Upload
shon-sanders
View
321
Download
10
Tags:
Embed Size (px)
Citation preview
Chapter 17 Amines ( 胺 )17.1 Amine Nomenclature 17.2 Structures of amines 17.3 Basicity of amines 17.4 Preparation of amines 17.4.1 Preparation of amines by alkylation of ammonia 17.4.2 The Gabriel synthesis of primary amines 17.4.3 Preparation of amines by reduction17.5 Reactions of amines17.5.1 Alkylation of amines17.5.2 Acylation of amines17.5.3 The Hofmann Elimination
17.5.4 Reactions of amines with nitrous acid(A) Reactions of primary aliphatic amines with nitrous acid(B) Reactions of primary arylamines with nitrous acid(C) Reactions of secondary amines with nitrous acid (D) Reactions of tertiary amines with nitrous acid 17.5.5 Synthetic transformations of aryl diazonium salt (A) Replacement of the diazonium group by - OH
(B) Replacement of the diazonium group by - X, - CN(c) Replacement of the diazonium group by - H 17.5.6 Azo coupling 17.6 Spectroscopic analysis of amines
17.1 Amine Nomenclature
R N NHH
H
Organic derivatives of ammonia
Alkylamines ArylaminesNAr
CH3NH2 CH2NH2CH3 CHCH2NH2CH3
Methylamine( 甲胺)
Isobutylamine( 异丁胺 )
2-Methylpropylamine( 2- 甲基丙胺)
Benzylamine( 苄胺)
Primary amines (伯胺) :
P380P380
Aniline( 苯胺 )
NHH
NCH3
CH3CH2
H (CH3CH2)2NH
Ethylmethylamine(甲乙胺)
N-Methylethylamine(N- 甲基乙胺)
Diethylamine(二乙胺)
Secondary amines:( 仲胺)
TrimethylamineN,N-Dimethylmethylamine
(三甲胺)( N,N- 二甲基甲胺)
N,N-Dimethyl-aniline
(N,N- 二甲基苯胺 )
Tertiary amines:(叔胺) (CH3)3N
N CH3H3C
NH2Cyclohexylamine
( 环己胺 )
H2NCH2CH2NH21,2-Ethyldiamine
( 1,2- 乙二胺)
Diamines:
Ammonium ions(铵离子)
Aminium salts(铵盐)
NH3 Cl C16H33N(C4H9)3 Br
Anilinium chloride(盐酸苯胺)
Quaternaryammonium
salts (季铵盐)HOCH2CH2NH2
2-Aminoethanol( 2- 氨基乙醇)
NH3C CH2CH3
N-Ethyl-N-methylcyclohexylamine(N- 甲基 -N- 乙基环己胺 )
Heterocyclic amine:( 杂环胺 )
Pyridine( 吡啶 )
Pyrrole( 吡咯 )
Quinoline( 喹啉 )
Indole( 吲哚 )
N N N N
H
Pyrrolidine ( 吡咯烷 )( 四氢吡咯 )
Piperidine ( 哌啶 )
N
H
N
H
17.2 Structures of amines
sp3-hybrid
sp3-sp3 hybridized orbitals overlapC - N :
N - H : sp3hybridized -1s orbitals overlap
N
R'R''
R'''
NR'
R''
R'''
Tertiary amines with 3 different groups:
Interconversion of amine enantiomers
NCH
N: 1s22s22px12py
12pz1N: 1s22s22px
12py12pz
1
P383,12.2P383,12.2
Pyramid( 棱锥型 )
17.3 Basicity of amines
N
CH3
Et C6H5
CH2CH CH2
X
N
CH3
C6H5CH2 CHCH2
Et
X(S) (R)
Quarternary ammonium salt:
RNH2 + H2O RNH3 + OH
Weak bases
Kb =[ RNH3 ] [ OH ]
[ RNH2 ]pKb = - log Kb
P384,12.3
P384,12.3
Amines pKb
NH3
CH3NH2
(CH3)2NH
(CH3)3NNH2
NH2O2N
NH2CH3O
4.7
3.4
3.3
4.3
9.4
13
8.7
Table 1 Basic strength of some aminesP385,Table12.1
P385,Table12.1
1. All amines are weak bases:H2O < RNH2 < < OH -
2. RNH2 > NH3 > NH2
Alkylamines are slightly stronger bases than ammonia; Arylamines are much weakerbases than ammonia and alkylamines.
R NH2 +I p -πconjugationDelocalization of nitrogen lone-pairelectrons
Decreasing the electron density at nitrogen.
P384,12.3
P384,12.3
NH
H
NH2 NH2 NH2 NH2 NH2
NH3 CH3 NH3pKa = 4.63 pKa = 10.66
R NH3 + H2O R NH2 + H3O
Ka =[RNH2][H3O+]
[RNH3+]
pKa = -logKa
pKa + pKb = 14
Weaker base:Smaller pKa for ammonium ionStronger base: Larger pKa for ammonium ionWeaker base:Smaller pKa for ammonium ionStronger base: Larger pKa for ammonium ion
3. R2NH > RNH2 > R3N >NH3
NR
RR
H Poorer solvation
+ HCl NH3ClNH2
Separation of amines from neutral organic compounds
17.4 Preparation of amines17.4.1 Preparation of amines by alkylation of ammonia
R X R NH3X NaOH R NH2NH3 (excess) +
P384,12.3
P384,12.3
Anilinium ionAnilinium ion
R NH2R X R2NH
2. OH
1. R X
2. OHR3N1.
17.4.2 The Gabriel synthesis of primary amines
R X R NH2
Reagent:C
CN
O
O
K
Potassium salt of Phthalimide
(邻苯二甲酰胺钾盐)
C
CN
O
O
HKOH C
CN
O
O
KR X C
CN
O
O
RDMF
Imide(酰亚胺)
Ch.P436Ch.P436
Primary alkyl halide, SN2Primary alkyl halide, SN2
RX: CHCR'
O
X
CHCOR'
O
X
ROTs
, ,ArX
17.4.3 Preparation of amines by reduction
CH2C N + 2 H2Raney Ni
140¡æ CH2CH2NH2
(71%)
LiAlH4
Reduction of nitriles to amines
C
C
O
O
N RNaOH, H2O
R NH2 +C
C
O
O
O
O
Siegmund Gabriel(1851-1924)
Siegmund Gabriel was born in Berlin,Germany,and received his Ph.D. in1874 at the University of Berlin,working with August von Hofmann. After furtherwork with Robert Bunsen,he became Professor of Chemistry at the Univ. of Berlin.
Robert Wilhelm Bunsen
1811-1899
poohbah.cem.msu.edu/Portraits/
Gabriel Synthesis. Gabriel, Ber. 20, 2224(1887). M. S. Gibson, R. W. Bradshaw, Angew. Chem. Int. Ed. 7, 919 (1968); B. Dietrich et al., J. Am. Chem. Soc. 103, 1282 (1981); O. Mitsunobu, Comp. Org. Syn. 6, 79-85 (1991). Modified conditions: S. E. Sen, S. L. Roach, Synthesis 1994, 756; M. N. Khan, J. Org. Chem. 61, 8063 (1996). Stereoselectivity: A. Kubo et al., Tetrahedron Letters 37, 4957 (1996).
