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Dr. Wolf's CHM 201 & 202 21-1
Chapter 21Chapter 21AminesAmines
Dr. Wolf's CHM 201 & 202 21-2
Amine NomenclatureAmine Nomenclature
Dr. Wolf's CHM 201 & 202 21-3
AlkylamineAlkylamine
N attached to alkyl groupN attached to alkyl group
ArylamineArylamine
N attached to aryl groupN attached to aryl group
Primary, secondary, or tertiaryPrimary, secondary, or tertiary
determined by number of carbon atoms determined by number of carbon atoms directly attached to nitrogendirectly attached to nitrogen
Classification of AminesClassification of Amines
Dr. Wolf's CHM 201 & 202 21-4
Two IUPAC stylesTwo IUPAC styles
1)1) analogous to alcohols: replace -analogous to alcohols: replace -e e ending by -ending by -amineamine
2)2) name alkyl group and attach -name alkyl group and attach -amineamineas a suffixas a suffix
Nomenclature of Primary Alkylamines (RNHNomenclature of Primary Alkylamines (RNH22))
Dr. Wolf's CHM 201 & 202 21-5
Examples: some primary alkylaminesExamples: some primary alkylamines
CHCH33CHCHCHCH22CHCH22CHCH33
NNHH22
(RNH(RNH22: one carbon directly attached to N): one carbon directly attached to N)
CHCH33CHCH22NNHH22 NNHH22
ethylamineethylamine or or ethanamineethanamine
cyclohexylaminecyclohexylamine or orcyclohexanaminecyclohexanamine
1-methylbutylamine 1-methylbutylamine oror2-pentanamine2-pentanamine
Dr. Wolf's CHM 201 & 202 21-6
Name as derivatives of aniline.Name as derivatives of aniline.
Nomenclature of Primary Arylamines (ArNHNomenclature of Primary Arylamines (ArNH22))
pp-fluoroaniline-fluoroaniline 5-bromo-2-ethylaniline5-bromo-2-ethylaniline
NNHH22FF
NNHH22
BrBr CHCH22CHCH33
Dr. Wolf's CHM 201 & 202 21-7
Amino groups as substituentsAmino groups as substituents
pp-aminobenzaldehyde-aminobenzaldehyde
amino groups rank below OH groups and higher amino groups rank below OH groups and higher
oxidation states of carbonoxidation states of carbon
in such cases name the amino group as a in such cases name the amino group as a
substituentsubstituent NNHH22HHCC
OO
HHOOCHCH22CHCH22NNHH22
2-aminoethanol2-aminoethanol
Dr. Wolf's CHM 201 & 202 21-8
Name as Name as NN-substituted derivatives of parent -substituted derivatives of parent primary amine.primary amine.
(N is a locant-it is not alphabetized, but(N is a locant-it is not alphabetized, butis treated the same way as a numericalis treated the same way as a numericallocant)locant)
Parent amine is one with longest carbonParent amine is one with longest carbonchain.chain.
Secondary and Tertiary AminesSecondary and Tertiary Amines
Dr. Wolf's CHM 201 & 202 21-9
ExamplesExamples
CHCH33NNHCHHCH22CHCH33 NN-methylethylamine-methylethylamine NNHCHHCH22CHCH33
NONO22
ClCl
4-chloro-4-chloro-NN-ethyl-3-nitroaniline-ethyl-3-nitroaniline
CHCH33
NN
CHCH33
NN,,NN-dimethylcycloheptylamine-dimethylcycloheptylamine
Dr. Wolf's CHM 201 & 202 21-10
A nitrogen with four substituents is positivelyA nitrogen with four substituents is positivelycharged and is named as a derivative of charged and is named as a derivative of ammonium ammonium ion (NHion (NH44
++).).
Ammonium SaltsAmmonium Salts
CHCH33NHNH33
++ClCl
––
methylammoniummethylammonium
chloridechloride
NN
CHCH33
HH
CHCH22CHCH33
++CFCF33COCO22
––
NN-ethyl--ethyl-NN-methylcyclopentylammonium-methylcyclopentylammonium
trifluoroacetatetrifluoroacetate
Dr. Wolf's CHM 201 & 202 21-11
When all four atoms attached to N are carbon,When all four atoms attached to N are carbon,the ion is called a the ion is called a quaternary ammonium quaternary ammonium ion andion andsalts that contain it are called salts that contain it are called quaternaryquaternary ammoniumammonium salts. salts.
Ammonium SaltsAmmonium Salts
++
CHCH22 NN
CHCH33
CHCH33
CHCH33 II––
benzyltrimethylammonium iodidebenzyltrimethylammonium iodide
Dr. Wolf's CHM 201 & 202 21-12
Structure and BondingStructure and Bonding
Dr. Wolf's CHM 201 & 202 21-13
147 pm147 pm
106°106°112°112°
AlkylaminesAlkylamines
Dr. Wolf's CHM 201 & 202 21-14
Most prominent feature is high electrostaticMost prominent feature is high electrostaticpotential at nitrogen. Reactivity of nitrogen lonepotential at nitrogen. Reactivity of nitrogen lonepair dominates properties of amines. pair dominates properties of amines.
AlkylaminesAlkylamines
Dr. Wolf's CHM 201 & 202 21-15
Compare geometry at N of methylamine, aniline,Compare geometry at N of methylamine, aniline,and formamide.and formamide.
spsp33 spsp22
Geometry at NGeometry at N
Pyramidal geometry at Pyramidal geometry at spsp33-hybridized N in -hybridized N in
methylamine.methylamine.
Planar geometry at Planar geometry at spsp22-hybridized N in formamide.-hybridized N in formamide.
CCOO
NNHH22
HH
CC NNHH22
HH
HH
HH
Dr. Wolf's CHM 201 & 202 21-16
Compare geometry at N of methylamine, aniline,Compare geometry at N of methylamine, aniline,and formamide.and formamide.
spsp33 spsp22
Geometry at NGeometry at N
Pyramidal geometry at Pyramidal geometry at spsp33-hybridized N in -hybridized N in
methylamine.methylamine.
Planar geometry at Planar geometry at spsp22-hybridized N in formamide.-hybridized N in formamide.
Dr. Wolf's CHM 201 & 202 21-17
Angle that the C—N bond makes with bisector ofAngle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.H—N—H angle is a measure of geometry at N.
spsp33 spsp22
Geometry at NGeometry at N
~125°~125°180°180°
Note: this is not the same as the H—N—H bond angleNote: this is not the same as the H—N—H bond angle
Dr. Wolf's CHM 201 & 202 21-18
Angle that the C—N bond makes with bisector ofAngle that the C—N bond makes with bisector ofH—N—H angle is a measure of geometry at N.H—N—H angle is a measure of geometry at N.
spsp33 spsp22
Geometry at NGeometry at N
~125°~125°180°180°
142.5°142.5°
Dr. Wolf's CHM 201 & 202 21-19
Geometry at N in aniline is pyramidal; closer toGeometry at N in aniline is pyramidal; closer tomethylamine than to formamide.methylamine than to formamide.
Geometry at NGeometry at N
142.5°142.5°
Dr. Wolf's CHM 201 & 202 21-20
Geometry at NGeometry at N
142.5°142.5°
Hybridization of N in aniline lies between Hybridization of N in aniline lies between spsp33 and and spsp22..
Lone pair of N can be delocalized into ring best if N is Lone pair of N can be delocalized into ring best if N is
spsp22 and lone pair is in a and lone pair is in a pp orbital. orbital.
