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19.4 Amines React as Bases

19.5 Heterocyclic Amines and Alkaloids

Chapter 19 Amines and Amides

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Like ammonia, amines are weak bases in water.

NH3 + H2O NH4+ + OH–

ammonium hydroxide

CH3—NH2 + H2O CH3—NH3+ +

OH–

methylammonium hydroxide

Amines React as Bases

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An amine salt: Forms when an amine is

neutralized by acid. Is named by replacing the amine

part of the name with ammonium followed by the name of the negative ion.

CH3—NH2 + HCl CH3—NH3+ Cl–

Methylamine methylammonium chloride

Neutralization forms Amine Salts

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Properties of Amine Salts

Amine salts are: Solids at room temperature. Soluble in water and body fluids. The form used for drugs.

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Cocaine

Cocaine is sold illegally as an amine salt. Cocaine is reacted with NaOH to produce the

free amine form known as “crack.”

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Heterocyclic Amines

In a heterocyclic amine, a five- or six-atom ring contains one or more nitrogen atoms.

N

NN

N

N

H

N

H

N

H

Pyrrolidine Pyrrole

Piperidine Pyridine Pyrimidine

N

N

N

N

H

Purine

N

H

Imidazole

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Alkaloids are: Physiologically active nitrogen-containing

compounds. Produced by plants. Used as stimulants, anesthetics, and

antidepressants. Often habit forming.

Alkaloids

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Caffeine: Is a stimulant of the

central nervous system.

Is found in coffee beans, tea, chocolate, and soft drinks.

Contains an imidazole ring.

Caffeine

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Nicotine

Nicotine: Increases the adrenaline level in the blood. Causes addiction to tobacco. Contains a pyrrolidine ring.

N

CH3

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Alkaloids Related to Morphine Alkaloids such as morphine and codeine are

produced by the poppy. For centuries, morphine and codeine have been

used as painkillers. Heroin is a modification of morphine.

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Pharmacology

An area of research in pharmacology is to design drugs with some of the characteristics of alkaloids.

The structures of cocaine and morphine are modified to produce anesthesia, but without the addictive side effects.

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Pharmacology

Parts of the morphine structure that produce anesthesia are found in procaine, lidocaine, and demerol.

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Nervous System Amines Derived from amino acids Neurotransmitters A nerve can be thought of as transmitting a stimulus from

one part of the body to another by means of a moving wave of ions.

When the wave reaches the end of a neuron, it causes the release of a transmitter that migrates to a receptor cell, where it triggers the propagation of another wave.

Neuron → Chemical transmitter → Receptor cell, muscle fiber, or another neuron

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Acetylcholine Muscles are sensitive to acetylcholine Acetylcholine is synthesized from amino acids serine and

methionineL-Serine → ethanolamine, amino alcohol

HO-CH2-CH2-NH3+ + methyl groups from methionine →

choline, another amino alcohol HO-CH2-CH2-N+(CH3)3 → O ||

acetylcholine, CH3-C-O-CH2-CH2-N+(CH3)3

Once the desired response has been provoked, the acetylcholine must be removed

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Catecholamines Derivatives of dopamine (3,4-dihydroxyphenethylamine) Precursor is amino acid tyrosine Include norepinephrinene, epinephrine (adrenaline), L-dopa Produced in the brain and adrenal gland These hormones permit the body to react to stress by increasing blood flow to

muscles, lungs, and brain. They also stimulate cellular metabolism.

HO

HO

H2C

H2C NH3

+

dopamine

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Stimulant Drugs: Amphetamines Synthetic amines related to β-phenylethylamine Act as stimulants by mimicking natural brain amines. Amphetamine has been used for weight reduction (no longer recommended;

weight loss was only temporary). Amphetamine induces excitability, restlessness, tremors, insomnia, dilated

pupils, increased pulse rate and blood pressure, hallucinations, and psychoses.

CH2

CH2

NH2

beta-Phenylethylamine

CH2

CH

NH2

CH2

CH

NH

H3C

CH3

Amphetamine(Benzedrine)

Methamphetamine(Methedrine)"speed"

H3C

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Serotonine (5-hydroxytryptamine, or 5-HT) Found in cells of the central

nervous system, where it functions as a transmitter in relation to sleep.

Also produced in the intestinal mucosa.

The drug lysergic acid diethylamide (LSD) probably competes with serotonin, since LSD toxicity can be treated by serotonin administration.

Precursor is amino acid L-Tryptophan.

H3+N CH2

CH2

HNOH

serotonin

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Serotonin (5-hydroxytryptamine, or 5-HT)

is a monoamine neurotransmitter Serotonin - Wikipedia, the free encyclopedia (http://en.wikipedia.org/wiki/Serotonin) Serotonin is involved in sleep, sensory perception, regulation of body

temperature, etc. Diets high in carbohydrate lead to high levels of serotonin. Lots of protein lowers the serotonin concentration. That may seem strange, because protein has lots of tryptophan and

carbohydrates have little. Protein is only 1% tryptophan. In the presense of all those other amino acids, little tryptophan reaches

the brain. With a carbohydrate meal, the hormone insulin lowers the level of the

other amino acids in the blood, allowing relatively high levels of tryptophan to reach the brain.

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γ-Aminobutyrate (GABA) Precursor is amino

acid L-Glutamate Present in high

concentrations in the brain

Inhibit synaptic transmission

H3+N CH2

CH2

CH2

C

O-

O

GABA

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Histamine Precursor is amino acid L-

Histidine Released as a result of allergies Causes the expansion of

capillaries and edema (probably by constricting the smaller veins that lead to them)

The resulting drop in blood pressure may induce shock

Antihistamines are structurally similar to histamine

Antihistamines can prevent the physiological changes produced by histamine release during allergic reactions

H3+N CH2

CH2

N

N+H2

histamine