Chapter 6 Amines and Amides

Nitrogen-Containing Functional Groups

• Nitrogen is in Group V of the periodic table, and in
Chapter 6 most of its compounds, it has three single bonds and
one lone pair:
Amines and Amides N

Chapter Objectives:
• Learn to recognize the amine and amide functional groups.
• In this chapter, we will take a look at two functional
• Learn the IUPAC system for naming amines and amides.
groups which contain nitrogen atoms connected to
• Learn the important physical properties of the amines and amides. carbons: the amines and the amides.
• Learn the major chemical reactions of amines and amides, and learn how to predict the O
products of amide synthesis and hydrolysis reactions.
• Learn some of the important properties of condensation polymers, especially the
polyamides. R N R'' R C N R'
Mr. Kevin A. Boudreaux
Angelo State University R' R"
CHEM 2353 Fundamentals of Organic Chemistry Amine Amide
Organic and Biochemistry for Today (Seager & Slabaugh)
www.angelo.edu/faculty/kboudrea 2

Amines
• Amines and amides are abundant in nature. They
are a major component of proteins and enzymes,
nucleic acids, alkaloid drugs, etc. (Alkaloids are N-
containing, weakly basic organic compounds;
thousands of these substances are known.)

Classification and
• Amines are organic derivatives of ammonia, NH3, in
which one or more of the three H’s is replaced by a
carbon group.
Nomenclature of Amines • Amines are classified as primary (1°), secondary
(2°), or tertiary (3°), depending on how many
carbon groups are connected to the nitrogen atom.

H N H R N H R N H R N R''

H H R' R'
3
Ammonia 1° Amine 2° Amine 3° Amine 4

Examples: Classifying Amines Nomenclature of Amines

• Classify the following amines as primary (1°), • Simple 1°, 2°, and 3° amines: common (trivial)
secondary (2°), or tertiary (3°). names are obtained by alphabetically arranging the
names of the alkyl substituents on the nitrogen and
H CH3 NH2 adding the suffix -amine (e.g., ethylmethylamine).

CH3CH2CH2 N H CH3CH2CHCH3
• Amines in the IUPAC system: the “e” ending of
CH3 N CH3
the alkane name for the longest chain is replaced
with –amine. The amine group is located by the
position number. Groups that are attached to the
nitrogen atom are located using “N” as the position
H
number. More complex primary amines are named
with —NH2 as the amino substituent.
CH3CH2 N CH3 N NH2
N • Aromatic amines: named as derivatives of the
H parent compound aniline. Substituents attached to
the nitrogen are indicated by using “N-” as the
location number.
5 aniline 6
Chapter 6 Amines and Amides

Examples: Nomenclature of Amines Examples: Nomenclature of Amines

• Provide common names for the following 2° and 3° • Provide common names for the following 2° and 3°
amines; for 1° amines, provide common and/or amines; for 1° amines, provide common and/or
IUPAC names where possible. IUPAC names where possible.
H NH2 CH3

CH3 NH2 CH3 N CH3 CH3CH2CH2CHCH3 CH3 N CH3

H
NH CH3 CH3CHCH2CH2 NH2
CH3 N CH2CH3 CH3CH2CH2 NH2
CH3CH2CH2CHCH3 NH2

7 8

Examples: Nomenclature of Amines Examples: Nomenclature of Amines

• Provide common names for the following 2° and 3° • Provide names for the following aromatic amines.
amines; for 1° amines, provide common and/or
IUPAC names where possible. NH CH3 NH2

OH

O NH2 NH2
CH3

CH3CCH2CH2CH2CHCH3
CH3 CH3 CH3 CH2CH3
N N

9 10

Examples: Nomenclature of Amines Examples: Nomenclature of Amines

• Provide names for the following aromatic amines. • Draw structural formulas for the following molecules:
– ethylisopropylamine
CH3 CH3 CH3 H
N N

– tert-butylamine
CH3 CH2CH3

CH3 CH3
N
– 2-pentanamine

CH3CH2 CH3
11 12
Chapter 6 Amines and Amides

Examples: Nomenclature of Amines Examples: Nomenclature of Amines

• Draw structural formulas for the following molecules: • Draw structural formulas for the following molecules:
– N-methyl-2-propanamine – N-methyl-2-chloroaniline

