8Chapter 21

8Chapter 21 - Chapter 21 Amines Dr. Wolf's CHM 201...

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Unformatted text preview: Chapter 21 Amines Dr. Wolf's CHM 201 & 202 21-1 21.1 Amine Nomenclature Dr. Wolf's CHM 201 & 202 21-2 Classification of Amines Alkylamine N attached to alkyl group Arylamine N attached to aryl group Primary, secondary, or tertiary determined by number of carbon atoms determined directly attached to nitrogen directly Dr. Wolf's CHM 201 & 202 21-3 Nomenclature of Primary Alkylamines (RNH2) Two IUPAC styles 1) analogous to alcohols: replace -e ending by -amine ending 2) name alkyl group and attach -amine as a suffix Dr. Wolf's CHM 201 & 202 21-4 Examples: some primary alkylamines (RNH2: one carbon directly attached to N) CH3CH2NH2 ethylamine or ethanamine ethanamine NH2 CH3CHCH2CH2CH3 NH2 Dr. Wolf's CHM 201 & 202 cyclohexylamine or cyclohexanamine 1-methylbutylamine or 1-methylbutylamine or 2-pentanamine 21-5 Nomenclature of Primary Arylamines (ArNH2) Name as derivatives of aniline. NH2 NH2 F p-fluoroaniline Dr. Wolf's CHM 201 & 202 Br CH2CH3 5-bromo-2-ethylaniline 21-6 Amino groups as substituents amino groups rank below OH groups and higher amino oxidation states of carbon oxidation iin such cases name the amino group as a n substituent substituent O HOCH2CH2NH2 HC 2-aminoethanol p-aminobenzaldehyde Dr. Wolf's CHM 201 & 202 NH2 21-7 Secondary and Tertiary Amines Name as N-substituted derivatives of parent Name -substituted primary amine. primary (N is a locant-it is not alphabetized, but iis treated the same way as a s numerical numerical locant) Parent amine is one with longest carbon chain. Dr. Wolf's CHM 201 & 202 21-8 Examples CH3NHCH2CH3 N-methylethylamine NHCH2CH3 4-chloro-N-ethyl-3-nitroaniline NO2 Cl CH3 N Dr. Wolf's CHM 201 & 202 CH3 N,N-dimethylcycloheptylamine 21-9 Ammonium Salts A nitrogen with four substituents is positively charged and is named as a derivative of charged ammonium ion (NH4+). ion + – CH3NH3 Cl methylammonium chloride Dr. Wolf's CHM 201 & 202 CH3 + – CF3CO2 N CH2CH3 H N-ethyl-N-methylcyclopentylammonium trifluoroacetate 21-10 Ammonium Salts When all four atoms attached to N are carbon, the ion is called a quaternary ammonium ion and the ion salts that contain it are called quaternary salts quaternary ammonium salts. ammonium CH3 + – CH2 N CH3 I CH CH3 benzyltrimethylammonium iodide Dr. Wolf's CHM 201 & 202 21-11 21.2 Structure and Bonding Dr. Wolf's CHM 201 & 202 21-12 Alkylamines 147 pm 112° Dr. Wolf's CHM 201 & 202 106° 21-13 Alkylamines Alkylamines Most prominent feature is high electrostatic potential at nitrogen. Reactivity of nitrogen lone pair dominates properties of amines. pair Dr. Wolf's CHM 201 & 202 21-14 Geometry at N Compare geometry at N of methylamine, aniline, and formamide. H H H sp3 sp2 NH2 C NH2 C O H Pyramidal geometry at sp3-hybridized N in Pyramidal sp -hybridized methylamine. methylamine. Planar geometry at sp2-hybridized N in Planar sp -hybridized formamide. formamide. Dr. Wolf's CHM 201 & 202 21-15 Geometry at N Compare geometry at N of methylamine, aniline, and formamide. sp3 sp2 Pyramidal geometry at sp3-hybridized N in Pyramidal sp -hybridized methylamine. methylamine. Planar geometry at sp2-hybridized N in Planar sp -hybridized formamide. formamide. Dr. Wolf's CHM 201 & 202 21-16 Geometry at N Angle that the C—N bond makes with bisector of H—N—H angle is a measure of geometry at N. sp3 ~125° sp2 180° Note: this is not the same as the H—N—H Note: bond angle bond Dr. Wolf's CHM 201 & 202 21-17 Geometry at N Angle that the C—N bond makes with bisector of H—N—H angle is a measure of geometry at N. sp3 sp2 180° ~125° 142.5° Dr. Wolf's CHM 201 & 202 21-18 Geometry at N Geometry at N in aniline is pyramidal; closer to methylamine than to formamide. 