Alcohols, Ethers, and Thiols

Chapter 8:
Alcohols, Ethers, and

Thiols
© 2005 John Wiley & Sons, Inc

All rights reserved 8-1
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

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

• Examples:
OH
OH OH
Ethanol 1-Propanol 2-Propanol
(Ethyl alcohol) (Propyl alcohol) (Isopropyl alcohol)
OH
OH OH
1-Butanol 2-Butanol 2-Methyl-1-propanol
(Butyl alcohol) (sec-Butyl alcohol) (Isobutyl alcohol)
OH OH
2-Methyl-2-propanol Cyclohexanol
(tert-Butyl alcohol) (Cyclohexyl alcohol)
• Problem: Write the IUPAC name of each alcohol
(a) CH3 ( CH2 ) 6 CH2 OH
OH
(b)
OH
(c)

• Compounds containing
• two -OH groups are named as diols,
• three -OH groups are named as triols, etc.
CH2 CH2 CH3 CHCH2 CH2 CHCH2

OH OH HO OH HO HO OH
1,2-Ethanediol 1,2-Propanediol 1,2,3-Propanetriol
(Ethylene glycol) (Propylene glycol) (Glycerol, Glycerin)

• Unsaturated alcohols
• the double bond is shown by the infix -en-
en
• the hydroxyl group is shown by the suffix -ol
• number the chain to give OH the lower number
6 4 2
5 3 1 OH
trans-3-hexene-1-ol
(E)-3-hexene-1-ol

Physical Properties
• Alcohols are polar compounds
• both the C-O and O-H bonds are polar covalent
H
+ -
C O
H +
H H

Hydrogen Bonding
• Alcohols associate in the liquid state by
hydrogen bonding
• Hydrogen bonding:
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

Hydrogen Bonding
• Figure 8.3 shows the association of ethanol molecules
in the liquid state (only two of the three possible
hydrogen bonds to the upper oxygen are shown here).

Boiling Points
• alcohols have higher boiling points and are more
soluble in water than hydrocarbons
Molecular Boiling
Weight Point Solubility
Structural Formula Name (g/mol) (°C) in Water
CH3 OH methanol 32 65 infinite
CH3 CH3 ethane 30 -89 insoluble
CH3 CH2 OH ethanol 46 78 infinite
CH3 CH2 CH3 propane 44 -42 insoluble
CH3 CH2 CH2 OH 1-propanol 60 97 infinite
CH3 CH2 CH2 CH3 butane 58 0 insoluble
CH3 CH2 CH2 CH2 CH2 OH 1-pentanol 88 138 2.3 g/100 g
HOCH2 CH2 CH2 CH2 OH 1,4-butanediol 90 230 infinite
CH3 CH2 CH2 CH2 CH2 CH3 hexane 86 69 insoluble
Acidity of Alcohols
• Most alcohols are about the same or slightly
weaker acids than water
+
CH3 O H + O H CH3 O + H O H
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

Acidity of Alcohols
• pKa values for several low-molecular-weight alcohols
Structural
Compound Formula pKa
hydrogen chloride HCl -7 Stronger
acid
acetic acid CH3 COOH 4.8
methanol CH3 OH 15.5
water H2 O 15.7
ethanol CH3 CH2 OH 15.9
2-propanol (CH3 ) 2 CHOH 17
Weaker
2-methyl-2-propanol (CH3 ) 3 COH 18 acid
*Also given for comparison are pKa values for water,

acetic acid, and hydrogen chloride.
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
ion
+ H2 S O4 +
CH3 CH2 -O-H + H O H CH3 CH2 -O H + O H
••
H H H
Ethanol Hydronium ion Ethyloxonium ion
(pKa -1.7) (pKa -2.4)
• thus, alcohols can function as both weak acids and

weak bases

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
2 CH3 CH2 OH + 2 Na 2 CH3 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 -elimination
reactions
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

