1. © 2013 Pearson Education, Inc. Outline 15.1Amines 15.2Properties of Amines 15.3Heterocyclic Nitrogen Compounds 15.4Basicity of Amines 15.5Amine Salts 15.6Amines in Plants: Alkaloids

2. © 2013 Pearson Education, Inc. Goals 1. What are the different types of amines? Be able to recognize primary, secondary, tertiary, and heterocyclic amines, as well as quaternary ammonium ions. 2.How are amines named? Be able to name simple amines and write their structures, given the names. 3.What are the general properties of amines? Be able to describe amine properties such as hydrogen bonding, solubility, boiling point, and basicity. 4.How do amines react with water and acids? Be able to predict the products of the acid–base reactions of amines and ammonium ions. 5.What are alkaloids? Be able to describe the sources of alkaloids, name some examples, and tell how their properties are typical of amines.

3. © 2013 Pearson Education, Inc. 15.1 Amines Amines contain one or more organic groups bonded to nitrogen. Amines are organic derivatives of ammonia (NH 3 ). They are classified as primary (1°), secondary (2°), or tertiary (3°), according to how many organic groups are individually bound directly to the nitrogen atom.

4. © 2013 Pearson Education, Inc. 15.1 Amines

5. © 2013 Pearson Education, Inc. 15.1 Amines Each amine nitrogen atom has a lone pair of electrons. The lone pair is responsible in large part for the chemistry of amines. When a fourth group bonds to the nitrogen through this lone pair, the product is a quaternary ammonium ion, which has a permanent positive charge and forms ionic compounds.

6. © 2013 Pearson Education, Inc. 15.1 Amines Each amine nitrogen atom has a lone pair of electrons. The lone pair is responsible in large part for the chemistry of amines. When a fourth group bonds to the nitrogen through this lone pair, the product is a quaternary ammonium ion, which has a permanent positive charge and forms ionic compounds.

7. © 2013 Pearson Education, Inc. 15.1 Amines Primary alkyl amines (RNH 2 ) are named by identifying the alkyl group attached to nitrogen and adding the suffix -amine to the alkyl group name.

8. © 2013 Pearson Education, Inc. 15.1 Amines Simple, non-heterocyclic secondary and tertiary amines are named by adding di- or tri- to the alkyl group name along with the suffix -amine.

9. © 2013 Pearson Education, Inc. 15.1 Amines When the R groups in secondary or tertiary amines are different, the compounds are named as N-substituted derivatives of a primary amine. The parent compound is the one that contains the largest of the R groups; all other groups are considered to be N-substituents.

10. © 2013 Pearson Education, Inc. 15.1 Amines The —NH 2 functional group is an amino group. When this group is a substituent, amino- is used as a prefix in the name of the compound. Aromatic amines are primarily known by their common names. The simplest aromatic amine is known as aniline. Proteins are polymers of amino acids; these have the general structure. H 2 N—CHR—COOH.

11. © 2013 Pearson Education, Inc. 15.1 Amines Knowing What You Work With: Material Safety Data Sheets There are millions of different chemical compounds. If a compound is spilled, inhaled, or ingested; what kind of clean up or first aid is required? All of the information is readily available through what are known as Material Safety Data Sheets (MSDSs). These documents contain basic information needed to insure the safety and health of the user of a given chemical. MSDSs are not meant for consumers, but for occupational use; this is primarily to limit confusion arising from the MSDSs themselves. What does a typical MSDS contain? 1.Composition and Information on ingredients; 2.Hazards Identification; 3.First Aid Measures; 4.Fire Fighting Measures; 5.Release Measures: how to deal with spills and leaks; 6.Handling and Storage: what precautions need to be used when handling the material; 7.Exposure Controls and Personal Protection: permissible exposure limits (PEL) for the material as well as a time weighted average (TWA) for exposure over an 8-hour work shift; this section also lists personal protective equipment required for handling the material; 8.Physical and Chemical Properties; 9.Stability and Reactivity: conditions to avoid and incompatibilities with other materials; 10.Toxicological Information; 11.Ecological Information: effects that the material has on the environment; 12.Disposal Considerations: how to safely and legally dispose of the material.

