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11-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Introduction to Introduction to Organic Organic
ChemistryChemistry2 ed2 ed
William H. BrownWilliam H. Brown
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11-2Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Aldehydes Aldehydes & &
KetonesKetones
Chapter 15
Chapter 11Chapter 11
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11-3Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
The Carbonyl GroupThe Carbonyl Group• In this and three following chapters we study the
physical and chemical properties of classes of compounds containing the carbonyl group, C=O• aldehydes and ketones (Chapter 11)• carboxylic acids (Chapter 12)• carboxyl derivatives (Chapter 13)• enolate anions (Chapter 14)
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11-4Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
The Carbonyl GroupThe Carbonyl Group• Consists of
• one sigma bond formed by overlap of sp2 hybrid orbitals
• one pi bond formed by overlap of parallel 2p orbitals
C Oσ
electron pairs in
sp2 hybrid orbitals
π
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11-5Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Structure of AldehydesStructure of Aldehydes• The functional group of an aldehyde is a carbonyl
group bonded to a H atom • in methanal, it is bonded to two H atoms• in all other aldehydes, it is bonded to one H and one
carbon atom
H
C
H
O
H3C
C
H
O
Methanal(formaldehyde)
Ethanal(acetaldehyde)
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11-6Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Structure of KetonesStructure of Ketones• The functional group of a ketone is a carbonyl
groups bonded to two carbon atoms
CH3-C-CH3
O O
Propanone(Acetone)
Cyclohexanone
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11-7Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Nomenclature - AldehydesNomenclature - Aldehydes• IUPAC namesIUPAC names: select as the parent alkane the
longest chain of carbon atoms that contains the carbonyl group• because the carbonyl group of the aldehyde must be
on carbon 1, there is no need to give it a number
• For unsaturated aldehydes, show the presence of the C=C by changing the infix -anan- to -enen- • the location of the suffix determines the numbering
pattern
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11-8Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Nomenclature - AldehydesNomenclature - Aldehydes
3-Methylbutanal
2-Propenal(Acrolein)
O
O
CH3CHCH2CH
CH2=CHCH H
O
(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)
1
2
3
4
5
6
7
8
1
1
2
2
3
34O
CH3CH2CH2CH2 CHPentanal
12345CH3
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11-9Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Nomenclature - AldehydesNomenclature - Aldehydes• For cyclic molecules in which the -CHO group is
attached to the ring, the name is derived by adding the suffix -carbaldehydecarbaldehyde to the name of the ring
2-Cyclopentene- carbaldehyde
2,2-Dimethylcyclo-hexanecarbaldehyde
CHO
CH3CH3
CHO
3
1
122
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11-10Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Nomenclature - KetonesNomenclature - Ketones• IUPAC names:
• select as the parent alkane the longest chain that contains the carbonyl group,
• changing the suffix -ee to -oneone • number to give C=O the smaller number
5-Methyl-3-hexanonePropanone (Acetone)
O O
CH3CCH3 CH3CH2CCH2CHCH31 2 3 4 5 6
CH3 CH3
O
2-Methylcyclo-hexanone
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11-11Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Nomenclature - KetonesNomenclature - Ketones• The IUPAC system retains these names
BenzophenoneAcetophenone
CCH3
OO
C-CH3CCH3
O
Acetone
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11-12Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Order of PrecedenceOrder of Precedence• For compounds that contain more than one
functional group indicated by a suffix
mercapto-amino-
oxo-
hydroxy-
oxo-
-thiol-amine-ol
-one
-al-oic acid
Prefix if Lowerin Precedence
Suffix if Higherin Precedence
FunctionalGroup
C=O
-CHO
-CO2H
-OH-NH2-SH
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11-13Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Physical PropertiesPhysical Properties• Oxygen is more electronegative than carbon (3.5
vs 2.5) and, therefore, a C=O group is polar
• aldehydes and ketones have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight
δ-δ+C O
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11-14Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Reaction ThemeReaction Theme• One of the most common reaction themes of the
carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound
