Amines and Amides - K. A. Boudreaux, Angelo State University, Lecture notes of Chemistry

Download Amines and Amides - K. A. Boudreaux, Angelo State University and more Lecture notes Chemistry in PDF only on Docsity! Chapter 6 Amines and Amides Chapter Objectives: • Learn to recognize the amine and amide functional groups. • Learn the IUPAC system for naming amines and amides. • Learn the important physical properties of the amines and amides. • Learn the major chemical reactions of amines and amides, and learn how to predict the products of amide synthesis and hydrolysis reactions. • Learn some of the important properties of condensation polymers, especially the polyamides. Chapter 6 Amines and Amides 2 Nitrogen-Containing Functional Groups • Nitrogen is in Group V of the periodic table, and in most of its compounds, it has three single bonds and one lone pair: • In this chapter, we will take a look at two functional groups which contain nitrogen atoms connected to carbons: the amines and the amides. R C O N R" R' Amide NR R'' R' Amine N Mr. Kevin A. Boudreaux Angelo State University CHEM 2353 Fundamentals of Organic Chemistry Organic and Biochemistry for Today (Seager & Slabaugh) Chapter 6 Amines and Amides 3 Classification and Nomenclature of Amines 4 Amines • Amines and amides are abundant in nature. They are a major component of proteins and enzymes, nucleic acids, alkaloid drugs, etc. (Alkaloids are N- containing, weakly basic organic compounds; thousands of these substances are known.) • Amines are organic derivatives of ammonia, NH3, in which one or more of the three H’s is replaced by a carbon group. • Amines are classified as primary (1°), secondary (2°), or tertiary (3°), depending on how many carbon groups are connected to the nitrogen atom. NR R'' R' 3° Amine NR H H 1° Amine NR H R' 2° Amine NH H H Ammonia Chapter 6 Amines and Amides 9 Examples: Nomenclature of Amines • Provide common names for the following 2° and 3° amines; for 1° amines, provide common and/or IUPAC names where possible. CH3CCH2CH2CH2CHCH3 O NH2 OH NH2 10 Examples: Nomenclature of Amines • Provide names for the following aromatic amines. N CH3 CH3 N CH3 CH2CH3 NH CH3 NH2 CH3 Chapter 6 Amines and Amides 11 Examples: Nomenclature of Amines • Provide names for the following aromatic amines. N CH3 CH3 CH3 N CH3 H CH2CH3 N CH3 CH3 CH3CH3CH2 12 Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – ethylisopropylamine – tert-butylamine – 2-pentanamine Chapter 6 Amines and Amides 13 Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – N-methyl-2-propanamine – 1,6-diaminohexane – 3-amino-1-propanol 14 Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – N-methyl-2-chloroaniline – N,3-diethylaniline – N,N-dimethylaniline Chapter 6 Amines and Amides 19 Physical Properties of Amines: Water Solubility • 1°, 2°, and 3° amines can all form hydrogen bonds with water. • Low-molecular weight amines are generally water- soluble. NCH3 H H H O H O H H O H H NCH3 CH3 H H O H O H H NCH3 CH3 CH3 H O H 20 Physical Properties of Amines: Odor • Low molecular-weight amines tend to have sharp, penetrating odors similar to ammonia • Higher molecular-weight amines often smell like rotting fish, and are often found in decaying animal tissues. NCH3 CH3 CH3 Trimethylamine Responsible for the odor of rotting fish CH2CH2CH2CH2 NH2 NH2 1,4-Diaminobutane (Putrescine) A poisonous oil present in rotting flesh; produced during the decomposition of the amino acid arginine; also partially responsible for the odor of urine and bad breath CH2CH2CH2CH2CH2 NH2 NH2 