William Brown
Thomas Poon
www.wiley.com/college/brown
Chapter Eight
Alcohols, Ethers, and Thiols
Alcohols - Structure
• The functional group of an alcohol is
an -OH group bonded to an sp3
hybridized carbon.
• Bond angles about the hydroxyl
oxygen atom are approximately
109.5°.
• Oxygen is also sp3 hybridized.
• Two sp3 hybrid orbitals form sigma
bonds to carbon and hydrogen.
• The remaining two sp3 hybrid orbitals
each contain an unshared pair of
electrons.
8-2
Alcohols - Nomenclature
• IUPAC names
• The parent chain is the longest chain that contains the
-OH group.
• Number the parent chain in the direction that gives the
-OH group the lower number.
• Change the suffix -e to -ol.
• Common names
• Name the alkyl group bonded to oxygen followed by the
word alcohol.
8-3
Alcohols - Nomenclature
OH
• Examples:
OH
Eth anol
(Ethyl alcoh ol)
OH
1-Propan ol
(Propyl alcohol)
2-Prop anol
(Is op ropyl alcohol)
OH
OH
1-Butanol
(Butyl alcohol)
OH
2-Bu tan ol
(s ec-Bu tyl alcohol)
OH
2-Methyl-1-propanol
(Is ob utyl alcoh ol)
OH
Cyclohexanol
2-Methyl-2-prop anol
(t ert-Butyl alcohol) (Cyclohexyl alcohol)
8-4
Alcohols - Nomenclature
• Problem: Write the IUPAC name of each alcohol.
(a) CH3 ( CH 2 ) 6 CH2 OH
OH
(b)
OH
(c)
8-5
Alcohols - Nomenclature
• Compounds containing
• two -OH groups are named as diols,
• three -OH groups are named as triols, etc.
• -OH groups on adjacent carbons are called glycols.
CH2 CH2
OH OH
1,2-Eth anediol
(Eth ylen e glycol)
CH3 CHCH2
HO OH
1,2-Propan ediol
(Propylene glycol)
CH2 CHCH2
HO HO OH
1,2,3-Propan etriol
(Glycerol, Glycerin)
8-6
Alcohols - Nomenclature
• Unsaturated alcohols
• The double bond is shown by the infix -en-.
• The hydroxyl group is shown by the suffix -ol.
• Number the chain to give OH the lower number.
6
4
5
3
2
1
OH
trans-3-hexen e-1-ol
(E)-3-h exene-1-ol
8-7
Physical Properties
• Alcohols are polar compounds.
• Both the C-O and O-H bonds are polar covalent.
H
+
C
H
H
O
+
H
8-8
Hydrogen Bonding
• Alcohols associate in the liquid state by hydrogen
bonding.
• Hydrogen bonding: The attractive force between a
partial positive charge on hydrogen and a partial
negative charge on a nearby oxygen, nitrogen, or
fluorine atom.
• The strength of hydrogen bonding in alcohols is
approximately 2 to 5 kcal/mol.
• Hydrogen bonds are considerably weaker than covalent
bonds (for example, 110 kcal/mol for an O-H bond).
• Nonetheless, hydrogen bonding can have a significant
effect on physical properties.
8-9
Hydrogen Bonding
• Figure 8.3 The association of ethanol molecules in the
liquid state.
8-10
Boiling Points
• Alcohols have higher boiling points and are more soluble
in water than alkanes of similar MW.
8-11
Acidity of Alcohols
• Most alcohols are about the same or slightly weaker
acids than water.
CH3 O H +
CH3 O
O H
H
-
+
+ H O H
H
+
[CH3 O ][ H3 O ]
Ka =
= 3.2 x 10-16
[ CH3 OH]
pK a = 15.5
• Aqueous solutions of alcohols have the same pH as that
of pure water.
