Chapter 22 Amines
22.1 Amine Nomenclature
Classification of Amines Alkylamine
Nomenclature of Primary Alkylamines (RNH2) Two IUPAC styles
N attached to alkyl group
1)
Analogous to alcohols: replace -e ending with -anamine
2)
Name alkyl group and attach -amine as a suffix
Arylamine N attached to aryl group Primary, secondary, or tertiary determined by number of carbon atoms directly attached to nitrogen
Examples: some primary alkylamines
Nomenclature of Primary Arylamines (ArNH2)
(RNH2: one carbon directly attached to N)
NH2
ethylamine or ethanamine
CH3CH2NH2 NH2
CH3CHCH2CH2CH3 NH2
Name as derivatives of aniline.
cyclohexylamine or cyclohexanamine 1-methylbutylamine or 2-pentanamine or pentan-2-amine
F
NH2
p-fluoroaniline or 4-fluoroaniline
Br
CH2CH3
5-bromo-2-ethylaniline
Amino Groups as Substituents
Secondary and Tertiary Amines
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
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 Ammonium Salts CH3NHCH2CH3
N-methylethylamine
NHCH2CH3 4-chloro-N-ethyl-3-nitroaniline NO2 Cl
+ – CH3NH3 Cl
CH3 N
A nitrogen with four substituents is positively charged and is named as a derivative of ammonium ion (NH4+).
CH3
N,N-dimethylcycloheptylamine
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.
CH2
CH3 + – N CH3 I CH3
benzyltrimethylammonium iodide
22.2 Structure and Bonding
Alkylamines
Alkylamines
147 pm
112°
106° Most prominent feature is high electrostatic potential at nitrogen. Reactivity of nitrogen lone pair dominates properties of amines.
Geometry at N
Geometry at N
Compare geometry at N of methylamine, aniline, and formamide. H H H sp3 sp2 NH2 C C NH2 O
Compare geometry at N of methylamine, aniline, and formamide.
H Pyramidal geometry at sp3-hybridized N in methylamine. Planar geometry at sp2-hybridized N in formamide.
sp3
sp2
Pyramidal geometry at sp3-hybridized N in methylamine. Planar geometry at sp2-hybridized N in formamide.
Geometry at N
Geometry at N
Angle that the C—N bond makes with bisector of H—N—H angle is a measure of 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
~125°
sp2 180°
Note: This is not the same as the H—N—H bond angle.
sp3
sp2 180°
~125°
142.5°
Geometry at N
Geometry at N
Geometry at N in aniline is pyramidal; closer to methylamine than to formamide.
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°
142.5°
Electrostatic Potential Maps of Aniline
22.3 Physical Properties 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 22.2 (page 947)
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 (µ):
0D
1.2 D
1.7 D
boiling point:
-42°C
17°C
78°C
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.
Effect of Structure on Basicity
1. Alkylamines are slightly stronger bases than ammonia.
22.4 Basicity of Amines
Table 22.1 Basicity of Amines in Aqueous Solution
Effect of Structure on Basicity
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
1. Alkylamines are slightly stronger bases than ammonia.
CH3CH2NH2
CH3CH2NH3+
10.8
2. Alkylamines differ very little in basicity.
CH3CH2NH3+ is a weaker acid than NH4+; therefore, CH3CH2NH2 is a stronger base than NH3.
Table 22.1 Basicity of Amines in Aqueous Solution Amine
Conj. Acid
pKa
+
NH3
NH4
CH3CH2NH2
CH3CH2NH3+
(CH3CH2)2NH (CH3CH2)3N
(CH3CH2)2NH2 (CH3CH2)3
+
NH+
Effect of Structure on Basicity
9.3
1. Alkylamines are slightly stronger bases than ammonia.
10.8
2. Alkylamines differ very little in basicity.
11.1
3. Arylamines are much weaker bases than ammonia.
10.8
Notice that the difference separating a primary, secondary, and tertiary amine is only 0.3 pK units.
