Transcript Organic Chemistry Fifth Edition

Chapter 21
Amines
21.1
Amine Nomenclature
Classification of Amines
Alkylamine
N attached to alkyl group
Arylamine
N attached to aryl group
Primary, secondary, or tertiary
determined by number of carbon atoms
directly attached to nitrogen
Nomenclature of Primary Alkylamines (RNH2)
Two IUPAC styles
1)
Analogous to alcohols: replace -e
ending with -amine
2)
Name alkyl group and attach -amine
as a suffix
Examples: some primary alkylamines
(RNH2: one carbon directly attached to N)
ethylamine or ethanamine
CH3CH2NH2
NH2
CH3CHCH2CH2CH3
NH2
cyclohexylamine or
cyclohexanamine
1-methylbutylamine or
2-pentanamine or
pentan-2-amine
Nomenclature of Primary Arylamines (ArNH2)
Name as derivatives of aniline.
NH2
F
NH2
p-fluoroaniline or
4-fluoroaniline
Br
CH2CH3
5-bromo-2-ethylaniline
Amino Groups as Substituents
Amino groups rank below OH groups and higher
oxidation states of carbon.
In such cases name the amino group as a
substituent.
O
HOCH2CH2NH2
HC
2-aminoethanol
p-aminobenzaldehyde
NH2
Secondary and Tertiary Amines
Name as N-substituted derivatives of parent
primary amine.
(N is a locant-it is not alphabetized, but
is treated the same way as a numerical
locant)
Parent amine is one with longest carbon chain.
Examples
CH3NHCH2CH3
N-methylethylamine
NHCH2CH3
4-chloro-N-ethyl-3-nitroaniline
NO2
Cl
CH3
N
CH3
N,N-dimethylcycloheptylamine
Ammonium Salts
A nitrogen with four substituents is positively
charged and is named as a derivative of
ammonium ion (NH4+).
+
–
CH3NH3 Cl
methylammonium
chloride
CH3
+
–
N CH2CH3 CF3CO2
H
N-ethyl-N-methylcyclopentylammonium
trifluoroacetate
Ammonium Salts
When all four atoms attached to N are carbon,
the ion is called a quaternary ammonium ion and
salts that contain it are called quaternary
ammonium salts.
CH3
CH2
+
N
CH3 I
–
CH3
benzyltrimethylammonium iodide
21.2
Structure and Bonding
Alkylamines
147 pm
112°
106°
Alkylamines
Most prominent feature is high electrostatic
potential at nitrogen. Reactivity of nitrogen lone
pair dominates properties of amines.
Geometry at N
Compare geometry at N of methylamine, aniline,
and formamide.
H
H
H
sp3
sp2
NH2
C
NH
C
2
O
H
Pyramidal geometry at sp3-hybridized N in
methylamine.
Planar geometry at sp2-hybridized N in
formamide.
Geometry at N
Compare geometry at N of methylamine, aniline,
and formamide.
sp3
sp2
Pyramidal geometry at sp3-hybridized N in
methylamine.
Planar geometry at sp2-hybridized N in
formamide.
Geometry at N
Angle that the C—N bond makes with bisector of
H—N—H angle is a measure of geometry at N.
sp3
sp2
180°
~125°
Note: This is not the same as the H—N—H
bond angle.
Geometry at N
Angle that the C—N bond makes with bisector of
H—N—H angle is a measure of geometry at N.
sp2
sp3
180°
~125°
142.5°
Geometry at N
Geometry at N in aniline is pyramidal; closer to
methylamine than to formamide.
142.5°
Geometry at N
Hybridization of N in aniline lies between sp3 and sp2.
Lone pair of N can be delocalized into ring best if N is
sp2 and lone pair is in a p orbital.
Lone pair bound most strongly by N if pair is in an sp3
orbital of N, rather than p.
Actual hybridization is a compromise that maximizes
binding of lone pair.
142.5°
Electrostatic Potential Maps of Aniline
Nonplanar geometry at
N. Region of highest
negative potential is at N.
Planar geometry at N.
High negative potential
shared by N and ring.
Figure 21.2 (page 934)
21.3
Physical Properties
Physical Properties
Amines are more polar and have higher boiling
points than alkanes; but are less polar and
have lower boiling points than alcohols.
