Amines and Amides: Nomenclature, Properties, and Reactions, Lecture notes of Organic Chemistry

Download Amines and Amides: Nomenclature, Properties, and Reactions and more Lecture notes Organic Chemistry in PDF only on Docsity! Chapter 6 Amines and Amides Mr. Kevin A. Boudreaux Angelo State University CHEM 2353 Fundamentals of Organic Chemistry Organic and Biochemistry for Today (Seager & Slabaugh) www.angelo.edu/faculty/kboudrea 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 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 5 Examples: Classifying Amines • Classify the following amines as primary (1°), secondary (2°), or tertiary (3°). NCH3CH2CH2 H H NCH3 CH3 CH3 CH3CH2CHCH3 NH2 NCH3CH2 H CH3 N H N 6 Nomenclature of Amines • Simple 1°, 2°, and 3° amines: common (trivial) names are obtained by alphabetically arranging the names of the alkyl substituents on the nitrogen and adding the suffix -amine (e.g., ethylmethylamine). • Amines in the IUPAC system: the “e” ending of the alkane name for the longest chain is replaced with –amine. The amine group is located by the position number. Groups that are attached to the nitrogen atom are located using “N” as the position number. More complex primary amines are named with —NH2 as the amino substituent. • Aromatic amines: named as derivatives of the parent compound aniline. Substituents attached to the nitrogen are indicated by using “N-” as the location number. NH2 aniline Chapter 6 Amines and Amides 7 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. CH3 NH2 CH3 N CH3 H CH3CH2CH2 NH2CH3 N CH2CH3 H 8 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. CH3CH2CH2CHCH3 NH2 CH3 N CH3 CH3 CH3CHCH2CH2 NH2 NH2 CH3CH2CH2CHCH3 NH CH3 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 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 25 N CH3 OCH3 O O H H O Cocaine The form which is “snorted” is the hydrochloride salt; the free-base “crack” form is burned and inhaled, and reaches the brain in 15 seconds. N CH3 O H O OH Atropine relaxes muscles and reduces secretion of saliva during surgery; used to dilate pupils for eye examinations. N CH3 O H O O OH Scopolamine used in treatment of motion sickness N H H Coniine Poison from hemlock Zephiran chloride (benzalkonium chloride) Antiseptic compound that kills bacteria and fungi on contact N+ R H3C CH3 26 N OO H H H H H N Strychnine A poison from strychnos plant (Nux vomica); used as a rat and mouse poison N N H O CH3O H Melatonin A naturally occuring hormone produced in the pineal gland; its production is triggered by the absence of light; causes drowsiness in humans at night, triggers birds to migrate, and signals dogs to shed their winter coats; sold as a treatment for jet lag. N CH3 O N CH2CH3 CH2CH3 H H N H Lysergic acid diethylamide (LSD) A synthetic hallucinogen from alkaloids obtained from ergot, a fungus which grows on rye Inosine Monophosphate (IMP) With monosodium glutamate (MSG), one of the major substances responsible for the flavor of meat N NN N OH O OHOH PHO OH O 27 O HO HO N CH3 Morphine Found in the opium poppy; a CNS depressant; very effective painkiller O CH3O HO N CH3 Codeine Used in some cough syrups to depress the action of the cough center of the brain O O O N CH3 CH3 O CH3 O Heroin More fat-soluble than morphine, and must be injected directly into the bloodstream, but crosses the blood-brain barrier more readily, causing it to be more potent than morphine 28 Nitrogen Wastes The disposal of waste nitrogen from the body is a problem which different species of animals have solved in different ways: NH2 NO N N O H HH O Allantoin Most mammals contain enzymes which metabolyze uric acid into allantoin. NH2 NO H O OH N H NH2 O Allantoic acid Marine vertebrates further metabolyze allantoin into allantoic acid. N N O O N N O H H H H Uric acid Birds, reptiles and insects excrete nigrogen wastes in the form of uric acid. Uric acid can be eliminated directly in the solid form, without being dissolved in water. It is produced in the body from foods and beverages rich in purines, such as claret and port. Lactic acid inhibits the removal of salts of uric acid in the urine; these salts instead deposit in the joints, causing gout. Dalmations have been bred to have black spots with no white hairs in them on their coats; however, the gene which determines the presence of white hairs is linked to the gene which codes the enzyme which breaks down uric acid into allantoin. Dalmations thus excrete uric acid instead of allantoin, and are very susceptible to gout. O N N H H H H Urea Urea is the major organic component of urine; about 25 g are excreted every day by humans. Cartilaginous fish and amphibians also excrete urea. NH4 + X– Marine invertebrates excrete ammonium salts. 