Chapter 19:Carboxylic Acids
0
Nomenclature:
-
ROH
0
II
1
+
OH
oic
acid
⑧
yMethanoic
Mor] *thataic
Acid
Bonding
structure's
↳
polar
H
:
I↳
-
A
--
CH
io
C
↳
.
...
-
H
-
-
C
+
0H
&
t
Physical Properties
↳higher melting s Boiling points
-
intermolecularforces
↳ Strong
8-St
0 ---H-
O_
HzC"
C
-o
-
-
-
-
!
He
3
hydrocarbons
than
(Hydrogen
is
oxygen containing organic
similar shape
of
is similar to
b
Size
bonding)
in water
solubility
4 carboxylic acids w/ four
in all
structures
alcohols
carbons
or less are
miscible
in
water
proportions
Acidity
-
↳
weak acids
↳ More acidic than
↳
carbonyl
10:
alconds
groups are
as
conjugate base
is
more stable
dueto
resonance
EWG
8
H3C
vs.
....
ate
H3c-cHz-
-
Conjugate
of
cany·ug
acid
carboxylic
of Alcohol
Estrength
↳ Ka of Carboxylic acids of form [nHan+ICOCH
↳ electronegative substituents
Cl
91
-
i
I
⑧
- ~,
-2
N
~
I
L
are
a carbon increase
attached to
relatively
the same
of
carboxylic acids
acidity
& As the number of bands between the 2-carbons,
increase, the inductive effects
electronegative substituent
decrease in strength
Formod 3
↳ Strong
than acetic adin
slightly stronger
⑧
11
* carbon
ENG
pka 4.7
=
Not
becomes
to
ortho to
more
electron-withdrawing
carboxyl groups
increases
as its
5
charcter increases
compared to
acidity
Parasmeta
Acid Salts
ylic
↳
in presence of
strong base,
carboxylic
⑧
CHOH
⑧
+
StrongBase
(Li-ot)
acetic
CHao
--
Lithium
acid
acetate
↳ Hydrophilic
↳
if
onthe
The
3
acids
are
rapidly neutralised
-ic--ate
3
Metal first
group
long hydrocarbonchain which are lipophilic (fat-loving) then
hydrophilic rest of chain is lipophilic amphiphilic molecule
end of
carboxyl
is
a
the end
=
3
have the
Micelles
carboxyl facing
↳
out
the hydrocarbon
on the
chain
inside
Acids
Doxylic
↳ require
↳
one
twolonisations to
carboxyl group
hadthe
boric
!
i
CO2
remove
acts as
a
H
each
EWG
we
-... -
-
H.0
H
carbonic acid
carboxylic acids
↳of
cobalt or
CHOH Comcat.,
+
heat, pressure
of the
carboxyl
which stabalises the
-
=
hydrogen
CH3CO,H
acetic acid
-
or
group
the other
ionization of
w/
Acids from Grignard
-ic
See
·Ngx
R
~-
3
a.
Hot
S
-
8t
↳ alkyl
or
aryl
halide into
In I.
Mg,diethylether
I
->
C
carboxylic acid using griguard
acidic
workup
reagents
I
·on
2. CO2
3. 5yO
are incompatible
have substituents that
* can't
w/ griguard
Brough
Hydrolysis
alkul
cyanides
of
reagents (OH,SH, NHD
Acid
↳ Nitriles
are
↑
- R.
RCEN+2H20
/1
M
-/
-
cHCl
Sw2
Nitriles
REN+ix:
-
Nitrice
ROH
+H
NaCN
->
DMSO
NHI
H20
Al
-CHICNI LY
BrBr
H20
+
91
CH20H
heat
NC
CN
-
⑧
120, HCI
-
Heat
Il
O
It
How CH
ism of Acid-Catalysed
Esterification
-
O
1"
I
I-
CH30H
t
OH
Eat
I
-
10-enriched
H20
+
Methanol
G
c-o band of
the alcohol
is
preserved
MECHANISM:
tabe
More S
-
Step 1:Protonate carboxylic acid
0:
I
11
W
IlT
I/
-
-
-
H
n
+
,[Hs
k
-
at0
-
=,To
I
H- CH3
:
0
-
2
Step3:deprotonate the
2
7 ~
//
I
I
-
I
x
L
-
.0
1
CH3
:
"H
·
O
-
-H
oxygen
carbon
Methand
bonds c0
to
...