– 1,6-diaminohexane – N,3-diethylaniline

– 3-amino-1-propanol – N,N-dimethylaniline

13 14

Physical Properties of Amines: H-Bonding

• 1° and 2° amines can hydrogen bond to each other:
CH3 N H CH3 N CH3

H H
H H

Physical Properties of CH3 N H N H CH3 N H N CH3

Amines
H CH3 CH3 CH3
• 3° amines cannot hydrogen bond to each other:
CH3 N CH3

CH3 CH3
X
CH3 N CH3 X N CH3
15 16
CH3 CH3

Physical Properties of Amines: Boiling Points Physical Properties of Amines: Boiling Points
• Nitrogen is less electronegative than oxygen, so the Boiling Point:
N—H bond is not quite as polar as the O—H bond. Carboxylic acid
– Hydrogen bonds from N—H’s are not as strong Alcohols
as those resulting from O—H’s. 1°/2° Amines
– Hydrogen bonding between 1° and 2° amines is 3° Amines/Alkanes
not as strong as those found in alcohols or
carboxylic acids. Name Molecular Boiling
weight point
• 1° and 2° amines have lower boiling points than
alcohols of similar molecular weight. Acetic acid 60.0 g/mol 118°C
1-propanol 60.1 g/mol 97°C
• 3° amines, since they do not hydrogen bond to each
other, have boiling points similar to hydrocarbons of propyl amine 59.1 g/mol 48°C
the same molecular weight. ethylmethylamine 59.1 g/mol 36°C
trimethylamine 59.1 g/mol 2.9°C
17
butane 58.1 g/mol -0.5°C 18
Chapter 6 Amines and Amides

Physical Properties of Amines: Water Solubility Physical Properties of Amines: Odor

• 1°, 2°, and 3° amines can all form hydrogen bonds • Low molecular-weight amines tend to have sharp,
with water. penetrating odors similar to ammonia
• Low-molecular weight amines are generally water- • Higher molecular-weight amines often smell like
soluble. rotting fish, and are often found in decaying animal
tissues.
H H H
NH2 NH2
O O O
CH3 N CH3 CH2CH2CH2CH2 CH2CH2CH2CH2CH2
H H H H H
CH3 NH2 NH2
CH3 N H O CH3 N H O CH3 N CH3
Trimethylamine 1,4-Diaminobutane 1,5-Diaminopentane
H H CH3 H CH3 Responsible for the (Putrescine) (Cadaverine)
odor of rotting fish A poisonous oil present in A poisonous, viscous liquid
O rotting flesh; produced present in rotting flesh;
H H during the decomposition of produced during the
the amino acid arginine; also decomposition of the amino
partially responsible for the acid lysine; also partially
odor of urine and bad breath responsible for the odor of
19 20
urine and bad breath

Examples: Predicting Physical Properties Examples: Predicting Physical Properties

• Arrange the following compounds in order of
increasing boiling point. (All of the compounds
have about the same molecular weight.)
propanoic acid, diethylamine, 1-butanol,
ethyldimethylamine
• Which member of each of the following pairs of
compounds would you expect to have a higher
boiling point?
– 2-aminopropane or 2-aminohexane

– triethylamine or 1-aminohexane

– propanoic acid or diethylamine

– 1-pentanol or 1-aminopentane
21 22

Important Alkaloids
O O
CH3 CH3 H
CH3 N H
N N
N N

CH3
O N N N N
O N
Nicotene

Some Important
CH3 CH3 Found in tobacco plants; mild
Caffeine Theobromine stimulant in small doses;
Found in the seeds of Coffea arabica, Found in the seeds of addictive, but not especially
roasted coffee beans; inhibits the action of Theobroma cacao; the harmful itself

Alkaloids
phosphodiesterase, an enzyme which stimulating ingredient in
inhibits cyclic adenosine monophosphate chocolate.
(AMP), which is responsible for forming
glucose in the bloodstream
CH3 N
HO
N

CH3O

N
Dextromethorphan Quinine
23 CH3O Antimalarial drug from cinchona tree 24
Ingredient in cough suppressants.
Chapter 6 Amines and Amides

CH3 CH3 CH3 O O CH2CH3

N O N N H N
N CH2CH3
OCH3 CH3O
O H
H N
H CH3
O H H N H
O O
H
O O O OH Melatonin
A naturally occuring hormone produced in the
pineal gland; its production is triggered by the N
absence of light; causes drowsiness in humans H
Lysergic acid diethylamide (LSD)
at night, triggers birds to migrate, and signals
OH A synthetic hallucinogen from alkaloids obtained
dogs to shed their winter coats; sold as a
from ergot, a fungus which grows on rye
Cocaine Atropine treatment for jet lag.
The form which is “snorted” relaxes muscles and reduces secretion OH
is the hydrochloride salt; the of saliva during surgery; used to Scopolamine
free-base “crack” form is dilate pupils for eye examinations. Strychnine N
used in treatment of motion H N N
burned and inhaled, and sickness A poison from strychnos
O
reaches the brain in 15 plant (Nux vomica); used
H3C CH3 as a rat and mouse poison N N
seconds. H H HO P
O
N+
R N OH
N Zephiran chloride H
OH OH
H H (benzalkonium chloride) O O
Coniine Antiseptic compound that kills H Inosine Monophosphate (IMP)
Poison from hemlock bacteria and fungi on contact With monosodium glutamate (MSG), one of the
25
major substances responsible for the flavor of meat 26

