Chapter 25 Amides and Amines: Organic Nitrogen Compounds Nylon is one of the materials used to give these colorful sails their strength and durability. Introduction to General, Organic, and Biochemistry, 10e John Wiley & Sons, Inc Morris Hein, Scott Pattison, and Susan Arena
Course 25.1 Amides: Nomenclature and Physical Properties 25.2 Chemical Properties of Amides 25.3 Polyamides: Condensation Polymers 25.4 Urea 25.5 Amines: Nomenclature and Physical Properties 25.6 Preparation of Amines 25.7 Chemical Properties of Amines 25.8 Sources and Uses of Selected Amines Chapter 25 Summary 2
Amides: Nomenclature and Physical Properties Chapter Amides are neutral nitrogen-containing compounds. They are not acidic or basic (neutral) and exist as molecules both in aqueous solution and as pure substances. These compounds contain carbonyl groups. The carbonyl group is directly connected to a nitrogen atom. 3
Amides: Nomenclature and Physical Properties Chapter Amides are prepared when a carboxylic acid is heated in the presence of ammonia. 4
Amides: Nomenclature and Physical Properties Chapter Ammonium salts of carboxylic acids can also be converted to amides by heating. 5
Amides: Nomenclature and Physical Properties Chapter IUPAC Rules for Naming Amides 1. Name the longest continuous carbon chain containing the amide group. The carbonyl carbon atom is the #1 carbon atom. 2. Drop oic from the corresponding carboxylic acid and add the suffix amide. 6
Amides: Nomenclature and Physical Properties Chapter IUPAC names for amides are formed from the IUPAC names of carboxylic acids. Here are two examples. 7
Amides: Nomenclature and Physical Properties Chapter 3. Use a capital N (italicized) as the prefix if alkyl groups or other groups are attached directly to the amide nitrogen atom. 8
Amides: Nomenclature and Physical Properties Chapter The common names for amides are formed from the common names of carboxylic acids. 9
Amides: Nomenclature and Physical Properties Chapter IUPAC and common names of some amides are on Table 25.1 on the next slide... 10
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Your Turn! Write formulas for N-methylpentanamide and N,Ndiethyl-2-methylhexanamide. 12
Your Turn! Write formulas for N-methylpentanamide and N,Ndiethyl-2-methylhexanamide. O O CH 3 CH 2 CH 2 CH 2 CHC N(CH 2 CH 3 ) 2 CH 3 CH 2 CH 2 CH 2 C NHCH 3 N-methylpentanamide CH 3 N,N-diethyl-2-methylhexanamide 13
Amides: Nomenclature and Physical Properties Chapter Physical Properties of Amides The physical properties of amides are determined largely by hydrogen bonding. 14
Amides: Nomenclature and Physical Properties Chapter High water solubility and high melting and boiling are the result of hydrogen bonding. A table summarizing the physical properties of amides is on the following slide... 15
Amides: Nomenclature and Physical Properties Chapter Property Description Polarity Polar Solubility Low molar mass amides are soluble in water M.P./B.P. Both m.p. & b.p. are high due to hydrogen bonding Physical State/Appearance Colorless/odorless solids at room temperature except formamide. 16
Chemical Properties of Amides An important reaction of amides is hydrolysis. Amides undergo acidic and basic hydrolysis producing a carboxylic acid or carboxylate salt. Acidic Hydrolysis Basic Hydrolysis 17
Your Turn! Write the equations for the acidic and basic hydrolysis of the following amide. O CH 3 CH 2 CH 2 CH 2 C NH 2 18
Your Turn! Write the equations for the acidic and basic hydrolysis of the following amide. O CH 3 CH 2 CH 2 CH 2 C O O NH 2 + H 2 O + H + CH 3 CH 2 CH 2 CH 2 C Acidic hydrolysis O OH + NH 4 + CH 3 CH 2 CH 2 CH 2 C NH 2 + NaOH CH 3 CH 2 CH 2 CH 2 C Basic hydrolysis O - + NH 3 19
Polyamides: Condensation Polymers Polyamides are condensation polymers that contain repeating amide linkages as shown here. 20
Polyamides: Condensation Polymers Polyamides are either synthetic like Nylon-66 or are biological like the protein chymotrypsin. The structure of chymotrypsin is shown below. 21
Polyamides: Condensation Polymers The structure of synthetic Nylon-66 is shown here. 22
Urea Urea is a simple diamide that is excreted in urine. Urea is the metabolite the body uses to excrete toxic ammonia. Urea is a white solid that melts at 133 C. It is very soluble in water. 23
Urea Urea is a common commercial product. It is widely used in fertilizers to add nitrogen to the soil and as a starting material in the production of plastics and barbiturates like barbituric acid. 24
Amines: Nomenclature and Physical Classification of Amines Properties Chapter Amines are basic nitrogen-containing compounds that are derivatives of ammonia. Amines are classified as: Primary (the nitrogen atom has one hydrocarbon group directly attached) Secondary (the nitrogen atom has two hydrocarbon groups directly attached) Tertiary (the nitrogen atom has three hydrocarbon groups directly attached). 25
Amines: Nomenclature and Physical Properties Chapter Examples of primary (1 o ), secondary (2 o ) and tertiary (3 o ) amines are shown here. 26
