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![23-23-1515
BasicityBasicity
All amines are weak bases, and aqueous
solutions of amines are basic.
• It is common to discuss their basicity by
reference to the acid ionization constant of the
conjugate acid.
CH3NH3
+
H2 O CH3 NH2 H3 O+++
[ CH3NH2] [H3 O
+
]
[CH3 NH3
+
]
2.29 x 10
-11
==Ka pKa = 10.64
H
H
CH3 - N H- O-H
H
H
CH3 - N- H O-H
Methylammonium hydroxideMethylamine
+
+
-](https://image.slidesharecdn.com/23amines-160131014750/85/amines-14-320.jpg)
More Related Content
amines
- 1.
- 2. 23-23-22 Structure & ClassificationStructure& Classification Amines are classified as: • 1° , 2° , or , 3° amines:1° , 2° , or , 3° amines: Amines in which there are 1, 2, or 3 alkyl or aryl groups. Methylamine (a 1° amine) Dimethylamine (a 2° amine) Trimethylamine (a 3° amine) CH3 - NH2 CH3 - NH CH3 - N CH3 CH3 CH3 : : :
- 3. 23-23-33 Structure & ClassificationStructure& Classification Amines are further divided into aliphatic, aromatic, and heterocyclic amines: • AliphaticAliphatic amine:amine: An amine in which nitrogen is bonded only to alkyl groups. • Aromatic amine:Aromatic amine: An amine in which nitrogen is bonded to one or more aryl groups. Aniline (a 1° aromatic amine) N-Methylaniline (a 2° aromatic amine) Benzyldimethylamine (a 3° aliphatic amine) NH2 N-H CH2 - N- CH3 CH3 CH3 : : :
- 4. 23-23-44 Structure & ClassificationStructure& Classification • Heterocyclic amine:Heterocyclic amine: An amine in which nitrogen is one of the atoms of a ring. PyrrolePiperidinePyrrolidine Pyridine (heterocyclic aliphatic amines) (heterocyclic aromatic amines) NN N H H N H
- 5. 23-23-66 NomenclatureNomenclature Aliphatic amines: replacethe suffix -ee of the parent alkane by -amineamine. 1,6-Hexanediamine(S)-1-Phenyl- ethanamine 2-Propanamine NH2 NH2 NH2 H2 N
- 6. 23-23-77 NomenclatureNomenclature The IUPAC systemretains the name aniline. 3-Methoxyaniline (m-Anisidine) 4-Methylaniline (p-Toluidine) Aniline 4-Nitroaniline (p-Nitroaniline) NH2 NH2 CH3 OCH3 NH2 NO2 NH2
- 7. 23-23-88 NomenclatureNomenclature Among the variousfunctional groups, -NH2 is one of the lowest in order of precedence. COOHH2 NOH NH2 H2 N OH 4-Aminobenzoic acid2-Aminoethanol (S)-2-Amino-3-methyl- 1-butanol Amine vs alcohol Amine vs acid
- 8. 23-23-99 NomenclatureNomenclature Common names formost aliphatic amines are derived by listing the alkyl groups bonded to nitrogen in one word ending with the suffix -amineamine. CH3 NH2 N H Et3 N NH2 TriethylamineDicyclopentylamineMethylamine tert-Butylamine
- 9. 23-23-1010 NomenclatureNomenclature When four groupsare bonded to nitrogen, the compound is named as a salt of the corresponding amine.
- 10. 23-23-1111 Chirality of AminesChiralityof Amines • Consider the unshared pair of electrons on nitrogen as a fourth group, then the arrangement of groups around N is approximately tetrahedral. • An amine with three different groups bonded to N is chiral and exists as a pair of enantiomers and, in principle, can be resolved.
- 11. 23-23-1212 Chirality of AminesChiralityof Amines • In practice, however, they cannot be resolved because they undergo inversion, which converts one enantiomer to the other.
