Download Document

O
Ch. 19 ALDEHYDES AND KETONES:
C
Aldehydes and ketones are both carbonyl compounds.
O
carbonyl group

Aldehydes have one aryl or alkyl group bonded to a carbonyl group.

Ketones have two aryl or alkyl groups bonded to a carbonyl group.
R
C
H
aldehyde
O
R
C
R'
ketone
The simplest aldehyde, formaldehyde, is polymerized with phenol to make adhesives for plywood and
particle board. It is prepared industrially by catalytic oxidation of methanol.
OH
H
C
D
O
[O]
H
catalyst
H
H
+
C
H2
H
The simplest ketone, acetone, is a common industrial solvent. It is prepared industrially by catalytic
oxidation of isopropyl alcohol.
D
H3C
CH
H3C
Sec. 19.1
OH
Nu:-
O
[O]
ZnO 380ºC
H3C
C
CH3
+
: O: 
H2
+
C 
Properties of Aldehydes and Ketones:
E+
The carbonyl group is strongly polar but does not produce hydrogen bonding. As a result, the boiling
points of aldehydes and ketones are higher than the nonpolar hydrocarbons and the alkyl halides but
lower than those of alcohols. Formaldehyde is a gas at room temperature (b.p. = -21 C) but heavier
aldehydes are liquids. Acetone, the simplest ketone, is a liquid at room temperature (b.p. = 56 C).
Lower molecular weight aldehydes and ketones are water soluble. Acetone, formaldehyde and
acetaldehyde are miscible in water.
Naming Aldehydes and Ketones:
Aldehydes: In the IUPAC system, aliphatic aldehydes are named by replacing the terminal -e in the
alkane name with -al. The alkane becomes ‘alkanal’. The parent chain must contain the CHOgroup, and this group is numbered as carbon 1 (because it is always at a chain end). If the aldehyde
group is attached to a large unit (usually a ring), the suffix -carbaldehyde is used.
Replacing ‘ic acid’ with ‘aldehyde’ converts common acid names to aldehyde names.
Substituents locations are given using Greek letters (, , , , , .) beginning with the carbon next
to the carbonyl carbon. (Recall that the -C bears the functional groups; the carbonyl group)
Structure
IUPAC
name
Common name
Structure
IUPAC
Common name
HCO2H
methanoic acid
formic acid
HCHO
methanal
formaldehyde
CH3CO2H
ethanoic acid
acetic acid
CH3CHO
ethanal
acetaldehyde
CH3CH2CO2H
propanoic acid
propionic acid
CH3CH2CHO
propanal
propionaldehyde
CH3(CH2)2CO2H
butanoic acid
butyric acid
CH3(CH2)2CHO
butanal
butyraldehyde
CH3(CH2)3CO2H
pentanoic acid
valeric acid
CH3(CH2)3CHO
pentanal
valeraldehyde
CH3(CH2)4CO2H
hexanoic acid
caproic acid
CH3(CH2)4CHO
hexanal
caproaldehyde
(CH3)2CHCO2H
2-methylpropanoic
acid
isobutyric acid
(CH3)2CHCHO
2-methylpropanal
iso-butyraldehyde
(CH3)2CHCH2CO2H
3-methylbutanoic
acid
isovaleric acid
(CH3)2CHCH2CHO
3-methylbutanal
iso-valeraldehyde
ALDEHYDES & KETONES
1
Name the following aldehydes.
O
OH
CH3 CHBrCH2 C H
O
O
(c)
-bromobutyraldehyde
-hydroxyvaleraldehyde
(I)
3-bromobutanal
4-hydroxypentanal
O
O
C H
C H
(c)
benzaldehyde
(I)
benzenecarbaldehyde
CH2 C H
CH3 CHCH2 CH2 C H
-phenylacetaldehyde
2-phenylethanal
HO
~
cyclohexanecarbaldehyde
CHO
~
3-hydroxycyclopentanecarbaldehyde
When it is necessary to name the -CHO group as a substituent, it is a ‘formyl’ group. The CH3COsubstituent is likewise named as an ‘acetyl’ group. The -CO- substituent is named ‘benzoyl’.
O
H C
O
HO3S
C H
O
O
C CH3
C O
O
O C
(c)
p-formylbenzaldehydep-acetylbenzenesulfonic acid
benzoyl peroxide
(I)
4-formylbenzaldehyde4-acetylbenzenesulfonic acid
(di)benzoyl peroxide
Ketones: In the IUPAC system, aliphatic ketones are named by replacing the terminal -e in the
alkane name with -one. The alkane becomes ‘alkanone’. The parent chain must contain the C=O
group, and this chain is numbered to give the carbonyl group as low a number as possible. In cyclic
ketones, the carbonyl group is assigned the number ‘1’.
In common nomenclature, the two groups attached to the carbonyl are named and the word ‘ketone’ is
added as a separate word. It is literally an ‘alkyl alkyl ketone’. As with aldehydes, substituents
locations are given in common names using Greek letters (, , , , , .) beginning with the carbon
next to the carbonyl carbon.
O
CH3 CCH2 CH3
O
CH3 CHCCHCH3
Cl
O
C CH2 CH2 CH3
CH3
(c)
methyl ethyl ketone (MEK)
-chloroethyl isopropyl ketone
phenyl propyl ketone
(I)
2-butanone
2-chloro-4-methyl-3-pentanone
1-phenyl-1-butanone
ALDEHYDES & KETONES
2
O
O
CH 2=CHCCH3
(c)
methyl vinyl ketone
(I)
3-buten-2-one
O
H3 C
CH3 CH2 CCH2 CCH3
O
~
~
2,4-hexanedione
4-methyl-2-cyclohexen-1-one
O
O
CH2 BrCH2 CCHCH3
CH3 CH2 CHCC(CH3 )3
OCH3
CH3
(c)
-bromoethyl isopropyl ketone
(I)
1-bromo-4-methyl-3-pentanone
t-butyl -methoxypropyl ketone
2,2-dimethyl-5-methoxy-3-hexanone
When it is necessary to name the -C=O group as a substituent, it is named as ‘oxo’.
O
O
CH3 CCH2 COOH
CH3 CH2 CCH2 CHO
(I)
3-oxopentanal
3-oxobutanoic acid
Some ketones have historical names that are commonly used. For example, dimethyl ketone is
always called acetone. Alkyl phenyl ketones are usually named as the acyl group followed by the
suffix ‘phenone’.
(h)