-cry
H
W
7
0
I
0
L
I/
-7
of
-
-
H
postivly charged oxygen
,a53
CH3
-H
I/
-
0
-
nucleophile
L
H0;
/
-
H
acts as a
/
I/
I
I/I
-H
-
-H
-
Step 2:alcohol
H,A
- a)
cresonancesarethe
C-
on
+
O-
-
(CA)
H0:
2
- W
I I
IL
I1
:
---
-
-
CH3
H
+
-
H-
the
=
w/
a
+-ve
charge
Step 4:Protonate oxygen
of -OH CA
Hi
//
I I-cH3
-
S
10.
Le
t
+
-
-H
Step 3:Protonated
0
or
10.
-
H
Step 6:Deprotonate
group
t
-
↓To -H
-
leaves
120
as
/
I I
11I/T
-
o-cr+x
-
H
t
C OH
=
↳1
/
7
11
=
H
-
-
I
I
-
H: -cH]
I
H3
-cts
L.
II
I I/
LI->I
-
H- 0:
↳ I
group
i
CH3
IH
... CH3
-
acts
0:
be"
-
6:
H- +
+
-H
:0- CH3
Ester Formation:Lactores
-
↳ Hydroxyl (-0H)
is carboxylic acid containing compounds
canform
cyclic Esters
called lactones
↳
Five or six
↓
membered rings
↳ 8-lactones
Flactones
O
11
OXoH
40
--
H,0
+
⑧
11
noteor
I O
1
->
-
0
H20
+
↳ Happens spontaneously
↳ Replace
-
↳ Reactions
oic
11
with -olide
that are expected to
produce
lactones if
O
acid
a
9
membered
5 or 6
u OH
1.
NaHy
->
2.
H30+
ring
acids often yield
hydroxy
can be formed
M
-
11I
O
off
0
I
via
0
It
not
Exylation
of Malonic Acid
-
RCO2H
Gloss
of
->
HO
CO2
+
CO2 from
↳ very hard I
0
I
RH
Carboxylic Acid decarboxylation
=
rarely happens
⑳
It
II
MoH
150°
->
0 =c 0
=
↳ only
one carboxylic acid group
H
of
·X
Slow
-o c 0
=
=
-
NoH
+
lost
0
0
ko
11
fast
~Or
-
+
on
↳ Keto-Enol in
9.11
escopic Analysisof
Carboxylic
Acids
-
↳ 1H NMR:
a
↳
The proton on the
13
hydroxyl group
CWMR:carbon of -CO2H
is
is
the most
deshielded
around 140-185 nm
Chapter 20:Carboxylic Acid Derivatives:Nuc Acyl Substitution
-
Hi
0
11
Ras
Acyl chloride
↳ all have
an
Acid
⑧
0
R
Ro-
Anhydride
acyl group bonded
Ester
to an
It
-N-
ative
electroney
element
Ri
Amide
R
⑧
O
H
R1 X
Il
-
Nu-H->
+
R
H X
-
+
Nu
Nomenclature
1) Acyl chloride
-
is
acid---yI
L-carbonyl chloride used for
attachments to
rings
other than benzene
0
I
Mc
Pentanoy
chloride
#)Acid
Anhydrides
"anhydride"
"acid"replaced with
99
No
Acetic Anhydride
#) Esters
↳ Named
as
alkyl
alkanoates
11
CH3 0 CH2CH3
Ethyl
#)
in
I
COCH2CH2CI
0
0
I
CH3CH2C0 CH3
acetate
-
L/
-
Methyl propanoate
2-chloroethyl
benzoate
Amides
-
is
acid/-oic acid
↳substituting
3-
on
->-amide
the
Methylbutahamide
Nitrogen
indicated by locant" the
/Ne
A
I
N-Ethyl-3-methyl
butanamide
↳ carboxamide
used when amide
N-Ethyl-N,3-dimethylbutah amide
group
is
attached to
a
ring
)Nitriles
↳
-oic acid/-ic acid ->
↳ "carbonitrile"if
-
CN group attached to
ring
a
↓
CH3CEN
Ethanenitrile
MEN
-
cyclopentane carbonitrile
5-methylhexahenitrile
or
or
Acetonitrile
Reactivity
onitrile
4-methylpentyl cyanide
Carboxylic Acid Derivatives
of
AcylChloride) anhydride ester) amide
(for reactivity)
↳ Amides
:
80.
R
4
R
is a
Sie
/
R1
7
C-clbond
-
cy
X:
+
IX:
electrons
Release of
::
R-cc!
:
"
Lonepairdonatich
ineffectivebecause
is
Not a significant
resonance contributeare
overlap
very long
(prevents effective
electron
#) Acid
delocalisation)
Anhydrides
↳ oxygen
:
↳I
R
C
is a
better electron donor than chlorine
:0:
A
I
vo -
I
--
11
C
:
5-
-R
R
/
·
.