142.5° Dr. Wolf's CHM 201 & 202 21-19 Geometry at N Hybridization of N in aniline lies between sp3 and sp2. Hybridization sp sp Lone pair of N can be delocalized into ring best if N is Lone sp2 and lone pair is in a p orbital. sp Lone pair bound most strongly by N if pair is in an sp3 Lone sp orbital of N, rather than p. Actual hybridization is a compromise that maximizes binding of lone pair. 142.5° Dr. Wolf's CHM 201 & 202 21-20 Electrostatic Potential Maps of Aniline Nonplanar geometry at Nonplanar N. Region of highest N. negative potential is at N. Dr. Wolf's CHM 201 & 202 Planar geometry at N. Planar High negative potential shared by N and ring. shared 21-21 21.3 Physical Properties Dr. Wolf's CHM 201 & 202 21-22 Physical Properties Amines are more polar and have higher boiling Amines points than alkanes; but are less polar and points have lower boiling points than alcohols. CH3CH2CH3 CH3CH2NH2 CH3CH2OH dipole moment (µ): 0D 1.2 D 1.7 D boiling point: -42°C 17°C 78°C Dr. Wolf's CHM 201 & 202 21-23 Physical Properties CH3CH2CH2NH2 CH3CH2NHCH3 50°C 34°C boiling point: (CH3)3N 3°C Boiling points of isomeric amines decrease in going from primary to secondary to tertiary amines. Primary amines have two hydrogens on N capable Primary of being involved in intermolecular hydrogen bonding. Secondary amines have one. Tertiary amines cannot be involved in intermolecular hydrogen bonds. hydrogen Dr. Wolf's CHM 201 & 202 21-24 21.4 Basicity of Amines Dr. Wolf's CHM 201 & 202 21-25 Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than 1. ammonia. ammonia. Dr. Wolf's CHM 201 & 202 21-26 Table 22.1 (page 920) Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 CH3CH2NH3+ is a weaker acid than NH4+; therefore, CH3CH2NH2 is a stronger base than NH3. than Dr. Wolf's CHM 201 & 202 21-27 Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than 1. ammonia. ammonia. 2. Alkylamines differ very little in basicity. Dr. Wolf's CHM 201 & 202 21-28 Table 22.1 (page 920) Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 (CH3CH2)3N (CH3CH2)3NH+ 10.8 Notice that the difference separating a primary, secondary, and tertiary amine is only 0.3 pK units. Dr. Wolf's CHM 201 & 202 21-29 Effect of Structure on Basicity 1. Alkylamines are slightly stronger bases than 1. ammonia. ammonia. 2. Alkylamines differ very little in basicity. 3. Arylamines are much weaker bases than ammonia. Dr. Wolf's CHM 201 & 202 21-30 Table 22.1 (page 920) Basicity of Amines in Aqueous Solution Amine Conj. Acid pKa NH3 NH4+ 9.3 CH3CH2NH2 CH3CH2NH3+ 10.8 (CH3CH2)2NH (CH3CH2)2NH2+ 11.1 (CH3CH2)3N (CH3CH2)3NH+ 10.8 C6H5NH2 C6H5NH3+ 4.6 Dr. Wolf's CHM 201 & 202 21-31 Decreased basicity of arylamines Decreased H + N Stronger pK = 4.6 a acid H+ NH2 + Dr. Wolf's CHM 201 & 202 H2N H •• Weaker base •• Stronger base + H3N pKa =10.6 Weaker acid 21-32 Decreased basicity of arylamines Decreased H + N H+ •• H2N H Stronger Stronger acid When anilinium ion loses a proton, the resulting lone pair is delocalized into the ring. •• NH2 + + H3N Weaker acid Dr. Wolf's CHM 201 & 202 21-33 Decreased basicity of arylamines Decreased H + N H+ •• H2N H Aniline is a weaker base because its lone pair is more strongly held. lone •• NH2 + Stronger base + H3N Weaker base Dr. Wolf's CHM 201 & 202 21-34 Decreased basicity of arylamines Increasing delocalization makes diphenylamine a Increasing weaker base than aniline, and triphenylamine a weaker base than diphenylamine. weaker C6H5NH2 pKa of conjugate acid: of 4.6 Dr. Wolf's CHM 201 & 202 (C6H5)2NH (C6H5)3N 0.8 ~-5 21-35 Effect of Substituents on Basicity of Arylamines 1. Alkyl groups on the ring increase basicity, but only slightly (less than 1 pK unit). X X H CH3 Dr. Wolf's CHM 201 & 202 NH2 pKa of conjugate acid of 4.6 5.3 21-36 Effect of Substituents on Basicity of Arylamines 2. Electron withdrawing groups, especially ortho and/or para to amine group, decrease basicity and can have a large effect. X X H CF3 O2N Dr. Wolf's CHM 201 & 202 NH2 pKa of conjugate acid of 4.6 3.5 1.0 21-37 p-Nitroaniline – •• •O• •• O• •+ N •O • – •• •• •• NH2 • •+ N + NH2 •O • – •• •• Lone pair on amine nitrogen is conjugated with Lone p-nitro group—more delocalized than in aniline -nitro itself. Delocalization lost on protonation. itself. Dr. Wolf's CHM 201 & 202 21-38 Effect is Cumulative Aniline is 3800 times more basic than p-nitroaniline. Aniline is ~1,000,000,000 times more basic than Aniline 2,4-dinitroaniline. 2,4-dinitroaniline. Dr. Wolf's CHM 201 & 202 21-39 Heterocyclic Amines Heterocyclic •• is more basic than N N •• H piperidine pKa of conjugate acid: 11.2 pyridine pKa of conjugate acid: 5.2 (an alkylamine) Dr. Wolf's CHM 201 & 202 •• (resembles an arylamine in basicity) 21-40 Heterocyclic Amines Heterocyclic •N • •N • H is more basic than imidazole pKa of conjugate acid: 7.0 Dr. Wolf's CHM 201 & 202 N •• •• pyridine pKa of conjugate acid: 5.2 21-41 Imidazole Which nitrogen is protonated in imidazole? •N • •N • H H+ + HN Dr. Wolf's CHM 201 & 202 H+ •N • H •N • +H N H 21-42 Imidazole Protonation in the direction shown gives a Protonation stabilized ion. stabilized •N • •N • H H+ + HN Dr. Wolf's CHM 201 & 202 •N • H H N• • + NH 21-43 21.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts Dr. Wolf's CHM 201 & 202 21-44 Phase-Transfer Catalysis Phase-transfer agents promote the solubility of ionic substances in nonpolar solvents. They transfer the ionic substance from an aqueous phase to a non-aqueous one. Phase-transfer agents increase the rates of Phase-transfer reactions involving anions. The anion is relatively unsolvated and very reactive in nonpolar media compared to water or alcohols. Dr. Wolf's CHM 201 & 202 21-45 Phase-Transfer Catalysis Quaternary ammonium salts are phase-transfer catalysts. They are soluble in nonpolar solvents. H3C CH2CH2CH2CH2CH2CH2CH2CH3 + CH2CH2CH2CH2CH2CH2CH2CH3 N Cl– CH2CH2CH2CH2CH2CH2CH2CH3 Methyltrioctylammonium chloride Dr. Wolf's CHM 201 & 202 21-46 Phase-Transfer Catalysis Quaternary ammonium salts are phase-transfer catalysts. They are soluble in nonpolar solvents. CH2CH3 + N CH2CH3 Cl– CH2CH3 Benzyltriethylammonium chloride Dr. Wolf's CHM 201 & 202 21-47 Example The SN2 reaction of sodium cyanide with butyl bromide occurs much faster when benzyltriethylammonium chloride is present than when it is not. CH3CH2CH2CH2Br + NaCN benzyltriethylammonium chloride CH3CH2CH2CH2CN Dr. Wolf's CHM 201 & 202 + NaBr 21-48 CH2CH3 + N CH2CH3 Cl– CH2CH3 Mechanism Mechanism + CN– (aqueous) (aqueous) (aqueous) CH2CH3 + N CH2CH3 CN– CH2CH3 (aqueous) Dr. Wolf's CHM 201 & 202 + Cl– (aqueous) 21-49 CH2CH3 + N CH2CH3 CN– CN Mechanism Mechanism CH2CH3 (in butyl bromide) CH2CH3 + CN N CH2CH3 CN– CH2CH3 (aqueous) Dr. Wolf's CHM 201 & 202 21-50 Mechanism Mechanism CH2CH3 + N CH2CH3 CN– + CH3CH2CH2CH2Br CN CH2CH3 (in butyl bromide) CH2CH3 + Br N CH2CH3 Br– + CH3CH2CH2CH2CN CH2CH3 (in butyl bromide) Dr. Wolf's CHM 201 & 202 21-51 21.6 Reactions of Amines: A Review and a Preview Dr. Wolf's CHM 201 & 202 21-52 Preparation of Amines Two questions to answer: 1) How is the C—N bond to be formed? 