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Chapter 21Chapter 21AminesAmines
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
21.121.1Amine NomenclatureAmine Nomenclature
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Alkylamine:
N attached to alkyl group.
Arylamine:
N attached to aryl group.
Primary, secondary, or tertiary:
is determined by number of carbon atoms directly attached to nitrogen.
Classification of Amines
Two IUPAC styles:
1) Analogous to alcohols: replace -e ending with –amine. E.g. pentanamine
2) Name alkyl group and attach -amine as a suffix. E.g. isopropylamine
Nomenclature of Primary Alkylamines (RNH2)
Examples: Some Primary Alkylamines
CH3CHCH2CH2CH3
NH2
(RNH2: one carbon directly attached to N)
CH3CH2NH2 NH2
ethylamine or ethanamine
cyclohexylamine orcyclohexanamine
1-methylbutylamine or2-pentanamine orpentan-2-amine
Name as derivatives of aniline.
Nomenclature of Primary Arylamines (ArNH2)
p-fluoroaniline or4-fluoroaniline
5-bromo-2-ethylaniline
NH2F
NH2
Br CH2CH3
Amino Groups as Substituents
p-aminobenzaldehyde
Amino groups rank below OH groups and higher oxidation states of carbon.
In such cases name the amino group as a substituent.
See list of functional group priorities, Ch 17. NH2HC
O
HOCH2CH2NH2
2-aminoethanol
Name as N-substituted derivatives of the parent primary amine.
(N is a locant and is not alphabetized. It is treated the same way as a numericallocant).
The parent amine is one with longest carbon chain.
Secondary and Tertiary Amines
Examples
CH3NHCH2CH3 N-methylethylamine NHCH2CH3
NO2
Cl
4-chloro-N-ethyl-3-nitroaniline
CH3
N
CH3
N,N-dimethylcycloheptylamine
From a primary From a tertiary amine. amine.
Ammonium Salts
CH3NH3
+Cl
–
methylammoniumchloride
+
N
CH3
H
CH2CH3 CF3CO2–
N-ethyl-N-methylcyclopentylammoniumtrifluoroacetate
When all four atoms attached to N are carbon,the ion is called a quaternary ammonium ion andsalts that contain it are called quaternary ammonium salts.
+
CH2 N
CH3
CH3
CH3 I–
benzyltrimethylammonium iodide
Ammonium Salts
21.221.2Structure and BondingStructure and Bonding
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
147 pm
106°112°
Alkylamines
The most prominent feature is high electrostaticpotential at nitrogen. Reactivity of nitrogen lonepair dominates properties of amines.
Compare geometry at N of: aniline (next slide), methylamine and formamide.
sp3 sp2
Geometry at N
Pyramidal geometry at sp3-hybridized N in methylamine.Planar geometry at sp2-hybridized N in formamide.
CO
NH2
H
C NH2
H
H
H
Angle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.
sp3 sp2
Geometry at N
~125°180°
142.5°Note: This angle is not the same as the
H—N—H bond angle.
aniline
Geometry at N
142.5°
Geometry at N in aniline is pyramidal; closer tomethylamine 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 maximizesbinding of lone pair.
Electrostatic Potential Maps of Aniline
Nonplanar geometry at N. Region of highestnegative potential is at N.
Planar geometry at N. High negative potential shared by N and ring.
Figure 21.2 (page 934)
21.321.3Physical PropertiesPhysical Properties
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Amines are more polar and have higher boiling points than alkanes; but are less polar andhave lower boiling points than alcohols.
Physical Properties
CH3CH2CH3 CH3CH2NH2 CH3CH2OH
dipolemoment ():
boiling point:
0 D 1.2 D 1.7 D
-42°C 17°C 78°C
Boiling points of isomeric amines decrease ingoing 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.
