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Biological Chemistry
FIRST YEAR ORGANIC CHEMISTRY
Lecture Six
Alcohols and Ethers
Convenor : Dr. Fawaz Aldabbagh
Alcohols and Ethers
Alcohols and Ethers can be regarded as derivatives of water
in which one or two of the H atoms has been replaced by an
alkyl group
Methanol, CH3OH
Water, H2O
H
O
0.96 Ao
o
0.96 A
H C
H
O
H
H H
104.5o
o
1.43 A
O
C H
H H H H
109.5o
111.7o
1.43 A
Saturated molecules
are sp3 hybridized
108.5o
Methoxymethane, CH3OCH3
H C
o
1.10 Ao
- I (net dipole)

O 
H3C
H
Electronegativity of oxygen causes an
unsymmetrical distribution of charge
Alcohols are found to have much higher bpt than those of alkanes or
haloalkanes of comparable size, e.g. Methanol (65 oC),
Chloromethane and Methane are gases ; Ethanol (78.5 oC),
Chloroethane (12 oC) and Ethane is a gas
Methanol and Ethanol are classed as Polar Molecules (Hydrophilic)
– They are Infinitely Soluble in Water
Why? Answer – Hydrogen
R
H
Bonding
H
R
O 
H

O
H
O
H
H
O 
H
R

H
O
O
H
H-bonds weaker than covalent bonds, although these bonds can be
continually broken and reformed – a highly ordered structure
results – H-Bonding to water can also occur
Water (mw = 18) is a liquid, bpt 100oC – otherwise a gas
Ethanol
H H
1-Pentanol
H C C O
H C C C C C O
H H
Hydrophilic end
H H H H H
H
H H H H H
H
As R-group increases in size,
so does the solubility in nonpolar solvents
Hydrophobic end
As the number –OHs increases so does solubility in water
Bpt increase with chain length and number of –OHs
Methanol, CH3OH
In the Liver
- Solvent in varnishes, paint
- Racing Car Fuel (easy to put
out flames)
- Highly Toxic – “Blindness” Formaldehyde
In
Ethanol, CH3OH
-Drinking Alcohol
- 50% Ethanol is
flammable
H3C
O
OH
H
C
H
Alcohol Dehydrogenase
the Liver
CH3CH2OH
O
H3C
Alcohol Dehydrogenase
C
O
[O]
H
Acetaldehyde
OH
O
[O]
H
C
H3C
C
OH
Acetic Acid
Odour on your breath
Symptoms - Hang-over
Ethanol content; Beer, 3-9% ; Wine, 11-13% ; Whisky, 40-45% ; Vanilla
Extracts, 35% ; Night Nurse, 25% ; Listerine, 25%
Preparation of Ethanol
- Fermentation of Sugar – Break down of sugar to CO2
and Ethanol by Yeast Enzymes
- Industrial Process – Hydration of Ethene
H
H
H2O
CH3CH2OH
H H3PO4 , 300C
H
Naming Alcohols
hydroxy or alcohol group
CH3
OH
CH3
CH2
OH
Methyl alcohol
Ethyl alcohol (ethanol)
(methanol)
CH3
CH OH
CH3
Isopropyl alcohol
CH3
CH3
CH2
CH2
CH2
OH
Propyl alcohol (propanol)
CH CH2 CH3
CH2 OH
2-Ethyl-1-butanol
Naming Alcohols
Polyhydroxy alcohols are alcohols that possess more than one
hydroxyl group
CH2
CH2
HO
CH2
CH3
CH CH2
HO
OH
OH
HO
CH CH2
HO
OH
1,2,3-Propanetriol (glycerol)
1,2-Propanediol (propylene glycol)
1,2-Ethanediol (ethylene glycol)
Harmless
Extremely Toxic
Calcium Oxalate
crystallises in the kidney
leading to renal problems
CH3
O
CH2
HO
CH2
OH
HO C
Liver Enzymes
HO
OH
H3C C
Liver Enzymes
C OH
Oxalic acid
O
CH CH2
O
O
C OH
Pyruvic acid
CH3
H
CH3
H3C C OH
H3C C OH
H
H
Primary (1o) Alcohol
H3C C OH
CH3
o
Secondary (2 ) Alcohol
Tertiary (3o) Alcohol
Alcohols are weak Acids
H
R O H
  
