Chapter 6 Amines and AmidesNitrogen-Containing Functional Groups Nitrogen is in Group V of the periodic table, and inmost of its compounds, it has three single bonds andone lone pair:Chapter 6Amines and AmidesNChapter Objectives: In this chapter, we will take a look at two functionalgroups which contain nitrogen atoms connected tocarbons: the amines and the amides. 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 theproducts of amide synthesis and hydrolysis reactions. Learn some of the important properties of condensation polymers, especially thepolyamides.ORMr. Kevin A. BoudreauxAngelo State UniversityCHEM 2353 Fundamentals of Organic ChemistryOrganic and Biochemistry for Today (Seager & 'R"AmineAmide2Amines Amines and amides are abundant in nature. Theyare a major component of proteins and enzymes,nucleic acids, alkaloid drugs, etc. (Alkaloids are Ncontaining, weakly basic organic compounds;thousands of these substances are known.) Amines are organic derivatives of ammonia, NH3, inwhich one or more of the three H’s is replaced by acarbon group. Amines are classified as primary (1 ), secondary(2 ), or tertiary (3 ), depending on how manycarbon groups are connected to the nitrogen atom.Classification andNomenclature of AminesH3Examples: Classifying nia1 Amine2 Amine3 Amine4 Amines in the IUPAC system: the “e” ending ofthe alkane name for the longest chain is replacedwith –amine. The amine group is located by theposition number. Groups that are attached to thenitrogen atom are located using “N” as the positionnumber. More complex primary amines are namedwith —NH2 as the amino substituent.CH3CH2CHCH3HCH3CH2R Simple 1 , 2 , and 3 amines: common (trivial)names are obtained by alphabetically arranging thenames of the alkyl substituents on the nitrogen andadding the suffix -amine (e.g., ethylmethylamine).NH2CH3HNomenclature of Amines Classify the following amines as primary (1 ),secondary (2 ), or tertiary (3 ).HNN Aromatic amines: named as derivatives of theparent compound aniline. Substituents attached tothe nitrogen are indicated by using “N-” as thelocation number.5NH2aniline 6

Chapter 6 Amines and AmidesExamples: Nomenclature of AminesExamples: Nomenclature of Amines Provide common names for the following 2 and 3 amines; for 1 amines, provide common and/orIUPAC names where possible. Provide common names for the following 2 and 3 amines; for 1 amines, provide common and/orIUPAC names where HCH3NCH3CH2CH2CH2CH3NH CH3NH2CH3CHCH2CH2CH3CH2CH2CHCH3NH2NH27Examples: Nomenclature of Amines8Examples: Nomenclature of Amines Provide common names for the following 2 and 3 amines; for 1 amines, provide common and/orIUPAC names where possible. Provide names for the following aromatic amines.NH2NH 9Examples: Nomenclature of AminesExamples: Nomenclature of Amines Provide names for the following aromatic amines.CH3NCH3CH310 Draw structural formulas for the following molecules:– ethylisopropylamineHN– tert-butylamineCH3CH2CH3CH3CH3CH2NCH3– 2-pentanamineCH31112

Chapter 6 Amines and AmidesExamples: Nomenclature of AminesExamples: Nomenclature of Amines Draw structural formulas for the following molecules:– N-methyl-2-propanamine Draw structural formulas for the following molecules:– N-methyl-2-chloroaniline– 1,6-diaminohexane– N,3-diethylaniline– 3-amino-1-propanol– N,N-dimethylaniline1314Physical Properties of Amines: H-Bonding 1 and 2 amines can hydrogen bond to each other:CH3NHHPhysical Properties ofAminesCH3NHCH3NHHHNCH3HCH3HNCH3HCH3NCH3CH3 3 amines cannot hydrogen bond to each other:CH3NCH3CH3CH3XCH315Physical Properties of Amines: Boiling Points Nitrogen is less electronegative than oxygen, so theN—H bond is not quite as polar as the O—H bond.NCH3CH3 X NCH3CH316Physical Properties of Amines: Boiling PointsBoiling Point:Carboxylic acidAlcohols1 /2 Amines3 Amines/Alkanes– Hydrogen bonds from N—H’s are not as strongas those resulting from O—H’s.– Hydrogen bonding between 1 and 2 amines isnot as strong as those found in alcohols orcarboxylic acids.Name 1 and 2 amines have lower boiling points thanalcohols of similar molecular weight. 3 amines, since they do not hydrogen bond to eachother, have boiling points similar to hydrocarbons ofthe same molecular weight.17Molecular BoilingweightpointAcetic acid60.0 g/mol 118 C1-propanol60.1 g/mol 97 Cpropyl amine59.1 g/mol 48 Cethylmethylamine 59.1 g/mol 36 Ctrimethylamine59.1 g/mol 2.9 Cbutane58.1 g/mol -0.5 C18

