Lecture 7: Amines and Amides 18.1 Amines Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Amines Amines Are derivatives of ammonia NH3. Contain N attached to one or more alkyl or aromatic groups. CH3 CH3   CH3—NH2 CH3—NH CH3—N—CH3

Classification of Amines Amines are classified as primary, secondary, or tertiary. In a primary (1°) amine, one carbon group is bonded to the nitrogen atom. A secondary (2°) amine has two carbon groups. A tertiary (3°) amine has three carbon groups. H CH3 CH3 | | | CH3—N—H CH3—N—H CH3—N—CH3 1° 2° 3°

Models of Amines The three-dimensional models show the shapes of amine molecules with one or more alkyl groups bonded to the nitrogen atom. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Naming Simple Amines Simple amines Are named as alkylamines. List the names of the alkyl groups bonded to the N atom in alphabetical order in front of amine. CH3—CH2—NH2 ethylamine CH3—NH—CH3 dimethylamine CH3 | CH3—N—CH2—CH3 ethyldimethylamine

IUPAC Names of Amines In the IUPAC system, Amines are named as alkanamines. The ­e in the alkane name of the longest chain is changed to ­amine. The chain is numbered to locate the amine group and substituents. NH2 | CH3—CH2—NH2 CH3—CH—CH3 Ethanamine 2-Propanamine

Naming Secondary and Tertiary Amines In a secondary or tertiary amine, The longest alkane chain is numbered. Each alkyl group bonded to the N atom is named as a N-alkyl group HN—CH3 | CH3—CH2—CH2—NH—CH3 CH3—CH—CH2—CH3 3 2 1 1 2 3 4 N-Methyl-1-propanamine N-Methyl-2-butanamine

Learning Check Give the common and IUPAC names, and classify as primary, secondary, or tertiary: A. CH3—CH2—CH2—NH2 CH3 | B. CH3—CH2—N—CH3

Learning Check Write a structural formula for A. 2-pentanamine B. N-methyl-1-butanamine

Aromatic Amines The amine of benzene is aniline. Alkyl groups on the N use the prefix N- and the alkyl name. Aniline 3-chloroaniline N-methylaniline

Learning Check Give a name for each: A. CH3—NH—CH2—CH3 CH3 | B. CH3—CH2—N—CH2—CH2—CH2—CH3 C.

Solution A. CH3—NH—CH2—CH3 ethylmethylamine; N-methylethanamine CH3 | B. CH3—CH2—N—CH2—CH2—CH2—CH3 N-ethyl-N-methyl-1-butanamine C. aniline

Lecture 7: Amines and Amides 18.2 Properties of Amines Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Boiling Points of Amines, Alcohols, and Alkanes The boiling points of amines are Higher than alkanes. Lower than alcohols of similar mass. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Hydrogen Bonding for Amines The polar N-H bond Provides hydrogen bonding in 1°and 2° amines, but not 3°. In amines is not as polar as the O-H bonds in alcohols. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Solubility in Water Amines are soluble in water If they have 1-5 carbon atoms. Because the N atom in smaller amines forms hydrogen bonds with the polar O-H bond in water. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Learning Check Consider the following compounds: 1. CH3—CH2—CH2—NH2 2. CH3—CH2—NH—CH3 3. CH3—CH2—CH2—CH3 A. Which compound has the highest boiling point? B. Which compound(s) is(are) soluble in water?

Solution Consider the following compounds: 1. CH3—CH2—CH2—NH2 2. CH3—CH2—NH—CH3 3. CH3—CH2—CH2—CH3 A. Which compound has the highest boiling point? 1. CH3—CH2—CH2—NH2 B. Which compound(s) is(are) soluble in water?

Amines React as Bases Amines are Bronsted-Lowry bases that attract a H+ from H2O to the N atom. Weak bases in water. NH3 + H2O NH4+ + OH– ammonium hydroxide CH3—NH2 + H2O CH3—NH3+ + OH– methylammonium hydroxide

Neutralization forms Amine Salts 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 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Properties of Amine Salts Amine salts are Solids at room temperature. Soluble in water and body fluids. The form used for drugs. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Cocaine Cocaine Is sold illegally as an amine salt. Is reacted with NaOH to produce the free amine form known as “crack”. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Learning Check Write the equation for ethylamine when it reacts with each of the following: 1. + H2O 2. + HCl

Solution Write the equation for ethylamine when it reacts with each of the following: 1. CH3—CH2—NH2 + H2O CH3—CH2—NH3+ OH– 2. CH3—CH2—NH2 + HCl CH3—CH2—NH3+ Cl–

Lecture 7: Amines and Amides 18.3 Heterocyclic Amines and Alkaloids Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Heterocyclic Amines A heterocyclic amine Is a cyclic organic compound. Has a five- or six-atom ring. Contains one or more nitrogen atoms.

Examples of Heterocyclic Amines Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Learning Check Identify the following heterocyclic amines: 1. 2. 3.

Solution Identify the following heterocyclic amines: 1. 2. 3. 1. 2. 3. 1. piperidine 2. pyrrole 3. imidazole

Alkaloids Alkaloids are Physiologically active nitrogen-containing compounds. Produced by plants. Used as stimulants, anesthetics, and antidepressants. Often habit forming.

