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CH 19: Aldehydes and Ketones Renee Y. Becker Valencia Community College CHM 2211 1
CH 19: Aldehydes and Ketones
Renee Y. BeckerValencia Community College
CHM 2211
1
Some Generalizations About Carbonyl Compounds
• The most important functional group in organic chemistry.
O
CRAcyl group
R = alkyl, aryl, or alkenyl
The other residue my be C, H, O, X, N, S, etc.
2
Some Generalizations About Carbonyl Compounds
• carbonyl compounds are planar about the double bond with bond angles 120 due to the sp2 hybridized carbon.
• Many types of carbonyl compounds have significant dipole moments.
• The polarity of the C-O bond plays a significant role in the reactivity of carbonyl compounds.
O
C
Nucleophilic oxygen reacts with acids and electrophiles.
Electrophilic carbon reacts with bases and nucleophiles. 3
Aldehydes and Ketones
CH3CH
O
EthanalCH3CCH3
O
Propanone
4
Aldehydes and Ketones
• Due to the polarity of the carbonyl C-O bond, aldehydes and ketones have higher BPs than alkanes with similar molecular weights.
• The lack of H-bonding hydrogens, results in lower BPs than similar alcohols.
CH3CH2CH2CH3 CH3CH2CH CH3CH2CH2OH
O
ButaneM.W. = 58BP = -0.45 oC
PropanalM.W. = 58BP = 49 oC
PropanolM.W. = 60BP = 97 oC
5
Naming Aldehydes
• Aldehydes are named by replacing the terminal-e of the corresponding alkane name with –al
• The parent chain must contain the CHO group– The CHO carbon is numbered as C1
• If the CHO group is attached to a ring, use the suffix carbaldehyde.
6
Naming Aldehydes
CHO
CH3trans-2-methylcyclohexanecarbaldehyde
CHO
Cyclopentanecarbaldehyde
CHO
Benzenecabaldehydeor
phenylmethanalor
benzaldehyde 7
Naming Aldehydes
8
Example 1: Name
9
1
2
3
4
H
O
H
O
Cl
H
O
O
H
1
2
3
4
H
O
H
O
Cl
H
O
O
H
Example 2: Draw
1. 3-Methylbutanal
2. 3-Methyl-3-butenal
3. cis-3-tert-Butylcyclohexanecarbaldehyde
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Naming Ketones
• Replace the terminal -e of the alkane name with –one
• Parent chain is the longest one that contains the ketone group– Numbering begins at the end nearer the
carbonyl carbon
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Naming Ketones
CH3CH2CCH2CCH3
O O
2,4-Hexanedione
CH3CHCH2CCH3
O
CH3
4-Methyl-2-pentanone
H3C O
4-Methylcyclohexanone
12
Naming Ketones
• Ketones with Common Names
13
Ketones and Aldehydes as Substituents
• The R–C=O as a substituent is an acyl group is used with the suffix -yl from the root of the carboxylic acid
– CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl
CR
O
An acyl group
CH3C
OC
H
O
Acetyl Formyl
CO
Benzoyl
14
Ketones and Aldehydes as Substituents
• The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain
15
Example 3: Name
CH3CH2CCH(CH3)2
O
O O
O
HHH3C
CH3
O
1.
2.
3.
4.
16
Example 4: Draw
1. 4-Chloro-2-pentanone
2. P-bromoacetophenone
3. 3-ethyl-4-methyl-2-hexanone
17
Preparation of Aldehydes
• Oxidize primary alcohols using pyridinium chlorochromate
18
Preparation of Aldehydes
• Oxidation of alkenes with a vinylic hydrogen
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O3
Zn, CH3CO2H
aldehydeketone
Dicarbonyl compound
6-oxoheptanal
O3
aldehyde aldehyde
O3
Zn, CH3CO2H
Zn, CH3CO2H
H
O H
O
H
H
OH
O
HO
H
O
+
+
O
3
Zn, CH3CO2H
aldehydeketone
Dicarbonyl compound
6-oxoheptanal
O3
aldehyde aldehyde
O3
Zn, CH3CO2H
Zn, CH3CO2H
H
O H
O
H
H
OH
O
HO
H
O
+
+
Preparation of Aldehydes
• The partial reduction of certain carboxylic acid derivatives. (esters)
RC
Y
OH
RC
H
O+ Y
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DIBAH, toluene
-78 C H3O+
DIBAH - diisobutylaluminum hydride
CH3O-
O
O O
H
Al
H
+DIBAH, toluene
-78 C H3O+
DIBAH - diisobutylaluminum hydride
CH3O-
O
O O
H
Al
H
+
Example 5
How would you prepare pentanal from the following:
1. 1-Pentanol
2.1-Hexene
3. O
O
21
Preparing Ketones
• Oxidation of secondary alcohols
RCHR'
OHPCCCH2Cl2
RCR'
O
22
Preparing Ketones
• Oxidation of alkenes if one unsaturated carbon is disubstituted
23
O3
Zn, CH3CO2H
aldehydeketone
O H
OH
+
O
3
Zn, CH3CO2H
aldehydeketone
O H
OH
+
Preparing Ketones
• Friedel-Crafts acylation of aromatic compounds with an acid chloride.