Chapter 6 Amines and AmidesPhysical Properties of Amines: Water SolubilityPhysical Properties of Amines: Odor 1 , 2 , and 3 amines can all form hydrogen bondswith water. Low molecular-weight amines tend to have sharp,penetrating odors similar to ammonia Low-molecular weight amines are generally watersoluble. Higher molecular-weight amines often smell likerotting fish, and are often found in decaying ane(Putrescine)A poisonous oil present inrotting flesh; producedduring the decomposition ofthe amino acid arginine; alsopartially responsible for theodor of urine and bad breathTrimethylamineResponsible for theodor of rotting rine)A poisonous, viscous liquidpresent in rotting flesh;produced during thedecomposition of the aminoacid lysine; also partiallyresponsible for the odor of20urine and bad breathExamples: Predicting Physical PropertiesExamples: Predicting Physical Properties Arrange the following compounds in order ofincreasing boiling point. (All of the compoundshave about the same molecular weight.) Which member of each of the following pairs ofcompounds would you expect to have a higherboiling point?– 2-aminopropane or 2-aminohexanepropanoic acid, diethylamine, 1-butanol,ethyldimethylamine– triethylamine or 1-aminohexane– propanoic acid or diethylamine– 1-pentanol or 1-aminopentane2122Important AlkaloidsOCH3OSome neFound in the seeds of Coffea arabica,roasted coffee beans; inhibits the action ofphosphodiesterase, an enzyme whichinhibits cyclic adenosine monophosphate(AMP), which is responsible for formingglucose in the bloodstreamCH3TheobromineFound in the seeds ofTheobroma cacao; thestimulating ingredient inchocolate.NHONCH3NicoteneFound in tobacco plants; mildstimulant in small doses;addictive, but not especiallyharmful itselfCH3ON23CH3ODextromethorphanIngredient in cough suppressants.QuinineAntimalarial drug from cinchona tree24

Chapter 6 Amines and OOHOOOOOHOHAtropinerelaxes muscles and reduces secretionof saliva during surgery; used todilate pupils for eye examinations.CocaineThe form which is “snorted”is the hydrochloride salt; thefree-base “crack” form isburned and inhaled, andreaches the brain in 15seconds.NHMelatoninA naturally occuring hormone produced in thepineal gland; its production is triggered by theabsence of light; causes drowsiness in humansat night, triggers birds to migrate, and signalsdogs to shed their winter coats; sold as atreatment for jet lag.Scopolamineused in treatment of motionsicknessH3CHCH3RNHLysergic acid diethylamide (LSD)A synthetic hallucinogen from alkaloids obtainedfrom ergot, a fungus which grows on ryeOHStrychnineA poison from strychnosplant (Nux vomica); usedas a rat and mouse poisonNNOHONPNOOHNHZephiran chloride(benzalkonium chloride)Antiseptic compound that killsbacteria and fungi on contactHConiinePoison from hemlockHHN NHNCH3HOHOHOOHInosine Monophosphate (IMP)With monosodium glutamate (MSG), one of themajor substances responsible for the flavor of meat 2625Nitrogen WastesThe disposal of waste nitrogen from the body is a problem which different species of animalshave solved in different ways:OHHOCH3OCH3NOOONOCH3HOMorphineFound in the opium poppy; aCNS depressant; very effectivepainkillerCH3CH3CH3HOCodeineUsed in some cough syrups todepress the action of the coughcenter of the brainNHONNONH2OHeroinMore fat-soluble than morphine,and must be injected directly intothe bloodstream, but crosses theblood-brain barrier more readily,causing it to be more potent thanmorphine27ONHOONNHHNH2NHAllantoic acidMarine vertebrates furthermetabolyze allantoin intoallantoic acid.NH4 X–Marine invertebrates excreteammonium salts.28OClHOHNOHNNOHFexofenadine (Allegra )A non-drowsy antihistamine; available byperscription onlyOOLoratadine (Claritin )A non-drowsy antihistamineCH3NCH3CH3NOHDiphenylhydraminean antihistamine; active ingredient in Benadryl;sometimes used in sleeping pillsOHAntihistaminesHistaminePeople who are allergic to pollen produce histamine, which causes blood vesselsto dilate and leak, releasing fluid into surrounding tissues, causing watery eyes,sniffles, congestion, and other symptoms of hay fever (allergic rhinitis); alsocauses the symptoms of the common cold and swelling after insect bites.ONHNH2NOAllantoinUric acidMost mammals contain enzymesBirds, reptiles and insects excrete nigrogenwhich metabolyze uric acid intowastes in the form of uric acid. Uric acid eliminated directly in the solid form, withoutbeing dissolved in water. It is produced in theObody from foods and beverages rich in purines,HHsuch as claret and port. Lactic acid inhibits theNNremoval of salts of uric acid in the urine; thesesalts instead deposit in the joints, causing gout.HHDalmations have been bred to have black spotsUreawith no white hairs in them on their coats;Urea is the major organichowever, the gene which determines thecomponent of urine; about 25 gpresence of white hairs is linked to the geneare excreted every day bywhich codes the enzyme which breaks downhumans. Cartilaginous fish anduric acid into allantoin. Dalmations thusamphibians also excrete urea.excrete uric acid instead of allantoin, and arevery susceptible to gout.AntihistaminesNONH2NOOOHHNCH3NHEphedrine / Pseudoephedrinefound in the Chinese ma-huang plant; adecongestant used in many cold remediesCl29NOCetrizide (Zyrtec )A stronger antihistamine than Allegra or OClaritin, but causes drowsiness in some peopleOH30