Physical Properties
CH3CH2NHCH3CH3CH2CH2NH2 (CH3)3N
b.p.
less H-bonding and more branching
50°C 34°C 3°C
21.421.4Basicity of AminesBasicity of Amines
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Amine Conj. Acid pKa
NH3 NH4+ 9.3
CH3CH2NH2 CH3CH2NH3+ 10.8
Table 21.1Basicity of Amines in Aqueous Solution
CH3CH2NH3+ is a weaker acid than NH4
+; therefore, CH3CH2NH2 is a stronger base than NH3.
1. Alkylamines are slightly stronger bases than ammonia (alkyl is weakly e-donating).
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.
Table 21.1Basicity of Amines in Aqueous Solution
2. Alkylamines differ very little in basicity.
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
3. Arylamines are much weaker bases thanammonia or alkyl amines. (Aryl is an EWG.)
Table 21.1Basicity of Amines in Aqueous Solution
Summary: Effects 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 thanammonia.
H2N•• Decreased Basicity of Arylamines
++H
N
H
H NH2 +•• +
H3N
pKa = 4.6
pKa =10.6
Strongeracid
Weakeracid
Strongerbase
Weakerbase
K = 106
Comparison of aryl and alkyl amine basicity.
aniline
cyclohexylamine
+ H2N••
+
H
H
N
H NH2 +•• +
H3N
Strongeracid
Weakeracid
When anilinium ion loses a proton, the resulting lone pair is delocalized into the ring through resonance. Thus, aniline is a weaker base since the electrons are less available.
Decreased Basicity of Arylamines
Weakerbase
Strongerbase
C6H5NH2 (C6H5)2NH (C6H5)3N
pKa of
conj. acid: 4.6 0.8 ~-5
Increasing delocalization (more possible resonance structures) makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine.
Decreased Basicity of Arylamines
Effect of Substituents on Basicity of Arylamines
1. Alkyl groups (EDG) on the ring increase basicity, but only slightly (less than 1 pK unit).
X NH2
X pKa of conjugate acidH 4.6CH3 5.3
Effect of Substituents on Basicity of Arylamines
2. Electron withdrawing groups (EWG), especially ortho and/or para to amine group, decrease basicity and can have a large effect.
X NH2
X pKa of conjugate acidH 4.6CF3 3.5
NO2 1.0
p-Nitroaniline NH2
O
N
O
– ••••••
••
+
••
••
N
O
O
– ••••••
•• ••••–
NH2
+ +
The lone pair on -NH2 is conjugated with the p-nitro group (more delocalization than in aniline). This delocalization is lost on protonation of -NH2.
Aniline is 3800 times more basic thanp-nitroaniline.
Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.
Heterocyclic Amines N
H
••
N••
is more basic than
piperidine pyridinepKa of conjugate acid:
11.2
pKa of conjugate acid:
5.2
(an alkylamine)(resembles anarylamine in
basicity)
Heterocyclic Amines N••
is more basic than
imidazole pyridinepKa of conjugate acid:
7.0
pKa of conjugate acid:
5.2
N HN••
••
Imidazole N HN••
••
Which nitrogen is protonated in imidazole ?
H+ H+ N HN ••H
+ +
N HN••
H
loss of aromaticity
Imidazole N HN••
••
Protonation in the direction shown gives a resonance stabilized cation.
H+ N HNH
+ ••
N HNH
••+ resonance
stabilizedcation
21.521.5Tetraalkylammonium SaltsTetraalkylammonium Salts
as Phase-Transfer Catalystsas Phase-Transfer Catalysts
Phase-Transfer Catalysis
Phase-transfer agents promote the solubility ofionic substances in nonpolar solvents. Theyare able to transfer the ionic substance from an aqueous phase to a non-aqueous one.
Phase-transfer agents increase the rates ofreactions involving anions. The anion when in nonpolar media is relatively unsolvated and very reactive compared to media like water or alcohols.
+
Phase-Transfer Catalysis
Quaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.
