Amines - Faculty Personal Homepage- KFUPM
Transcript of Amines - Faculty Personal Homepage- KFUPM
![Page 1: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/1.jpg)
1
Chapter 18
Amines
![Page 2: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/2.jpg)
2
Classification of Amines• Amines are classified as primary,
secondary , or tertiary according to the number of alkyl or aryl groups bonded to the nitrogen.
Note: The designation of 1o, 2oand 3o amine does not depend in any way on the structure of the R group.
![Page 3: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/3.jpg)
3
Examples
(CH3CH2)3NCH3NHCH2CH3CH3CH2NH2
ethylamine(a 1o amine)
Two alkyl groups attached to N
Three alkyl groups attached to N
(a 2o amine) (a 3o amine)
CH3 C
CH3
CH3
NH2 CH3 C
CH3
CH3
OH
One C attached to N(a 1o amine)
3 C’s attached to head Ca 3o alcohol
tert-butyl amine tert.-Butyl alcohol
![Page 4: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/4.jpg)
4
Amine Salt
• If four groups attached to N amine saltnitrogen is a positive ion
(CH3)2NH2+ Cl-
dimethyl ammonium chloride
Salt of 2° amine
N-methylpipridiniumbromide
NH
CH3+ Br-
Salt of 3° amine
![Page 5: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/5.jpg)
5
Quaternary Ammonium Salts• If all the four groups on N are alkyl or aryl (no
H’s on N) the compound is quternaryammonium salt
(CH3)4N+ Cl- NCH3
CH3+ Br-
tetramethylammoniumchloride N,N-dimethylpipridinium
bromide
![Page 6: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/6.jpg)
6
Nomenclature of Amines•Primary amines are named by replacing the -e of the corresponding parent alkane with –amine (functional group system)•Amines may also be named as alkylamines (substitutive system)
![Page 7: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/7.jpg)
7
If more than one alkyl group is attached to the nitrogen, the largest group is considered the parent. A subsidiary alkyl group is designated by an N-Alkyl- prefix
N-ethyl-N-methyl propylamine
![Page 8: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/8.jpg)
8
• Diamines are named by the name of the parent alkane followed by ending – diamine.
H2NCH2CH2CH2NH2
1,3-propanediamine• The substitutent -NH2 is called the amino group if present with a higher priprity functional group
CH3CHCO2H
NHCH3
2-(N-methylamino)-propanoic acid
![Page 9: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/9.jpg)
9
Nonaromatic Heterocylic Amines
N
H
NHpyrrolidine pipieridine
HN NH O NH
morpholinepiperizine
Note: in numbering of the heterocyclic rings, the hetroatom is considered position 1. oxygen has a higher priority than nitrogen
![Page 10: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/10.jpg)
10
Examples
N
O
CH3 CH2CH3
H
1
35N1
H
CH3
2
34
5
2- methylpyrrolidine 3-ethyl-5-methylmorpholine
![Page 11: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/11.jpg)
11
Bonding in Amines•The nitrogen atom in an amine is sp3 hybridized–The three groups and the unshared electron pair around nitrogen result in a tetrahedral geometry–If only the location of the groups (and not the unshared electron pair) are considered, the shape of the amine is trigonal pyramidal–Partial negative charge is localized in the region of the nonbonding electrons
![Page 12: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/12.jpg)
12
•It is usually impossible to resolve amine enantiomers that are chiral at nitrogen because they interconvert rapidly
– The interconversion occurs through a pyramidal or nitrogen inversion involving the unshared electron pair
![Page 13: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/13.jpg)
13
• Quaternary ammonium salts can be resolved into enantiomers
– Chiral quaternary ammonium salts cannot undergo nitrogen inversion because they lack an unshared electron pair on the nitrogen atom
![Page 14: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/14.jpg)
14
Spectral properties of Amines•Infrared Spectra– Primary and secondary amines are characterized by N-H
stretching vibrations in the 3300-3555 cm -1 region– Primary amines give 2 absorptions (from symmetric and
asymmetric stretching); secondary amines give one absorption
![Page 15: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/15.jpg)
15
Proton NMR•1H NMR–Primary and secondary amines have broad, uncoupled N-H peaks at δ 0.5-5–N-H protons will exchange with D2O and disappear from the 1H spectrum–Protons on carbons adjacent to the nitrogen appear at δ 2.2-2.9
![Page 16: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/16.jpg)
16
Preparation of Amines
![Page 17: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/17.jpg)
17
A. Synthesis of Amines by Substitution Reactions
1.By Nucleophilic Substitution Reactions.•Alkylation of Ammonia– Reaction of ammonia with an alkyl halide leads to
an aminium salt– The salt is treated with base to give the primary
amine
![Page 18: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/18.jpg)
18
• The method is limited because multiple alkylations usually occur.