Tetrahedral carbonyl addition compound
+ CR
RO CNu
OH
RR
H-Nu
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11-15Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Add’n of C NucleophilesAdd’n of C Nucleophiles• Addition of carbon nucleophiles is one of the
most important types of nucleophilic additions to a C=O group • a new carbon-carbon bond is formed in the process
• We study addition of carbon nucleophiles called Grignard reagents• Victor Grignard was awarded the Nobel Prize for
Chemistry in 1912 for their discovery and application to organic synthesis
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11-16Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• Magnesium metal reacts with alkyl and aryl
halides to give organomagnesium halides
+
1-Chlorobutane
Butylmagnesium chloride
ether
CH
3
CH
2
CH
2
CH
2
Cl
Mg
CH
3
CH
2
CH
2
CH
2
MgCl
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11-17Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• Given the difference in electronegativity between
carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Cδ and Mgδ
• a Grignard reagent behaves as a carbanion and as a nucleophile
• CarbanionCarbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge
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11-18Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• Grignard reagents are very strong bases and
react with a variety of acids to give alkanes
Weaker acid
Stronger acid
pKa 51pKa 15.7++ H-OHCH3CH2-MgBr Mg(OH)BrCH3CH2-H
δ+δ-
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11-19Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• they also react with these acids ( proton donors) to
give alkanes
Amines Alcohols
pKa 16-18pKa 38-40R2NH ROH
Phenols Thiols Carboxylic acids
pKa 4-5pKa 8-9pKa 9-10ArOH RSH RCO2H
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11-20Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• Grignard reagents provide a way to form new
carbon-carbon bonds• a carbanion is a good nucleophile and adds to the
carbonyl group of an aldehyde or ketone to form a tetrahedral carbonyl addition compound
• the driving force for this reaction is the attraction of the partial negative charge on the carbon of the Grignard reagent for the partial positive carbon of the carbonyl group
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11-21Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• addition of a Grignard reagent to formaldehyde
followed by H3O+ gives a 1° alcohol
ether
1-Propanol(a primary alcohol)
Formaldehyde
Mg2++
+δ+
δ- δ+
δ-O
OH
CH3 CH2 -MgBr H-C-H
CH3 CH2 -CH2 HClH2 O A magnesium alkoxide
CH3 CH2 -CH2
O- [ MgBr ] +
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11-22Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• addition to any other RCHO gives a 2° alcohol
ether
A magnesium alkoxide
Acetaldehyde(an aldehyde)
1-Cyclohexylethanol(a secondary alcohol)
+ Mg2+
+δ-
δ+
δ+
δ-
MgBr
O
CHCH3
O- [ MgBr ] +
OH
CHCH3
CH3 -C-H
HClH2 O
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11-23Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• addition to a ketone gives a 3° alcohol
ether
2-Phenyl-2-propanol (a tertiary alcohol)
Acetone
Mg2++
+δ-δ+
δ+
δ-
A magnesiumalkoxide
C6 H5 MgBr
O
C6 H5 CCH3
CH3
O- [ MgBr] + OH
CH3
C6 H5 CCH3
CH3 -C-CH3
HClH2 O
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11-24Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• addition to CO2 gives a carboxylic acid
MgBr CO-[MgBr]+
O
HClH2O
COH
O
Cyclopentane-carboxylic acid
δ- δ+
δ-
C
O
O
+
Carbondioxide + Mg 2 +
ether
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11-25Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• addition to ethylene oxide gives a 1° alcohol
etherSN2
+
2-Phenylethanol
CH2CH2
O
C6 H5-MgBr
C6 H5CH2 CH2 O-[MgBr]+ HCl
H2 OC6 H5CH2 CH2 OH
Ethylene oxide
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11-26Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Grignard ReagentsGrignard Reagents• ProblemProblem: 2-phenyl-2-butanol can be synthesized
by three different combinations of a Grignard reagent and a ketone. Show each combination
C-CH2CH3
OH
CH3
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11-27Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• Addition of one molecule of alcohol to the C=O
group of an aldehyde or ketone gives a hemiacetal
• HemiacetalHemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon
A hemiacetal
+
O OHH
CH3
CH3CCH3 OCH2CH3 CH3COCH2CH3
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11-28Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• Hemiacetals are only minor components of an
equilibrium mixture, except where a five- or six-membered ring can form• (the trans isomer is shown here)
4-Hydroxypentanal A cyclic hemiacetal(major form present