Decreased Basicity of Arylamines
Table 22.1 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)3
C6H5NH2
C6H5NH3+
NH+
H + N H Stronger pKa = 4.6 acid
NH2 +
Weaker base
Decreased Basicity of Arylamines H + N
H +
H + N
H2N
Weaker acid
NH2 +
Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine. (C6H5)2NH
(C6H5)3N
0.8
~-5
••
H2N
Aniline is a weaker base because its lone pair is more strongly held. ••
Decreased Basicity of Arylamines
pKa of conjugate acid: 4.6
H +
H
+ H3N Weaker acid
C6H5NH2
+ H3N pKa =10.6
••
resulting lone pair is delocalized into the ring. NH2 +
Stronger base
Decreased Basicity of Arylamines
H Stronger acid When anilinium ion loses a proton, the ••
••
H2N
K = 106
••
10.8 4.6
H +
Stronger base
+ H3N
Weaker base
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
p-Nitroaniline
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 O2 N
NH2
– •• •• O ••
••
O ••
+ N
•O • –• •• •
pKa of conjugate acid 4.6 3.5 1.0
+ N
••
NH2
+ NH2
•O • –• •• •
Lone pair on amine nitrogen is conjugated with p-nitro group—more delocalized than in aniline itself. Delocalization lost on protonation.
Heterocyclic Amines 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.
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 Imidazole
•• N
•• N
is more basic than H
Which nitrogen is protonated in imidazole? N ••
imidazole
pyridine
pKa of conjugate acid: 7.0
pKa of conjugate acid: 5.2
•N •
•• N
H
H+
H
+ N
H+
•• N
H
•N •
+ N H H
Imidazole Protonation in the direction shown gives a stabilized ion. •N •
•• N
22.5 Tetraalkylammonium Salts
H
as Phase-Transfer Catalysts H+
H
+ N
•• N
N ••
H
H
+ N H
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. CH2CH3 + N CH2CH3
Cl–
Phase-Transfer Catalysis Quaternary ammonium salts are phase-transfer catalysts. They are soluble in nonpolar solvents.
H3C
CH2CH2CH2CH2CH2CH2CH2CH3 + N CH2CH2CH2CH2CH2CH2CH2CH3 CH2CH2CH2CH2CH2CH2CH2CH3 Methyltrioctylammonium 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 +
CH2CH3 Benzyltriethylammonium chloride
Cl–
NaCN benzyltriethylammonium chloride
CH3CH2CH2CH2CN +
NaBr
CH2CH3 + N CH2CH3 Cl– (aqueous)
CH2CH3
Mechanism +
CH2CH3 + N CH2CH3 CN–
CN– (aqueous)
Mechanism
CH2CH3 (in butyl bromide)
CH2CH3 + N CH2CH3 CN– CH2CH3
+
CH2CH3 + N CH2CH3 CN–
Cl–
(aqueous)
(aqueous)
CH2CH3 (aqueous)
Mechanism CH2CH3 + N CH2CH3 CN– + CH3CH2CH2CH2Br CH2CH3 (in butyl bromide)
22.6 Reactions that Lead to Amines:
CH2CH3 + N CH2CH3 Br– + CH3CH2CH2CH2CN
A Review and a Preview
CH2CH3 (in butyl bromide)
Preparation of Amines
Methods for C—N Bond Formation Nucleophilic substitution by azide ion (N3–) (Section 8.1, 8.11)
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)?
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 α-halo acids (Section 19.16) Nucleophilic acyl substitution (Sections 20.4, 20.5, and 20.11)
Alkylation of Ammonia Desired reaction is: 2 NH3 +
22.7 Preparation of Amines by Alkylation of Ammonia
R—X
R—NH2 +
NH4X
+ H3N
•• – • X •• • ••
via: H3N •• + R then: H3N •• +
H
••
X •• ••
R +
H
H + N R
+ H3N
H + •• N H
H
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.
R
Example CH3(CH2)6CH2Br
NH3
CH3(CH2)6CH2NH2 (45%) +
NH3
RX
RNH2
RX
R2NH RX
+ R4N
X
–
RX
R3N
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.
Gabriel Synthesis Gives primary amines without formation of secondary, etc. amines as byproducts.
