AMIDE

BY: ENCABO, STEPHEN O.

 AMIDE
 FUNCTIONALITY
 NOMENCLATURE
 PROPERTIES
 SOURCES AND USES
 PREPARATIONS
 REACTIONS
 ANALYSIS
 FUNCTIONALITY
 An amide is a functional group containing a
carbonyl group linked to a nitrogen atom or
any compound.
 Amides are an amine that has a single

attached carbonyl group.

Figure1: General formula of amide

 Functionality

STRUCTURE OF AMIDE

Figure 2: Structures of amide

• Primary (1°) amide has nitrogen attached to a single

carbon.
• Secondary (2°) amide has the nitrogen attached to two
carbons.
• Tertiary (3°) amide has the nitrogen attached to three
carbons.
• Lactam is a cyclic amide.
 NOMENCLATURE
 Amides are amine derivatives of carboxylic acids.
 The root name is based on the longest chain including the
carbonyl group of the amide group.
 Since the amide group is at the end of the chain, the C=O
carbon must be C-1.
 The amide suffix is appended after the hydrocarbon suffix
minus the "e" : e.g.  -ane + -amide = -anamide etc.
 If the amide nitrogen is substituted, then these substituents
are given N- as the locant.
 The N- locant is listed first.
 Nomenclature

Butanamide N-methylbutanamide N,N-dimethylethanamide

Benzamide N-phenylethanamide
3-chlorobenzamide
 Nomenclature

4-ethyl-5-hydroxyhexanamide 3-bromo-5-chloro-4-
fluorocyclohexanecarboxamide

N-phenylbutanamide
Nomenclature
 PROPERTIES
Acidity and Basicity of Amides
 Amides (RCONH2) are non-basic. Amides aren’t protonated by
aqueous acids, and they are poor nucleophiles.
 Amide is stabilized by delocalization of the nitrogen lone-pair

electrons through orbital overlap with the carbonyl group.

Delocalization reduces an amide's basicity because the electron
pair is not associated with a single atom reducing the intensity
and
focus of its proton drawing ability. Delocalization also helps to
stabilize the overall structure of the amide and as a result more
energy would be required to break the shared electron structure.
This amide resonance stabilization is lost when the nitrogen atom
is protonated, so protonation is disfavored.

Figure 3: Delocalization of Nitrogen Lone Pair

 Properties

 The N–H bonds of amides are much more acidic than the N–H
bonds of amines. This is to delocalization. The attached carbonyl
group allows the lone pair of the conjugate base to be
delocalized through resonance.

Figure 4: N-H bonds of Amides

 Properties

Solubility of Amide
 Amides contain (C=O) and (N-C) dipoles arising from covalent
bonding between electronegative oxygen and nitrogen atoms
and electro-neutral carbon atoms. Primary and secondary
amides also contain two- and one N-H dipoles, respectively.
Because of the pi-bonding arrangement of the carbonyl and
the greater electronegativity of oxygen, the carbonyl (C=O) is
a stronger dipole than the N-C dipole. The presence of a C=O
dipole and, to a lesser extent a N-C dipole, allows amides to
act as H-bond acceptors. In primary and secondary amides,
the presence of N-H dipoles allows amides to function as H-
bond donors as well. Thus amides can participate in hydrogen
bonding with water and other protic solvents; the oxygen and
nitrogen atoms can accept hydrogen bonds from water and
the N-H hydrogen atoms can donate H-bonds. As a result of
interactions such as these, the water solubility of amides is
greater than that of corresponding hydrocarbons.
 Properties

Boiling Point and Melting Point

 Amides have relatively high boiling points

and melting points due to the hydrogen

bonding between the partially positive
hydrogen atoms the –NH2 group and another
electronegative oxygen. Each simple amide
has two partially positive hydrogen atoms and
two pairs of electrons on the oxygen allowing
for multiple possible sites of hydrogen
bonding. A lot of energy is required to break
these hydrogen bonds increasing the melting
point of amides.
 Properties

Figure 5: Hydrogen Bonding in Amides. Amide molecules can engage in hydrogen

bonding with water molecules (a). Those amides with a hydrogen atom on the
nitrogen atom can also engage in hydrogen bonding (b). Both hydrogen bonding
networks extend in all directions.
 Properties

Table 1. Physical properties of some unsubstituted amide

 SOURCES AND USES
 Amides occur naturally in plant and animals.
 Nicotinamide occurs in trace amounts mainly

in meat, fish, nuts, rice and mushrooms, as

well as to a lesser extent in some vegetables
as a source of vitamin B.
 Yeast (Saccharomyces cerevisiae-acetamide),

and liver extract and milk are important

sources of amides.

Nicotinamide Acetamide
 Sources and Uses

 Proteins are large biological molecules made

up of long chains of smaller molecules called
amino acids. Amino acids are organic
molecules that contain an amine functional
group (–NH2), a carboxylic acid functional
group (–COOH), and a side chain (that is
specific to each individual amino acid).
Organisms rely on proteins for a variety of
functions—proteins transport molecules
across cell membranes, replicate DNA, and
catalyze metabolic reactions. 
 Sources and Uses

 Urea is the end product of protein

metabolism that is most commonly used as
nitrogen fertilizer.
 Amides such as phenobarbital, Nembutal and

Seconal are barbiturates. Barbiturates are

sedative-hypnotics, a type of central nervous
system (CNS) depressant used to treat
insomnia, seizures, and headaches.

Urea Barbiturates
 Sources and Uses

 Acetaminophen, also known as paracetamol

is used to reduce fever and pain.
 Saccharin is an artificial sweetener.