• water-soluble 3° alcohols react very rapidly with HCl,
HBr, and HI
CH3 CH3
25°C
CH3 COH + HCl CH3 CCl + H2 O
CH3 CH3
2-Methyl-2- 2-Chloro-2-
propanol methylpropane
• low-molecular-weight 1° and 2° alcohols are unreactive

under these conditions

• water-insoluble 3° alcohols react by bubbling gaseous
HCl through a solution of the alcohol dissolved in
diethyl ether or THF
OH 0°C Cl
+ HCl + H2 O
CH3 ether CH3
1-Methyl- 1-Chloro-1-methyl
cyclohexanol cyclohexane
• 1° and 2° alcohols require concentrated HBr and HI to
form alkyl bromides and iodides
OH + HBr Br + H2 O
1-Butanol 1-Bromobutane
(Butyl bromide)

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
CH3 rapid and

CH3 H
•• ••+ reversible + ••
CH3 -C O H + H O H CH3 -C O + O H
•
•
••
CH3 H CH H
3
H
2-Methyl-2-propanol An oxonium ion
(tert-Butyl alcohol)
• this proton-transfer converts the leaving group from
OH-, a poor leaving group, to H2O, a better leaving
group

• Step 2: loss of H2O from the oxonium ion gives a 3°
carbocation intermediate
CH3 H slow, rate CH3
+ determining +
CH3 -C O CH3 -C + O H
SN 1
CH H
3 CH3 H
An oxonium ion A 3° carbocation
intermediate
• Step 3: reaction with halide ion completes the reaction
CH3 CH3
fast
CH3 -C+ + Cl CH3 -C Cl
CH3 CH3
2-Chloro-2-methylpropane
(tert-Butyl chloride)
• 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 and
+ reversible H
OH + H O H O + O H
H H H
An oxonium ion
• Step 2: nucleophilic displacement of H2O by Br-

slow, rate
- H determining H
Br + O Br + O
SN2 H
H

Reaction of ROH with HX
• Reactions are governed by a combination of
electronic and steric effects
governed
by steric factors
never react by SN2
Increasing rate of displacement of H2 O SN2
3° alcohol 2° alcohol 1° alcohol
SN 1 Increasing rate of carbocation formation

never react by SN1
governed by
electronic factors

Reaction with SOCl2
• Thionyl chloride, SOCl2, is the most widely used
reagent for conversion of alcohols to alkyl
chlorides
OH + SOCl pyridine
2
1-Heptanol Thionyl
chloride
Cl + SO2 + HCl
1-Chloroheptane

Dehydration of Alcohols
• An alcohol can be converted to an alkene by
elimination of H and OH from adjacent carbons (a
-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 only at or
slightly above room temperature

• examples:
H2 SO 4
CH3 CH2 OH CH2 =CH 2 + H 2 O
o
180 C
OH
H2 SO 4
+ H 2O
140oC
Cyclohexanol Cyclohexene
CH3 CH3
H2 S O 4
CH3 COH CH3 C= CH2 + H2 O
50oC
CH3 2-Methylpropene
(Isobutylene)
• 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)
rule
OH 8 5 % H3 PO4
CH3 CH2 CHCH3 CH3 CH=CHCH3 + CH3 CH2 CH=CH2
he at
2-Butanol 2-Butene 1-Butene
(80%) (20%)

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
+ H
rapid and H
HO O
+ reversible
CH3 CHCH2 CH3 + H O H CH3 CHCH2 CH3 + O H
H An oxonium ion H

• Step 2: loss of H2O gives a carbocation intermediate
H + H
O slow, rate
determining +
CH3 CHCH2 CH3 CH3 CHCH2 CH3 + H2 O
A 2° carbocation
intermediate
• Step 3: proton transfer from an adjacent carbon to H2O
gives the alkene and regenerates the acid catalyst
H
+ rapid +
CH3 -CH-CH- CH3 + O H CH3 -CH=CH-CH3 + H O H
H H

• A two-step mechanism
• Step 1: proton transfer gives an oxonium ion
rapid and
reversible H
CH3 CH2 -O-H + H O H CH3 CH2 O + O H
H H H
• Step 2: proton transfer to solvent and loss of H2O gives

the alkene and regenerates the acid catalyst
H
H slow, rate + H H
H O + H C CH2 O determining HO H + C C + O H
H E2 H
H H H H H

