Amides are named by replacing the suffix -oic acid in the carboxylic acid name with -amide. Nitriles are named by adding the suffix -nitrile to the alkane name. The nitrile carbon is assigned position 1. α-Hydrogen atoms of carbonyl compounds are acidic due to stabilization of the resulting enolate anion. This allows for halogenation and reactions involving enolate intermediates, such as aldol condensations.

1. Amides
Amides
1
: Nomenclature
IUPAC
An amide has NH2, NHR ,or NR2 group in place of the OH group of a
carboxylic acid.
Amides are named by using the acid name, replacing oic acid or ic acid with
amide. For acids ending with carboxylic acid, ylic acid is replaced with amide.

2. Amides
Amides
2
: Nomenclature
IUPAC
In case of 2ry and 3ry amides, the name of substituent is preceded by N.

3. Nitriles
Nitriles
3
: Nomenclature
IUPAC
They are considered carboxylic acid derivatives because they react with water
to form carboxylic acids. Nitriles are named by adding the suffix -nitrile to the
alkane name. The nitrile carbon is assigned position 1
***Ethanenitrile is usually called acetonitrile

4. Nitriles
Nitriles
4
: Nomenclature
IUPAC
Nitriles can also be named as alkyl cyanides-starting the name by the alkyl
group that is attached to the CN group.

5. Amides
5
: Preparation
1) From Acyl Chlorides
Ammonia, 1ry or 2ry amines react with acid chlorides to form amides.
An excess of amine is added to neutralize the HCl formed in the
reaction.
Carboxylic acids can be converted to amides via the corresponding
acid chloride

6. Amides
6
: Preparation
2) From Carboxylic Anhydrides
Anhydrides react with 2 equivalents of amine to produce an
amide & ammonium carboxylate

7. Amides
7
: Preparation
2) From Carboxylic Acids & Ammonium Carboxylates
Direct reaction of carboxylic acids & ammonia yields ammonium salts
Some ammonium salts of carboxylic acids can be dehydrated to the amide at
high temperatures .This is generally a poor method of amide synthesis

8. Amides
8
: Reaction
Amides are very unreactive compounds

9. Amides
9
: Reaction
1) Amides react with water or alcohol if the reaction is heated
in presence of an acid

10. Amides
10
: Reaction
1) Amides react with water or alcohol if the reaction is heated
in presence of an acid

11. Amides
11
: Reaction
1) Amides react with water or alcohol if the reaction is
heated in presence of an acid
Hydrolysis of Amides
Heating an amide in
concentrated aqueous
acid or base causes
hydrolysis

12. Amides
12
: Reaction
2) 1ry amides can be dehydrated to nitriles. Dehydrating
reagents such as P2O5, POCl3, SOCl2 can be used.

13. Hofmann degradation
13
Conversion of primary amide to primary amine

14. Lactams
14
Cyclic amides are called lactams. The size of the lactam ring is designated by
Greek letters in a way that is analogous to lactone nomenclature
• γ-Lactams and δ-lactams often form spontaneously from γ- and δ-amino acids.
• β-Lactams, however, are highly reactive; their strained four-membered rings open
easily in the presence of nucleophilic reagents.

15. Nitriles
15
: Preparation
A nitrile can be formed by reaction of an amide with
phosphorous pentoxide or boiling acetic anhydride

16. Nitriles
16
: Reaction
Hydrolysis of Nitriles

17. Nitriles
17
: Reaction
Hydrolysis of Nitriles in acidic medium

18. Nitriles
18
: Reaction
Hydrolysis of Nitriles in basic medium

19. Tautomerism
19
Tautomerism
keto and enol forms of carbonyl compounds are constitutional isomers,
but of a special type. Because they are easily interconverted by proton
transfers in the presence of an acid or base. Interconvertible keto and
enol forms are called tautomers, and their interconversion is called
tautomerization
enol form
keto form
C
OH
C
C C
O
H
The keto form is usually predominant with few exceptions.