CH3CH2CH3 CH3CH2NH2 CH3CH2OH
dipole
moment ():
0D
1.2 D
1.7 D
boiling point:
-42°C
17°C
78°C
Physical Properties
CH3CH2CH2NH2 CH3CH2NHCH3
boiling
point:
50°C
34°C
(CH3)3N
3°C
Boiling points of isomeric amines decrease in
going from primary to secondary to tertiary amines.
Primary amines have two hydrogens on N capable
of being involved in intermolecular hydrogen
bonding. Secondary amines have one. Tertiary
amines cannot be involved in intermolecular
hydrogen bonds.
21.4
Basicity of Amines
Effect of Structure on Basicity
1. Alkylamines are slightly stronger bases than
ammonia.
Table 21.1
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
CH3CH2NH3+ is a weaker acid than NH4+;
therefore, CH3CH2NH2 is a stronger base
than NH3.
Effect of Structure on Basicity
1. Alkylamines are slightly stronger bases than
ammonia.
2. Alkylamines differ very little in basicity.
Table 21.1
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
(CH3CH2)2NH
(CH3CH2)2NH2+
11.1
(CH3CH2)3N
(CH3CH2)3NH+
10.8
Notice that the difference separating a primary,
secondary, and tertiary amine is only 0.3 pK units.
Effect of Structure on Basicity
1. Alkylamines are slightly stronger bases than
ammonia.
2. Alkylamines differ very little in basicity.
3. Arylamines are much weaker bases than
ammonia.
Table 21.1
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
(CH3CH2)2NH
(CH3CH2)2NH2+
11.1
(CH3CH2)3N
(CH3CH2)3NH+
10.8
C6H5NH2
C6H5NH3+
4.6
Decreased Basicity of Arylamines
H
+
N
H +
H
Stronger
pKa = 4.6
acid
••
NH2 +
Weaker
base
••
H2N
K = 106
Stronger
base
+
H3N
pKa =10.6
Weaker
acid
Decreased Basicity of Arylamines
H
+
N
H +
••
H2N
H
Stronger
acid When anilinium ion loses a proton, the
resulting lone pair is delocalized into the ring.
••
NH2 +
+
H3N
Weaker
acid
Decreased Basicity of Arylamines
H
+
N
H +
••
H2N
H
Aniline is a weaker base because its
lone pair is more strongly held.
••
NH2 +
Weaker
base
+
H3N
Stronger
base
Decreased Basicity of Arylamines
Increasing delocalization makes diphenylamine a
weaker base than aniline, and triphenylamine a
weaker base than diphenylamine.
C6H5NH2
pKa of conjugate acid:
4.6
(C6H5)2NH
(C6H5)3N
0.8
~-5
Effect of Substituents on Basicity of Arylamines
1. Alkyl groups on the ring increase basicity, but
only slightly (less than 1 pK unit).
X
X
H
CH3
NH2
pKa of conjugate acid
4.6
5.3
Effect of Substituents on Basicity of Arylamines
2. Electron withdrawing groups, especially ortho
and/or para to amine group, decrease basicity
and can have a large effect.
X
X
H
CF3
O2N
NH2
pKa of conjugate acid
4.6
3.5
1.0
p-Nitroaniline
– ••
•• O ••
••
O ••
+
N
•• O ••
– ••
••
NH2
+
N
•• O ••
– ••
Lone pair on amine nitrogen is conjugated with
p-nitro group—more delocalized than in aniline
itself. Delocalization is lost on protonation.
+
NH2
Effect is Cumulative
Aniline is 3800 times more basic than
p-nitroaniline.
Aniline is ~1,000,000,000 times more basic than
2,4-dinitroaniline.
Heterocyclic Amines
••
is more basic than
N
N
H
piperidine
pyridine
pKa of conjugate acid:
11.2
pKa of conjugate acid:
5.2
(an alkylamine)
(resembles an
arylamine in
basicity)
••
Heterocyclic Amines
•• N
•• N
is more basic than
H
N
••
imidazole
pyridine
pKa of conjugate acid:
7.0
pKa of conjugate acid:
5.2
Imidazole
Which nitrogen is protonated in imidazole?
•• N
•• N
H
H+
+
H N
H+
•N
•
H
•• N
+ H
N
H
Imidazole
Protonation in the direction shown gives a
stabilized ion.