Hydration-Dehydration
• Acid-catalyzed hydration of an alkene and
dehydration of an alcohol are competing
processes
acid
catalyst
C C + H2 O C C
H OH
An alkene An alcohol
• large amounts of water favor alcohol formation
• scarcity of water or experimental conditions where
water is removed favor alkene formation

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
H2 S O4
CrO3 + H2 O H2 CrO4
Chromium(VI) Chromic acid
oxide
• chromic acid oxidation of 1-octanol gives octanoic acid
O O
CrO3
CH3 (CH2 ) 6 CH2 OH CH3 (CH2 ) 6 CH CH3 (CH2 ) 6 COH
H2 S O4 , H2 O
1-Octanol Octanal Octanoic acid
(not isolated)

Oxidation of Alcohols
• to oxidize a 1° alcohol to an aldehyde, use PCC
CrO3 + HCl + CrO3 Cl-

N N+
H
Pyridine Pyridinium chlorochromate
(PCC)
• PCC oxidation of geraniol gives geranial
O
PCC
OH CH Cl H
2 2
Geraniol Geranial
• Tertiary alcohols are not oxidized by either of
these reagents; they are resistant to oxidation
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 O
••
C H
H H

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
Ethoxyethane
(Diethyl ether)
CH3
OH
CH3 OCCH3
CH3
OEt
2-Methoxy-2-methylpropane trans-2-Ethoxycyclohexanol
(methyl tert-butyl ether, MTBE)
Ethers - Nomenclature
• Although cyclic ethers have IUPAC names, their
common names are more widely used
O
O O O O
Ethylene Tetrahydro- Tetrahydro- 1,4-Dioxane
oxide furan, THF pyran

Ethers - Physical Properties
• Ethers are polar molecules
• each C-O bond is polar covalent
• however, only weak attractive forces exist between
ether molecules

• boiling points are lower than those of alcohols
Boiling
Molecular Point Solubility
Structural Formula Name Weight (°C) in Water
CH3 CH2 OH ethanol 46 78 infinite
CH3 OCH3 dimethyl ether 46 -24 7.8 g/100 g
CH3 CH2 CH2 CH2 OH 1-butanol 74 117 7.4 g/100 g
CH3 CH2 OCH2 CH3 diethyl ether 74 35 8 g/100 g
CH3 CH2 CH2 CH2 CH2 OH 1-pentanol 88 138 2.3 g/100 g

HOCH2 CH2 CH2 CH2 OH 1,4-butanediol 90 230 infinite
CH3 CH2 CH2 CH2 OCH3 butyl methyl ether 88 71 slight
CH3 OCH2 CH2 OCH3 ethylene glycol 90 84 infinite
dimethyl ether

• ethers are hydrogen bond donors

• the effect of hydrogen bonding is illustrated by
comparing the boiling points of ethanol and dimethyl
ether
CH3 CH2 OH CH3 OCH3

Ethanol Dimethyl ether
bp 78°C bp -24°C

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

Epoxides
• Epoxide: a cyclic ether in which oxygen is one
atom of a three-membered ring
C C H2 C CH2 CH3 CH CH2

O O O
Functional group Ethylene oxide Propylene oxide
of an epoxide
• ethylene oxide is synthesized from ethylene and O2

Ag
CH2 =CH2 + O2 CH2 CH2
heat
O
Ethylene Ethylene oxide

Epoxides
• other epoxides are synthesized from an alkene and a
peroxycarboxylic acid, RCO3H
O H
O
+ RCOOH O + RCOH
CH2 Cl2
H
Cyclohexene A peroxy- 1,2-Epoxycyclohexane A carboxylic
carboxylic acid (Cyclohexene oxide) acid

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
H+
CH2 CH2 + H2 O HOCH2 CH2 OH
O
Ethylene oxide 1,2-Ethanediol
(Ethylene glycol)
H
+ OH
H
O + H2 O
H OH
1,2-Epoxycyclopentane trans-1,2-Cyclopentanediol
(Cyclopentene oxide)
A Cycloalkene to a Glycol
• both cis and trans glycols can be prepared
H OH
+
RCO3 H H
O
H2 O
OH
H
trans-1,2-Cyclopentanediol
OH
Os O4 , t-BuOOH
OH
cis-1,2-Cyclopentanediol