12. © 2013 Pearson Education, Inc. 15.2 Properties of Amines The lone electron pair on the nitrogen in amines causes amines to act as weak Brønsted–Lowry bases or Lewis bases. A Lewis base is a compound containing an unshared pair of electrons.

13. © 2013 Pearson Education, Inc. 15.2 Properties of Amines Primary and secondary amines can hydrogen bond with one another. Because of hydrogen bonding, primary and secondary amines have higher boiling points than alkanes of similar size. Oxygen can form more hydrogen bonds per molecule than nitrogen; alcohols have even higher boiling points.

14. © 2013 Pearson Education, Inc. 15.2 Properties of Amines All amines can form hydrogen bonds with water. Amines with up to about 6 carbon atoms have appreciable solubility in water. Oxygen can form more hydrogen bonds per molecule than nitrogen; alcohols have even higher boiling points than amines.

15. © 2013 Pearson Education, Inc. 15.2 Properties of Amines Many volatile amines have strong odors. Some smell like ammonia and others like stale fish or decaying meat. Simpler amines are irritating to the skin, eyes, and mucous membranes and are toxic by ingestion. Some more complex amines from plants can be very poisonous. All living things contain a wide variety of amines, and many useful drugs are amines.

16. © 2013 Pearson Education, Inc. 15.2 Properties of Amines Properties of Amines Primary and secondary amines can hydrogen-bond with each other and thus, are higher boiling than alkanes, but lower boiling than alcohols. Tertiary amines are lower boiling than secondary or primary amines because hydrogen bonding between tertiary amines is not possible. The simplest amines are gases; other common amines are liquids. Volatile amines have unpleasant odors. Simple amines are water-soluble because of hydrogen bonding with water. Amines are weak Brønsted–Lowry/Lewis bases. Many amines are physiologically active, and many are toxic.

17. © 2013 Pearson Education, Inc. 15.3 Heterocyclic Nitrogen Compounds In many nitrogen-containing compounds, the nitrogen atom is in a ring with carbon atoms. Compounds that contain atoms other than carbon in the ring are known as heterocycles. Heterocyclic nitrogen compounds may be nonaromatic or aromatic.

18. © 2013 Pearson Education, Inc. 15.3 Heterocyclic Nitrogen Compounds

19. © 2013 Pearson Education, Inc. 15.4 Basicity of Amines Aqueous solutions of amines are weakly basic. CH 3 CH 2 NH 2 + H 2 O ⇆ CH 3 CH 2 NH 3 + + OH – (CH 3 CH 2 ) 2 NH + H 2 O ⇆ (CH 3 CH 2 ) 2 NH 2 + + OH – (CH 3 CH 2 ) 3 N + H 2 O ⇆ (CH 3 CH 2 ) 3 NH + + OH – An ammonium ion is a positive ion formed by addition of hydrogen to an amine.

20. © 2013 Pearson Education, Inc. 15.4 Basicity of Amines Alkylamine cations are named by replacing the ending -amine with -ammonium.

21. © 2013 Pearson Education, Inc. 15.4 Basicity of Amines Heterocyclic amine cations are named by replacing the -e with -ium.

22. © 2013 Pearson Education, Inc. 15.4 Basicity of Amines In general, nonaromatic amines are slightly stronger bases than ammonia, and aromatic amines are weaker bases than ammonia. nonaromatic amines > ammonia > aromatic amines