Alcohol
O H
H
+
R O
Alkoxide
Relative Acidity ; H2O > ROH > R
H O H
C C H > RH
pKa CH3OH (15.5), H2O (15.74), CH3CH2OH (15.9), (CH3)3COH (18.0)
The Conjugate base of an alcohol is an alkoxide ion
Because most alcohols are weaker acids than water ;
they’re respective alkoxide is a stronger base than
hydroxide ion OH -
2 CH3CH2OH + 2 Na
2 CH3CH2
Vigorous Reaction
Na
O
+ H2
Sodium Ethoxide
-OH is a Poor Leaving Group
Weak acids make Poor Leaving Groups in Organic Reactions
Strong Acids have Conjugate Bases that are Good Leaving Groups
in Organic Reactions
H
C O H
+
H A
+
C O H
A
Strong Acid
Protonated Alcohol
H
C O H
Nu
C Nu
+
H2O
We have to convert OH into a
Good Leaving Group
Base
C O H
O
Na
C O
O
HO S OH
C O
Cl
O
Sulfuric Acid
Cl
C O SO2CH3
S CH3
O
Ms
C OMs
Methanesulfonyl chloride
Alkanesulfonate(Alkane Mesylate)
Similiarly,
O
NaOH , - HCl
CH3CH2O H
CH3CH2O S
O
+ Cl
S
CH3
O
CH3
O
p-Toluenesulfonyl chloride
(Tosyl Chloride)
CH3CH2-OTs
Ethyl-p-toluenesulfonate
(Ethyltosylate)
OMs and OTs are excellent leaving groups in Nucleophilic
Substitution Reactions- Derivatives of Sulfuric Acid
Other Good Leaving Groups ;
R-I > R-Br > R-Cl > R-F -------------It follows Acid Strength
HI > HBr > HCl > HF
SN2 – Substitution, Nucleophilic, Bimolecular
H3C
Nu
H C OTs
H
CH3
Nu C OTs
H
H
CH3
Nu
H
H
Transition State
Rate = k [CH3CH2OTs] [ Nu- ] ---------Bimolecular
Backside Nucleophilic Attack – Inversion in Configuration
H3C
HO
H C Br
C6H13
R-(-)-2-Bromooctane
Concerted Mechanism
CH3
CH3
HO C Br
H
C6H13
Transition State
HO
H
C6H13
S-(+)-2-Octanol
Optically Active
Enantiomericaly Pure
Inversion of Stereochemistry
SN1 – Substitution, Nucleophilic, Unimolecular
(CH3)3COH + 2 H3O+ + Cl Slow Step (RDS)
CH3
CH2
Cl
H3C C Cl
+
H3C
CH3
CH3
(CH3)3CCl + 2 H2O
Aided by polar Solvent
Stable 3o Carbocation
ions are stabilized via solvation
CH2
CH3
Fast Step
H 3C C O H
Professor George Olah
Nobel Prize 1994
H3C
CH3
O H
H
Front or Backside Attack
Carbocation is sp2-planar
CH3 H
- H+
more stable
R
R C
>
> R C
R
H
H
R
CH3
H3C C O H
R C
H
R groups are electron releasing
- delocalise the positive charge
CH3
tert-Butyl alcohol
Evidence for SN1 is Racemization of an optically active compound
H3CH2CH2C
CH2CH3
HO C CH3
CH2CH2CH3
- HBr
H3C C Br
H3CH2C
H3CH2CH2C
S-3-Bromo-3-methylhexane
The Carbocation
intermediate is attacked
by water from either side
by the same rate
Much high bpt, because
of H-Bonding
(e.g. Phenol, 182C,
toluene, 111C
Phenol
+
H3C C OH
H3CH2C
1:1 Mixture of R- and S-3-Methyl-3-hexanol
Phenols
OH
OH
OH
1-Naphthol
H3C
2-Naphthol
OH
4-Methylphenol
Phenols are much stronger acids than alcohols
OH
OH
pKa = 18
H O
CH3
O
cyclohexene
OH
pKa = 10
O
CH3
cyclic ether
O
Resonance Stabilised Phenoxide anion
phenol
Tetrahydrocannabinol
H3C
O
ETHERS, RO-OR
CH3CH2
O CH2CH3
Diethyl Ether
H3CO
O
Methoxycyclohexane
Methoxy group
H3C O
Ethoxy group
CH3CH2 O
Non-Flammable Anaesthetics
OCH 3 1-Propoxypropane
Methoxybenzene
Cl F
F
Bpt are similar to alkanes – No H-bonding to one another H C C O C H
But are soluble in water- H-bonding to water - Polar
F F
F
Flammable – Ether can cause flash fires
Enflurane
Low Reactivity – Make Good Reaction Solvents
F
F
O
Furan
O
Tetrahydrofuran (THF)
Cyclic Ethers
O
Pyran
H
F
C C O C H
F Cl
F
Isoflurane