Chapter 18 Ketones and Aldehydes
Carbonyl Compounds
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Chapter 18: Aldehydes and Ketones Slide 18-2
1 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 18-3
IUPAC Names for Ketones
• Replace -e with -one. Indicate the position of the carbonyl with a number. • Number the chain so that carbonyl carbon has the lowest number. • For cyclic ketones the carbonyl carbon is assigned the number 1.
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Chapter 18: Aldehydes and Ketones Slide 18-4
2 Examples
O O
CH3 C CH CH3
CH3 Br 3-methyl-2-butanone 3-methylbutan-2-one 3-bromocyclohexanone O
CH3 C CH CH2OH
CH3 4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbutan-2-one =>
Chapter 18: Aldehydes and Ketones Slide 18-5
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 18-6
3 Examples
CH3 O
CH3 CH2 CH CH2 C H
3-methylpentanal CHO
2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbaldehyde
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Chapter 18: Aldehydes and Ketones Slide 18-7
Name as Substituent
• On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl. • Aldehyde priority is higher than ketone. COOH
O CH3 O CH C CH CH C H 3 2 CHO
3-methyl-4-oxopentanal 3-formylbenzoic acid =>
Chapter 18: Aldehydes and Ketones Slide 18-8
4 Common Names for Ketones
• Named as alkyl attachments to -C=O. • Use Greek letters instead of numbers.
O O
CH3 C CH CH3 CH3CH C CH CH3 Br CH CH3 3 methyl isopropyl ketone α−bromoethyl isopropyl ketone
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Chapter 18: Aldehydes and Ketones Slide 18-9
Historical Common Names
O C O CH3
CH3 C CH3 acetone acetophenone O C
benzophenone =>
Chapter 18: Aldehydes and Ketones Slide 18-10
5 Aldehyde Common Names
• Use the common name of the acid. • Drop -ic acid and add -aldehyde. 1 C: formic acid, formaldehyde 2 C’s: acetic acid, acetaldehyde 3 C’s: propionic acid, propionaldehyde 4 C’s: butyric acid, butyraldehyde.
Br O β-bromobutyraldehyde CH3 CH CH2 C H 3-bromobutanal =>
Chapter 18: Aldehydes and Ketones Slide 18-11
Boiling Points
• More polar, so higher boiling point than comparable alkane or ether. • Cannot H-bond to each other, so lower boiling point than comparable alcohol.
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Chapter 18: Aldehydes and Ketones Slide 18-12
6 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 18-13
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 18-14
7 1H NMR Spectroscopy
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Chapter 18: Aldehydes and Ketones Slide 18-15
13C NMR Spectroscopy
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Chapter 18: Aldehydes and Ketones Slide 18-16
8 MS for 2-Butanone
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Chapter 18: Aldehydes and Ketones Slide 18-17
MS for Butyraldehyde
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Chapter 18: Aldehydes and Ketones Slide 18-18
9 McLafferty Rearrangement
• Loss of alkene (even mass number) • Must have γ-hydrogen
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Chapter 18: Aldehydes and Ketones Slide 18-19
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 18-20
10 UV Spectra, n → π*
• Small molar absorptivity. • “Forbidden” transition occurs less frequently.
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Chapter 18: Aldehydes and Ketones Slide 18-21
Synthesis Review
• Oxidation
2° alcohol + Na2Cr2O7 → ketone 1° alcohol + PCC → aldehyde • Ozonolysis of alkenes.
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Chapter 18: Aldehydes and Ketones Slide 18-22
11 Synthesis Review (2)
• Friedel-Crafts acylation
Acid chloride/AlCl3 + benzene → ketone
CO + HCl + AlCl3/CuCl + benzene → benzaldehyde (Gatterman-Koch) • Hydration of terminal alkyne
Use HgSO4, H2SO4, H2O for methyl ketone
Use Sia2BH followed by H2O2 in NaOH for aldehyde. =>
Chapter 18: Aldehydes and Ketones Slide 18-23
Synthesis Using 1,3-Dithiane
• Remove H+ with n-butyllithium.
• Alkylate with primary alkyl halide, then hydrolyze.
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Chapter 18: Aldehydes and Ketones Slide 18-24
12 Ketones from 1,3-Dithiane
After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze.
+ O BuLi CH3Br H , HgCl2 S S S S C S S _ H2O CH3 CH2CH3 CH3 CH2CH3 H CH2CH3 CH2CH3
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Chapter 18: Aldehydes and Ketones Slide 18-25
Ketones from Carboxylates
• Organolithium compounds attack the carbonyl and form a dianion. • Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone.
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Chapter 18: Aldehydes and Ketones Slide 18-26
13 Ketones from Nitriles
• A Grignard or organolithium reagent attacks the nitrile carbon. • The imine salt is then hydrolyzed to form a ketone.
MgBr N O C N C CH2CH3 + C CH CH MgBr + H O CH2CH3 3 2 ether 3
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Chapter 18: Aldehydes and Ketones Slide 18-27
Aldehydes from Acid Chlorides
Use a mild reducing agent to prevent reduction to primary alcohol. Bulk of reagent helps also.
O O LiAlH(O-t-Bu)3 CH3CH2CH2C Cl CH3CH2CH2C H
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Chapter 18: Aldehydes and Ketones Slide 18-28
14 Ketones from Acid Chlorides
Use lithium dialkylcuprate (R2CuLi), formed by the reaction of 2 moles of R-Li with cuprous iodide.
CuI 2 CH3CH2CH2Li (CH3CH2CH2)2CuLi
O O
(CH3CH2CH2)2CuLi + CH3CH2C Cl CH3CH2C CH2CH2CH3
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Chapter 18: Aldehydes and Ketones Slide 18-29
Nucleophilic Addition
• A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. • A weak nucleophile will attack a carbonyl if it has been protonated, thus increasing its reactivity. • Aldehydes are more reactive than ketones.