- 12. 23-23-1313 Chirality of AminesChiralityof Amines • Pyramidal inversion is not possible with quaternary ammonium ions, and their salts can be resolved. N Me Et N Me Et Cl - Cl- S Enantiomer R Enantiomer
- 13. 23-23-1414 Physical PropertiesPhysical Properties Aminesare polar compounds, and both 1° and 2° amines form intermolecular hydrogen bonds. • N-H- - -N hydrogen bonds are weaker than O-H- - -O hydrogen bonds because the difference in electronegativity between N and H (3.0 - 2.1 =0.9) is less than that between O and H (3.5 - 2.1 = 1.4). bp (°C) -6.3 65.0-88.6 32.031.130.1MW (g/mol) CH3 CH3 CH3 NH2 CH3 OH Using bp as an indication of H bonding Increasing strength
- 14. 23-23-1515 BasicityBasicity All amines areweak bases, and aqueous solutions of amines are basic. • It is common to discuss their basicity by reference to the acid ionization constant of the conjugate acid. CH3NH3 + H2 O CH3 NH2 H3 O+++ [ CH3NH2] [H3 O + ] [CH3 NH3 + ] 2.29 x 10 -11 ==Ka pKa = 10.64 H H CH3 - N H- O-H H H CH3 - N- H O-H Methylammonium hydroxideMethylamine + + -
- 15. 23-23-1616 BasicityBasicity • Using valuesof pKa, we can compare the acidities of amine conjugate acids with other acids. CH3NH2 CH3 COOH CH3NH3 + CH3COO - Keq = 7.6 x 10 5 + + pKa 10.64pKa 4.76 (stronger acid) (weaker acid) pKeq = -5.88
- 16. 23-23-1717 Basicity-Aliphatic AminesBasicity-Aliphatic Amines AliphaticAmines • note that pKa + pKb = 14 Tertiary Amines diethylamine dimethylamine cyclohexylamine ethylamine methylamine Secondary Amines Primary Amines Ammonia pKaStructureAmine trimethylamine triethylamine 9.26 10.64 10.81 10.66 10.73 10.98 9.81 10.75 pKb 4.74 3.36 3.34 3.19 3.27 3.02 4.19 3.25 CH3 NH2 NH3 CH3 CH2 NH2 C6 H1 1 NH2 ( CH3 ) 2 NH ( CH3 CH2 ) 2 NH ( CH3 ) 3 N ( CH3 CH2 ) 3 N Stronger bases
- 17. 23-23-1818 Basicity-Aromatic AminesBasicity-Aromatic Amines NH2CH3 NH2Cl NH2O2N NH2 N N N H HeterocyclicAromatic Amines Aromatic Amines StructureAmine Aniline 4-Chloroaniline 4-Nitroaniline 4-Methylaniline Pyridine Imidazole 4.63 5.08 4.15 1.0 5.25 6.95 pKa of Conjugate Acid Weaker bases Intermediate
- 18. 23-23-1919 Basicity-Aromatic AminesBasicity-Aromatic Amines •Aromatic amines are considerably weaker bases than aliphatic amines. NH2 H2 O H2 ONH2 NH3 + OH - NH3 + OH- Cyclohexylamine pKa = 4.63 Aniline pKa = 10.66+ + Cyclohexylammonium hydroxide Anilinium hydroxide
- 19. 23-23-2020 Basicity-Aromatic AminesBasicity-Aromatic Amines Aromaticamines are weaker bases than aliphatic amines because of two factors: • Resonance stabilization of the free base, which is lost on protonation. N HH H HH H H .. . . . . . . unhybridized 2p orbital of N nitrogen is sp2 hybridized N N N H H H H H N H HH +++
- 20. 23-23-2121 Basicity-Aromatic AminesBasicity-Aromatic Amines •The greater electron-withdrawing inductive effect of the sp2 -hybridized carbon of an aromatic amine compared with that of the sp3 -hybridized carbon of an aliphatic amine. And note the effect of substituents Electron-releasing groups, such as alkyl groups, increase the basicity of aromatic amines. Electron-withdrawing groups, such as halogens, the nitro group, and a carbonyl group decrease the basicity of aromatic amines by a combination of resonance and
- 21. 23-23-2222 Example: Basicity-Aromatic AminesExample:Basicity-Aromatic Amines 3-nitroaniline is a stronger base than 4- Nitroaniline. NH2 O2 N NH2O2 N pKa 1.0pKa 2.47 4-Nitroaniline3-Nitroaniline delocalization of the nitrogen lone pair onto the oxygen atoms of the nitro group ++ - - - N NH2 NH2 + N O O O O Cannot do this kind of resonance in 3 nitroaniline
- 22. 23-23-2323 Basicity-Aromatic AminesBasicity-Aromatic Amines Heterocyclicaromatic amines are weaker bases than heterocyclic aliphatic amines. Piperidine ImidazolePyridine pKa 10.75 pKa 5.25 pKa 6.95 N N H N N H
- 23. 23-23-2424 Basicity-Aromatic AminesBasicity-Aromatic Amines •In pyridine, the unshared pair of electrons on N is not part of the aromatic sextet. • Pyridine is a weaker base than heterocyclic aliphatic amines because the free electron pair on N lies in an sp2 hybrid orbital (33% s character) and is held more tightly to the nucleus than the free electron pair on N in an sp3 hybrid orbital (25% s character). :N HH H HH nitrogen is sp2 hybridized an sp2 hybrid orbital; the electron pair in this orbital is not a part of the aromatic sextet . .. . . .