Lone pair bound most strongly by N if pair is in an Lone pair bound most strongly by N if pair is in an spsp33
orbital of N, rather than orbital of N, rather than pp..
Actual hybridization is a compromise that maximizesActual hybridization is a compromise that maximizes
binding of lone pair.binding of lone pair.
Dr. Wolf's CHM 201 & 202 21-21
Electrostatic Potential Maps of AnilineElectrostatic Potential Maps of Aniline
Nonplanar geometry at Nonplanar geometry at N. Region of highestN. Region of highestnegative potential is at N.negative potential is at N.
Planar geometry at N. Planar geometry at N. High negative potential High negative potential shared by N and ring.shared by N and ring.
Dr. Wolf's CHM 201 & 202 21-22
Physical PropertiesPhysical Properties
Dr. Wolf's CHM 201 & 202 21-23
Amines are more polar and have higher boiling Amines are more polar and have higher boiling points than alkanes; but are less polar andpoints than alkanes; but are less polar andhave lower boiling points than alcohols.have lower boiling points than alcohols.
Physical PropertiesPhysical Properties
CHCH33CHCH22CHCH33 CHCH33CHCH22NNHH22 CHCH33CHCH22OOHH
dipoledipolemoment (moment ():):
boiling point:boiling point:
0 D0 D 1.2 D1.2 D 1.7 D1.7 D
-42°C-42°C 17°C17°C 78°C78°C
Dr. Wolf's CHM 201 & 202 21-24
Boiling points of isomeric amines decrease inBoiling points of isomeric amines decrease ingoing from primary to secondary to tertiary amines.going from primary to secondary to tertiary amines.
Primary amines have two hydrogens on N capable Primary amines have two hydrogens on N capable of being involved in intermolecular hydrogen of being involved in intermolecular hydrogen bonding. Secondary amines have one. Tertiary bonding. Secondary amines have one. Tertiary amines cannot be involved in intermolecular amines cannot be involved in intermolecular hydrogen bonds.hydrogen bonds.
Physical PropertiesPhysical Properties
CHCH33CHCH22NNHCHHCH33CHCH33CHCH22CHCH22NNHH22 (CH(CH33))33NN
boilingboilingpoint:point:
50°C50°C 34°C34°C 3°C3°C
Dr. Wolf's CHM 201 & 202 21-25
Basicity of AminesBasicity of Amines
Dr. Wolf's CHM 201 & 202 21-26
Effect of Structure on BasicityEffect of Structure on Basicity
1. Alkylamines are slightly stronger bases than 1. Alkylamines are slightly stronger bases than ammonia.ammonia.
Dr. Wolf's CHM 201 & 202 21-27
AmineAmine Conj. AcidConj. Acid pKpKaa
NHNH33 NHNH44++ 9.39.3
CHCH33CHCH22NHNH22 CHCH33CHCH22NHNH33++ 10.810.8
Table 22.1 (page 920)Table 22.1 (page 920)Basicity of Amines in Aqueous SolutionBasicity of Amines in Aqueous Solution
CHCH33CHCH22NHNH33++ is a weaker acid than NH is a weaker acid than NH44
++;;therefore, CHtherefore, CH33CHCH22NHNH22 is a stronger base is a stronger base than NHthan NH33..
Dr. Wolf's CHM 201 & 202 21-28
Effect of Structure on BasicityEffect of Structure on Basicity
1. Alkylamines are slightly stronger bases than 1. Alkylamines are slightly stronger bases than ammonia.ammonia.
2. Alkylamines differ very little in basicity.2. Alkylamines differ very little in basicity.
Dr. Wolf's CHM 201 & 202 21-29
AmineAmine Conj. AcidConj. Acid pKpKaa
NHNH33 NHNH44++ 9.39.3
CHCH33CHCH22NHNH22 CHCH33CHCH22NHNH33++ 10.810.8
(CH(CH33CHCH22))22NHNH (CH(CH33CHCH22))22NHNH22++ 11.111.1
(CH(CH33CHCH22))33NN (CH(CH33CHCH22))33NHNH++ 10.810.8
Table 22.1 (page 920)Table 22.1 (page 920)Basicity of Amines in Aqueous SolutionBasicity of Amines in Aqueous Solution
Notice that the difference separating a primary,Notice that the difference separating a primary,secondary, and tertiary amine is only 0.3 pK units.secondary, and tertiary amine is only 0.3 pK units.
Dr. Wolf's CHM 201 & 202 21-30
Effect of Structure on BasicityEffect of Structure on Basicity
1. Alkylamines are slightly stronger bases than 1. Alkylamines are slightly stronger bases than ammonia.ammonia.
2. Alkylamines differ very little in basicity.2. Alkylamines differ very little in basicity.
3. Arylamines are much weaker bases than3. Arylamines are much weaker bases thanammonia.ammonia.
Dr. Wolf's CHM 201 & 202 21-31
AmineAmine Conj. AcidConj. Acid pKpKaa
NHNH33 NHNH44++ 9.39.3
CHCH33CHCH22NHNH22 CHCH33CHCH22NHNH33++ 10.810.8
(CH(CH33CHCH22))22NHNH (CH(CH33CHCH22))22NHNH22++ 11.111.1
(CH(CH33CHCH22))33NN (CH(CH33CHCH22))33NHNH++ 10.810.8
CC66HH55NHNH22 CC66HH55NHNH33++ 4.64.6
Table 22.1 (page 920)Table 22.1 (page 920)Basicity of Amines in Aqueous SolutionBasicity of Amines in Aqueous Solution
Dr. Wolf's CHM 201 & 202 21-32
HH22NN•••• Decreased basicity of arylaminesDecreased basicity of arylamines
++HH
NN
HH
HH
++ NNHH22 ++•••• ++
HH33NN
ppKKaa = 4.6 = 4.6
ppKKaa =10.6 =10.6
StrongerStrongeracidacid
WeakerWeakeracidacid
StrongerStrongerbasebase
WeakerWeakerbasebase
Dr. Wolf's CHM 201 & 202 21-33
HH22NN•••• Decreased basicity of arylaminesDecreased basicity of arylamines
++HH
NN
HH
HH
++ NNHH22 ++•••• ++
HH33NN
StrongerStrongeracidacid
WeakerWeakeracidacid
When anilinium ion loses a proton, theWhen anilinium ion loses a proton, theresulting lone pair is delocalized into the ring.resulting lone pair is delocalized into the ring.
Dr. Wolf's CHM 201 & 202 21-34
HH22NN•••• Decreased basicity of arylaminesDecreased basicity of arylamines
++HH
NN
HH
HH
++ NNHH22 ++•••• ++
HH33NN
Aniline is a weaker base because its Aniline is a weaker base because its lone pair is more strongly held.lone pair is more strongly held.
StrongerStrongerbasebase
WeakerWeakerbasebase
Dr. Wolf's CHM 201 & 202 21-35
Decreased basicity of arylaminesDecreased basicity of arylamines
CC66HH55NNHH22 (C(C66HH55))22NNHH (C(C66HH55))33NN
ppKKa a of conjugate acid:of conjugate acid:
4.64.6 0.80.8 ~-5~-5
Increasing delocalization makes diphenylamine a Increasing delocalization makes diphenylamine a
weaker base than aniline, and triphenylamine a weaker weaker base than aniline, and triphenylamine a weaker
base than diphenylamine.base than diphenylamine.