•• N
•• N
H
H+
+
H N
•N
•
H
H
N ••
+
N H
21.5
Tetraalkylammonium Salts
as Phase-Transfer Catalysts
Phase-Transfer Catalysis
Phase-transfer agents promote the solubility of
ionic substances in nonpolar solvents. They
transfer the ionic substance from an aqueous
phase to a non-aqueous one.
Phase-transfer agents increase the rates of
reactions involving anions. The anion is relatively
unsolvated and very reactive in nonpolar media
compared to water or alcohols.
Phase-Transfer Catalysis
Quaternary ammonium salts are phase-transfer
catalysts. They are soluble in nonpolar solvents.
H3C
CH2CH2CH2CH2CH2CH2CH2CH3
+
N CH2CH2CH2CH2CH2CH2CH2CH3
CH2CH2CH2CH2CH2CH2CH2CH3
Methyltrioctylammonium chloride
Cl–
Phase-Transfer Catalysis
Quaternary ammonium salts are phase-transfer
catalysts. They are soluble in nonpolar solvents.
CH2CH3
+
N CH2CH3
Cl–
CH2CH3
Benzyltriethylammonium chloride
Example
The SN2 reaction of sodium cyanide with butyl
bromide occurs much faster when benzyltriethylammonium chloride is present than when
it is not.
CH3CH2CH2CH2Br +
NaCN
benzyltriethylammonium chloride
CH3CH2CH2CH2CN
+
NaBr
Mechanism
CH2CH3
+
N CH2CH3 Cl–
CH2CH3
CN–
+
(aqueous)
(aqueous)
CH2CH3
+
N CH2CH3 CN–
CH2CH3
(aqueous)
+
Cl–
(aqueous)
Mechanism
CH2CH3
+
N CH2CH3 CN–
CH2CH3
(in butyl bromide)
CH2CH3
+
N CH2CH3 CN–
CH2CH3
(aqueous)
Mechanism
CH2CH3
+
N CH2CH3 CN– + CH3CH2CH2CH2Br
CH2CH3
(in butyl bromide)
CH2CH3
+
N CH2CH3 Br– + CH3CH2CH2CH2CN
CH2CH3
(in butyl bromide)
21.6
Reactions that Lead to Amines:
A Review and a Preview
Preparation of Amines
Two questions to answer:
1) How is the C—N bond to be formed?
2) How do we obtain the correct oxidation
state of nitrogen (and carbon)?
Methods for C—N Bond Formation
Nucleophilic substitution by azide ion (N3–) (Section 8.1, 8.11)
Nitration of arenes (Section 12.3)
Nucleophilic ring opening of epoxides by ammonia (Section
16.12)
Nucleophilic addition of amines to aldehydes and ketones
(Sections 17.10, 17.11)
Nucleophilic substitution by ammonia on a-halo acids
(Section 20.15)
Nucleophilic acyl substitution (Sections 19.4, 19.5, and
19.11)
21.7
Preparation of Amines
by Alkylation of Ammonia
Alkylation of Ammonia
Desired reaction is:
2 NH3
+
R—X
R—NH2 +
NH4X
+
H3N
•• –
•• X ••
••
via:
H3N •• + R
then:
H3N •• + H
••
X ••
••
H
+
N R
H
R +
H
+
H3N
H + •• N
H
R
Alkylation of Ammonia
But the method doesn't work well in practice.
Usually gives a mixture of primary, secondary,
and tertiary amines, plus the quaternary salt.
NH3
RX
RNH2
RX
R2NH
RX
+
R4N
X
–
RX
R3 N
Example
CH3(CH2)6CH2Br
NH3
CH3(CH2)6CH2NH2
(45%)
+
CH3(CH2)6CH2NHCH2(CH2)6CH3
(43%)
As octylamine is formed, it competes with
ammonia for the remaining 1-bromooctane.
Reaction of octylamine with 1-bromooctane
gives N,N-dioctylamine.
21.8
The Gabriel Synthesis of Primary Alkylamines
Gabriel Synthesis
Gives primary amines without formation of
secondary, etc. amines as byproducts.
Uses an SN2 reaction on an alkyl halide to form
the C—N bond.
The nitrogen-containing nucleophile
is N-potassiophthalimide.
Gabriel Synthesis
Gives primary amines without formation of
secondary, etc. amines as byproducts.
Uses an SN2 reaction on an alkyl halide to form
the C—N bond.