NH3C
CH2CH2CH2CH2CH2CH2CH2CH3
CH2CH2CH2CH2CH2CH2CH2CH3
CH2CH2CH2CH2CH2CH2CH2CH3Cl–
Methyltrioctylammonium chloride
Phase-Transfer Catalysis
The substituents on N are nonpolar thus enhance the solubility of the ion in nonpolar solvents.
Benzyltriethylammonium chloride
Cl–
+N
CH2CH3
CH2CH3
CH2CH3
CH2
Example
The SN2 reaction of sodium cyanide with butyl
bromide occurs much faster when benzyl-triethylammonium chloride is present than whenit is not.
CH3CH2CH2CH2Br + NaCN
CH3CH2CH2CH2CN + NaBr
benzyltriethylammonium chloride
Cl–
(aqueous)
(aqueous)
CN–+
Cl–+CN–
(aqueous)
(aqueous)
Anion exchange in the aqueous phase
+N
CH2CH3
CH2CH3
CH2CH3
CH2
+N
CH2CH3
CH2CH3
CH2CH3
CH2
Mechanism
CN–
(aqueoussolvent)
(butyl bromide used as solvent)
CN–
Mechanism
Transfer to the organic phase
+N
CH2CH3
CH2CH3
CH2CH3
CH2
+N
CH2CH3
CH2CH3
CH2CH3
CH2
CN–
CH3CH2CH2CH2Br+
Br–
CH3CH2CH2CH2CN+
Mechanism
SN2 reaction in the organic phase
+N
CH2CH3
CH2CH3
CH2CH3
CH2
+N
CH2CH3
CH2CH3
CH2CH3
CH2
(butyl bromide solvent)
(butyl bromide solvent)
21.621.6Reactions That Lead to Amines:Reactions That Lead to Amines:
A Review and a PreviewA 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
1. Nucleophilic substitution by azide ion (N3–)
(Section 8.1, 8.11)
2. Nitration of arenes (Section 12.3)
3. Nucleophilic ring opening of epoxides by ammonia or amines (Section 16.12)
4. Nucleophilic addition of amines to aldehydes and ketones (Sections 17.10, 17.11)
5. Nucleophilic substitution by ammonia on -halo acids (Section 20.15)
6. Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)
21.721.7Preparation of Amines by Preparation of Amines by
Alkylation of AmmoniaAlkylation of Ammonia
Alkylation of Ammonia
Desired reaction is:
2 NH3 + R—X R—NH2 + NH4X
via:
H3N •••• ••R X••
H3N R+ •• ••X
••••
–+ +
then:
H3N •• +
+
H N
H
H
R H3N H+
+ N
H
H
R••
Alkylation of Ammonia
The method doesn't work well in practice becauseit usually gives mixtures of primary, secondary,and tertiary amines, plus the quaternary salt due to multiple alkylation.
NH3
RXRNH2
RXR2NH
RX
R3NRX
R4N+
X–
(mixtures)
Example
CH3(CH2)6CH2BrNH3 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.
21.821.8The Gabriel Synthesis The Gabriel Synthesis
of Primary Alkyl Aminesof Primary Alkyl Amines
This method yields primary amines without formation of secondary or other amines as byproducts.It uses an SN2 reaction on an alkyl halide to form the C—N bond.
The nitrogen-containing nucleophileis N-potassiophthalimide.
Gabriel Synthesis
O
O
N•• •• K+–
The pKa of phthalimide is 8.3.
N-potassiophthalimide is easily prepared bythe reaction of phthalimide with KOH. O
O
N•• ••–
K+
O
O
NH••
KOH
N-Potassiophthalimide
••–
N-Potassiophthalimide as a Nucleophile O
O
N•••• ••R X••
+
O
O
N R••
+ •• ••X••
••–
SN2
The N of phthaIimide becomes the N in the primary amine.
