Transcript
General
Organic ChemistryTwo credits
Second Semester 2009
King Saud bin Abdulaziz University for Health Science
Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. CareyThird Edition
Instructor: Rabih O. Al-Kaysi, PhD.
Chapter 14Chapter 14
AminesAmines
Lecture 23
Preparation of Amines by Preparation of Amines by
ReductionReduction
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
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
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
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
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
Reductive AminationReductive Amination
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.
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
Reactions of Amines:Reactions of Amines:
A Review and a PreviewA Review and a Preview
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:
Reactions of AminesReactions of Amines
basicity basicity
reaction with aldehydes and ketones reaction with aldehydes and ketones
reaction with acyl chlorides reaction with acyl chlorides
Reactions already discussedReactions already discussed
Reactions of Amines with Alkyl Reactions of Amines with Alkyl
HalidesHalides
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++
Example: excess amineExample: excess amine NNHH22 ++ ClClCHCH22
NNHCHHCH22
(85-87%)(85-87%)
NaHCONaHCO33 90°C90°C
(4 mol)(4 mol) (1 mol)(1 mol)
Nitrosation of AlkylaminesNitrosation of Alkylamines
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
••••
Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation
++••••NN OO
•••• ••••
Nitrosyl Cation and NitrosationNitrosyl Cation and Nitrosation
++••••NN OO
•••• ••••++••••NN
NN••••NN OO
•••• ••••++
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
ExampleExample
(CH(CH33))22NNHH•••• NaNONaNO22, HCl, HCl
HH22OO(88-90%)(88-90%)
••••(CH(CH33))22NN
••••NN OO
•••• ••••
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)
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
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
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
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 ••••••••
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
Nitrosation of ArylaminesNitrosation of Arylamines
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
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
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
Example:Example: (CH(CH33))22CHCH NNHH22
NaNONaNO22, H, H22SOSO44
HH22O, 0-5°CO, 0-5°C (CH(CH33))22CHCH NN NN
++HSOHSO44
––
Synthetic Origin of Aryl Diazonium SaltsSynthetic Origin of Aryl Diazonium Salts
ArAr HH
ArAr NNOO22
ArAr NNHH22
ArAr NN NN++
Synthetic TransformationsSynthetic Transformations
of Aryl Diazonium Saltsof Aryl Diazonium Salts
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
Preparation of PhenolsPreparation of Phenols
ArAr NN NN++
ArAr OOHH
HH22OO, heat, heat
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%)
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
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
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
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
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
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
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
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
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
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
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
ExampleExample
(64-70%)(64-70%)
2. CuCN, heat2. CuCN, heat
1. NaNO1. NaNO22, HCl,, HCl,
HH22O, 0°CO, 0°CNNHH22
CHCH33
CNCN CHCH33
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
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
ExampleExample
(70-75%)(70-75%)
NaNONaNO22, H, H22SOSO44,,
HH33POPO22
NNHH22
CHCH33 CHCH33
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
ExampleExample BrBr
BrBrBrBr
NNHH22
BrBr
BrBr
BrBr
(74-77%)(74-77%)
NaNONaNO22, H, H22SOSO44,,
HH22O, CHO, CH33CHCH22OHOH
NNHH22 BrBr22
HH22OO
(100%)(100%)
Azo CouplingAzo Coupling
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..
ExampleExample OHOH
++ CC66HH55NN NN++ OHOH
NN NCNC66HH55
ClCl––
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