Nitrogen Wastes
The disposal of waste nitrogen from the body is a problem which different species of animals
have solved in different ways:
O H O OH
H
O NH2 O
H N
N NH2
HO CH3O CH3 O N O
O O N N NH2
O N N
O N N
O H H
H H
H H
O O O Allantoic acid
N N N Allantoin Marine vertebrates further
Uric acid
O Most mammals contain enzymes metabolyze allantoin into
CH3 CH3 CH3 Birds, reptiles and insects excrete nigrogen
which metabolyze uric acid into allantoic acid.
wastes in the form of uric acid. Uric acid can
allantoin.
HO HO CH3 O be eliminated directly in the solid form, without
being dissolved in water. It is produced in the O
Morphine Codeine Heroin body from foods and beverages rich in purines,
Found in the opium poppy; a Used in some cough syrups to More fat-soluble than morphine, such as claret and port. Lactic acid inhibits the H H
CNS depressant; very effective depress the action of the cough and must be injected directly into removal of salts of uric acid in the urine; these N N NH4+ X–
painkiller center of the brain the bloodstream, but crosses the salts instead deposit in the joints, causing gout. Marine invertebrates excrete
blood-brain barrier more readily, Dalmations have been bred to have black spots H H ammonium salts.
causing it to be more potent than with no white hairs in them on their coats; Urea
morphine however, the gene which determines the Urea is the major organic
presence of white hairs is linked to the gene component of urine; about 25 g
which codes the enzyme which breaks down are excreted every day by
uric acid into allantoin. Dalmations thus humans. Cartilaginous fish and
excrete uric acid instead of allantoin, and are amphibians also excrete urea.
27 28
very susceptible to gout.

Antihistamines Antihistamines
O
NH2
Cl

N N HO
H N OH
Histamine
People who are allergic to pollen produce histamine, which causes blood vessels
to dilate and leak, releasing fluid into surrounding tissues, causing watery eyes,
sniffles, congestion, and other symptoms of hay fever (allergic rhinitis); also N N
causes the symptoms of the common cold and swelling after insect bites. OH

O Fexofenadine (Allegra®)
CH3 O
A non-drowsy antihistamine; available by
Loratadine (Claritin®)
N perscription only
A non-drowsy antihistamine
O CH3 CH3

CH3
N

OH H N

Diphenylhydramine Ephedrine / Pseudoephedrine N OH

an antihistamine; active ingredient in Benadryl; found in the Chinese ma-huang plant; a Cl O
sometimes used in sleeping pills decongestant used in many cold remedies Cetrizide (Zyrtec®)
A stronger antihistamine than Allegra or O
29 Claritin, but causes drowsiness in some people 30
Chapter 6 Amines and Amides

Bases
• A base takes a proton (H+) from another species.
A base produces hydroxide ions, OH–, when
dissolved in water:
B + H2O  BH+ + OH–
• A strong base is one that completely dissociates in

Reactions of Amines
water (i.e., every molecule of the acid splits apart).
• A weak base is one in which only a small
percentage of the molecules are dissociated at any
one time.

• Acidic solution: pH < 7.00 ([H3O+] > [OH-])

• Basic solution: pH > 7.00 ([H3O+] < [OH-])
31 • Neutral solution: pH = 7.00 ([H3O+] = [OH-]) 32

Chemical Properties of Amines: Basicity Alkylammonium Salts

• Amines are weak organic bases. They react with • Salts of amines are named by changing “amine” to
water to produce alkylammonium ions and “ammonium” and adding the name of the negative
hydroxide anions: ion to the end of the word:
H C2 H3 O 2
H H

+ + OH CH3 NH3 Cl CH3 N CH2CH3

R N H O R N H
methylammonium
H chloride H
H H ethylmethylammonium
acetate
• and with acids to produce alkylammonium salts: CH2CH3
H H
CH3CH2 N CH2CH3
R N + H Cl R N H Cl Br
H
H H triethylammonium
33 bromide 34

Alkylammonium Salts Chemical Properties of Amines: Basicity

• Salts of amines are generally white crystalline solids • Ammonium salts may be converted back into neutral
with high melting points. amines by a strong base:
• The ionic charges makes these salts more soluble in
water than the neutral amines. Many amine- R—NH3+ Cl- + NaOH  R—NH2 + H2O + NaCl
containing drugs are administered in the form of
alkylammonium salts to increase their solubility in
bodily fluids.
H3 C H3C H • Thus, by adjusting the pH of the solution, it is
N HSO4- N
possible to influence whether an amine is present in
the neutral form or as its ammonium cation form:
acid
+ H2SO4 (low pH)
-
R NH2 + H2O R NH3+ + OH
base
amine alkylammonium
(high pH)
ion
O O
HO OH HO OH
Morphine Morphine sulfate 35 36
water-insoluble water-soluble
Chapter 6 Amines and Amides

