ACTIVITY IV
AMINES AND AMIDES
I. OBJECTIVES
1. Describe the structure and properties of an amine
2. Describe the structure and properties of an amide
3. Learn the IUPAC system for naming amines and amides
II. NITROGEN-CONTAINING FUNCTIONAL GROUPS
Nitrogen is in Group V of the periodic table, and in most of its
compounds, it has three single bonds and one lone pair.
Two functional groups which contain nitrogen atoms connected to
carbons: the amines and the amides.
III. CLASSIFICATION OF AMINES AND AMIDES
NOMENCLATURE OF AMINES AND AMIDES
A. 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.)
Amines are organic derivatives of ammonia, NH3, in which one or
more of the three H’s is replaced by a carbon group.
Amines are classified as primary (1◦), secondary (2◦), or tertiary
(3◦), depending on how many carbon groups are connected to the
nitrogen atom.
Simple 1◦, 2◦, and 3◦ amines: common (trivial) names are obtained
by alphabetically arranging the names of the alkyl substituents on
the nitrogen and adding the suffix -amine (e.g., ethyl
methylamine).
Amines in the IUPAC system: the “e” ending of 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 number. More
complex primary amines are named with -NH2 as the amino
substituent.
Aromatic amines: named as derivatives of the parent compound
aniline. Substituents attached to the nitrogen are indicated by
using "N-" as the location number.
PHYSICAL PROPERTIES OF AMINES
H-Bonding
Primary and secondary amines can hydrogen bond to each other.
Tertiary amines cannot hydrogen bond to each other.
Boiling Points
Nitrogen is less electronegative than oxygen, so the N-H bond is
not quite as polar as the O-H bond.
-Hydrogen bonds from N-H’s are not as strong as those resulting
from O-H’s
-Hydrogen bonding between primary and secondary amines is not
as strong as those found in alcohols or carboxylic acids.
Primary and secondary amines have lower boiling points than
alcohols of similar molecular weight.
Tertiary amines, since they do not hydrogen bond to each other,
have boiling points similar to hydrocarbons of the same molecular
weight.
Water Solubility
Primary, secondary and tertiary amines can all form hydrogen
bonds with water.
Low-molecular weight amines are generally water-soluble.
Odor
Low molecular-weight amines tend to have sharp, penetrating
odors similar to ammonia.
Higher molecular-weight amines often smell like rotting fish, and
are often found in decaying animal tissues.
SOME IMPORTANTS ALKALOIDS
IMPORTANT ALKALOIDS
Caffeine. Found in the seeds of coffee arabica; roasted coffee
beans; inhibits the action of phosphodiesterase, an enzyme which
inhibits cyclic adenosine monophosphate, which is responsible for
forming glucose in the bloodstream.
Theobromine. Found in the seeds of Theobroma cacao; the
stimulating ingredient in chocolate.
Nicotine. Found in tobacco plants; mild stimulant in small doses;
addictive, but not especially harmful itself.
Dextromethorphan. Ingredient in cough suppressants.
Quinine. Antimalaria drug from cinchona tree.
Cocaine. The form which is “snorted” is the hydrochloride salt; the
free-base “crack” form is burned and inhaled, and reaches the
brain in 15 seconds.
Atropine. Relaxes muscles and reduces secretion of saliva during
surgery; used to dilate pupils for eye examinations.
Scopolamine. Used in treatment of motion sickness.
Coniine. Poison from hemlock.
Zephiran chloride (benzalkonium chloride). Antiseptic compound
that kills bacteria and fungi on contact.
Melatonin. A naturally occurring hormones produced in the pineal
gland; its production is triggered by the absence of light; causes
drowsiness in humans at night, triggers birds to migrate, and
signals dog to shed their winter coats; sold as a treatment for jet
lag.
Lysergic acid diethylamide (LSD). A synthetic hallucinogen from
alkaloids obtained from ergot, a fungus which grows on rye.