23. © 2013 Pearson Education, Inc. 15.4 Basicity of Amines Organic Compounds in Body Fluids and the “Solubility Switch” Chemical reactions that keep us alive and functioning occur in body­fluids, and waste products from these metabolic reactions are excreted in urine. Water solubility decreases as hydrocarbon-like portions of molecules become larger, but many biomolecules contain acidic and basic functional groups. At the pH of body fluids (approximately 7.2), many of these groups are ionized and soluble. The most common functional groups are carboxylate groups, phosphate groups, and ammonium groups. Most biochemical pathways occur in the cytosol. Diffusion of reactants does not occur because the intermediates are ionized; as a result, they cannot pass through the nonpolar cell wall. Medications must be soluble in body fluids to be transported from their entry point to their site of action. Weak acids are un-ionized in the acidic environment in the stomach and are therefore readily absorbed there. Weak bases are completely ionized in the stomach. In the basic environment of the small intestine, weak bases revert to their neutral form and are absorbed. Converting amines such as phenylephrine (the decongestant in Neo-Synephrine) to ammonium hydrochlorides increases their solubility to the point where delivery in solution is possible.

24. © 2013 Pearson Education, Inc. 15.5 Amine Salts Ammonium salt is an ionic compound composed of an ammonium cation and an anion; an amine salt. They are named by combining the ion names; NH 4 Cl is ammonium chloride. Ammonium salts are generally odorless, white, crystalline solids that are much more soluble than neutral amines.

25. © 2013 Pearson Education, Inc. 15.5 Amine Salts In medicinal chemistry, amine salt formulas are quite often written and named by combining the structures and names of the amine and the acid used to form its salt. By this system, methylammonium chloride is written CH 3 NH 2 HCl and named methylamine hydrochloride. If a free amine is needed, it is easily regenerated by treatment with a base.

26. © 2013 Pearson Education, Inc. 15.5 Amine Salts Quaternary ammonium ions have four organic groups bonded to the nitrogen atom, giving the nitrogen a positive charge. With no H atom and no lone pair, ammonium ions are neither acidic nor basic, and their structures in solution are unaffected by changes in pH. Their salts are known as quaternary ammonium salts.

27. © 2013 Pearson Education, Inc. 15.5 Amine Salts Benzalkonium chlorides have antimicrobial and detergent properties. As dilute solutions, they are used in surgical scrubs and for sterile storage of instruments.

28. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Alkaloids are naturally occurring, nitrogen-containing compounds isolated from a plant; usually basic, bitter, and poisonous. Many thousands of alkaloids have been characterized. The bitterness and poisonous nature of alkaloids probably protects plants from being devoured by animals.

29. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Coniine is extracted from poison hemlock (Conium maculatum). Socrates used this poison to end his life after being convicted of corrupting Greek youth with his philosophical discussions.

30. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Atropine is the toxic substance in the herb known as deadly nightshade or belladonna (Atropa belladonna). Atropine acts on the central nervous system, a property applied in medications to reduce cramping of the digestive tract. Atropine is also used as an antidote against nerve gases, such as Sarin.

31. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Solanine is found in potatoes and tomatoes, both of which belong to the same botanical family as the deadly nightshade (Solanaceae).

32. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids When potatoes are exposed to sunlight or stored under very cold or very warm conditions, the production of solanine is increased to levels that can be dangerous. Alkaloids are not destroyed during cooking but can be removed by peeling. Sunlight also stimulates the formation of chlorophyll under the skin of the potato, and the green color of the chlorophyll provides a warning.

33. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids About 20 alkaloids are present in the poppy, including morphine and codeine. The free alkaloids are oily liquids. The medicinal use of morphine for pain was expanded when the German physician Paracelsus extracted opium into brandy to produce laudanum. A similar extract is still sometimes prescribed, as is paregoric, a more dilute solution of opium combined with anise oil, glycerin, benzoic acid, and camphor.

34. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Heroin does not occur naturally, but is easily synthesized from morphine. Within the body, removal of the CH 3 =O groups (highlighted in orange) converts heroin back to morphine.