XR
O
..
C
:
:
->
R
-
c
I +-
C
.. xR
O
5>
R-
jo
from X stabalises the
poor electron pair donor
-
-
R
-
C
I
carbonyl group
I) Acyl Chlorides
↳ chlorine
-
resistant to hydrolysis
are more
↳ Both carbonyl groups fighting for
Esters
the same
stability
lone pair which reduces
#
↳ only
R
carbonyl group they
one
:
-
C
is more
are more stable
x
pro&9
effective than
2
R
IV) Amides
↳ Nitrogen
is less
electronegative
-:
B
-
C ~I..
-
↳ High
Ni
than
R-swan3
oxygen
very
effective
resonance
rotational energy barrier for C-U bond
meaning there
double bond character
Nudeophilic Acyl Substitution
HoX
.0:
11
R
addition
-
Nu-H->
RNU
+
X
(Mechanisms]
(slow)
(fast)
significant
0
#Nu H
Elimination
->
is
+
-
X
R
I
Rate determining
Step
↳ Depending on
acid-base
intermediate is formed
H-
j*
-H
RV
Nu
I
tetrahedral
↳ once formed
Product of
stable
pH
of
R
-NoI
tetrahedral
solution)
·X
-
R
~Nu
Tr
conjugate base of
tetrahedral
intermediate
intermediate
↳ Reactions
/
on
T
conjugate acid
~
(depends
H
-
-
T1-Ht
of
a cation, anion, or neutral
chemistry
the TI can revert to
tetrahedral
original
intermediate
derivative
CA
or
form
nucleophilic acyl substitution
will
one
generally convert
least stable
carbonyl groupto a more
↳ Alternative
↳
R1
Slow
ix
- >
R
+
-
mechanism is observed
of cases
↳ ionisation
ai
-x
mechanism
+Nu-
Nucleophilic Acyl
↳ Acyl
only
with
:0:
11
acyl chlorides
3
Sv1
↑Nu
R
in a
limited number
(Sw2)
R
1) Acyl
d:
=
·Nut
fast
-
X
↳ This
nucleophilic acyl substitution
..........
YN
- Nu
xx
R
Substitutich
chlorides
chlorides
through
readily
converted to acid
anhydrides, esters,
isamides
Nuc substitution
& pyridine acts as
B
is
a
a
catalyst
weak base
↳ increases rate of
aculation
↳ Base helps prevent build up of
HC
#) Acid Anhydrides
⑧
To
E
9
I
CH320CCH3
Acetic
anhydride
↳ Acid anhydrides
I
"
patholic anhydride
are two
-cr
Maleic anhydride
acyl groups bonded to the same oxygen
O
O
It
I
HY:-
+
0
ROY HOR
+
carboxylic
Nucleophile
Bond Cleavage
acid
~Bond
S
Bond
5
aree
+Ho
Cleavage
⑧
⑧
0
It
11
-
No
0.NA-owa
-
,
02
i
N-
ov
+Howa
Mechanism:
:
Step 1:
o
II
II
·
+.
-
I
I
oT
slow
->
X
0=
T
1//
1
o-
-
-
NO2
Step 2:
:
↳1
o
=
o
i
o
T
1
I
-
-
Physical Properties
4 Esters
NO,
10:
T
-
T
Fast
->
-
1-
NO2
+
:
&Sources of Esters
moderately polar
↳ lack hydroxyl groups so they hydrogen bonds by each other
are
↳ But they
can
groups
↳ low MW
form
hydrogen
bonds with substances that contain
esters are water solvable
↳ Solubility 1
When # of
C4
hydroxyl
Reactions of Esters
Ester Hydrolysis
Acid-Catalysed
O
11
0
H20
RCOR'
+
ROH
Alcohol
carboxylic
Ester
acid
↳ generous
excess of water
"
- d
11 -
ROH
+
10X
-or
H,0,x
↑T I
heat
+
NoH
+
Mechanism
Step 1:
I
0:
-
Il
-
1o
R
H
+
-8
Step 2:
I
!
o
i
III
H
-
R of
-I
I
H
I
I
0:
-
:or
fast
-
**
It
- or
10:
0
H
-
+
-
R
H
/
t
.
.
t
H
slow
-
-
R
-
-H
/
- or
L
3:
Step
H
10:
or
=
fast
1.
V
I
i-
i
HO
·H
V
X
~I
S
R
H
+
or
..
-
or
t
-
I
"H
Step
4:
..
H0
A H-
H
V
--
+
I
RX or
i
*
-
H0
fast
I
I
-
VH
R
-
H0:
-
i.
slow
-
-
<
↳O
-s
-
H.