1) How 2) How do we obtain the correct oxidation 2) state of nitrogen (and carbon)? state Dr. Wolf's CHM 201 & 202 21-53 Methods for C—N Bond Formation Nucleophilic substitution by azide ion (N3–) (Section 8.1, 8.13) Nitration of arenes (Section 12.3) Nucleophilic ring opening of epoxides by ammonia (Section Nucleophilic 16.12) 16.12) Nucleophilic addition of amines to aldehydes and ketones Nucleophilic (Sections 17.10, 17.11) (Sections Nucleophilic acyl substitution (Sections 19.4, 19.5, and Nucleophilic 19.11) 19.11) Nucleophilic substitution by ammonia on α-halo acids Nucleophilic -halo (Section 20.15) (Section Dr. Wolf's CHM 201 & 202 21-54 21.7 Preparation of Amines by Alkylation of Ammonia Dr. Wolf's CHM 201 & 202 21-55 Alkylation of Ammonia Desired reaction is: 2 NH3 + R—X R—NH2 + NH4X + H3N •• – • X• •• •• via: H3N • + R • then: then: H3N • + H • Dr. Wolf's CHM 201 & 202 •• X• •• • H + NR R+ H + H3N H + •N • H H R 21-56 Alkylation of Ammonia But the method doesn't work well in practice. Usually gives a mixture of primary, secondary, and tertiary amines, plus the quaternary salt. and NH3 RX RNH2 RX R2NH RX – + R4N X Dr. Wolf's CHM 201 & 202 RX R3N 21-57 Example CH3(CH2)6CH2Br NH3 CH3(CH2)6CH2NH2 (45%) + CH3(CH2)6CH2NHCH2(CH2)6CH3 (43%) As octylamine is formed, it competes with As ammonia for the remaining 1-bromooctane. Reaction of octylamine with 1-bromooctane gives N,N-dioctylamine. Dr. Wolf's CHM 201 & 202 21-58 21.8 The Gabriel Synthesis of The Primary Alkylamines Primary Dr. Wolf's CHM 201 & 202 21-59 Gabriel Synthesis gives primary amines without formation of secondary, etc. amines as byproducts uses an SN2 reaction on an alkyl halide to form the C—N bond the nitrogen-containing nucleophile iis N-potassiophthalimide s Dr. Wolf's CHM 201 & 202 21-60 Gabriel Synthesis gives primary amines without formation of secondary, etc. amines as byproducts uses an SN2 reaction on an alkyl halide to form the C—N bond the nitrogen-containing nucleophile iis N-potassiophthalimide s O – •N • • K + • O Dr. Wolf's CHM 201 & 202 21-61 N-Potassiophthalimide the pKa of phthalimide is 8.3 N-potassiophthalimide is easily prepared by the reaction of phthalimide with KOH O O • NH • O Dr. Wolf's CHM 201 & 202 KOH – •N • • K + • O 21-62 N-Potassiophthalimide as a nucleophile O O – •N • + R • • •• X• SN2 •N • •• • O O + Dr. Wolf's CHM 201 & 202 R •• – •• • X• •• •• 21-63 Cleavage of Alkylated Phthalimide O •N • R + H2O O iimide hydrolysis is mide nucleophilic acyl substitution substitution acid or base CO2H CO + H2N R CO2H Dr. Wolf's CHM 201 & 202 21-64 Cleavage of Alkylated Phthalimide hydrazinolysis is an alternative method of releasing hydrazinolysis the amine from its phthalimide derivative the O O •N R H2NNH2 NH • NH O O + Dr. Wolf's CHM 201 & 202 H2N R 21-65 Example O – •N • • K + + C6H5CH2Cl • DMF O O •N • CH2C6H5 (74%) O Dr. Wolf's CHM 201 & 202 21-66 Example O NH + C6H5CH2NH2 (97%) NH H2NNH2 O O •N • CH2C6H5 O Dr. Wolf's CHM 201 & 202 21-67 21.9 Preparation of Amines by Preparation Reduction Reduction Dr. Wolf's CHM 201 & 202 21-68 Preparation of Amines by Reduction almost any nitrogen-containing compound can be reduced to an amine, including: azides nitriles nitro-substituted benzene derivatives amides Dr. Wolf's CHM 201 & 202 21-69 Synthesis of Amines via Azides SN2 reaction, followed by reduction, gives a reaction, primary alkylamine. primary NaN3 CH2CH2Br CH2CH2N3 CH CH (74%) 1. LiAlH4 2. H2O azides may also be reduced by catalytic hydrogenation CH2CH2NH2 CH (89%) Dr. Wolf's CHM 201 & 202 21-70 Synthesis of Amines via Nitriles SN2 reaction, followed by reduction, gives a reaction, primary alkylamine. primary NaCN CH3CH2CH2CH2Br CH3CH2CH2CH2CN nitriles may also be reduced by lithium aluminum hydride (69%) H2 (100 