1,5-Diaminopentane (Cadaverine) A poisonous, viscous liquid present in rotting flesh; produced during the decomposition of the amino acid lysine; also partially responsible for the odor of urine and bad breath Chapter 6 Amines and Amides 21 Examples: Predicting Physical Properties • Arrange the following compounds in order of increasing boiling point. (All of the compounds have about the same molecular weight.) propanoic acid, diethylamine, 1-butanol, ethyldimethylamine 22 Examples: Predicting Physical Properties • Which member of each of the following pairs of compounds would you expect to have a higher boiling point? – 2-aminopropane or 2-aminohexane – triethylamine or 1-aminohexane – propanoic acid or diethylamine – 1-pentanol or 1-aminopentane Chapter 6 Amines and Amides 23 Some Important Alkaloids 24 Important Alkaloids N N N N O CH3 O CH3 CH3 Caffeine Found in the seeds of Coffea arabica, roasted coffee beans; inhibits the action of phosphodiesterase, an enzyme which inhibits cyclic adenosine monophosphate (AMP), which is responsible for forming glucose in the bloodstream N N N N O H O CH3 CH3 Theobromine Found in the seeds of Theobroma cacao; the stimulating ingredient in chocolate. N N CH3 H Nicotene Found in tobacco plants; mild stimulant in small doses; addictive, but not especially harmful itself N HO N CH3O Quinine Antimalarial drug from cinchona treeCH3O N CH3 Dextromethorphan Ingredient in cough suppressants. Chapter 6 Amines and Amides 29 Antihistamines N N NH2 H Histamine People who are allergic to pollen produce histamine, which causes blood vessels to dilate and leak, releasing fluid into surrounding tissues, causing watery eyes, sniffles, congestion, and other symptoms of hay fever (allergic rhinitis); also causes the symptoms of the common cold and swelling after insect bites. O N CH3 CH3 Diphenylhydramine an antihistamine; active ingredient in Benadryl; sometimes used in sleeping pills OH CH3 N CH3 H Ephedrine / Pseudoephedrine found in the Chinese ma-huang plant; a decongestant used in many cold remedies 30 Antihistamines Loratadine (Claritin®) A non-drowsy antihistamine N Cl N O O Cetrizide (Zyrtec®) A stronger antihistamine than Allegra or Claritin, but causes drowsiness in some people O OH O N N Cl Fexofenadine (Allegra®) A non-drowsy antihistamine; available by perscription only O HO N OH OH Chapter 6 Amines and Amides 31 Reactions of Amines 32 Bases • A base takes a proton (H+) from another species. A base produces hydroxide ions, OH–, when dissolved in water: B + H2O  BH+ + OH– • A strong base is one that completely dissociates in water (i.e., every molecule of the acid splits apart). • A weak base is one in which only a small percentage of the molecules are dissociated at any one time. • Acidic solution: pH < 7.00 ([H3O+] > [OH-]) • Basic solution: pH > 7.00 ([H3O+] < [OH-]) • Neutral solution: pH = 7.00 ([H3O+] = [OH-]) Chapter 6 Amines and Amides 33 Chemical Properties of Amines: Basicity • Amines are weak organic bases. They react with water to produce alkylammonium ions and hydroxide anions: • and with acids to produce alkylammonium salts: N H R H OH H N H R H H+ + OH N H R H + ClH N H R H H Cl 34 Alkylammonium Salts • Salts of amines are named by changing “amine” to “ammonium” and adding the name of the negative ion to the end of the word: CH3 NH3 Cl methylammonium chloride CH3CH2 N CH2CH3 CH2CH3 H Br triethylammonium bromide CH3 N CH2CH3 H C2H3O2 ethylmethylammonium acetate H Chapter 6 Amines and Amides 39 Amides 40 Amides • Amides contain a nitrogen which is directly