Dr. Wolf's CHM 201 & 202 21-36
Effect of Substituents on Basicity of ArylaminesEffect of Substituents on Basicity of Arylamines
1. Alkyl groups on the ring increase basicity, but1. Alkyl groups on the ring increase basicity, butonly slightly (less than 1 ponly slightly (less than 1 pKK unit). unit).
XX NHNH22
XX ppKKa a of conjugate acidof conjugate acid
HH 4.64.6CHCH33 5.35.3
Dr. Wolf's CHM 201 & 202 21-37
Effect of Substituents on Basicity of ArylaminesEffect of Substituents on Basicity of Arylamines
2. Electron withdrawing groups, especially ortho2. Electron withdrawing groups, especially orthoand/or para to amine group, decrease basicityand/or para to amine group, decrease basicityand can have a large effect.and can have a large effect.
XX NHNH22
XX ppKKa a of conjugate acidof conjugate acid
HH 4.64.6CFCF33 3.53.5
OO22NN 1.01.0
Dr. Wolf's CHM 201 & 202 21-38
p-Nitroanilinep-Nitroaniline NNHH22
OO
NN
OO
–– ••••••••••••
••••
++
••••
••••
OO
NN
OO
–– ••••••••••••
•••• ••••••••––
NNHH22
++ ++
Lone pair on amine nitrogen is conjugated with Lone pair on amine nitrogen is conjugated with
pp-nitro group—more delocalized than in aniline -nitro group—more delocalized than in aniline
itself. Delocalization lost on protonation.itself. Delocalization lost on protonation.
Dr. Wolf's CHM 201 & 202 21-39
Effect is CumulativeEffect is Cumulative
Aniline is 3800 times more basic thanAniline is 3800 times more basic than
pp-nitroaniline.-nitroaniline.
Aniline is ~1,000,000,000 times more basic than Aniline is ~1,000,000,000 times more basic than
2,4-dinitroaniline.2,4-dinitroaniline.
Dr. Wolf's CHM 201 & 202 21-40
Heterocyclic Amines Heterocyclic Amines NN
HH
••••
NN••••
is more basic thanis more basic than
piperidinepiperidine pyridinepyridineppKKaa of conjugate acid: of conjugate acid:
11.211.2
ppKKaa of conjugate acid: of conjugate acid:
5.25.2
(an alkylamine)(an alkylamine)(resembles an(resembles anarylamine inarylamine in
basicity)basicity)
Dr. Wolf's CHM 201 & 202 21-41
Heterocyclic Amines Heterocyclic Amines NN••••
is more basic thanis more basic than
imidazoleimidazole pyridinepyridineppKKaa of conjugate acid: of conjugate acid:
7.07.0
ppKKaa of conjugate acid: of conjugate acid:
5.25.2
NN HHNN•••• ••••
Dr. Wolf's CHM 201 & 202 21-42
ImidazoleImidazole NN HHNN•••• ••••
Which nitrogen is protonated in imidazole?Which nitrogen is protonated in imidazole?
HH++ HH++ NN HHNN ••••HH
++
NN HHNN••••
HH
++
Dr. Wolf's CHM 201 & 202 21-43
ImidazoleImidazole NN HHNN•••• ••••
Protonation in the direction shown gives a Protonation in the direction shown gives a
stabilized ion.stabilized ion.
HH++ NN HHNNHH
++ ••••
NN HHNNHH
••••++
Dr. Wolf's CHM 201 & 202 21-44
Tetraalkylammonium SaltsTetraalkylammonium Salts
as Phase-Transfer Catalystsas Phase-Transfer Catalysts
Dr. Wolf's CHM 201 & 202 21-45
Phase-Transfer CatalysisPhase-Transfer Catalysis
Phase-transfer agents promote the solubility ofPhase-transfer agents promote the solubility ofionic substances in nonpolar solvents. Theyionic substances in nonpolar solvents. Theytransfer the ionic substance from an aqueoustransfer the ionic substance from an aqueousphase to a non-aqueous one.phase to a non-aqueous one.
Phase-transfer agents increase the rates ofPhase-transfer agents increase the rates ofreactions involving anions. The anion is relativelyreactions involving anions. The anion is relativelyunsolvated and very reactive in nonpolar mediaunsolvated and very reactive in nonpolar mediacompared to water or alcohols.compared to water or alcohols.
Dr. Wolf's CHM 201 & 202 21-46
Phase-Transfer CatalysisPhase-Transfer Catalysis
Quaternary ammonium salts are phase-transferQuaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.catalysts. They are soluble in nonpolar solvents.
NNHH33CC
CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH33
CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH33
CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH22CHCH33
++ClCl––
Methyltrioctylammonium chlorideMethyltrioctylammonium chloride
Dr. Wolf's CHM 201 & 202 21-47
Phase-Transfer CatalysisPhase-Transfer Catalysis
Quaternary ammonium salts are phase-transferQuaternary ammonium salts are phase-transfercatalysts. They are soluble in nonpolar solvents.catalysts. They are soluble in nonpolar solvents.
ClCl––
Benzyltriethylammonium chlorideBenzyltriethylammonium chloride
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
Dr. Wolf's CHM 201 & 202 21-48
ExampleExample
The SThe SNN2 reaction of sodium cyanide with butyl2 reaction of sodium cyanide with butyl
bromide occurs much faster when benzyl-bromide occurs much faster when benzyl-triethylammonium chloride is present than whentriethylammonium chloride is present than whenit is not.it is not.
CHCH33CHCH22CHCH22CHCH22BrBr ++ NaNaCNCN
CHCH33CHCH22CHCH22CHCH22CNCN ++ NaNaBrBr
benzyltriethylammonium chloridebenzyltriethylammonium chloride
Dr. Wolf's CHM 201 & 202 21-49
MechanismMechanismMechanismMechanism
ClCl––
(aqueous)(aqueous)
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
(aqueous)(aqueous)
CNCN––++
ClCl––NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
++CNCN––
(aqueous)(aqueous)
(aqueous)(aqueous)
Dr. Wolf's CHM 201 & 202 21-50
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
CNCN––
(aqueous)(aqueous)
(in butyl bromide)(in butyl bromide)
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
CNCN––
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 21-51
(in butyl bromide)(in butyl bromide)
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
CNCN––
MechanismMechanismMechanismMechanism
CHCH33CHCH22CHCH22CHCH22BrBr++
NN
CHCH22CHCH33
CHCH22CHCH33
CHCH22CHCH33
++
BrBr––
(in butyl bromide)(in butyl bromide)
CHCH33CHCH22CHCH22CHCH22CNCN++
Dr. Wolf's CHM 201 & 202 21-52
Reactions of Amines:Reactions of Amines:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 21-53
Preparation of AminesPreparation of Amines
Two questions to answer:Two questions to answer:
1) 1) How is the C—N bond to be formed?How is the C—N bond to be formed?
2) 2) How do we obtain the correct oxidation How do we obtain the correct oxidation
state of nitrogen (and carbon)?state of nitrogen (and carbon)?
Dr. Wolf's CHM 201 & 202 21-54
Methods for C—N Bond FormationMethods for C—N Bond Formation
Nucleophilic substitution by azide ion (NNucleophilic substitution by azide ion (N33––) (Section 8.1, 8.13)) (Section 8.1, 8.13)
Nitration of arenes (Section 12.3)Nitration of arenes (Section 12.3)
Nucleophilic ring opening of epoxides by ammonia (Section Nucleophilic ring opening of epoxides by ammonia (Section
16.12)16.12)
Nucleophilic addition of amines to aldehydes and ketones Nucleophilic addition of amines to aldehydes and ketones
(Sections 17.10, 17.11)(Sections 17.10, 17.11)
Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)Nucleophilic acyl substitution (Sections 19.4, 19.5, and 19.11)
Nucleophilic substitution by ammonia on Nucleophilic substitution by ammonia on -halo acids -halo acids
(Section 20.15)(Section 20.15)
Dr. Wolf's CHM 201 & 202 21-55
Preparation of AminesPreparation of Amines
by Alkylation of Ammoniaby Alkylation of Ammonia
Dr. Wolf's CHM 201 & 202 21-56
Alkylation of AmmoniaAlkylation of Ammonia
Desired reaction is:Desired reaction is:
2 2 NNHH33 ++ R—R—XX R—R—NNHH22 ++ NNHH44XX
via:via:
HH33NN •••••••• ••••RR XX••••
HH33NN RR++ •••• ••••XX
••••••••
––++ ++
then:then:
HH33NN •••• ++
HH NN
HH
HH
RR++ HH33NN HH
++++ NN
HH
HH
RR••••
Dr. Wolf's CHM 201 & 202 21-57
Alkylation of AmmoniaAlkylation of Ammonia
But the method doesn't work well in practice.But the method doesn't work well in practice.Usually gives a mixture of primary, secondary,Usually gives a mixture of primary, secondary,and tertiary amines, plus the quaternary salt. and tertiary amines, plus the quaternary salt.
NNHH33
RRXXRRNNHH22
RRXXRR22NNHH
RRXX
RR33NNRRXX
RR44NN++
XX––
Dr. Wolf's CHM 201 & 202 21-58
ExampleExample
CHCH33(CH(CH22))66CHCH22BrBrNHNH33
CHCH33(CH(CH22))66CHCH22NHNH22
(45%)(45%)
++
CHCH33(CH(CH22))66CHCH22NHNHCHCH22(CH(CH22))66CHCH33
(43%)(43%)As octylamine is formed, it competes with ammonia for As octylamine is formed, it competes with ammonia for
the remaining 1-bromooctane. Reaction of octylamine the remaining 1-bromooctane. Reaction of octylamine
with 1-bromooctane gives with 1-bromooctane gives NN,,NN-dioctylamine.-dioctylamine.
Dr. Wolf's CHM 201 & 202 21-59
The Gabriel Synthesis of The Gabriel Synthesis of
Primary AlkylaminesPrimary Alkylamines
Dr. Wolf's CHM 201 & 202 21-60
gives primary amines without formation ofgives primary amines without formation ofsecondary, etc. amines as byproductssecondary, etc. amines as byproducts
uses an Suses an SNN2 reaction on an alkyl halide to form2 reaction on an alkyl halide to form
the C—N bondthe C—N bond
the nitrogen-containing nucleophilethe nitrogen-containing nucleophileis is NN-potassiophthalimide-potassiophthalimide
Gabriel SynthesisGabriel Synthesis
Dr. Wolf's CHM 201 & 202 21-61
gives primary amines without formation ofgives primary amines without formation ofsecondary, etc. amines as byproductssecondary, etc. amines as byproducts
uses an Suses an SNN2 reaction on an alkyl halide to form2 reaction on an alkyl halide to form
the C—N bondthe C—N bond
the nitrogen-containing nucleophilethe nitrogen-containing nucleophileis is NN-potassiophthalimide-potassiophthalimide
Gabriel SynthesisGabriel Synthesis
OO
OO
NN•••• ••••––
KK++
Dr. Wolf's CHM 201 & 202 21-62
the pthe pKKa of phthalimide is 8.3a of phthalimide is 8.3
NN-potassiophthalimide is easily prepared by-potassiophthalimide is easily prepared bythe reaction of phthalimide with KOHthe reaction of phthalimide with KOH
N-PotassiophthalimideN-Potassiophthalimide OO
OO
NN•••• ••••––
KK++
OO
OO
NNHH••••
KOHKOH
Dr. Wolf's CHM 201 & 202 21-63
N-Potassiophthalimide as a nucleophileN-Potassiophthalimide as a nucleophile OO
OO
NN•••• ••••–– •••• ••••RR XX
••••++
OO
OO
NN RR••••
+ + •••• ••••XX••••
••••––
SSNN22
Dr. Wolf's CHM 201 & 202 21-64
Cleavage of Alkylated PhthalimideCleavage of Alkylated Phthalimide
OO
OO
NN RR•••• ++ HH22OO
HH22NN RR++
COCO22HH
COCO22HH
acid or baseacid or baseimide hydrolysis is imide hydrolysis is
nucleophilic acyl nucleophilic acyl
substitutionsubstitution
Dr. Wolf's CHM 201 & 202 21-65
Cleavage of Alkylated PhthalimideCleavage of Alkylated Phthalimide
hydrazinolysis is an alternative method of releasing the hydrazinolysis is an alternative method of releasing the
amine from its phthalimide derivativeamine from its phthalimide derivative
OO
OO
NN RR••••
HH22NN RR++
OO
OO
NHNH
NHNH
HH22NNHNNH22
Dr. Wolf's CHM 201 & 202 21-66
ExampleExample OO
OO
NN•••• ••••––
KK++ ++ CC66HH55CHCH22ClCl
DMFDMF
OO
OO
NN CHCH22CC66HH55
•••• (74%)(74%)
Dr. Wolf's CHM 201 & 202 21-67
ExampleExample
++ CC66HH55CHCH22NNHH22
OO
OO
NN CHCH22CC66HH55
••••
HH22NNHNNH22
(97%)(97%)
OO
OO
NHNH
NHNH
Dr. Wolf's CHM 201 & 202 21-68
Preparation of Amines by Preparation of Amines by
ReductionReduction
Dr. Wolf's CHM 201 & 202 21-69
almost any nitrogen-containing compound canalmost any nitrogen-containing compound canbe reduced to an amine, including:be reduced to an amine, including:
azidesazidesnitrilesnitrilesnitro-substituted benzene derivativesnitro-substituted benzene derivativesamidesamides
Preparation of Amines by ReductionPreparation of Amines by Reduction
Dr. Wolf's CHM 201 & 202 21-70
SSNN2 reaction, followed by reduction, gives a 2 reaction, followed by reduction, gives a
primary alkylamine.primary alkylamine.
Synthesis of Amines via AzidesSynthesis of Amines via Azides CHCH22CHCH22BrBr
CHCH22CHCH22NN33
NaNaNN33
(74%)(74%) CHCH22CHCH22NNHH22
(89%)(89%)
1. LiAlH1. LiAlH44
2. H2. H22OO
azides may also bereduced by catalytichydrogenation
Dr. Wolf's CHM 201 & 202 21-71
SSNN2 reaction, followed by reduction, gives a 2 reaction, followed by reduction, gives a
primary alkylamine.primary alkylamine.
Synthesis of Amines via NitrilesSynthesis of Amines via Nitriles
CHCH33CHCH22CHCH22CHCH22BrBrNaNaCCNN
(69%)(69%)
CHCH33CHCH22CHCH22CHCH22CCNN
CHCH33CHCH22CHCH22CHCH22CCHH22NNHH22
(56%)(56%)
HH22 (100 atm), Ni (100 atm), Ni
nitriles may also bereduced by lithiumaluminum hydride
Dr. Wolf's CHM 201 & 202 21-72
SSNN2 reaction, followed by reduction, gives a 2 reaction, followed by reduction, gives a
primary alkylamine.primary alkylamine.
