1 derivatives of carboxylic acids and nucleophilic acyl substitution

1

Derivatives of Derivatives of Carboxylic Acids Carboxylic Acids and Nucleophilic and Nucleophilic Acyl SubstitutionAcyl Substitution

2

Carboxylic Carboxylic AcidsAcids• A class of organic compounds

containing at least one carboxyl group

C

O

OH

3

R C

O

OH

R = alkyl group or H alkanoic acid(sat’d)R = aryl group aromatic carboxylic acid

4

R C

O

OH

Aliphatic carboxylic acid = fatty acids (sat’d or unsat’d)∵ obtained from fat/oil

E.g.stearic acid, CH3(CH2)16COOHoleic acid,

CH3(CH2)7CH=CH(CH2)7COOH

5

Carboxylic Carboxylic AcidsAcids• Carboxyl group

combination of the carbonyl group and the hydroxyl group

6

Nomenclature

Suffix : carboxylic acid or oic acidPrefix : carboxy

7

Q.62

C C

COOH

HH

H3C

C C

O

OHHO

O

COOH

butanoic acid

(2Z)-but-2-enoic acid

ethanedioic acid

8

Q.62

HOOC

COOH

OH

COOH COOHHOOC

butanedioic acid 2-hydroxypropane-

1,2,3-tricarboxylic acid(citric acid)

3-carboxy-3-hydroxypentainedicarboxylic

acid

9

Q.62

COOH HOOC

COOHbenzoic acid

Benzene-1,3-dicarboxylic acid

10

Q.62

HO

COOH

COOH

phenylethanoic acid

4-hydroxybenzoic

acid

11

Derivatives of carboxylic acids (pp.9-10)

Name Structure

Acyl(Acid) chlorides

Acid anhydride

s

Esters

Acid Amides

12

Acyl (Acid) ChloridesAcyl (Acid) Chlorides

Suffix : -oic acid replaced by –oyl chloride

Prefix : chlorocarbonyl

R C

O

Cl

13

Acyl (Acid) ChloridesAcyl (Acid) Chlorides

H2C C

O

ClCO

OH

3-chloro-3-oxopropanoic acid

Priority : --COOH > anhydride > ester > acid chloride > acid amideThe carbonyl C is counted as part of the carbon skeleton

14

CHH2C C

Cl

OHOOC

H3C

4-chloro-2-methyl-4-oxobutanoic acid

C

C

Cl

O

Cl

O

hexanedioyl dichloride

HOOC

COOH

C

ClO

3-(chlorocarbonyl)hexanedioic

acid

Q.63

15

Acid anhydrideAcid anhydride

Suffix : -acid replaced by –anhydride

R C

O

O

CR'

O

16

C

O

O

CR

O


Prefix : n-(alkanoyloxy)-n-oxo (if *C is counted as part of the main chain) n indicates the position of the *C in the main chain

*

17

C

O

O

CR

O


Prefix : (alkanoyloxy)carbonyl (if *C is not counted as part of the main chain)

*

18


H3C C

O

O

CH3C

O

H3C C

O

O

CC2H5

O

ethanoic anhydride

ethanoic propanoic anhydride

19


H3C C

O

O

C

O

C

O

C

O

O

benzoic ethanoic

anhydride

butanedioic anhydride

20

Q.64

C

O

C

O

O

Benzene-1,2-dioic anhydride

21

EsterEster

Suffix : -oic acid replaced by –oate preceded by the name of R’

R C

O

O

R'

22

R

O

C

O

Prefix : n-alkoxy-n-oxo(if *C is counted as part of the main chain) n indicates the position of the *C in the main chain

*

EsterEster

23

Prefix : alkoxycarbonyl (if *C is not counted as part of the main chain)

EsterEster R

O

C

O

*

24

EsterEster

H3C C

O

O

CH3

H3C C

O

O

CH

CH2

C

O

O

CH3

Br

methyl ethanoate

ethenyl ethanoate

methyl 4-bromobenzoat

e

25

Q.65

COOH

C

O

CH3

O COOH

O

C

CH3

O

2-(methoxycarbonyl)benzoic

acid

2-(ethanoyloxy)benzoic acid2-(acetyloxy)benzoic acid

26

Acid amideAcid amide

Suffix : -oic acid replaced by -amide

R C

NH2

O

27

NH2

C

O

Prefix : n-amino-n-oxo (if *C is counted as part of the main chain) n indicates the position of the *C in the main chain

*

EsterEster

28

NH2

C

O

Prefix : aminocarbonyl (if *C is not counted as part of the main chain)

EsterEster

*

29

C

NH2

O

H3C C

HN

O

H3C

CH3

C

N

O

H3C

CH3

H3C

ethanamide(1)

N-methylethanamide(2)

N,N-dimethylethanamide(3)

EsterEster

30

Q.66

C

NH2

O

(CH2)2 HOOC COOH

C

O NH2

C

NH2

O

HOOC

benzamide

4-amino-4-oxobutanoic

acid

3-(aminocarbonyl)heptanedioic

acid

31

Physical Physical Properties of Properties of

Alkanoic AcidsAlkanoic Acids

33

OdourOdour

Methanoic / ethanoic acid

sharp, irritating odours

Propanoic to heptanoic acid

strong, unpleasant odours

Butanoic acid body odour

Higher members low volatility little odour

34

Alkanoic acidMelting point /oC

Boiling point/oC

Density/g cm-3

Solubility in water/g per H2O

Methanoic acid 8.4 101 1.220 Ethanoic acid 16.6 118 1.047 Propanoic acid 20.8 141 0.992 Butanoic acid 6.5 164 0.964 Pentanoic acid 34.5 186 0.939 3.7Hexanoic acid 1.5 205 0.927 1.0Heptanoic acid 10 224 0.913 0.25Octanoic acid 16 239 0.910 0.7Nonanoic acid 12.5 253 0.907 0.07Decanoic acid 31 269 0.886 0.2

b.p. steadily as the number of C atoms ∵ London dispersion forces become stronger as the size of electron cloud

35


Boiling point/oC

Density/g cm-3



HCOOH/CH3COOH have exceptionally high m.p.∵ smaller size 1.closer packing 2.forming H-bonds more extensitively

36


Boiling point/oC

Density/g cm-3



Members with EVEN no. of C atoms aremore symmetrical Higher packing efficiency Higher m.p.