0
-
Ii
I
R
H
+
0
-
of
·o-
fast
: ot
H+
-2
Ester
+
9
-
.H
methand
Step 6:
-
H
H
-
+:
H
X
is
·
I
~
Step 5:
or
In
-
.
R
+-
H
Ai
-
H
+
-+
H
-
carboxylic
acid
Hydrolysis
in
Base:Saponification
↳ Irreversable
↳
hydroxide (-OH)
not a
is a reactant
RYOR'
Ho-->
+
catalyst
O
0
Ro-+ROH
carboxylate
alcohol
ich
T
watermethand
⑧
+
NaOH
->
heat
⑧
I
ol
Al-
1oNa+
v//
I
I
↳ To
separate acidification step
carboxylic acid, a
isolate
is
O
O
It
=-
heaton
or 20,
I
I
+
CHOH
H2SOY
2.
↳ Saponification:Ester hydrolysis
in a
base
Mechanism
-..H
Step 1:
"
S
:0:
H
&II ....or
RV..
Step
V
Mor
R
,w
SIOW
-
I
~ I
2:
:0:
r
:
↳I
Fast
-
R1 o -
↳
It
-
-
I
-
H
R
-
-
:or
-
Step 3:
⑧
R
:
-
11
-
~
0
-
H
H
+.
-
H
1
R
0
.....
(weaker base)
:
X A
+
-
-_-n
-
Reaction of Esters with
↳
Ester
ammonia
+
=
RCOR'
Ester
amines
amide
0
0
11
iH
+
Ammonia,
NH3 ->
+
ammonia
RINHL+BOH
Amide
0
:H
(weaker acid)
H
I
H- 0 .
·
-
+
alcohol
needed
0
⑧
It
-
+
I
* NH,
N,
NH,
*
FLHEY
-
amine
↳ Tertiary
CH3OH
⑧
Fo+N
be
& The amine must
+
(RNH2)
primand
have no proton
on
or
nitrogen to
HO
+
Secondary (R2NH)
be
replaced by
an
acyl group
Grignard, organolithium, Lithium Aluminum Hydride
Esters with
Grignards organolithium
I
↳ Needs
2
equiv. Grighard
P
No
+
R
2R'MgX
or
or
organolithium
R R
2R'Li
1, diethyl ether
->
2.
H30t
11
I
-1
⑧
H30+
+MgX
R'MgX
diethyl
ether
HAIHs
~AIAS
diethyl ether
X or
-
+
:
.
- R CH3
S
R
Ketone
intermediate
Wig
D
↳
H
.0:
II
->
--
R
-H
-CH3
Aldehyde
↳ Aldehyde
gives
Yor H01
1
-
-
->
N
Hydride ((AH)
-
:
Nor
-
#) Lithium Aluminum
R
i
-
X ·
O
diethyl ether
-
2CH3MgI2.
+
A
R
CH30H
alcohol
⑧
11
I
Tertiary
Methyl ester
O
W
RXoH
2
is
rapidly
alcohols:
II
reduced under
-
intermediate
intermediate
primary derived from aldehyde
one from the
alkoxy portion of the original ester
one
11
--oX
the conditions
1. LiAIHy, diethul ether
2.
H30
I
IX
~
-
or,on
Amides
↳ CN bond is
shorter in amides
↳ energy forrotation is higher than
-H
H
I
↳ Amides
:
I
HXN
A
I
Fr ->
H
i
I
very polar
forces
stronger intermolecular attractive
causes
GN< 0
for
electronegativity making
Amides
of
RCOR
acid
Amine
RNH
of
salt
-
CNRn
+
O
RNHOR
carboxylate salt
Amide
Anhydride
amine
of Amine
0
YoCHs -RNRL CHOH
+
+
ester
↳ Esters?Amines
1:1 ratio
react in a
4 No acidic product
iX
Methano
Amide
Methyl
Amine
:
or of
Hydrochloride
Amide
acylchloride
+
-
It
O
2RNH
acid than
RCNR2 +R,NH, C1-
R'Cl->
Amine
weaker
O
O
+
it a
(BPM)
acid
carboxylic
zRcNH
...