20. 20
The keto form is usually predominant with few exceptions.
2,4-Pentanedione
Enol form (76%)
Tautomerism

21. Decarboxylation of Carboxylic Acids
21
Loss of CO2 from a carboxyl group = Decarboxylation
• Carboxylic acids undergo thermal decarboxylation, when heated to a very high
temperature and most carboxylic acids are resistant to moderate heat.
• Exceptions are carboxylic acids that have a carbonyl group β to the carboxyl group
(β-ketoacids undergo decarboxylation readily on mild heating).

22. Decarboxylation of Carboxylic Acids
22
Loss of CO2 from a carboxyl group = Decarboxylation
• There are two reasons for this ease of decarboxylation:
1. When the acid itself decarboxylates, it can do so through a six-membered
cyclic transition state:
This reaction produces an enol (alkene-alcohol) directly and avoids an anionic
intermediate. The enol then tautomerizes to a methyl ketone.

23. Decarboxylation of Carboxylic Acids
23
Loss of CO2 from a carboxyl group = Decarboxylation
• There are two reasons for this ease of decarboxylation:
2. When the carboxylate anion decarboxylates, it forms a resonance-stabilized
anion:.
This type of anion is much
more stable than simply
RCH2:−, the anion that would
have been produced by
decarboxylation in the absence
of a β-carbonyl group. It is
known as an enolate.

24. Decarboxylation of Carboxylic Acids
24
Loss of CO2 from a carboxyl group = Decarboxylation
• β-Dicarboxylic acids (1,3-dicarboxylic acids, also called malonic acids)
decarboxylate readily for reasons similar to β-keto acids.

25. Decarboxylation of Carboxylic Acids
25
Loss of CO2 from a carboxyl group = Decarboxylation
• COOH group at o-or p-position to OH group is easily replaced by Br or NO2 group

26. Nuclear substitution reactions
26
COOH is deactivator , thus
m-directing group:

27. 27
Enolate formation
• The pKa values for the α hydrogens of most simple aldehydes or ketones
are of the order of 19–20 that are more acidic than hydrogen atoms of
ethyne (pKa = 25), and ethene (pKa = 44) or of ethane (pKa = 50).
• The carbonyl group is strongly electron withdrawing, and when a carbonyl
compound loses an α proton, the anion that is produced, called an
enolate, is stabilized by delocalization.
The Acidity of the α Hydrogens
of Carbonyl Compounds

28. 28
Carbonyl compounds bearing an α hydrogen can undergo halogen
substitution at the α carbon in the presence of acid or base.
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon
+ H2O
+
Br -
C
CH3
O
CH2Br
Br2 / OH -
C
CH3
O
CH3
+ HBr
C
CH3
O
CH2Br
Br2 / H+
C
CH3
O
CH3

29. 29
Carbonyl compounds bearing an α hydrogen can undergo halogen
substitution at the α carbon in the presence of acid or base.
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon
(multiple halogenations can occur) Ex: Haloform reaction

30. 30
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon

31. 31
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon

32. 32
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon
α-Halo Carboxylic Acids: The Hell–Volhard–Zelinski Reaction
Carboxylic acids bearing α hydrogen atoms react
with bromine or chlorine in the presence of
phosphorus (or a phosphorus halide) to give α-
halo carboxylic acids through a reaction known as
the Hell–Volhard–Zelinski (or HVZ) reaction.
α-Iodo acyl chlorides can be obtained by using molecular iodine in a similar reaction.

33. 33
The Acidity of the α Hydrogens
of Carbonyl Compounds
Halogenation at the α Carbon

34. 34
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
Aldehydes or ketones containing α-H's, in the presence of alkali, give carbanion.

35. 35
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
Aldol condensation:
Aldehydes or ketones containing α-H's, in the presence of alkali, give carbanion.
The resulting carbanion attacks the carbonyl carbon of a second molecule. e.g.,
aldol condensation:

36. 36
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
a- Claisen-Schmidt reaction (crossed aldol):
Condensation between benzaldehyde (which does not contain α-H) and aliphatic
aldehyde or ketone (which contain α-H):

37. 37
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
a- Claisen-Schmidt reaction (crossed aldol):
Condensation between benzaldehyde (which does not contain α-H) and aliphatic
aldehyde or ketone (which contain α-H):

38. 38
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
b- Claisen reaction (for ester):
Condensation of esters (containing at least 2 α-H's) in the presence of sodium
ethoxide.
N.B. NaOH causes hydrolysis to the ester.