atm), Ni CH3CH2CH2CH2CH2NH2 (56%) Dr. Wolf's CHM 201 & 202 21-71 Synthesis of Amines via Nitriles SN2 reaction, followed by reduction, gives a reaction, primary alkylamine. primary NaCN CH3CH2CH2CH2Br CH3CH2CH2CH2CN the reduction also works with cyanohydrins (69%) H2 (100 atm), Ni CH3CH2CH2CH2CH2NH2 (56%) Dr. Wolf's CHM 201 & 202 21-72 Synthesis of Amines via Nitroarenes HNO3 Cll C H2SO4 nitro groups may also be reduced with tin (Sn) + HCl or by catalytic hydrogenation Cll C (88-95%) 1. Fe, HCl 2. NaOH NH2 (95%) Dr. Wolf's CHM 201 & 202 NO2 Cll C 21-73 Synthesis of Amines via Amides O COH COH O 1. SOCl2 CN(CH3)2 2. (CH3)2NH (86-89%) only LiAlH4 is an appropriate reducing agent for this reaction 1. LiAlH4 2. H2O CH2N(CH3)2 CH (88%) Dr. Wolf's CHM 201 & 202 21-74 21.10 Reductive Amination Dr. Wolf's CHM 201 & 202 21-75 Synthesis of Amines via Reductive Amination In reductive amination, an aldehyde or ketone is subjected to catalytic hydrogenation in the presence of ammonia or an amine. R fast C R' R O + NH3 C NH + H2O R' The aldehyde or ketone equilibrates with the iimine faster than hydrogenation occurs. mine hydrogenation Dr. Wolf's CHM 201 & 202 21-76 Synthesis of Amines via Reductive Amination The imine undergoes hydrogenation faster than the aldehyde or ketone. An amine is than the product. the R fast R O + NH3 C R' Dr. Wolf's CHM 201 & 202 C H NH + H2O R' R R' C H2, Ni NH2 21-77 Example: Ammonia gives a primary amine. O + NH3 H2, Ni H ethanol NH2 (80%) via: Dr. Wolf's CHM 201 & 202 NH 21-78 Example: Primary amines give secondary amines O CH3(CH2)5CH CH + H2N H2, Ni ethanol CH3(CH2)5CH2NH CH via: Dr. Wolf's CHM 201 & 202 CH3(CH2)5CH CH (65%) N 21-79 Example: Secondary amines give tertiary amines O CH3CH2CH2CH + N H H2, Ni, ethanol N Dr. Wolf's CHM 201 & 202 CH2CH2CH2CH3 (93%) 21-80 Example: Secondary amines give tertiary amines possible intermediates include: N HO + N CHCH2CH2CH3 CHCH2CH2CH3 N CH Dr. Wolf's CHM 201 & 202 CHCH2CH3 21-81 21.11 Reactions of Amines: A Review and a Preview Dr. Wolf's CHM 201 & 202 21-82 Reactions of Amines Reactions of amines almost always involve the nitrogen lone pair. as a base: as N• H X C O • as a nucleophile: N• • Dr. Wolf's CHM 201 & 202 21-83 Reactions of Amines Reactions already discussed basicity (Section 21.4) reaction with aldehydes and ketones (Chapter 17) reaction with acyl chlorides, reaction anhydrides, and esters anhydrides, Dr. Wolf's CHM 201 & 202 21-84 21.12 Reactions of Amines with Alkyl Reactions Halides Halides Dr. Wolf's CHM 201 & 202 21-85 Reaction with Alkyl Halides Amines act as nucleophiles toward alkyl halides. N• + R • + •• – N R + • X• •• X• •• • • •• • H H N •• Dr. Wolf's CHM 201 & 202 R + H + 21-86 Example: excess amine NH2 + ClCH2 (4 mol) (1 mol) NaHCO3 90°C NHCH2 (85-87%) (85-87%) Dr. Wolf's CHM 201 & 202 21-87 Example: excess alkyl halide CH2NH2 CH methanol + 3CH3I heat + – CH2N (CH3)3 I (99%) Dr. Wolf's CHM 201 & 202 21-88 21.13 The Hofmann Elimination Dr. Wolf's CHM 201 & 202 21-89 The Hofmann Elimination a quaternary ammonium hydroxide is the reactant and an alkene is the product is an anti elimination the leaving group is a trialkylamine the regioselectivity is opposite to the Zaitsev rule. Dr. Wolf's CHM 201 & 202 21-90 Quaternary Ammonium Hydroxides are prepared by treating quaternary ammmonium halides with moist silver oxide CH2N (CH3)3 I Ag2O – H2O, CH3OH + – CH2N (CH3)3 HO (CH Dr. Wolf's CHM 201 & 202 21-91 The Hofmann Elimination on being heated, quaternary ammonium on hydroxides undergo elimination hydroxides CH2 + CH N(CH3)3 + H2O (69%) 160°C + – CH2N (CH3)3 HO Dr. Wolf's CHM 201 & 202 21-92 Mechanism – •• •O H • •• H H •• O •• H