to form 3o Alcohols
O
OH
C
C CH
3
CH3
OCH3
1) 2 CH3MgBr
2) H3O
+
CH3
O
C OCH
3
CH3
2nd eq.
1) CH3MgBr
+
2) H3O
O
C
CH3
ketone
(more reactive than ester)
Grignard Summary
H
H
R
MgX
+
+
C
O
H3O workup
R
H formaldehyde
R
MgX
R'
+
O
R'
H3O workup
R
H aldehyde
R
MgX
R'
+
C
R''
ketone
C
OH
H
R'
+
O
OH
H
+
C
C
H3O workup
R
C
R''
OH
Grignard Summary
R
O
H3O workup
R'
MgX +
epoxide
R''
R
R'
2 R
MgX
+
OH
+
R'
+
C
O
RO ester
H3O workup
R
C
OH
R + ROH
Grignard Reagents are
exceptionally strong bases
H2O
CH3OH
CH3CH2CH2MgBr +
CH3CO2H
HC
CH
CH3NH2
CH3CH2CH3
Synthesis
OH
?
Retrosynthetic Analysis
OH
?
Br
MgBr
4-Step Synthesis
OH
1) HCHO
+
2) H3O
Br 2, h
Br
Mg in ether
MgBr
Synthesize Using Only 1,2, or
3-Carbon Reagents
OH
HC
CH
Retrosynthesis
+
OH
O 
MgBr
HC
Mg
Br
CH
HBr
CH3X
CH3X
reduce