O
O
O
C CH3
C CH2 CH3
C
acetophenone
propiophenone
benzophenone
Do problems 19.1 & 19.2
Sec. 19.2 Preparation of Aldehydes:
1. Oxidation of 1 Alcohols: (review Sec. 17.9) with mild (anhydrous) oxidizing agents, i.e., PCC
or Collins reagent (CrO3 in pyridine) in dichloromethane solvent at room temperature.
CH3CH2
PCC
OH
CH2Cl2 25ºC
ethanol
2. Cleavage of Alkenes by O3: (review Sec. 7.8) Note that tetrasubstituted alkenes yield ketones,
but the presence of  1 vinylic H’s ensures aldehyde formation.
CH3
1.
H
2. Zn, CH3COOH
ALDEHYDES & KETONES
O3
3
3. Reduction of Carboxylic Acid Derivatives: (acid chlorides, esters, or nitriles)
It is not possible to directly prepare aldehydes by reduction of carboxylic acid because any
reducing agents strong enough to reduce a carboxylic acid (LiAlH4) will also immediately reduce
the aldehyde formed to a 1 alcohol. However, there is a way around the problem.

Several derivatives of carboxylic acids, i.e., acid chlorides, esters, and nitriles are more easily
reduced than the parent carboxylic acid. These can be reduced to aldehydes with 1 equivalent of a
milder reducing agent, which will not further reduce the aldehyde to a 1 alcohol.
A suitable, ‘mild’ reducing agent is diisobutylaluminum hydride (DIBAH). The reaction is
carried out in a cold, inert solvent (toluene at -78 C) to prevent further reduction to the alcohol.
This low temperature is obtained by cooling the solvent with dry ice.

Carboxylic acids can readily be converted into any of these derivatives and we will study these
reactions in a later section.
CH3
H
CH3CHCH2
Al
CH3
CH3
CH2CHCH3
CH3CHCH2
+
Al
CH3
CH2CHCH3
H:
+
_
diisobutyl aluminum hydride (DIBAH)
toluene
1. DIBAH -78ºC
O
CH3CH2 C O CH3
methyl propanoate
2. H3O+
O
_
CH3CH2
O
C
_
HCl
CH3CH2 C Cl
propanoyl chloride

propanal
H
NH3
+
CH3OH
CH3CH2C
N
propanenitrile
Do problem 19.3
Sec. 19.4 Preparation of Ketones:
1. Oxidation of 2 Alcohols: (recall Sec. 17.9) 2 alcohols are oxidized to ketones by mild
(anhydrous) or strong (aqueous) oxidants like Jones reagent, cold KMnO4, cold HNO3, etc.
PCC
(CH3 )3 C
OH
or Jones reagent
2. Ozonolysis of Alkenes Yields Ketones: (recall Sec. 7.8) whenever any of the unsaturated alkenes
are disubstituted.
H3C
1.
C
CH2
O3
2. Zn, CH3COOH
H3C
3. Friedel Crafts Acylation of Aromatics: (recall Sec. 16.4) yield ketones when an acid chloride is
used as the electrophile.
O
HO
+
CH3CH2 C
AlCl3
Cl
propanoyl chloride
ALDEHYDES & KETONES
EAS
4
4. Hydration of Terminal Alkynes: (recall Sec. 8.5) with Hg+2 and H3O+ catalyst yields methyl
ketones.
Hg(OAc)2
CH3 (CH2)3 C
CH
+
H3O
1-hexyne
5. Acid Chlorides + Lithium Dialkyl Copper: produces ketones (Sec. 21.5). The reaction is
unique to these two reagents and the mechanism is uncertain. Again, a low temperature (-78 C)
solvent (ether) is used to prevent reduction of the ketone product (to an alcohol). Acids, esters,
anhydrides and amides are not reduced by diorganocopper reagents.
O
CH3 (CH2)4 C
Cl
dimethyl copper lithium
Gilman reagent
hexanoyl chloride

(CH3)2 Cu- Li+
+
- 78ºC
ether
Do Problem 19.4
Sec. 19.3 Oxidation of Aldehydes and Ketones:
Aldehydes are easily oxidized to carboxylic acids, but ketones are rather inert.
R
C
[O]
R
H
C
OH
aldehyde proton replaced

R
C
R'
R
C
OH
no proton on carbonyl
The -CHO proton is abstracted during oxidation. Ketones have none which is why they are more
resistant to oxidation. Many oxidants give good yields, e.g., hot HNO3, and KMnO4, various
peroxy acids (RCOOOH) and often, Jones reagent (CrO3 in aq. H2SO4). Recall Sec. 17.9.
O
Jones reagent
CH3CH2 CH2 C
H
0ºC
butanal

O
O
O
O
Because the aldehyde group is so easily oxidized, atmospheric air must be excluded from their
containers. Even weak oxidants such as Ag2O will oxidize aldehydes. This reagent is preferred
when other oxidizable groups are present (such as alkene and alkyne groups). When dissolved in
aqueous ammonia it is called Tollens reagent. Ammonia dissolves the solid Ag2O producing
diaminosilver (I) ion, Ag (NH3)2+. Ag+ oxidizes aldehydes to carboxylic acids and is reduced to
metallic silver. If the reaction is carried out slowly (cold), the metallic Ag deposits in the walls of
the container as a silver mirror. If carried out quickly (hot), it precipitates as a black solid.
1º alcohol will not oxidize
OH
O
CH2CH2 CH2 C
Ag2O
H
4-hydroxybutanal
NH4OH , H2O
ethanol

Tollens reagent is used as a qualitative test for identifying aldehydes. Simple hydrocarbons,
ethers, ketones and alcohols do not react in the Tollens test. (only -hydroxy ketones react).

