Carboxylic Acids

1
 Importance of -COOH
O COOH
O O COH O O O O CH2
CH3C COH HO H HOC COH HOCCH2CH2COH HO COOH
pyruvic acid CH3 oxalic acid succinic acid CH2
(S)-(+)-lactic acid spinach COOH
sour milk citric acid
lemon
O O
O HO
COOH COH COH
HOOCCH2 H
OH
(S)-()-malic acid H OH H OH
HO
apple prostaglandin A2 prostaglandin F2

Hormones ( inflammation/hypertension/pain and sw

2
 Structure of Carboxyl
 Carbon is sp2 hybridized
 Bond angles are close to 120
 Three resonance structures

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 Physical properties

Boiling point (BP)

• Carboxylic Acids have higher BP than other
organic molecules with comparable MW.

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 Boiling point

Higher boiling points than similar alcohols,

due to dimer formation.

Acetic acid, b.p. 118C 5

 Physical properties
Melting Point
• Aliphatic acids with more than 8 carbons are
usually solids at room temperature.
• Double bonds (especially cis) may lower the
melting point significantly
• Note these 18-C acids:
– Stearic acid (saturated): 72C
– Oleic acid (one cis double bond): 16C
– Linoleic acid (two cis double bonds): -5C

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Physical properties
CO2H

Stearic acid (abundant in beef talow): MP = 72C

CO2H

Oleic acid (abundant in olive oil): MP = 16C

CO2H

Linoleic acid (abundant in corn oil): MP = -5C 7

 Physical properties
Solubility
• Water solubility decreases with the length of the
carbon chain.
• Up to 4-6 carbons, acid is miscible in water.
• More soluble in alcohol.
• Also soluble in relatively nonpolar solvents
– i.e. Chloroform - CHCl3

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 Acid Dissociation Constant = Ka

For Acetic Acid, Ka ~ 10-5 So, for Acetic Acid pKa ~ 5

pKa provides a relative measure of acidity among compounds

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 Acidity Compared to Alcohols
• Carboxylic acids better H+ donors than alcohols
– pKa of ethanol is ~16, compared to ~5 for acetic acid

• Alkoxide ion (R-O-), negative charge is localized on O

• Carboxylate ion (COO-) negative charge is delocalized over two equivalent O atoms: Resonance stabilization

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 Substituent Effects

• An electronegative group will drive the ionization

equilibrium toward dissociation, increasing
acidity
• An electron-donating group destabilizes the
carboxylate anion and decreases acidity 11
 Substituent Effects

Electronegative substituents promote stability of the carboxylate

anion which promotes acid strength 12
Substituent Effects

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 Substituent Effects
Distance from carboxylic acid: butanoic acid:

CH3CH2CHClCOOH pK 2.9
CH3CHClCH2COOH pK 4.1
ClCH2CH2CH2COOH pK 4.5
CH3CH2CH2COOH pK 4.8

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IUPAC nomenclature for carboxylic acids:
parent chain = longest, continuous carbon chain that contains
the carboxyl group  alkane, drop –e, add –oic acid

HCOOH methanoic acid

CH3CO2H ethanoic acid
CH3CH2CO2H propanoic acid

CH3
CH3CHCOOH 2-methylpropanoic acid

Br
CH3CH2CHCO2H 2-bromobutanoic acid 15
dicarboxylic acids:
HOOC-COOH oxalic acid
HO2C-CH2-CO2H malonic acid
HO2C-CH2CH2-CO2H succinic acid
HO2C-CH2CH2CH2-CO2H glutaric acid
HOOC-(CH2)4-COOH adipic acid
HOOC-(CH2)5-COOH pimelic acid

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 CO2H CO2H
CO2H

CO2H CO2H
CO2H
phthalic acid isophthalic acid
terephthalic acid

H COOH H COOH
C C
C C
H COOH HOOC H

maleic acid fumaric acid

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salts of carboxylic acids:
name of cation + name of acid: drop –ic acid, add –ate