22.8 The Gabriel Synthesis of Primary Alkylamines
Uses an SN2 reaction on an alkyl halide to form the C—N bond. The nitrogen-containing nucleophile is N-potassiophthalimide.
Gabriel Synthesis
N-Potassiophthalimide
Gives primary amines without formation of secondary, etc. amines as byproducts.
The pKa of phthalimide is 8.3. N-potassiophthalimide is easily prepared by the reaction of phthalimide with KOH.
Uses an SN2 reaction on an alkyl halide to form the C—N bond.
O
O
The nitrogen-containing nucleophile is N-potassiophthalimide.
O – •N • • •
K
+
•• NH
–
KOH
•• N • •
K
O
O O
N-Potassiophthalimide as a Nucleophile
Cleavage of Alkylated Phthalimide O
O
O –
•N • • •
+ R
••
X •• ••
S N2
•N •
O
O
•• –
+ •• X ••
R + H2O
•• N
R
O
Imide hydrolysis is nucleophilic acyl substitution.
acid or base CO2H +
••
H2N
R
CO2H
Example
Cleavage of Alkylated Phthalimide
O Hydrazinolysis is an alternative method of releasing the amine from its phthalimide derivative. O
O •N •
R
H2NNH2
–
•• N • •
K
+
C6H5CH2Cl DMF
O NH
+
O
NH
O
•N •
O +
H2N
R
O
CH2C6H5
(74%)
+
Example O NH
C6H5CH2NH2 (97%)
+
NH
22.9
H2NNH2
O
Preparation of Amines by Reduction
O •N •
CH2C6H5
O
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.
CH3CH2CH2CH2Br Nitriles may also be reduced by lithium aluminum hydride.
NaCN
Synthesis of Amines via Nitriles SN2 reaction, followed by reduction, gives a primary alkylamine.
CH3CH2CH2CH2CN (69%) H2 (100 atm), Ni
CH3CH2CH2CH2Br
NaCN
The reduction also works with cyanohydrins.
CH3CH2CH2CH2CN (69%) H2 (100 atm), Ni
CH3CH2CH2CH2CH2NH2
CH3CH2CH2CH2CH2NH2
(56%)
(56%)
Synthesis of Amines via Nitroarenes
Synthesis of Amines via Amides O
HNO3
Cl
NO2
Cl
H2SO4
Nitro groups may also be reduced with tin (Sn) + HCl or by catalytic hydrogenation.
(88-95%)
COH
O 1. SOCl2
(86-89%)
Only LiAlH4 is an appropriate reducing agent for this reaction.
1. Fe, HCl 2. NaOH NH2
Cl
CN(CH3)2
2. (CH3)2NH
1. LiAlH4 2. H2O
CH2N(CH3)2
(95%)
(88%)
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. 22.10
R
Reductive Amination
fast C
R
O + NH3
C
R'
NH +
H2O
R'
The aldehyde or ketone equilibrates with the imine faster than hydrogenation occurs.
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'
C H
C
NH +
H2, Ni
H
ethanol
NH2
H2O
(80%)
R'
R R'
O + NH3
R
O + NH3
Example: Ammonia Gives a Primary Amine
H2, Ni NH2
via:
NH
Example: Primary Amines Give Secondary Amines
Example: Secondary Amines Give Tertiary Amines
O CH3(CH2)5CH
O + H2N
H2, Ni
+
CH3CH2CH2CH
ethanol
N H
H2, Ni, ethanol (65%)
CH3(CH2)5CH2NH
via:
CH3(CH2)5CH
N
N
CH2CH2CH2CH3
Example: Secondary Amines Give Tertiary Amines
Possible intermediates include:
HO
22.11
N
+ N
CHCH2CH2CH3
CHCH2CH2CH3
Reactions of Amines: A Review and a Preview
N CH
CHCH2CH3
Reactions of Amines
Reactions of Amines
Reactions of amines almost always involve the nitrogen lone pair.
Reactions already discussed basicity (Section 22.4)
as a base:
N ••
H
X
reaction with aldehydes and ketones (Sections 17.10, 17.11) reaction with acyl chlorides (Section 20.4), anhydrides (Section 20.6), and esters (Section 20.12)
as a nucleophile:
N ••
C
O
(93%)
Reaction with Alkyl Halides Amines act as nucleophiles toward alkyl halides. 22.12
N •• + R
Reactions of Amines with Alkyl Halides
+ N R +
••
X •• ••
H
H
N
R
••
Example: excess amine
NH2
+
•• – •• X •• ••
+
H
+
Example: excess alkyl halide
ClCH2
(4 mol)
CH2NH2
+
3CH3I
(1 mol)
NaHCO3
90°C
methanol
heat
+ – CH2N(CH3)3 I
NHCH2 (85-87%)
(99%)
The Hofmann Elimination a quaternary ammonium hydroxide is the reactant and an alkene is the product 22.13 The Hofmann Elimination
is an anti elimination the leaving group is a trialkylamine the regioselectivity is opposite to the Zaitsev rule.
Quaternary Ammonium Hydroxides
The Hofmann Elimination
are prepared by treating quaternary ammmonium halides with moist silver oxide CH2N(CH3)3 I
on being heated, quaternary ammonium hydroxides undergo elimination CH2 +
–
+
N(CH3)3
H2O
(69%) Ag2O
H2O, CH3OH
160°C
+ – CH2N(CH3)3 HO
+ – CH2N(CH3)3 HO
Regioselectivity
Mechanism – •• •• O
H
••
H
H
•• ••
O
H
CH2 CH2
Elimination occurs in the direction that gives the less-substituted double bond. This is called the Hofmann rule. H2C
CH3CHCH2CH3
N(CH3)3 +
+ N(CH3)3 •• N(CH3)3
HO
+
–
CH3CH
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.
CHCH2CH3 (95%)
heat CHCH3 (5%)
Regioselectivity
H CH3CH2
H
H
H
H
CH3CH2
+ N(CH3)3 largest group is between two H atoms
C C
H
H
major product
Regioselectivity
H CH3
CH3
H CH3
H
H
+ N(CH3)3
C C
H
22.14 Electrophilic Aromatic Substitution
CH3
in Arylamines
minor product
largest group is between an H atom and a methyl group
Nitration of Anililne
Nitration of Anililne
NH2 is a very strongly activating group NH2 not only activates the ring toward electrophilic aromatic substitution, it also makes it more easily oxidized
Strategy: decrease the reactivity of aniline by converting the NH2 group to an amide O NH2
O O
NHCCH3
CH3COCCH3
(98%)
attemped nitration of aniline fails because nitric acid oxidizes aniline to a black tar CH(CH3)2
CH(CH3)2
(acetyl chloride may be used instead of acetic anhydride)
Nitration of Anililne
Nitration of Anililne
Strategy: nitrate the amide formed in the first step O O NHCCH3 NO2
NHCCH3
Strategy: remove the acyl group from the amide by hydrolysis O NHCCH3 NO2
HNO3
NH2 NO2
KOH ethanol, heat
CH(CH3)2 (94%)
CH(CH3)2
CH(CH3)2
CH(CH3)2 (100%)
Monohalogenation of Arylamines
Halogenation of Arylamines
Decreasing the reactivity of the arylamine by converting the NH2 group to an amide allows halogenation to be limited to monosubstitution
occurs readily without necessity of protecting amino group, but difficult to limit it to monohalogenation NH2
NH2 Br
Br2
Br
O
O
NHCCH3
NHCCH3
CH3
acetic acid
CH3
Cl2 acetic acid
CO2H
CO2H (82%)
Cl
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
22.15
NHCCH3
O
Nitrosation of Alkylamines
CH3
CH3CCl AlCl3
CCH3 (57%)
O
Nitrite Ion, Nitrous Acid, and Nitrosyl Cation
– •• •• O
••
••
O ••
N
••
H
+ H
••
H • O •• •
H
+
••
N +
••
O ••
+
•O •
H
O ••
N
••
H H
••
••
O
••
N
Nitrosyl Cation and Nitrosation
+
••
O ••
••
N +
••
O ••
(74%)
Nitrosyl Cation and Nitrosation + N
Nitrosation of Secondary Alkylamines + N
••
••
O ••
N
••
••
O ••
N
+ H
••
••
+
N ••
O ••
N +
O ••
N +
Some N-Nitroso Amines
Example
N
(CH3)2N NaNO2, HCl
••
(CH3)2NH
H2O
••
O
N-nitrosodimethylamine (leather tanning)
••
••
O ••
N
(CH3)2N
N
N
(88-90%)
N
Nitrosation of Primary Alkylamines R ••
••
O ••
•• N
H
H
H
+
••
N +
••
O ••
••
••
O ••
+ H
R H N ••
R N
O
N-nitrosonornicotine (tobacco smoke)
Nitrosation of Primary Alkylamines
R N
N
N
O
N-nitrosopyrrolidine (nitrite-cured bacon)
+ N
+
Nitrosation of secondary amines gives an N-nitroso amine.