Quaternary Ammonium Salts Examples: Basicity of Amines

• In addition to salts of 1°, 2°, and 3° amines, it is • Complete the following reactions:
possible to have amine cations which contain four
alkyl groups attached to a nitrogen atom, which will CH3NH2 + HCl
always carry a positive charge, regardless of the pH
of the surrounding solution. These are known as
quaternary ammonium salts. NHCH3

R''' CH2CH3 + HCl

R N+ R'' X- CH3 N+ CH2CH3 Cl-

R' CH2CH3
CH3
quaternary triethylmethylammonium chloride Cl
ammonium salt
CH3 N H + NaOH
• These salts are present in many antiseptics and
antibacterial agents. CH3
37 38

Amides
• Amides contain a nitrogen which is directly attached
to a carbon in a carbonyl group:
O amide linkage (peptide bond)

R C N R'

Amides R"
Amide

O O O

R C N H R C N CH3 R C N CH3

H H CH3
N,N-unsubstituted amide N-substituted amide N,N-disubstituted amide
39 40

Nomenclature of Amides Examples: Nomenclature of Amides

• Amides are named by changing the -oic acid ending • Name the following compounds:
of the corresponding carboxylic acid to -amide. If O O
alkyl groups are attached to the nitrogen, they are
named as N-alkyl substituents. CH3 C N CH3 CH3 N C CH3
O O H CH3
O
H C OH H C NH2
methanoic acid methanamide C
(formic acid) (formamide) NH2
O CH3
O O
CH3 N C C CH3
benzamide
CH3 C OH CH3 C NH2
ethanoic acid ethanamide CH3 CH3
(acetic acid) (acetamide)

41 42
Chapter 6 Amines and Amides

Examples: Nomenclature of Amides Examples: Nomenclature of Amides

• Name the following compounds: • Name the following compounds:
CH2CH3 O CH3
O CH3
CH3CH2CH2CHCH2 C N CH2CH3
CH3CH2CH2 C N CH2CH3

NH2 O
CH3
CH3CH2CH2CHCH C N CH3
CH3 O CH2CH3 CH2CHCH3

CH3 H CH3 N C CHCH2CH2CCH3

CH3
43 44

Examples: Nomenclature of Amides Examples: Nomenclature of Amides

• Name the following compounds: • Name the following compounds:
O O

C CH3 C
CH3 N N CH3
H
H

O O

C CH3 C
N CH3 N CH3

CH3 CH3

CH3
45 46

Examples: Nomenclature of Amides Examples: Nomenclature of Amides

• Draw structural formulas for the following molecules: • Draw structural formulas for the following molecules:
– 2-methylpropanamide – N,2-diethylbenzamide

– N,2,4-trimethylpentanamide – N,N,2,3,4-pentamethylbenzamide

– N-ethyl-N-methylacetamide – N,N,4,4-tetramethylbutanamide (what’s wrong with this name?)

47 48
Chapter 6 Amines and Amides

Physical Properties of Amides

• N,N-unsubstituted amides can form a complex
network of hydrogen bonds. They tend to have high
melting points and also high boiling points.
O

Physical Properties of
R C N H

H
H

Amides R
O

C N H O
N

C
H

H R

R C N H
49 50
H

Physical Properties of Amides Examples: Predicting Physical Properties

• N-substituted amides often have lower melting
points and boiling points than N,N-unsubstituted
amides because fewer hydrogen bonds can form.
• N,N-disubstituted amides cannot form hydrogen
bonds, and have even lower melting points and
boiling points.
• All amides can hydrogen bond with water, so low-
molecular weight amides are water-soluble.
• Arrange the following compounds in order of
increasing boiling point. (All of the compounds
have about the same molecular weight.)
N-ethylethanamide
butanamide
N,N-dimethylethanamide

Boiling Point:
N,N-unsubstituted amides
N-substituted amides
N,N-disubstituted amides
51 52

Important Amides

H O
O
N
N
CH2CH3
Cl N O
O N

Important Amides
CH2CH3 O N O

Diazepam (Valium)
A benzodiazepene
tranquilizer; acts by
enhancing the inhibitory
neurotransmitter GABA;
since it binds to the same
protein as ethanol,
combinations of valium and
ethanol can be deadly
H
Thalidomide
Until 1956, a very popular, safe
sedative; the largest market was for
CH3
pregnant women who were
experiencing morning sickness.
N,N-Diethyl-m-toluamide
Active ingredient in OFF However, it caused massive birth
defects in women who used it in the
early states of pregnancy, and was
banned in Europe; it was never
authorized for sale in the U.S.