8-12
Acidity of Alcohols
• Table 8.2 pKa Values for Selected Alcohols in Dilute
Aqueous Solution
8-13
Basicity of Alcohols
• In the presence of strong acids, the oxygen atom of an
alcohol behaves as a weak base.
• Proton transfer from the strong acid forms an oxonium
H2 SO4
ion.
+
+
CH3 CH2 -O-H + H O H
••
H
Eth anol Hydron ium ion
(pK a -1.7)
CH3 CH2 -O H + O H
H
H
Ethyloxon ium ion
(pK a -2.4)
• Thus, alcohols can function as both weak acids and weak
bases.
8-14
Reaction with Active Metals
• Alcohols react with Li, Na, K, and other active metals to
liberate hydrogen gas and form metal alkoxides.
• Na is oxidized to Na+ and H+ is reduced to H2.
2CH3 CH2 OH + 2Na
-
+
2CH3 CH2 O Na
+ H2
Sodium ethoxide
• Alkoxides are somewhat stronger bases that OH-.
• Alkoxides can be used as nucleophiles in nucleophilic
substitution reactions.
• They can also be used as bases in b-elimination
reactions.
8-15
Conversion of ROH to RX
• Conversion of an alcohol to an alkyl halide involves
substitution of halogen for -OH at a saturated carbon.
• The most common reagents for this purpose are the
halogen acids, HX, and thionyl chloride, SOCl2.
8-16
Conversion of ROH to RX
• Water-soluble 3° alcohols react very rapidly with HCl,
HBr, and HI.
CH3
25°C
CH3 COH + HCl
CH3
2-Methyl-2prop anol
CH3
CH3 CCl + H2 O
CH3
2-Chloro-2methylpropane
• Low-molecular-weight 1° and 2° alcohols are
unreactive under these conditions.
8-17
Conversion of ROH to RX
• Water-insoluble 3° alcohols react by bubbling gaseous
HCl through a solution of the alcohol dissolved in diethyl
ether or THF.
OH
CH3
1-Meth ylcyclohexanol
+
HCl
0°C
eth er
Cl
CH3
+ H2 O
1-Chloro-1-meth yl
cyclohexan e
• 1° and 2° alcohols require concentrated HBr and HI to
form alkyl bromides and iodides.
OH
1-Butanol
+ HBr
Br
+ H2 O
1-Bromobutan e
(Butyl bromide)
8-18
Reaction of a 3° ROH with HX
• 3° Alcohols react with HX by an SN1 mechanism
• Step 1: A rapid, reversible acid-base reaction transfers a
proton to the OH group.
• This proton-transfer converts the leaving group from OH-,
a poor leaving group, to H2O, a better leaving group.
8-19
Reaction of a 3° ROH with HX
• Step 2: Loss of H2O from the oxonium ion gives a 3°
carbocation intermediate.
CH3 H
+
CH 3 -C O
CH H
slow , rate
determining
SN 1
3
A n oxon ium ion
CH 3
+
CH3 -C
+
CH 3
A 3° carbocation
in termediate
O H
H
• Step 3: Reaction with halide ion completes the reaction.
CH3
+
CH3 -C
CH3
+
Cl
fast
CH3
CH3 -C Cl
CH3
2-Chloro-2-methylprop ane
(t ert -Bu tyl ch loride)
8-20
Reaction of a 1° ROH with HX
• 1° alcohols react by an SN2 mechanism.
• Step 1: Proton transfer to OH converts the leaving group
from OH-, a poor leaving group, to H2O a better leaving
group.
rapid an d
reversib le
+
OH + H O H
O
H
+ O H
H
An oxonium ion
H
H
• Step 2: Nucleophilic displacement of H2O by Br-.