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Chapter 18: Aldehydes and Ketones Slide 18-30
• Nucleophilic addition of phosphorus ylides. • Product is alkene. C=O becomes C=C.
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Chapter 18: Aldehydes and Ketones Slide 18-31
Phosphorus Ylides
• Prepared from triphenylphosphine and an unhindered alkyl halide. • Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.
+ _ Ph P CH CH Br 3 + 3 2 Ph3P CH2CH3 Br _ + + BuLi Ph3P CH2CH3 Ph3P CHCH3 ylide =>
Chapter 18: Aldehydes and Ketones Slide 18-32
16 Mechanism for Wittig
• The negative C on ylide attacks the positive C of carbonyl to form a betaine. • Oxygen combines with phosphine to form the phosphine oxide. + Ph P O _ H C 3 + 3 CH C O H C C 3 Ph3P CHCH3 Ph Ph CH3 _ + Ph3P O Ph3P O Ph3P O H CH3 H C C CH3 H C C CH3 C C H C Ph CH Ph CH Ph 3 3 3 =>
Chapter 18: Aldehydes and Ketones Slide 18-33
Phosphonate Modification
Chapter 18: Aldehydes and Ketones Slide 18-34
17 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.
OH O HO C C + H2O H H H H K = 2000
OH O HO + H O C C 2 K = 0.002 CH3 CH3 CH3 CH3 =>
Chapter 18: Aldehydes and Ketones Slide 18-35
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.
O CN HO C C CH3CH2 CH3 + HCN CH3CH2 CH3
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Chapter 18: Aldehydes and Ketones Slide 18-36
18 Formation of Imines
• Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. • C=O becomes C=N-R
CH3 CH3 H3C R R C O C _ C RNH2 H2N O N OH Ph + Ph H Ph
CH CH3 R 3 R C N C OH N H Ph Ph =>
Chapter 18: Aldehydes and Ketones Slide 18-37
pH Dependence
• Loss of water is acid catalyzed, but acid destroys nucleophiles. + + • NH3 + H → NH4 (not nucleophilic). • Optimum pH is around 4.5.
Chapter 18: Aldehydes and Ketones Slide 18-38
19 Other Condensations
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Chapter 18: Aldehydes and Ketones Slide 18-39
Addition of Alcohol
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Chapter 18: Aldehydes and Ketones Slide 18-40
20 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. =>
Chapter 18: Aldehydes and Ketones Slide 18-41
Mechanism for Hemiacetal
• Oxygen is protonated. • Alcohol is the nucleophile. • H+ is removed. =>
Chapter 18: Aldehydes and Ketones Slide 18-42
21 Hemiacetal to Acetal
H + OCH3 HO OCH3 HO OCH3 + H+ + HOH
HOCH3 H OCH + 3 CH3O OCH3 CH3O OCH3 + HOCH3
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Chapter 18: Aldehydes and Ketones Slide 18-43
Cyclic Acetals
• Addition of a diol produces a cyclic acetal. • Sugars commonly exist as acetals or hemiacetals.
CH CH2 2 O O O CH CH + 2 2 HO OH
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Chapter 18: Aldehydes and Ketones Slide 18-44
22 Acetals as Protecting Groups
• Hydrolyze easily in acid, stable in base. • Aldehydes more reactive than ketones.
O O CH2 CH2 HO OH + O H H C C O O =>
Chapter 18: Aldehydes and Ketones Slide 18-45
Selective Reaction of Ketone
• React with strong nucleophile (base). • Remove protective group.
+ _ MgBr O CH3 O CH3 HO + CH3MgBr H3O H O O C C C O O O =>
Chapter 18: Aldehydes and Ketones Slide 18-46
23 Oxidation of Aldehydes Easily oxidized to carboxylic acids.
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Chapter 18: Aldehydes and Ketones Slide 18-47
Tollens Test
• Add ammonia solution to AgNO3 solution until precipitate dissolves. • Aldehyde reaction forms a silver mirror. • Mild, basic way to make carboxylic acids.
O O _ _ + H2O R C H + 2 Ag(NH3)2 + 3 OH 2 Ag + R C O + 4 NH3 + 2 H2O O O _ _ + H2O R C H + 2 Ag(NH3)2 + 3 OH 2 Ag + R C O + 4 NH3 + 2 H2O =>
Chapter 18: Aldehydes and Ketones Slide 18-48
24 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. =>
Chapter 18: Aldehydes and Ketones Slide 18-49
Catalytic Hydrogenation
• Widely used in industry. • Raney nickel, finely divided Ni powder saturated with hydrogen gas. • Pt and Rh also used as catalysts.
O OH Raney Ni H
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Chapter 18: Aldehydes and Ketones Slide 18-50
25 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 18-51
Clemmensen Reduction
O
C CH2CH2CH3 CH2CH3 Zn(Hg)
HCl, H2O
O Zn(Hg) CH2 C CH2 CH3 H HCl, H2O
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Chapter 18: Aldehydes and Ketones Slide 18-52
26 Wolff-Kisher Reduction
• Form hydrazone, then heat with strong base like KOH or potassium t-butoxide. • Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO.
CH2 H CH2 H KOH CH2 C H2N NH2 C CH3 heat O NNH2
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Chapter 18: Aldehydes and Ketones Slide 18-53
End of Chapter 18
Homework: 40, 46, 47, 49, 51, 52, 56, 61, 62, 66, 68, 70, 74, 75
Chapter 18: Aldehydes and Ketones Slide 18-54
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