37


Boiling point/oC

Density/g cm-3



Pure ethanoic acid = glacial ethanoic acidIt freezes in cold weather

38

More extensive H-bonds

H-bondsDipole-dipole interaction

Dispersion forces ONLY

39


Boiling point/oC

Density/g cm-3



Less dense than water exceptHCOOH/CH3COOH

40


Boiling point/oC

Density/g cm-3



as R.M.M. R.M.M. extent of H-bond formation

molecules not drawn closer lower packing efficiency

41


Boiling point/oC

Density/g cm-3


Methane GasEthane GasPropane GasButane GasPentane 0.626Hexane 0.655Heptane 0.684Octane 0.703Nonane 0.718Decane 0.730

For alkanes, as R.M.M. ∵ no intermolecular H-bondsR.M.M. Dispersion forces become stronger

closer packing

42


Boiling point/oC

Density/g cm-3



First FOUR members are miscible with water in all proportions due to extensive H-bond formation between acid molecules and water molecules

43


Boiling point/oC

Density/g cm-3



From pentanoic acid, solubility as R.M.M. The bulky R groups prevent formation of H-bonds between –COOH and H2O

44

COOH

H

O

H

H

O

H

H

O

H

H

O

H

45

C

O

O

Na

Emulsifying action of soap (salts of carboxylic acids) depends on the length of the hydrocarbon chain

Non-polar

ionic

46

Length of hydrocarbon chain Property

Short ( 15 C atoms)Ionic properties

predominate

Long ( 19 C atoms)Non-polar properties

predominate

Intermediate(16-18 C atoms)

e.g. palmitic acid, C15H31COOH

stearic acid, C17H35COOH

Possess both ionic/non-polar

properties

47

Preparation of Carboxylic

Acids

48

1.1. Hydrolysis of NitrilesHydrolysis of Nitriles

RCN

R C

O

OH

heat

R C

O

O

H3O+

RX(1o)

C O

'R

"R

Elimination occurs for 2 and 3 RX as CN is a relatively strong base

49

ExampleExampless

50

2.2. Oxidation of aldehydes and 1Oxidation of aldehydes and 1 alcohols (pp.83-84, 93)alcohols (pp.83-84, 93)

3.3. Oxidation of aromatic side Oxidation of aromatic side chainschains (pp.54-55)(pp.54-55)

4.4. Iodoform reactions Iodoform reactions (p.92)(p.92)

51

C

H

O

Q.67 COOH

COOH

52

Q.68

H3C C

CH3

O

H3C COOH

HOOC C

O

CH3

1… 2…

Prolonged

heating

HOOC COOH

53

5.5. Hydrolysis of EstersHydrolysis of Esters

R C

O

O

R'

NaOH(aq)

heat

R C

O

O

Na

+ R'OH

removed by distillation

E.g.

Fat/oil Soap + glycerol

NaOH(aq)

heat

54

5.5. Hydrolysis of EstersHydrolysis of Esters

R C

O

O

R'

NaOH(aq)

heat

R C

O

O

Na

+ R'OH

H3O+

R C

OH

O

55

6.6. Carbonation of Grignard Carbonation of Grignard reagentsreagents

R-X R[MgBr]+Mg

Dry etherGrignard reagent

R : CH3-, 1/2/3 alkyl, benzyl, aryl

56


R-X R[MgX]+Mg

Dry etherDry ice (CO2)

R C

OMgX

O

R C

OH

O

H3O+

+ 1 C

57

R [MgX] C OO

+


R-X R[MgX]+Mg

Dry ether

CR

OMgX

O

58

7.7. Cannizzaro reactionsCannizzaro reactions

H3O+

C

OH

O

C

H

O

conc. NaOH

heat

C

ONa

O

+OH

For aldehydes

without HC

C

O

H

H

H

removed by distillation

59

Reactions of Carboxylic

Acids

60

Acidity of Carboxylic AcidsAcidity of Carboxylic Acids

• weak acids

RCOOH + H2O RCOO- + H3O+

[RCOOH]]O][H[RCOO

K 3-

a

pKa = –log Ka

The smaller the value of pKa, the stronger the acid

61

Acid

RCOOH

H2CO3 H2O

pKa 4-5 6.4 ~10 15.7

OH

Acidity as pKa

62

Formation of Formation of SaltsSalts1. 1. Reaction with Reactive Reaction with Reactive MetalsMetals

Irreversible as H2 leaves the reaction mixture

63

2. Reaction with 2. Reaction with BasesBases

RCOOH + NaOH RCOONa + H2O

Weaker acid

Stronger acid

Equilibrium positions lie on the right

2RCOOH + K2CO3 2RCOOK + H2CO3

RCOOH + KHCO3 RCOOK + H2CO3

64

OH + KHCO3 + H2CO3OK

Stronger acidWeaker

acid

Phenols react with OH, but they do not react with HCO3

OH + NaOH + H2OONa

Stronger acid

Weaker acid

No observable change

(effervescence)

65

Is there effervescence when Na is added to phenol? Explain.

OH + 2Na + H2(g)ONa22

Yes. The reaction proceeds to the completion as H2 leaves the reaction mixture.

