2. 1 Derivatives of Carboxylic Acids and Nucleophilic Acyl Substitution

3. 2 Carboxylic Acids A class of organic compounds containing at least one carboxyl group

4. 3 R = alkyl group or H  alkanoic acid(sat’d) R = aryl group  aromatic carboxylic acid

5. 4 Aliphatic carboxylic acid = fatty acids (sat’d or unsat’d) ∵ obtained from fat/oil E.g.stearic acid, CH 3 (CH 2 ) 16 COOH oleic acid, CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 COOH

6. 5 Carboxylic Acids Carboxyl group  combination of the carbonyl group and the hydroxyl group

7. 6 Nomenclature Suffix : carboxylic acid or oic acid Prefix : carboxy

8. 7 Q.62 butanoic acid (2Z)-but-2-enoic acid ethanedioic acid

9. 8 Q.62 butanedioic acid 2-hydroxypropane- 1,2,3-tricarboxylic acid (citric acid) 3-carboxy-3- hydroxypentainedicarboxylic acid

10. 9 Q.62 benzoic acid Benzene-1,3- dicarboxylic acid

11. 10 Q.62 phenylethanoic acid 4-hydroxybenzoic acid

12. 11 Derivatives of carboxylic acids (pp.9-10) NameStructure Acyl(Acid) chlorides Acid anhydrides Esters Acid Amides

13. 12 Acyl (Acid) Chlorides Suffix : -oic acid replaced by –oyl chloride Prefix : chlorocarbonyl

14. 13 Acyl (Acid) Chlorides 3-chloro-3-oxopropanoic acid Priority : - -COOH > anhydride > ester > acid chloride > acid amide The carbonyl C is counted as part of the carbon skeleton

15. 14 4-chloro-2-methyl-4- oxobutanoic acid hexanedioyl dichloride 3-(chlorocarbonyl)hexanedioic acid Q.63

16. 15 Acid anhydride Suffix : -acid replaced by –anhydride

17. 16 Acid anhydride 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 *

18. 17 Acid anhydride Prefix : (alkanoyloxy)carbonyl (if *C is not counted as part of the main chain) *

19. 18 Acid anhydride ethanoic anhydride ethanoic propanoic anhydride

20. 19 Acid anhydride benzoic ethanoic anhydride butanedioic anhydride

21. 20 Q.64 Benzene-1,2-dioic anhydride

22. 21 Ester Suffix : -oic acid replaced by –oate preceded by the name of R’

23. 22 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 * Ester

24. 23 Prefix : alkoxycarbonyl (if *C is not counted as part of the main chain) Ester *

25. 24 Ester methyl ethanoate ethenyl ethanoate methyl 4- bromobenzoate

26. 25 Q.65 2-(methoxycarbonyl)benzoic acid 2-(ethanoyloxy)benzoic acid 2-(acetyloxy)benzoic acid

27. 26 Acid amide Suffix : -oic acid replaced by -amide

28. 27 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 * Ester

29. 28 Prefix : aminocarbonyl (if *C is not counted as part of the main chain) Ester *

30. 29 ethanamide (1  ) N-methylethanamide (2  ) N,N-dimethylethanamide (3  ) Ester

31. 30 Q.66 benzamide 4-amino-4- oxobutanoic acid 3-(aminocarbonyl)heptanedioic acid

32. 31 Physical Properties of Alkanoic Acids

33. 32

34. 33 Odour Methanoic / ethanoic acid  sharp, irritating odours Propanoic to heptanoic acid  strong, unpleasant odours Butanoic acid  body odour Higher members  low volatility  little odour

35. 34 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 b.p.  steadily as the number of C atoms  ∵ London dispersion forces become stronger as the size of electron cloud 

36. 35 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 HCOOH/CH 3 COOH have exceptionally high m.p. ∵ smaller size  1.closer packing  2.forming H-bonds more extensitively

37. 36 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 Members with EVEN no. of C atoms are more symmetrical  Higher packing efficiency  Higher m.p.

