Chemistry, Organic 5th Edition L. G. Wade, Jr.
Chapter 18 Ketones and Aldehydes
Jo Blackburn Richland College, Dallas, TX Dallas County Community College District 2003, Prentice Hall
Carbonyl Compounds
Chapter 18
2
IUPAC Names for Aldehydes/Ketones
#1 Identify longest chain. #2 Number longest chain.
Aldehyde/ketone higher in priority than alcohols Aldehyde group is highest in priority Rings should be numbered with carbonyl at 1.
#3 Name groups
R=O is oxo- and R-CHO is formyl. -CHO attached to a ring, suffix is -carbaldehyde.
Chapter 18 3
IUPAC Names for Aldehydes/Ketones
#4 Organize name
Ketones: Replace -e with -one. Indicate the position of the carbonyl with a number. Aldehydes: Replace -e with -al.
#5 Assign Stereochemistry
Chapter 18
4
O CH3 C CH CH2OH CH3
CH3 CH3 CH2 CH CH2
O CH
O
CHO
Br
Chapter 18
5
CH3 CH3 CH2 CH CH2
O CH
O CH3 C
CH3 CH CH2
O C H
CHO
CO OH
Chapter 18
6
Common Names for Ketones
Named as alkyl attachments to -C=O. Use Greek letters instead of numbers.
O CH3 C CH CH3 CH3
Br O CH3CH C CH CH3 CH3
methyl isopropyl ketone
bromoethyl isopropyl ketone
Chapter 18
7
Historical Common Names
O CH3 C CH3
acetone
O C
O C CH3
acetophenone
benzophenone
Chapter 18 8
Aldehyde Common Names
Use the common name of the acid. Drop -ic acid and add -aldehyde.
1 C: formic acid, formaldehyde 2 Cs: acetic acid, acetaldehyde 3 Cs: propionic acid, propionaldehyde 4 Cs: butyric acid, butyraldehyde.
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9
Carbonyl Structure
Hybridization - Carbon is _____ Compared to C=C
Bond Length - C=O bond is ______ Bond Strength C=O bond is _______ Polarity - C=O bond is _______
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10
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.
Chapter 18
11
Solubility
Good solvent for alcohols/amines.
Lone pair of electrons accept a hydrogen bond from OH or NH
Somewhat soluble in water.
Acetone and acetaldehyde are miscible in water.
Chapter 18
12
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.
Chapter 18
13
1
H NMR Spectroscopy
Chapter 18
14
13
C NMR Spectroscopy
Chapter 18
15
MS for 2-Butanone
Chapter 18
16
MS for Butyraldehyde
Chapter 18
17
McLafferty Rearrangement
Loss of alkene (even mass number) Must have -hydrogen
Chapter 18
18
UV Spectra, *
C=O conjugated with another double bond. Large molar absorptivities (> 5000)
max base value is 210 + 30 for additional conjugation hapter 18 + 10 for additional alkylCgroups
19
UV Spectra, n *
Small molar absorptivity. Forbidden transition occurs less frequently.
max base value is 280 to 300
Chapter 18
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Industrial Importance
Acetone and methyl ethyl ketone are important solvents. Formaldehyde used in polymers like Bakelite. Flavorings and additives like vanilla, cinnamon, artificial butter.
Chapter 18
21
Synthesis Review
Oxidation of alcohols.
2 alcohol + Na2Cr2O7 ketone 1 alcohol + PCC aldehyde
Chapter 18
22
Synthesis Review
Oxidative Cleavage of alkenes.
Ozonolysis
H C R C
R' R''
1) O3 2) (CH3)2S
H CO R +OC
R' R''
Permanganate Cleavage
H CC R
R' R''
KMnO4, warm
HO CO R +OC
R' R''
23
Chapter 18
Synthesis Review
Hydration of terminal alkyne
Ketone (Markovnikov hydration)
HgSO4, H2SO4, H2O HC R
R OH O
Aldehyde (anti-Markovnikov hydration)
HC R 1. Sia2BH THF 2. H2O2, NaOH OH
Chapter 18
R
O
24
Synthesis Review
Friedel-Crafts acylation of aromatic
Acylation (limitation on alkyl length)
O
O AlCl3
R
+
Cl
R
Gatterman-Koch Formylation
O CO2, HCl, AlCl3/CuCl H
Chapter 18 25
Aldehydes from 1,3-Dithiane
Remove H+ with n-butyllithium.
BuLi S H S H S _ H S
Alkylate with primary alkyl halide, then hydrolyze.
CH3CH2Br S _ H S H , HgCl2 S H S H2O H CH2CH3
Chapter 18 26
+
O C
CH2CH3
Ketones from 1,3-Dithiane
After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze.
BuLi S H S CH2CH3 CH3Br S _ S H , HgCl2 H2O CH3
+
O C CH2CH3
S CH3
S
CH2CH3
CH2CH3
Chapter 18
27
Ketones from Carboxylates
Organolithium attacks the carbonyl forming a diion. Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone.
O
LiOH
OH
O
R'Li
O-+Li
O-+Li
R
R
R
R'
O-+Li
lithium carboxylate
OH
dianion H3O+
O
(-H2O)
R'
R
R
R'
OH
ketone
Chapter 18
hydrate
28
What about aldehydes from carboxylates?
Aldehydes from Acid Chlorides
Use a mild reducing agent to prevent reduction to primary alcohol.