![Page 19: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/19.jpg)
19
–Using an excess of ammonia helps to minimize multiple alkylations
CH3CH2CH2Br + NH3excess CH3CH2CH2NH2
propylamine1-bromopropane
- Using an excess of Alkyl Halides quaternary ammonium salt
NH3RX
RNH2RX R2NH
RX RXR3N R4N+ X-
CH3CH2I+NH3 excess (CH3CH2)4N+ I--OH
Example
![Page 20: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/20.jpg)
20
2) Gabrial phthalimide synthesis
H2O, OH-
heatCO2
-
CO2-
+ H2NRPrimary amine
Potassium phthalimide
![Page 21: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/21.jpg)
21
Examples
N- K+
O
O
CH3CH2Br1)
2) H2O,OH-
heat
CH3CH2NH2
N- K+
O
O
C6H5CH2Br1)
2) H2O,OH-
heatC6H5CH2NH2
![Page 22: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/22.jpg)
22
Synthesis of aminoacids by GabrialPhthalimide method
N-
O
O
+ BrCH(CO2C2H5)2NCH(CO2C2H5)2
O
O -OC2H5
NC(CO2C2H5)2
O
O
-RXSN2
NC(CO2C2H5)2
O
OR
Bromomalonicester
continued
![Page 23: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/23.jpg)
23
NC(CO2C2H5)2
O
OR
H+, H2Oheat
CO2H
CO2H
+CO2 + C2H5OH
H3NCHCO2H
R
+
H2O, OH-
+
H2NCHCO2H
R
An α aminoacid
![Page 24: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/24.jpg)
24
Example
NH
O
O
1) KOH
2) BrCH(CO2C2H5)2
3) -OC2H5
NC(CO2C2H5)2
O
O
-
C6H5CH2Cl
NC(CO2C2H5)2
O
OCH2C6H5
1) H+, H2O
2) OH-C6H5CH2CHCO2H
NH2
![Page 25: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/25.jpg)
25
3) Nucleophilic Aromatic Substitution
NO2
ClO2N + NH3heatpressure
NO2
NH2O2N
![Page 26: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/26.jpg)
26
B. Synthesis By Reduction1) Reduction of aromatic nitro compounds to
aryl amines
NO2
CH3O2N 1) Fe, HCl
2) OH-
NH2
CH3H2N
2,4-dinitrotoluene 2,4-toluenediamine
![Page 27: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/27.jpg)
27
2) Reduction of Nitriles
• Nitriles undergo hydrogenation or reduction with LiAlH4 to yield primary amines
CH3CH2CH2Br CN-1) LiAlH4
2) H+, H2OCH3CH2CH2CN
CH3CH2CH2CH2NH2
![Page 28: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/28.jpg)
28
3) Reduction of amides
• Reduction of amides can yield primary, secondary or tertiary amines using LiAlH4.
![Page 29: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/29.jpg)
29
4) Reductive Amination
![Page 30: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/30.jpg)
30
C. Synthesis by Amide Rearrangement
• An unsubstituted amide can be converted to a primary amine(Hofmann rearrangement )
1. The first two steps of the mechanism result in N-bromination of the amide.2. The N-bromoamide is deprotonated and rearranges to an isocyanate.3. The isocyanate is hydrolyzed to a carbamatewhich decarboxylates to the amine.
![Page 31: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/31.jpg)
31
Mechanism
![Page 32: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/32.jpg)
32
Mechanism continued
Notice: the amine contain one less carbon than the starting amide.
![Page 33: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/33.jpg)
33
Exampels
CH3CH2CH2CNH2
O+ Br2 + 4 OH-H2O
CH3CH2CH2NH2
CH3CH2 C NH2
CH3
H
CH3CH2 C C
CH3
H NH2
O Br2, OH-
(R)-2-butylamine(R)-2-methylbutanamide
Migration proceeds with retention of configuration
![Page 34: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/34.jpg)
34
![Page 35: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/35.jpg)
35
Basicity of Amines
R3N + H2O R3NH+ + OH-
If the amine is stabilized relative to the cation the amine is less basic
If the cation is stabilized relative to the free amine the amine is a stronger base
![Page 36: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/36.jpg)
36
Factors affect the relative base strength
1. An electron releasing group on the nitrogen increases basicity by dispersing the positive charge in the cation.
NH3 CH3NH2 CH3NHCH3pKb 4.75 3.34 3.27
Increasing Basicity
![Page 37: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/37.jpg)
37
2. The cation is stabilized by increasing solvation( the solvent help disperse the positive charge)
pKb 3.27 3.34 4.19 4.75
The trimethylaminium ion is solvated less well (and therefore stabilized less) than the dimethylaminiumion due to steric hinderance.