Br
-
+
O
H
slow , rate
H determinin g
SN2
Br
+
O
H
H
8-21
Reaction of ROH with HX
• Reactions are governed by a combination of electronic
and steric effects
governed
by steric factors
n ever react by SN 2
Increas ing rate of dis placement o f H2 O
3° alcoh ol
SN 1
2° alcohol
Increas ing rate of carbo cati on formatio n
SN 2
1° alcoh ol
n ever react by SN 1
governed by
electronic factors
8-22
Reaction with SOCl 2
• Thionyl chloride, SOCl2, is the most widely used reagent
for conversion of alcohols to alkyl chlorides.
pyridine
OH + SOCl
2
1-Hep tanol
Thionyl
ch loride
Cl + SO + HCl
2
1-Chlorohep tane
8-23
Dehydration of Alcohols
• An alcohol can be converted to an alkene by elimination
of H and OH from adjacent carbons (a b-elimination).
• 1° alcohols must be heated at high temperature in the
presence of an acid catalyst, such as H2SO4 or H3PO4.
• 2° alcohols undergo dehydration at somewhat lower
temperatures.
• 3° alcohols often require temperatures at or only slightly
above room temperature.
8-24
Dehydration of Alcohols
• examples:
H2 SO 4
CH3 CH2 OH
180o C
OH
CH2 =CH 2 + H 2 O
H2 SO 4
+ H 2O
140o C
Cyclohexanol
CH3
CH3 COH
CH3
Cyclohexene
H2 SO 4
o
50 C
CH3
CH3 C= CH2
+
H2 O
2-Methylpropene
(Is obutylene)
8-25
Dehydration of Alcohols
• When isomeric alkenes are obtained, the more stable
alkene (the one with the greater number of substituents
on the double bond) generally predominates (Zaitsev’s
rule).
OH
8 5 % H3 PO4
CH3 CH2 CHCH3
CH3 CH=CHCH3 + CH3 CH2 CH=CH2
heat
2-Butan ol
2-Butene
1-Butene
(80%)
(20%)
8-26
Dehydration of a 2° Alcohol
• A three-step mechanism
• Step 1: Proton transfer from H3O+ to the -OH group
converts OH-, a poor leaving group, into H2O, a better
leaving group.
HO
CH3 CHCH2 CH3 + H
+
O H
H
rapid and
reversible
H
+ H
O
CH3 CHCH2 CH3 + O H
An oxonium ion
H
8-27
Dehydration of a 2° Alcohol
• Step 2: Loss of H2O gives a carbocation intermediate.
H
+ H
O
s low , rate
determin ing
CH3 CHCH2 CH3
+
CH3 CHCH2 CH3 + H2 O
A 2° carbocation
intermed iate
• Step 3: Proton transfer from an adjacent carbon to H2O
gives the alkene and regenerates the acid catalyst.
H
+
CH3 -CH-CH-CH3 + O H
H
rapid
+
CH3 -CH=CH-CH3 + H O H
H
8-28
Dehydration of a 1° Alcohol
• A two-step mechanism
• Step 1: Proton transfer gives an oxonium ion.
rapid an d
reversib le
CH3 CH2 -O-H + H O H
H
H
+
CH3 CH2 O
H
O H
H
• Step 2: Proton transfer to solvent and loss of H2O gives
the alkene and regenerates the acid catalyst.
H
H O + H C CH2
H
H
H slow , rate
determinin g
O
E2
H
H
H
+
HO H + C C +
H
H
H
O H
H
8-29
Hydration-Dehydration
• Acid-catalyzed hydration of an alkene and dehydration
of an alcohol are competing processes.
C C
+ H2 O
An alk ene
acid
catalyst
C
C
H OH
An alcoh ol
• Large amounts of water favor alcohol formation.
• Scarcity of water or experimental conditions where water
is removed favor alkene formation.
8-30
Oxidation of Alcohols
• Oxidation of a 1° alcohol gives an aldehyde or a
carboxylic acid, depending on the oxidizing agent and
experimental conditions.
• The most common oxidizing agent is chromic acid.
CrO3
+ H2 O
Chromium(VI)
oxide
H2 SO4
H2 CrO4
Chromic acid
• Chromic acid oxidation of 1-octanol gives octanoic acid.