O CH3CH2CH2C Cl LiAlH(O-t-Bu)3 O CH3CH2CH2C H
Reducing agent = Lithium aluminum tri(t-butoxy)hydride
Chapter 18
29
Ketones Acid from Chlorides
Use lithium dialkylcuprate (R2CuLi) instead of a Grignard or organolithium reagent. R2CuLi formed by the reaction of 2 moles of R-Li with cuprous iodide.
CH3CH2CH2Br Li, ether 2 CH3CH2CH2Li CuI (CH3CH2CH2)2CuLi
O (CH3CH2CH2)2CuLi + CH3CH2C Cl
Chapter 18
O CH3CH2C CH2CH2CH3
30
Ketones from Nitriles
A Grignard or organolithium reagent attacks the nitrile carbon. The imine salt is then hydrolyzed to form a ketone.
CN CH3CH2MgBr + ether N MgBr C CH2CH3 H3O
+
O C CH2CH3
Chapter 18
31
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 (electrophilic) than ketones because it has fewer electron donating groups.
Work up in acid or use alcohol solvent
Chapter 18
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Nucleophilic Addition Review
Grignard Reaction
O
CH3CH2
MgBr
+
H3C
CH3
Chapter 18
33
Nucleophilic Addition Review
Reduction
Na H + HBH H
+
O
+
H3C
CH3
Chapter 18
34
Benzene as nucleophile?
Chapter 18
35
Wittig Reaction
Nucleophilic addition of phosphorus ylides. Product is alkene. C=O becomes C=C.
Chapter 18
36
Phosphorus Ylides
Reagent Preparation
Triphenylphosphine + unhindered alkyl halide. Deprotonation with butyllithium.
+ Ph3P BuLi
Chapter 18
Ph3P + Ph3P
+ CH3CH2Br
CH2CH3 Br _
_
CH2CH3
+ Ph3P
ylide
CHCH3
37
Mechanism for Wittig
#1 Formation of betaine. #2 Formation of phosphine oxide
+ Ph3P _ CHCH3 H3C Ph + Ph3P CO O
-
HC
C CH3 CH3 Ph
Ph3P H H3C C O C CH3 Ph
38
H C C CH3 CH3 Ph
+ Ph3P
_ O
H C C CH3 CH3 Ph
Chapter 18
Ph3P
O
Addition of Water
In acid, water is the nucleophile. In base, hydroxide is the nucleophile. Mechanism?
O H C
O CH3 C CH3 + H2O
H
+ H2O
HO H
HO CH3
Chapter 18
OH C H
OH C CH3 K = 0.002
39
K = 2000
Addition of HCN
-CN attacks carbonyl carbon Intermediate is protonated by HCN
HCN is highly toxic so can use NaCN or KCN and base.
Reactivity formaldehyde > aldehydes > ketones >> bulky ketones.
O CH3CH2 C HO CH3 + HCN
Chapter 18
CN C CH3
40
CH3CH2
Addition of Amine
Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. C=O (carbonyl) becomes C=N-R (imine).
H RN H H3 C CO Ph H CH3 R+ O N Ph H H CH3 + R NC Chapter 18 Ph
+ H CH3 H R OH N Ph
H CH3 R OH2 + N Ph
O H2 H CH3 R + C+ N Ph
CH3 R NC 41 Ph
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
42
Other Condensations
Chapter 18
43
Addition of Alcohol
Readily Hydrolyzes!!
Chapter 18
44
Mechanism (1) formation of Hemiacetal
O H+ + OH OH +
OH + HOCH3
H HO HO OCH3 + HOCH3 OCH3 + + H2OCH3
Chapter 18
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Mechanism (2) Hemiacetal to Acetal
HO H+ OCH3 + HO H OCH3 + OCH3 + HOH
HOCH3 OCH3 HOCH3 + + CH3O H OCH3 CH3O OCH3
Chapter 18
46
Cyclic Acetals
Addition of a diol produces a cyclic acetal. Sugars commonly exist as acetals or hemiacetals.
O + CH2 HO CH2 OH CH2 CH2 O O
Chapter 18
47
Application - Acetals as Protecting Groups
Hydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones.
O O CH2 HO C O
Chapter 18
CH2 OH
+
H
H
C O
O
48
Example- Selective Reaction of Ketone
React with strong nucleophile (base) Remove protective group.
O + _ MgBr O CH 3 CH3MgBr C O O C O
Chapter 18
HO H3O O
+
CH3 H
C O
49
Oxidation of Aldehydes
Easily oxidized to carboxylic acids.
Chapter 18
50
Tollens Test
Add ammonia solution to AgNO3 solution until precipitate dissolves. Aldehyde reaction forms a silver mirror.
O RC
+ H3)2
H+
2
+ Ag(NH3)2
+
3 OH
_
H2O
O 2 Ag + R C O
_
+
4
+
3 OH
_
H2O
O 2 Ag + R C O
Chapter 18
_
+
4 NH3 + 2 H2O
51
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
52
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
53
Chapter 18
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.
Chapter 18
54
Clemmensen Reduction
O C CH2CH3 Zn(Hg) HCl, H2O CH2CH2CH3
O CH2 C H
Zn(Hg) HCl, H2O
CH2
CH3
Chapter 18
55
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 CH O H2N NH2 CH2 CH NNH2 KOH heat CH2 CH3
Chapter 18
56
End of Chapter 18
Chapter 18
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