Your Turn! Classify the following amines as 1 o, 2 o or 3 o. CH 3 NH 2 NHCH 3 CH 3 CH 2 CHCH 3 N(CH 3 ) 2 27
Your Turn! Classify the following amines as 1 o, 2 o or 3 o. CH 3 NH 2 NHCH 3 CH 3 CH 2 CHCH 3 N(CH 3 ) 2 1 O 3 O 2 O 28
Amines: Nomenclature and Physical Properties Chapter IUPAC Rules for Naming Amines 1. Name the longest continuous carbon chain containing the amine group. The carbon atom attached to the amine group is the #1 carbon atom. 2. Drop e from the corresponding alkane and add the suffix amine. 29
Amines: Nomenclature and Physical Properties Chapter Here are some examples of primary amines. 30
Amines: Nomenclature and Physical Properties Chapter 3. Use a prefix with a capital N (italicized) if the amine nitrogen atom has an alkyl group or other group attached (2 o and 3 o amines). 31
Amines: Nomenclature and Physical Properties Chapter 4. In naming diamines, the final -e of the alkane name is not omitted. 32
Amines: Nomenclature and Physical Properties Simple amines are most often referred to by their common names. Chapter The common names for aliphatic amines are formed by naming the alkyl group or groups attached to the nitrogen atom, followed by the ending amine. 33
Amines: Nomenclature and Physical Properties Chapter The common names of some amines are shown here. 34
Amines: Nomenclature and Physical Properties Chapter The most important aromatic amine is aniline (C 6 H 5 NH 2 ). Derivatives are named as substituted anilines. 35
Amines: Nomenclature and Physical Properties Chapter When a group is substituted for a hydrogen atom in the ring, the resulting ring substituted aniline is named as we have previously done with aromatic compounds. 36
Your Turn! Give names for the following amines. CH 3 N CH 2 CH 3 NH 2 CH 2 CH 2 CH 3 IUPAC and common names CH 3 CH 2 CHCH 2 CH 3 IUPAC name 37
Your Turn! Give names for the following amines. CH 3 N CH 2 CH 3 NH 2 CH 2 CH 2 CH 3 IUPAC: N-ethyl-N-methyl-1-propanamine Common: ethylmethylpropylamine CH 3 CH 2 CHCH 2 CH 3 IUPAC name: 3-pentanamine 38
Amines: Nomenclature and Physical Properties Chapter Heterocyclic Compounds Heterocyclic compounds are ring compounds which have two or more atoms in the ring that are different. O, N, and S are common heteroatoms found in heterocyclic compounds. Nitrogen-based heterocyclic compounds like those shown on the next slide are found in DNA... 39
Amines: Nomenclature and Physical Properties Chapter Some heterocyclic amines. 40
Amines: Nomenclature and Physical Properties Chapter Physical Properties of Amines Amines are capable of hydrogen bonding with water. As a result, the aliphatic amines with up to six carbons are quite soluble in water. Methylamine and ethylamine are flammable gases with a strong ammoniacal odor. Trimethylamine has a fishy odor. 41
Amines: Nomenclature and Physical Properties Chapter Amines are responsible for the strong odors of decaying flesh which are produced by bacterial decomposition. Two of these compounds are actually diamines as shown here. 42
Preparation of Amines Amines are prepared by: 1. Alkylation of ammonia and amines 2. Reduction of amides 3. Reduction of nitriles 4. Reduction of aromatic nitro compounds 43
Preparation of Amines Alkylation of Ammonia and Amines Ammonia can be alkylated producing primary, secondary and tertiary amines in successive reacctions. 44
Preparation of Amines Four successive alkylations of ammonia eventually yields a quaternary ammonium salt as seen in the last reaction. 45
Preparation of Amines Reduction of Amides Lithium aluminum hydride (LiAlH 4 ) reduces amides to an amines. 46
Preparation of Amines Reduction of Nitriles Nitriles are reduced to amines using hydrogen gas and a metal catalyst. 47
Preparation of Amines Reduction of Aromatic Nitro Compounds Nitrobenzene is reduced to aniline which is a common aromatic amine. 48
Your Turn! Write the structure of an amide and a nitrile that when reduced would form 2-methyl-1-butanamine. 49
Your Turn! Write the structure of an amide and a nitrile that when reduced would form 2-methyl-1-butanamine. O CH 3 CH 2 CHC NH 2 reduction CH 3 CH 2 CHCH 2 NH 2 CH 3 CH 3 CH 2 CHC N reduction CH 3 2-methyl-1-butanamine CH 3 50
Chemical Properties of Amines Alkaline Properties of Amines Amines resemble ammonia in their reactions. Amines are bases, and like ammonia, produce OH - ions in water 51
Chemical Properties of Amines The ions formed in the reaction of amines with water are substituted ammonium ions. 52
Chemical Properties of Amines Amines are weak bases. Compare the ph of the following amines with the ph of ammonia. A 0.1M solution of NH 3 has a ph of 11.1 CH 3 NH 2 is more basic at a ph of 11.8. An aromatic amine like aniline is less basic at a ph of 8.8. 53
Chemical Properties of Amines Amines are much more basic than amides and the body uses this fact to convert toxic ammonia into urea as shown here. 54
Chemical Properties of Amines Amines also are a source of positive charges on biological molecules under physiological conditions. The neurotransmitters dopamine and serotonin are typical examples of these charged amines. 55