Synthesis of Amines via NitrilesSynthesis of Amines via Nitriles
CHCH33CHCH22CHCH22CHCH22BrBrNaNaCCNN
(69%)(69%)
CHCH33CHCH22CHCH22CHCH22CCNN
CHCH33CHCH22CHCH22CHCH22CCHH22NNHH22
(56%)(56%)
HH22 (100 atm), Ni (100 atm), Ni
the reduction alsothe reduction alsoworks with cyanohydrinsworks with cyanohydrins
Dr. Wolf's CHM 201 & 202 21-73
Synthesis of Amines via NitroarenesSynthesis of Amines via Nitroarenes
HHNNOO33
(88-95%)(88-95%)
ClCl
ClCl NNOO22
HH22SOSO44
(95%)(95%)
1. Fe, HCl1. Fe, HCl
2. NaOH2. NaOH ClCl NNHH22
nitro groups may alsobe reduced with tin (Sn)+ HCl or by catalytichydrogenation
Dr. Wolf's CHM 201 & 202 21-74
Synthesis of Amines via AmidesSynthesis of Amines via Amides
(86-89%)(86-89%)
COHCOH
OO1. SOCl1. SOCl22
2. (CH2. (CH33))22NNHH
CCNN(CH(CH33))22
OO
(88%)(88%)
1. LiAlH1. LiAlH44
2. H2. H22OO CHCH22NN(CH(CH33))22
only LiAlH4 is an
appropriate reducingagent for this reaction
Dr. Wolf's CHM 201 & 202 21-75
Reductive AminationReductive Amination
Dr. Wolf's CHM 201 & 202 21-76
The aldehyde or ketone equilibrates with theThe aldehyde or ketone equilibrates with theimine faster than imine faster than hydrogenationhydrogenation occurs. occurs.
Synthesis of Amines via Reductive AminationSynthesis of Amines via Reductive Amination
OOCC
RR
R'R'
++ NNHH33
fastfast
NNHHCC
RR
R'R'
++ HH22OO
In reductive amination, an aldehyde or ketoneIn reductive amination, an aldehyde or ketoneis subjected to catalytic hydrogenation in theis subjected to catalytic hydrogenation in thepresence of ammonia or an amine.presence of ammonia or an amine.
Dr. Wolf's CHM 201 & 202 21-77
Synthesis of Amines via Reductive AminationSynthesis of Amines via Reductive Amination
OOCC
RR
R'R'
++ NNHH33
fastfast
NNHHCC
RR
R'R'
++ HH22OO
HH22, Ni, Ni
NNHH22
RR
R'R' CC
HH
The imine undergoes hydrogenation fasterThe imine undergoes hydrogenation fasterthan the aldehyde or ketone. An amine is than the aldehyde or ketone. An amine is the product.the product.
Dr. Wolf's CHM 201 & 202 21-78
Example: Ammonia gives a primary amine.Example: Ammonia gives a primary amine. OO ++ NNHH33
HH
NNHH22
HH22, Ni, Ni
ethanolethanol
(80%)(80%)
via:via:
NNHH
Dr. Wolf's CHM 201 & 202 21-79
Example: Primary amines give secondary aminesExample: Primary amines give secondary amines
HH22, Ni, Ni ethanolethanol
(65%)(65%)
CHCH33(CH(CH22))55CHCH22NNHH
++ HH22NN
CHCH33(CH(CH22))55CHCH
OO
via:via: NN
CHCH33(CH(CH22))55CHCH
Dr. Wolf's CHM 201 & 202 21-80
Example: Secondary amines give tertiary aminesExample: Secondary amines give tertiary amines
HH22, Ni, ethanol, Ni, ethanol
(93%)(93%)
++CHCH33CHCH22CHCH22CHCH
OO
NN
HH NN
CHCH22CHCH22CHCH22CHCH33
Dr. Wolf's CHM 201 & 202 21-81
Example: Secondary amines give tertiary aminesExample: Secondary amines give tertiary amines
CHCHCHCH22CHCH22CHCH33
NN++
possible intermediates include:possible intermediates include: NN
CHCH CHCHCHCH22CHCH33
CHCHCHCH22CHCH22CHCH33
NN
HOHO
Dr. Wolf's CHM 201 & 202 21-82
Reactions of Amines:Reactions of Amines:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 21-83
Reactions of AminesReactions of Amines
Reactions of amines almost always involve theReactions of amines almost always involve thenitrogen lone pair.nitrogen lone pair.
••••NN HH XX
as a base:as a base:
••••NN
CC OOas a nucleophile:as a nucleophile:
Dr. Wolf's CHM 201 & 202 21-84
Reactions of AminesReactions of Amines
basicity (Section 21.4)basicity (Section 21.4)
reaction with aldehydes and ketones (Chapter 17)reaction with aldehydes and ketones (Chapter 17)
reaction with acyl chlorides, reaction with acyl chlorides, anhydrides, and estersanhydrides, and esters
Reactions already discussedReactions already discussed
Dr. Wolf's CHM 201 & 202 21-85
Reactions of Amines with Alkyl Reactions of Amines with Alkyl
HalidesHalides
Dr. Wolf's CHM 201 & 202 21-86
Reaction with Alkyl HalidesReaction with Alkyl Halides
Amines act as nucleophiles toward alkyl halides.Amines act as nucleophiles toward alkyl halides.
•••• XX++ ••••••••
••••
••••NN RR
HH
++ XX ••••••••
••••NN RR
HH
++ ––
++NN RR••••
HH++
Dr. Wolf's CHM 201 & 202 21-87
Example: excess amineExample: excess amine NNHH22 ++ ClClCHCH22
NNHCHHCH22
(85-87%)(85-87%)
NaHCONaHCO33 90°C90°C
(4 mol)(4 mol) (1 mol)(1 mol)
Dr. Wolf's CHM 201 & 202 21-88
Example: excess alkyl halideExample: excess alkyl halide
++ 3CH3CH33II
(99%)(99%)
methanolmethanol heatheat
CHCH22NN (CH (CH33))33
CHCH22NNHH22
++
II––
Dr. Wolf's CHM 201 & 202 21-89
The Hofmann EliminationThe Hofmann Elimination
Dr. Wolf's CHM 201 & 202 21-90
The Hofmann EliminationThe Hofmann Elimination
a quaternary ammonium hydroxide is the reactanta quaternary ammonium hydroxide is the reactantand an alkene is the productand an alkene is the product
is an anti eliminationis an anti elimination
the leaving group is a trialkylaminethe leaving group is a trialkylamine
the regioselectivity is opposite to the Zaitsev rule.the regioselectivity is opposite to the Zaitsev rule.