CH3 (CH2 ) 6 CH2 OH
1-Octan ol
CrO3
H2 SO4 , H2 O
O
CH3 (CH2 ) 6 CH
Octan al
(not isolated)
O
CH3 (CH2 ) 6 COH
Octan oic acid
8-31
Oxidation of Alcohols
• To oxidize a 1° alcohol to an aldehyde, use PCC.
CrO3 Cl-
CrO3 + HCl +
N
Pyridine
N+
H
Pyridiniu m chloroch romate
(PCC)
• PCC oxidation of geraniol gives geranial.
O
Geraniol
PCC
OH CH Cl
2
2
H
Geranial
• Tertiary alcohols are not oxidized by either of these
reagents; they are resistant to oxidation.
8-32
Ethers - Structure
• The functional group of an ether is an oxygen atom
bonded to two carbon atoms.
• Oxygen is sp3 hybridized with bond angles of
approximately 109.5°.
• In dimethyl ether, the C-O-C bond angle is 110.3°.
H
H
••
H
C
H
O
••
C
H
H
8-33
Ethers - Nomenclature
• IUPAC
• The longest carbon chain is the parent alkane.
• name the -OR group as an alkoxy substituent.
• Common names:
• Name the groups bonded to oxygen followed by the word ether.
O
Et 2 O
Eth oxyethane
(D i ethyl eth er)
CH3
CH3 OCCH3
CH3
2-Metho xy-2-methy lpropane
(methy l t ert -buty l ether, MTBE)
OH
OEt
t rans-2-Etho xy cycl ohexanol
8-34
Ethers - Nomenclature
• Although cyclic ethers have IUPAC names, their
common names are more widely used.
O
O
O
O
O
Eth ylen e
oxide
Tetrahydrofu ran , THF
Tetrahydropyran
1,4-D ioxane
8-35
Ethers - Physical Properties
• Figure 8.5 Ethers are polar molecules.
• Each C-O bond is polar covalent.
• However, only weak attractive forces exist between ether
molecules in the pure liquid.
8-36
Ethers - Physical Properties
• Boiling points of ethers are lower than those of alcohols.
8-37
Ethers - Physical Properties
• Figure 8.6 Ethers are hydrogen bond acceptors. They are
not hydrogen bond donors.
8-38
Ethers - Physical Properties
• The effect of hydrogen bonding is illustrated by comparing
the boiling points of ethanol and dimethyl ether.
CH3 CH2 OH
Ethan ol
b p 78°C
CH3 OCH3
Dimethyl ether
bp -24°C
8-39
Reactions of Ethers
• Ethers resemble hydrocarbons in their resistance to
chemical reaction.
• They do not react with strong oxidizing agents such as
chromic acid, H2CrO4.
• They are not affected by most acids and bases at
moderate temperatures.
• Because of their good solvent properties and general
inertness to chemical reaction, ethers are excellent
solvents in which to carry out organic reactions.
8-40
Epoxides
• Epoxide: A cyclic ether in which oxygen is one atom of a
three-membered ring.
C
C
O
Function al group
of an epoxide
H2 C
CH 2
CH3 CH
O
Ethylene oxide
CH2
O
Prop ylen e oxide
• Ethylene oxide is synthesized from ethylene and O2.
CH2 =CH2
Ethylen e
+ O2
Ag
heat
CH2
CH2
O
Ethylen e oxid e
8-41
Epoxides
• Other epoxides can be synthesized from an alkene by
oxidation with a peroxycarboxylic acid, RCO3H.
+
Cyclohexene
O
RCOOH
H
CH2 Cl2
A peroxycarb oxylic acid
O
+
O
RCOH
H
1,2-Epoxycyclohexane A carboxylic
(Cyclohexen e oxid e)
acid
8-42
Reactions of Epoxides
Ethers are generally unreactive to aqueous acid.