Cleavage of Alkylated Phthalimide
O
O
N R•• + H2O
H2N R+
CO2H
CO2H
acid or base
Imide hydrolysis is nucleophilic acyl substitution.
primary amine
Cleavage of Alkylated Phthalimide
Hydrazinolysis is an alternative method of releasing the amine from its phthalimide derivative.
O
O
N R••
H2N R+
O
O
NH
NH
H2NNH2
–
O
O
K+
N + C6H5CH2Cl
DMF
O
O
N CH2C6H5
•• (74%)
•• ••
Example
Example
+ C6H5CH2NH2
O
O
N CH2C6H5
••
H2NNH2
(97%)
O
O
NH
NH
21.921.9Preparation of AminesPreparation of Amines
by Reductionby Reduction
Almost any nitrogen-containing compound canbe reduced to an amine, including:
azides,nitriles,nitro-substituted benzene derivatives, andamides.
Preparation of Amines by Reduction
SN2 reaction, followed by reduction, gives a
primary alkylamine.
Synthesis of Amines via Azides CH2CH2Br
CH2CH2N3
NaN3
(74%) CH2CH2NH2
(89%)
1. LiAlH4
2. H2O
Azides may also bereduced by catalytichydrogenation.
Synthesis of Amines via Nitriles
CH3CH2CH2CH2BrNaCN
(69%)
CH3CH2CH2CH2CN
CH3CH2CH2CH2CH2NH2 (56%)
H2 (100 atm), Ni
Nitriles may also bereduced by lithiumaluminum hydride.
SN2 reaction, followed by reduction, gives a
primary alkylamine.
The reduction also works with cyanohydrins.
Synthesis of Amines via Nitroarenes
HNO3
(88-95%)
Cl
Cl NO2
H2SO4
(95%)
1. Fe, HCl
2. NaOH Cl NH2
Aryl nitro groups may be reduced with Sn or Fe+ HCl or by catalytichydrogenation.
Synthesis of Amines via Amides
(86-89%)
COH
O1. SOCl2
2. (CH3)2NH
CN(CH3)2
O
(88%)
1. LiAlH4
2. H2O CH2N(CH3)2
Only LiAlH4 is an
appropriate reducingagent for this reaction.
21.1021.10Reductive AminationReductive Amination
The aldehyde or ketone equilibrates with theimine faster than hydrogenation of C=O occurs.
Synthesis of Amines via Reductive Amination
+ NH3
fast+ H2O
In reductive amination, an aldehyde or ketoneis subjected to catalytic hydrogenation in thepresence of ammonia or an amine.
OC
R
R'
NHC
R
R'
Synthesis of Amines via Reductive Amination
OC
R
R'
+ NH3
fastNHC
R
R'
+ H2O
H2, Ni
NH2
R
R' C
H
And the imine undergoes hydrogenation faster than the aldehyde or ketone, so an amine is the product.
Example: Ammonia Gives a Primary Amine O + NH3
H
NH2
H2, Ni
ethanol
(80%)
via:
NH
Sodium triacetoxyborohyride, Na(CH3CO2)3BH, is a useful chemical reagent for this reduction. It is readily available and non-toxic. Catalytic reduction is shown below.
Example: Primary Amines Give Secondary Amines
H2, Ni ethanol
(65%)
CH3(CH2)5CH2NH
+ H2N
CH3(CH2)5CH
O
via: N
CH3(CH2)5CH
Example: Secondary Amines Give Tertiary Amines
H2, Ni, ethanol
(93%)
+CH3CH2CH2CH
O
N
H N
CH2CH2CH2CH3
CHCH2CH2CH3
N+
Possible intermediates for the prevoius reaction include:
N
CH CHCH2CH3
CHCH2CH2CH3
N
HO
Example: Secondary Amines Give Tertiary Amines
21.1121.11Reactions of Amines:Reactions of Amines:
A Review and a PreviewA Review and a Preview
Reactions of Amines
Reactions of amines almost always involve the nitrogen lone pair, either:
••N H X
as a base:
••N
C Oas a nucleophile:
or Attacks H
Attacks C
Reactions of Amines
1. Basicity (Section 21.4).
2. Reaction with aldehydes and ketones (Sections 17.10, 17.11).
3. Reaction with acyl chlorides (Section 19.4),anhydrides (Section 19.5), and esters
(Section 19.11).