38. 37 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid 16.6 1181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 Pure ethanoic acid = glacial ethanoic acid It freezes in cold weather

39. 38 More extensive H-bonds H-bonds Dipole-dipole interaction Dispersion forces ONLY

40. 39 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 Less dense than water except HCOOH/CH 3 COOH

41. 40 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2  as R.M.M.  R.M.M.  extent of H-bond formation   molecules not drawn closer  lower packing efficiency

42. 41 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O MethaneGas EthaneGas PropaneGas ButaneGas Pentane0.626 Hexane0.655 Heptane0.684 Octane0.703 Nonane0.718 Decane0.730 For alkanes,   as R.M.M.  ∵ no intermolecular H-bonds R.M.M.  Dispersion forces become stronger  closer packing

43. 42 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 First FOUR members are miscible with water in all proportions due to extensive H-bond formation between acid molecules and water molecules

44. 43 Alkanoic acid Melting point / o C Boiling point / o C Density /g cm -3 Solubility in water /g per H 2 O Methanoic acid8.41011.220  Ethanoic acid16.61181.047  Propanoic acid  20.81410.992  Butanoic acid  6.51640.964  Pentanoic acid  34.51860.9393.7 Hexanoic acid  1.52050.9271.0 Heptanoic acid  102240.9130.25 Octanoic acid162390.9100.7 Nonanoic acid12.52530.9070.07 Decanoic acid312690.8860.2 From pentanoic acid, solubility  as R.M.M.  The bulky R groups prevent formation of H-bonds between –COOH and H 2 O

45. 44

46. 45 Emulsifying action of soap (salts of carboxylic acids) depends on the length of the hydrocarbon chain Non-polarionic

47. 46 Length of hydrocarbon chainProperty Short (  15 C atoms) Ionic properties predominate Long (  19 C atoms) Non-polar properties predominate Intermediate(16-18 C atoms) e.g. palmitic acid, C 15 H 31 COOH stearic acid, C 17 H 35 COOH Possess both ionic/non-polar properties

48. 47 Preparation of Carboxylic Acids

49. 48 1.Hydrolysis of Nitriles 1. Hydrolysis of Nitriles Elimination occurs for 2  and 3  RX as CN  is a relatively strong base

50. 49 Examples

51. 50 2.Oxidation of aldehydes and 1  alcohols (pp.83-84, 93) 2. Oxidation of aldehydes and 1  alcohols (pp.83-84, 93) 3.Oxidation of aromatic side chains (pp.54-55) 3. Oxidation of aromatic side chains (pp.54-55) 4.Iodoform reactions (p.92) 4. Iodoform reactions (p.92)

52. 51 Q.67

53. 52 Q.68 1… 2… Prolonged heating

54. 53 5.Hydrolysis of Esters 5. Hydrolysis of Esters removed by distillation E.g. Fat/oil Soap + glycerol NaOH(aq) heat

55. 54 5.Hydrolysis of Esters 5. Hydrolysis of Esters

56. 55 6.Carbonation of Grignard reagents 6. Carbonation of Grignard reagents R-X R  [MgBr] + Mg Dry ether Grignard reagent R : CH 3 -, 1  /2  /3  alkyl, benzyl, aryl

57. 56 6.Carbonation of Grignard reagents 6. Carbonation of Grignard reagents R-X R  [MgX] + Mg Dry ether Dry ice (CO 2 ) H3O+H3O+ + 1 C

58. 57 ++ 6.Carbonation of Grignard reagents 6. Carbonation of Grignard reagents R-X R  [MgX] + Mg Dry ether

59. 58 7.Cannizzaro reactions 7. Cannizzaro reactions For aldehydes without  H removed by distillation

60. 59 Reactions of Carboxylic Acids

61. 60 Acidity of Carboxylic Acids weak acids pK a = –log K a The smaller the value of pK a, the stronger the acid

62. 61 Acid RCOOHH 2 CO 3 H2OH2O pK a 4-56.4~1015.7 Acidity  as pK a 

63. 62 Formation of Salts 1. Reaction with Reactive Metals Irreversible as H 2 leaves the reaction mixture

64. 63 2. Reaction with Bases Weaker acid Stronger acid Equilibrium positions lie on the right

65. 64 Stronger acid Weaker acid Phenols react with OH , but they do not react with HCO 3  Stronger acid Weaker acid No observable change (effervescence)

66. 65 Is there effervescence when Na is added to phenol? Explain. Yes. The reaction proceeds to the completion as H 2 leaves the reaction mixture.

67. 66 Carboxylic acids and phenols can be distinguished by their different acidities 1989 AL Paper I Q.4 (modified)

68. 67 (a) Outline a chemical test to distinguish between A and B. Add NaHCO 3 (aq) to A and B separately. Ony B reacts apparently to give gas bubbles of CO 2

69. 68 (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.