53 54
Chapter 6 Amines and Amides

Hot Stuff Barbiturates

O H
O H
O N C S N
N
O
CH3O S
Allyl isocyanate
N N
Capsaicin Used in horseradish flavor, N
H Found in red and green chili mustard oil, pickles, salad O H
HO peppers; active component of dressings and sauces; mustard Barbituric acid O H
paprika plasters, medications and First synthesized by Adolf von Baeyer in 1864; Thiopental (Pentothal)
fumigants barbiturates are soporifics, and are used as An intravenous anesthetic
tranquilizers and anesthetics; many are also
addictive, and overdoses can be fatal. (Other
barbiturates include Seconal, Veronal,
Phenobarbitol, Thiopental, Amobarbitol, etc.)
O O
Piperine
O Component of white and O H O H
CH3O
black pepper N N
N O O
HO Zingerone
N N
The pungent, hot component of ginger
O O H
O H
Amobarbital (Amytal) Phenobarbitol
Used in the treatment of insomnia Anti-seizure medication, sedative
55 56

Sulfa Drugs Penicillin

N O O R=
N S NH2 H2N S NH2
NH2 O O H Penicillin G
O
Prontosil Sulfanilamide N
O OH S
O CH3
R
OH O
O Penicillin V
N N CH3
H H O OH
O
O N CO2H
H N Folic acid
N
H2N Penicillin Ampicillin
para-Aminobenzoic aid
(PABA) NH2
H2N N N
OCH3
Penicillin is an antibiotic compound produced by
Sulfanilamide, the first antibiotic, was discovered by Gerhard Damagk (Nobel Prize, the molds Penicillium notatum and Penicillium
1939), who observed the antibacterial action of the red dye Protonsil; further researched chrysogenum; it was discovered by Alexander
showed that it was the metabolic byproduct, sulfanilamide, which was the active form. Fleming in 1928 in a culture of bread mold. There Methicillin
It prevents bacteria from synthesizing folic acid, which they need in order to grow. are several varieties: Penicillin G and Methicillin
Bacterial enzymes synthesize folic acid using para-aminobenzoic acid (PABA); are administered by injection; Penicillin V is an
sulfanilamide fits into the enzyme more tightly, blocking it from taking up PABA, and oral form which is not broken down in the OCH3
thus blocking folic acid synthesis. The bacterium cannot grow, and eventually dies. stomach; Ampicillin is a broad spectrum penicillin
Humans obtain folic acid from their diet (an essential vitamin), so sulfa drugs do not which can be administered by injection or orally
harm people in this way (although they can cause allergic reactions). 57 58

Molecules To Dye For Molecules To Dye For

• Dyes are compounds that can be used to color other materials, such as
clothing, paper, hair, etc.
CH3 N CH3
• Many organic dyes contain a long series of double bonds that are close
together. If the chain of double bonds is long enough, these molecules
can absorb low-energy light in the visible region of the electromagnetic H
N N NH2
spectrum, resulting in colors that are visible to the human eye. 2_
SO4
O H O H

N N Br

N N
H O
Indigo
A naturally occurring blue dye which has been
used for thousands of years. It is obtained
from an Indian plant (Indigofera tinctoria) and
the European woad (Isatis tinctoria). Today,
indigo can be made synthetically, and is used
in dyeing denim to make blue jeans.
Br
H O
Tyrian purple
6,6'-dibromoindigo
Tyrian purple, or “royal purple,” is a purple dye
originally obtained from a species of mollusk (Murex)
found near the cities of Tyre and Sidon in ancient
Phoenicia. It took about 9,000 mollusk shells to
obtain one gram of the dye, making it very expensive.
This dye was used by royalty (hence the name “royal
purple”) and the Roman aristocracy.
59
CH3 2
Mauve
This is the first of the synthetic dyes. It was discovered by the
18-year-old English chemist William Henry Perkin in his home
laboratory, while attempting to synthesize quinine (the only known
treatment for malaria at that time). While cleaning up the sludge
from one of his failed attempts, he noticed that the sludge was turning
the water in his sink violet, and that cloth would pick up this purple
color. Perkin patented his serendipitous discovery, and went into
business making dyes, becoming so successful that he was able to
retire at the age of 36 to focus his attention on chemical research.
60
Chapter 6 Amines and Amides