• Epoxides, however, react readily because of the angle
strain in the three-membered ring.
• Reaction of an epoxide with aqueous acid gives a glycol.
CH2
CH2 + H2 O
H+
HOCH2 CH2 OH
O
Eth ylene oxide
1,2-Eth anediol
(Eth ylen e glycol)
H
+
O
+ H2 O
H
1,2-Epoxycyclopentane
(Cyclopen tene oxid e)
H
OH
OH
trans-1,2-Cyclopentaned iol
8-43
Other Epoxide Ring Openings
• The value of epoxides lies in the number of nucleophiles
that will bring about ring opening, and the combinations of
functional groups that can be synthesized from them.
NH3
CH 3
H2 C
CH
O
Methyloxirane
(Prop ylen e oxid e)
H2 N
b
+
H2 O/ H3 O
+
HO
b
-
Na SH / H2 O
HS
b
CH3

A b-aminoalcohol
OH
CH 3

OH
CH 3

OH
A glycol
A b-mercaptoalcohol
8-44
Epoxides as Building Blocks
• Following are structural formulas for two common drugs,
each synthesized in part from ethylene oxide.
CH3
O
O
N
CH3
O
CH3
N
CH3
H2 N
Procaine
(N ovocain e)
D iph enhydramine
(Benad ryl)
8-45
Thiols - Structure
• The functional group of a thiol is an -SH (sulfhydryl) group
bonded to an sp3 hybridized carbon.
8-46
Thiols - Nomenclature
• IUPAC names
• The parent chain is the longest chain containing the -SH
group.
• Add -thiol to the name of the parent chain.
• Common names
• Name the alkyl group bonded to sulfur followed by the
word mercaptan.
• Alternatively, indicate the -SH by the prefix mercapto.
SH
SH
Ethaneth iol
2-Methyl-1-propanethiol
(Ethyl mercap tan)
(Is ob utyl mercaptan)
OH
HS
2-Mercaptoethanol
8-47
Thiols - Physical Properties
• Low-molecular-weight thiols have a STENCH
Present in the
scen t of skunks :
CH3 CH=CHCH2 SH
2-Butene-1-th iol
CH3
CH3 CHCH2 CH2 SH
3-Methyl-1-butanethiol
(Is obutyl mercaptan)
CH3
SH
N atu ral gas
CH3 -C-SH
CH3 -CH-CH3
odorants:
CH3
2-Meth yl-2-propaneth iol
2-Propaneth iol
(tert -Butyl mercaptan ) (Isop ropyl mercaptan)
8-48
Thiols - Physical Properties
• The difference in electronegativity between S and H is
2.5 - 2.1 = 0.4
• Because of their low polarity, thiols
• show little association by hydrogen bonding.
• have lower boiling points and are less soluble in water
than alcohols of comparable MW.
8-49
Acidity of Thiols
• Thiols are stronger acids than alcohols.
-
+
CH3 CH2 OH + H2 O
CH3 CH2 O + H3 O
pK a = 15.9
CH3 CH2 SH + H2 O
+
CH3 CH2 S + H3 O
pK a = 8.5
• Thiols react with strong bases to form salts.
+
-
CH3 CH2 SH + Na OH
pK a 8.5
Stronger
Stronger
acid
base
-
CH3 CH2 S Na
Weaker
base
+
+
H2 O
pKa 15.7
Weaker
acid
8-50
Oxidation of Thiols
• Thiols are oxidized by a variety of oxidizing agents,
including O2, to disulfides.
• Disulfides, in turn, are easily reduced to thiols by
several reagents.
2 HOCH2 CH2 SH
A th iol
oxid ation
redu ction
HOCH2 CH2 S-SCH2 CH2 OH
A disu lfid e
• This easy interconversion between thiols and disulfides is
very important in protein chemistry.
8-51
Alcohols, Ethers,
and Thiols
End Chapter 8
8-52