Dr. Wolf's CHM 201 & 202 21-91
Quaternary Ammonium HydroxidesQuaternary Ammonium Hydroxides
AgAg22OO HH22O, CHO, CH33OHOH
CHCH22N N (CH(CH33))33
++
HOHO––
are prepared by treating quaternary ammmoniumare prepared by treating quaternary ammmoniumhalides with moist silver oxidehalides with moist silver oxide
CHCH22NN (CH (CH33))33
II––
Dr. Wolf's CHM 201 & 202 21-92
The Hofmann EliminationThe Hofmann Elimination
160°C160°C
CHCH22NN (CH (CH33))33
++
HOHO––
on being heated, quaternary ammonium on being heated, quaternary ammonium hydroxides undergo eliminationhydroxides undergo elimination
CHCH22
(69%)(69%)
++ NN(CH(CH33))33 ++ HH22OO
Dr. Wolf's CHM 201 & 202 21-93
MechanismMechanismMechanismMechanism HH
CCHH22
++NN(CH(CH33))33
––OO•••••••• HH••••
OO••••
HH••••
HH
NN(CH(CH33))33••••
CCHH22
Dr. Wolf's CHM 201 & 202 21-94
RegioselectivityRegioselectivity
heatheat
Elimination occurs in the direction that gives Elimination occurs in the direction that gives the less-substituted double bond. This is called the less-substituted double bond. This is called the the Hofmann rule.Hofmann rule.
NN(CH(CH33))33++
HOHO––
CHCH33CHCHCHCH22CHCH33HH22CC CHCHCHCH22CHCH33
CHCH33CHCH CHCHCHCH33
++
(95%)(95%)
(5%)(5%)
Dr. Wolf's CHM 201 & 202 21-95
RegioselectivityRegioselectivity
Steric factors seem to control the regioselectivity.Steric factors seem to control the regioselectivity.The transition state that leads to 1-butene isThe transition state that leads to 1-butene isless crowded than the one leading to cisless crowded than the one leading to cisor trans-2-butene.or trans-2-butene.
Dr. Wolf's CHM 201 & 202 21-96
RegioselectivityRegioselectivity
NN(CH(CH33))33++
HH
HH
HH HH
CHCH33CHCH22
largest group is between two H atomslargest group is between two H atoms
CC
HHCC
HHHH
CHCH33CHCH22
major productmajor product
Dr. Wolf's CHM 201 & 202 21-97
RegioselectivityRegioselectivity
NN(CH(CH33))33++
HH
HH
HH
CHCH33
largest group is between anlargest group is between anH atom and a methyl groupH atom and a methyl group
CC
HHCC
CHCH33 HH
CHCH33
minor productminor product
CHCH33
Dr. Wolf's CHM 201 & 202 21-98
Electrophilic Aromatic Electrophilic Aromatic
SubstitutionSubstitution
in Arylaminesin Arylamines
Dr. Wolf's CHM 201 & 202 21-99
Nitration of AnililneNitration of Anililne
NHNH22 is a very strongly activating group is a very strongly activating group
NHNH22 not only activates the ring toward not only activates the ring toward
electrophilic aromatic substitution, it also electrophilic aromatic substitution, it also makes it more easily oxidizedmakes it more easily oxidized
attemped nitration of aniline fails because attemped nitration of aniline fails because nitric acid oxidizes aniline to a black tarnitric acid oxidizes aniline to a black tar
Dr. Wolf's CHM 201 & 202 21-100
Nitration of AnililneNitration of Anililne
Strategy: decrease the reactivity of aniline by Strategy: decrease the reactivity of aniline by
converting the NHconverting the NH22 group to an amide group to an amide CH(CHCH(CH33))22
NNHH22 CH(CHCH(CH33))22
NNHCCHHCCH33
OO
OO
CHCH33COCCHCOCCH33
OO
(98%)(98%)
(acetyl chloride may be used instead of acetic anhydride)(acetyl chloride may be used instead of acetic anhydride)
Dr. Wolf's CHM 201 & 202 21-101
Nitration of AnililneNitration of Anililne
Strategy: nitrate the amide formed in the first Strategy: nitrate the amide formed in the first
stepstep CH(CHCH(CH33))22
NNHCCHHCCH33
OO
HNOHNO33
CH(CHCH(CH33))22
NNHCCHHCCH33
OO NONO22
(94%)(94%)
Dr. Wolf's CHM 201 & 202 21-102
Nitration of AnililneNitration of Anililne
Strategy: remove the acyl group from the amide Strategy: remove the acyl group from the amide
by hydrolysisby hydrolysis
CH(CHCH(CH33))22
NNHCCHHCCH33
OO NONO22
KOHKOH
ethanol,ethanol,heatheat
CH(CHCH(CH33))22
NNHH22 NONO22
(100%)(100%)
Dr. Wolf's CHM 201 & 202 21-103
occurs readily without necessity of protecting occurs readily without necessity of protecting
amino group, but difficult to limit it to amino group, but difficult to limit it to
monohalogenationmonohalogenation
Halogenation of ArylaminesHalogenation of Arylamines COCO22HH
NNHH22
BrBr22
acetic acidacetic acid
(82%)(82%)
COCO22HH
NNHH22
BrBr BrBr
Dr. Wolf's CHM 201 & 202 21-104
Monohalogenation of ArylaminesMonohalogenation of Arylamines
ClCl
NNHCCHHCCH33
OO CHCH33
(74%)(74%)
ClCl22
acetic acidacetic acid
NNHCCHHCCH33
OO
CHCH33
Decreasing the reactivity of the arylamine by converting Decreasing the reactivity of the arylamine by converting
the NHthe NH22 group to an amide allows halogenation to be group to an amide allows halogenation to be
limited to monosubstitutionlimited to monosubstitution
Dr. Wolf's CHM 201 & 202 21-105
Friedel-Crafts ReactionsFriedel-Crafts Reactions
The amino group of an arylamine must be protected The amino group of an arylamine must be protected
as an amide when carrying out a Friedel-Crafts as an amide when carrying out a Friedel-Crafts
reaction.reaction. NNHCCHHCCH33
OO
CHCH33 CHCH33CClCCl
OO
AlClAlCl33
(57%)(57%)
NNHCCHHCCH33
OO CHCH33
CCHCCH33OO
Dr. Wolf's CHM 201 & 202 21-106
Nitrosation of AlkylaminesNitrosation of Alkylamines
Dr. Wolf's CHM 201 & 202 21-107