- 24. 23-23-2525 Basicity-Aromatic AminesBasicity-Aromatic Amines ImidazoleWhich N lone pair is protonated? The one which is not part of the aromatic system. This electron pair is not a part of the aromatic sextet This electron pair is a part of the aromatic sextet + + Aromaticity is maintained when imidazole is protonated + Imidazole Imidazolium ion N N H H N N H H2 O OH - : : :
- 25. 23-23-2626 Basicity-GuanidineBasicity-Guanidine Guanidine is thestrongest base among neutral organic compounds. • Its basicity is due to the delocalization of the positive charge over the three nitrogen atoms. : C NH2 NH2H2 N H2 N C NH2 NH2 C NH2 NH2H2 N Three equivalent contributing structures + + + : : : : : ++ Guanidine Guanidinium ion C NH NH2H2 N H2 N C NH2 NH2 + H2 O OH - pKa = 13.6
- 26. 23-23-2727 Reaction with AcidsReactionwith Acids All amines, whether soluble or insoluble in water, react quantitatively with strong acids to form water-soluble salts. HO HO NH2 OH HCl H2 O HO HO NH3 + Cl - OH (R)-Norepinephrine hydrochloride (a water-soluble salt) + (R)-Norepinephrine (only slightly soluble in water)
- 27. 23-23-2828 Reaction with acidsReactionwith acids Separation and purification of an amine and a neutral compound.
- 28. 23-23-2929 PreparationPreparation We have alreadycovered these methods • nucleophilic ring opening of epoxides by ammonia and amines. • addition of nitrogen nucleophiles to aldehydes and ketones to form imines • reduction of imines to amines • reduction of amides to amines by LiAlH4 • reduction of nitriles to a 1° amine • nitration of arenes followed by reduction of the NO2 group to a 1° amine
- 29. 23-23-3030 PreparationPreparation Alkylation of ammoniaand amines by SN2 substitution. • Unfortunately, such alkylations give mixtures of products through a series of proton transfer and nucleophilic substitution reactions. CH3Br NH3 CH3NH3 + Br - (CH3) 2NH2 + Br - (CH3) 3NH + Br - (CH3) 4N + Br - + + + + + SN2 Methylammonium bromide CH3 Br NH3 CH3 NH3 + Br- polyalkylations
- 30. 23-23-3131 Preparation via AzidesPreparationvia Azides Alkylation of azide ion. -- + + - Azide ion (a good nucleophile) An alkyl azide N NN NN NRN3 - RN3:: : : : : : Ph CH2 Cl K + N3 - Ph CH2 N3 1. LiAlH4 2. H2O Ph CH2 NH2 Benzyl chloride Benzyl azide Benzylamine Overall Alkyl Halide Alkyl amine
- 31. 23-23-3232 Example: Preparation viaAzidesExample: Preparation via Azides • Alkylation of azide ion. Cyclohexene trans-2-Amino- cyclohexanol (racemic) 1,2-Epoxy- cyclohexane trans-2-Azido- cyclohexanol (racemic) ArCO3 H 1 . K + N3 - 2 . H2 O 1 . LiAlH4 2 . H2 O N3 OH NH2 OH O Note retention of configuration, trans trans
- 32. 23-23-3333 Reaction with HNOReactionwith HNO22 Nitrous acid, a weak acid, is most commonly prepared by treating NaNO2 with aqueous H2SO4 or HCl. In its reactions with amines, nitrous acid: • Participates in proton-transfer reactions. • A source of the nitrosyl cation, NO+ , a weak electrophile. HNO2 H2O H3O+ NO2 - + pKa = 3.37+