66

Carboxylic acids and phenols can be distinguished by their different acidities

1989 AL Paper I Q.4 (modified)

67

COOH

COOH OH

A B C

COOHOH

OH

(a) Outline a chemical test to distinguish between A and B.

Add NaHCO3(aq) to A and B separately.Ony B reacts apparently to give gas bubbles of CO2

68

COOH

COOH OH

A B C

COOHOH

OH

(b) C also gives a +ve result in (a). Show how you would determine whether the sample is C or a mixture of A and B.Determine the melting point of the sample.

If the sample is pure C, it will give a sharp m.p..

The identity of C can be confirmed by carrying out mixted melting point test.

69

(c) Outline a scheme to extract A from a mixture containing A, B and C.

Mixture of A, B and C

ether

Ether solution of A, B and C

Ether layer, A

Aqueous layer, sodium salts of B and C

Shaken with NaHCO3(aq)

Evaporation of ether

Pure A

Sodium salts of B and C dissolve in water

b.p. = 34.6C

O C2H5

C2H5

70

Q.69

COOH OH OH

A B C

Outline a scheme to separate completely A, B and C from a mixture of them in ether.

Acidity : A > H2CO3 > B > H2O > CA, B are sparingly soluble solids in water

71

Ether solution of A, B ands C

Ether layer, B + C

Aqueous layer, sodium salt of A

shaken with NaHCO3(aq)

H3O+

Ppt of A

filtration

Impure A

Pure A

recrystallization

(m.p. = 122.4C)

COOH OH

A B

OH

C

COO + H+ COOH

p.120

72

Ether layer, B + C Shaken with

NaOH(aq)

Aqueous layer, sodium salt of B

Ether layer, C


Pure C

H3O+

Ppt of B

filtration

Impure B

Pure B

recrystallization

(m.p. = 40.5C)

OH

B

OH

C

O + H+ OH

73

CH3COONaNaOH(s) from soda lime

fusion

NaOH(s) from soda lime

fusionCOONa

CH4 + Na2CO3

+ Na2CO3

Applied ONLY to synthesis of methane and benzene

DecarboxylationDecarboxylation

74

DecarboxylationDecarboxylation

On the contrary,

2HCOO-Na+heat

COO-Na+

COO-Na+

H2 +

RCH2COO-Na+ + NaOHmore

difficultNa2CO3 + RCH3 + other by-products

decarboxylation is widely applied to synthesis of carbonyl compounds (refer to p.85)

75

RCOOH RCH2OH (1o)

R C

O

O

R'

1. LiAlH4 / dry ether

2. H3O+

(Ester is more easily reduced)

ReductionReduction

H2/Pt

No reaction

or, NaBH4/H2O

76

OxidationOxidation

Not easily oxidized except : -

HCOOH CO 2 + H2OKMnO4 / H+

heat

COOH

COOH

KMnO4 / H+

heat2CO2 + H2O

77

DehydrationDehydration

Not easily dehydrated except : -

HCOOH CO + H 2O

COOH

COOH

CO2 + CO + H 2Oconc. H2SO4

conc. H2SO4

78

Q.70

Conc. H2SO4

C

C

O OH

HO O

CO2 + CO + H2O

+3

+3

+4

+2

79

Formation of acid derivativesFormation of acid derivatives

Refer to preparation of acid derivatives (pp.115-120)

80

Acidity of Organic Acidity of Organic CompoundsCompounds(Bronsted/Lowry Concept)

[HA(aq)](aq)](aq)][AO[H

K-

3a

smaller pKa higher acidity

larger pKa lower acidity

HA(aq) + H2O(l) H3O+(aq) + A(aq)

81

Two factors affecting the acidity of H–A : -(1) Strength of H–A bond (minor effect)

(2) Stability of the conjugate base, A (major effect)

82

Two factors affecting the acidity of H–A : -(1) Strength of H–A bond (minor effect)

Stronger H–A bond lower acidity

Acidity : H-I > H-Br > H-Cl >> H-FCan be ignored for organic cpds ∵(i) H is always bonded to C, N or

O;(ii) C-H, N-H and O-H bonds have

similar bond strengths

83

(2) Stability of the conjugate base, A (major effect)

higher stability of A weaker basicity of A

higher acidity of H-A

Stability of A depends on(i) Electronegativity of A

Higher EN better accomodation of –ve charge by A higher stability of A

84

Stability of A depends on(ii) Electronic effect

- Inductive effect (+ve or –ve)- resonance effect (more important)

85

Organic Compound pKa Organic Compound pKa

CH3CH2–H 50 CH3CH2CH2O–H ~17

H–H 50 HO – H 15.7

CH2=CH–H 44 C6H5O–H (phenol) ~10

NH2–H 36 4.87

CHC–H 25 CH3COO–H 4.76

CH3COCH2–H 20 4.20

C

O

O H

C

O

O H

86

Interpretation of the Relative Stability of Typical Organic Compounds

HO-H H2N-H H3C-H

pKa 15.7 36 50

Electronegativity : - - O > N > CStability of conjugate base : -HO > H2N > H3C

The more electronegative atom can accommodate the negative charge more easily

87

CH3COCH2-H H3C-H

pKa 20 50

C

O

CH2H3CC

O

CH2H3C

The -ve charge on C becomes less available for attracting a proton CH3COCH2

becomes a weaker base CH3COCH2-H becomes a stronger conjugate acid

Resonance effect

88

CHC-H CH2=CH-HCH3CH2-

H

pKa 25 44 50

Stability of conjugate base : -CHC > CH2=CH > CH3CH2

sp sp2 sp3

Ease of accommodation of the –ve charge : -sp C > sp2 C > sp3 C

89

CH3COO-HCH3CH2CH2O-

H

pKa 4.74 ~10 ~17

O H

CH3CH2CH2 OH3C C

O

O

O

> >

Stability of conjugate base : -

Destabilized by +ve inductive effect

Stabilized by resonance effect

90

Q.71

H3C C

O

O

H3C C

O

O

The two structures are equally stableThe –ve charge is shared by two electronegative O atoms Delocalization of –ve charge is more favoured