Chapter 6 Amines and AmidesBases A base takes a proton (H ) from another species.A base produces hydroxide ions, OH–, whendissolved in water:B H2O BH OH– A strong base is one that completely dissociates inwater (i.e., every molecule of the acid splits apart).Reactions of Amines A weak base is one in which only a smallpercentage of the molecules are dissociated at anyone time.31 Acidic solution:pH 7.00([H3O ] [OH-]) Basic solution:pH 7.00([H3O ] [OH-]) Neutral solution: pH 7.00([H3O ] [OH-])Chemical Properties of Amines: BasicityAlkylammonium Salts Amines are weak organic bases. They react withwater to produce alkylammonium ions andhydroxide anions:HR Salts of amines are named by changing “amine” to“ammonium” and adding the name of the negativeion to the end of the word:H NHROHHNH CH3OHCH3NH3 ClmethylammoniumchlorideHR HClRHNCH2CH3HCH3CH2H ium SaltsChemical Properties of Amines: Basicity Salts of amines are generally white crystalline solidswith high melting points. Ammonium salts may be converted back into neutralamines by a strong base: The ionic charges makes these salts more soluble inwater than the neutral amines. Many aminecontaining drugs are administered in the form ofalkylammonium salts to increase their solubility inbodily fluids.H3 CH3CHSO4-NR—NH3 Cl- NaOH R—NH2 H2O NaCl Thus, by adjusting the pH of the solution, it ispossible to influence whether an amine is present inthe neutral form or as its ammonium cation form:HNacid(low pH) H2SO4RNH2amineHOC2 H3 O 2NCH2CH3HNHethylmethylammoniumacetate and with acids to produce alkylammonium salts:HOMorphinewater-insolubleOHHO32OMorphine sulfatewater-soluble H2ORbase(high pH)NH3 OHalkylammoniumionOH3536

Chapter 6 Amines and AmidesQuaternary Ammonium SaltsExamples: Basicity of Amines In addition to salts of 1 , 2 , and 3 amines, it ispossible to have amine cations which contain fouralkyl groups attached to a nitrogen atom, which willalways carry a positive charge, regardless of the pHof the surrounding solution. These are known asquaternary ammonium salts.R'''CH3NH2 HClNHCH3 HClCH2CH3N R Complete the following reactions:R'' X-CH3R'N CH2CH3 Cl-CH2CH3CH3triethylmethylammonium chloridequaternaryammonium saltCH3N These salts are present in many antiseptics andantibacterial agents.ClH NaOHCH33738Amides Amides contain a nitrogen which is directly attachedto a carbon in a carbonyl group:amide linkage (peptide stituted amideNCH3N-substituted amideN,N-disubstituted amide39Nomenclature of Amides Name the following compounds:CCH3OOHmethanoic acid(formic acid)HCCH3CCNCH3CH3ethanoic acid(acetic amide)OOOOH40Examples: Nomenclature of Amides Amides are named by changing the -oic acid endingof the corresponding carboxylic acid to -amide. Ifalkyl groups are attached to the nitrogen, they arenamed as N-alkyl tamide)41CH3CH342

Chapter 6 Amines and AmidesExamples: Nomenclature of AmidesExamples: Nomenclature of Amides Name the following compounds: Name the following NCH2CH3CH2CH3NH2OCH3CH2CH2CHCHCCH3NCH3HCH3CH3CH3 OCH2CH3NCHCH2CH2CCH3CCH2CHCH3CH34344Examples: Nomenclature of AmidesExamples: Nomenclature of Amides Name the follow

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 NCH3 H CH3 NCH2CH3 CH3CH2CH2 NH2 H 8 Examples: