Amines and Heterocycles McMurry: Chapter 24
Introduction to Amines and Heterocycles Amines and heterocycles (cyclic amines) are ammonia derivatives, many of whichare found widely in livingorganisms: 2
Colourful Amines and Heterocycles Nature has inspired chemists to duplicate natural dyes and create new synthetic ones to introduce colour to our world: King George VI O H N Br Br N H O - purpura molluscs 3
Heterocyclic c Amines Heterocycles are cyclic compounds containing at least one heteroatom: 4
Heterocyclic c Amines Heterocycles are found in many natural products that exhibit useful biologicalactivityactivity and in widely used pharmaceuticals: 5
Amine Nomenclature Amines are named by added the suffix amine, but in more complex compounds, the amine can be an amino substituent or an aniline derivative: 2 2 2 Complex compounds are treated as alkanamines with simpler alkylgroups on the amine identified with the locant N : N 6
Take Home: ae e: Nomenclature catu e Draw the following compounds: 4 bromo N isopropyl 3 methylaniline (R,E) oct 6 en 3 amine 7
Amine Structure and Properties Alkyl amines have an sp 3 N with approximately tetrahedral geometry. The N H groups participate ii in hd hydrogen bonding: Small amines have a bad odor resembling fish/decaying i material: 8
Basicity of Alkyl Amines Amines have a lone pair of electrons on the nitrogen that make them both hbasic and nucleophilic in nature: Nucleophilic amine: Basic amine: ammonium salt ammonium salt The relative base strengths of amines are calculated using the pk a of the ammonium salt! 9
Basicity of Amines ammonium salt weak conjugate base (NR 3 ) Low pk a (strong acid) strong conjugate base (NR 3 3) High pk a (weak acid) stronger base weaker base 10
Explaining Relative Basicity of Amines Amides are non basic and non nucleophilic due to resonance with the carbonyl: Aryl amines are less basic than alkyl amines due to electron delocalization into the aromatic ring: 11
Basicity of Aryl Amines Substituents on the aromatic ring varies the amine basicity: Electron donors: increase basicity adds electron density to nitrogen Electron withdrawing: decrease basicity withdraws electron density from nitrogen strong base weak base 12
IR Spectroscopy of Amines N H stretch: 3500 3300 cm 1 R 2 NH have 1 band while RNH 2 have 2 bands sharper and less intense than O H stretch 13
NMR Spectroscopy ofamines 13 C NMR: Carbons attached to amines are deshielded and are found between 30 65 ppm. 1 H NMR: RNH: variable chemical shift (1.0 4.0 ppm, broad singlet) R 2 CHNH: deshielded and found in the 2.0 3.0 ppm range 2 14
Amine Synthesis: S N 2 Reactions Amines are good nucleophiles, so they readily participate in S N 2 reactions with alkyl halides: N 15
Amine Synthesis: S N 2 Reactions How can S N 2 reactivity be limited? Use a large excess of amine to maximize i monoalkylation: l N How can the excessive S N 2 reactivity it be made and utilized? If the quaternary salt is desired, use excess alkylating reagent: 16
Alkyl Amine Reactivity: ty: Hofmann Elimination Amines (like alcohols) can be eliminated to give alkenes. Just like H 2 O is a better leaving group than OH, the amide ion ( NH 2 ) must be converted to a better LG for elimination to occur: 17
Alkyl Amine Reactivity: ty: Hofmann Elimination Elimination of the ammonium salt is promoted by silver oxide, which exchanges the iodide ion for a hydroxide ion. Then, an E2 reaction occurs to give the less substituted alkene due to sterics: 18
Synthesis Problems Predict the products of the following Hofmann elimination reactions: * 2 2 2 2 19
Amine Synthesis: Azides Azide ions ( N 3 ) are useful alternatives to NH 3 since they only undergo S N 2 reactivity ii once and can be reduced dto 1 amines: 3 N alkyl azide 4 2 2 2 20
Amine Synthesis: Gabriel Synthesis The Gabriel synthesis of 1 amines utilizes phthalimide alkylation l and imide id hd hydrolysis steps: N phthalimide 2 2 2 2 21
Take Home ae emechanism Problem Draw the imide hydrolysis mechanism: *Hint: an imide is just like 2 amide functional groups! 22
Amine Synthesis: Reductive Amination Reductive amination is another common amine synthesis whichinvolves involves converting an aldehyde or ketone to an imine and then reduced it with sodium cyanoborohydride: H H B H Na CN O NaBH 3 CN OH O 3 H very slow NH NaBH 3 CN NH 2 H very fast 23
Synthesis s Problems Complete the following Gabriel synthesis: 24
Take Home ae esynthesis s Problems Predict the starting material or product in the following reactions: 25
Aryl Amine Reactivity: ty: Diazonium ao Salts When aryl amines are treated with nitrous acid (made in situ), the reaction produces very useful and reactive intermediates called diazonium salts: Diazonium salts from alkyl l amines cannot be used since they spontaneously decompose! 26
Diazonium ao Salts in Sandmeyer Reactions Diazonium salts are useful because they can be replaced with a variety of substituents including halides in Sandmeyer reactions: The mechanism is believed to occur via radical intermediates. 27
Diazonium ao Salts in S E Ar Reactions Diazonium salts also couple with phenols and anilines in an S E Ar reaction to give azo compounds: 28
y Connections Chemistry Azo Compounds: Keeping Things Colourful! Azo compounds have extended conjugation so they absorb in the visible region, which we perceive as colour: Small structural changes to the azo compound allows a variety of colours to be made. These compounds p are used widelyy as dyes y ((called azo dyes) for textiles, paint, food, cosmetics, and indicators. 29
In Class CassSynthesis s Problem Predict the products of the following reactions: 2 2 2 30
Take Home ae esynthesis s Problem * Propose a synthesis for the following compounds using benzene and phenol as your starting materials: 31