15.13 Amines as Bases

Learning Objectives

  1. Name the typical reactions that take place with amines.
  2. Describe heterocyclic amines.

Recall that ammonia (NH3) acts as a weak base because the nitrogen atom has a lone pair of electrons that can accept a proton. Amines also have a lone electron pair on their nitrogen atoms and can accept a proton from water to form substituted ammonium (NH4+) ions and hydroxide (OH−) ions:

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As a specific example, methylamine reacts with water to form the methylammonium ion and the OH− ion.

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Nearly all amines, including those that are not very soluble in water, will react with strong acids to form salts that are soluble in water.

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Amine salts are named like other salts: the name of the cation is followed by the name of the anion.

Example 15

What are the formulas of the acid and base that react to form [CH3NH2CH2CH3]+CH3COO−?

Skill-Building Exercise

  1. What are the formulas of the acid and base that react to form (CH3CH2CH2)3NH+I−?

To Your Health: Amine Salts as Drugs

Salts of aniline are properly named as anilinium compounds, but an older system, still in use for naming drugs, identifies the salt of aniline and hydrochloric acid as “aniline hydrochloride.” These compounds are ionic—they are salts—and the properties of the compounds (solubility, for example) are those characteristic of salts. Many drugs that are amines are converted to hydrochloride salts to increase their solubility in aqueous solution.

Heterocyclic Amines

Looking back at the various cyclic hydrocarbons introduced in Chapter 12 “Organic Chemistry: Alkanes and Halogenated Hydrocarbons” and Chapter 13 “Unsaturated and Aromatic Hydrocarbons”, we see that all the atoms in the rings of these compounds are carbon atoms. In other cyclic compounds, called heterocyclic compounds, one or more atoms in the ring is an element other than a carbon atom. Nitrogen, oxygen, and sulfur are elements which may be incorporated into rings. Many heterocyclic compounds are important in medicine and biochemistry. Some compose part of the structure of the nucleic acids, which in turn compose the genetic material of cells and direct protein synthesis. (For more information about nucleic acids, see Chapter 19 “Nucleic Acids”.)

Many heterocyclic amines occur naturally in plants. Like other amines, these compounds are basic. Nitrogen-containing organic compounds obtained from plants are called alkaloids,a name that means “like alkalis.” Many alkaloids are physiologically active, including the familiar drugs caffeine, nicotine, and cocaine.

To Your Health: Three Well-Known Alkaloids

Caffeine is a stimulant found in coffee, tea, and some soft drinks. Its mechanism of action is not well understood, but it is thought to block the activity of adenosine, a heterocyclic base that acts as a neurotransmitter, a substance that carries messages across a tiny gap (synapse) from one nerve cell (neuron) to another cell. The effective dose of caffeine is about 200 mg, corresponding to about two cups of strong coffee or tea.

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Nicotine acts as a stimulant by a different mechanism; it probably mimics the action of the neurotransmitter acetylcholine. People ingest this drug by smoking or chewing tobacco. Its stimulant effect seems transient, as this initial response is followed by depression. Nicotine is highly toxic to animals. It is especially deadly when injected; the lethal dose for a human is estimated to be about 50 mg. Nicotine has also been used in agriculture as a contact insecticide.

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Cocaine acts as a stimulant by preventing nerve cells from taking up dopamine, another neurotransmitter, from the synapse. High levels of dopamine are therefore available to stimulate the pleasure centers of the brain. The enhancement of dopamine action is thought to be responsible for cocaine’s “high” and its addictive properties. After the binge, dopamine is depleted in less than an hour. This leaves the user in a pleasureless state and (often) craving more cocaine.

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Cocaine is used as the salt cocaine hydrochloride and in the form of broken lumps of the free (unneutralized) base, which is called crack cocaine.

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Because it is soluble in water, cocaine hydrochloride is readily absorbed through the watery mucous membranes of the nose when it is snorted. Crack cocaine is more volatile than cocaine hydrochloride. It vaporizes at the temperature of a burning cigarette. When smoked, cocaine reaches the brain in 15 s.

Concept Review Exercises

  1. Explain the basicity of amines.

  2. Contrast the physical properties of amines with those of alcohols and alkanes.

  3. What is a heterocyclic compound?

Key Takeaways

  • Amines are bases; they react with acids to form salts.
  • Salts of aniline are properly named as anilinium compounds, but an older system is used to name drugs: the salts of amine drugs and hydrochloric acid are called “hydrochlorides.”
  • Heterocyclic amines are cyclic compounds with one or more nitrogen atoms in the ring.

Exercises

  1. What salt is formed in each reaction? Write its condensed structural formula.

    1. CH3NH2(aq) + HBr(aq) →
    2. CH3NHCH3(aq) + HNO3(aq) →

  2. What salt is formed in each reaction? Draw its structure.

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