attached to a carbon in a carbonyl group: R C O N H H N,N-unsubstituted amide R C O N H CH3 N-substituted amide R C O N CH3 CH3 N,N-disubstituted amide R C O N R" R' Amide amide linkage (peptide bond) Chapter 6 Amines and Amides 41 Nomenclature of Amides • Amides are named by changing the -oic acid ending of the corresponding carboxylic acid to -amide. If alkyl groups are attached to the nitrogen, they are named as N-alkyl substituents. H C NH2 methanamide (formamide) O CH3 C OH ethanoic acid (acetic acid) O C NH2 O benzamide H C OH methanoic acid (formic acid) O CH3 C NH2 ethanamide (acetamide) O 42 Examples: Nomenclature of Amides • Name the following compounds: CH3 C N H CH3 O CH3CN CH3 CH3 O CN CH3 CH3 O C CH3 CH3 CH3 Chapter 6 Amines and Amides 43 Examples: Nomenclature of Amides • Name the following compounds: CH3CH2CH2 C N CH2CH3 O CH3 CH3CH2CH2CHCH C N H CH3 CH3 NH2 O 44 Examples: Nomenclature of Amides • Name the following compounds: CH3CH2CH2CHCH2 C N CH2CH3 CH2CH3 O CH3 CHCH2CH2CCH3CNCH3 O CH2CHCH3 CH3 CH3 CH2CH3CH3 Chapter 6 Amines and Amides 49 Physical Properties of Amides 50 Physical Properties of Amides • N,N-unsubstituted amides can form a complex network of hydrogen bonds. They tend to have high melting points and also high boiling points. R C O N H H R C N H H O R C N H H O R C O N H H Chapter 6 Amines and Amides 51 Physical Properties of Amides • N-substituted amides often have lower melting points and boiling points than N,N-unsubstituted amides because fewer hydrogen bonds can form. • N,N-disubstituted amides cannot form hydrogen bonds, and have even lower melting points and boiling points. • All amides can hydrogen bond with water, so low- molecular weight amides are water-soluble. Boiling Point: N,N-unsubstituted amides N-substituted amides N,N-disubstituted amides 52 Examples: Predicting Physical Properties • Arrange the following compounds in order of increasing boiling point. (All of the compounds have about the same molecular weight.) N-ethylethanamide butanamide N,N-dimethylethanamide Chapter 6 Amines and Amides 53 Important Amides 54 Important Amides O N CH2CH3 CH2CH3 CH3 N,N-Diethyl-m-toluamide Active ingredient in OFF Cl N N H O Diazepam (Valium) A benzodiazepene tranquilizer; acts by enhancing the inhibitory neurotransmitter GABA; since it binds to the same protein as ethanol, combinations of valium and ethanol can be deadly NO O N O O H Thalidomide Until 1956, a very popular, safe sedative; the largest market was for pregnant women who were experiencing morning sickness. However, it caused massive birth defects in women who used it in the early states of pregnancy, and was banned in Europe; it was never authorized for sale in the U.S. Chapter 6 Amines and Amides 59 Molecules To Dye For • Dyes are compounds that can be used to color other materials, such as clothing, paper, hair, etc. • Many organic dyes contain a long series of double bonds that are close together. If the chain of double bonds is long enough, these molecules can absorb low-energy light in the visible region of the electromagnetic spectrum, resulting in colors that are visible to the human eye. N N HO H O Indigo A naturally occurring blue dye which has been used for thousands of years. It is obtained from an Indian plant (Indigofera tinctoria) and the European woad (Isatis tinctoria). Today, indigo can be made synthetically, and is used in dyeing denim to make blue jeans. N N HO H O Br Br Tyrian purple 6,6'-dibromoindigo Tyrian purple, or “royal purple,” is a purple dye originally obtained from a species of mollusk (Murex) found near the cities of Tyre and Sidon in ancient Phoenicia. It took about 9,000 mollusk shells to obtain one gram of the dye, making it very expensive. This dye was used by royalty (hence the name “royal purple”) and the Roman aristocracy. 