Amines Chapter 20 PDF

Chapter 20 Amines Chapter 20 In this chapter we will consider: ❖ The properties, structure, and nomenclature of amines ❖ The ability of amines to act as bases, salts, and resolving agents ❖ The synthesis of amines Chapter 20 1. Nomenclature ❖ 1...

Chapter 20 Amines Chapter 20 In this chapter we will consider: ❖ The properties, structure, and nomenclature of amines ❖ The ability of amines to act as bases, salts, and resolving agents ❖ The synthesis of amines Chapter 20 1. Nomenclature ❖ 1o Amines NH2 NH2 Butylamine Cyclohexylamine ❖ 2o Amines N N H H Butylethylamine Diethylamine Chapter 20 ❖ 3o Amines N N Triethylamine Butylethylmethylamine Chapter 20 1A. Arylamines Chapter 20 1B. Heterocyclic Amines Chapter 20 2. Physical Properties and Structure of Amines 2A. Physical Properties Chapter 20 2B. Structure of Amines N R3 R1 R2 ❖ N: sp3 hybridized ❖ Trigonal pyramidal ❖ Bond angles close to 109.5o Chapter 20 ❖ 3o Amines with three different groups R 3 R3 R 2 R2 N N R1 R1 The two enantiomeric forms interconvert rapidly ⧫ Impossible to resolve enantiomers Pyramidal or nitrogen inversion ⧫ Barrier ~ 25 kJ/mol ⧫ Low enough to occur rapidly at room temperature Chapter 20 ❖ Ammonium salts with four different groups R3 R3 R2 R2 N R4 R4 N R 1 X X R1 enantiomers can be resolved Chapter 20 3. Basicity of Amines: Amine Salts RNH3+ + H2O RNH2 + H3O+ [RNH2][H3O+] Ka = [RNH3+] pKa = − log Ka Chapter 20 ❖ The aminium ion of a more basic amine will have a larger pKa than the aminium ion of a less basic amine H H H H N H CH3 N H CH3CH2 N H H H H Aminium 9.26 10.64 10.75 ion pKa Chapter 20  H R>N H + H OH R> N H + OH2 H H By releasing electrons, R—> stabilizes the alkylaminium ion through dispersal of charge Chapter 20 (CH3)3N > (CH3)2NH > CH3NH2 > NH3 o o o 3 2 1 Gas phase (CH3)2NH > CH3NH2 > (CH3)3N > NH3 2o 1o 3o Aqueous solution Chapter 20 3A. Basicity of Arylamines H H H H N H H N H H N H CH3 Aminium 10.64 4.58 5.08 ion pKa Chapter 20  NH2 NH2 NH2 NH2 NH2 Five resonance structures Chapter 20  NH2 NH3 + H2O + OH Anilinium ion NH3 NH3 Only two resonance structures Chapter 20 3B. Basicity of Heterocyclic Amines Chapter 20 Chapter 20 3C. Amines versus Amides ❖ Amides are far less basic than amines (even less basic than arylamines). The pKa of the conjugate acid of a typical amide is ~zero Amide Larger : :O: : :O: :O: : resonance : R NH2 R NH2 R NH2 stabilization N-Protonated Amide Smaller : :O: :O: resonance R NH3 R NH3 stabilization Chapter 20  O O + H2O + OH : R NH2 R NH3 R > NH2 : + H2O R NH3 + OH Chapter 20 3D. Aminium Salts and Quaternary Ammonium Salts 2 R R2 1 N 3 + H Cl R1 N R3 Cl R R H2O H Cannot act (aminium salt) as bases R2 R2 N + R 4 Br R 1 N R3 