CH3CH2NHCH2CH3 is weaker base than N
HpKb 3.01pKb= 2.73
![Page 38: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/38.jpg)
38
3. Hybridization of the nitrogen atomAn sp2 orbital contain more s character than an sp3 orbital An sp2-hybridized nitrogen is less basic than sp3-hybridized because its unshared electrons are more tightly held
N NH
pyridine (sp2)
pKb= 8.75piperidine (sp3)
pKb = 2.88
![Page 39: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/39.jpg)
39
4. Resonance
NH2 NH2
aniline cyclohexylaminepKb = 9.37 pKb = 3.3
No resonance
stabilization
The unshared electron pair on nitrogen of an arylamine is delocalized the lone pair is less available for protonation, i.e., it is less basic
![Page 40: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/40.jpg)
40
Amine Salts
The reaction of amine with acids amine salts.
(CH3)3N: + HCl (CH3)3NH+Cl-triethylamine triethylammonium
chloride( triethylamine hydrochloride)
CH3CH2NH2 + CH3CO2H CH3CH2NH3+ -O2CCH3
ethylamie(ethylamine acetate)
ethylammonium acetate
![Page 41: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/41.jpg)
41
Applications of Quaternary Ammonium Salts
1. Quaternary Ammonium Salts with along hydrocarbon chain are used as detergents.
2. Quaternary Ammonium Salts can act as phase-transfer agents.
(C4H9)4N+Cl- + CN- (C4H9)4N+CN- + Cl-Soluble in organic phase
SN2 reaction in the organic phase
CH3(CH2)7Cl + (C4H9)4N+CN- CH3(CH2)7CN
![Page 42: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/42.jpg)
42
Reactions of Amines
![Page 43: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/43.jpg)
43
1) Substitution Reactions with Amines
1. SN2 ( alkyl halides + amines)
RNH2 + R’Cl RR’NH2+Cl- + RR’2NH+Cl-
![Page 44: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/44.jpg)
44
2. Acylation of amines (amine + acid chloride) synthesis of amides
CH3CCl
O+ 2(CH3)2NH CH3CNHCH3
OCH3NH3
+ Cl-+N-methylacetamide
Amines can be used to synthesize other amines by conversion to amides followed by reduction
a new amine
![Page 45: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/45.jpg)
45
Reactions of Amines with Sulfonyl Chlorides
Primary and secondary amines react with sulfonyl chlorides to produce sulfonamides
![Page 46: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/46.jpg)
46
The Hinsberg Test• This test can distinguish between 1o, 2o and 3o
amines.• A benzenesulfonamide from a primary amine is soluble
in basic solution, but precipitates upon acidification
![Page 47: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/47.jpg)
47
• A secondary amine forms a precipitate directly because an N,N-disubstituted sulfonamide remains insoluble in basic solution.
• There is no acidic hydrogen in an N,N-disubstituted sulfonamide
Insoluble in acid or base
A tertiary amine will not react to form a sulfonamide, but will dissolve upon acidification.
Acidification converts the amine to a water soluble amine salt
![Page 48: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/48.jpg)
48
Imines and Enamines• Amines react with aldehydes and ketones to form
imines or enamines.
O
RNH2
R2NH
NR
NR2
+ H2O
+ H2O
H+
H+
An imine
An enamine
![Page 49: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/49.jpg)
49
Reactions of Amines with Nitrous Acid
• Primary amines undergo diazotization with nitrous acid.
![Page 50: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/50.jpg)
50
Example
(CH3)2CHNH2NaNO2
HCl, 0 Co(CH3)2CHN2
+ Cl--N2- Cl
(CH3)2CH+H2O
(CH3)2CHOH + CH3CH CH2
Secondary amines yield N-nitrosoamines when treated with nitrous acid
NaNO2
HCl, 0 CoNHCH3 N
CH3
NO
An N-nitrosoamine
![Page 51: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/51.jpg)
51
The Hofmann Elimination• An E2-type reaction occurs when a quaternary
ammonium hydroxide is heated.• An amine is a relatively good leaving group
![Page 52: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/52.jpg)
52
Formation of Quaternary Ammonium Hydroxides
A quaternary ammonium hydroxide can be made from a quaternary ammonium halide using silver oxide
![Page 53: Amines - Faculty Personal Homepage- KFUPM](https://reader036.fdocuments.in/reader036/viewer/2022071601/613d492f736caf36b75b86c6/html5/thumbnails/53.jpg)
53
Example
• Hofmann elimination proceeds to give the least substituted double bond
+ H2O