chapter 18 ketones aldehydes - san diego miramar collegefaculty.sdmiramar.edu/choeger/chapter 18...
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Chapter 18Ketones and Aldehydes
Chapter 18: Aldehydes and Ketones Slide 18-2
Carbonyl Compounds
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Chapter 18: Aldehydes and Ketones Slide 18-3
Carbonyl Structure
• Carbon is sp2 hybridized.• C=O bond is shorter, stronger, and more polar than C=C
bond in alkenes.
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Chapter 18: Aldehydes and Ketones Slide 18-4
IUPAC Names for Ketones
• Replace -e with -one. Indicate the position of the carbonylwith a number.
• Number the chain so that carbonyl carbon has the lowestnumber.
• For cyclic ketones the carbonyl carbon is assigned thenumber 1.
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Chapter 18: Aldehydes and Ketones Slide 18-5
Examples
CH3 C
O
CH
CH3
CH3
O
Br
CH3 C
O
CH
CH3
CH2OH
3-methyl-2-butanone3-methylbutan-2-one 3-bromocyclohexanone
4-hydroxy-3-methyl-2-butanone4-hydroxy-3-methylbutan-2-one =>
Chapter 18: Aldehydes and Ketones Slide 18-6
Naming Aldehydes
• IUPAC: Replace -e with -al.• The aldehyde carbon is number 1.• If -CHO is attached to a ring, use the suffix -carbaldehyde.
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Chapter 18: Aldehydes and Ketones Slide 18-7
Examples
CH3 CH2 CH
CH3
CH2 C H
O
CHO
3-methylpentanal
2-cyclopentenecarbaldehydecyclopent-2-en-1-carbaldehyde
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Chapter 18: Aldehydes and Ketones Slide 18-8
Name as Substituent
• On a molecule with a higher priorityfunctional group, C=O is oxo- and -CHO isformyl.
• Aldehyde priority is higher than ketone.
CH3 C CH
CH3
CH2 C H
OO
COOH
CHO
3-methyl-4-oxopentanal 3-formylbenzoic acid =>
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Chapter 18: Aldehydes and Ketones Slide 18-9
Common Names for Ketones
• Named as alkyl attachments to -C=O.• Use Greek letters instead of numbers.
CH3 C
O
CH
CH3
CH3CH3CH C
O
CH
CH3
CH3
Br
methyl isopropyl ketone α−bromoethyl isopropyl ketone
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Chapter 18: Aldehydes and Ketones Slide 18-10
Historical Common Names
CH3 C
O
CH3
C
CH3
O
C
O
acetone acetophenone
benzophenone =>
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Chapter 18: Aldehydes and Ketones Slide 18-11
Aldehyde Common Names
• Use the common name of the acid.• Drop -ic acid and add -aldehyde.
1 C: formic acid, formaldehyde2 C’s: acetic acid, acetaldehyde3 C’s: propionic acid, propionaldehyde4 C’s: butyric acid, butyraldehyde.
CH3 CH
Br
CH2 C H
O β-bromobutyraldehyde 3-bromobutanal
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Chapter 18: Aldehydes and Ketones Slide 18-12
Boiling Points
• More polar, so higher boiling point thancomparable alkane or ether.
• Cannot H-bond to each other, so lowerboiling point than comparable alcohol.
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Chapter 18: Aldehydes and Ketones Slide 18-13
Solubility
• Good solvent for alcohols.• Lone pair of electrons on oxygen of carbonyl
can accept a hydrogen bond from O-H or N-H.• Acetone and acetaldehyde are miscible in
water.
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Chapter 18: Aldehydes and Ketones Slide 18-14
IR Spectroscopy
• Very strong C=O stretch around 1710 cm-1.• Conjugation lowers frequency.• Ring strain raises frequency.• Additional C-H stretch for aldehyde: two
absorptions at 2710 cm-1 and 2810 cm-1.
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Chapter 18: Aldehydes and Ketones Slide 18-15
1H NMR Spectroscopy
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Chapter 18: Aldehydes and Ketones Slide 18-16
13C NMR Spectroscopy
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Chapter 18: Aldehydes and Ketones Slide 18-17
MS for 2-Butanone
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Chapter 18: Aldehydes and Ketones Slide 18-18
MS for Butyraldehyde
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Chapter 18: Aldehydes and Ketones Slide 18-19
McLafferty Rearrangement
• Loss of alkene (even mass number)• Must have γ-hydrogen
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Chapter 18: Aldehydes and Ketones Slide 18-20
UV Spectra, π → π*
• C=O conjugated with another double bond.• Large molar absorptivities (> 5000)
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Chapter 18: Aldehydes and Ketones Slide 18-21
UV Spectra, n → π*
• Small molar absorptivity.• “Forbidden” transition occurs less frequently.
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Chapter 18: Aldehydes and Ketones Slide 18-22
Synthesis Review
• Oxidation2° alcohol + Na2Cr2O7 → ketone1° alcohol + PCC → aldehyde
• Ozonolysis of alkenes.