CH3CO2Na sodium acetate or sodium ethanoate

CH3CH2CH2CO2NH4 ammonium butyrate

ammonium butanoate

(CH3CH2COO)2Mg magnesium propionate

magnesium propanoate
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 O O
C C
HO OH HO ONa

carbonic acid sodium bicarbonate

sodium hydrogen carbonate
NaHCO3
O
C
NaO ONa
sodium carbonate

Na2CO3

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physical properties:
polar + hydrogen bond  relatively high mp/bp
water insoluble
exceptions: four carbons or less
acidic turn blue litmus  red
soluble in 5% NaOH

RCO2H + NaOH  RCO2-Na+ + H2O

stronger stronger weaker weaker
acid base base acid

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 RCO2H RCO2-
covalent ionic
water insoluble water soluble

Carboxylic acids are insoluble in water, but soluble in 5%

NaOH.

1. Identification.
2. Separation of carboxylic acids from basic/neutral organic
compounds.
The carboxylic acid can be extracted with aq. NaOH and
then regenerated by the addition of strong acid.
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Carboxylic acids, syntheses:
1. oxidation of primary alcohols
RCH2OH + K2Cr2O7  RCOOH
2. oxidation of arenes
ArR + KMnO4, heat  ArCOOH
3. carbonation of Grignard reagents
RMgX + CO2  RCO2MgX + H+ 
RCOOH
4. hydrolysis of nitriles
RCN + H2O, H+, heat  RCOOH
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1. oxidation of 1o alcohols:

CH3CH2CH2CH2-OH + CrO3  CH3CH2CH2CO2H

n-butyl alcohol butyric acid
1-butanol butanoic acid

CH3 CH3
CH3CHCH2-OH + KMnO4  CH3CHCOOH
isobutyl alcohol isobutyric acid
2-methyl-1-propanol` 2-methylpropanoic acid

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2. oxidation of arenes: (aromatic acids only!)
KMnO4, heat
CH3 COOH

toluene benzoic acid

CH3 COOH
KMnO4, heat

H3C HOOC

p-xylene terephthalic acid

KMnO4, heat
CH2CH3 COOH + CO2

ethylbenzene benzoic acid 25

3. carbonation of Grignard reagent:

Mg CO2 H+
R-X RMgX RCO2MgX RCOOH
Increases the carbon chain by one carbon.

Mg CO2 H+
CH3CH2CH2-Br CH3CH2CH2MgBr CH3CH2CH2COOH
n-propyl bromide butyric acid

H+
O O O
+
RMgX + C R C + MgX R C
O- OH
O

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CH3 CH3 CH3
Mg CO2 H+

Br MgBr COOH

p-toluic acid

Br2, hv Mg
CH3 CH2Br CH2MgBr

CO2

H+

CH2 COOH

phenylacetic acid
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4. Hydrolysis of a nitrile:

H2O, H+
R-CN R-CO2H
heat

H2O, OH-
R-CN R-CO2- + H+  R-CO2H
heat

R-X + NaCN  R-CN + H+, H2O, heat  RCOOH

1o alkyl halide

Adds one more carbon to the chain.

R-X must be 1o or CH3
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29
 Br2, hv NaCN
CH3 CH2Br CH2 CN

toluene
H2O, H+, heat

CH2 COOH

phenylacetic acid

KCN
CH3CH2CH2CH2CH2CH2-Br CH3CH2CH2CH2CH2CH2-CN
1-bromohexane
H2O, H+, heat

CH3CH2CH2CH2CH2CH2-COOH
heptanoic acid
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CH2OH

KMnO4

CH3
KMnO4, heat
CO2H

Br MgBr
Mg
CO2; then H+

C N
H2O, H+, heat

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carboxylic acids, reactions:
1. as acids
2. conversion into functional derivatives
a)  acid chlorides
b)  esters
c)  amides
3. reduction
4. alpha-halogenation
5. EAS

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as acids:
a) with active metals
RCO2H + Na  RCO2-Na+ + H2(g)
b) with bases
RCO2H + NaOH  RCO2-Na+ + H2O
c) relative acid strength?
CH4 < NH3 < HCCH < ROH < HOH < H2CO3 < RCO2H < HF
d) quantitative
HA + H2O  H3O+ + A- ionization in water
Ka = [H3O+] [A-] / [HA]
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Effect of substituent groups on acid strength?