CH2 CH2 N(CH3)3 + • N(CH3)3 • Dr. Wolf's CHM 201 & 202 21-93 Regioselectivity Elimination occurs in the direction that gives Elimination the less-substituted double bond. This is called the Hofmann rule. Hofmann H2C CH3CHCH2CH3 + N(CH3)3 – HO Dr. Wolf's CHM 201 & 202 CHCH2CH3 (95%) heat + CH3CH CHCH3 (5%) 21-94 Regioselectivity Steric factors seem to control the regioselectivity. The transition state that leads to 1-butene is less crowded than the one leading to cis or trans-2-butene. Dr. Wolf's CHM 201 & 202 21-95 Regioselectivity H CH3CH2 H H H H CH3CH2 + N(CH3)3 C C H H major product largest group is between two H atoms Dr. Wolf's CHM 201 & 202 21-96 Regioselectivity H CH3 H CH3 H + N(CH3)3 CH3 H C C H CH3 minor product largest group is between an H atom and a methyl group Dr. Wolf's CHM 201 & 202 21-97 21.14 Electrophilic Aromatic Electrophilic Substitution Substitution in Arylamines Dr. Wolf's CHM 201 & 202 21-98 Nitration of Anililne NH2 is a very strongly activating group NH2 not only activates the ring toward electrophilic aromatic substitution, it also makes it more easily oxidized makes attemped nitration of aniline fails because attemped nitric acid oxidizes aniline to a black tar nitric Dr. Wolf's CHM 201 & 202 21-99 Nitration of Anililne Strategy: decrease the reactivity of aniline by Strategy: converting the NH2 group to an amide converting O NH2 OO CH3COCCH3 CH(CH3)2 CH(CH NHCCH3 (98%) CH(CH3)2 CH(CH (acetyl chloride may be used instead of acetic anhydride) Dr. Wolf's CHM 201 & 202 21-100 Nitration of Anililne Strategy: nitrate the amide formed in the first Strategy: step step O O NHCCH3 NO2 NO CH(CH3)2 NHCCH3 HNO3 CH(CH3)2 CH(CH (94%) Dr. Wolf's CHM 201 & 202 21-101 Nitration of Anililne Strategy: remove the acyl group from the amide Strategy: by hydrolysis by O NHCCH3 NO2 NO NH2 NO2 NO KOH ethanol, heat CH(CH3)2 CH(CH3)2 (100%) Dr. Wolf's CHM 201 & 202 21-102 Halogenation of Arylamines occurs readily without necessity of protecting occurs amino group, but difficult to limit it to monohalogenation monohalogenation NH2 NH2 Br2 Br Br acetic acid CO2H CO Dr. Wolf's CHM 201 & 202 CO2H CO (82%) 21-103 Monohalogenation of Arylamines Decreasing the reactivity of the arylamine by Decreasing converting the NH2 group to an amide allows converting halogenation to be limited to monosubstitution halogenation O O NHCCH3 CH3 NHCCH3 CH3 CH Cl2 acetic acid Dr. Wolf's CHM 201 & 202 Cl (74%) 21-104 Friedel-Crafts Reactions The amino group of an arylamine must be The protected as an amide when carrying out a Friedel-Crafts reaction. Friedel-Crafts O O NHCCH3 CH3 NHCCH3 O CH3 CH CH3CCl AlCl3 O Dr. Wolf's CHM 201 & 202 CCH3 (57%) 21-105 21.15 Nitrosation of Alkylamines Dr. Wolf's CHM 201 & 202 21-106 Nitrite Ion, Nitrous Acid, and Nitrosyl Cation – •• •O • N •• H •• •• O• + H •• O •• • N H H •O • H• • H + Dr. Wolf's CHM 201 & 202 •• N + •• O• • + •O H• •• •• •• N O• + • •• O• • 21-107 Nitrosyl Cation and Nitrosation •• N + Dr. Wolf's CHM 201 & 202 •• O• • 21-108 Nitrosyl Cation and Nitrosation + N •• •• N O• • N• + • Dr. Wolf's CHM 201 & 202 •• N + •• O• • 21-109 Nitrosation of Secondary Alkylamines + N •• •• N O• •N • • H N N• + • H Dr. Wolf's CHM 201 & 202 N + •• O• • O• • + H •• •• •• + nitrosation of secondary amines gives an N-nitroso -nitroso amine amine 21-110 Example •• (CH3)2NH Dr. Wolf's CHM 201 & 202 NaNO2, HCl H2O •• (CH3)2N •• N (88-90%) •• O• • 21-111 Some N-Nitroso Amines N (CH3)2N N-nitrosodimethylamine O (leather tanning) N N N N O N-nitrosopyrrolidine (nitrite-cured bacon) Dr. Wolf's CHM 201 & 202 N O N-nitrosonornicotine (tobacco smoke) 21-112 Nitrosation of Primary Alkylamines Nitrosation