Fehling’s reagent (blue Cu+2 in aq. Na tartrate) and Benedict’s reagent (blue Cu+2 in aq. Na
citrate) also oxidize aldehydes precipitating Cu2O as a brick red precipitate.
ALDEHYDES & KETONES
5
Ketones are inert to most oxidants but undergo slow cleavage when treated with hot oxidants like
HNO3, or acidic or alkaline KMnO4. The carbonyl-C bond on either side of the carbonyl group will
cleave producing 2 carboxylic acid groups. Only symmetrical ketones are used in this reaction since
product mixtures result from unsymmetrical ketones.
O
1.
KMnO4 , H2O , NaOH, D
2.
H3O+
O
H3C
C
[O]
CH3
cyclohexanone
Sec. 19.4
Nucleophilic Addition Reactions of Aldehydes and Ketones:
This is the most common reaction of carbonyls. A nucleophile (Nu:-) attacks the electrophilic C in
the carbonyl. The sp2 C rehybridizes to sp3 and a tetrahedral alkoxide is formed.

The nucleophile may be ‘-’ (Nu:-) or neutral (:Nu-H), i.e., carrying one or more H’s that can be
subsequently eliminated, e.g., NH3.

Negative nucleophiles, Nu:-, include hydroxide (OH-), hydride (:H-), carbanion (R3C:-), alkoxide
(RO-), cyanide (:NC:-), etc.

Neutral nucleophiles, :Nu-H, include water (HOH), alcohols (ROH), ammonia (:NH3), 1 amines
(RNH2), 2 amines (R2NH), etc.
Nucleophilic addition to ketones and aldehydes proceed with 2 general products.
1. The tetrahedral alkoxide intermediate is protonated by HOH or HA to yield an alcohol
2. The carbonyl O can be eliminated (as HOH) yielding C=Nu, reforming the sp2 C.
_
:Nu-
A
Nu
C
H
R
..
..O
..
:O
..
R
C
sp 3
Nu
C
R
R
_
:NuH2
H
R
..
:O
..
H
Nu +
_ HO
2
sp 2
R
C
Nu
R
H
R
hybridized
product
hybridized
product
sp 3 hybridized
intermediates
Sec. 19.5
Relative Reactivity of Aldehydes and Ketones:
Aldehydes are generally more reactive than ketones toward nucleophilic addition for 2 reasons.
1. Ketones are more sterically hindered, inhibiting the approach of the Nu:- and yielding a
more crowded, higher-energy transition state (hence a higher activation energy).
2. The carbonyl C in aldehydes is more electrophilic than that of ketones because aldehydes
only have one alkyl group. An alkyl groups is weakly electron donating rendering the
carbonyl C less electrophilic. Formaldehyde, with no alkyl groups, has a very
electrophilic carbonyl carbon.