60 Molecules To Dye For N N CH3 NH2 CH3 N H CH3 SO4 2_ 2 Mauve This is the first of the synthetic dyes. It was discovered by the 18-year-old English chemist William Henry Perkin in his home laboratory, while attempting to synthesize quinine (the only known treatment for malaria at that time). While cleaning up the sludge from one of his failed attempts, he noticed that the sludge was turning the water in his sink violet, and that cloth would pick up this purple color. Perkin patented his serendipitous discovery, and went into business making dyes, becoming so successful that he was able to retire at the age of 36 to focus his attention on chemical research. Chapter 6 Amines and Amides 61 FD&C Dyes These color additives are approved by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (FD&C, 1938, amended 1997) for use in foods. SO3 - N SO3Na N NaO3S FD&C Blue No. 1 Brilliant Blue FCF FD&C Blue No. 2 Indigo Carmine, Indigotine N N HO H O NaO3S SO3Na SO3 - N SO3Na N NaO3S FD&C Green No. 3 Fast Green FCF OH FD&C Red No. 3 Erythrosine ONaO I I I I O CO2Na 62 FD&C Dyes FD&C Red No. 40 Allura Red AC N N HO SO3Na OCH3 NaO3S CH3 FD&C Yellow No. 5 Tartrazine NaO3S N N N N HO CO2Na SO3Na FD&C Yellow No. 6 Sunset Yellow FCF N N HO SO3Na NaO3S Orange B Used in sausage and frankfurter casings N N N N HO CO2CH2CH3 SO3Na NaO3S Citrus Red No. 2 Used to color orange skins N N HO OCH3CH3 Chapter 6 Amines and Amides 63 Molecules To Dye For Butter yellow N CH3 CH3 N N Chicago blue N OCH3CH3O N NN OH HO NH2 H2NHO3S SO3H SO3H HO3S Methyl orange N CH3 CH3 N N SO3Na Para red N OH N NO2 Methyl red N CH3 CH3 N N OH O 64 Molecules To Dye For Resazurin O N OHO O Methylene Blue S N NN CH3 CH3 CH3 CH3 Cl N N N N NH2 H2N S S NaO O O ONa O O Congo red N CH3 N H3C CH3 N H3C CH3 CH3 Cl Methyl violet 10B (crystal violet) Chapter 6 Amines and Amides 69 Examples: Formation of Amides • Complete the following reactions: CH3 C O C CH3 OO + CH3CH2CH2NH2 70 Examples: Formation of Amides • Complete the following reactions: CH3 C Cl NCH3 CH3+ CH3O Chapter 6 Amines and Amides 71 Chemical Properties of Amides • Unlike amines, amides are not basic. • Amide hydrolysis can take place under acidic or basic conditions: R C O N R' R C O OH N+ H R' Cl-H R''R'' H2O+ + HCl + R C O N R' R C O O- Na+ N R'H R'' R'' NaOH+ + 72 Examples: Reactions of Amines and Amides • Complete the following reactions: CH3 C O N CH3 H H2O+ + HCl CH3 C O N CH3 H NaOH+ Chapter 6 Amines and Amides 73 Condensation Polymers: Polyamides 74 Condensation Polymers: Polyamides (CH2)10 C Cl O C Cl O sebacoyl chloride1,6-diaminohexane H2N (CH2)6 NH2 1,6-diaminohexane H2N (CH2)6 NH2 (CH2)10 C O C O H2N (CH2)6 N N (CH2)6 NH2 H H (CH2)10 C O C O (CH2)6 N N (CH2)6 H H (CH2)10 C Cl O C N O (CH2)10 C N O C Cl O H H (CH2)10 C O C O (CH2)6 N N (CH2)6 H H (CH2)10 C O C N O (CH2)10 C N O C O H H N (CH2)6 NH2H2N (CH2)6 N H H (CH2)10 C O C O (CH2)6 N N (CH2)6 H H (CH2)10 C O C N O (CH2)10 C N O C O H H N (CH2)6(CH2)6 N H H (CH2)10 C Cl O C N O (CH2)10 C N O C Cl O H H etc. Chapter 6 Amines and Amides 79 Neurotransmitters 80 Neurotransmitters • Neurotransmitters are small molecules that carry nerve impulses from one neuron to the next. • Neurons consist of the main cell body (the soma), long stemlike projections (the axons), and short fibers connected