- 33. 23-23-3434 Reaction with HNOReactionwith HNO22 NO+ is formed in the following way. • Step 1: Protonation of HONO. • Step 2: Loss of H2O. • We study the reactions of HNO2 with 1° , 2° , and 3° aliphatic and aromatic amines. H H N O + OH H + OH N ONO OH N O + + + + The nitrosyl cation (1) (2)
- 34. 23-23-3535 Tertiary Amines withHNOTertiary Amines with HNO22 • 3° Aliphatic amines, whether water-soluble or water-insoluble, are protonated to form water- soluble salts. • 3° Aromatic amines: NO+ is a weak electrophile and participates in Electrophilic Aromatic Substitution. Me2 N 1. NaNO2 , HCl, 0-5°C 2. NaOH, H2O N=OMe2 N N,N-Dimethyl-4-nitrosoanilineN,N-Dimethylaniline
- 35. 23-23-3636 Secondary Amines withHNOSecondary Amines with HNO22 • 2° Aliphatic and aromatic amines react with NO+ to give N-nitrosamines. N-H HNO2 N-N=O H2 O Piperidine N-Nitrosopiperidine + + carcinogens N H N O N H N=O H O H N N=O H O H H+ + + + +• • • • • • • • • • • • • • • • • • • • • • • • • • (1) (2) Mechanism:
- 36. 23-23-3737 RNHRNH22 with HNOwithHNO22 1° aliphatic amines give a mixture of unrearranged and rearranged substitution and elimination products, all of which are produced by way of a diazonium ion and its loss of N2 to give a carbocation. Diazonium ion:Diazonium ion: An RN2 + or ArN2 + ion
- 37. 23-23-3838 1° RNH1° RNH22with HNOwith HNO22 Formation of a diazonium ion. Step 1: Reaction of a 1° amine with the nitrosyl cation. Step 2: Protonation followed by loss of water. : :+ keto-enol tautomerism A 1° aliphatic amine An N-nitrosamine R-NH2 N R-N-N=OO + : : : H : : : A diazotic acid R-N=N-O-H : : :: A diazotic acid R-N=N-O-H : : :: + A diazonium ion + + A carbo- cation O-HNR-N H N NR N N H + - H2 O R + •• •• •• •• •• ••
- 38. 23-23-3939 1° RNH1° RNH22with HNOwith HNO22 (Aliphatic)(Aliphatic) Aliphatic diazonium ions are unstable and lose N2 to give a carbocation which may: 1. Lose a proton to give an alkene. 2. React with a nucleophile to give a substitution product. 3. Rearrange and then react by Steps 1 and/or 2. (25%) (5.2%) (13.2%) (25.9%) (10.6%) 0-5o C NaNO2 , HClNH2 OH Cl OH + +
- 39. 23-23-4040 1° RNH1° RNH22with HNOwith HNO22 Tiffeneau-Demjanov reaction:Tiffeneau-Demjanov reaction: Treatment of a β-aminoalcohol with HNO2 gives a ketone and N2.. CH2 NH2 OH HNO2 O H2 O N2 β + + + A β-aminoalcohol Cycloheptanone α
- 40. 23-23-4141 Mechanism of Tiffeneau-DemjanovMechanismof Tiffeneau-Demjanov • Reaction with NO+ gives a diazonium ion. • Concerted loss of N2 and rearrangement followed by proton transfer gives the ketone. :OH CH2NH2 HNO2 O-H CH2 N N + (A diazonium ion) -N2 O + CH2 OH CH2 O H+ proton transfer to H2O A resonance-stabilized cation Cycloheptanone : : : : : : : : Similar to pinacol rearrangement
- 41. 23-23-4242 Pinacol Rearrangement: anexample ofPinacol Rearrangement: an example of stabilization of a carbocation by anstabilization of a carbocation by an adjacent lone pair.adjacent lone pair. Overall:
- 42. 23-23-4343 MechanismMechanism Reversible protonation. Elimination of water to yield tertiary carbocation. 1,2 rearrangemen tto yield resonance stabilized cation. Deprotonation. This is a protonated ketone!