at equilibrium)
O
OH O OHH3CCH3CHCH2CH2CH
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11-29Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• Hemiacetals react with alcohols to form acetals• AcetalAcetal: a molecule containing two -OR or -OAr
groups bonded to the same carbon
A diethyl acetal
+
+
A hemiacetal
OH
CH3
CH3
OCH2CH3
CH3COCH2CH3 CH3CH2 OHH
+
CH3COCH2CH3 H2 O
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11-30Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• Steps 1 and 2: proton transfer from the acid catalyst,
HA, to the carbonyl oxygen followed by loss of H2O
+••
+
++
•• ••
••
••
••
••
••
••
••
••
(1) (2)
An oxonium ion
HO
H
HA
HHO
H
H
OCH3
R-C-OCH3
A -
R-C-OCH3
R-C H2 O
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11-31Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• Steps 3 and 4: reaction of the oxonium ion with ROH
followed by proton transfer to A-
••
++
••••
••+
+
••
••
••
••
••
••••
(3) (4)OCH3
H
H
H
OH CH3
O-CH3
H
A -
R-CCH3 -O R-C-OCH3
R-C-OCH3 H-A
An acetal
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11-32Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Addition of AlcoholsAddition of Alcohols• with a glycol, such as ethylene glycol, the product is a
five-membered cyclic acetal
A cyclic acetalO CH2
CH2O
+O HOCH2CH2OHH
+
+ H2O
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11-33Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Add’n of N NucleophilesAdd’n of N Nucleophiles• Ammonia, 1° aliphatic amines, and 1° aromatic
amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases)
An imine(a Schiff base)
Methylamine
Cyclopent-anone
++O NCH3H
+
H2NCH3 H2O
+ +
Ethanal Aniline An imine(A Schiff base)
H2NO
CH3CH=NCH3CHH+
H2 O
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11-34Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Add'n of N NucleophilesAdd'n of N Nucleophiles• Formation of an imine occurs in two steps
• Step 1: formation of a TCAI • Step 2: loss of water
••••
••+ N-R
H
C
O -
H2 N-R
••••
••N-R
H
C
OH
TCAI
••H+
C
O••••
••••
••N-R
H
C
O H
C NR
••+ H2O
••••
(1) (1)
(2)
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11-35Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Add'n of N NucleophilesAdd'n of N Nucleophiles• Rhodopsin (visual purple) is the imine formed
between 11-cis-retinal (vitamin A aldehyde) and the protein opsin
123
5
67
8
9
10
1112
1314
15 Rhodopsin(Visual purple)
4
C=N-OPSINH
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11-36Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
RhodopsinRhodopsin
OPSIN
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11-37Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Keto-Enol TautomerismKeto-Enol Tautomerism• A carbon adjacent to a carbonyl group is called
an -carbon-carbon, and a hydrogen atom bonded to it is called an -hydrogen-hydrogen.
-carbons
α-hydrogens
CH3 -C-CH2-CH3
O
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11-38Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Keto-Enol TautomerismKeto-Enol Tautomerism• A carbonyl compound with an a-hydrogen is in
equilibrium with a constitutional isomer called an enol (an alkene + an alcohol)
CH3-C-CH3
O
CH3-C=CH2
OH
Acetone(keto form)
Acetone(enol form)
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11-39Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Keto-Enol TautomerismKeto-Enol Tautomerism• keto-enol
equilibria for simple aldehydes and ketones lie far toward the keto form
OH
O
O
CH3CH CH2=CH
CH3CCH3
Keto form Enol form% Enol at
Equilibrium
6 x 10-5
OH
CH3C=CH2 6 x 10-7
O OH4 x 10-5
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11-40Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Keto-Enol TautomerismKeto-Enol Tautomerism• Keto-enol tautomerism is acid catalyzed
Step 1: proton transfer from H-A
Step 2: proton transfer to A-
O
CH3-C-CH3 + H-A
O
CH3-C-CH3
H+
fast+ A-
keto form
••
•• ••••
the conjugate acidof the ketone
Enol form
OH
CH3-C=CH2+ A-
O
CH3-C-CH2-H
H+
slow+ H-A
••
••••••
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11-41Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
RacemizationRacemization• Racemization at an -carbon is catalyzed by acid
An achiral enol(R)-3-Phenyl-2-butanone
(S)-3-Phenyl-2-butanone
C C
O
CH3
Ph
HH3C
CH
H3C
Ph
C
CH3
OOH
CCCH3
Ph
H3C
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11-42Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Oxidation of AldehydesOxidation of Aldehydes• Aldehydes are oxidized to carboxylic acids by a
variety of oxidizing agents, including chromic acid
CH3(CH2)4CH
OH2CrO4
O
Hexanal Hexanoic acid
CH3(CH2)4COH
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11-43Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Oxidation of AldehydesOxidation of Aldehydes• Aldehydes are also oxidized by Ag(I)