Nitrite Ion, Nitrous Acid, and Nitrosyl CationNitrite Ion, Nitrous Acid, and Nitrosyl Cation
HH++
––OO••••••••
••••NN OO
•••• ••••••••
OO•••• ••••
NN OO•••• ••••
••••HH
HH++
OO••••NN OO
•••• ••••
HH
HH
++••••++
••••NN OO
•••• ••••++OO ••••
HH
HH
••••
Dr. Wolf's CHM 201 & 202 21-108
Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation
++••••NN OO
•••• ••••
Dr. Wolf's CHM 201 & 202 21-109
Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation
++••••NN OO
•••• ••••++••••NN
NN••••NN OO
•••• ••••++
Dr. Wolf's CHM 201 & 202 21-110
Nitrosation of Secondary AlkylaminesNitrosation of Secondary Alkylamines
++••••NN OO
•••• ••••••••NN
HH
++
NN••••NN OO
•••• ••••++
HH++
HH
++
NN••••NN OO
•••• •••••••• nitrosation of secondary nitrosation of secondary
amines gives an amines gives an NN--
nitroso aminenitroso amine
Dr. Wolf's CHM 201 & 202 21-111
ExampleExample
(CH(CH33))22NNHH•••• NaNONaNO22, HCl, HCl
HH22OO(88-90%)(88-90%)
••••(CH(CH33))22NN
••••NN OO
•••• ••••
Dr. Wolf's CHM 201 & 202 21-112
Some N-Nitroso AminesSome N-Nitroso Amines
NN-nitrosopyrrolidine-nitrosopyrrolidine(nitrite-cured bacon)(nitrite-cured bacon)
NN
NNOO
NN-nitrosonornicotine-nitrosonornicotine(tobacco smoke)(tobacco smoke)
NN
NNOONN
(CH(CH33))22NN NN OONN-nitrosodimethylamine-nitrosodimethylamine
(leather tanning)(leather tanning)
Dr. Wolf's CHM 201 & 202 21-113
Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines
++ analogous to analogous to
nitrosation of nitrosation of
secondary amines to secondary amines to
this pointthis point
++••••NN OO
•••• ••••••••NN
HH
HHRR
NN••••NN OO
•••• ••••++
HH
HHRR
++HH
++
NN••••NN OO
•••• ••••••••
RR
HH
Dr. Wolf's CHM 201 & 202 21-114
Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines
NN••••NN OO
•••• ••••••••
RR
HH
HH++
NN••••NN OO
••••••••
RR
HH HH
++
this species reacts furtherthis species reacts further
••••NN
••••NN OO
••••••••
RR
HHHH
++
++
HHHH
++••••NN
••••NN OO••••
RR
HH
Dr. Wolf's CHM 201 & 202 21-115
Nitrosation of Primary AlkylaminesNitrosation of Primary Alkylamines
++
HH
••••NN••••NN OO••••
RR
HH
++NN NN ••••RR
HH
••••OO
HH
••••++nitrosation of a nitrosation of a
primary alkylamine primary alkylamine
gives an alkyl gives an alkyl
diazonium iondiazonium ion
process is called process is called
diazotizationdiazotization
Dr. Wolf's CHM 201 & 202 21-116
Alkyl Diazonium Ions Alkyl Diazonium Ions
++NN NN ••••RR
alkyl diazonium ions alkyl diazonium ions
readily lose Nreadily lose N22 to to
give carbocationsgive carbocations
RR++ ++ NN NN ••••••••
Dr. Wolf's CHM 201 & 202 21-117
Example: Nitrosation of 1,1-DimethylpropylamineExample: Nitrosation of 1,1-Dimethylpropylamine NNHH22
NN NN++
HONOHONO
HH22OO
OOHH
(80%)(80%) ++
(2%)(2%)(3%)(3%)
++
– – NN22
Dr. Wolf's CHM 201 & 202 21-118
There is no useful chemistry associated with the There is no useful chemistry associated with the nitrosation of tertiary alkylamines.nitrosation of tertiary alkylamines.
Nitrosation of Tertiary Alkylamines Nitrosation of Tertiary Alkylamines
••••NNRR
RR
RR
NN••••NN OO
•••• ••••++RR
RR
RR
Dr. Wolf's CHM 201 & 202 21-119
Nitrosation of ArylaminesNitrosation of Arylamines
Dr. Wolf's CHM 201 & 202 21-120
reaction that occurs is reaction that occurs is electrophilic aromatic substitutionelectrophilic aromatic substitution
Nitrosation of Tertiary ArylaminesNitrosation of Tertiary Arylamines NN(CH(CH22CHCH33))22
(95%)(95%)
1. NaNO1. NaNO22, HCl,, HCl,
H H22O, 8°CO, 8°C
2. HO2. HO––
NN(CH(CH22CHCH33))22
NNOO
Dr. Wolf's CHM 201 & 202 21-121
similar to secondary alkylamines;similar to secondary alkylamines;
gives gives NN-nitroso amines-nitroso amines
Nitrosation of N-AlkylarylaminesNitrosation of N-Alkylarylamines
NaNONaNO22, HCl,, HCl,
HH22O, 10°CO, 10°C
NNHCHHCH33
(87-93%)(87-93%)
NNCHCH33
NN OO
Dr. Wolf's CHM 201 & 202 21-122
Nitrosation of Primary Nitrosation of Primary ArylaminesArylamines
gives aryl diazonium ionsgives aryl diazonium ions
aryl diazonium ions are much more stable thanaryl diazonium ions are much more stable than
alkyl diazonium ionsalkyl diazonium ions
most aryl diazonium ions are stable under the most aryl diazonium ions are stable under the
conditions of their formation (0-10°C) conditions of their formation (0-10°C)
ArArNN NN++
RRNN NN++ fastfast
slowslow
RR++ ++ NN22
ArAr++ ++ NN22
Dr. Wolf's CHM 201 & 202 21-123
Example:Example: (CH(CH33))22CHCH NNHH22
NaNONaNO22, H, H22SOSO44
HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH NN NN
++HSOHSO44
––
Dr. Wolf's CHM 201 & 202 21-124
Synthetic Origin of Aryl Diazonium SaltsSynthetic Origin of Aryl Diazonium Salts
ArAr HH
ArAr NNOO22
ArAr NNHH22
ArAr NN NN++
Dr. Wolf's CHM 201 & 202 21-125
Synthetic TransformationsSynthetic Transformations
of Aryl Diazonium Saltsof Aryl Diazonium Salts
Dr. Wolf's CHM 201 & 202 21-126
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-127
Preparation of PhenolsPreparation of Phenols
ArAr NN NN++
ArAr OOHH
HH22OO, heat, heat
Dr. Wolf's CHM 201 & 202 21-128
ExampleExample
2. H2. H22O, heatO, heat
(CH(CH33))22CHCH NNHH22
1. NaNO1. NaNO22, H, H22SOSO44
HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH OOHH
(73%)(73%)