91

Q.71O O O O

The –ve charge is accommodated by the less electronegative C atoms less stable delocalization is less favoured

92

Q.72

pKa 4.20 4.87

C

O

O

H

C

O

O

H

C

OO

C

OOThe –ve charge is not shared by the ring less extensive

delocalization

93

C

OO

C

OO

C

OOC

OO

C

OO

The –ve charge is shared by the ring slightly more extensive delocalizationThe effect is small since the three structures are less stable due to separation of opposite charges

94

Effects of substituents on acidity of carboxylic acids1. Aliphatic carboxylic acids

RCOOH + H2O RCOO- + H3O+

Electron-donating R groups destabilize the RCOO

RCOOH is less acidicElectron-withdrawing R groups stabilize the RCOO

RCOOH is more acidic

95

Carboxylic acid pKa Conjugate base

CF3COO–H 0 CF3COO

CCl3COO–H 0.65 CCl3COO

CH2FCOO–H 2.66 CHCOO

CH2ClCOO–H 2.81 CH2ClCOO

CH2BrCOO–H 2.87 CH2BrCOO

CH2ICOO–H 3.13 CH2ICOO

HCOO–H 3.77 HCOO

CH3COO–H 4.76 CH3 COO

96

Inductive effect on acidity rapidly when the substituents are placed farther away from the carboxyl group

pKa 2.85 4.05 4.52 4.82

COOH COOH COOHCOOH

Cl

Cl

Cl

> > >

97

2. Aromatic carboxylic acids CH3

COOHCOOHCOOH

CF3

> >

Acidity :-

Electron-donating group on the ring reduces the acidity by destabilizing the conjugate base.Electron-donating group on the ring increases the –ve charge on the conjugate base, making it more available for attracting a proton Stronger conjugate base Weaker acid

98

2. Aromatic carboxylic acids CH3

COOHCOOHCOOH

CF3

> >

Acidity :-

Electron-withdrawing group on the ring increases the acidity by stabilizing the conjugate base.Electron-withdrawing group on the ring disperses the –ve charge on the conjugate base, making it less available for attracting a proton Weaker conjugate base Stronger acid

99

Q.73

pKa 2.98 4.20 4.58

COOHCOOH

OH

> >

COOH

HO

100

Q.73COOH COOH

OHpKa = 4.20

pKa = 4.58

OH withdraws electrons by –ve inductive effect

-OH donates electrons by resonance effect

Resonance effect > inductive effectThe net effect is electron-donating

101

COOH COOH

OH

pKa = 4.20

pKa = 2.98

C

O

O O

HThe conjugate base is stabilized by intramolecular hydrogen bond

102

(1) Acidity : dioic acids > monocarboxylic acidThe conjugate bases are stabilized by intramolecular H-bonds

C

C

O O

OO

H

Acid pKa1 pKa2

pKa2 – pKa1

HOOCCOOH 1.2 4.2 3.0HOOCCH2COOH 2.9 5.7 2.8

HOOC (CH2)2COOH 4.2 5.6 1.4HOOC (CH2)3COOH 4.3 5.5 1.2HOOC (CH2)4COOH 4.4 5.6 1.2

CH3COOH 4.76 - -

103

Acid pKa1 pKa2

pKa2 – pKa1



CH3COOH 4.76 - -

(i) The repulsion between two –COO groups does not favour the 2nd dissociation

(2) pKa2 > pKa1

C

C

O O

OO

H

C

C

O O

OO

104

Acid pKa1 pKa2

pKa2 – pKa1



CH3COOH 4.76 - -

(ii) The doubly charged anion attracts the proton more strongly

(2) pKa2 > pKa1

C

C

O O

OO

H

C

C

O O

OO

H+

105

Acid pKa1 pKa2

pKa2 – pKa1



CH3COOH 4.76 - -

∵ intramolecular H-bonds are less easily formed

(3) pKa1 as the two –COOH groups are further apart

106

Acid pKa1 pKa2

pKa2 – pKa1



CH3COOH 4.76 - -

The repulsion between the two –COO groups down the series pKa2 remains relatively constantSince, pKa1 down the series(pKa2-pKa1) down the series

(4) (pKa2-pKa1) down the series

107

[B(aq)](aq)](aq)][OH[HB

K-

b

smaller pKb higher basicity

larger pKb lower basicity

B(aq) + H2O(l) HB+(aq) + OH(aq)

Basicity of Organic Basicity of Organic CompoundsCompounds

108

Two factors affecting the basicity: -

(1) Ability to donate a lone pair to a proton

Basicity : -

More electron-donating alkyl group attached to NMore available to donate a lone pair to a proton

N

R

R'

R''

N

R

R'

H

N

R

H

H

N

H

H

H

> > >

3 2 1

109

(2) The extent of solvation of the conjugate acid

Extent of solvation : -

N

R

R'

R''

N

R

R'

H

N

R

H

H

N

H

H

H

HHHH > > >

1 2 3More H attached to NMore available to form H-bond with water(solvent)Extent of solvation Stability of conjugate acid Basicity of amine

110

N

H

H

H

H

O

HH

H

O

H

H

O

HH

O

H

Good solvationExtensive formation of H-bonds with water

111

Overall Basicity (from experiments) : -2 amines > 1 amines > 3 amines > NH3

pKb 3.27 3.36 4.22 4.74

N H

H3C

H3C

N H

H

H3C

N CH3

H3C

H3C

N H

H

H

>> > >

112

NH2

H3C NH2

pKb 9.38 3.36

(a)Q.74(a)