to the soma (the dendrites). • Neurons are not connected directly to each other, but are separated by a small gap called a synapse. • When an electrical current originating in a neuron reaches the synaptic terminals at the end of the axon, the terminals release neurotransmitter molecules into the synapse; these molecules diffuse across the synapse and bind to receptors on the dendrites of the next neuron, stimulating an electrical current, which travels along that neuron until it reaches the next synapse, and so on until the nerve impulse reaches the brain. Chapter 6 Amines and Amides 81 Figure 6.5 A nerve cell and the transmission of a nerve signal. 82 HO HO NH2 Dopa Synthesized from the amino acid tyrosine; used as a treatment for Parkinson's disease, which is caused by a breakdown of dopamine-based neurons that control the brain's motor system (dopamine cannot be administered directly because it does not cross the blood-brain barrier; however, the L-form of dopa does) CO2H HO HO NH2 Dopamine Synthesized from dopa; used as a treatment for low blood pressure HO HO OH NH2 Norepinephrine (NE) Synthesized from dopamine; an excess of NE in the brain is related to feelings of elation or manic states; low NE levels are linked to depression; the stimulant action of epinephrine and NE in some cells can be reduced by beta blockers, which are used to treat cardiac arrhythmias, angina, and hypertension N H NH2 Serotonin Synthesized from the amino acid tryptophan; influences sleeping, body temperature, and sensory perception; drugs that mimic serotonin are used to treat depression, anxiety, and obsessive-compulsive disorder; serotonin blockers are used to treat migraine headaches and nausea resulting from chemotherapy Chapter 6 Amines and Amides 83 HO HO OH N CH3 H Epinephrine (Adrenalin) More important as a hormone than a neurotransmitter; synthesized in the adrenal glad; release of adrenalin into the bloodstream in response to pain, anger, or fear increases blood glucose levels, and provides a sudden burst of energy (fight-or-flight response); increases force of heart contractions (raising blood pressure); also a vasoconstrictor; used in local anesthetics to keep the anesthetic from being washed away O O N+ CH3 CH3 CH3 Acetylcholine H2N OH O Gamma-aminobutanoic acid (GABA) A inhibitory neurotransmitter 84 Pheynlephrines and Amphetamines NH2 CH3 Amphetamine (Benzedrine) a powerful nervous stimulant; raises blood glucose levels, increases heart rate and blood pressure N CH3 CH3 H N-Methylamphetamine (Methedrine, "speed") Also a powerful nervous stimulant NH2 CH3O CH3O CH3O Mescaline Hallucinogen from peyote cactus OH CH3 N CH3 H Ephedrine / Pseudoephedrine found in the Chinese ma-huang plant; a decongestant used in many cold remedies N CH3 CH3 H 3,4-Methylenedioxymethamphetamine (MDMA), "Ectasy" O O OH N CH3 H Phenylephrine Common decongestant HO Chapter 6 Amines and Amides 89 Aspartate (Asp) Tryptophan (Try) O H2N O N CH3 H O N OH O H O OH N N H H Glycine (Gly) Alanine (Ala) etc. a protein (a polyamide) Instructions for making proteins are encoded in DNA. Gly Ala Asp Try 90Three levels of structure in a telephone cord Chapter 6 Amines and Amides 91R-group interactions leading to a protein tertiary structure 92 Segment of a protein showing -helix, -pleated sheet, and random coil structures Chapter 6 Amines and Amides 93 Some Hideously Complex Molecules 94 O OH O O O O H OH N(CH3)2 H OCH3 OH Erythromycin an antibiotic OH HO OH H O H NH NH2N NH NH2 NH O H H O CHO CH3 OH O H OHN OH CH3 H OHStreptomycin an antibiotic