ArH + RCClO AlCl3 ArCR
O+ HCl
Occurs only once!
24
Preparing Ketones
• Hydrations of terminal alkynes– Methyl ketone synthesis– Hg2+ catalyst
25
H3O+
HgSO4
OH3O+
HgSO4
O
Example 6
How would you carry out the following reactions? More than 1 step might be necessary.
1. 3-Hexyne 3-Hexanone
2. Benzene m-Bromoacetophenone
3. Bromobenzene Acetophenone26
Reactions of Aldehydes and Ketones
• Oxidation reactions
• Nucleophilic addition reactions
• Conjugate nucleophilic addition reactions
27
Oxidation of Aldehydes
• Jones’ Reagent (preferred)– Preferred over other oxidation reagents due to
Room temp. reaction with high yields– Run under acidic conditions (con)
• Will react with C=C and any acid sensitive functionality
28
CrO3, H3O+
acetone, 0 CH
O
OH
OC r O
3, H3O+
acetone, 0 CH
O
OH
O
Oxidation of Aldehydes
• Tollen’s reagent• For use with C=C double bonds
29
Ag2O
NH4OH, H2OAg
O
H
O
OH +A g
2O
NH4OH, H2OAg
O
H
O
OH +
Oxidation of Ketones
• Ketones are resistant toward oxidation due to the missing hydrogen on the carbonyl carbon
• Treatment of ketones with hot KMnO4 will cleave the C-C bond adjacent to the carbonyl group:
30
KMnO4, H2O, NaOH
H3O+
KMnO4, H2O, NaOH
H3O+
O
OH
O
O
OHH
CO2H
CO2H
O
+KMnO4, H2O, NaOH
H3O+
KMnO4, H2O, NaOH
H3O+
O
OH
O
O
OHH
CO2H
CO2H
O
+
Nucleophilic Addition Reactions of Aldehydes and Ketones
• Nu- approaches 45° to the plane of C=O and adds to C
• A tetrahedral alkoxide ion intermediate is produced
31
32
Nucleophiles
• Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site
• The overall charge on the nucleophilic species is not considered
33
Nucleophilic Addition Reactions
34
Relative Reactivity of Aldehydes and Ketones
• Aldehydes are generally more reactive than ketones in nucleophilic addition reactions
• The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b)
35
Electrophilicity of Aldehydes and Ketones
• Aldehyde C=O is more polarized than ketone C=O• As in carbocations, more alkyl groups stabilize +
character• Ketone has more alkyl groups, stabilizing the C=O
carbon inductively
36
Reactivity of Aromatic Aldehydes
• Aromatic aldehydes are less reactive in nucleophilic addition than straight chain aldehydes– Due to electron-donating resonance effect of aromatic
ring• Makes carbonyl group less electrophilic
37
Nucleophilic Addition of H2O: Hydration
• Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols)
• Hyrdation is reversible: a gem diol can eliminate water
38
Relative Energies
• Equilibrium generally favors the carbonyl compound over hydrate for steric reasons– Acetone in water is 99.9% ketone form
• Exception: simple aldehydes– In water, formaldehyde consists is 99.9%
hydrate
39
Acid & Base-Catalyzed Addition of Water
• Addition of water is catalyzed by both acid and base
• The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water
• Acid-Catalyzed Addition of Water• Protonation of C=O makes it more electrophilic
40
Mechanism 1: Base catalyzed hydration of an aldehyde/ketone
41
NaOH
H2O
Na+ -OH-OH
NaOH
NaOH
O OH
OH
O O–
OH
OHH
OH
OH
+
+
+
+
N a O H
H
2O
Na+ -OH-OH
NaOH
NaOH
O OH
OH
O O–
OH
OHH
OH
OH
+
+
+
+
Mechanism 2: Acid catalyzed hydration of an aldehyde/ketone
42
H2O
H3O+
H3O+
H3O+O OH
OH
O O+H
OH
O+
H H
O+H
H
H OH H
OH H
OH
OH+
+
+
+
H2O
H3O+
H3O+
H3O+O OH
OH
O O+H
OH
O+
H H
O+H
H
H OH H
OH H
OH
OH+
+
+
+
Addition of H-Y to C=O
• Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (“adduct”)
• Formation is readily reversible
43
Nucleophilic Addition of HCN: Cyanohydrin Formation
• Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN
RC
R'
O+
OHC
R'RHC N N
a cyanohydrinAldehyde or
ketoneHydrogencyanide
44
Mechanism of Formation of Cyanohydrins
• Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN
• Addition of CN to C=O yields a tetrahedral intermediate, which is then protonated
• Equilibrium favors adduct
45
Mechanism 3: Formation of Cyanohydrins
46
H--CN
NH3
-CN NH4+
H--CN NH3 -CN
H--CN
NH4+
-CN-CN
O
H H
OH CN
O
H
O–
H
CN
H
OH CN
++
+
++
H - - C N
N H
3
-CN NH4+
H--CN NH3 -CN
H--CN
NH4+
-CN-CN
O
H H
OH CN
O
H
O–
H
CN
H
OH CN
++
+
++
Uses of Cyanohydrins
• Nitriles can be reduced with LiAlH4 to yield primary amines:
Cl
Cl
CHO HCN
Cl
Cl
CCNOH
1. LiAlH4, THF2. H2O
Cl
Cl
CCH2NH2
OH
2,4-Dichlorobenzaldehydecyanohydrin
(2,4-Dichloro-phenyl)-2-aminoethanol 47
Uses of Cyanohydrins
• Nitriles can be hydrolyzed with hot aqueous acid to yield carboxylic acids:
Cl
Cl
CHO HCN
Cl
Cl
CHCNOH
H3O+, heat
Cl
Cl
CHCOOHOH
2,4-Dichlorobenzaldehydecyanohydrin
(2,4-Dichloro-phenyl)-2-hydroxy-ethanoic acid 48
Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation
• Treatment of aldehydes or ketones with Grignard reagents yields an alcohol– Nucleophilic addition of the equivalent of a carbon
anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +.
49
Mechanism of Addition of Grignard Reagents
• Complexation of C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol
• Grignard additions are irreversible because a carbanion is not a leaving group
50
Mechanism 4: Addition of Grignard Reagents
51
RC
R'
OR" MgX
OC R"
R'R
H3O+ OHC R"
R'R
adehyde orketone
an alcoholalkoxide
Hydride Addition
• Convert C=O to CH-OH
• LiAlH4 and NaBH4 react as donors of hydride ion
• Protonation after addition yields the alcohol
52
H-
NaBH4 or LiAlH4
H3O+
H2OO O–
H H
OH
+H -
NaBH4 or LiAlH4
H3O+
H2OO O–
H H
OH
+
Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 (primary amines) adds to C=O to form imines, R2C=NR (after loss of HOH)
R2NH (secondary amines) yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine)
53
54
Mechanism of Formation of Imines
• Primary amine adds to C=O
• Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine)
• Protonation of OH converts into water as the leaving group
• Result is iminium ion, which loses proton
• Acid is required for loss of OH – too much acid blocks RNH2
Note that overall reaction is substitution of RN for O 55
Mechanism 5: Imine Formation
56
Imine Derivatives
• Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines
• For example, hydroxylamine forms oximes and 2,4-dinitrophenylhydrazine readily forms 2,4-dinitrophenylhydrazones
– These are usually solids and help in characterizing liquid ketones or aldehydes by melting points
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Mechanism 6: Enamine Formation
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Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction
• Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane
• Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature
60
Mechanism 7: The Wolff–Kishner Reaction
61
Nucleophilic Addition of Alcohols: Acetal Formation
• Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O
• Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur
• Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal
62
Uses of Acetals
• Acetals can serve as protecting groups for aldehydes and ketones
• It is convenient to use a diol, to form a cyclic acetal (the reaction goes even more readily)
63
Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
• The sequence converts C=O is to C=C• A phosphorus ylide adds to an aldehyde or ketone to
yield a dipolar intermediate called a betaine • The intermediate spontaneously decomposes through a
four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O
• Formation of the ylide is shown below
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Mechanism 8: The Wittig Reaction
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Uses of the Wittig Reaction
• Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure
• For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes
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The Cannizaro Reaction
• The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)
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Conjugate Nucleophilic Addition to -Unsaturated Aldehydes and Ketones
• A nucleophile can add to the C=C double bond of an ,-unsaturated aldehyde or ketone (conjugate addition, or 1,4 addition)
• The initial product is a resonance-stabilized enolate ion, which is then protonated
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Conjugate Addition of Amines
• Primary and secondary amines add to , -unsaturated aldehydes and ketones to yield -amino aldehydes and ketones
71
Conjugate Addition of Alkyl Groups: Organocopper Reactions
• Reaction of an , -unsaturated ketone with a lithium diorganocopper reagent
• Diorganocopper (Gilman) reagents from by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium
• 1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups
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RX2 Li
pentaneRLi + Li + X
RLi2CuIether
Li+(RCuR) + Li+ + I-
Gilman Reagent
74
Mechanism of Alkyl Conjugate Addition
• Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, an enone
• Transfer of an R group and elimination of a neutral organocopper species, RCu
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Example 7
CH3CCHO
CH23-Buten-2-one
1. Li(CH3)2Cu, ether
2. H3O+
O
2-Cyclohexenone
1. Li(H2C=CH)2Cu, ether
2. H3O+
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