Br R 1 R3 4 R ⊕ ⊖ However, R4N OH are strong (quaternary bases (as strong as NaOH) ammonium salt) Chapter 20 3E. Solubility of Amines in Aqueous Acids Chapter 20 3F. Amines as Resolving Agents ❖ Enantiomerically pure amines are often used to resolve racemic forms of acidic compounds by the formation of diastereomeric salts Chapter 20  O O + H2N OH HO HO H H OH H3C H (R) (S) (R)-Amine (optically pure) Racemic (R,S)-acid This is the resolving agent O O H3N H3N O O HO H H3C H H OH H3C H (R) (R,R)-salt (R) (S) (S,R)-salt (R) separate O H3O+ H3O+ O OH HO (R)-Acid (S)-Acid HO H H OH Chapter 20 4. Preparation of Amines 4A. Through Nucleophilic Substitution Reactions ❖ Alkylation of ammonia NH3 X NH2 X H NH3 NH2 Chapter 20  H X NH2 N (over-alkylation) H X NH3 X N NH3 H N + N X Chapter 20 ❖ Alkylation of azide ion and reduction NaN3 X N N N Na/EtOH or LiAlH4 NH2 Chapter 20 ❖ The Gabriel synthesis O O 1. KOH N H N 2. Br O O NH2NH2 EtOH, heat O H N H2N + N H O Chapter 20 ❖ Alkylation of 3o amines R R N + Br R (SN2) R R N Br R Chapter 20  4B. Preparation of Aromatic Amines through Reduction of Nitro Compounds H2, catalyst H NO2 NH2 HNO3 H2SO4 R R R 1. Fe, HCl 2. NaOH Chapter 20 4C. Preparation of 1o, 2o, & 3o Amines through Reductive Amination H H N NH3 1o amine [H] R R' H H R" O N R"NH2 2o amine R R' [H] R R' H aldehyde R"' R" or N R"R"'NH ketone 3o amine [H] R R' H Chapter 20 ❖ Mechanism two O steps + H2N R" R R' R" HO NHR" (- H2O) N R R' R R' Hemiaminal Imine [H] NHR" R R' H Chapter 20 ❖ Examples NH3, H2/Ni (1) O NH2 heat & pressure H O N 1. NH2 (2) 2. NaBH3CN H N 1. O N (3) 2. LiBH3CN Chapter 20 4D. Preparation of 1o, 2o, & 3o Amines through Reduction of Nitriles, Oximes, and Amides H [H] R C N or C OH RCH2NH2 R N O R' C R' [H] R N RCH2N R" R" Chapter 20 ❖ Examples OH O N NH2 H2N OH Na (2) EtOH Chapter 20 ❖ Examples O N Cl N (3) H pyridine O 1. LiAlH4 2. H2O N Chapter 20 4E. Preparation of Primary Amines through the Hofmann and Curtius Rearrangements ❖ Hofmann rearrangement Chapter 20 ❖ Examples O Br2 NH2 (1) NH2 NaOH O Br2 (2) NH2 NaOH NH2 Chapter 20 ❖ Mechanism O OH O Br Br O H Br R N R N R N H H H HO OH HO O C O C N O R (Hofmann Br N R (isocyanate) rearr.) R N O H OH O C N + CO2 R NH2 H R N R H Chapter 20  ❖ Curtius rearrangement O O NaN3 heat O C N + N2 (g) R Cl R N N N R H2O CO2 (g) + R NH2 e.g. O NH2 Cl 1. NaN3 2. heat 3. H2O Chapter 20 13. Summary of Preparations of Amines O O R= N H 2 2 R1 R R1 R 1. KOH O NH3 2. R-X [H] 3. NH2NH2, EtOH, heat H2, cat. or R NH2 1. Fe, HCl 1. NaN3 2. NaOH 2. LiAlH4 R NO2 R Br Chapter 20  OH N R= R1 R2 R1 R2 Na EtOH 1. NaN3 2. heat 1. LiAlH4 O 3. H2O 2. H2O R NH2 R C N R Cl Br2 O NaOH R NH2 Chapter 20  END OF CHAPTER 20  Chapter 20