The nitrogen-containing nucleophile
is N-potassiophthalimide.
O
–
•• N •
•
O
K
+
N-Potassiophthalimide
The pKa of phthalimide is 8.3.
N-potassiophthalimide is easily prepared by
the reaction of phthalimide with KOH.
O
O
•• NH
O
KOH
–
•• N •
•
O
K
+
N-Potassiophthalimide as a Nucleophile
O
O
–
•• N • + R
•
••
X ••
SN2
•• N
••
O
O
+
•• –
•• X ••
••
R
Cleavage of Alkylated Phthalimide
O
•• N
R + H2O
O
Imide hydrolysis is
nucleophilic acyl
substitution.
acid or base
CO2H
+
CO2H
H2N
R
Cleavage of Alkylated Phthalimide
Hydrazinolysis is an alternative method of releasing
the amine from its phthalimide derivative.
O
O
•• N
R
H2NNH2
NH
NH
O
O
+
H2N
R
Example
O
–
•N•
• •
K
+
+
C6H5CH2Cl
DMF
O
O
•• N
O
CH2C6H5
(74%)
Example
O
NH
+
C6H5CH2NH2 (97%)
NH
H2NNH2
O
O
•• N
O
CH2C6H5
21.9
Preparation of Amines by Reduction
Preparation of Amines by Reduction
Almost any nitrogen-containing compound can
be reduced to an amine, including:
azides
nitriles
nitro-substituted benzene derivatives
amides
Synthesis of Amines via Azides
SN2 reaction, followed by reduction, gives a
primary alkylamine.
CH2CH2Br
NaN3
CH2CH2N3
(74%)
1. LiAlH4
2. H2O
Azides may also be
reduced by catalytic
hydrogenation.
CH2CH2NH2
(89%)
Synthesis of Amines via Nitriles
SN2 reaction, followed by reduction, gives a
primary alkylamine.
NaCN
CH3CH2CH2CH2Br
Nitriles may also be
reduced by lithium
aluminum hydride.
CH3CH2CH2CH2CN
(69%)
H2 (100 atm), Ni
CH3CH2CH2CH2CH2NH2
(56%)
Synthesis of Amines via Nitriles
SN2 reaction, followed by reduction, gives a
primary alkylamine.
NaCN
CH3CH2CH2CH2Br
CH3CH2CH2CH2CN
The reduction also
works with cyanohydrins.
(69%)
H2 (100 atm), Ni
CH3CH2CH2CH2CH2NH2
(56%)
Synthesis of Amines via Nitroarenes
HNO3
Cl
H2SO4
Nitro groups may also
be reduced with tin (Sn)
+ HCl or by catalytic
hydrogenation.
Cl
NO2
Cl
(88-95%)
1. Fe, HCl
2. NaOH
NH2
(95%)
Synthesis of Amines via Amides
O
COH
O
1. SOCl2
CN(CH3)2
2. (CH3)2NH
(86-89%)
Only LiAlH4 is an
appropriate reducing
agent for this reaction.
1. LiAlH4
2. H2O
CH2N(CH3)2
(88%)
21.10
Reductive Amination
Synthesis of Amines via Reductive Amination
In reductive amination, an aldehyde or ketone
is subjected to catalytic hydrogenation in the
presence of ammonia or an amine.
R
fast
C
R'
R
O + NH3
C
NH +
R'
The aldehyde or ketone equilibrates with the
imine faster than hydrogenation occurs.
H2O
Synthesis of Amines via Reductive Amination
The imine undergoes hydrogenation faster
than the aldehyde or ketone. An amine is
the product.
R
fast
C
R
O + NH3
R'
C
H
NH +
R'
R
R'
C
H2, Ni
NH2
H2O
Example: Ammonia Gives a Primary Amine
O + NH3
H2, Ni
H
ethanol
NH2
(80%)
via:
NH
Example: Primary Amines Give Secondary Amines
O
CH3(CH2)5CH
+ H2N
H2, Ni
ethanol
CH3(CH2)5CH2NH
via:
CH3(CH2)5CH
N
(65%)
Example: Secondary Amines Give Tertiary Amines
O
CH3CH2CH2CH
+
N
H
H2, Ni, ethanol
N
CH2CH2CH2CH3
(93%)
Example: Secondary Amines Give Tertiary Amines
Possible intermediates include:
HO
N
+
N
CHCH2CH2CH3
CHCH2CH2CH3
N
CH
CHCH2CH3
21.11
Reactions of Amines:
A Review and a Preview
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
Reactions of Amines
Reactions already discussed
basicity (Section 21.4)
reaction with aldehydes and ketones (Sections
17.10, 17.11)
reaction with acyl chlorides (Section 19.4),
anhydrides (Section 19.5), and esters (Section 19.11)
21.12
Reactions of Amines with Alkyl Halides
Reaction with Alkyl Halides
Amines act as nucleophiles toward alkyl halides.