Ar H HNO3 Ar NO2[ H]
Ar NH2H2SO4
Reduction of nitro compounds to arylamines
NO21) Fe, HCl
2) OH
NH2H2, cat
Reduction of amides to amines:
N
CH3
CCH3
O
+ LiAlH4Et2O
2) H2ON CH2CH3
CH3
1)
P389P389
Reductive amination:
CR
(R')H O + NH3(or R''NH2)
-H2O CR
(R')H NH(R'')
Imine(亚胺)H2, Ni
CHR
(R')H
NH2(R'')
C O
H
+ NH3H2, Ni90 atm
40 ~ 70¡æ
CH2NH2(89%)
(CH3)2C O + H2NCH2CH2OHH2, Ni, EtOH
95£¥(CH3)2CNHCH2CH2OH
Ch.P435Ch.P435
17.5 Reactions of amines
NUnshared electron pair of nitrogen:
Basicity: N + H X
Nucleophilicity:
N + C O
17.5.1 Alkylation of amines
RNH2R'CH2X RNHCH2R'
R'CH2X RN(CH2R')2
R'CH2X RN(CH2R')3X
CH2NH2 + 3 CH3IMeOH
heatCH2N(CH3)3 I
(Cyclohexyl-methyl)-
amine
(Cyclohexyl-methyl)-
amineMethyliodideMethyliodide
(cyclohexylmethyl)-trimethyl-
ammonium iodide(99%)
(cyclohexylmethyl)-trimethyl-
ammonium iodide(99%)
17.5.2 Acylation of aminesAcylating agents: acyl chlorides, carboxylic acid anhydrides
Cl NO21) NaOH, H2O
2) H3+O
HO NO2H2, Ni
HO NH2(CH3CO)2O
HO NHCCH3
O
Synthesis of Paracetamol (扑热息痛) :
17.5.3 The Hofmann Elimination
Decreasing the activity of aryl ring or Protecting amino groups :
NH2(CH3CO)2O
NHCOCH3
Br2, ¡÷
NHCOCH3
Br
H2O,OH- ,¡÷
NH2
Br
RNH2 C C
Methylation of an amine by excess CH3I:CH3CH2CH2CH2CH2CH2NH2
CH3Iexcess
CH3CH2CH2CH2CH2CH2N(CH3)3IHexylamine
Hexyltrimethylammonium iodide
Ch.P448
( 六 )Ch.P448
( 六 )
Quaternary ammonium hydroxides (氢氧化季铵碱) can be prepared from Quaternary ammonium halides:2 RCH2CH2N(CH3)3X + Ag2O + H2O 2 RCH2CH2N(CH3)3OH
+ 2AgX
CH2N(CH3)3 I Ag2OH2O, CH3OH
CH2N(CH3)3 OH
Quaternary ammonium hydroxidesheat β- Elimination to form alkenes
and an amineCH2H
N(CH3)3
OH
160¡æ CH2 + (CH3)3N + H2O
Methylenecyclohexane(亚甲基环己烷)
(69%)
RCH CH2
N(CH3)3
HHO¦Ä
¦Ä
Transition stateThe base attacks the mostacidic hydrogen or least hinder hydrogen.
E2 Reaction
Anti relationship
Regioselectivity of Hofmann elimination:
To give a less substituted alkene.
C C
N(CH3)3+
HHO E2 reactionC C + N(CH3)3 + H2O
HO
CH3CH2CHNH2
CH31) 3CH3I
2) AgOHCH3 CH
H
CH
H2C H
N(CH3)3OH
CH3CH2CH CH2 CH3CH CHCH3(95%) (5%)
¡÷ +
H
HHN(CH3)3
CH3CH2 H
HO
-H2O-N(CH3)3 H
HCH3CH2
H
H
HHN(CH3)3
CH3CH2 H
HO
-H2O-N(CH3)3 H
HCH3CH2
H N(CH3)3
H CH3
H
CH3H
HO
-H2O
-N(CH3)3
H CH3
CH3 HN(CH3)3
H CH3
H
CH3H
HO
-H2O
-N(CH3)3
H CH3
CH3 H
Hofmann rule is opposed to the Zaitsev rule.C1–C2
C2–C3
August Wilhelm von1818–1892
August Wilhelm von , 1818–1892,German organic chemist. He wasProfessor at the Univ. of Berlin from 1865 and was a founder (1868) of the German ChemicalSociety. He studied the constitu-tion of aniline and was the firstto prepare rosaniline and its derivatives, thereby laying the basis for the aniline dye industry. He also discovered a reaction forderiving amines from amides anddeveloped the Hofmann methodof finding the vapor densities, and from these the molecular weights, of liquids. He also helped topopularize the concept of valence(the word comes from his termquantivalence
17.5.4 Reactions of amines with nitrous acid (Nitrosation 亚硝化反应 )
(A) Reactions of primary aliphatic amines with nitrous acid
NaNO2 + HCl1/2 H2SO4
HNO2 + NaCl1/2 Na2SO4