Saccharin Acetaminophen
(Sulfobenzimide) N-(4-Hydroxyphenyl)acetamide
 Sources and Uses

 Kevlar
Kevlar is a very strong material - about five times as
strong as steel, weight for weight. It is used in
bulletproof vests, in composites for boat construction,
in lightweight mountaineering ropes, and for
lightweight skis and racquets - amongst many other
things.
 The line up and removing of water between the -COOH
and -NH2 groups of two monomers, benzene-1,4-
dicarboxylic acid and 1,4-diaminobenzene.
 Sources and Uses

 Polyamides (Nylons)
First prepared by Wallace Carothers at the DuPont Company
by heating a diamine with a diacid. For example, nylon 66 is
prepared by reaction of adipic acid (hexanedioic acid) with
hexamethylenediamine (1,6-hexanediamine) at 280 °C. The
designation “66” indicates the number of carbon atoms in the
diamine (the first 6) and the diacid (the second 6).
Sources and Uses
 PREPARATIONS
 Conversion of Carboxylic Acids into Amides
Amides are usually prepared by activating the carboxylic
acid with dicyclohexylcarbodiimide (DCC), followed by addition
of the amine. The acid first adds to a C=N double bond of
DCC, and nucleophilic acyl substitution by amine then ensues.
Alternatively, and depending on the reaction solvent, the
reactive acyl intermediate might also react with a second
equivalent of carboxylate ion to generate an acid anhydride
that then reacts with the amine. The DCC-induced method of
amide formation is the key step in the laboratory synthesis of
small proteins, or peptides.
 Preparation

 Conversion of Acid Halides into Amides:

Aminolysis 
Acid chlorides react rapidly with ammonia and amines to
give amides. The reaction of acid chlorides with amines is the
most commonly used laboratory method for preparing amides.
Both monosubstituted and disubstituted amines can be used,
but not trisubstituted amines (R3N). Because HCl is formed
during the reaction, two equivalents of the amine must be
used. One equivalent reacts with the acid chloride, and one
equivalent reacts with the HCl by-product to form an
ammonium chloride salt.
 Preparation

If, however, the amine component is valuable, amide

synthesis is often carried out using one equivalent of the
amine plus one equivalent of an inexpensive base such as
NaOH.
 Preparation

 Conversion of Acid Anhydrides into Amides 

Acetic anhydride is also commonly used to prepare N-
substituted acetamides from amines. For example,
acetaminophen, a drug used in over-the-counter analgesics
such as Tylenol, is prepared by reaction of p hydroxyaniline
with acetic anhydride. Only the more nucleophilic -NH2 group
reacts rather than the less nucleophilic -OH group. Only half of
the anhydride molecule is used, while the other half acts as the
leaving group during the nucleophilic acyl substitution step
and produces acetate ion as a by-product. Thus, anhydrides
are inefficient, and acid chlorides are normally preferred for
introducing acyl substituents other than acetyl groups.
 Preparation

 Conversion of Esters into Amides: Aminolysis 

Esters react with ammonia and amines to yield amides. The
reaction is not often used, however, because it’s usually easier
to prepare an amide by starting with an acid chloride.
 REACTIONS
 Conversion of Amides into Carboxylic Acids:
Hydrolysis 
Amides undergo hydrolysis to yield carboxylic acids plus
ammonia or an amine upon heating in either aqueous acid or
aqueous base. Acidic hydrolysis reaction occurs by
nucleophilic addition of water to the protonated amide,
followed by transfer of a proton from oxygen to nitrogen to
make the nitrogen a better leaving group, and subsequent
elimination. The steps are reversible, with the equilibrium
shifted toward product by protonation of NH3 in the final step.
 Reaction

Basic hydrolysis occurs by nucleophilic addition of OH- to

the amide carbonyl group, followed by elimination of amide
ion (-NH2) and subsequent deprotonation of the initially
formed carboxylic acid by ammonia. The steps are reversible,
with the equilibrium shifted toward product by the final
deprotonation of the carboxylic acid. Basic hydrolysis is
substantially more difficult than the analogous acid-catalyzed
reaction because amide ion is a very poor leaving group,
making the elimination step difficult.
 Reaction

 Conversion of Amides into Amines: Reduction

Amides can be reduced by LiAlH4. The product of the
reduction is an amine. The net effect of an amide reduction
reaction is thus the conversion of the amide carbonyl group
into a methylene group (C=O → CH2). This kind of reaction is
specific to amides and does not occur with other carboxylic
acid derivatives.
 Reaction

Amide reduction occurs by nucleophilic addition of hydride

ion to the amide carbonyl group, followed by expulsion of the
oxygen atom as an aluminate anion leaving group to give an
iminium ion intermediate. The intermediate iminium ion is
further reduced by LiAlH4 to yield the amine.

The reaction is effective with both acyclic and cyclic

amides, or lactams, and is a good method for preparing cyclic
amines.
 ANALYSIS
 Infrared Spectroscopy
All carbonyl-containing compounds have intense IR
absorptions in the range 1650 to 1850 cm-1. The exact
position of the absorption provides information about the
specific kind of carbonyl group.
 Amides absorb near the low-wave number end of the carbonyl
region, with the degree of substitution on nitrogen affecting
the exact position of the IR band. That is, for amides, the
delocalization of electron density (resonance) from nitrogen
into the carbonyl lengthens the C=O bond and lowers its
stretching frequency.
Analysis
QUIZ
 I. Give the IUPAC names for the following compounds.

2. 3.
1.

II. Draw the structure of the following:

4. N-(4-Hydroxyphenyl)acetamide
5. 3-bromo-5-chloro-4-fluorocyclohexanecarboxamide
6. 4-ethyl-5-hydroxyhexanamide
ANSWERS
 1. 2,2,2-tribromo-4-hydroxyheptanamide
 2. N-ethyl-N-methylbenzamide
 3. N-phenylbenzamide
 4. 5.

 6.