Reactions already discussed
21.1221.12Reaction of Amines with Alkyl HalidesReaction of Amines with Alkyl Halides
Amines act as nucleophiles toward alkyl halides.
•• X+ ••••
••••N R
H
+ X ••••
••N R
H
+ –
+N R••
H+
Reaction with Alkyl Halides
NH2 + ClCH2
NHCH2
(85-87%)
NaHCO3 90°C
(4 mol) (1 mol)
Example: Excess amine
+ CH3I
(99%)
methanol heat
CH2N(CH3)3
CH2NH2
+
I–
Example: Excess alkyl halide
(3 mol)(1 mol)
This is referred to as exhaustive methylation.
21.1421.14Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution
in Aryl Aminesin Aryl Amines
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.
Attempted nitration of aniline fails because nitric acid oxidizes aniline to a black tar.
Strategy for Nitration of Aniline
Step 1: Decrease the reactivity of aniline by converting the NH2 group to an amide.
CH(CH3)2
NH2
CH(CH3)2
NHCCH3
O
O
CH3COCCH3
O
(98%)
(acetyl chloride may be used instead of acetic anhydride)
Step 2: Nitrate the amide formed in the first step.
CH(CH3)2
NHCCH3
O
HNO3
CH(CH3)2
NHCCH3
O NO2
(94%)
Strategy for Nitration of Aniline
Step 3: Remove the acyl group from the amide by hydrolysis.
CH(CH3)2
NHCCH3
O NO2
KOH
ethanol,heat
CH(CH3)2
NH2 NO2
(100%)
Strategy for Nitration of Aniline
This occurs readily without necessity of protecting amino group, but difficult to limit it to monohalogenation.
Halogenation of Arylamines CO2H
NH2
Br2
acetic acid
(82%)
CO2H
NH2
Br Br
Monohalogenation of Arylamines
Cl
NHCCH3
O CH3
(74%)
Cl2
acetic acid
NHCCH3
O
CH3
Decreasing the reactivity of the arylamine by converting the NH2 group to an amide allows halogenation to be limited to monosubstitution.
Friedel-Crafts Reactions
The amino group of an arylamine must be protected as an amide when carrying out a Friedel-Crafts reaction3 NHCCH3
O
CH2CH3 CH3CCl
O
AlCl3
(57%)
NHCCH3
O CH2CH3
CCH3OOtherwise –NH2 will complex with the AlCl3.
21.1521.15Nitrosation of AlkylaminesNitrosation of Alkylamines
Nitrite Ion, Nitrous Acid, and Nitrosyl Cation
H+–
O••••
••N O
•• ••••
O•• ••
N O•• ••
••H
H+
O••N O
•• ••
H
H
+••+
••N O
•• ••+O ••
H
H
•• nitrite ion
nitrous acid
nitrosyl cation
Nitrosyl Cation and Nitrosation
+
••N O
•• ••+••N N••N O
•• ••+
The nitrosation reaction.
Nitrosation of Secondary Alkylamines
+
••N O
•• ••
+H + N
••N O
•• ••••
N••N O
•• ••+
H
Nitrosation of secondary amines gives an N-nitroso amine.
••N
H
RR
RR
R
R
Example
(CH3)2NH•• NaNO2, HCl
H2O(88-90%)
••(CH3)2N
••N O
•• ••
N-nitrosodimethylamine(leather tanning)
Some N-Nitroso Amines
N-nitrosopyrrolidine(nitrite-cured bacon)
N
NO
N-nitrosonornicotine(tobacco smoke)
N
NON
Nitrosation of Primary Alkylamines
+
Analogous to nitrosation of secondary amines to this point.