Nitrosating agent:
Primary aliphatic amines Nitrous acidto yield unstable aliphatic diazonium salt ( 重氮盐 )Diazotization ( 重氮化反应 )Aliphatic diazonium salts decompose to formcarbocations and nitrogen:
CH3CH2CH2NH2NaNO2, HCl
CH3CH2CH2N NCl
CH3CH2CH2 + N2 + HCl
Alkene, alcohol, alkyl halide
(B) Reactions of primary arylamines with nitrous acid
Primary arylamines form diazonium salt on nitrosation:
NH2 + NaNO2 + 2 HCl 0 ~ 5¡æ N N Cl + H2O + NaCl
Aryl diazoniumsalts are stable below 5℃
P390P390
(C) Reactions of secondary amines with nitrous acidSecondary amines: both aryl amines and alkyl amines react with nitrous acid to yieldN-nitrosoamines (亚硝胺)
+ NaNO2 + 2 HCl NN
CH3
ONHCH3
N-nitrosoamines are usually separated from the reaction mixture as oily yellow liquids(D) Reactions of tertiary amines with nitrous acid
R3N NaNO2, HCl
No reaction
Tertiary aryl amines react with nitrous acid to form C-nitroso aromatic compounds:
N(CH3)2NaNO2, HCl
N(CH3)2ON
Electrophilic aromatic substitution
17.5.5 Synthetic transformations of aryl diazonium saltThe diazonium group (重氮基) may be replaced by other atomes or groups: -X, - OH, - CN and - H.
( )
P391P391
:Electron-withdrawing group
ArH ArNO2 ArNH2 ArN N
Aryl diazonium salts can be prepared from arene:
(A) Replacement of the diazonium group by - OH
Aryl diazonium ion is converted to phenols( 酚 ) (CH3)2CH NH2
1. NaNO2, H2SO4, H2O2. H2O, heat
(CH3)2CH OH
Sulfuric acid is usually used instead of hydrochloric acidQuestion: Design a synsthesis of
OH
Br
Hydrolysis N2+
p-Isopropylaniline p-Isopropylphenol (73%)
(B) Replacement of the diazonium group by - X, - CN
NO2
NH2
H2SO4, NaNO2
H2O, 0 ~ 5¡æ
NO2
N2+HSO4
KI
NO2
I
+ N2
The preparation of aryl iodides
The preparation of aryl fluorides:Treating the diazonium salt with fluoboricacid (HBF4)
CH3
NH2
1) NaNO2, H+
2) HBF4
CH3
N2+BF4
¡÷
CH3
F+ N2 + BF3
(69%)
(81%)
The Sandmeyer reaction:Aryl diazonium salts react with cuprouschloride, cuprous bromide, cuprous cyanide
£ N2 -X or -CN
NH2
Cl
HBr, NaNO2
H2O0 ~ 5¡æ
N2+ Br -
Cl
CuBr
100¡æ
Br
Cl
+ N2
NO2
NH2HCl, NaNO2
H2O(r.t)
NO2N2
+Cl CuCN
90 ~ 100¡æ
NO2CN
+ N2
(70% overall)
(65% overall)
Born inWettingen near Zurich, and lived in the Zurich area for nearly all of his life. He trained as a precision instrument-maker, but became interested in chemistry. Self-educated in chemistry, he carried out chemical experiments in his kitchen. In 1881, he became a lecture assistant to Victor Meyer (1848-1897). He followed Meyer to Göttingen in 1886, but soon returned to Zurich and worked for Arthur Hantzsch (1857-1935). Sandmeyer joined Geigy as a research scientist in 1888, and eventually became a director of the firm. He discovered the decomposition of aryl diazonium Chlorides to chloroarenes in the presence of copper (I) chloride in 1884. He also worked on the triphenylmethane dyes and the synthesisof isatin. Many years before, he had suggested to Victor Meyer an impurity in commerical benzene was responsible for the isatin reaction with sulphuric acid, thereby paving the way for Meyer's discovery of thiophen.