70. 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 NaHCO 3 (aq) Evaporation of ether Pure A Sodium salts of B and C dissolve in water b.p. = 34.6  C

71. 70 Q.69 Outline a scheme to separate completely A, B and C from a mixture of them in ether. Acidity : A > H 2 CO 3 > B > H 2 O > C A, B are sparingly soluble solids in water

72. 71 Ether solution of A, B ands C Ether layer, B + CAqueous layer, sodium salt of A shaken with NaHCO 3 (aq)H3O+H3O+ Ppt of A filtration Impure A Pure A recrystallization (m.p. = 122.4  C) p.120

73. 72 Ether layer, B + C Shaken with NaOH(aq) Aqueous layer, sodium salt of B Ether layer, C Evaporation of ether Pure C H3O+H3O+ Ppt of B filtration Impure B Pure B recrystallization (m.p. = 40.5  C)

74. 73 Applied ONLY to synthesis of methane and benzene Decarboxylation

75. 74 Decarboxylation On the contrary, decarboxylation is widely applied to synthesis of carbonyl compounds (refer to p.85)

76. 75 Reduction H 2 /Pt No reaction or, NaBH 4 /H 2 O

77. 76 Oxidation Not easily oxidized except : -

78. 77 Dehydration Not easily dehydrated except : -

79. 78 Q.70 Conc. H 2 SO 4 CO 2 + CO + H 2 O +3 +4+2

80. 79 Formation of acid derivatives Refer to preparation of acid derivatives (pp.115-120)

81. 80 Acidity of Organic Compounds (Bronsted/Lowry Concept) smaller pK a  higher acidity larger pK a  lower acidity HA(aq) + H 2 O(l) H 3 O + (aq) + A  (aq)

82. 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)

83. 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-F Can 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

84. 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 

85. 84 Stability of A  depends on (ii)Electronic effect - Inductive effect (+ve or –ve) - resonance effect (more important)

86. 85 Organic CompoundpK a Organic CompoundpK a CH 3 CH 2 –H50CH 3 CH 2 CH 2 O–H~17 H–H50HO – H15.7 CH 2 =CH–H44C 6 H 5 O–H (phenol)~10 NH 2 –H364.87 CH  C–H25CH 3 COO–H4.76 CH 3 COCH 2 –H204.20

87. 86 Interpretation of the Relative Stability of Typical Organic Compounds HO-HH 2 N-HH 3 C-H pK a 15.73650 Electronegativity : - - O > N > C Stability of conjugate base : - HO  > H 2 N  > H 3 C  The more electronegative atom can accommodate the negative charge more easily

88. 87 CH 3 COCH 2 -HH 3 C-H pK a 2050 The -ve charge on C becomes less available for attracting a proton  CH 3 COCH 2  becomes a weaker base  CH 3 COCH 2 -H becomes a stronger conjugate acid Resonance effect

89. 88 CH  C-HCH 2 =CH-HCH 3 CH 2 -H pK a 254450 Stability of conjugate base : - CH  C  > CH 2 =CH  > CH 3 CH 2  spsp 2 sp 3 Ease of accommodation of the –ve charge : - sp C > sp 2 C > sp 3 C

90. 89 CH 3 COO-HCH 3 CH 2 CH 2 O-H pK a 4.74~10~17 CH 3 CH 2 CH 2 O  > > Stability of conjugate base : - Destabilized by +ve inductive effect Stabilized by resonance effect

91. 90 Q.71 The two structures are equally stable The –ve charge is shared by two electronegative O atoms  Delocalization of –ve charge is more favoured

92. 91 Q.71 The –ve charge is accommodated by the less electronegative C atoms  less stable  delocalization is less favoured

93. 92 Q.72 pK a 4.204.87 The –ve charge is not shared by the ring  less extensive delocalization

94. 93 The –ve charge is shared by the ring slightly  more extensive delocalization The effect is small since the three structures are less stable due to separation of opposite charges

95. 94 Effects of substituents on acidity of carboxylic acids 1. Aliphatic carboxylic acids Electron-donating R groups destabilize the RCOO   RCOOH is less acidic Electron-withdrawing R groups stabilize the RCOO   RCOOH is more acidic