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Chapter 18: Aldehydes and Ketones Slide 18-23
Synthesis Review (2)
• Friedel-Crafts acylationAcid chloride/AlCl3 + benzene → ketoneCO + HCl + AlCl3/CuCl + benzene → benzaldehyde
(Gatterman-Koch)• Hydration of terminal alkyne
Use HgSO4, H2SO4, H2O for methyl ketoneUse Sia2BH followed by H2O2 in NaOH for aldehyde.
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Chapter 18: Aldehydes and Ketones Slide 18-24
Synthesis Using 1,3-Dithiane
• Remove H+ with n-butyllithium.
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• Alkylate with primary alkyl halide, then hydrolyze.
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Chapter 18: Aldehydes and Ketones Slide 18-25
Ketones from 1,3-Dithiane
After the first alkylation, remove the second H+, react withanother primary alkyl halide, then hydrolyze.
BuLi
S S
H CH2CH3
H+, HgCl2
H2OCH3
C
O
CH2CH3_
S S
CH2CH3
CH3Br
S S
CH3 CH2CH3
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Chapter 18: Aldehydes and Ketones Slide 18-26
Ketones from Carboxylates
• Organolithium compounds attack the carbonyl and form adianion.
• Neutralization with aqueous acid produces an unstablehydrate that loses water to form a ketone.
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Chapter 18: Aldehydes and Ketones Slide 18-27
Ketones from Nitriles
• A Grignard or organolithium reagent attacks the nitrile carbon.• The imine salt is then hydrolyzed to form a ketone.
H3O+
CH3CH2MgBr +
C N
ether
CCH2CH3
N MgBr
CCH2CH3
O
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Chapter 18: Aldehydes and Ketones Slide 18-28
Aldehydes from Acid Chlorides
Use a mild reducing agent to prevent reduction to primaryalcohol. Bulk of reagent helps also.
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CH3CH2CH2C
O
HLiAlH(O-t-Bu)3
CH3CH2CH2C
O
Cl
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Chapter 18: Aldehydes and Ketones Slide 18-29
Ketones from Acid Chlorides
Use lithium dialkylcuprate (R2CuLi), formed by the reaction of 2moles of R-Li with cuprous iodide.
CH3CH2CH2Li2CuI
(CH3CH2CH2)2CuLi
(CH3CH2CH2)2CuLi + CH3CH2C
O
Cl CH3CH2C
O
CH2CH2CH3
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Chapter 18: Aldehydes and Ketones Slide 18-30
Nucleophilic Addition
• A strong nucleophile attacks the carbonyl carbon, formingan alkoxide ion that is then protonated.
• A weak nucleophile will attack a carbonyl if it has beenprotonated, thus increasing its reactivity.
• Aldehydes are more reactive than ketones.
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Chapter 18: Aldehydes and Ketones Slide 18-31
Wittig Reaction
• Nucleophilic addition of phosphorus ylides.• Product is alkene. C=O becomes C=C.
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Chapter 18: Aldehydes and Ketones Slide 18-32
Phosphorus Ylides
• Prepared from triphenylphosphine and an unhindered alkylhalide.
• Butyllithium then abstracts a hydrogen from the carbonattached to phosphorus.
Ph3P + CH3CH2Br Ph3P CH2CH3
+ _Br
Ph3P CH2CH3
+_
Ph3P CHCH3BuLi
+
ylide =>
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Chapter 18: Aldehydes and Ketones Slide 18-33
Mechanism for Wittig
• The negative C on ylide attacks the positive C of carbonylto form a betaine.
• Oxygen combines with phosphine to form the phosphineoxide.
_
Ph3P CHCH3
+C O
H3C
Ph
Ph3P
CH
CH3
C
O
CH3
Ph
+
Ph3P O
C CCH3
Ph
H
H3C
Ph3P
CH
CH3
C
O
CH3
Ph
_+Ph3P
CH
CH3
C
O
CH3
Ph=>
Chapter 18: Aldehydes and Ketones Slide 18-34
Phosphonate Modification
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Chapter 18: Aldehydes and Ketones Slide 18-35
Addition of Water
• In acid, water is the nucleophile.• In base, hydroxide is the nucleophile.• Aldehydes are more electrophilic since they have fewer e--
donating alkyl groups.
K = 2000C
H H
HOOH
H2O+
HC
O
H
=>K = 0.002
C
CH3 CH3
HOOH
H2O+
CH3
C
O
CH3
Chapter 18: Aldehydes and Ketones Slide 18-36
Addition of HCN (Cyanohydrins)
• HCN is highly toxic.• Use NaCN or KCN in base to add cyanide, then protonate to
add H.• Reactivity formaldehyde > aldehydes > ketones >> bulky
ketones.