• in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide
Vanillic acid
Vanillin
+
+CH
HO
CH3O
O
O
CH3O
HO
COH
Ag2OTHF, H2O
NaOH
Ag
HClH2O
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11-44Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Oxidation of AldehydesOxidation of Aldehydes• Tollens’ reagent, another form of Ag(I), is
prepared by dissolving silver nitrate in water, adding NaOH to precipitate Ag(I) as Ag2O, and then adding aqueous ammonia to redissolve Ag(I) as a silver-ammonia complex ion
+Ag+NO3
-2NH3 Ag(NH3)2
+ NO3-NH3, H2O
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11-45Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Oxidation of AldehydesOxidation of Aldehydes• Tollens’ reagent oxidizes an aldehyde to a carboxylic
anion and silver(1) is reduced to metallic silver• this reaction is used to silver mirrors
Precipitates as silver mirror
++
+
ONH3, H2O
RCH 2Ag(NH3)2+
RCO2-
2Ag 4NH3
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11-46Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Oxidation of AldehydesOxidation of Aldehydes• aldehydes are oxidized by molecular oxygen and by
hydrogen peroxide
• liquid aldehydes are so sensitive to air that they must stored under N2
Benzoic acidBenzaldehyde
+CH
O O
COH2O22
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11-47Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
ReductionReduction• An aldehyde can be reduced to a 1° alcohol and a
ketone to a 2° alcoholO
O OH
RCH RCH2 OH
RCR' RCHR'
reduction
An aldehyde
A ketone
A 1° alcohol
A 2° alcohol
reduction
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11-48Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Catalytic ReductionCatalytic Reduction• Catalytic reductions are generally carried out
from 25° to 100°C under 1 to 5 atm H2
+25oC, 2 atm
Pt
Cyclohexanone Cyclohexanol
O OH
H2
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11-49Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Catalytic ReductionCatalytic Reduction• A carbon-carbon double bond may also be
reduced under these conditions
• by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone
1-Butanol trans-2-Butenal(Crotonaldehyde)
2H2
NiCH3 CH2CH2 CH2 OH
HC C
CH
H3C H
O
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11-50Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Metal Hydride ReductionMetal Hydride Reduction• The most common laboratory reagents for the
reduction of aldehydes and ketones are NaBH4 and LiAlH4
• both reagents are sources of hydride ion, H:-, a very powerful nucleophile
Hydride ionLithium aluminumhydride (LAH)
Sodium borohydride
••H
H H
HH-B-H H-Al-HLi+Na
+H
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11-51Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
NaBHNaBH44 Reduction Reduction• Reductions with NaBH4 are most commonly
carried out in aqueous methanol, in pure methanol, or in ethanol• one mol of NaBH4 reduces four mol of aldehyde or
ketone
A tetraalkyl borateborate salts
+
+methanol
O
4RCH NaBH4
(RCH2O)4B-
Na+ 4RCH2 OH
H2 O
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11-52Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
NaBHNaBH4 4 ReductionReduction• the key step in metal hydride reduction is transfer of a
hydride ion to the C=O group to form a tetrahedral carbonyl addition compound
from water
from the hydride reducing agent
+
H
H O O-BH3 Na+
OH
H
H
H-B-HNa+
R-C-R' R-C-R'H2 O
R-C-R'
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11-53Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
LiAlHLiAlH4 4 ReductionReduction• Unlike NaBH4, LiAlH4 reacts violently with water,
methanol, and other protic solvents • reductions using this reagent are carried out in diethyl
ether or tetrahydrofuran (THF)
+
+ aluminum salts
etherO
OH
4RCR LiAlH4
4RCHRA tetraalkyaluminate
(R2CHO)4Al- Li+ H2 O
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11-54Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Metal Hydride ReductionMetal Hydride Reduction• Metal hydride reducing agents do not normally
reduce carbon-carbon double bonds, and selective reduction of C=O or C=C is often possible
O OH
RCH=CHCR' RCH=CHCHR'1. NaBH4
2. H2O
+Rh
O O
RCH=CHCR' RCH2 CH2CR'H2
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11-55Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Reductive AminationReductive Amination• A value of imines is that the carbon-nitrogen
double bond can be reduced to a carbon-nitrogen single bond
+
Dicyclohexylamine
Cyclohexanone
(An imine)
Cyclohexylamine
O H2N
N N
H
-H2O
H2/Ni
H+
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11-56Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Aldehydes Aldehydes & &
KetonesKetonesEnd Chapter 11End Chapter 11