Traugott Sandmeyer (1854-1922).
(C) Replacement of the diazonium group by - H Aryl diazonium salts react with hypophosphorous acid (H3PO2) ( 次磷酸)or ethanol to yield the product:
£ N2Ar £ HAr
CH3
NH2
(CH3CO)2O
CH3
NHCOCH3
1) Br2
2) OH -, H2O,¡÷
CH3
NH2
Br
H2SO4, NaNO2
H2O, 0 ~ 5¡æ
CH3
N2+
Br
H2PO2
H2Or.t
CH3
Br
Deamination(脱氨基作用)
(85%)
P392P392
The value of diazonium salts in synthesis:1. Substituents that are otherwise accessible only with difficulty, such as - F, - I, - CN, - OH, may be introduced onto a benzene ring.2. Compounds that have substitution patterns not directly available by electrophilic aromatic substitution can be prepared
Br
Br
BrNH2 Br2
H2O
Br
Br
BrNH2 NaNO2, H2SO4
H2O
EtOH
Aniline 2,4,6-Tribromoaniline(100%)
1,3,5-Tribromo-Benzene(74-77%)
17.5.6 Azo coupling ( 偶氮偶合反应 )Aryl diazonium salts are weak electrophiles, they react with highly reactive aromatic compounds, to yield azo compounds
N2+Cl + N(CH3)2
CH3COO -Na+
0¡æH2O
N N N(CH3)2
OH OpH = ~ 8
Azo dyes (偶氮染料)
OHN N SO3 NaOrange II :
P393P393
Alkaline solution
17. 6 Spectroscopic analysis of aminesIR :N H: Streching
vibration Primary amine3000-3500 cm-1
two peaks
Secondary amines 3280 cm-1
one peakTertiary amines No peak
C N: Streching vibration
1020-1220 cm-1Aliphaticamines
Aromaticamines 1250-1360 cm-1
Ch.P437( 四 )Ch.P437( 四 )
Infrared spectrum of isobutylamineCH3
CH3CH CH2 N H
H
C–N Stretchingvibration
C–N Stretchingvibration
N–H Stretchingvibration
N–H Stretchingvibration
N- 甲基苯胺的红外光谱
N-H伸缩 C-N
伸缩
苯环伸缩
1H NMR
N - H δ: 0. 6 ~ 5 ppm
C NR2
Hδ: 2.2 ~ 2.8 ppm
Problems to Chapter 17
P40212.21 (a), (d),(e)12.22 (a), (c),(f)12.24 酶斯卡灵,一种 高效的致幻剂。从 仙人掌中得来。12.27(b), (d),12.29(b), (c)12.30 (a)12.31(b), (c)12.3712.39
12.4112.4212.4812.5112.52
Additional Problems to Chapter 17
11. What are the major products you would expect from Hofmann elimination of the following amines? Show the reactions.
(a)N-Methylcyclopentylamine(c)
CH3CHCHCH2CH2CH3
CH3
NH2
2. Predict the product(s) of the following reactions.Give the major product.
N
H
(CH3)3I
excessA? Ag2O, H2O
B?heat
C?
(3) How would you prepare the following compounds from toluene? A diaonio ( 重氮盐 )replacement reaction is needed in some instances.
H3C
NH2(a) (b)
CH3
CH2NH2 (c)I C
OCH3
O
(4) Ch.P464 ( 十六 ), ( 十七 )