FD&C Dyes FD&C Dyes

NaO3S
These color additives are approved by the Food and Drug Administration NaO3S
(FDA) under the Federal Food, Drug, and Cosmetic Act (FD&C, 1938,
amended 1997) for use in foods. CH3 OCH3
O H
NaO3S N N N
N N
- SO3Na
SO3
SO3Na
N SO3Na HO
HO
H O
FD&C Red No. 40 CO2Na
NaO3S SO3Na FD&C Blue No. 2
Indigo Carmine, Indigotine Allura Red AC FD&C Yellow No. 6
N N
N Sunset Yellow FCF
FD&C Blue No. 1 N
Brilliant Blue FCF N
NaO3S N
I I
OH HO
NaO O O
FD&C Yellow No. 5
SO3Na
Tartrazine
CO2CH2CH3 CH3 OCH3
I I
-
SO3
CO2Na N
N N N
N
NaO3S N
NaO3S SO3Na HO HO
N N FD&C Red No. 3
Erythrosine Orange B SO3Na
FD&C Green No. 3 Used in sausage and Citrus Red No. 2
Fast Green FCF 61 frankfurter casings Used to color orange skins 62

Molecules To Dye For Molecules To Dye For

O
CH3 H3C CH3
N N N N

CH3 N SO3Na
Methyl orange N
HO O O
N NO2 Resazurin
OH OH
CH3 O Para red N
CH3 Cl
N N
N N CH3 CH3 H3C Cl CH3
CH3 N N S N N N
Methyl red CH3 N
CH3 Methylene Blue CH3 Methyl violet 10B
Butter yellow CH3 (crystal violet) CH3

OH HO
NH2 H2N

N N
N N
N N
N N
HO3S NH2 H2N SO3H O O
S S
CH3O Chicago blue OCH3 O O
NaO Congo red ONa
SO3H HO3S 63 64

Amide Formation
• Amides are formed when acid chlorides react with
1° or 2° amines; 3° amines cannot form amides:
O H O H

R C Cl + R' N H R C N R' + HCl

Reactions of Amides O R'' O R''

R C Cl + R' N H R C N R' + HCl

O R''

R C Cl + R' N R''' no reaction

65 66
Chapter 6 Amines and Amides

Amide Formation Examples: Formation of Amides

• Amides are also formed when acid anhydrides react • Complete the following reactions:
with 1° or 2° amines.
O CH3
O O H O H O
C Cl + CH3 N H
R C O C R + R' N H R C N R' + HO C R

O O R'' O R'' O

R C O C R + R' N H R C N R' + HO C R

O O R''

R C O C R + R' N R''' no reaction

67 68

Examples: Formation of Amides Examples: Formation of Amides

• Complete the following reactions: • Complete the following reactions:
O O O CH3

CH3 C O C CH3 + CH3CH2CH2NH2 CH3 C Cl + CH3 N CH3

69 70

Chemical Properties of Amides Examples: Reactions of Amines and Amides

• Unlike amines, amides are not basic. • Complete the following reactions:
• Amide hydrolysis can take place under acidic or O H
basic conditions:
CH3 C N CH3 + H2O + HCl
O R'' O R''

R C N R' + H2O + HCl R C OH + H N+ R' Cl-

H O H

O R'' O R'' CH3 C N CH3 + NaOH

- +
R C N R' + NaOH R C O Na + H N R'

71 72
Chapter 6 Amines and Amides

Condensation Polymers: Polyamides

O O
H2N (CH2)6 NH2 C (CH2)10 C H2N (CH2)6 NH2

1,6-diaminohexane Cl sebacoyl chloride Cl 1,6-diaminohexane

O O

C (CH2)10 C

H2N (CH2)6 N N (CH2)6 NH2

H H

Condensation Polymers: O
C (CH2)10 C
O O
C (CH2)10 C
O O
C (CH2)10 C
O

Polyamides
Cl N (CH2)6 N N (CH2)6 N Cl
H H H H

O O O O O O

C (CH2)10 C C (CH2)10 C C (CH2)10 C

H2N (CH2)6 N N (CH2)6 N N (CH2)6 N N (CH2)6 NH2

H H H H H H

O O O O O O O O O O

C (CH2)10 C C (CH2)10 C C (CH2)10 C C (CH2)10 C C (CH2)10 C

Cl N (CH2)6 N N (CH2)6 N N (CH2)6 N N (CH2)6 N Cl

H H H H H H H H

73 74
etc.

Condensation Polymers: Polyamides Polyamides

O O

C (CH2)10 C
NH2 O
Cl NH—(CH2)6—HN H
n
Nylon-6,12 H
H2N
a polyamide N
Discovered by Wallace Carrothers at DuPont in 1934; polymers + O
average about 10,000 g/mol; 3 billion pound of Nylon made per O
O
year; 60% used for nylon fiber in home furnishings (carpet); also N
used in textile fibers, tire cord, rope, parachutes, paint brushes, Cl
H
Velcro, electrical parts, medical applications (sutures, etc.) Kevlar
Cl used in bullet-proof vests and tire cords
O O O O (an aramid, "aromatic polyamide")
O
C N N C C N N C
O
H H H H
O O O O