••
••
+
H
H
O ••
N
H
N ••
••
••
•• N
•• N
••
N
H
••
O+ H
H R •N •
H
+
••
N
••
O •• H
R ••
••
•• N
O ••
N
H
+
Analogous to nitrosation of secondary amines to this point.
+
H
+
This species reacts further. R H •N •
••
N
O• + • H
Nitrosation of Primary Alkylamines
Alkyl Diazonium Ions H
Nitrosation of a primary alkylamine gives an alkyl diazonium ion. Process is called diazotization.
R
+ N
+
N ••
• O •• •
R
+ +
•N •
N ••
R
+ N
N ••
H R
H
•N •
••
Alkyl diazonium ions readily lose N2 to give carbocations.
O• + •
N
H
Example: Nitrosation of 1,1-Dimethylpropylamine
HONO
NH2
OH
+ N
H2O
N
– N2
+
Nitrosation of Tertiary Alkylamines There is no useful chemistry associated with the nitrosation of tertiary alkylamines. R
R
R
R
+ N
N ••
••
••
O ••
N
(80%) R
+ Mechanism 22.1
(3%)
R
(2%)
Nitrosation of Tertiary Arylamines Reaction that occurs is electrophilic aromatic substitution.
22.16 Nitrosation of Arylamines
N(CH2CH3)2
1. NaNO2, HCl, H2O, 8°C
N(CH2CH3)2
2. HO– N (95%)
O
Nitrosation of N-Alkylarylamines
Nitrosation of Primary Arylamines
Similar to secondary alkylamines;
Gives aryl diazonium ions.
Gives N-nitroso amines
Aryl diazonium ions are much more stable than alkyl diazonium ions.
NaNO2, HCl, H2O, 10°C
N
NHCH3
O
Most aryl diazonium ions are stable under the conditions of their formation (0-10°C).
NCH3 (87-93%)
+ RN
N
+ ArN
N
fast
+ R
+ N2
slow
+ Ar
+ N2
Synthetic Origin of Aryl Diazonium Salts
Example:
Ar
H
NH2
(CH3)2CH
NO2
Ar NaNO2, H2SO4 H2O, 0-5°C + N
(CH3)2CH
Ar
NH2
N HSO4–
Ar
+ N
N
Transformations of Aryl Diazonium Salts Ar
Cl
Ar
Br
22.17 Synthetic Transformations
Ar
CN
of Aryl Diazonium Salts
+ N
Ar Ar
F
Ar
I
N
H Ar
Ar
OH
Example
Preparation of Phenols
NH2
(CH3)2CH
+ N
Ar
1. NaNO2, H2SO4 H2O, 0-5°C
N
2. H2O, heat
H2O, heat OH
(CH3)2CH
OH
Ar
(73%)
Transformations of Aryl Diazonium Salts Ar
Cl
Ar
+ N
Ar Ar
Br
Reaction of an aryl diazonium salt with potassium iodide: Ar
CN
Ar
F
N
H
KI Ar
I
OH
Transformations of Aryl Diazonium Salts Ar
Br
N
I
Example
NH2
+ N
Ar Ar
Ar
Preparation of Aryl Iodides
1. NaNO2, HCl H2O, 0-5°C
Cl
Ar
Br
I Br
Ar
CN + N
Ar
2. KI, room temp. (72-83%)
Ar
F
Ar
I
N
H Ar
Ar
OH
Example
Preparation of Aryl Fluorides
NH2 Ar + N
Ar
1. NaNO2, HCl, H2O, 0-5°C
F
N CCH2CH3
Heat the tetrafluoroborate salt of a diazonium ion; process is called the Schiemann reaction.