N •• + R
+
•• –
N R + •• X ••
••
X ••
••
••
H
H
N
••
R
+
H
+
Example: excess amine
NH2
+
ClCH2
(4 mol)
(1 mol)
NaHCO3
90°C
NHCH2
(85-87%)
Example: excess alkyl halide
CH2NH2
methanol
+
3CH3I
heat
+
CH2N(CH3)3
(99%)
I
–
21.13
The Hofmann Elimination
The Hofmann Elimination
A quaternary ammonium hydroxide is the reactant
and an alkene is the product.
It is an anti elimination.
The leaving group is a trialkylamine.
The regioselectivity is opposite to the Zaitsev rule.
Quaternary Ammonium Hydroxides
are prepared by treating quaternary ammmonium
halides with moist silver oxide
CH2N(CH3)3
Ag2O
I
–
H2O, CH3OH
+
CH2N(CH3)3
–
HO
The Hofmann Elimination
on being heated, quaternary ammonium
hydroxides undergo elimination
CH2 +
N(CH3)3
+
(69%)
160°C
+
CH2N(CH3)3
–
HO
H2O
Mechanism
– ••
•• O
••
••
O
••
H
H
H
H
CH2
CH2
N(CH3)3
+
•• N(CH3)3
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%)
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.
Regioselectivity
H
CH3CH2
H
H
H
H
CH3CH2
+N(CH3)3
largest group is between two H atoms
H
C
C
H
major product
Regioselectivity
H
H
CH3
CH3
H
+N(CH3)3
largest group is between an
H atom and a methyl group
CH3
H
H
C
C
CH3
minor product
21.14
Electrophilic Aromatic Substitution
in Arylamines
Nitration of Aniline
NH2 is a very strongly activating group.
NH2 not only activates the ring toward
electrophilic aromatic substitution, it also makes
it more easily oxidized.
Attemped nitration of aniline fails because nitric
acid oxidizes aniline to a black tar.
Nitration of Aniline
Strategy: decrease the reactivity of aniline by
converting the NH2 group to an amide
O
NH2
O O
CH3COCCH3
CH(CH3)2
NHCCH3
(98%)
CH(CH3)2
(acetyl chloride may be used instead of acetic anhydride)
Nitration of Aniline
Strategy: nitrate the amide formed in the first
step
O
O
NHCCH3
NO2
CH(CH3)2
(94%)
NHCCH3
HNO3
CH(CH3)2
Nitration of Aniline
Strategy: remove the acyl group from the amide
by hydrolysis
O
NHCCH3
NO2
NH2
NO2
KOH
ethanol,
heat
CH(CH3)2
CH(CH3)2
(100%)
Halogenation of Arylamines
occurs readily without necessity of protecting
amino group, but difficult to limit it to
monohalogenation
NH2
NH2
Br2
Br
Br
acetic acid
CO2H
CO2H
(82%)
Monohalogenation of Arylamines
Decreasing the reactivity of the arylamine by
converting the NH2 group to an amide allows
halogenation to be limited to monosubstitution.
O
O
NHCCH3
NHCCH3
CH3
CH3
Cl2
acetic acid
Cl
(74%)
Friedel-Crafts Reactions
The amino group of an arylamine must be
protected as an amide when carrying out a
Friedel-Crafts reaction.