C N N C C N N C

H H H H
O O O O

C N N C C N N C
75 76
H H H H

Polyamides Polyurethanes
R N C O R N C O
O
H OR H OR
C
H2N NH2 Isocyanate + alcohol A Urethane
N

O O O O OH
H3C N C O
+ HO OH
O O N N
Toluene diisocyanate Glycerol
H H
Cl Cl OH
Nomex O OH
Insulates ceramic tiles on the space shuttle; used in firefighting
equipment, race car driver suits, flight suits, the airbags on the Mars O C
Pathfinder, Spirit, and Opportunity rovers (less strong than Kevlar,
but has excellent thermal, chemical, and radiation resistance) HN
OH

O OH
H3C H C
N
O
77 78
A Polyurethane
Chapter 6 Amines and Amides

Neurotransmitters
• Neurotransmitters are small molecules that carry
nerve impulses from one neuron to the next.
• Neurons consist of the main cell body (the soma),
long stemlike projections (the axons), and short
fibers connected to the soma (the dendrites).
• Neurons are not connected directly to each other, but
Neurotransmitters are separated by a small gap called a synapse.
• When an electrical current originating in a neuron
reaches the synaptic terminals at the end of the
axon, the terminals release neurotransmitter
molecules into the synapse; these molecules diffuse
across the synapse and bind to receptors on the
dendrites of the next neuron, stimulating an
electrical current, which travels along that neuron
until it reaches the next synapse, and so on until the
79 nerve impulse reaches the brain. 80

HO
Figure 6.5 A nerve cell
and the transmission of a
nerve signal. HO NH2
HO

CO2H
Dopa
HO NH2
Synthesized from the amino acid tyrosine; used as a
treatment for Parkinson's disease, which is caused by a Dopamine
breakdown of dopamine-based neurons that control the Synthesized from dopa; used as a
brain's motor system (dopamine cannot be administered treatment for low blood pressure
directly because it does not cross the blood-brain barrier;
however, the L-form of dopa does)

HO
NH2

HO NH2
OH
Norepinephrine (NE)
Synthesized from dopamine; an excess of NE in the
brain is related to feelings of elation or manic states;
low NE levels are linked to depression; the stimulant
action of epinephrine and NE in some cells can be
reduced by beta blockers, which are used to treat
cardiac arrhythmias, angina, and hypertension
81
N
H
Serotonin
Synthesized from the amino acid tryptophan;
influences sleeping, body temperature, and
sensory perception; drugs that mimic serotonin
are used to treat depression, anxiety, and
obsessive-compulsive disorder; serotonin
blockers are used to treat migraine headaches
and nausea resulting from chemotherapy 82

Pheynlephrines and Amphetamines

HO
CH3 CH3 CH3
CH3
HO N CH3 CH3
NH2 N N
OH H Amphetamine (Benzedrine) H OH H
Epinephrine (Adrenalin) a powerful nervous stimulant; raises N-Methylamphetamine
More important as a hormone than a neurotransmitter; blood glucose levels, increases heart (Methedrine, "speed") Ephedrine / Pseudoephedrine
synthesized in the adrenal glad; release of adrenalin into rate and blood pressure Also a powerful nervous found in the Chinese ma-huang plant; a
the bloodstream in response to pain, anger, or fear stimulant decongestant used in many cold remedies
increases blood glucose levels, and provides a sudden
burst of energy (fight-or-flight response); increases force
of heart contractions (raising blood pressure); also a
vasoconstrictor; used in local anesthetics to keep the O
CH3
anesthetic from being washed away
CH3 CH3
HO N O N
O CH3O
O CH3 CH3 OH H H
H2N CH3O 3,4-Methylenedioxymethamphetamine
N+ OH Phenylephrine (MDMA), "Ectasy"
O CH3 Common decongestant
Acetylcholine Gamma-aminobutanoic acid (GABA)
A inhibitory neurotransmitter
CH3O NH2
Mescaline
83 Hallucinogen from peyote cactus 84
Chapter 6 Amines and Amides

Amino Acids
O
H
H2N
OH

R
Amino Acids

O O O O

Amino Acids and

H2N H2N H2N H2N
OH OH OH OH
Glycine (Gly)

Proteins
CH3
Alanine (Ala)
Valine (Val)
Leucine (Leu)

O O H O O

H2N H2N N H2N

OH OH OH OH

S
Proline (Pro)
Isoleucine (Ile) Methionine (Met)

85 86
Phenylalanine (Phe)