Transformations of Aryl Diazonium Salts Ar
Cl
Ar
+ N
Ar Ar
Ar
Preparation of Aryl Chlorides and Bromides
Ar I
OH
Ar
Br
+ N
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
1. NaNO2, HCl, H2O, 0-5°C NO2
Cl
F
Example
NH2
(68%)
Ar
Ar
CCH2CH3
3. heat
O
N
H
2. HBF4
O
Br Ar
CN
Ar
F
2. CuCl, heat
Cl
NH2 Cl NO2
(68-71%)
1. NaNO2, HBr, H2O, 0-10°C
Br Cl
2. CuBr, heat (89-95%)
Transformations of Aryl Diazonium Salts Ar
Cl
Ar
+ N
Ar
F
OH
Transformations of Aryl Diazonium Salts Ar
CH3
1. NaNO2, HCl, H2O, 0°C
Cl
Ar
CH3
CN
Ar
+ N
Ar
(64-70%)
Ar
Transformations of Aryl Diazonium Salts Hypophosphorous acid (H3PO2) reduces diazonium salts; ethanol does the same thing. This is called reductive deamination.
H
+ N
Ar
F
Ar
I
N
H Ar
Ar
Br
CN
2. CuCN, heat
Ar
N
Aryl nitriles are prepared by heating a diazonium salt with copper(I) cyanide. This is another type of Sandmeyer reaction.
I
Example
NH2
+ N
Ar Ar
Ar
CN
Ar
N
H
Ar
Br Ar
CN
Ar
Preparation of Aryl Nitriles
OH
Example
NH2 CH3
NaNO2, H2SO4, H3PO2
CH3
N
(70-75%)
Example
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.
NH2
NH2 Br2
Br
NaNO2, H2SO4, Br H O, CH CH OH 2 3 2
H2O Br
Br
Br
(100%) Br (74-77%)
Azo Coupling Diazonium salts are weak electrophiles. React with strongly activated aromatic compounds by electrophilic aromatic substitution.
22.18 Azo Coupling
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
Cl– Section 22.19 Spectroscopic Analysis of Amines
OH N
NC6H5
Infrared Spectroscopy
Infrared Spectroscopy
Primary amines give two N—H stretching peaks, secondary amines give one.
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
RNH2
H
N
N
R H
H
symmetric
antisymmetric
1H
NMR
13C
Compare chemical shifts in:
H3C
R2NH
Carbons bonded to N are more shielded than those bonded to O.
CH2NH2 H3C
CH2OH CH3NH2
δ 3.9 ppm N
C
NMR
CH3OH
δ 4.7 ppm
H is more shielded than
O
C
H
δ 26.9 ppm
δ 48.0 ppm
UV-VIS Mass Spectrometry
An amino group on a benzene ring shifts λmax to longer wavelength. Protonation of N causes UV spectrum to resemble that of benzene. + NH3
NH2
λmax 204 nm 256 nm
λmax 230 nm 280 nm
λmax 203 nm 254 nm
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.
Mass Spectrometry
••
(CH3)2NCH2CH2CH2CH3 e–
Nitrogen stabilizes carbocations, which drives the fragmentation pathways.
CH2
e– •+
•+
CH3NHCH2CH2CH(CH3)2
(CH3)2NCH2CH2CH2CH3
+ (CH3)2N
••
CH3NHCH2CH2CH(CH3)2
+ •CH2CH2CH3
+ CH3NH
CH2
+ •CH2CH(CH3)2