Strychnine. A poison from strychnos plant (Nix Vomica); used as a
rat and mouse poison.
Inosine Monophosphate (IMP). With monosodium glutamate (MSG),
one of the major substances responsible for the flavor of meat.
Morphine. Found in the opium poppy; a CNS depressant; very
effective painkiller.
Codeine. Used in some cough syrups to depress the action of the
cough center of the brain.
Heroin. More fat-soluble than morphine and must be injected
directly into the bloodstream, but crosses the blood-brain barrier
more readily, causing it to be more potent than morphine.
Nitrogen Waste. The disposal of waste nitrogen from the body is a
problem which different species of animals have solved in different ways.
Uric acid. Birds, reptiles and insects excrete nitrogen wastes in the
form of uric acid. Uric acid can de eliminated directly in the solid
form, without being dissolved in water. It is produced in the body
from foods and beverages rich in purines, such as claret and port.
Lactic acid inhibits the removal of salts of uric acid in the urine;
theses salts instead deposit in the joints, causing gout.
Allantoin. Most mammals contain enzymes which metabolize uric
acid into allantoin.
Allantoic acid. Marine vertebrate further metabolizes allantoin into
allantoic acid.
Antihistamines
Histamines. People who are allergic to pollen produce histamine,
which causes vessels to dilate and leak, releasing fluid
surrounding tissues, causing watery eyes, sniffles, congestion, and
other symptoms of hay fever (allergic rhinitis); also causes the
symptoms of the common cold and swelling after insect’s bites.
Diphenylhydramine. An antihistamine, active ingredient in
Benadryl; sometimes used in sleeping pills.
Ephedrine/Pseudoephedrine. Found in the Chinese ma-huang
plant; a decongestant used in many cold remedies.
Loratadine (Claritin). A non-drowsy antihistamine.
Fexofenadine (Allegra). A non-drowsy antihistamine; available by
prescription only.
Cetrizide (Zyrtec). A stronger antihistamine than Allegra or
Claritin, but causes drowsiness in some people.
REACTIONS OF AMINES
Bases
A base takes a proton (H+) from another species. A base produces
hydroxide ions, OH-, when dissolved in water.
Strong base is one that completely dissociates in water.
A weak base is one in which only a small percentage of the
molecules are dissociated at any one time.
CHEMICAL PROPERTIES OF AMINES: BASICITY
Amines are weak organic bases. They react with water to produce
alkylammonium ions and hydroxide anions.
And with acids to produce alkylammonium salts.
Ammonium salts may be converted back into neutral amines by a
strong base.
Thus, by adjusting th pH of the solution, it is possible to influence
whether an amine is present in the neutral form or as its
ammonium cation form.
Alkylammonium Salts
Salts of amines are named by changing “amine” to “ammonium
“and adding the name of the negative ion to the end of the word.
Salts of amines are generally white crystalline solids with high
melting points.
The ionic charges make these salts more soluble in water than the
neutral amines. Many amine-containing drugs are administered in
the form of alkylammonium salts to increase their solubility in
bodily fluids.
Quaternary Ammonium Salts
In addition to salts of primary, secondary and tertiary amines, it is
possible to have amine cations which contain four alkyl groups
attached to a nitrogen atom, which will always carry a positive
charge, regardless of the pH of the surrounding solution. These are
known as quaternary ammonium salts.
These salts are present in many antiseptics and antibacterial
agents.
B. AMIDES
Amides contain a nitrogen which is directly attached to a carbon in
a carbonyl group.
NOMENCLATURE OF AMIDES
Amides are named by changing the -oic acid ending of the
corresponding carboxylic acid to -amide. If alkyl groups are
attached to the nitrogen, they are named as N-alkyl substituents.
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.
N-substituted amides often have lower melting points and boiling
points than N, N-unsubstituted amides because fewer hydrogen
bonds can form.
N, N-unsubstituted 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.