+
••N O
•• ••••N
H
HR
N••N O
•• ••+
H
HR
+H + N
••N O
•• ••••
R
H
Nitrosation of Primary Alkylamines
H+
N••N O
••••
R
H H
+
This species reacts further.
••N
••N O
••••
R
H
H+
H+
+
H
••N••N O••
R
H
+
N••N O
•• ••••
R
H
Nitrosation of Primary Alkylamines
H
••O
H
••+
Nitrosation of a primary alkylamine gives an alkyl diazonium ion.
Process is called diazotization.
+
H
••N••N O••
R
H
+N N ••R
Primary Alkyl Diazonium Ions
+N N ••R
Primary alkyl diazonium ions are unstable and readily lose N2 to give carbocations.
R+ + N N ••••
Example: Nitrosation of 1,1-Dimethylpropylamine NH2
N N+
HONO
H2O
OH
(80%) +
(2%)(3%)
+
– N2
Mechanism 21.2
There is no useful chemistry associated with the nitrosation of tertiary alkylamines.
Nitrosation of Tertiary Alkylamines
••NR
R
R
N••N O
•• ••+R
R
R
21.1621.16Nitrosation of ArylaminesNitrosation of Arylamines
Reaction that occurs is electrophilic aromatic substitution.
Nitrosation of Tertiary Arylamines N(CH2CH3)2
(95%)
1. NaNO2, HCl, H2O, 8°C
2. HO–
N(CH2CH3)2
NO
Similar to secondary alkylamines;
Gives N-nitroso amines
Nitrosation of N-Alkylarylamines
NaNO2, HCl,H2O, 10°C
NHCH3
(87-93%)
NCH3
N O
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).
ArN N+
RN N+ fast
slow
R+ + N2
Ar+ + N2
Alkyl:
Aryl:
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+
21.1721.17Synthetic Transformations ofSynthetic Transformations of
Aryl Diazonium SaltsAryl Diazonium Salts
Transformations of Aryl Diazonium Salts
Ar N N+
Ar H
Ar OH
Ar I
Ar F
Ar BrAr Cl
Ar CN
Preparation of Phenols
Ar OH
H2O, heat
Ar N N+
Example
2. H2O, heat
(CH3)2CH NH2
1. NaNO2, H2SO4
H2O, 0-5°C (CH3)2CH OH
(73%)
Preparation of Aryl Iodides
Ar I
Reaction of an aryl diazonium salt with potassium iodide:
KIAr N N
+
Example
2. KI, room temp.
1. NaNO2, HCl
H2O, 0-5°C
(72-83%)
NH2
Br
I Br
Preparation of Aryl Fluorides
Ar F
Heat the tetrafluoroborate salt of a diazonium ion;
process is called the Schiemann reaction.
Ar N N+
Example
(68%)
NH2 CCH2CH3
O
2. HBF4
1. NaNO2, HCl,
H2O, 0-5°C
3. heat
F CCH2CH3
O
Preparation of Aryl Chlorides and Bromides
Ar BrAr Cl
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.
Ar N N+
Example
(68-71%)
NH2 NO2
2. CuCl, heat
1. NaNO2, HCl,
H2O, 0-5°C
Cl NO2
Example
(89-95%)
2. CuBr, heat
1. NaNO2, HBr,
H2O, 0-10°C
NH2
Cl
Br Cl
Preparation of Aryl Nitriles
Ar CN
Aryl nitriles are prepared by heating a diazonium salt with copper(I) cyanide.
This is another type of Sandmeyer reaction.
Ar N N+
Example
(64-70%)
2. CuCN, heat
1. NaNO2, HCl,
H2O, 0°C
NH2
CH3
CN CH3
Transformations of Aryl Diazonium Salts
Ar N N+
Ar H
Hypophosphorous acid (H3PO2) reduces diazonium salts; ethanol does the same thing.
This is called reductive deamination.