R H + N R •• N •• O• •N • • H H H N N• + • H Dr. Wolf's CHM 201 & 202 •• N + •• O• • O• • + H R •• •• + analogous to analogous nitrosation of secondary amines to this point to 21-113 Nitrosation of Primary Alkylamines R •N • •• N H •• + O H H •N • H N + Dr. Wolf's CHM 201 & 202 •• O• • H •• N •N • •• O• • H R •• + R H + this species reacts further R H •N • •• N O• + • H 21-114 Nitrosation of Primary Alkylamines Nitrosation nitrosation of a nitrosation primary alkylamine gives an alkyl diazonium ion diazonium process is called process diazotization diazotization H R + N • R •N • Dr. Wolf's CHM 201 & 202 N• + •O • •• H H •• N O• + • H 21-115 Alkyl Diazonium Ions Alkyl ++ R •N • N• • R + N N• • alkyl diazonium ions alkyl readily lose N2 to readily give carbocations give Dr. Wolf's CHM 201 & 202 21-116 Example: Nitrosation of 1,1-Dimethylpropylamine NH2 OH + N HONO H2O N – N2 + (80%) + (3%) Dr. Wolf's CHM 201 & 202 (2%) 21-117 Nitrosation of Tertiary Alkylamines Nitrosation There is no useful chemistry associated with the There nitrosation of tertiary alkylamines. nitrosation R R R R + N N• • R Dr. Wolf's CHM 201 & 202 •• N •• O• • R 21-118 21.16 Nitrosation of Arylamines Dr. Wolf's CHM 201 & 202 21-119 Nitrosation of Tertiary Arylamines reaction that occurs is reaction electrophilic aromatic substitution electrophilic N(CH2CH3)2 1. NaNO2, HCl, H2O, 8°C N(CH2CH3)2 2. HO– N O (95%) Dr. Wolf's CHM 201 & 202 21-120 Nitrosation of N-Alkylarylamines similar to secondary alkylamines; gives N-nitroso amines gives NHCH3 NaNO2, HCl, H2O, 10°C N O NCH3 (87-93%) Dr. Wolf's CHM 201 & 202 21-121 Nitrosation of Primary Nitrosation Arylamines Arylamines gives aryl diazonium ions aryl diazonium ions are much more stable than alkyl diazonium ions most aryl diazonium ions are stable under the most conditions of their formation (0-10°C) + RN + ArN Ar Dr. Wolf's CHM 201 & 202 N N fast + R + N2 slow + Ar + N2 21-122 Example: (CH3)2CH (CH NH2 NaNO2, H2SO4 H2O, 0-5°C (CH3)2CH (CH Dr. Wolf's CHM 201 & 202 + N HSO4– N 21-123 Synthetic Origin of Aryl Diazonium Salts Ar H Ar NO2 Ar NH2 Ar Dr. Wolf's CHM 201 & 202 + N N 21-124 21.17 Synthetic Transformations of Aryl Diazonium Salts Dr. Wolf's CHM 201 & 202 21-125 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-126 Preparation of Phenols + N Ar N H2O, heat Ar Dr. Wolf's CHM 201 & 202 OH 21-127 Example NH2 (CH3)2CH (CH 1. NaNO2, H2SO4 H2O, 0-5°C 2. H2O, heat OH (CH3)2CH (CH (73%) Dr. Wolf's CHM 201 & 202 21-128 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-129 Preparation of Aryl Iodides reaction of an aryl diazonium salt with reaction potassium iodide potassium Ar + N N KI Ar Dr. Wolf's CHM 201 & 202 I 21-130 Example NH2 Br Br 1. NaNO2, HCl H2O, 0-5°C I Br Br 2. KI, room temp. (72-83%) Dr. Wolf's CHM 201 & 202 21-131 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-132 Preparation of Aryl Fluorides Ar Ar + N F N heat the tetrafluoroborate salt of a diazonium ion; process is called the Schiemann reaction Dr. Wolf's CHM 201 & 202 21-133 Example NH2 1. NaNO2, HCl, F H2O, 0-5°C CCH2CH3 CCH O 2. HBF4 3. heat CCH2CH3 CCH O (68%) Dr. Wolf's CHM 201 & 202 21-134 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-135 Preparation of Aryl Chlorides and Preparation Bromides Bromides Ar Cl Ar Ar + N Br N aryl chlorides and aryl bromides are prepared by aryl heating a diazonium salt with copper(I) chloride or bromide bromide substitutions of diazonium salts that use copper(I) substitutions halides are called Sandmeyer reactions Sandmeyer reactions Dr. Wolf's CHM 201 & 202 21-136 Example NH2 1. NaNO2, HCl, Cl H2O, 0-5°C NO2 NO 2. CuCl, heat NO2 NO (68-71%) Dr. Wolf's CHM 201 & 202 