35. © 2013 Pearson Education, Inc. 15.6 Amines in Plants: Alkaloids Toxicology is the science devoted to poisons—identification, effects, modes of action, and methods of protecting against them. Clinical toxicology is concerned with the treatment of individuals harmed by toxic agents. Forensic toxicology deals with the effects of toxic agents as they relate to criminal cases, most notably in drug abuse or intentional poisonings. Environmental toxicology—is concerned with toxic substances purposefully or accidentally introduced into our surroundings. Many poisons have a molecular structure that allows them to interact with a specific biomolecule. Several of the most poisonous substances known are neurotoxins, which bind to proteins that form ion channels in nerve cell membranes. Blocking these channels prevents transmission of nerve impulses, causing paralysis and death by suffocation. A number of poisons act at receptors that normally bind acetylcholine, a neurotransmitter (a molecule that carries chemical messages between nerve cells). A thorough understanding of any poison includes knowing how it acts at the molecular level and knowing a molecular mechanism by which its effects can be reversed.

36. © 2013 Pearson Education, Inc. Chapter Summary Summary of Reactions 1. Reactions of amines (Section 15.4) a.Acid–base reaction with water: CH 3 CH 2 NH 2 + H 2 O ⇆ CH 3 CH 2 NH 3 + + OH – b.Acid–base reaction with a strong acid to yield an ammonium ion: CH 3 CH 2 NH 2 + HCl ⇆ CH 3 CH 2 NH 3 + + Cl –

37. © 2013 Pearson Education, Inc. Chapter Summary, Continued Summary of Reactions 1. Reaction of ammonium ion (Section 15.4) or amine salt (Section 15.5) a.Acid–base reaction of primary, secondary, or tertiary amine salt (or ion) with a base to regenerate the amine: CH 3 CH 2 NH 3 + Cl – + NaOH ⇆ CH 3 CH 2 NH 2 + NaCl + H 2 O

38. © 2013 Pearson Education, Inc. Chapter Summary, Continued 1.What are the different types of amines? Amines are classified as primary, secondary, or tertiary, depending on whether they have one, two, or three organic groups individually bonded to nitrogen. These amines can all add hydrogen to form ammonium ions, which have four bonds to the nitrogen, which bears a single positive charge. Ions with four organic groups bonded to nitrogen are known as quaternary ammonium ions. In heterocyclic amines, the nitrogen of the amine group is bonded to 2 carbon atoms that are part of a ring.

39. © 2013 Pearson Education, Inc. Chapter Summary, Continued 2.How are amines named? Primary amine names have -amine added to the alkyl group name, and secondary and tertiary amines with identical R groups have di- and tri- prefixes. When the R groups are different, amines are named as N-substituted derivatives of the amine with the largest R group. Ions derived from amines are named by replacing -amine in the name with -ammonium. The NH 2 group as a substituent is called an amino group.

40. © 2013 Pearson Education, Inc. Chapter Summary, Continued 3.What are the general properties of amines? Amines have an unshared electron pair on nitrogen that is available to accept a proton or for hydrogen bonding. Primary and secondary amine molecules hydrogen- bond to each other, but tertiary amine molecules cannot do so. Thus, the general order of boiling points for molecules of comparable size is: Hydrocarbons<tertiary amines< primary and secondary amines< alcohols All amines can, however, hydrogen-bond to other molecules containing OH and NH groups, and for this reason small amine molecules are water-soluble. Many amines are physiologically active. Volatile amines have strong, unpleasant odors.

41. © 2013 Pearson Education, Inc. Chapter Summary, Continued 4.How do amines react with water and acids? Amines are weak bases and establish equilibria with water by adding H + to form ammonium ions (RNH 3 +, R 2 NH 2 +, and R 3 NH + ) and hydroxide ions (OH – ). They react with acids to form ammonium salts. Ammonium ions react as acids (proton donors) in the presence of a base. Quaternary ammonium ions R 4 N have no lone electron pair and are not bases, nor can they form hydrogen bonds.

42. © 2013 Pearson Education, Inc. Chapter Summary, Continued 5.What are alkaloids? Alkaloids are naturally occurring nitrogen compounds found in plants. They are all bases, most with a bitter taste. Like other amines, many are physiologically active, notably as poisons or analgesics.