-

:O:
Do problem 19.6
C
R
ALDEHYDES & KETONES

+
-

: O:
-

:O:
C
R
R

+
H
C
H
+
no hyperconjugation
H
6
Sec. 19.6
Nucleophilic Addition of HOH, i.e. Hydration:
Aldehydes and ketones react with HOH producing 1,1-diols or geminal (gem) diols. The reaction is
reversible.
O
OH
C
H3C
CH3
H2O
+
CH3
acetone hydrate
(a gem diol)
CH3
C
OH
In most cases the equilibrium favors the carbonyl over the diol. Ketones have values of Keq of about
10-4 to 10-2. For example, acetone hydration yields 99.9% ketone, 0.1% gem diol. For most
aldehydes, Keq is ~ 1. Formaldehyde is an exception, i.e., 99.9% diol, 0.1% aldehyde. Formaldehyde
(b.p. = -21 C) is commonly sold as a 40% aqueous solution called formalin.
Nucleophilic addition of HOH to a ketone or aldehyde is slow in pure water (because water is a weak
nucleophile), but is catalyzed by both acid and base.
Base-catalyzed Hydration Mechanism:
..
_
: O:
H
: O:
sp 2
C
.. : ..
OH
C
+
: OH
..
-
E
Nu:
Acid-catalyzed Hydration Mechanism:
: O:
: O+
+
H3O
C
_
..
..
..OH
.. : ..
OH
:O H
C
sp 3 gem diol
: OH
..
catalyst
sp 3
H
: O:
:O
..
C
H
catalyst
_
+
H3O
H
C
H
+O
..
Nu:-
H
gem diol
..
:O H
..
..
C
H2O
: OH
..
Note that OH is a better Nu: than HOH so that base catalysis is effective. Acid catalysis is also
effective because protonation of the carbonyl oxygen makes the carbonyl C a better electrophile so
that it reacts with the weak Nu:-, HOH.
A variety of acids will add to ketones and aldehydes by the same mechanism as acid catalyzed
hydration, e.g., HCl, HBr, H2SO4, HCN, etc. As with hydration, these additions are reversible and
the equilibrium strongly favors the carbonyl. HCN is an exception, in that equilibrium favors its
addition product, a cyanohydrin.
+
E
-

H
-
Do problems 19.7 & 19.8
Nucleophilic Addition of HCN  Cyanohydrin:
Sec. 19.7
Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN
OH
CH
O
C H
-
HCN, CN
C H
N
pH 8
benzaldehyde
ALDEHYDES & KETONES
NH2
1. LiAlH4 in THF
OH
C
CH2
mandelontrile
(a cyanohydrin)
2.
2-amino-1-phenylethanol
H2O
+
H3O
D
OH
O
CH
C
OH
mandelic acid
7
The reaction occurs slowly with pure HCN (pKa = 9.3) but addition of a small amount of base
generates the strongly nucleophilic CN-. Equilibrium favors the addition product.
The reaction is useful because the nitrile group (-CN) can be further reacted, i.e., reduced by LiAlH4
to a 1 amine (R-CH2-NH2) or oxidized to a carboxylic acid (-COOH) by heating in aqueous acid.

Write out the mechanism for the formation of mandelonitrile. Note that both HCN and CN- are
present at the pH of the reaction (pH 8).

Do problem 19.9
Nucleophilic Addition of a Grignard  Alcohol:
Sec. 19.8
Grignards, RMgX, react with aldehydes and ketones yielding alcohols. The C-Mg bond in the
Grignard is so strongly polarized that it is essentially ionic, R:- +MgX.
: O:
H
1. :CH +MgBr
3
C
H
2.
H3O+
A carbanion, :R-, is added, creating a ‘-’ intermediate which is protonated by dilute aq. acid yielding a
neutral alcohol. Unlike nucleophilic additions of HOH, ROH, etc., Grignard additions are
irreversible because a carbanion is a very poor leaving group in a reversal step.
Nucleophilic Addition of a Hydride, i.e., Reduction  Alcohol:
LiAlH4 and NaBH4 yield hydride nucleophiles (:H-) that add to aldehydes and ketones. Subsequent
addition of HOH or aq. acid protonates the tetrahedral intermediate yielding the alcohol.
: O:
H
C
_
1.
H:
2.
H3O+
H
Sec. 19.9
Nucleophilic Addition of Amines  Imines & Enamines:
1 amines (RNH2) add to aldehydes and ketones producing imines (R2C=NR)
2 amines (R2NH) add similarly producing enamines (R2N-CR=CR2)
..
H
N
H
: O:
NH2R
H
C
C
H
R
+ H2O
C
imine
NHR2
N:
H
C
R
aldehyde or ketone
R
N
R
1º amine
2º amine
R
..
R
N
enamine
C
+
H2O
C
In both cases, after nucleophilic addition, HOH is eliminated.
ALDEHYDES & KETONES
8
Imines: Acid-catalyzed nucleophilic attack of a 1 amine on the carbonyl, followed by proton
transfer from NO produces a neutral amino-alcohol (carbinolamine).