96. 95 Carboxylic acidpK a Conjugate base CF 3 COO–H 0 CF 3  COO  CCl 3 COO–H 0.65 CCl 3  COO  CH 2 FCOO–H 2.66 CH  COO  CH 2 ClCOO–H 2.81 CH 2 Cl  COO  CH 2 BrCOO–H 2.87 CH 2 Br  COO  CH 2 ICOO–H 3.13 CH 2 I  COO  HCOO–H 3.77 HCOO  CH 3 COO–H 4.76 CH 3  COO 

97. 96 Inductive effect on acidity  rapidly when the substituents are placed farther away from the carboxyl group pK a 2.85 4.05 4.52 4.82

98. 97 2. Aromatic carboxylic acids 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

99. 98 2. Aromatic carboxylic acids 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

100. 99 Q.73 pK a 2.98 4.20 4.58

101. 100 Q.73 pK a = 4.20pK a = 4.58  OH withdraws electrons by –ve inductive effect -OH donates electrons by resonance effect Resonance effect > inductive effect The net effect is electron-donating

102. 101 pK a = 4.20pK a = 2.98 The conjugate base is stabilized by intramolecular hydrogen bond

103. 102 (1)Acidity : dioic acids > monocarboxylic acid The conjugate bases are stabilized by intramolecular H-bonds AcidpK a1 pK a2 pK a2 – pK a1 HOOC  COOH 1.24.23.0 HOOC  CH 2  COOH 2.95.72.8 HOOC  (CH 2 ) 2  COOH 4.25.61.4 HOOC  (CH 2 ) 3  COOH 4.35.51.2 HOOC  (CH 2 ) 4  COOH 4.45.61.2 CH 3 COOH 4.76--

104. 103 AcidpK a1 pK a2 pK a2 – pK a1 HOOC  COOH 1.24.2 3.0 HOOC  CH 2  COOH 2.95.7 2.8 HOOC  (CH 2 ) 2  COOH 4.25.6 1.4 HOOC  (CH 2 ) 3  COOH 4.35.5 1.2 HOOC  (CH 2 ) 4  COOH 4.45.6 1.2 CH 3 COOH 4.76- - (i)The repulsion between two –COO  groups does not favour the 2 nd dissociation (2)pK a2 > pK a1

105. 104 AcidpK a1 pK a2 pK a2 – pK a1 HOOC  COOH 1.24.2 3.0 HOOC  CH 2  COOH 2.95.7 2.8 HOOC  (CH 2 ) 2  COOH 4.25.6 1.4 HOOC  (CH 2 ) 3  COOH 4.35.5 1.2 HOOC  (CH 2 ) 4  COOH 4.45.6 1.2 CH 3 COOH 4.76- - (ii)The doubly charged anion attracts the proton more strongly (2)pK a2 > pK a1 H+H+

106. 105 AcidpK a1 pK a2 pK a2 – pK a1 HOOC  COOH 1.24.2 3.0 HOOC  CH 2  COOH 2.95.7 2.8 HOOC  (CH 2 ) 2  COOH 4.25.6 1.4 HOOC  (CH 2 ) 3  COOH 4.35.5 1.2 HOOC  (CH 2 ) 4  COOH 4.45.6 1.2 CH 3 COOH 4.76- - ∵ intramolecular H-bonds are less easily formed (3)pK a1  as the two –COOH groups are further apart

107. 106 AcidpK a1 pK a2 pK a2 – pK a1 HOOC  COOH 1.24.2 3.0 HOOC  CH 2  COOH 2.95.7 2.8 HOOC  (CH 2 ) 2  COOH 4.25.6 1.4 HOOC  (CH 2 ) 3  COOH 4.35.5 1.2 HOOC  (CH 2 ) 4  COOH 4.45.6 1.2 CH 3 COOH 4.76- - The repulsion between the two –COO  groups  down the series  pK a2 remains relatively constant Since, pK a1  down the series (pK a2 -pK a1 )  down the series (4)(pK a2 -pK a1 )  down the series

108. 107 smaller pK b  higher basicity larger pK b  lower basicity B(aq) + H 2 O(l) HB + (aq) + OH  (aq) Basicity of Organic Compounds

109. 108 Two factors affecting the basicity: - (1) Ability to donate a lone pair to a proton Basicity : - More electron-donating alkyl group attached to N More available to donate a lone pair to a proton > > > 33 22 11