O
O
NHCCH3
CH2CH3
NHCCH3
O
CH2CH3
CH3CCl
AlCl3
O
CCH3
(57%)
21.15
Nitrosation of Alkylamines
Nitrite Ion, Nitrous Acid, and Nitrosyl Cation
– ••
•• O
••
••
O ••
N
••
H
+
••
O
H
••
+
H
• O ••
•
H
O ••
N
H
H
••
••
+
••
N
+
+
•• O
••
O ••
H
••
N
••
O ••
Nitrosyl Cation and Nitrosation
••
N
+
••
O ••
Nitrosyl Cation and Nitrosation
+
N
N ••
+
••
••
O ••
N
••
N
+
••
O ••
Nitrosation of Secondary Alkylamines
+
N
••
••
O ••
N
•• N
H
H
O ••
N
+
H
N ••
••
••
+
••
N
+
••
O ••
+
Nitrosation of
secondary amines
gives an N-nitroso
amine.
Example
••
(CH3)2NH
NaNO2, HCl
H2O
••
(CH3)2N
••
N
(88-90%)
••
O ••
Some N-Nitroso Amines
(CH3)2N
N
O
N-nitrosodimethylamine
(leather tanning)
N
N
N
N
O
N-nitrosopyrrolidine
(nitrite-cured bacon)
N
O
N-nitrosonornicotine
(tobacco smoke)
Nitrosation of Primary Alkylamines
R
H
+
N
R
••
N
••
O ••
•• N
H
H
H
N ••
H
+
••
N
+
••
O ••
O ••
N
+
H
R
••
••
+
Analogous to
nitrosation of
secondary amines
to this point.
Nitrosation of Primary Alkylamines
R
•• N
••
N
H
•• +
H
•• N
H
+
N
O ••
H
O ••
N
H
R
••
••
••
•• N
O
H
••
+
R
H
+
This species reacts further.
R
H
•• N
••
N
O ••
+
H
Nitrosation of Primary Alkylamines
Nitrosation of a
primary alkylamine
gives an alkyl
diazonium ion.
Process is called
diazotization.
H
R
+
N
N ••
+
•• O ••
H
R
•• N
H
••
N
O ••
+
H
Alkyl Diazonium Ions
+ + •N
R
•
N ••
Alkyl diazonium ions
readily lose N2 to
give carbocations.
R
+
N
N ••
Example: Nitrosation of 1,1-Dimethylpropylamine
HONO
NH2
OH
+
N
H2O
– N2
+
(80%)
+
Mechanism 21.2
(3%)
N
(2%)
Nitrosation of Tertiary Alkylamines
There is no useful chemistry associated with the
nitrosation of tertiary alkylamines.
R
R
R
R
+
N
N ••
R
R
••
N
••
O ••
21.16
Nitrosation of Arylamines
Nitrosation of Tertiary Arylamines
Reaction that occurs is
electrophilic aromatic substitution.
N(CH2CH3)2
1. NaNO2, HCl,
H2O, 8°C
N(CH2CH3)2
2. HO–
N
(95%)
O
Nitrosation of N-Alkylarylamines
Similar to secondary alkylamines;
Gives N-nitroso amines
NaNO2, HCl,
H2O, 10°C
NHCH3
N
O
NCH3
(87-93%)
Nitrosation of Primary Arylamines
Gives aryl diazonium ions.
Aryl diazonium ions are much more stable than
alkyl diazonium ions.
Most aryl diazonium ions are stable under the
conditions of their formation (0-10°C).
+
RN
+
ArN
N
N
fast
+
R
+ N2
slow
+
Ar
+ N2
Example:
(CH3)2CH
NH2
NaNO2, H2SO4
H2O, 0-5°C
(CH3)2CH
+
N
N HSO4–
Synthetic Origin of Aryl Diazonium Salts
Ar
H
Ar
NO2
Ar
NH2
Ar
+
N
N
21.17
Synthetic Transformations
of Aryl Diazonium Salts
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Preparation of Phenols
+
N
Ar
N
H2O, heat
Ar
OH
Example
NH2
(CH3)2CH
1. NaNO2, H2SO4
H2O, 0-5°C
2. H2O, heat
OH
(CH3)2CH
(73%)
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Preparation of Aryl Iodides
Reaction of an aryl diazonium salt with
potassium iodide:
Ar
+
N
N
KI
Ar
I
Example
NH2
Br
1. NaNO2, HCl
H2O, 0-5°C
I
Br
2. KI, room temp.
(72-83%)
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Preparation of Aryl Fluorides
Ar
Ar
+
N
F
N
Heat the tetrafluoroborate salt of a diazonium ion;
process is called the Schiemann reaction.