Example
(70-75%)
NaNO2, H2SO4,
H3PO2
NH2
CH3 CH3
or NaNO2, HCl,
CH3CH2OH
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 Br
BrBr
NH2
Br
Br
Br
(74-77%)
NaNO2, H2SO4,H2O, CH3CH2OH
NH2 Br2
H2O
(100%)
21.1821.18Azo CouplingAzo 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–
21.1321.13The Hofmann EliminationThe Hofmann Elimination
The Hofmann Elimination
This is an elimination reaction involving a quaternary ammonium hydroxide as 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.
Ag2O H2O, CH3OH
CH2N(CH3)3
+
HO–
These are prepared by treating quaternary ammmonium halides with moist silver oxide.HO replaces I and AgI precipitates.
CH2N(CH3)3
I–+
Quaternary Ammonium Hydroxides
+ AgI ↓
– –
160°C
CH2N(CH3)3
+
HO–
When heated, quaternary ammonium hydroxides undergo elimination.
CH2
(69%)
+ N(CH3)3 + H2O
The Hofmann Elimination
H
CH2
+N(CH3)3
–O•••• H••
O••
H••
H
N(CH3)3••
CH2
The Hofmann Elimination
+
+
heat
Elimination occurs in the direction that gives the less-substituted double bond. This is called the Hofmann rule.
N(CH3)3+
HO–
CH3CHCH2CH3H2C CHCH2CH3
CH3CH CHCH3
+
(95%)
(5%)
Regioselectivity
1 2 3
4
Steric factors are important in the determining the regioselectivity of this elimination.
The transition state that leads to 1-butene isless crowded than the one leading to cisor trans-2-butene.
Regioselectivity
+N(CH3)3
H
H
H H
CH3CH2
largest group is between two H atoms.
C
HC
HH
CH3CH2
major product
Regioselectivity
Looking down the 1-2 bond
+N(CH3)3
H
H
H
CH3
largest group is between anH atom and a methyl group.
C
HC
CH3 H
CH3
minor product
CH3
Regioselectivity
Looking down the 2-3 bond
21.1921.19Spectroscopic Analysis of AminesSpectroscopic Analysis of Amines
The N—H stretching band appears in the range3000-3500 cm-1.
Primary amines give two peaks in this region, onefor a symmetrical stretching vibration, the other foran antisymmetrical stretch.
Infrared Spectroscopy
R N
H
H
symmetric
R N
H
H
antisymmetric
Primary amines give two N—H stretching peaks, secondary amines give one (Figure 21.8).
Infrared Spectroscopy
Compare chemical shifts in:
1H NMR H3C CH2NH2
H3C CH2OH
N C H is more shielded than
3.9 ppm 4.7 ppm
O C H
13C NMR
Carbons bonded to N are more shielded than those bonded to O.
CH3NH2 CH3OH
26.9 ppm 48.0 ppm
max
204 nm256 nm
max
230 nm280 nm
max
203 nm254 nm
An amino group on a benzene ring shifts max
to longer wavelength. Protonation of N causesUV spectrum to resemble that of benzene.
UV-VIS NH2
NH3
+
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.
In fragmentation, a primary amine generates an M/Z of 30 and the (+) fragment is a monosubstituted N. (CH2NH2)+
(CH3)2NCH2CH2CH2CH3
••
e–
(CH3)2NCH2CH2CH2CH3
•+
•CH2CH2CH3+(CH3)2N CH2
+
Mass Spectrometry
Nitrogen stabilizes carbocations, which drives the fragmentation pathways.
With a 3o amine, the (+) fragment is a trisubstituted N.
CH3NHCH2CH2CH(CH3)2
••
e–
CH3NHCH2CH2CH(CH3)2
•+
•CH2CH(CH3)2+CH3NH CH2
+
Mass Spectrometry
And with a 2o amine, the (+) fragment is a disubstituted N.
End of Chapter 21End of Chapter 21AminesAmines