Organic Chemistry, 5th ed. Marc Loudon

Chapter
8


Introduc)on
to
Alkyl
Halides,
Alcohols,
Ethers,
 Thiols,
and
Sulfides


Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA

Chapter
8
Overview
 •  8.1
Nomenclature
 •  8.2
Structures
 •  8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
 Physical
ProperAes
 •  8.4
Solvents
in
Organic
Chemistry
 •  8.5
ApplicaAons
of
Solubility
and
SolvaAon
Principles
 •  8.6
Acidity
of
Alcohols
and
Thiols
 •  8.7
Basicity
of
Alcohols
and
Ethers
 •  8.8
Grignard
and
Organolithium
Reagents
 •  8.9
Industrial
PreparaAon
and
Use
of
Alkyl
Halides,
Alcohols,
 and
Ethers
 2


General
Classifica4ons
 •  Inspect
the
carbon
bearing
the
halogen
or
 hydroxy
group
 •  Classify
as
primary,
secondary,
or
terAary


8.1
Nomenclature


3


General
Classifica4ons
 •  Carbons
that
contain
two
or
more
hydroxy
 groups
on
adjacent
carbons
are
glycols


•  Thiols,
or
mercaptans,
are
the
sulfur
analogs
 of
alcohols
 •  The
–SH
group
is
called
the
sul=ydryl
or
 mercapto
group
 8.1
Nomenclature


4


General
Classifica4ons
 •  In
an
ether
an
oxygen
is
bonded
to
two
carbon
 groups


•  A
thioether,
or
sulfide,
is
the
sulfur
analog
of
 an
ether


8.1
Nomenclature


5


IUPAC
Nomenclature
 •  Subs4tu4ve
nomenclature:
Most
broadly
 applicable
system
 •  Common
nomenclature
(aka
radicofunc4onal
 nomenclature):
Used
for
simplest
and
most
 common
compounds


8.1
Nomenclature


6


Alkyl
Halides
 •  The
common
name
uses
the
name
of
the
alkyl
 group
followed
by
the
halide


8.1
Nomenclature


7


Alkyl
Halides
 •  Other
common
names
to
learn:


8.1
Nomenclature


8


Alkyl
Halides
 •  The
subs)tu)ve
name
treats
the
halide
as
a
 subsAtuent


8.1
Nomenclature


9


Alcohols
and
Thiols
 •  The
common
name
is
derived
by
specifying
 the
alkyl
group,
followed
by
“alcohol”


•  A
few
glycols
have
tradiAonal
names


8.1
Nomenclature


10


Alcohols
and
Thiols
 •  The
common
name
used
for
a
thiol
is
 mercaptan
 •  Thiols
readily
combine
with
heavy
metals;
the
 name
derives
from
“mercury
capture”


8.1
Nomenclature


11


Alcohols
and
Thiols
 •  The
subs)tu)ve
name
is
generated
from
the
 principle
group
 •  The
principle
group
is
the
chemical
group
on
 which
the
name
is
based
and
is
always
the
 suffix
in
the
name


•  The
priori)es
of
principle
groups
will
be
given
 as
they
are
encountered
in
upcoming
chapters
 8.1
Nomenclature


12


Principle
Group
and
Principle
Chain
 1.
IdenAfy
the
principle
group
(e.g.,
‐OH
>
‐SH)
 2.
IdenAfy
the
principle
chain
which
is
the
chain:
 •  With
the
greatest
number
of
principle
groups
 •  With
the
greatest
number
of
double
and
 triple
bonds
 •  Of
greatest
length
 •  With
the
greatest
number
of
other
 subsAtuents
 8.1
Nomenclature


13


Principle
Group
and
Principle
Chain
 3.
Number
the
carbons
of
the
principle
chain
 giving
the
lowest
numbers:
 •  For
the
principle
groups
 •  For
mulAple
bonds
(C=C
>
C≡C)
 •  For
other
subsAtuents
 •  For
the
subsAtuent
cited
first
in
the
name


8.1
Nomenclature


14


Principle
Group
and
Principle
Chain
 4.
Begin
construcAon
of
the
name
with
the
 name
of
the
hydrocarbon
corresponding
to
 the
principle
chain
 •  Cite
principle
group
by
suffix
and
number
 •  If
there
is
no
principle
group,
name
the
 compound
as
a
subsAtuted
hydrocarbon
 •  Cite
the
names
and
numbers
of
other
 subsAtuents
in
alphabeAcal
order


8.1
Nomenclature


15


Other
Alcohols
 •  For
alcohols
with
more
than
one
–OH
group
 use
diol,
triol,
etc.
 •  Do
not
drop
the
final
e
of
the
alkane