Example
NH2
1. NaNO2, HCl,
H2O, 0-5°C
CCH2CH3
O
2. HBF4
3. heat
F
CCH2CH3
O
(68%)
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Preparation of Aryl Chlorides and Bromides
Ar
Cl
Ar
Ar
+
N
Br
N
Aryl chlorides and aryl bromides are prepared by
heating a diazonium salt with copper(I) chloride or
bromide.
Substitutions of diazonium salts that use copper(I)
halides are called Sandmeyer reactions.
Example
NH2
1. NaNO2, HCl,
H2O, 0-5°C
NO2
2. CuCl, heat
Cl
NO2
(68-71%)
Example
NH2
Cl
1. NaNO2, HBr,
H2O, 0-10°C
Br
Cl
2. CuBr, heat
(89-95%)
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Preparation of Aryl Nitriles
Ar
CN
Ar
+
N
N
Aryl nitriles are prepared by heating a diazonium
salt with copper(I) cyanide.
This is another type of Sandmeyer reaction.
Example
NH2
CH3
1. NaNO2, HCl,
H2O, 0°C
CN
CH3
2. CuCN, heat
(64-70%)
Transformations of Aryl Diazonium Salts
Ar
Ar
Cl
Ar
CN
+
N
Ar
Ar
Ar
F
Ar
I
N
H
Ar
Br
OH
Transformations of Aryl Diazonium Salts
Hypophosphorous acid (H3PO2) reduces diazonium
salts; ethanol does the same thing.
This is called reductive deamination.
Ar
Ar
H
+
N
N
Example
NH2
CH3
NaNO2, H2SO4,
H3PO2
or NaNO2, HCl,
CH3CH2OH
CH3
(70-75%)
Value of Diazonium Salts
1) Allows introduction of substituents such as
OH, F, I, and CN on the ring.
2) Allows preparation of otherwise difficultly
accessible substitution patterns.
Example
NH2
NH2
Br2
NaNO2, H2SO4,
Br H O, CH CH OH
2
3
2
Br
H2O
Br
Br
Br
(100%)
Br
(74-77%)
21.18
Azo Coupling
Azo Coupling
Diazonium salts are weak electrophiles.
React with strongly activated aromatic
compounds by electrophilic aromatic
substitution.
Ar
+
N
N + Ar'
H
Ar
N
N
Ar'
an azo compound
Ar' must bear a strongly electron-releasing group
such as OH, OR, or NR2.
Example
OH
+
+ C6H5N
N
OH
N
NC6H5
Cl–
Section 21.19
Spectroscopic Analysis of Amines
Infrared Spectroscopy
The N—H stretching band appears in the range
3000-3500 cm-1.
Primary amines give two peaks in this region, one
for a symmetrical stretching vibration, the other for
an antisymmetrical stretch.
H
R
N
H
R
H
symmetric
N
H
antisymmetric
Infrared Spectroscopy
Primary amines give two N—H stretching peaks,
secondary amines give one (Figure 21.8).
1H
NMR
Compare chemical shifts in:
H3C
CH2NH2 H3C
 3.9 ppm
N
C
H is more shielded than O
CH2OH
 4.7 ppm
C
H
13C
NMR
Carbons bonded to N are more shielded than
those bonded to O.
CH3NH2
 26.9 ppm
CH3OH
 48.0 ppm
UV-VIS
An amino group on a benzene ring shifts max
to longer wavelength. Protonation of N causes
UV spectrum to resemble that of benzene.
+
NH3
NH2
max
204 nm
256 nm
max
230 nm
280 nm
max
203 nm
254 nm
Mass Spectrometry
Compounds that contain only C, H, and O
have even molecular weights. If an odd number
of N atoms is present, the molecular weight is
odd.
A molecular-ion peak with an odd m/z value
suggests that the sample being analyzed
contains N.
Mass Spectrometry
Nitrogen stabilizes
carbocations, which
drives the fragmentation
pathways.
••
(CH3)2NCH2CH2CH2CH3
e–
•+
(CH3)2NCH2CH2CH2CH3
+
(CH3)2N
CH2
+ •CH2CH2CH3
Mass Spectrometry
Nitrogen stabilizes
carbocations, which
drives the fragmentation
pathways.
••
CH3NHCH2CH2CH(CH3)2
e–
•+
CH3NHCH2CH2CH(CH3)2
+
CH3NH
CH2
+ •CH2CH(CH3)2