110. 109 (2) The extent of solvation of the conjugate acid Extent of solvation : - > >> 11 22 33 More H attached to N More available to form H-bond with water(solvent) Extent of solvation   Stability of conjugate acid   Basicity of amine 

111. 110 Good solvation Extensive formation of H-bonds with water

112. 111 Overall Basicity (from experiments) : - 2  amines > 1  amines > 3  amines > NH 3 pK b 3.27 3.36 4.22 4.74 >

113. 112 Q.74(a) CH 3  NH 2 -CH 3 is electron-donating  The lone pair on N is more available to abstract a proton

114. 113 The lone pair on N is shared by the benzene ring due to resonance effect  Less available to abtract a proton

115. 114 Both –OH and –CH 3 groups are electron-donating  Lone pair on N is more available to abstract a proton  Stronger base than phenylamine >& Q.74(b)

116. 115 > Q.74(b) Resonance effect is more electron-donating than positive inductive effect

117. 116 Q.74(b) > -NO 2 group is electron-withdrawing  Lone pair on N is less available to abstract a proton  Weaker base than phenylamine

118. 117 > Q.74(c) Oxygen is more electronegative than N and C  Lone pair on N is withdrawn more  Less basic than phenylamine

119. 118 Basicity of organic compounds : - Aliphatic > NH 3 > Aromatic > Amides amines (2  > 1  > 3  )

120. 119 Amines form water-soluble salts with mineral acids CH 3 NH 2 + HCl(aq)  CH 3 NH 3 + Cl  (CH 3 ) 2 NH + HCl(aq)  (CH 3 ) 2 NH 2 + Cl  (CH 3 ) 3 N + HCl(aq)  (CH 3 ) 3 NH + Cl  1. Used in drug formulation for easier absorption 2. Used in purification of amines from other organic compounds

121. 120 Ether solution of A, B, C and D Ether layer, A,B,DAqueous layer, sodium salt of C shaken with NaHCO 3 (aq)H3O+H3O+ Ppt of C filtration Impure C Pure C recrystallization Q.75

122. 121 Ether solution of A, B and D Ether layer, B,DAqueous layer, sodium salt of A shaken with NaOH(aq)H3O+H3O+ Ppt of A filtration Impure A Pure A recrystallization Q.75

123. 122 Ether layer, B + D Shaken with HCl(aq) Aqueous layer, sodium salt of B Ether layer, D Evaporation of ether Pure C OH - B + Aq. solution Shaken with ether B in ether layer Pure B Evaporation of ether (liquid)

124. 123 Reactivity of carboxylic acids and their derivatives towards nucleophilic reactions 1. Aldehydes/ketones undergo Ad N rather than S N Carboxylic acids/derivatives undergo S N rather than Ad N

125. 124 Strong bases, unstable A discussion on the reactivity of carboxylic acids and their derivatives towards nucleophilic rxs 1. Aldehydes/ketones undergo Ad N rather than S N

126. 125 Reactivity of carboxylic acids and their derivatives towards nucleophilic reactions 1. Carboxylic acids/derivatives undergo S N rather than Ad N Weak base, stable

127. 126 Strength of acids : - HCl > RCOOH > HOH > ROH > H 2 NH > RH > HH Strength of bases : - Cl  < RCOO  < HO  < RO  < H 2 N  < R  < H 

128. 127 Reactivity : -

129. 128 Reactivity : - (i)Ease of leaving(Stability of bases) : - Cl  > RCOO  > HO  > RO  > H 2 N  > R  > H  ∵ Strength of bases : - Cl  < RCOO  < HO  < RO  < H 2 N  < R  < H  Reasons : -

130. 129 Reasons : - Increasing resonance effect ( 2p ) (3p) ( 2p) (ii)Resonance effect : - Efficiency of orbital overlap : 2p/2p > 3p/2p Less stable More reactive More stable Less reactive

131. 130 Reactivity : - The less reactive derivatives can be prepared from the more reactive derivative via nucleophilic substitution reactions.