Protonation of the carbinolamine O by acid catalyst converts -OH into HOH, a better leaving
ether
group. Elimination
of HOH produces an iminium ion which loses a proton and regenerates the
acid catalyst.
H
H
.. _
H ..
: O:
+
: O:
:O H
H3O
+
N
R
:O:
H
C +
C ..
C ..
H
H
C
H
H
N
H
C
_
..
H
H3O+
N
H
R
imine

H
R
carbinolamine
H
N
H
H
H
R
proton transfer
pH = 4.5
N
H
H
H
C
H
R
H2O
+
N
H
R
imimium ion
The reaction is catalyzed in weak acid (pH = 4.5) but not strong acid or base because a little acid
is required to protonate the -OH group but too much would neutralize the basic amine.
Enamines: Enamine formation is similar to imine formation up to the iminium ion stage but there is
no proton on N to be lost so the -C loses H yielding the enamine. Write the complete mechanism.
R
..
R
N
: O:
H
H
C
C
pH = 4.5

Do problems 19.10 & 19.12
Derivatives of NH3, i.e., derived from NH3
 Solid amine derivatives of aldehydes and ketones are useful for identifying unknown compounds.
Important derivatives are made from hydroxylamine, semicarbazide, phenylhydrazine, and
2,4-dinitrophenylhydrazine.
H
N
OH
H
hydroxylamine
ALDEHYDES & KETONES
aldoximes
carbonyls
oximes
ketoximes
9
O
H
N
N
carbonyls
C
NH2
semicarbazone
H
H
semicarbazide
NO2
H
carbonyls
N
N
H
2,4-dinitrophenylhydrazone
NO2
H
2,4-dinitrophenylhydrazine
 These reagents are often sold as the hydrochloride salt (R-NH3+Cl-) because the free amine
reagents are prone to oxidation whereas the hydrochloride salts are very stable.
 2,4-dinitrophenylhydrazine forms yellow to orange solid derivatives (precipitates) with almost all
aldehydes and ketones (some long chain aldehydes form oils) and thus is commonly used in
qualitative testing.
O
CH3CH2
H
+
C
N
H
OH
- H2O
CH3CH2
H
mp = 40ºC
O
H
C
H
+
N
OH
- H2O
CH3
H
O
H
CH3
+
N
OH
- H2O
CH3
OH
C
N
OH
CH3
H
acetoxime
acetone
2-propanone oxime
dimethyl ketoxime
2-propanone
dimethyl ketone
mp = 60ºC
bp = 50ºC
H
O
C
N
mp = 47ºC
bp = 20ºC
CH3
C
H
acetaldoxime
acetaldehyde
C
OH
propionaldoxime
bp = 49ºC
CH3
N
H
propionaldehyde
CH3
C
CH3
acetone
+
N
H
N
H
phenylhydrazine
- H2O
CH3
C
N
CH3
N
H
acetone phenylhydrazone
mp = 42ºC
ALDEHYDES & KETONES
10
CH3
C
+
CH3
N
H
acetone
O
O
H
O
N
C
NH2
CH3
- H2O
C
N
CH3
H
semicarbazide
N
C
NH2
H
acetone semicarbazone
mp = 190ºC
 Discretion must be applied since this reagent also forms precipitates with phenols, alkyl and aryl
amines, acid anhydrides and some reactive esters.
Note that oximes, semicarbazones, and phenylhydrazones are all “imines”
N
R
OH
C
oximes
(aldoximes & ketoximes)
H
O
R
+
C
N
R
H
O
N
R
NH
C
- H 2O
NH2
C
semicarbazone
N
R
R
C
IMINES
N
R
NH
C
phenylhydrazone
Note: In the CRC, some of these derivatives are listed under parent compound names, e.g., ...
2-propanone, oxime
2-propanone, 4-nitrophenylhydrazone
2-propanone, semicarbazone
ALDEHYDES & KETONES
11
Sec. 19.10
Nucleophilic Addition of Hydrazine: (The Wolf-Kishner Reaction)
Similar to imine-forming reactions, hydrazine, H2NNH2, in the presence of KOH reduces aldehydes
and ketones to alkanes, R2C=O  R2CH2. DMSO solvent allows the reaction to proceed at room
temperature. We will not study the mechanism, however, the student should appreciate that the
reaction is nucleophilic addition and so as we might expect, this reaction will not reduce olefinic
unsaturation since C-to-C unsaturation is also nucleophilic.
O
C
NH2NH2
CH2CH3
KOH
DMSO
propiophenone
Clemmensen Reduction likewise reduces aldehydes and ketones to alkanes. The reducing agent is
amalgamated zinc, (Zn[Hg]) and conc. HCl. The acid is an alternate to the strong basic conditions of
the Wolf-Kishner reduction. Both Clemmensen and Wolf Kishner reduce nitro groups but do not
reduce alkenes or alkynes.
O
Zn[Hg]
C
H
H3O+
cyclobutanecarbaldehyde
Sec. 19.11
Nucleophilic Addition of Alcohols  Acetals (gem diethers):
Alcohols add reversibly (acid catalyzed) to aldehydes and ketones yielding acetals, R2C(OR’)2.
: O:
+
C
H+
2 ROH
aldehyde
R
..
O
..
..
..O
C
R
+
H2O
acetal

