Gentilucci, Amines Nomenclature of Aliphatic Amines 1. Alkane + the suffix -amine, or -amino to name a numbered substituent. 2. Select the longest carbon chain containing the amino group 3. Number the carbon chain, beginning at the end nearest to the amino group, or, to give the lowest number at the first point of difference. 4. Number the substituents and write the name, listing substituents alphabetically. 3-methylpentanamine 5-methyl-2-hexanamine Gentilucci, Amines Amines are further categorized as "primary, secondary, tertiary and quarternary" based on the number of substituents on the nitrogen: 1 Gentilucci, Amines + - Physical properties NH 3 + H 2O NH 4 + OH Polar compounds [NH +] [OH -] Keq = 4 H-bonds [NH 3] [H 2O ] Basicity [NH ] [H O+] Et NH EtNH 3 3 NH3 Et3N 2 2 Ka = + [NH 4 ] pKb = 4.74 3.25 3.02 3.19 NO2 Kb = keq [H2O] N N H NH2 NH2 8.75 13.6 9.37 13.0 Gentilucci, Amines Reactions of Aliphatic Amines SN2 . Amines are good nucleophiles and will undergo an SN2 reaction with R-X (X = good leaving group). Acylation . They react with activated carbonyl compounds: synthesis of amides. Sulfonation . The reaction with a sulfonyl halide forms the sulfonamide. E.g. Ts -Cl, producing the corresponding p-toluenesulfonamide. Ts-Cl acid halides, anhydrides, carboxylate esters amide 2 Gentilucci, Amines Reactions that Yield Aliphatic Amines Simple amines and ammonia will undergo an SN2 reaction to give further substitution on the nitrogen. Ammonia reacts with alkyl halides to give a mixture of the primary and secondary amines, with a trace of tertiary and quarternary amines. Gentilucci, Amines Synthesis of primary amines . In the Gabriel Synthesis , pthalimide anion is reacted with the alkyl halide to give the intermediate N-substituted pthalimide. On acid hydrolysis (or reaction with hydrazine), this releases the primary amine. pthalic acid 3 Gentilucci, Amines Synthesis of amines . Primary amines can also be prepared by the reduction of nitriles and amides. Reduction of a nitrile by LiAlH4 gives the primary amine. Reduction of an amide can yield a 1°, 2° or 3° amine, depending on the amide. Gentilucci, Amines Reductive amination An aldehyde or ketone will react with ammonia to give an intermediate imine. Reduction of this imine with Raney Ni/H2 gives the corresponding amine. imine Primary and secondary amines can also be utilized in reductive amination reactions, typically using NaBH3CN (Na- cyanoborohydride) to trap the intermediate immonium ion. 4 Gentilucci, Amines Hofmann Elimination Reaction of primary amines with an excess of iodomethane CH3-I converts the primary amine into the quarternary ammonium salt. The cationic nitrogen which is now formed is a good leaving group, and will undergo E2 elimination on reaction with Ag2O to give the alkene, in a reaction known as the Hofmann Elimination. What is the origin of OH- ? Why an Ag oxide ?! Gentilucci, Amines The Hofmann Elimination is unusual for an E2 elimination because the least substituted alkene is typically formed. Hofmann and Curtius rearrangements Amides and acid azides can also be converted to amines. Both the amide and acyl azide can be prepared from an intermediate acid halide, and the reaction results in the shortening of the alkyl chain by one carbon (the carbonyl is lost as CO2). 5.