Unidad 19: Aminas Basado en: McMurry’s

Unidad 19:
Aminas
Basado en:
McMurry’s Organic Chemistry, 6th
edition, Chapter 24
Reactions of Amines
Reactions of amines almost always involve the
nitrogen lone pair.
as a base:
N ••
H
X
as a nucleophile:
N ••
C
O
2
Reactions of Amines
3
Reactions of Amines, SN2
n
Ammonia and other amines are good nucleophiles
4
Uncontrolled Multiple Alkylation
n
Primary, secondary, and tertiary amines all have similar reactivity,
the initially formed monoalkylated substance undergoes further
reaction to yield a mixture of products
5
Reaction with Alkyl Halides
Amines act as nucleophiles toward alkyl halides.
N •• + R
+
•• –
N R + •• X ••
••
X ••
••
••
H
H
N
••
R
+
H
+
6
Reaction with Alkyl Halides
Amines act as nucleophiles toward alkyl halides.
7
Example: excess amine
NH2
+
ClCH2
(4 mol)
(1 mol)
NaHCO3
90°C
NHCH2
(85-87%)
8
Example: excess alkyl halide
CH2NH2
methanol
+
3CH3I
heat
+
–
CH2N(CH3)3 I
(99%)
9
Reactions of Amines
n
Alkylation and acylation have already been presented
10
Reacción con RSO2Cl
n
La reacción con un cloruro de sulfonilo produce una sulfonamida
11
Reaction with HNO2
n
Primary arylamines react with HNO2, yielding
stable arenediazonium salts
12
Alkylamines and Nitrous Acid
n
Alkylamines react with HNO2 but the
alkanediazonium products of these
reactions lose N2 rapidly, leaving
carbocations
13
Hofmann Elimination
n
n
Converts amines into alkenes
NH2− is very a poor leaving group so it converted to an
alkylammonium ion, which is a good leaving group
14
Silver Oxide Is Used for the
Elimination Step
n
Exchanges hydroxide ion for iodide ion in the quaternary
ammonium salt, thus providing the base necessary to cause
elimination
15
Orientation in Hofmann Elimination
n
n
n
We would expect that the more highly substituted alkene
product predominates in the E2 reaction of an alkyl halide
(Zaitsev's rule)
However, the less highly substituted alkene predominates
in the Hofmann elimination due to the large size of the
trialkylamine leaving group
The base must abstract a hydrogen from the most sterically
accessible, least hindered position
16
Steric Effects Control the
Orientation
17
The Hofmann Elimination
a quaternary ammonium hydroxide is the reactant
n
and an alkene is the product
is an anti elimination
n
the leaving group is a trialkylamine
n
the regioselectivity is opposite to the Zaitsev rule.
n
18
Reactions of Quaternary Ammonium Hydroxides
A Hofmann elimination is an E2 reaction
The leaving group of a quaternary ammonium ion has
about the same leaving tendency as a protonated amino
group
19
Quaternary Ammonium Hydroxides
are prepared by treating quaternary ammmonium
halides with moist silver oxide
CH2N(CH3)3 I
Ag2O
–
H2O, CH3OH
+
–
CH2N(CH3)3 HO
20
The Hofmann Elimination
on being heated, quaternary ammonium
hydroxides undergo elimination
CH2 +
N(CH3)3
+ H2O
(69%)
160°C
+
–
CH2N(CH3)3 HO
21
Mechanism
– ••
•• O
••
••
O
••
H
H
H
H
CH2
CH2
N(CH3)3
+
•• N(CH )
3 3
22
Regioselectivity
Elimination occurs in the direction that gives
the less-substituted double bond. This is called
the Hofmann rule.
H2C
CH3CHCH2CH3
CHCH2CH3 (95%)
heat
+ N(CH3)3
–
HO
+
CH3CH
CHCH3 (5%)
23
Regioselectivity
Steric factors seem to control the regioselectivity.
The transition state that leads to 1-butene is
less crowded than the one leading to cis
or trans-2-butene.
24
Regioselectivity
H
CH3CH2
H
H
H
H
CH3CH2
+ N(CH3)3
H
C
C
H
major product
largest group is between two H atoms
25
Regioselectivity
H
H
CH3
CH3
H
+ N(CH3)3
CH3
H
C
C
H
CH3
minor product
largest group is between an
H atom and a methyl group
26