Caffeine Caffeine Is a stimulant of the central nervous system. Is found in coffee beans, tea, chocolate, and soft drinks. Contains an imidazole ring. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

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

Alkaloids Related to Morphine Such as morphine and codeine are produced by the poppy. Have been used for centuries as painkillers. Such as heroin and codeine are modifications of morphine. Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Morphine and Codeine Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Pharmacology An area of research in pharmacology Is to design drugs such as procaine, lidocaine, and demerol that retain some of the characteristics of alkaloids. Is to modify the structures of cocaine and morphine to produce anesthesia, but without the addictive side effects.

Pharmacology Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Learning Check Identify the heterocyclic amine in serotonin. serotonin

Solution Identify the heterocyclic amine in serotonin. pyrrole

Lecture 7: Amines and Amides 18.4 Amides Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Preparation of Amides Amides are prepared By reacting a carboxylic acid with ammonia or an amine (1° or 2°). Using heat. O O  Heat  CH3—C—OH + NH3 CH3—C—NH2 + H2O O O  Heat  CH3—C—OH + CH3—NH2 CH3—C—NH—CH3 + H2O

Amides In amides, an amino group(–NH2) replaces the –OH group of carboxylic acids. O O || || CH3—C—OH CH3—C—NH2 Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Naming Amides Amides are named as alkanamides. IUPAC replaces –oic acid ending with –amide. Common names replace -ic acid ending with –amide. O  Methanamide (IUPAC) H—C—NH2 Formamide (common)  Propanamide (IUPAC) CH3—CH2—C—NH2 Propionamide (common)

Naming Amides with N Groups An alkyl group bonded to the N atom is named as N-alkyl in front of the amide name. O H  │ CH3 —C—N—CH3 N-methylethanamide (IUPAC) N-methylacetamide (common) CH3—CH2 —C—N—CH2—CH3 N-ethylpropanamide (IUPAC) N-ethylpropionamide (common)

Aromatic Amides The amide of benzene is named benzamide.

Learning Check Give the IUPAC and common names for the following: O  A. CH3–CH2–CH2–C–NH2 O H  │ B. CH3–C–N–CH2–CH3

Solution O  A. CH3–CH2–CH2–C–NH2 butanamide; butryamide O H  │  │ B. CH3–C–N–CH2–CH3 N-ethylethanamide; N-ethylacetamide

Learning Check Draw the structures of A. pentanamide B. N-methylbutyramide

Solution O  CH3–CH2–CH2–CH2–C–NH2 B. N-methylbutyramide A. pentanamide O  CH3–CH2–CH2–CH2–C–NH2 B. N-methylbutyramide CH3–CH2–CH2–C–NH–CH3

Classification of Amides Amides are classified according to the number of carbon atoms bonded to the nitrogen atom. O H || | CH3—C—N—H Primary (1°) amide O H CH3—C—N—CH3 Secondary (2°) amide O CH3 || | CH3 —C—N—CH3 Tertiary (3°) amide

Learning Check Give the common and IUPAC names for the following amides and classify as primary, secondary, or tertiary: O || A. CH3—CH2—CH2—C—NH2 O CH3 || | B. CH3—C—N—CH2—CH3

Solution || A. CH3—CH2—CH2—C—NH2 butryamide (common); butanamide (IUPAC) primary(1°) amide O CH3 || | B. CH3—C—N—CH2—CH3 N-ethyl-N-methylacetamide (common); N-ethyl-N-methylethanamide (IUPAC) tertiary (3°) amide

Some Amides in Health and Medicine Urea is the end product of protein metabolism. Saccharin is an artificial sweetener. Some amides such as phenobarbital, Nembutal and Seconal are barbiturates. Acetaminophen is used to reduce fever and pain.

Some Amides in Health and Medicine Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Physical Properties of Amides That are primary (−NH2) or secondary (−NH−) form hydrogen bonds. That are primary have higher melting points than secondary. That are tertiary (no H on N) do not form hydrogen bonds and have lower melting points. All form hydrogen bonds with water. With 1-5 carbon atoms are soluble in water.

Hydrogen Bonding of Amides || CH3—C—N—H | H Hydrogen bonding occurs between primary amides. H

Lecture 7: Amines and Amides 18.5 Hydrolysis of Amides Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings

Hydrolysis of Amides acid hydrolysis base hydrolysis Amides undergo acid hydrolysis base hydrolysis carboxylic acid salt of carboxylic acid ammonium salt and an amine or ammonia

Hydrolysis Reactions O || O CH3—C—OH + NH4+Cl– || HCl + H2O CH3—C—NH2 acid hydrolysis O || O CH3—C—OH + NH4+Cl– || HCl + H2O CH3—C—NH2 NaOH O CH3—C—O– Na+ + NH3 base hydrolysis

Learning Check N-ethylpropanamide with NaOH. Write the equation for the hydrolysis of N-ethylpropanamide with NaOH.

Solution N-ethylpropanamide with NaOH. O  CH3—CH2—C—N—CH2—CH3 + NaOH Write the products of the hydrolysis of N-ethylpropanamide with NaOH. O  CH3—CH2—C—N—CH2—CH3 + NaOH N-ethylpropanamide CH3—CH2—C—O– Na+ + CH3—CH2—NH2