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-]) 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 35 Alkylammonium Salts • Salts of amines are generally white crystalline solids with high melting points. • The ionic charges makes these salts more soluble in water than the neutral amines. Many amine- containing drugs are administered in the form of alkylammonium salts to increase their solubility in bodily fluids. OHO OH N H3C H Morphine sulfate water-soluble HSO4 - OHO OH N H3C Morphine water-insoluble H2SO4+ 36 Chemical Properties of Amines: Basicity • Ammonium salts may be converted back into neutral amines by a strong base: • Thus, by adjusting the pH of the solution, it is possible to influence whether an amine is present in the neutral form or as its ammonium cation form: R—NH3 + Cl- + NaOH  R—NH2 + H2O + NaCl R NH2 + H2O + -OHR NH3 + base (high pH) acid (low pH) amine alkylammonium ion Chapter 6 Amines and Amides 37 Quaternary Ammonium Salts • In addition to salts of 1°, 2°, and 3° amines, it is possible to have amine cations which contain four alkyl groups attached to a nitrogen atom, which will always carry a positive charge, regardless of the pH of the surrounding solution. These are known as quaternary ammonium salts. • These salts are present in many antiseptics and antibacterial agents. N+R R'' R' R''' X- quaternary ammonium salt N+CH3 CH2CH3 CH2CH3 CH2CH3 Cl- triethylmethylammonium chloride 38 Examples: Basicity of Amines • Complete the following reactions: CH3NH2 + HCl NHCH3 + HCl NCH3 CH3 H CH3 + NaOH Cl 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) 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 55 Hot Stuff CH3O HO N O H Capsaicin Found in red and green chili peppers; active component of paprika O O N O Piperine Component of white and black pepper Allyl isocyanate Used in horseradish flavor, mustard oil, pickles, salad dressings and sauces; mustard plasters, medications and fumigants N C S Zingerone The pungent, hot component of ginger CH3O HO O 56 Barbiturates N N O O O H H Barbituric acid First synthesized by Adolf von Baeyer in 1864; barbiturates are soporifics, and are used as tranquilizers and anesthetics; many are also addictive, and overdoses can be fatal. (Other barbiturates include Seconal, Veronal, Phenobarbitol, Thiopental, Amobarbitol, etc.) N N O H S O H Thiopental (Pentothal) An intravenous anesthetic N N O H O O H Amobarbital (Amytal) Used in the treatment of insomnia N N O O O H H Phenobarbitol Anti-seizure medication, sedative 57 Sulfa Drugs Sulfanilamide, the first antibiotic, was discovered by Gerhard Damagk (Nobel Prize, 1939), who observed the antibacterial action of the red dye Protonsil; further researched showed that it was the metabolic byproduct, sulfanilamide, which was the active form. It prevents bacteria from synthesizing folic acid, which they need in order to grow. Bacterial enzymes synthesize folic acid using para-aminobenzoic acid (PABA); sulfanilamide fits into the enzyme more tightly, blocking it from taking up PABA, and thus blocking folic acid synthesis. The bacterium cannot grow, and eventually dies. Humans obtain folic acid from their diet (an essential vitamin), so sulfa drugs do not harm people in this way (although they can cause allergic reactions). para-Aminobenzoic aid (PABA) OH O H2N N N N N N H O H2N H N O H O OH OH O Folic acid Prontosil S NH2 O O N N NH2 S NH2 O O H2N Sulfanilamide 58 Penicillin N S CH3 CH3 O N H OCH3 OCH3 CO2H O R Penicillin Penicillin G Methicillin R = Penicillin V Ampicillin NH2 O Penicillin is an antibiotic compound produced by the molds Penicillium notatum and Penicillium chrysogenum; it was discovered by Alexander Fleming in 1928 in a culture of bread mold. There are several varieties: Penicillin G and Methicillin are administered