Chapter 14. Amines (Text 1 Chapter 19, p 836-899Text 2 Chapter 14

Nitro-compounds 1. Structure of nitro group Nsp2

: 3.5 ~ 4.0 Dbp: CH3NO2 bp 101 CH3COCH3 bp 56 Solubility: 10%2. Physical properties of nitro-compounds 3. Preparation of nitro-compounds

1Reduction of nitro-compounds 4. Reactions of nitro-compounds FeZnSn

2acidity of -H (-H

3Condensation with carbonyl compounds ----HenrySimilar to aldol condensation

3Aromatic nitro-compounds Increasing the reactivity of halobenzene for aromatic nucleophilic substitutionIncreasing the acidity of phenol ()

Amine () a

Some biologically important amines

Alkaloid

14.1 structure of aminesammonia ammonium salts amine primary aminesecondary aminetertiary aminequaternary ammonium saltsWhich is chiral compound ?

enantiomers that can not be resolved

enantiomers that can be resolved

14.2 NomenclatureCommon name: alkylamineIUPAC name: alkane ------- alkanaminemethylaminemethanamineethylamineethanaminepropylaminepropanamineethylmethylamineN-methylethanaminecyclohexylmethylamineN-methylcyclohexanamineN-

triethylamineN,N-diethylethanamineethylmethylpropylamineN-ethyl-N-methyl-1-propanamineN--N--1-anilinebenzeneamineN-methylanilineN-methylbenzenamineN-N,N-dimethylanilineN,N-dimethylbenzenamineN,N-

PyrrolePyrazoleImidazoleIndole(yndu)Heterocyclic amines PyridinePyridazinePyrimidineQuinolineIsoquinolinePiperidinePyrrolidine

2-aminoethanol2-3-aminopropanoic acid3-ethylenediamineethane-1,2-diamine

14.3 Physical properties and spectroscopy of aminespolar substances boiling points: alcohol > amine > alkanessoluble in water, alcohols

IRN-H streching vibrationC-N Streching vibration

Primary amine3200-3500 cm-1 two peaksSecondary amines3280 cm-1, one peakTertiary aminesNo peak

Aliphatic amines1020-1220 cm-1Aromatic amines1250-1360 cm-1

CH3CH2CH2NH2IR33693291

CH3CH2CH2NH21H NMRN-H: 1~4 ppm-H: 2~3 ppm-H: 1.1~1.8 ppm

13C NMR-C: 30~50 ppm-C: 15~40 ppmCH3CH2CH2NH2

MS-cleavage (-)M+odd mass number when one nitrogen is present.NIminium ion CH3CH2CH2NH2Similar to alcohol and ether

14.4 Basicity of amines (Basicity: H2O < RNH2 < OH- < RO- < C-Effects on amine basicitySubstituent effects Resonance effects : weakenHybridization effects N: sp3 > sp2

In gas phase in aqueous solution

Resonance effectsHybridization effects

14.5 Salts of amines (

Q+OH- are strong bases---as strong as sodium or potassium hydroxide.Q+X-

Quaternary ammonium salts as Phase-Transfer catalysts (PTC, ) Without catalyst, long time is needed to finish this reaction. Addition of Q+X- can speed up the reaction.

14.6 Reactions of amines1. Reactions with ketones and aldehydes (review)imine Shiff base enamine 2amine 1amine

2. Acylation (review)

3. Reactions of amines with sulfonyl chlorides() 19-14R3Nno reactionAr: Ph, p-CH3Phsulfonamide

The Hinsberg test (No reactionsolubleinsoluble

The Sulfa Drugs: Sulfanilamide

Synthesis of sulfa Druges

4. Reactions with alkyl halides: direct alkylation()1amine2amine3amineReactivity: 2> 1amineProducts: mixture of 1,2,3,4amines19-12

Useful direct alkylationExaustive alkylation()Reaction with a large excess of ammonia ()

5. Amines as leaving groups----The Hofmann elimination () 19-15-NH2 -NHR -NRR are poor leaving groups.-NR3+ are good leaving groups.(similar to OH2+)Hofmann alkene

Hofmann alkeneSaytzeff alkeneA Hofmann elimination is an E2 reaction. TS: anti-coplanar

The Hofmann rule----yield mainly the least substituted alkene.-----anti-coplanarbut unstablestablebut not anti-coplanaranti-coplanarbut unstablestableanti-coplanar

Problem: predict products for the following reactions.--Hofmannmajormajor

A Hofmann elimination is an E2 reaction. TS: anti-coplanar Yield mainly the least substituted alkene ----The Hofmann rule. -----The -H with stronger acidity is eliminated first. --HofmannSummary for the The Hofmann eliminationThe Hofmann elimination is frequently used to determine the structures of complex amines.

6. Oxidation of amines----The Cope elimination () 19-161amine2amine3amineamine oxide hydroxylamine hydroxylamine nitrosonitro[O]: H2O2, etc

TS: 5 membered ring; stereochemistry: syn-elimination milder condition than Hofmann elimination product: Hofmann products The Cope elimination ()-H5 membered ring

Problem: predict products for the following reactions.

majorminor

7. Reactions of amines with nitrous acidN2Primary amines:

Mechanism of diazotization

Secondary amines: N-Tertiary amines:

Distinguish of 1, 2, and 3 amineRNH2R2NHR3NRNH2R2NHR3NRNH2R2NHR3NNo reactiongasN2Yellow oil or solid

8. Reactions of arylamines Amino group: electron donating, activiting group, o-, p- directing group easily to be oxidized to give a complicated mixture aniline(1) Aromatic substitution ()

Strongly acidic reagents are unsuitable for substitution of aniline Oxidizing acids (such as nitric acid and sulfuric acid) may oxidize the amino group.()

(2) reactions of arenediazonium salts ( Coupling reactions of arenediazonium salts (Substitution ()

The Sandmeyer reaction Substitution ()phenol

Coupling reactions of arenediazonium salts (a diazo coupling reaction(.weak electrophilesazo compounds

Azo dyes methyl orange

Synthesis of methyl orange

14.7 Preparation of amines1. Amines through alkylation of ammonia or amines

2. Preparation of amines through reduction of nitro compounds Reduction methods H2 / Pt, Pd, or NiFe, HCl

3. Preparation of amines through reduction of azides [H] LiAlH4, H2/catPrimary amine

4. Preparation of amines through reduction of amides, nitrilesPrimary amine

5. Preparation of amines through reductive amination [H] LiAlH4, NaBH4, H2/cat, Na(CH3COO)3BH

Primary amine

Mechanism for reductive amination

Na(CH3COO)3BH, NaBH3CN can reduce imines and imine salts, but does not reduce the carbonyl group.()

6. Preparation of amines through the Hofmann and curtius rearrangements1) Hofmann rearrangement or Hofmann degradation R = alkyl, ArPrimary amidePrimary amine

the Curtius rearrangement (

7. Gabriel synthesis () Primary amine

Assignment 19-2, 6, 37, 38, 40, 41, 42, 44, 51568