Dr. Wolf's CHM 201 & 202 21-129
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-130
Preparation of Aryl IodidesPreparation of Aryl Iodides
ArAr NN NN++
ArAr II
reaction of an aryl diazonium salt with reaction of an aryl diazonium salt with
potassium iodidepotassium iodide
KKII
Dr. Wolf's CHM 201 & 202 21-131
ExampleExample
2. K2. KII, room temp., room temp.
1. NaNO1. NaNO22, HCl, HCl
HH22O, 0-5°CO, 0-5°C
(72-83%)(72-83%)
NNHH22
BrBr
II BrBr
Dr. Wolf's CHM 201 & 202 21-132
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-133
Preparation of Aryl FluoridesPreparation of Aryl Fluorides
ArAr NN NN++
ArAr FF
heat the tetrafluoroborate salt of a diazonium ion;heat the tetrafluoroborate salt of a diazonium ion;
process is called the Schiemann reactionprocess is called the Schiemann reaction
Dr. Wolf's CHM 201 & 202 21-134
ExampleExample
(68%)(68%)
NNHH22 CCHCCH22CHCH33
OO
2. HBF2. HBF44
1. NaNO1. NaNO22, HCl,, HCl,
HH22O, 0-5°CO, 0-5°C
3. heat3. heat
FF CCHCCH22CHCH33
OO
Dr. Wolf's CHM 201 & 202 21-135
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-136
Preparation of Aryl Chlorides and Preparation of Aryl Chlorides and BromidesBromides
ArAr NN NN++
ArAr BrBrArAr ClCl
aryl chlorides and aryl bromides are prepared by heating aryl chlorides and aryl bromides are prepared by heating
a diazonium salt with copper(I) chloride or bromidea diazonium salt with copper(I) chloride or bromide
substitutions of diazonium salts that use copper(I) substitutions of diazonium salts that use copper(I)
halides are called halides are called SandmeyerSandmeyer reactionsreactions
Dr. Wolf's CHM 201 & 202 21-137
ExampleExample
(68-71%)(68-71%)
NNHH22 NONO22
2. Cu2. CuClCl, heat, heat
1. NaNO1. NaNO22, HCl,, HCl,
HH22O, 0-5°CO, 0-5°C
ClCl NONO22
Dr. Wolf's CHM 201 & 202 21-138
ExampleExample
(89-95%)(89-95%)
2. Cu2. CuBrBr, heat, heat
1. NaNO1. NaNO22, HBr,, HBr,
HH22O, 0-10°CO, 0-10°CNNHH22
ClCl
BrBr ClCl
Dr. Wolf's CHM 201 & 202 21-139
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-140
Preparation of Aryl NitrilesPreparation of Aryl Nitriles
ArAr NN NN++
ArAr CNCN
aryl nitriles are prepared by heating a diazonium aryl nitriles are prepared by heating a diazonium
salt with copper(I) cyanidesalt with copper(I) cyanide
this is another type of Sandmeyer reactionthis is another type of Sandmeyer reaction
Dr. Wolf's CHM 201 & 202 21-141
ExampleExample
(64-70%)(64-70%)
2. CuCN, heat2. CuCN, heat
1. NaNO1. NaNO22, HCl,, HCl,
HH22O, 0°CO, 0°CNNHH22
CHCH33
CNCN CHCH33
Dr. Wolf's CHM 201 & 202 21-142
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
ArAr OOHH
ArAr II
ArAr FF
ArAr BrBrArAr ClCl
ArAr CNCN
Dr. Wolf's CHM 201 & 202 21-143
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
ArAr NN NN++
ArAr HH
hypophosphorous acid (Hhypophosphorous acid (H33POPO22) reduces diazonium ) reduces diazonium
salts; ethanol does the same thingsalts; ethanol does the same thing
this is called this is called reductive deaminationreductive deamination
Dr. Wolf's CHM 201 & 202 21-144
ExampleExample
(70-75%)(70-75%)
NaNONaNO22, H, H22SOSO44,,
HH33POPO22
NNHH22
CHCH33 CHCH33
Dr. Wolf's CHM 201 & 202 21-145
Value of Diazonium SaltsValue of Diazonium Salts
1) 1) allows introduction of substituents such as OH, F, allows introduction of substituents such as OH, F,
I, and CN on the ringI, and CN on the ring
2) 2) allows preparation of otherwise difficultly allows preparation of otherwise difficultly
accessible substitution patternsaccessible substitution patterns
Dr. Wolf's CHM 201 & 202 21-146
ExampleExample BrBr
BrBrBrBr
NNHH22
BrBr
BrBr
BrBr
(74-77%)(74-77%)
NaNONaNO22, H, H22SOSO44,,
HH22O, CHO, CH33CHCH22OHOH
NNHH22 BrBr22
HH22OO
(100%)(100%)
Dr. Wolf's CHM 201 & 202 21-147
Azo CouplingAzo Coupling
Dr. Wolf's CHM 201 & 202 21-148
Azo CouplingAzo Coupling
Diazonium salts are weak electrophiles.Diazonium salts are weak electrophiles.
React with strongly activated aromatic compounds React with strongly activated aromatic compounds
by electrophilic aromatic substitution.by electrophilic aromatic substitution.
ArAr NN NN++
Ar'Ar' HH++ ArAr NN NN Ar'Ar'
an azo compoundan azo compound
Ar'Ar' must bear a strongly electron-releasing group must bear a strongly electron-releasing group such as OH, OR, or NR such as OH, OR, or NR22..
Dr. Wolf's CHM 201 & 202 21-149
ExampleExample OHOH
++ CC66HH55NN NN++ OHOH
NN NCNC66HH55
ClCl––
Dr. Wolf's CHM 201 & 202 21-150
Spectroscopic Analysis of AminesSpectroscopic Analysis of Amines
Dr. Wolf's CHM 201 & 202 21-151
the N—H stretching band appears in the rangethe N—H stretching band appears in the range3000-3500 cm3000-3500 cm-1-1
primary amines give two peaks in this region, oneprimary amines give two peaks in this region, onefor a symmetrical stretching vibration, the other forfor a symmetrical stretching vibration, the other foran antisymmetrical stretchan antisymmetrical stretch
Infrared SpectroscopyInfrared Spectroscopy
RR NN
HH
HH
symmetricsymmetric
RR NN
HH
HH
antisymmetricantisymmetric
Dr. Wolf's CHM 201 & 202 21-152
Infrared SpectroscopyInfrared Spectroscopy
RNHRNH22 RR22NHNH
primary amines give two N—H stretching peaks, primary amines give two N—H stretching peaks,
secondary amines give onesecondary amines give one
Dr. Wolf's CHM 201 & 202 21-153
compare chemical shifts in:compare chemical shifts in:
11H NMRH NMR HH33CC CHCH22NNHH22
HH33CC CHCH22OOHH
NN CC HH is more shielded than is more shielded than
3.9 ppm3.9 ppm 4.7 ppm4.7 ppm
OO CC HH
Dr. Wolf's CHM 201 & 202 21-154
1313C NMRC NMR
Carbons bonded to N are more shielded than Carbons bonded to N are more shielded than
those bonded to O.those bonded to O.
CHCH33NNHH22 CHCH33OOHH
26.9 ppm26.9 ppm 48.0 ppm48.0 ppm
Dr. Wolf's CHM 201 & 202 21-155
maxmax
204 nm204 nm256 nm256 nm
maxmax
230 nm230 nm280 nm280 nm
maxmax
203 nm203 nm254 nm254 nm
An amino group on a benzene ring shifts An amino group on a benzene ring shifts maxmax
to longer wavelength. Protonation of N causesto longer wavelength. Protonation of N causesUV spectrum to resemble that of benzene.UV spectrum to resemble that of benzene.
UV-VISUV-VIS NHNH22
NHNH33
++
Dr. Wolf's CHM 201 & 202 21-156
Mass SpectrometryMass Spectrometry
Compounds that contain only C, H, and O have Compounds that contain only C, H, and O have
even molecular weights. If an odd number of N even molecular weights. If an odd number of N
atoms is present, the molecular weight is odd.atoms is present, the molecular weight is odd.
A molecular-ion peak with an odd A molecular-ion peak with an odd mm//zz value value
suggests that the sample being analyzed contains suggests that the sample being analyzed contains
N.N.
Dr. Wolf's CHM 201 & 202 21-157
Mass SpectrometryMass Spectrometry
Nitrogen stabilizes Nitrogen stabilizes
carbocations, which carbocations, which
drives the fragmentation drives the fragmentation
pathways.pathways.
(CH(CH33))22NCHNCH22CHCH22CHCH22CHCH33••••
ee––
(CH(CH33))22NCHNCH22CHCH22CHCH22CHCH33
••++
••CHCH22CHCH22CHCH33++(CH(CH33))22NN CHCH22
++
Dr. Wolf's CHM 201 & 202 21-158
Mass SpectrometryMass Spectrometry
Nitrogen stabilizes Nitrogen stabilizes
carbocations, which carbocations, which
drives the fragmentation drives the fragmentation
pathways.pathways.
CHCH33NHCHNHCH22CHCH22CH(CHCH(CH33))22••••
ee––
CHCH33NHCHNHCH22CHCH22CH(CHCH(CH33))22
••++
••CHCH22CH(CHCH(CH33))22++CHCH33NHNH CHCH22
++
Dr. Wolf's CHM 201 & 202 21-159
End of Chapter 21End of Chapter 21