8.1
Nomenclature


16


Ethers
and
Sulfides
 •  The
common
name
is
constructed
by
ciAng
the
 two
groups
adached
to
O
or
S


8.1
Nomenclature


17


Ethers
and
Sulfides
 •  Ethers
and
sulfides
are
never
treated
as
 principle
groups
 •  The
subs)tu)ve
name
makes
use
of
the
terms
 alkoxy
(RO‐)
and
alkylthiol
(RS‐)


8.1
Nomenclature


18


Heterocycles
 •  Some
important
ethers
and
sulfides
are
part
 of
a
cyclic
structure


•  An
important
subclass
of
heterocyclic
ethers
 are
epoxides


8.1
Nomenclature


19


Bond
Angles
and
Lengths


8.2
Structures


20


Boiling
Points
of
Ethers
and
Alkyl
Halides
 •  Most
alkyl
halides,
alcohols,
and
ethers
are
 polar
molecules
 •  They
possess
permanent
dipoles


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


21


Boiling
Points
of
Ethers
and
Alkyl
Halides
 •  Polarity
leads
to
greater
intermolecular
 adracAon
in
the
liquid
state


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


22


Boiling
Points
of
Ethers
and
Alkyl
Halides
 •  Molecular
size
and
shape
can
dramaAcally
 affect
physical
properAes


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


23


Boiling
Points
of
Alcohols
 •  Alcohols
have
unusually
high
boiling
points
 when
compared
to
structurally
similar
 compounds


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


24


Hydrogen
Bonding
 •  An
adracAon
between
the
H
on
one
atom
with
 an
unshared
electron
pair
on
another


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


25


Hydrogen
Bonding
 •  FormaAon
of
a
hydrogen
bond
requires
a
H‐ bond
donor
and
a
H‐bond
acceptor


8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


26


Hydrogen
Bonding
 •  FormaAon
of
a
hydrogen
bond
requires
a
H‐ bond
donor
and
a
H‐bond
acceptor


•  Best
donors:
O,
N,
halogens
 •  Best
acceptors:
O,
N,
F
 8.3
Effect
of
Molecular
Polarity
and
Hydrogen
Bonding
on
Physical
Proper)es


27


Classifica4on
of
Solvents
 •  Pro4c
(H‐bond
donors)
or
apro4c
 •  Polar
(high
dielectric
constant)
or
apolar
 •  Donor
(Lewis
base)
or
nondonor


8.4
Solvents
in
Organic
Chemistry


28


Solubility
of
Covalent
Compounds
 •  Rule
of
thumb:
Like
dissolves
like


8.4
Solvents
in
Organic
Chemistry


29


Solubility
of
Covalent
Compounds
 •  A
compound
is
miscible
if
a
soluAon
is
 obtained
when
mixed
in
any
proporAon
with
 water


8.4
Solvents
in
Organic
Chemistry


30


Solubility
of
Ionic
Compounds
 •  Ionic
compounds
in
soluAon
can
exist
as
ion
 pairs
or
dissociated
ions
 •  In
an
ion
pair,
each
ion
is
closely
associated
 with
an
ion
of
opposite
charge
 •  Dissociated
ions,
surrounded
by
a
solvent
 shell,
move
more
or
less
independently


8.4
Solvents
in
Organic
Chemistry


31


Ions
in
Solu4on


8.4
Solvents
in
Organic
Chemistry


32


Donor
Interac4ons


8.4
Solvents
in
Organic
Chemistry


33


Cell
Membranes
and
Drug
Solubility
 •  Solubility
is
crucial
for
drug
acAon
 •  Water
solubility
is
important,
but
the
drug
 must
also
be
able
to
arrive
at
its
target
site
 •  The
drug
must
be
able
to
pass
through
the
cell
 membrane
 •  Cell
membranes
are
composed
of
 phospholipids


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


34


Lipids
and
Phospholipids
 •  A
lipid
is
a
compound
that
shows
significant
 solubility
in
apolar
solvents
 •  Lipids
are
defined
by
behavior
rather
than
a
 precise
structure
 •  They
typically
contain
polar
funcAonal
groups,
 but
have
significant
hydrocarbon
character
 •  Phospholipids
are
lipids
that
contain
the
 phosphate
group


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


35


Lipids
and
Phospholipids
 •  Membrane
phospholipids
are
built
on
a
 glycerol
“scaffold”


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


36


Structure
of
Phospholipids
 •  Polar
head
group:
A
hydrophilic
group
that
 interacts
favorably
with
water
 •  Nonpolar
tail:
A
hydrophobic
group
that
is
not
 well
solvated
by
water;
oienAmes
referred
to
 as
a
“greasy
group”
 •  Molecules
that
contain
these
two
discrete
 regions
are
called
amphipathic