132. 131 Preparation of Acid Derivatives

133. 132 Preparation of Acid Derivatives

134. 133 Preparation of Acid Derivatives

135. 134 Preparation of Acid Derivatives

136. 135 Preparation of Acid Derivatives Non-S N reactions

137. 136 C – O  bond of benzoyl chloride has less mesomeric effect  Carbonyl C of benzoyl chloride is less positive  Less susceptible to nucleophilic attack

138. 137  + ++  The carbonyl C is attached to TWO electron-withdrawing atoms  more positive  more susceptible to electrophilic attacks

139. 138  + ++  Also, the nucleophile experiences less steric hindrance with acyl chloride because the reaction site is planar

140. 139 A.Preparation of Acid Chlorides SOCl 2 : thionyl chloride or sulphur oxychloride

141. 140 (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 by fractional distillation Phosphorus oxychloride (>170  C)

142. 141 (2)Acid chloride with high/intermediate/low b.p. can be removed easily b.p. = 74.6 ℃ (l) (85  C < b.p. < 170  C) Most useful or b.p. < 65  C

143. 142 (3)Acid chloride with low b.p. decomposes at 200 ℃ b.p. = 79 ℃ (l) (3)Acid chloride with low b.p. (< 69  C) Removed first by fractional distillation

144. 143 Q.76 b.p.=197.2  C b.p.=106  C b.p.=249  C s.t.=160  C b.p.=74.6  C

145. 144 Q.76 b.p.  51  Cb.p.=118  C d.c.  200  C b.p.=76  C Removed first by fractional distillation

146. 145 B. Preparation of Acid Anhydrides Acyl chlorides must be stored in anhydrous conditions  they hydrolyze rapidly in the presence of even a trace amount of water(p.122) RCOCl + H 2 O  RCOOH + HCl

147. 146 B. Preparation of Acid Anhydrides R  R’  unsymmetrical anhydride R = R’  symmetrical anhydride

148. 147 B. Preparation of Acid Anhydrides pyridine Equilibrium position shifts to the right  Yield 

149. 148 B. Preparation of Acid Anhydrides R  R’  unsymmetrical anhydride R = R’  symmetrical anhydride

150. 149 B. Preparation of Acid Anhydrides NaCl(s) produced is removed by precipitation  Equilibrium position shifts to the right  Yield 

151. 150 B. Preparation of Acid Anhydrides Only suitable for preparing symmetrical anhydrides dehydrating agent P 4 O 10 = P 2 O 5 Non-S N reaction

152. 151 Q.77 It gives a mixture of three acid anhydrides. RCOOH + R’COOH P 4 O 10 heat

153. 152 Preparation of Acid Amides Ammonolysis NH 3

154. 153 C. Preparation of Acid Amides The overall reaction is : - (1)Ammonolysis of Carboxylic Acids breaking of ammonia = ammonolysis

155. 154 C. Preparation of Acid Amides (1)Ammonolysis of Carboxylic Acids neutralizationdehydration

156. 155 C. Preparation of Acid Amides (1)Ammonolysis of Carboxylic Acids prevent hydrolysis of the ammonium carboxylate excess

157. 156 (2)Ammonolysis of Acid Chlorides(better method) (Acylation of NH 3 /amines) NH 3 (aq) excess (2  ) excess R’NH 2 (aq) (1  ) excess (1  ) (2  ) (3  ) Acyl group Aminolysis

158. 157 (2)Ammonolysis of Acid Chlorides (benzoylation of NH 3 /amines) benzoyl group

159. 158 NH 3 (aq) excess (2  ) excess R’NH 2 (aq) (1  ) excess Removed by excess NH 3 /amines  Yield 

160. 159 NOT applicable to 3  amine due to absence of H

161. 160 Further acylation is inhibited because amides are weaker nucleophiles than amines

162. 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)

163. 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

164. 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).

165. 164 Why is hot filtration done in ways as described by step 3 ? (a) Hot filtration is to minimize the crystallization 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.

166. 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.

167. 166 (3)Ammonolysis of Acid Anhydrides The yield is increased by removing the products with excess NH 3 or amine (1  ) (2  )

168. 167 (4)Partial Hydrolysis of Nitriles Non-S N reaction

169. 168 Further hydrolysis gives carboxylic acids (in acidic medium) or carboxylate in (basic medium).

170. 169 Hydrolysis of amide = The reverse of ammonolysis of RCOOH H2OH2O

171. 170 Preparation of Esters R’’OH Alcoholysis

172. 171 R’O – H C. Preparation of Esters (1)Alcoholysis of Carboxylic Acids Esterification

173. 172 (2)Alcoholysis of Acid Chlorides Faster and irreversible OH  ions serve to (i)  the yield by removing HCl phenolysis

174. 173 (2)Alcoholysis of Acid Chlorides OH  ions serve to (ii)Speed up the nucleophilic attack by generating the more powerful nucleophile.