CH3NH2

-CH3 is electron-donating

The lone pair on N is more available to abstract a proton

113

NH2

The lone pair on N is shared by the benzene ring due to resonance effect

Less available to abtract a proton

NH2 NH2 NH2

114

Both –OH and –CH3 groups are electron-donating

Lone pair on N is more available to abstract a proton

Stronger base than phenylamine

NH2

OH

NH2

CH3

NH2

>&

Q.74(b)

115

NH2

OH

NH2

CH3

>

Q.74(b)

Resonance effect is more electron-donating than positive inductive effect

116

NH2

NO2

NH2Q.74(b)

>

-NO2 group is electron-withdrawing

Lone pair on N is less available to abstract a proton

Weaker base than phenylamine

117

NH2

H3C C

NH2

O

>

Q.74(c)

H3C C

NH2

O

H3C C

NH2

O

Oxygen is more electronegative than N and C

Lone pair on N is withdrawn more

Less basic than phenylamine

118

Basicity of organic compounds : -

Aliphatic > NH3 > Aromatic > Amidesamine

s

amines

(2 > 1 > 3)

119

Amines form water-soluble salts with mineral acids

CH3NH2 + HCl(aq) CH3NH3

+Cl(CH3)2NH + HCl(aq) (CH3)2NH2

+Cl

(CH3)3N + HCl(aq) (CH3)3NH+Cl1. Used in drug formulation for easier

absorption2. Used in purification of amines from other organic compounds

120

Ether solution of A, B, C and D

Ether layer, A,B,DAqueous layer, sodium salt of C

shaken with NaHCO3(aq)

H3O+

Ppt of C

filtration

Impure C

Pure C

recrystallization

COO + H+ COOH

Q.75

OH NH2 COOH CH3

121

Ether solution of A, B and D

Ether layer, B,DAqueous layer, sodium salt of A

shaken with NaOH(aq)

H3O+

Ppt of A

filtration

Impure A

Pure A

recrystallization

Q.75

OH NH2 COOH CH3

O + H+ OH

122

Ether layer, B + D Shaken with HCl(aq)

Aqueous layer, sodium salt of B

Ether layer, D


Pure C

OH-

B + Aq. solutionShaken with ether

B in ether layer

Pure B


(liquid)

(liquid)

OH NH2 COOH CH3

123

Reactivity of carboxylic acids and their derivatives towards nucleophilic reactions

1. Aldehydes/ketones undergo AdN rather than SNCarboxylic acids/derivatives undergo SN rather than AdN

124

O C

H

R

Nu

C

R

Nu

O

H O C

Nu

R

+ H

O C

R'

R

Nu

C

R

Nu

O

R' O C

Nu

R

+ R'

Strong bases, unstable

A discussion on the reactivity of carboxylic acids and their derivatives towards nucleophilic rxs1. Aldehydes/ketones undergo AdN rather than SN

125

Reactivity of carboxylic acids and their derivatives towards nucleophilic reactions

1. Carboxylic acids/derivatives undergo SN rather than AdN

O C

L

R

Nu

C

R

Nu

O

L O C

Nu

R

+ L

Weak base,stable

126

Strength of acids : - HCl > RCOOH > HOH > ROH > H2NH > RH > HH

Strength of bases : -Cl < RCOO < HO < RO < H2N < R < H

O C

L

R

Nu

C

R

Nu

O

L O C

Nu

R

+ L

O C

H

R

Nu

C

R

Nu

O

H O C

Nu

R

+ H

O C

R'

R

Nu

C

R

Nu

O

R' O C

Nu

R

+ R'

127

O C

L

R

Nu

C

R

Nu

O

L O C

Nu

R

+ L

Reactivity : -

R C

Cl

O R C

O

O

C

O

'R

R C

OH

O

R C

O

O

R'

R C

NH2

O

>> > >

(2)

128

Reactivity : -

R C

Cl

O R C

O

O

C

O

'R

R C

OH

O

R C

O

O

R'

R C

NH2

O

>> > >

(2)

(i) Ease of leaving(Stability of bases) : -Cl > RCOO > HO > RO > H2N > R > H

∵ Strength of bases : -Cl < RCOO < HO < RO < H2N < R <

H

Reasons : -

129

Reasons : -

R C

Cl

O

R C

Cl

O

R C

O/N

O

R C

O/N

O

Incre

asin

g

reso

nan

ce e

ffect

(2p)

(2p)

(3p)

(2p)

(2p)

(2p)

(ii) Resonance effect : -

Efficiency of orbital overlap : 2p/2p > 3p/2p

Less stableMore reactive

More stableLess reactive

130

Reactivity : -

The less reactive derivatives can be prepared from the more reactive derivative via nucleophilic substitution reactions.

R C

Cl

O R C

O

O

C

O

'R

R C

OH

O

R C

O

O

R'

R C

NH2

O

>> > >

(2)

131

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3

Preparation of Acid Derivatives

132

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3


133

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3


134

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3


135

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3

Preparation of Acid Derivatives Non-SN reactions

136

R C

Cl

O

C

Cl

O

>(3)

C

O

Cl

C – O bond of benzoyl chloride has less mesomeric effect

Carbonyl C of benzoyl chloride is less positive

Less susceptible to nucleophilic attack

137

(4) R C

Cl

O

ClC>+ +

The carbonyl C is attached to TWO electron-withdrawing atoms

more positive

more susceptible to electrophilic attacks

138

(4) R C

Cl

O

ClC>+ +

Also, the nucleophile experiences less steric hindrance with acyl chloride because the reaction site is planar

139

A. Preparation of Acid Chlorides

R C

O

OH

PCl5/SOCl2/PCl5

heatR C

O

Cl

SOCl2 : thionyl chloride or sulphur oxychloride

140

R C

OH

O

+ PCl 5 R C

Cl

O

+ POCl3 + HCl(g)(l)(s)

b.p. = 106℃

sublimes at 160℃

(1) Acid chloride with high b.p.