:O
are
->
Synthesis
amines
is
formed so
no
base
is
:X
I-
H-
+NH
R2
↳ Amides
are
-
- -
I
formed
NE"
required
it
"WNR,
-
R
rapidly
R
+
HX
a
Amides
Hydrolysis of
I) Heating
↳
strong acid
in
Amide bond is cleaved
RR' HzOT
+
heating
on
in the
REoM +RINH,
-
Ammonium
carboxylic
Amide
ion
acid
#) Heating in
a
presence of
0
strong
Base
0
RR
+-OH
-
RYo
RNH
↳ Both are irreversible
EHNH
so
heat
I
19
Tr I 1/
I
-
-
H
Mechanism
Br
kOH
->
ethanol-water
heat
of
Step 1:
Hydrolysis in
on Nason
I
O
or HN-X-Br
+
Acid
in
HEPA
an
: - +H
RNH,
I
H
Step 2:
+- H
o
+:
w
H:
1..
↳
0
+
-
H
RXNH2
Step 3:
Efast
H0:
-
BXNHz
HO
W
OH
B XNAz
+
-H
o
H-
"
H
a
strong
acid
Step 4:
O
H.:
of
--
I-
~v
=
H
+
RXNH,
-
0·
↓ (H
-H
REFs
"I-
-
Step 6:
0 -H
1x
R10
-
:
t
H
Ho
-
i
-
I
2:
Step 3:
Step 4:
0-
I
H
Mechanism of
Step 1:
H
I
D
I
-H
I
Step
L
->
V
t
H
i
0-
-H
..- H
Step 5:
4
rei
-
A
+
+:
I
&+- H
R1
+iNHs
!+
H-
-
↳
↓
NH3
Hydrolysis
20:
I
H
in
2
+
Basic solution
e
-
NH3
Step 5:
Lactames
↳ cyclic Amides
To
wil
-Y
in 48
N-methylpyrrolidone
H
e-caprolactam
↳ lactams> lactones for
stability
↓
↓
esters for stability
amides)
Preparation of Nitriles
0
11
RCNH2
Amide
CAryail
RCEN
->
Nitrile
+
H,0
,
200C
Hydrolysis of
Nitriles
↳ Nitriles-> carboxylic acids upon hydrolysis
Acid Hydrolysis
#
RCEN
H0
+
H0
+
Carboxylic
acid
Nitrile
Y
T
EY
-
02-
#)
Base
Ammonium
ion
0
-
ON -
H20, H2SO4
H
I
I
->
heat
Hydrolysis
carboxylate ion, second step (acidification) would
Carboxylate to carboxylic Acid
↳ yields
the
RYOH+NHy
->
a
Ro
RCEN H20 +OH-->
+
-+
Carboxylate
Nitrile
NHS
Ammonia
ioh
CH3(CH2)qCN
O
11
1. OH, H2O, heat
->
2.
H30t
CH3CCHJaCOH
Mechanism
Step 1:
H.
RE:
Step 2:
:
"H
0
g"v
ask:+
~
-
H
O"
H-*
I
- -
I
a
-
TNA
Ti
convert
Step 3:
H
I
H-RXH
:0:
A
R
-N -At
o
-
11
H
W
HO:
-
+
-
-
H
I
A
Step 4:
:
RX
-
+
H
~
-
H
-
0:
-
0
It
I
-
RNN
-
I
..
in Basic
Hydrolysis
R XXN
-
H
::
X
OH
:.
+
H
Step 6:
H I
Ho:.
V
H- 0
RUNH2
K
-
Step
7:
HO
it
W
-
OX.oH
-
r
RLNH2 +CH-
->
H&OH
A
H-OH- RUNH5
OH
.
RX NH2
↳
-
=
H
+
I o
Solution
H.
-
+-OH
-
RV THz
~
Step 8:
*
HO
*
-j
RYNHs
I
O
·-H
RYOH
- >
↑
RTO
.
-
-
+
Yo-H
-
Step 9:Irreversible formation
9:
+iNHs
I
H
+
-H
carboxylate
of
H
O
11
RVo +H-0!
-
·
~
.
ion
H
=
-I
"
H
·
It2
H
I
·
Step 5: Amide
-
Addition of
↳ Triple
Grignard to
bond of
Nitriles
reactive to
is less
Nitriles
4 Need strongly basic nucleophiles
ether
diethyl
RCEN+R'MgX1.
2.
TE
N
Y
Y
H30t
CHaMgI
+
=
Nucleophilic attack
(Grignard)
NH
I
c
RCR
Idiethulether
->
2. H30+, heat
FC
0
H30t
Teat?
II
RCR
,
IT
L/
-
Fac
Spectroscopic Analysis
I) 'H NMR
4 Methyl propanate
↳ Ethyl
Acetate
4 Methyl Hydrogens
are
MORE
shielded when
carbonyl group (a) than just
#)
an
attached directly
oxygen (b)
CNMR
↳
160-1808
↳ More shielded
↳
N
c=
↑8120
than carbons in
AldehydessKetones
to a