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


37


Structure
of
Phospholipids


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


38


Structure
of
Cell
Membrane
Bilayer


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


39


Ca4on‐Binding
Molecules
 •  Ionophores
are
molecules
that
form
strong
 complexes
with
specific
ions
 •  Crown
ethers
are
heterocyclic
ethers
with
 regularly
spaced
oxygen
atoms


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


40


[18]‐Crown‐6
and
Potassium
Ion


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


41


Ca4on‐Binding
Molecules
 •  Cryptands
are
 nitrogen‐containing
 analogs
of
the
crown
 ethers


8.5
Applica)ons
of
Solubility
and
Solva)on
Principles


42


Acidity
of
Alcohols
and
Thiols
 •  Alcohols
and
thiols
are
weak
acids
 •  pKa
(ROH)
≈
16;
pKa
(RSH)
≈
10


•  The
conjugate
bases
of
alcohols
are
alkoxides
 •  The
conjugate
bases
of
thiols
are
mercap4des


8.6
Acidity
of
Alcohols
and
Thiols


43


Forma4on
of
Alkoxides
 •  An
alcohol
cannot
be
fully
converted
into
an
 alkoxide
with
aqueous
hydroxide


•  Sodium
hydride
or
sodium
metal
must
be
used


8.6
Acidity
of
Alcohols
and
Thiols


44


Forma4on
of
Mercap4des
 •  Thiols
are
much
more
acidic
and
can
be
 deprotonated
with
hydroxide
or
alkoxide



8.6
Acidity
of
Alcohols
and
Thiols


45


Polar
Effects
on
Alcohol
Acidity
 •  SubsAtuted
alcohols
and
thiols
show
the
same
 type
of
polar
effect
on
acidity
seen
for
 carboxylic
acids


8.6
Acidity
of
Alcohols
and
Thiols


46


Role
of
Solvent
in
Alcohol
Acidity
 •  Alkoxide
basicity:
TerAary
>
secondary
>
 primary


•  This
trend
is
reversed
in
the
gas
phase


8.6
Acidity
of
Alcohols
and
Thiols


47


Acidity
of
Alcohols
 •  Alcohols
and
ethers
have
the
similar
basicity
 •  Thiols
are
much
less
basic


8.7
Basicity
of
Alcohols
and
Ethers


48


Organometallic
Compounds
 •  Compounds
that
contain
carbon‐metal
bonds
 •  Organomagnesium
and
organolithium
are
two
 of
the
most
useful
types
 •  Grignard
reagents
(R‐Mg‐X):


•  Organolithium
reagents
(R‐Li):


8.8
Grignard
and
Organolithium
Reagents


49


Forma4on
of
Organometallic
 •  Grignard:


•  Organolithium:


8.8
Grignard
and
Organolithium
Reagents


50


Charge
Distribu4on
for
C‐M
 •  Carbon
is
more
electronegaAve
than
Mg
or
Li
 •  This
places
nega)ve
charge
at
the
carbon


8.8
Grignard
and
Organolithium
Reagents


51


Protonolysis
of
Organometallic
Compounds
 •  Therefore,
carbon
may
be
conceptually
viewed
 as
a
carbanion


8.8
Grignard
and
Organolithium
Reagents


52


Free‐Radical
Halogena4on
of
Alkanes
 •  SubsAtuAon
of
a
hydrogen
by
a
halogen


8.9
Industrial
Prepara)on
and
Use
of
Alkyl
Halides,
Alcohols,
and
Ethers


53


Uses
of
Halogen‐Containing
Compounds
 •  Alkyl
halides
and
other
halogen‐containing
 compounds
have
important
uses
 •  Solvents:
CH2Cl2,
CH3Cl
 •  Monomers
for
PVC,
Teflon,
Kel‐F
 •  Herbicides
and
pesAcides:


8.9
Industrial
Prepara)on
and
Use
of
Alkyl
Halides,
Alcohols,
and
Ethers


54


Produc4on
and
Use
of
Alcohols
and
Ethers


8.9
Industrial
Prepara)on
and
Use
of
Alkyl
Halides,
Alcohols,
and
Ethers


55


Produc4on
and
Use
of
Alcohols
and
Ethers


8.9
Industrial
Prepara)on
and
Use
of
Alkyl
Halides,
Alcohols,
and
Ethers


56


Safety
Hazards
of
Ethers
 •  Ethers
undergo
autoxidaAon
in
the
presence
 of
oxygen
from
air


•  The
resultant
peroxides
and
hydroperoxides
 are
explosive
 8.9
Industrial
Prepara)on
and
Use
of
Alkyl
Halides,
Alcohols,
and
Ethers


57