by injection; Penicillin V is an oral form which is not broken down in the stomach; Ampicillin is a broad spectrum penicillin which can be administered by injection or orally 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 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) 65 Reactions of Amides 66 Amide Formation • Amides are formed when acid chlorides react with 1° or 2° amines; 3° amines cannot form amides: R C Cl NR' H R C N R' ++ H HO O HCl R C Cl NR' H R C N R' ++ R'' R''O O HCl R C Cl + NR' R''' no reaction R''O Chapter 6 Amines and Amides 67 Amide Formation • Amides are also formed when acid anhydrides react with 1° or 2° amines. NR' H R C N R'R C O C R OO HO C R O + + H HO NR' H R C N R'R C O C R OO HO C R O + + R'' R''O NR' R'''R C O C R OO + R'' no reaction 68 Examples: Formation of Amides • Complete the following reactions: C Cl NCH3 H+ CH3O 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 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 85 Amino Acids and Proteins 86 Amino Acids O OH H2N R H Amino Acids O OH H2N Glycine (Gly) O OH H2N CH3 Alanine (Ala) O OH H2N Valine (Val) O OH H2N Leucine (Leu) O OH H2N Isoleucine (Ile) O OH H2N Phenylalanine (Phe) O OH N Proline (Pro) H O OH H2N S Methionine (Met) 87 O OH H2N OH Serine (Ser) O OH H2N OH Threonine (Thr) O OH H2N OH Tyrosine (Tyr) O OH H2N N H Tryptophan (Try) O OH H2N SH Cysteine (Cys) O OH H2N O NH2 Glutamine (Gln) O OH H2N N NH Histidine (His) O OH H2N NH2 O Asparagine (Asn) O OH H2N NH2 Lysine (Lys) Aspartate (Asp) O OH H2N OH O O OH H2N O OH Glutamate (Glu) Arginine (Arg) O OH H2N N H NH2 O 88 O OH H2N Glycine (Gly) O OH H2N CH3 Alanine (Ala) O H2N O OH N CH3 H Glycine (Gly) Alanine (Ala) O OH H2N OH O Aspartate (Asp) O H2N O N CH3 H O OH N OH O H Glycine (Gly) Alanine (Ala) Aspartate (Asp) O OH H2N N H Tryptophan (Try) 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 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 95 O O O O OH O O NO H O OH N NH2 H N H Bufotoxin isolated from the toad Bufo marinus; increases the contractive power of weak heart muscles; also causes terrifying hallucinations O O OH O O O O H OO OHN O O OH HO Taxol potential anti-cancer drug isolated from the Pacific yew tree 96 Vitamin B12 (cobalamine) Found in meat, fish, eggs, and milk; a coenzyme involved in amino acid metabolism; needed for the production of red blood cells (a deficiency in vitamin B12 results in anemia) N N NN CH3 Co O H2N CH3 H3C O H2N H3C H CH3 H2N O NH O NH2 O CH3 CH3 O NH2 CH3 NH2 O OH3C P O O O O OH HO N N CH3 CH3 Chapter 6 Amines and Amides 97 CR OH H H CR OH H R CR OH R R R O R O H R C O H R O C R CR H OH OR CR H OR OR CR R OH OR CR R OR OR C C R R R R C C RR primary (1°) alcohol (-ol) secondary (2°) alcohol (-ol) tertiary (3°) alcohol (-ol) ether (alkoxy-, -ether) phenol (-phenol) ketone (-one) aldehyde (-al) hemiacetal acetal hemiketal ketal alkane (-ane) alkene (-ene) alkyne (-yne) aromatic ring (phenyl-, -benzene) SHR thiol C C HH H H H H Functional Groups 98 R O C OH R O C O- M+ R O C O R R C O C R OO R C O Cl RO O P OH OH NR H H NR H R NR R R N+R R R R R C O NHR R C O acid anhydrideacid chloride N ester (alkyl + -oate) phosphate ester R carboxylate salt (metal + -oate) R carboxylic acid (-oic acid) R C O primary (1°) amine (amino-, -amine) secondary (2°) amine (-amine) NH2 tertiary (3°) amine (-amine) quaternary ammonium salt (alkyl ammonium + anion) amide (N-alkyl + -amide) 99 3. Conversion of an alkylammonium salt back to an amine. R—NH3 + Cl- + NaOH  R—NH2 + H2O + NaCl Reactions of Amines and Amides N H R H OH H N H R H H+ 1. Reaction of an amine with water to produce an alkylammonium ion. amine alkylammonium ion + -OH N H R H ClH N H R H H -Cl+ 2. Reaction of an amine with acid to produce an alkylammonium salt. amine hydrochloric acid alkylammonium chloride 100 R' C N R R' C OH N+ R R Cl-H H 5. Hydrolysis of amides under acidic and basic conditions. amide carboxylic acid alkylammonium salt O O R + R' C N R R' C O- Na+ N R RH amide carboxylate salt amine O O R + H2O NaOH HCl+ + + R' C Cl NR H R' C N R+ 4. Formation of an amide. (NR with tertiary amines.) acid chloride amine (1° or 2°) amide HCl+ R RO O O C R NR H R' C N R+ acid anhydride amine (1° or 2°) amide + R RO O CR' O R' C OH carboxylic acid O 101 The End