The reaction is similar to hydration and the formation of gem diols. Alcohols, like HOH, are
weak nucleophiles and add to aldehydes and ketones slowly except under acid conditions when
the carbonyl is protonated.

Nucleophilic addition of alcohol to the carbonyl initially yields a hydroxy ether (a hemiacetal).
Equilibrium favors the carbonyl. However, further protonation of the hydroxyl and E-1 like loss
of HOH produces an oxonium ion, R2C=OR+, which reacts with a second equivalent of alcohol
producing an acetal.

Write a mechanism for this reaction.
2 CH3OH
O
+
ALDEHYDES & KETONESH
12

The reversible reaction is driven to acetal formation by removing HOH by distillation. The
reverse reaction occurs with excess aq. acid. Alternately, acetal formation is often carried out
using the alcohol as the solvent and using dry HCl (gas) or p-toluenesulfonic acid. The alcohol is
present in excess and drives the reaction to the acetal. The reaction is reversed by placing an
acetal in water and adding a small quantity of acid catalyst. Acetals are stable in basic solution
because they are ethers.

Acetals are useful as protecting groups for aldehydes and ketones.
For example, ethyl 4-oxopentanoate (ester) needs ketone protection to selectively reduce the ester
group to an alcohol. This can be done by converting the ketone to an acetal, then reducing the
ester. Ethylene glycol is used since it forms a cyclic acetal, which is like using 2 equivalents of
alcohol.
Note that acetals are inert to bases, hydrides, Grignards and catalytic hydrogen.
Esters react with alcohols in the presence of an acid catalyst and heat to undergo
transesterification. The acetal reaction is also done with heating and so it must use a
stoichiometric amount of alcohol to avoid transesterification.
O
O
C
CH3
CH2CH2
C
O
O
CH2CH3
C
CH3
ethyl 4-oxopentanoate
CH2CH2
CH2OH
5-hydroxy-2-pentanone
HOCH2CH2OH
+
H3O
+
H
CH2
CH2
O
O
CH3
C
O
CH2CH2
C
O
HOCH2CH2OH
+
1.
LiAlH4
2.
H3O
+
CH2CH3
CH2
CH2
O
O
CH3
C
CH2CH2
CH2OH
+
CH3CH2OH
Write equations to show how phenyl 2-propenyl ketone can be reduced to phenyl propyl
ketone (propiophenone).
O
O
C CH2CH
CH2
phenyl 2-propenyl ketone