Chemical Properties of Amines Salt Formation Because amines are weak bases, they react with strong acids to form ammonium salts. Methylamine for example reacts with strong acid yielding the corresponding methylammonium salt. 56
Chemical Properties of Amines Methylammonium chloride is a white crystalline solid made up of methylammonium ions, CH 3 NH 3+, and chloride ions, Cl -. Many amines or amino compounds are more stable in the form of the hydrochloride salt. When the free amine is wanted, the HCl is neutralized to liberate the free amine. 57
Chemical Properties of Amines Formation of Amides Amides are produced when primary and secondary amines react with acid chlorides. 58
Your Turn! Show the products of the following reaction. O CH 3 CH 2 C Cl + H 2 NCH 2 CH 3 59
Your Turn! Show the products of the following reaction. O O CH 3 CH 2 C Cl + H 2 NCH 2 CH 3 CH 3 CH 2 C NCH 2 CH 3 + HCl 60
Sources and Uses of Selected Amines Chapter Nitrogen compounds are found throughout the plant and animal kingdoms. Amines, substituted amines, and amides occur in every living cell. Many of these compounds have important physiological effects. 61
Sources and Uses of Selected Amines Chapter Biogenic amines are derived from amino acids and act as neurotransmitters and hormones in animals. GABA (γ-aminobutyric acid) slows nerve action and can bring relaxation. Norepinephrine shown below affects our focus and concentration. 62
Sources and Uses of Selected Amines Chapter Biogenic amines that act as hormones include the fight-orflight hormone epinephrine (also a catecholamine) as well as histamine, an important component in allergic reactions. 63
Sources and Uses of Selected Amines Chapter Amphetamines are designed to mimic the action of biogenic amines and act as stimulants. They are used to treat depression, narcolepsy, and obesity. The most widely abused amphetamine is methamphetamine, commonly called speed. 64
Sources and Uses of Selected Amines Chapter Barbiturates are another class of drugs that are amines. These drugs are classified as sedatives and depress the activity of brain cells. An example is pentobarbital. 65
Sources and Uses of Selected Amines Chapter Basic compounds that are derived from plants and show physiological activity are known as alkaloids. These substances are usually amines. Nicotine, an alkaloid derived from tobacco leaves, acts to stimulate the nervous system. 66
Sources and Uses of Selected Amines Chapter Coffee beans and tea leaves contain caffeine, an alkaloid stimulant. 67
Sources and Uses of Selected Amines Chapter The opium alkaloids are often called opiates and include both compounds derived from the opium poppy and synthetic compounds that have morphine-like activity. These compounds are sleep-inducing and have analgesic properties. 68
Sources and Uses of Selected Amines Chapter These drugs are classified as narcotics because they produce physical addiction, and they are strictly regulated by federal law. An example is methadone. 69
Sources and Uses of Selected Amines Chapter Another common narcotic alkaloid, cocaine, is obtained from the leaves of the coca plant. 70
Chapter 25 Summary Carboxylic acids react with ammonia to form salts. Amides are neutral, nonionic compounds. The IUPAC naming of amides follows a similar process to that used for other organic molecules. Strong intermolecular hydrogen bonding accounts for the amides high melting, boiling points and water solubility. 71
Chapter 25 Summary Amide hydrolysis uses water to split an amide into a carboxylic acid portion and a nitrogen-containing portion. Polyamides form when a carboxylic acid from one monomer reacts with an amine from a second monomer. Urea is a simple diamide of the structure. Animals excrete nitrogen in the form of urea. Urea is also a valuable fertilizer and industrial chemical. 72
Chapter 25 Summary An amine is a substituted ammonia molecule bonded to at least one alkyl or aryl group. Many simple amines are referred to by their common names. The most important aromatic amine is aniline. Heterocyclic compounds are ring structures where the atoms forming the ring are not all alike. 73
Chapter 25 Summary Intermolecular hydrogen bonding accounts for the amines high water solubility. Alkylation of ammonia (with alkyl halides) will successively form primary, secondary, and tertiary amines. Reduction of several different nitrogen-containing compounds will form amines. 74
Chapter 25 Summary Amines are bases. Amines react with strong acids to form salts. Primary and secondary amines react with acid chlorides to form amides. Proteins are polymers of amino acids linked by amide bonds. Biogenic amines are derived from amino acids and act as neurotransmitters and hormones in animals. 75
Chapter 25 Summary Many powerful drugs act by changing the biochemistry of biogenic amines. Basic compounds that are derived from plants and show physiological activity are known as alkaloids. 76