CH3CH2
C
O
CH3 +C
CH3CH2 CH3
HOCN
HCN
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Chapter 18: Aldehydes and Ketones Slide 18-37
Formation of Imines
• Nucleophilic addition of ammonia or primary amine,followed by elimination of water molecule.
• C=O becomes C=N-R
C O
H3C
PhRNH2
C
CH3
O
Ph
H2N
R
+
_ C
CH3
OH
Ph
N
R
H
C
CH3
Ph
N
R
C
CH3
OH
Ph
N
R
H =>
Chapter 18: Aldehydes and Ketones Slide 18-38
pH Dependence
• Loss of water is acid catalyzed, but acid destroysnucleophiles.
• NH3 + H+ → NH4+ (not nucleophilic).
• Optimum pH is around 4.5.
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Chapter 18: Aldehydes and Ketones Slide 18-39
Other Condensations
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Chapter 18: Aldehydes and Ketones Slide 18-40
Addition of Alcohol
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Chapter 18: Aldehydes and Ketones Slide 18-41
Mechanism
• Must be acid-catalyzed.• Adding H+ to carbonyl makes it more reactive with weak
nucleophile, ROH.• Hemiacetal forms first, then acid-catalyzed loss of water,
then addition of second molecule of ROH forms acetal.• All steps are reversible.
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Chapter 18: Aldehydes and Ketones Slide 18-42
Mechanism for Hemiacetal
• Oxygen is protonated.• Alcohol is the nucleophile.• H+ is removed. =>
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Chapter 18: Aldehydes and Ketones Slide 18-43
Hemiacetal to Acetal
+
OCH3HO OCH3
H+
H+
HO OCH3
HOH+
=>
OCH3CH3OOCH3CH3O
H
+
OCH3+
HOCH3
HOCH3
Chapter 18: Aldehydes and Ketones Slide 18-44
Cyclic Acetals
• Addition of a diol produces a cyclic acetal.• Sugars commonly exist as acetals or hemiacetals.
O
CH2 CH2
HO OH+
OO
CH2CH2
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Chapter 18: Aldehydes and Ketones Slide 18-45
Acetals as Protecting Groups
• Hydrolyze easily in acid, stable in base.• Aldehydes more reactive than ketones.
O
C
O
H
CH2 CH2
HO OH
O
CO
O
H+
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Chapter 18: Aldehydes and Ketones Slide 18-46
Selective Reaction of Ketone
• React with strong nucleophile (base).• Remove protective group.
O
CO
O
CH3MgBr
CO
O
O CH3MgBr+ _
H3O+
C
O
H
HO CH3
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Chapter 18: Aldehydes and Ketones Slide 18-47
Oxidation of AldehydesEasily oxidized to carboxylic acids.
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Chapter 18: Aldehydes and Ketones Slide 18-48
Tollens Test
• Add ammonia solution to AgNO3 solution until precipitatedissolves.
• Aldehyde reaction forms a silver mirror.• Mild, basic way to make carboxylic acids.
R C
O
H + 2 + 3 + 2+ 4+Ag(NH3)2+
OH_ H2O
2 Ag R C
O
O_
NH3 H2O
R C
O
H + 2 + 3 + 2+ 4+Ag(NH3)2+
OH_ H2O
2 Ag R C
O
O_
NH3 H2O
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Chapter 18: Aldehydes and Ketones Slide 18-49
Reduction Reagents
• Sodium borohydride, NaBH4, reduces C=O, but not C=C.• Lithium aluminum hydride, LiAlH4, much stronger,
difficult to handle.• Hydrogen gas with catalyst also reduces the C=C bond.
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Chapter 18: Aldehydes and Ketones Slide 18-50
Catalytic Hydrogenation
• Widely used in industry.• Raney nickel, finely divided Ni powder saturated with
hydrogen gas.• Pt and Rh also used as catalysts.
ORaney Ni
OH
H
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Chapter 18: Aldehydes and Ketones Slide 18-51
Deoxygenation
• Reduction of C=O to CH2
• Two methods:Clemmensen reduction if molecule is stable in hot acid.Wolff-Kishner reduction if molecule is stable in very
strong base.
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Chapter 18: Aldehydes and Ketones Slide 18-52
Clemmensen Reduction
C
O
CH2CH3 Zn(Hg)
HCl, H2O
CH2CH2CH3
CH2 C
O
H HCl, H2O
Zn(Hg)CH2 CH3
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Chapter 18: Aldehydes and Ketones Slide 18-53
Wolff-Kisher Reduction
• Form hydrazone, then heat with strong base like KOH orpotassium t-butoxide.
• Use a high-boiling solvent: ethylene glycol, diethyleneglycol, or DMSO.
CH2 C
O
HH2N NH2
CH2 C
NNH2
H KOH
heat
CH2 CH3
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Chapter 18: Aldehydes and Ketones Slide 18-54
End of Chapter 18
Homework: 40, 46, 47, 49, 51, 52, 56, 61, 62,66, 68, 70, 74, 75