Higher b.p. than acid chloride due to intermolecular H-bonds

removed first byfractional distillation

Phosphorus oxychloride

(>170C)

141

(2) Acid chloride with high/intermediate/low b.p.

R C

OH

O

+ SOCl2 R C

Cl

O

+ SO2(g) + HCl(g)

can be removed

easily

b.p. = 74.6℃

(l)

(85C < b.p. < 170C)

Most useful

or b.p. < 65C

142

(3) Acid chloride with low b.p.

R C

OH

O

+ PCl3 R C

Cl

O

33 + H3PO3(s)

decomposes at 200℃

b.p. = 79℃

(l)

(3) Acid chloride with low b.p.

(< 69C)

Removed first by fractional distillation

143

Q.76

COOH + PCl5(s)heat

COCl + POCl3(l) + HCl(g)

b.p.=197.2C

b.p.=106C

b.p.=249C

s.t.=160C

COOH + SOCl2(l)heat

COCl + SO2(g) + HCl(g)

b.p.=74.6C

144

Q.76

b.p.51C

b.p.=118C

heatH3C C

OH

O

+ PCl3(l) H3C C

Cl

O

+ H3PO3(l)

d.c.200C

b.p.=76C

Removed first by fractional distillation

145

B. Preparation of Acid Anhydrides

R C

Cl

O

'R C

OH

O

pyridine

R C

O

O

C'R

O

+ HCl+

(1)

Acyl chlorides must be stored in anhydrous conditions

they hydrolyze rapidly in the presence of even a trace amount of water(p.122)

RCOCl + H2O RCOOH + HCl

146


R C

Cl

O

'R C

OH

O

pyridine

R C

O

O

C'R

O

+ HCl+

(1)

R R’ unsymmetrical anhydride

R = R’ symmetrical anhydride

147


R C

Cl

O

'R C

OH

O

pyridine

R C

O

O

C'R

O

+ HCl+

(1)

+ HClN NH Cl

pyridineEquilibrium position shifts to the right

Yield

148


R C

Cl

O

'R C

O Na

O

pyridine

R C

O

O

C'R

O

+

(2)

+ NaCl(s)

R R’ unsymmetrical anhydride

R = R’ symmetrical anhydride

149


R C

Cl

O

'R C

O Na

O

pyridine

R C

O

O

C'R

O

+

(2)

+ NaCl(s)

NaCl(s) produced is removed by precipitation

Equilibrium position shifts to the right

Yield

150


R C

OH

O R C

O

O

CR

O

(3)

+ H2OP2O5

heat2

Only suitable for preparing symmetrical anhydrides

dehydrating agent

P4O10 = P2O5

Non-SN reaction

151

Q.77

It gives a mixture of three acid anhydrides.

RCOOH + R’COOH

P4O10heat

CR

O

O

C'R

O

CR

O

O

CR

O

C'R

O

O

C'R

O

+ +

152

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3

Preparation of Acid AmidesAmmonolysis

NH

3

NH3

NH3

NH3

153

C. Preparation of Acid Amides

The overall reaction is : -

R C

OH

O

R C

NH2

O

+ H2OH2N H+heat

(excess)

(1) Ammonolysis of Carboxylic Acids

breaking of ammonia= ammonolysis

154

heatR C

NH2

O

+ H2O


R C

OH

O

+ NH3(aq) R C

O NH4

O


neutralization

dehydration

155

heatR C

NH2

O

+ H2O


R C

OH

O

+ NH3(aq) R C

O NH4

O


prevent hydrolysis of the ammonium carboxylate

R C

OH

O

+ H2O(l)R C

O NH4

O

+ NH3(aq)

excess

excess RCOOH

excess

156

(2) Ammonolysis of Acid Chlorides(better method)(Acylation of NH3/amines)

R C

Cl

O

+ NH3(aq) R C

NH2

O

+ HCl

(1o)

R C

Cl

O

R C

NHR'

O

+ HCl

(2o)

+ R'NH2

(1o)

R C

Cl

O

R C

N

O

+ HCl

(3o)(2o)

N H

"R

'R

+

R'

"R

(excess)NH3(aq) excess

(2) excess

R’NH2(aq) (1)

excess

(1)

(2)

(3)

Acyl group

Aminolysis

157

(2) Ammonolysis of Acid Chlorides

(benzoylation of NH3/amines)

C

O

Cl

+ NH3C

O

NH2

+ HCl

C

O

Cl

+ RNH2 C

O

NH

+ HCl

R

C

O

Cl

+ C

O

N

+ HClN

R

R' H

R

R'

benzoyl group

158

R C

Cl

O

+ NH3(aq) R C

NH2

O

+ HCl

(1o)

R C

Cl

O

R C

NHR'

O

+ HCl

(2o)

+ R'NH2

(1o)

R C

Cl

O

R C

N

O

+ HCl

(3o)(2o)

N H

"R

'R

+

R'

"R

(excess)NH3(aq) excess

(2) excess

R’NH2(aq) (1)

excess

Removed by excess NH3/amines Yield

159

NOT applicable to 3 amine due to absence of H

R C

Cl

O

+ N R'''

''R

'R

no reaction

160

H3C C

NH2

O

Further acylation is inhibited because amides are weaker nucleophiles than amines

H3C C

NH2

O

161

The acyl and benzoyl derivatives of amines are usually crystalline solids with sharp m.p..

Thus, amines can be identified by

1. preparing their acyl/benzoyl derivatives

2. recrystallization

3. melting point determination

Similar to identification of carbonyl compounds (pp.91-92)

162

Q. 78

Why is the impure solid dissolved in the minimum quantity of hot solvent?

