Chem 225 Notes Page 128 Chapter 23: Amines I. Introduction A. Classification of Amines Amines are classified by the number of carbon groups attached to the nitrogen: ammonia primary (1 o ) secondary (2 o ) tertiary (3 o ) quaternary ammonium ion B. IUPAC Nomenclature 1) Find the longest carbon chain which contains the carbon attached to the NR 3 group. 2) Count the number of carbons in this chain and determine the parent stem name. 3) Add the suffix -anamine. 1 carbon group 2 carbon groups 3 carbon groups 4 carbon groups 4) Number the carbon chain starting from the end closest to the NR 3 group. For cyclic compounds, the carbon with the NR 3 group is carbon 1. 5) Indicate the position of the nitrogen atom on the parent chain by adding the number, separated by dashes, in between the stem name and the -amine suffix (ie. stem-#- amine). 6) Add substituent names, with appropriate numbers, in front of the amine name. 7) Add the name of any other alkyl groups on the nitrogen in front, with an N- prefix. 8) For complicated carbon chains, name the NH 2 group as an amino substituent.
Chem 225 Notes Ch 23: Amines Page 129 C. Common Names Name all the carbon groups attached to nitrogen as alkyl groups, then add amine. D. Special Common Names (MEMORIZE) E. Nomenclature: Ammonium Salts Nitrogen with four groups attached has a positive formal charge. These compounds are called ammonium ions, and they usually exist as salts with a corresponding anion. To name ammonium compounds: 1) Name all of the carbon groups attached to the nitrogen as alkyl groups. 2) Add the name ammonium at the end. When the compound is a salt with an anion, add the name of the anion after the name of the ammonium ion.
Chem 225 Notes Ch 23: Amines Page 130 II. Properties of Amines A. Lone Pair Inversion at Nitrogen If the nitrogen of an amine has three different groups attached (plus the lone pair), it is a stereocenter. However, nitrogen stereocenters do not hold their configuration. They racemize because the lone pair can invert through the nitrogen: B. Basicity of Amines, Anilines, and Amides Carbon groups donate electrons to the nitrogen, which increases the electron density of the lone pair and increases the basicity of the amine: Conj. Acid pka Amine Base NH 4 EtNH 3 9.26 NH 3 10.75 EtNH 2 Et 3 NH 10.76 Et 3 N Et 2 NH 2 10.98 Et 2 NH However, the ammonium ion is stabilized by solvation. Tertiary ammonium ions are sterically hindered, which reduces solvation and makes them less stable. Therefore, tertiary amines are less basic than secondary amines.
Chem 225 Notes Ch 23: Amines Page 131 In aromatic amines (anilines) and amides, the nitrogen lone pair participates in resonance: Resonance reduces the electron density of the lone pair on nitrogen, so anilines and amides are less basic than amines: Conj. Acid pka Base 0 PhNH 3 4.58 PhNH 2 NH 4 9.2 NH 3 RNH 3 R 3 NH R 2 NH 2 10 11 RNH 2 R 3 N R 2 NH
Chem 225 Notes Ch 23: Amines Page 132 III.Synthesis of Amines A. S N 2 Alkylation Observed reaction: Ammonia Problem: Polyalkylation Ammonia can deprotonate the ammonium salt of the product. The product amine can then react by S N 2 again: One solution is to use a large excess of ammonia, so that the product can t compete. The two reactions below also are used to avoid polyalkylation Observed reaction: Azide Ion Observed reaction: Gabriel Synthesis
Chem 225 Notes Ch 23: Amines Page 133 Mechanism of Gabriel Synthesis B. Reduction of Aromatic Nitro Groups Observed Reaction: C. Reductive Amination Observed Reaction: Mechanism:
Chem 225 Notes Ch 23: Amines Page 134 Example: D. Reduction of Amides and Nitriles Observed Reactions:
Chem 225 Notes Ch 23: Amines Page 135 IV.Reactions of Amines A. Reaction with Nitrous Acid Observed Reaction (1 o Amines): Observed Reaction (2 o amines): Alkyl diazonium ions are unstable and lose nitrogen (N 2 ) to form carbocations. N-Nitrosoamines are carcinogens. Aromatic diazonium (arenediazonium) ions are more stable, and can be used to put groups on the aromatic ring (see next reaction).
Chem 225 Notes Ch 23: Amines Page 136 B. Arenediazonium Replacement Reactions 1) Hydroxylation N N dil. H OH 2 SO 4, 2) Fluorination N N HBF F 4 3) Sandmeyer Reaction: Chlorination N N Cl CuCl 4) Sandmeyer Reaction: Bromination N N Br CuBr 5) Sandmeyer Reaction: Cyanation N N C N CuCN 6) Iodination N N I KI 7) Hydrogen Replacement N N H H 3 PO 2 8) Diazonium Coupling N N N N EDG EDG
Chem 225 Notes Ch 23: Amines Page 137 C. Hofmann Elimination Observed Reaction: Mechanism: Regioselectivity: The less substituted alkene is preferred (Hofmann rule):