175. 174 (3)Alcoholysis of Acid Anhydrides Heating is required as acid anhydrides are less reactive than acid chlorides

176. 175 Reactions of the Derivatives of Carboxylic Acids

177. 176 Nucleophilic Acyl Substitution HZ:  nucleophile L  leaving group slowfast

178. 177 Nucleophilic Acyl Substitution HZ:  nucleophile L  leaving group slowfast

179. 178 Nucleophilic Acyl Substitution More stable intermediate slowfast Less steric hindrance than the 5-coordinated transition state of RX(S N 2) Obeying octet rule while the 3-coordinated carbocation of RX(S N 1) is not

180. 179 Nucleophilic Acyl Substitution HZ: = H-OH, H-OR, H-NH 2, H-NHR, H-NRR’ slowfast

181. 180 A.Hydrolysis (Reactions with water) HZ = H-OH Decreasing reactivity catalysts

182. 181 Acid-catalyzed Carbonyl C becomes more susceptible to nucleophilic attacks

183. 182 Base-catalyzed OH  ion is a stronger nucleophile than H 2 O

184. 183 A.Hydrolysis (Reactions with water) HZ = H-OH Decreasing reactivity Or, CH 3 COO 

185. 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

186. 185 C.Ammonolysis (Reactions with NH 3 ) HZ = H-NH 2 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

187. 186 2.Reduction A.LiAlH 4 (p.95)

188. 187 2.Reduction B.H 2 /Pd poisoned with S (p.84) High yield

189. 188 3.Other reactions of acid amides A.Hofmann Degradation Cf. Iodoform reaction One Carbon less

190. 189 Synthetic application 1. LiAlH 4 /dry ether 2. H 3 O + CH 3 CH 2 OH 1. I 2, conc. NaOH 2. H 3 O +

191. 190 B.Dehydration

192. 191 RCOOH / RCN cycle : -

193. 192 Q. 81 (excess) Nylon 6,6 Excess NH 3 better

194. 193 The END

195. 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

196. 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.

197. 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

198. 197 Complete the following table. Answer Molecular formula Structural formulaIUPAC name C 3 H 7 COOH(a)(b) (c)(d) (e)(f) (g)(h)Trichloroethanoic acid

199. 198 (a) (b) Butanoic acid (c)CH 3 CH(CH 3 )CH 2 COOH (d) 3-Methylbutanoic acid (e)C 6 H 4 ClCOOH (f)2-Chlorobenzoic acid (g)CCl 3 COOH (h) Back

200. 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

201. 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.

202. 201 (b)Arrange the following compounds in decreasing order of solubility in water: CH 3 CH 2 CH 2 COOH, CH 3 CH 2 COOCH 3, CH 3 COOH Answer (b)The solubility of the compounds in water decreases in the order: CH 3 COOH > CH 3 CH 2 CH 2 COOH > CH 3 CH 2 COOCH 3

203. 202 (c)Propanedioic acid forms intramolecular hydrogen bonds. Draw its structural formula, showing clearly the formation of intramolecular hydrogen bonds. Answer (c) Back

204. 203 Write the chemical equations for the acid-catalyzed and alkali-catalyzed hydrolyses of each of the following compounds: (a) Ethyl butanoate Answer (a)

205. 204 Write the chemical equations for the acid-catalyzed and alkali-catalyzed hydrolyses of each of the following compounds: (b) Propanamide Answer (b)

206. 205 Write the chemical equations for the acid-catalyzed and alkali-catalyzed hydrolyses of each of the following compounds: (c) Benzoyl chloride Answer (c) Back

207. 206 Outline how a mixture of butanone and ethanoic acid can be separated in the laboratory. Answer Back

208. 207 (a)Complete and balance the following chemical equations: (i) (ii) Answer

209. 208 (a)(i) (ii)

210. 209 (b)Complete the following chemical equations: (i) (ii) (iii) Answer

211. 210 (b)(i) (ii) (iii) Back

212. 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

213. 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. Answer Acyl chlorides > acid anhydrides > esters > amides Back

214. 213 Draw the structural formulae of the missing compounds A to H: (a) (b) (c) Answer

215. 214 (a) (b) (c)

216. 215 Draw the structural formulae of the missing compounds A to H: (d) (e) (f) Answer

217. 216 (d) (e) (f) Back