IMPORTANT AMIDES
Diazepam (Valium). A benzodiazepine 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.
N, N-Diethyl-m-toluamide. Active ingredient in OFF.
Thalidomide. Until 1956, a very popular, safe sedative; the largest
market was for pregnant women who were experiencing morning
sickness. 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.
HOT STUFF
Capsaicin. Found in red and green chili peppers; active component
of paprika.
Ally isocyanate. Used in horseradish flavor, mustard oil, pickles,
salad dressings and sauces; mustard plasters, medications and
fumigants.
Piperine. Component of white and black pepper.
Zingerone. The pungent, hot component of ginger.
BARBITURATES
Barbituric acid. First synthesized by Adolf von Baeyer in 1864;
barbiturates are soporifics, and are used as tranquilizers and
anesthetics; many are also addictive, and overdoses can be fatal.
Thiopental (Pentothal). An intravenous anesthetic.
Amobarbital (Amytal). Used in the treatment of insomnia.
Phenobarbital. Anti-seizure medication, sedative.
PENICILIN
Penicillin is an antibiotic compound produced by the molds
Penicillium notatum and Penicillium chrysogenum; it was
discovered by Alexander Fleming in 1928 in a culture of bread
mold. There are administered by injection; penicillin V is an oral
form which is not broken down in the stomach; ampicillin is a
broad-spectrum penicillin which can be administered by injection
or orally.
REACTIONS OF AMIDES
Amide Formation
Amides are formed when acid chlorides react with primary or
secondary amines; tertiary amines cannot form amides.
Amides are also formed when acid anhydrides react with primary
or secondary amines.
CHEMICAL PROPERTIES OF AMIDES
Unlike amines, amides are not basic.
Amide hydrolysis can take place under acidic or basic conditions.
CONDENSATION POLYMERS
POLYAMIDES
Nylon-6,12 a polyamide. Discovered by Wallace Carrothers at
DuPont in 1934; polymers average about 10,000g/mol; 3 billion
pounds of Nylon made per year, 60% used for nylon fiber in home
furnishings (carpet); also used in textile fibers, tire cord, rope,
parachutes, paint brushes, Velcro, electrical parts, medical
applications (sutures, etc.)
Kevlar. Used in bullet-proof vests and tire cords (an aramid,
“aromatic polyamide”).
Nomex. Insulates ceramic tiles on the space shuttle; used in
firefighting equipment race car driver suits, flight suits, the airbags
on the Mars Pathfinder, Spirit, and Opportunity rovers (less strong
than Kevlar, but has excellent thermal, chemical, and radiation
resistance).
NEUROTRANSMITTERS
Neurotransmitters are small molecules that carry nerve impulses
from one neuron to the next.
Neurons consists 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 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 nerve impulse reaches the brain.
Dopa. Synthesized from the amino acid tyrosine; used as a
treatment for Parkinson’s disease, which is caused by a breakdown
of dopamine-based neurons that control the brain’s motor system
(dopamine cannot be administered directly because it does not
cross the blood-brain barrier, however, the L-form of dopa does).
Dopamine. Synthesized from dopa; used as a treatment for low
blood pressure.
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.
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.
Epinephrine (Adrenalin). More important as a hormone than a
neurotransmitter; synthesized in the adrenal gland; release of
adrenalin into the bloodstream in response to pain, anger, ore fear
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 anesthetic from being washed
away.
Gamma-aminobutanoic acid (GABA). A inhibitory
neurotransmitter.
FUNCTIONAL GROUPS
REACTIONS OF AMINES AND AMIDES
Reaction of an amine with water to produce an alkylammonium
ion.
Reaction of an amine with acid to produce an alkylammonium salt.
Conversion of an alkylammonium salt back to an amine.
Formation of an amide. (NR with tertiary amines).
Hydrolysis of amides under acidic and basic conditions.
IV. REFERENCES
Boudreaux, K.A. CHEM 2353 Fundamentals of Organic Chemistry.
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