A hot solvent is used to ensure

maximum dissolution of target product

163

Q. 78

Why is the impure solid dissolved in the minimum quantity of hot solvent?

If minimum quantity of solvent is used to ensure

(a) minimum dissolution of insoluble impurities during hot filtration(step 3)

(b) minimum loss of target product during suction filtration (step 5).

164

Why is hot filtration done in ways as described by step 3 ?

(a) Hot filtration is to minimize thecrystallization of filtrate on the funnel.

Q. 79

(b) A shot-stem funnel fitted with a piece of fluted filter paper is to speed up the filtration so as to minimize the crystallization of filtrate on the funnel.

165

Q. 80

Why are the crystals washed in ways as described by step 6 ?

(a) Washing the crystals with the mother liquor (a saturated solution) can dissolve no more target product.

the yield is not reduced

(b) Washing the crystals with solvent can remove the mother liquor (containing dissolved impurities) from the crystals

Only a little cold solvent is used to minimize the loss of target product.

166

(3) Ammonolysis of Acid Anhydrides

R C

O

O

C

O

R

R C

NH2

O

R C

NHR'

O

+

+

R C

OH

O

R C

OH

O

The yield is increased by removing the products with excess NH3 or amine

(1)

(2)

167

(4) Partial Hydrolysis of Nitriles

RCNH2O

H+or OH-, reflux

R C

NH2

O

Non-SN reaction

168

Further hydrolysis gives carboxylic acids (in acidic medium) orcarboxylate in (basic medium).

R C

NH2

OH2O

R C

O NH4

O

R C

OH

O

R C

O

O

169

R C

OH

O

R C

O NH4

O

+ H2OR C

NH2

Ohydrolysishydrolysis

Hydrolysis of amide = The reverse of ammonolysis of RCOOH

H2O+ NH3

heatammonolysis

170

R C

OH

O

R C

Cl

O

R C

O

O

C

O

'R

R C

O

O

R"

R C

NH2

O

NH3

Preparation of Esters

R’’O

HR’

’OH

R’’O

H

Alcoholysis

171

R C

OH

O

+ R'OHH+

refluxR C

O

O

R'

+ H2OR’O – H

C. Preparation of Esters

(1) Alcoholysis of Carboxylic Acids

Esterification

172

(2) Alcoholysis of Acid Chlorides

R C

Cl

O

+ R'OH R C

O

O

R'

+ HClOH-

R C

Cl

O

R C

O

O

+ HClOH-

OH+

Faster and irreversibleOH ions serve to

(i) the yield by removing HCl

phenolysis

173

(2) Alcoholysis of Acid Chlorides

R C

Cl

O

+ R'OH R C

O

O

R'

+ HClOH-

R C

Cl

O

R C

O

O

+ HClOH-

OH+

OH ions serve to

(ii) Speed up the nucleophilic attack by generating the more powerful nucleophile.

OH + OH- O + H2O

174

(3) Alcoholysis of Acid Anhydrides

R C

O

O

+ R'OH R C

O

O

R'C

O

R

heatR C

OH

O

+

Heating is required as acid anhydrides are less reactive than acid chlorides

175

Reactions of Reactions of the the

Derivatives of Derivatives of Carboxylic Carboxylic

AcidsAcids

176

Z

C

RL

O

H

Nucleophilic Acyl Substitution

C O

L

R

HZ C O

R

Z

H

L+

C O

R

Z

+ HL

HZ: nucleophile

L leaving group

slow

fast

fast

177

Z

C

RL

O

H


C O

L

R

HZ

HZ: nucleophile

L leaving group

slow

fast

+C O

R

Z

H2Z

fast

C O

R

Z

H

L+

HZ

178

Z

C

RL

O

H


C O

L

R

HZ

More stable intermediate

slow

fast

+C O

R

Z

H2Z

fast

C O

R

Z

H

L+

HZ

Less steric hindrance than the 5-coordinated transition state of RX(SN2)Obeying octet rule while the 3-coordinated carbocation of RX(SN1) is not

179

Z

C

RL

O

H


C O

L

R

HZ

HZ: = H-OH, H-OR, H-NH2, H-NHR, H-NRR’

slow

fast

+C O

R

Z

H2Z

fast

C O

R

Z

H

L+

HZ

180

A. Hydrolysis (Reactions with water)HZ = H-

OHDecre

asin

g re

activ

ity

H3C CCl

O+ H2O

coldH3C C

OH

O + HCl

H3C CO

O

CO

H3C

+ H2O H3C COH

OH3C C

OH

O

+

H3C CO

O

CH3

+ H2OH+ or OH-

heatH3C C

OH

OCH3OH+

H3C CNH2

O

+ H2OH+ or OH-

heatH3C C

OH

O

+ H2N H

catalysts

catalysts

181

C O

L

R

+ H+ C OH

L

R

Acid-catalyzed

Carbonyl C becomes more susceptible to nucleophilic attacks

182

Base-catalyzed

C O

L

R

+ OH-

OH ion is a stronger nucleophile than H2O

183

A. Hydrolysis (Reactions with water)HZ = H-

OHH3C C

Cl

O+ H2O

coldH3C C

OH

O + HCl

H3C CO

O

CO

H3C

+ H2O H3C COH

OH3C C

OH

O

+

H3C CO

O

CH3

+ H2OH+ or OH-

heatH3C C

OH

OCH3OH+

H3C CNH2

O

+ H2OH+ or OH-

heatH3C C

OH

O

+ H2N H

Decre

asin

g re

activ

ity

Or, CH3COO

184

B. Alcoholysis (Reactions with alcohols)HZ = H-OR

Phenolysis (Reactions with phenols)HZ = H-OAr

Refer to the preparation of ester (p.121) Esters and amides do not undergo alcoholysis/phenolysis