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
CH3
NH3 H2 N  A-aminoalcohol
CH3 OH

H2 C CH +
CH3
H2 O/ H3 O 
O HO A glycol
OH
Methyloxirane 
(Propylene oxide) + - CH3
Na SH / H2 O 
HS A-mercaptoalcohol
OH


Epoxides as Building Blocks
• following are structural formulas for two common
drugs, each synthesized in part from ethylene oxide
CH3
CH3
O N
O CH3
N CH3
O
H2 N
Procaine Diphenhydramine
(Novocaine) (Benadryl)

Thiols - Structure
• The functional group of a thiol is an -SH
(sulfhydryl) group bonded to an sp3 hybridized
carbon

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 OH
HS
Ethanethiol 2-Methyl-1-propanethiol 2-Mercaptoethanol
(Ethyl mercaptan) (Isobutyl mercaptan)

Thiols - Physical Properties
• Low-molecular-weight thiols have a STENCH
CH3
Present in the CH3 CH=CHCH2 SH CH3 CHCH2 CH2 SH
scent of skunks:
2-Butene-1-thiol 3-Methyl-1-butanethiol
(Isobutyl mercaptan)
CH3 SH
Natural gas CH3 -C-SH CH3 -CH-CH3
odorants:
CH3
2-Methyl-2-propanethiol 2-Propanethiol
(tert-Butyl mercaptan) (Isopropyl mercaptan)

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
Boiling Point Boiling Point

Thiol (°C) Alcohol (°C)
methanethiol 6 methanol 65
ethanethiol 35 ethanol 78
1-butanethiol 98 1-butanol 117

Acidity of Thiols
• Thiols are stronger acids than alcohols
- +
CH3 CH2 OH + H2 O CH3 CH2 O + H3 O pKa = 15.9
-
CH3 CH2 S H + H2 O CH3 CH2 S + H3 O+ pKa = 8.5
• Thiols react with strong bases to form salts

+ - - +
CH3 CH2 S H + Na OH CH3 CH2 S Na + H2 O
pK a 8.5 pKa 15.7
Stronger Stronger Weaker Weaker
acid base base acid

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
oxidation
2 HOCH2 CH2 SH HOCH2 CH2 S -S CH2 CH2 OH
reduction
A thiol A disulfide
• this easy interconversion between thiols and disulfides

is very important in protein chemistry

Alcohols, Ethers, and
Thiols
End Chapter 8

Alcohols, Ethers, and Thiols

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Chapter 8:

Alcohols, Ethers, and

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

(a) CH3 ( CH2 ) 6 CH2 OH

© 2005 John Wiley & Sons, Inc

CH2 CH2 CH3 CHCH2 CH2 CHCH2

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

• aqueous solutions of alcohols have the same pH as

© 2005 John Wiley & Sons, Inc

*Also given for comparison are pKa values for water,

• thus, alcohols can function as both weak acids and

© 2005 John Wiley & Sons, Inc

2 CH3 CH2 OH + 2 Na 2 CH3 CH2 O-Na+ + H2

© 2005 John Wiley & Sons, Inc

• low-molecular-weight 1° and 2° alcohols are unreactive

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

CH3 rapid and

© 2005 John Wiley & Sons, Inc

• Step 3: reaction with halide ion completes the reaction

• Step 2: nucleophilic displacement of H2O by Br-

© 2005 John Wiley & Sons, Inc

3° alcohol 2° alcohol 1° alcohol

SN 1 Increasing rate of carbocation formation

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© 2005 John Wiley & Sons, Inc

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• Step 2: proton transfer to solvent and loss of H2O gives

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

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CrO3 + HCl + CrO3 Cl-

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

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CH3 CH2 CH2 CH2 CH2 OH 1-pentanol 88 138 2.3 g/100 g

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

CH3 CH2 OH CH3 OCH3

© 2005 John Wiley & Sons, Inc

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C C H2 C CH2 CH3 CH CH2

• ethylene oxide is synthesized from ethylene and O2

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

© 2005 John Wiley & Sons, Inc

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Boiling Point Boiling Point

© 2005 John Wiley & Sons, Inc

• Thiols react with strong bases to form salts