- 43. 23-23-4444 1°1° Primary AminesPrimaryAmines with HNOwith HNO22 (Aromatic)(Aromatic) The -N2 + group of an arenediazonium salt can be replaced in a regioselective manner by these groups. Ar-NH2 HNO2 Ar-N2 + (-N2) HCl, CuCl H2O HBF4 HBr, CuBr KCN, CuCN KI H3PO2 Ar-I Ar-F Ar-H Ar-Cl Ar-Br Ar-CN Ar-OH Schiemann reaction Sandmeyer reaction0-5°C
- 44. 23-23-4545 1° ArNH1° ArNH22with HNOwith HNO22 A 1° aromatic amine converted to a phenol. 2-Bromo-4- methylaniline 2-Bromo-4- methylphenol 1. HNO2 2. H2O, heat NH2 Br CH3 OH Br CH3
- 45. 23-23-4646 1° ArNH1° ArNH22with HNOwith HNO22 Problem:Problem: What reagents and experimental conditions will bring about this conversion? (1) (2) (3) (4) CH3 CH3 NO2 COOH NO2 COOH NH2 COOH OH
- 46. 23-23-4747 1° ArNH1° ArNH22with HNOwith HNO22 Problem:Problem: Show how to bring about each conversion. NH2 CH3 Cl CH3 C CH3 N NH2 CH3 ClCl CH2 NH2 CH3 CH3 ClCl (5) (6) (7) (8) (9)
- 47. 23-23-4848 Hofmann EliminationHofmann Elimination Hofmannelimination:Hofmann elimination: Thermal decomposition of a quaternary ammonium hydroxide to give an alkene. • Step 1: Formation of a 4° ammonium hydroxide. (Cyclohexylmethyl)trimethyl- ammonium hydroxide Silver oxide (Cyclohexylmethyl)trimethyl- ammonium iodide + + H2 O Ag2 O AgI CH2 -N- CH3 CH3 CH3 I- + + CH2 -N- CH3 CH3 CH3 OH-
- 48. 23-23-4949 Hofmann EliminationHofmann Elimination •Step 2: Thermal decomposition of the 4° ammonium hydroxide. (Cyclohexylmethyl)trimethyl- ammonium hydroxide TrimethylamineMethylene- cyclohexane ++CH2 ( CH3 ) 3 N H2 O 160°+ CH2 -N- CH3 CH3 CH3 OH-
- 49. 23-23-5050 Hofmann EliminationHofmann Elimination Hofmannelimination is regioselective - the major product is the least substituted alkene. Hofmann’s rule:Hofmann’s rule: Any β-elimination that occurs preferentially to give the least substituted alkene as the major product is said to follow Hofmann’s rule. CH3 N(CH3)3 OH - CH2 (CH3 )3N H2O++ heat +
- 50. 23-23-5151 Hofmann EliminationHofmann Elimination •The regioselectivity of Hofmann elimination is determined largely by steric factors, namely the bulk of the -NR3 + group. • Hydroxide ion preferentially approaches and removes the least hindered hydrogen and, thus, gives the least substituted alkene. • Bulky bases such as (CH3)3CO- K+ give largely Hofmann elimination with haloalkanes. + E2 reaction (concerted elimination) C C H N( CH3 ) 3 H H H C H H C H CH3 CH2 HO- N( CH3 ) 3 HOH CH3 CH2
- 51. 23-23-5252 Cope EliminationCope Elimination Copeelimination:Cope elimination: Thermal decomposition of an amine oxide. Step 1: Oxidation of a 3° amine gives an amine oxide. Step 2: If the amine oxide has at least one β- hydrogen, it undergoes thermal decomposition to give an alkene. CH2 N-CH3 CH3 H2 O2 O CH3 CH2 N-CH3 H2 O+ + + - An amine oxide O CH3 CH2 N-CH3 H 100-150°C CH2 (CH3 ) 2 NOH+ N,N-Dimethyl- hydroxylamine Methylene- cyclohexane + -
- 52. 23-23-5353 Cope EliminationCope Elimination •Cope elimination shows syn stereoselectivity but little or no regioselectivity. • Mechanism: a cyclic flow of electrons in a six- membered transition state. :O heat + - Transition state an alkene N,N-dimethyl- hydroxylamine C C H N CH3 CH3 N CH3 CH3 O H C C :