?
C CH2CH2CH3
propiophenone
Write equations to show how 6-bromo-2-hexanone can be reduced to 6-hydroxy-2-hexanone
ALDEHYDES & KETONES
13
Sec. 19.14
Nucleophilic Addition to Conjugated Enones and Enals
The direct addition of nucleophiles to carbonyls (which we have studied thus far) is called a 1,2addition; the nucleophile being added to the #1 C and H being added to the negatively charged
oxygen atom, i.e., position #2. Examples include reaction with Grignards, LiAlH4, HCN/CN, OH-,
OR-, etc.
When the carbonyl is ,-unsaturated, certain nucleophiles will add by 1,4 addition, i.e. conjugate
addition across conjugated double bonds. An enolate intermediate is formed.
..
.. _
: O:
2. : O :
:O H
+
H3O
C
C
Nu:-
Nu:-
direct addition
(1,2-addition)
1. C
-
Nu:
E+
: O:
C
3
4
..
_
: O:
2
C
-
C
1
Nu:
: O:
-
C
C
 , -unsaturated carbonyl
Nu:
C
C
H3O+
_
..
C
C
Nu:-
enolate ion
: O:
C
H
C
C
Nu:-
1,4-conjugate addtion
product
Conjugate addition of amines: 1 and 2 amines add to ,-unsaturated aldehydes and ketones
producing -amino ketones and aldehydes. The reaction occurs rapidly at room temperature with
good yield. Note that only 1 equivalent of amine is used to avoid direct addition from also occurring
O
..
CH3 C CH
3-buten-2-one
CH2
+
H N(CH2CH3)2
diethylamine
O
..
CH3NH2
2-cyclohexanone
Conjugate addition of alkyl groups:
 Gilman reagent (lithium diorganocopper) adds organo groups to ,-unsaturated ketones (but not
aldehydes) via 1,4 addition. 1, 2, 3 alkyl, alkenyl and aryl organo groups all work well. This
reagent adds directly only to acid chlorides.
 Diorganocopper reagents can be prepared by reaction between 1 equivalent of CuI and
2 equivalents of organolithium.
RX + 2 Li  R- Li+ + Li+X2 R- Li+ + CuI  Li+(RCu-R) + Li+ IALDEHYDES & KETONES
14
 Unlike diorganocopper reagents, stronger nucleophiles like Grignards and alkyl lithium (Li+R-) add
only by the usual 1,2-addition and have no effect on the conjugate double bond (or any other
unsaturation).
: O:
4
1.
2
C
C
3
C
1
2.
Li R2 Cu
: O:
C
+
H3O
H
C
1,4-conjugate addtion
product
C
R
 , -unsaturated carbonyl

Write the products of the following reactions.
O
CH3
C
CH
CH2
3-buten-2-one
1.
Li (CH3)2 Cu, ether
+
2.
H3O
O
1. Li (CH2
2.
O
CH)2 Cu , ether
H3O+
1. Li (C6H5)2 Cu , ether
2.
H3O+
O
1. CH3 Mg Br , ether
2.
H3O+
O
C
CH
1.
CH3 Li
2.
H3O+
CH2
In general, strongly basic nucleophiles (like OH-) add quickly and irreversibly to carbonyl carbons but weakly
basic nucleophiles (NH3, R2CuLi, HS-) add reversibly to the carbonyl but irreversibly to the -unsat’d C.

Do problem 19.18
Omit Sec. 19.12
Whittig Reaction
Omit Sec. 19.13
Cannizaro Reaction
Omit Sec. 19.15
Biological Nucleophilic Addition Reactions
Omit Sec. 19.16
Spectroscopic Analysis of Ketones and Aldehydes

Do end-of-chapter problems:
19.25, 27, 28(all except g), 30(all except g), 31, 34, 37, 38a,b, 39(all except g), 41, 43 & 44.
ALDEHYDES & KETONES
15