Text 1 Chapter 19, p 836-899 Text 2 Chapter 14 Chapter 14. Amines (胺)
Feb 14, 2016
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