39. 39
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
c- Crossed Claisen reaction (for ester):
Aromatic aldehydes (or esters, which do not contain α-H) condense with an ester
(which contains α-H) in the presence of sodium ethoxide.

40. 40
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
d- Knoevenagel condensation:
Aromatic aldehydes (or other aldehydes or ketones) condense with esters having
active α- H's in the presence of weak bases (amines).

41. 41
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
e- Perkin condensation:
Aromatic aldehydes condense with a carboxylic acid anhydride to give α,b-
unsaturated acid. The reaction is catalyzed by potassium salt of the carboxlic acid.
NaOH should not be used, why ??
Benzaldehyde undergoes another reaction in the presence of NaOH.
In all these aldol-type condensations, the principle involves abstraction of α-H by a
base such as NaOH, NaOC2H5, amines, or salt of carboxlic acid.

42. 42
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
Cannizzaro reaction:
Aldehydes that do not contain α-H, in the presence of concentrated NaOH, undergo
selfoxidation-reduction reaction

43. 43
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
Crossed Cannizzaro reaction:
A mixture of two aldehydes (with no α-H's), in the presence of concentrated sodium
hydroxide, will give all possible products. If one aldehyde is formaldehyde, the
reaction yields, exclusively sodium formate and the alcohol corresponding to the
other aldehyde

44. 44
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
Crossed Cannizzaro reaction:
A mixture of two aldehydes (with no α-H's), in the presence of concentrated sodium
hydroxide, will give all possible products. If one aldehyde is formaldehyde, the
reaction yields, exclusively sodium formate and the alcohol corresponding to the
other aldehyde
C
Ar O
H
OH -
Ar C O-
H
OH
C
Ar O
H
+ Ar C O-
H
OH
Ar C
H
H
O-
+ Ar C
O
OH
H+
- H+
Ar CH2OH Ar COO-
Mechanism
Not methyl alcohol and sodium benzoate are formed.
Because the initial nucleophilic addition of hydroxide
anion is faster on formaldehyde as there are no
electron donating groups on it.

45. 45
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
intermolecular cannizzaro

46. 46
The Acidity of the α Hydrogens
of Carbonyl Compounds
Reactions of carbanion
intermolecular cannizzaro

47. 48
a,b-Unsaturated Carbonyl
compounds
1,4-addition
b a
R CH CH C
O
R'
An a,b-unsaturated carbonyl compound has a carbon-carbon double
bond in conjugation with a carbonyl group.
The resonance structures show that the b-carbon, as well as the
carbonyl carbon, carries a partial positive charge, while the
carbonyl oxygen carries a partial negative charge. This can lead to
1,4-addition.
+
CH2 CH C
O-
H
+
CH2 CH C H
O-
CH2 CH C H
O

48. 49
a,b-Unsaturated Carbonyl
compounds
1,4-addition: A) Electrophilic 1,4-Addition
So the Nucleophilic part (CN
-, Cl
-, OH
-) is added to the b-carbon,
which has a partial positive charge.
keto form
enol form
Cl CH2 CH2 C
O
H
CH2 CH C
O
Cl H
H
Cl -
+
CH2 CH C
OH
H
CH2 CH C H
OH+
H+
CH2 CH C H
O

49. 50
a,b-Unsaturated Carbonyl
compounds
1,4-addition: B) Nucleophilic 1,4-Addition
Both carbonyl carbon and b carbon can be attacked by nucleophiles
(CN-, NH2
-, OH-) to give (A) or (B).
(B)
(A)
CH2
CN CH2 C
O
CH3
CH2 CH C
OH
CH3
CN
CN -
CH2 CH C
O
CH3
The mechanism in (A) is the
same as shown in the
formation of cyanohydrin,
but in the formation of (B),
it is 1,4-addition. Both
reactions are possible.
**A highly basic reagents such as, RMgX, attack C=O, while a
weaker bases such as, CN- or R2NH, usually attack C=C.
** Aldehydes, being less hindered than ketones, usually undergo
carbonyl attack.