21-137 Example 1. NaNO2, HBr, NH2 Cll C H2O, 0-10°C Br Cll C 2. CuBr, heat (89-95%) Dr. Wolf's CHM 201 & 202 21-138 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-139 Preparation of Aryl Nitriles Ar CN Ar + N N aryl nitriles are prepared by heating a diazonium aryl salt with copper(I) cyanide salt this is another type of Sandmeyer reaction Dr. Wolf's CHM 201 & 202 21-140 Example 1. NaNO2, HCl, NH2 CH3 CH H2O, 0°C CN CH3 CH 2. CuCN, heat (64-70%) Dr. Wolf's CHM 201 & 202 21-141 Transformations of Aryl Diazonium Salts Ar Ar Cl Ar Ar + N Dr. Wolf's CHM 201 & 202 I N H Ar F Ar CN Ar Ar Br OH 21-142 Transformations of Aryl Diazonium Salts hypophosphorous acid (H3PO2) reduces diazonium reduces salts; ethanol does the same thing salts; this is called reductive deamination this reductive + NN Ar Ar H Dr. Wolf's CHM 201 & 202 21-143 Example NaNO2, H2SO4, NH2 CH3 CH H3PO2 CH3 (70-75%) Dr. Wolf's CHM 201 & 202 21-144 Value of Diazonium Salts 1) allows introduction of substituents such as 1) OH, F, I, and CN on the ring OH, 2) allows preparation of otherwise difficultly 2) accessible substitution patterns accessible Dr. Wolf's CHM 201 & 202 21-145 Example NH2 NH2 Br2 Br Br NaNO2, H2SO4, Br H2O, CH3CH2OH H2O Br Br Br (100%) Br Br (74-77%) Dr. Wolf's CHM 201 & 202 21-146 21.18 Azo Coupling Dr. Wolf's CHM 201 & 202 21-147 Azo Coupling Diazonium salts are weak electrophiles. React with strongly activated aromatic React compounds by electrophilic aromatic substitution. substitution. + +Ar' H NN N Ar Ar N Ar' an azo compound Ar' must bear a strongly electron-releasing group such as OH, OR, or NR2. Dr. Wolf's CHM 201 & 202 21-148 Example OH OH + + C6H5N N Cl– OH OH N Dr. Wolf's CHM 201 & 202 NC6H5 21-149 Section 21.19 Spectroscopic Analysis of Amines Dr. Wolf's CHM 201 & 202 21-150 Infrared Spectroscopy the N—H stretching band appears in the range 3000-3500 cm-1 primary amines give two peaks in this region, one for a symmetrical stretching vibration, the other for an antisymmetrical stretch H R N R H symmetric Dr. Wolf's CHM 201 & 202 H N H antisymmetric 21-151 Infrared Spectroscopy primary amines give two N—H stretching peaks, primary secondary amines give one secondary RNH2 Dr. Wolf's CHM 201 & 202 R2NH 21-152 H NMR 1 compare chemical shifts in: H3C CH2NH2 H3C δ 3.9 ppm 3.9 N C s H iis more shielded than O Dr. Wolf's CHM 201 & 202 CH2OH δ 4.7 ppm 4.7 C H 21-153 C NMR 13 Carbons bonded to N are more shielded than Carbons those bonded to O. those CH3NH2 δ 26.9 ppm 26.9 Dr. Wolf's CHM 201 & 202 CH3OH δ 48.0 ppm 48.0 21-154 UV-VIS An amino group on a benzene ring shifts λmax An to longer wavelength. Protonation of N causes UV spectrum to resemble that of benzene. + NH2 NH3 NH NH λmax 204 nm 256 nm Dr. Wolf's CHM 201 & 202 λmax 230 nm 280 nm λmax 203 nm 254 nm 21-155 Mass Spectrometry Compounds that contain only C, H, and O Compounds have even molecular weights. If an odd number of N atoms is present, the molecular weight is odd. weight A molecular-ion peak with an odd m/z value molecular-ion suggests that the sample being analyzed contains N. contains Dr. Wolf's CHM 201 & 202 21-156 Mass Spectrometry Nitrogen stabilizes Nitrogen carbocations, which drives the fragmentation pathways. pathways. •• (CH3)2NCH2CH2CH2CH3 e– •+ (CH3)2NCH2CH2CH2CH3 + (CH3)2N Dr. Wolf's CHM 201 & 202 CH2 + •CH2CH2CH3 21-157 Mass Spectrometry Nitrogen stabilizes Nitrogen carbocations, which drives the fragmentation pathways. pathways. •• CH3NHCH2CH2CH(CH3)2 e– •+ CH3NHCH2CH2CH(CH3)2 + CH3NH Dr. Wolf's CHM 201 & 202 CH2 + •CH2CH(CH3)2 21-158 End of Chapter 21 Dr. Wolf's CHM 201 & 202 21-159 ...
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