O O O O O

H2N H2N H2N H2N H2N

O OH
OH OH OH OH
H2N OH
OH O
OH OH O
H O
Serine (Ser) Threonine (Thr) CH3 H2N
H2N O
N Alanine (Ala) N
OH OH Aspartate (Asp)
Tyrosine (Tyr) H Glycine (Gly) OH
Tryptophan (Try) Glycine (Gly)
O O O O CH3
Alanine (Ala)
H2N H2N H2N H2N
OH OH OH OH O
O
NH2 H2N
SH OH
NH2 NH
Cysteine (Cys)
Glutamine (Gln) N O O
Asparagine (Asn) H O
Histidine (His) H2N O
H
O O O O N
Glycine (Gly) N N
OH H
H2N H2N H2N H2N Tryptophan (Try)
OH OH OH OH O CH3
O Alanine (Ala) OH
NH2 OH
N NH2
Lysine (Lys) OH H O
Glutamate (Glu) Arginine (Arg)
O 87 Aspartate (Asp) 88
Aspartate (Asp)

O
H O
H2N H O
N H O
Glycine (Gly) N
N
CH3 OH
Alanine (Ala) OH etc.

O
Aspartate (Asp)
N
H
Tryptophan (Try)

Gly Ala Asp Try

a protein
(a polyamide)
Instructions for making proteins
are encoded in DNA.

89 Three levels of structure in a telephone cord 90

Chapter 6 Amines and Amides

Segment of a protein showing -helix, -pleated sheet,

R-group interactions leading to a protein tertiary structure 91 and random coil structures 92

OH
O

O N(CH3)2

Some Hideously Complex

H
OH
O
H
Erythromycin

Molecules
an antibiotic
O

OCH3
OH H
H N NH2 CH3
OH H2N N H N OH
NH H
NH O H O
HO OH
H H
OH O
O CHO
Streptomycin OH OH
93 an antibiotic CH3 94

O O
H2N
O

O O O
OH CH3 NH2
O CH3 O
H2N

HN O H3C NH2
N N
O H3C
H
N OH H Co
O HO O H
H Taxol O O O N N
CH3
N NH2 potential anti-cancer
CH3
drug isolated from the
Pacific yew tree H2N O
O
Bufotoxin O O CH3 CH3
isolated from the toad Bufo O
marinus; increases the NH2 Vitamin B12
OH
contractive power of weak (cobalamine)
O
O N heart muscles; also causes Found in meat, fish, eggs, and milk; a
NH coenzyme involved in amino acid
H terrifying hallucinations
metabolism; needed for the production
O of red blood cells (a deficiency in
N vitamin B12 results in anemia)
O H3C O P O OH
O N
O CH3
OH O O
95
HO 96
O CH3
Chapter 6 Amines and Amides

Functional Groups O O O O O O
O H
H H R C OH R C O- M+ R C O R R C Cl R C O C R
R R ester acid chloride acid anhydride
carboxylic acid carboxylate salt
H C C H C C R C C R (-oic acid) (metal + -oate) (alkyl + -oate)

H H R R
alkane alkene alkyne aromatic ring phenol
(-ane) (-ene) (-yne) (phenyl-, -benzene) (-phenol)

R N H R N H R N R R N+ R
H H R
H R R R
R C OH R C OH R C OH R O R R SH primary (1°) amine secondary (2°) amine tertiary (3°) amine quaternary ammonium salt
thiol
(amino-, -amine) (-amine) (-amine) (alkyl ammonium + anion)
ether
H R R (alkoxy-, -ether)
primary (1°) alcohol secondary (2°) alcohol tertiary (3°) alcohol
(-ol) (-ol) (-ol)

O O O O
O O OH OR OH OR
R C NH2 R C NHR R C N R RO P OH
R C H R C R R C H R C H R C R R C R
R OH
aldehyde ketone OR OR OR OR phosphate ester
(-one) amide
(-al)
hemiacetal acetal hemiketal ketal 97 (N-alkyl + -amide) 98

Reactions of Amines and Amides 4. Formation of an amide. (NR with tertiary amines.)
O R O R
1. Reaction of an amine with water to produce an alkylammonium ion.
H H R' C Cl + R N H R' C N R + HCl
acid chloride amine amide
R N + H O R N H + -OH (1° or 2°)
H H H O O R O R O
amine alkylammonium ion R' C O C R + R N H R' C N R + R' C OH
acid anhydride amine amide carboxylic
(1° or 2°) acid
2. Reaction of an amine with acid to produce an alkylammonium salt.
H H 5. Hydrolysis of amides under acidic and basic conditions.
O O H
R N + H Cl R N H -Cl
+ -
R' C N R + H2O + HCl R' C OH + H N R Cl
H H carboxylic
amine hydrochloric alkylammonium R acid R
acid chloride amide alkylammonium
salt
O O
- +
3. Conversion of an alkylammonium salt back to an amine. R' C N R + NaOH R' C O Na + H N R
R—NH3+ Cl- + NaOH  R—NH2 + H2O + NaCl carboxylate
R salt R
99
amide amine 100

The End
101