185

C. Ammonolysis (Reactions with NH3)HZ = H-NH2

Aminolysis (Reactions with amines)HZ = H-NHR, H-NRR’ Refer to the preparation of amides (pp.119-121)

Amides do not undergo

ammonolysis/aminolysis Acid derivatives do not react with

3 amines

186

2. Reduction

R CCl

O

R CO

O

CO

R

R CO

O

R'

R CNH2

O


2. H3O+


2. H3O+


2. H3O+


2. H3O+

RCH2OH

2RCH2OH

RCH2OH + R'OH

RCH2NH2

A. LiAlH4 (p.95)

187

2. Reduction

B. H2/Pd poisoned with S (p.84)

High yield

188

3. Other reactions of acid amides

A. Hofmann Degradation

CR

O

NH2

Br2, conc. NaOHRNH2

CR

O

CH3

1. I2, conc. NaOHRCOOH

2. H3O+

Cf. Iodoform reaction One Carbon less

189

Synthetic application

H3C COH

O Br2 , conc. NaOHNH3

heatH3C C

NH2

OCH3NH2

HNO2CH3OH

[O]HCOOH

H3C CCl

O H2, Pd

sulphurH3C C

H

O

1. LiAlH4 /dry ether

2. H3 O +

CH3CH2OH

1. I 2

, con

c.

NaOH 2. H

3O

+

190

B. Dehydration

R CNH2

O P2O5

heatC NR + H2O

191

RCOOH / RCN cycle : -

R COH

O

R CNH2

O

C NR

R CNH2

O

192

Q. 81Br

C2H5ONaC2H5OH

heat

KMnO4H3O+heat

COOH

COOH

(excess)CONH2

CONH2NH3

heat

Nylon 6,6

C

CCl

O

Cl

O

1. LiAlH4, dry ether2. H3O+

NH2

H2N

Excess NH3

better

193

The END

194

Give the IUPAC names for the following compounds:

(a) (b)

(c) (d)

Answer

(a) 3-Methylbutanoic acid

(b) N-Methylethanamide

(c) Ethyl benzoate

(d) Benzoic anhydride

Back

195

An ester is formed by reacting an alcohol with a carboxylic acid. Draw the structural formulae of the following esters and in each case, give the names of the alcohol and the carboxylic acid that form the ester.

(a) Methyl ethanoate Answer(a) The structural formula of methyl ethanoate is:

It is formed from the reaction of ethanoic acid and

methanol.

196

32.2 Nomenclature of Carboxylic Acids and their Derivatives (SB p.26)

An ester is formed by reacting an alcohol with a carboxylic acid. Draw the structural formulae of the following esters and in each case, give the names of the alcohol and the carboxylic acid that form the ester.

(b) Ethyl methanoate Answer(b) The structural formula of ethyl methanoate is:

It is formed from the reaction of methanoic acid and

ethanol.

Back

197

Complete the following table.Answer

Molecular formula

Structural formula

IUPAC name

C3H7COOH (a) (b)

(c) (d)

(e) (f)

(g) (h) Trichloroethanoic acid

198

(a) (b) Butanoic acid

(c) CH3CH(CH3)CH2COOH (d) 3-Methylbutanoic acid

(e) C6H4ClCOOH (f) 2-Chlorobenzoic acid

(g) CCl3COOH (h)

Back

199

(a)Propanoic acid has a boiling point of 141°C which is considerably higher than that of butan-1-ol (117°C), although they have the same molecular mass. Explain why.

Answer

200

(a) Each propanoic acid molecule forms two intermolecular hydrogen

bonds with other propanoic acid molecules. However, each butan-

1-ol molecule can form only one intermolecular hydrogen bond with

other butan-1-ol molecules. Since molecules of propanoic acid

form more extensive intermolecular hydrogen bonds than those of

butan-1-ol, the boiling point of propanoic acid is higher than that of

butan-1-ol.

201

(b) Arrange the following compounds in decreasing order of solubility in water:

CH3CH2CH2COOH, CH3CH2COOCH3, CH3COOH

Answer(b) The solubility of the compounds in water decreases in

the order:

CH3COOH > CH3CH2CH2COOH > CH3CH2COOCH3

202

(c)Propanedioic acid forms intramolecular hydrogen bonds. Draw its structural formula, showing clearly the formation of intramolecular hydrogen bonds. Answer

(c)

Back

203

Write the chemical equations for the acid-catalyzed and alkali-catalyzed hydrolyses of each of the following compounds:

(a) Ethyl butanoateAnswer

(a)

204


(b) PropanamideAnswer

(b)

205


(c) Benzoyl chlorideAnswer

(c)

Back

206

Outline how a mixture of butanone and ethanoic acid can be separated in the laboratory. Answer

Back

207

(a)Complete and balance the following chemical equations:

(i)

(ii)

Answer

208

(a) (i)

(ii)

209

(b) Complete the following chemical equations:

(i)

(ii)

(iii)Answer

210

(b) (i)

(ii)

(iii)

Back

211

Explain why ethanoyl chloride must be protected from atmospheric moisture during storage. Answer

This is because ethanoyl chloride reacts

readily with water (from atmospheric

moisture) to form ethanoic acid.

Back

212

The characteristic reaction of the derivatives of carboxylic acids is nucleophilic acyl substitution.

Arrange the derivatives of carboxylic acids in decreasing order of reactivity towards nucleophilic

acyl substitution.

AnswerAcyl chlorides > acid anhydrides > esters > amides

Back

213

Draw the structural formulae of the missing compounds A to H:

(a)

(b)

(c)

Answer

214

(a)

(b)

(c)

215

Draw the structural formulae of the missing compounds A to H:

(d)

(e)

(f)

Answer

216

(d)

(e)

(f)

Back

1 derivatives of carboxylic acids and nucleophilic acyl substitution

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