CH3COOH 1.75 x 10-5

ClCH2COOH 136 x 10-5
Cl2CHCOOH 5,530 x 10-5
Cl3CCOOH 23,200 x 10-5

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Effect of substituent groups on acid strength of benzoic acids?

Electron withdrawing groups will stabilize the anion, decrease the ΔH, shift
the ionization to the right, increasing the Ka, increasing acid strength.

COO-

Electron donating groups will destabilize the anion, increase the ΔH, shift the
ionization in water to the left, decreasing the Ka, decreasing acid strength.

COO-

G
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-NH2, -NHR, -NR2
-OH
-OR electron donating
-NHCOCH3
-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR electron withdrawing
-CN
-NR3+
-NO2
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Relative acid strength?
Ka
p-aminobenzoic acid 1.4 x 10-5
p-hydroxybenzoic acid 2.6 x 10-5
p-methoxybenzoic acid 3.3 x 10-5
p-toluic acid 4.2 x 10-5
benzoic acid 6.3 x 10-5
p-chlorobenzoic acid 10.3 x 10-5
p-nitrobenzoic acid 36 x 10-5

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2. Conversion into functional derivatives:
a)  acid chlorides

O SOCl2 O
R C R C
OH or PCl3 Cl
orPCl5

CO2H + SOCl2 COCl

O PCl3 O
CH3CH2CH2 C CH3CH2CH2 C
OH Cl
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39
40
b)  esters
“direct” esterification: H+
RCOOH + R´OH  RCO2R´ + H2O
-reversible and often does not favor the ester
-use an excess of the alcohol or acid to shift equilibrium
-or remove the products to shift equilibrium to completion

“indirect” esterification:
RCOOH + PCl3  RCOCl + R´OH  RCO2R´
-convert the acid into the acid chloride first; not reversible
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 O H+ O
C + CH3OH C + H2O
OH O CH3

SOCl2

O CH3OH
C
Cl

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c)  amides
“indirect” only!
RCOOH + SOCl2  RCOCl + NH3  RCONH2
amide
O O
PCl3 NH3 O
OH Cl NH2
3-Methylbutanoic acid

Directly reacting ammonia with a carboxylic acid results in

an ammonium salt:
RCOOH + NH3  RCOO-NH4+
acid base

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 O PCl3 O NH3 O
C C C
OH Cl NH2

amide

NH3

O
C ammonium salt
O NH4

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 3. Reduction:
RCO2H + LiAlH4; then H+  RCH2OH
1o alcohol

LiAlH4 H+
CH3CH2CH2CH2CH2CH2CH2COOH
Octanoic acid
(Caprylic acid)
CH3CH2CH2CH2CH2CH2CH2CH2OH
1-Octanol

Carboxylic acids resist catalytic reduction under normal

conditions.
RCOOH + H2, Ni  NR 45
 O H2, Pt
CH2 C NR
OH

LiAlH4

H+

CH2CH2OH

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4. Alpha-halogenation: (Hell-Volhard-Zelinsky reaction)

RCH2COOH + X2, P  RCHCOOH + HX

X
α-haloacid
X2 = Cl2, Br2

CH3CH2CH2CH2COOH + Br2,P CH3CH2CH2CHCOOH

pentanoic acid Br
2-bromopentanoic acid

COOH
Br2,P
NR (no alpha H)

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RCH2COOH + Br2,P RCHCOOH + HBr
+ Br
n H
H; the
O NH3
Na

RCHCOOH RCHCOOH
aminoacid
NH2
OH

KOH(alc)
RCH2CHCOOH RCH=CHCOOH
Br then H+

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5. EAS: (-COOH is deactivating and meta- directing)
CO2H
HNO3,H2SO4

NO2

CO2H
H2SO4,SO3
CO2H

SO3H

CO2H
benzoic acid Br2,Fe

Br

CH3Cl,AlCl3
NR
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