1
ALDEHYDES & KETONES
(ALKANALS & ALKANONES)
2
ALDEHYDES & KETONES (ALKANALS & ALKANONES)
The simplest aldehyde is formaldehyde (CH2O). It is the only aldehyde without an alkyl group attached to the carbonyl C.
C
O
carbonyl group
: :
R C
O
R'ketone
: :
R C
O
H
aldehyde
: :Aldehydes & ketones both contain the carbonyl group.
All other aldehydes, such as acetaldehyde (CH3CHO), have one alkyl group and one H attached to the carbonyl C.formaldehyde
C
O
HH
: :
C
O
HCH3
: :
acetaldehyde
All ketones have two alkyl groups attached to the carbonyl C.
: :
CCH3
O
methyl phenyl ketone (acetophenone)
: :
CH3C CH3
O
dimethyl ketone (acetone)
: :
CH3C CH2CH3
O
methyl ethyl ketone (MEK)
3
Aldehydes and Ketones are Electrophiles
The carbonyl group has a strong dipole.
EN(O-C) = (3.5-2.5) = 1.0 (a polar bond) The + carbon is an electron acceptor,
(an electrophile). Good nucleophiles (CH3MgBr) and even fair nucleophiles (NH3)
will readily add to the carbonyl group of aldehydes and ketones.
Nu:-
E+
C
O
+
: :
The alkyl group and the H atom bonded to the carbonyl are not leaving groups. They are not displaced because hydride (H:-) and alkanides (R:-) are extremely strong bases.
pKb H:- = -21 and pKb :CH3- = -40! (:CH3
- = methide).
: :
R C
O
HNu:-
: :
R C
O
R
Nu
..
sp2 sp3
tetrahedralalkoxide
The weak bond breaks as the Nu:- adds, so that C remains tetravalent ( 5 bonds).
4
Aldehydes and Ketones are Electrophiles Aldehydes and ketones are moderately reactive as electrophiles
(electron acceptors) among the carboxylic acid derivatives.
most
reactive
acid chloride
acid anhydride
aldehyde
ketone
ester
carboxylic acid
amide
nitrile
carboxylate
least
reactive
R C
O
Cl
: :
:....
R RC
O
O C
O: : : :....
R C
O
H
: :
R RC
O: :
R RC
O
O....
: :
R C
O
OH
: :
..
..
R N
H
HC
O: :..
R
_
C
O
O:
::....
R C N:
5
H+HSO4-: :
R C
O
R
Basicity of Aldehydes and Ketones
The - oxygen is a weak base (pKb ca. 21)Its non bonded e’s are protonated by strong acids.
: :
R C
O
R
H
+
:
R C
O
R
H+
The + charge is shared with the carbonyl C by resonance forming a carbocation – a very good E+.
Even weak Nu:-’s (like H2O and ROH) will donate electrons to an aldehyde or ketone in the presence of a strong acid catalyst, e.g., H2SO4 or HCl.
Nu:-
E+
C
O
+
: :
H+HSO4-: :
R C
O
R
: :
R C
O
R
H
+ CH3CH2OH..
..
: :
R C
O
R
H
CH3CH2OH..
+
6
Acidity of Aldehydes and Ketones
The -carbon is the carbon bonded to the carbonyl, not the carbonyl carbon itself.
Hydrogens bonded to the carbonyl carbon, the -carbon, the -carbon, etc. are not polar and thus are not acidic hydrogens.
C
H
H
C
O: :
C
H
H
HH
-hydrogenspKa = ca. 17 in aldehydespKa = ca. 19 in ketones
pKa = ca. 55 for-hydrogens in aldehydes and ketones
The carbonyl H of analdehyde is not acidic.It's pKa is ca. 50.
The -hydrogens can be removed by strong bases because the carbanion that forms is stabilized by resonance with the adjacent carbonyl oxygen forming an enolate.
C
H
C
O: :
C
H
H
HH..
enolate
C
H
H
C
O: :
C
H
H
HH
OH-
C
H
C
O: :
C
H
H
HH
..
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Boiling Points and Solubility of Aldehydes and Ketones
The carbonyl group is strongly polar but does not produce hydrogen bonding (It has no polar hydrogens). 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.
8
IUPAC Nomenclature of Aldehydes
Aldehydes: in open chains:
alkane+al “alkanal”
Aldehydes: attached to rings:
ring+carbaldehyde “ringcarbaldehyde”
1234
3-bromobutanal 4-hydroxypentanal 12345
2-phenylethanal
12
The parent chain must contain the CHO- group, and this group is numbered as carbon 1 (because it is always at a chain end).
C
O
H C
O
HHO CHO
benzenecarbaldehyde 3-hydroxycyclopentanecarbaldehyde
cyclohexanecarbaldehyde
CH3CHBrCH2C
O
H CH3CHCH2CH2C
O
H
OH
CH2C
O
H
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Functional Group Precedence in Nomenclature Functional Group Name as Suffix Name as Prefix
Principal Groups
Carboxylic Acids -oic acid –carboxylic acid
carboxy
Acid Anhydrides -oic anhydride -carboxylic anhydride
Esters -oate -carboxylate
alkoxycarbonyl
Acid Halides -oyl halide -carbonyl halide
halocarbonyl
Amides -amide -carboxamide
amido
Nitriles -nitrile -carbonitrile
cyano
Aldehydes -al -carbaldehyde
oxo
Ketones -one oxo
Alcohols -ol hydroxy
Phenols -ol hydroxy
Thiols -thiol mercapto
Amines -amine amino
Imines -imine imino
Alkenes -ene alkenyl
Alkynes -yne alkynyl
Alkanes -ane alkyl
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Common Names of Aldehydes
In the common system, aldehydes are named from the common names of the corresponding carboxylic acid.
The ‘ic acid’ ending is replaced with ‘aldehyde’.
Substituents locations are given using Greek letters (, , , , , .) beginning with the carbon next to the carbonyl carbon, the -carbon.
Structure IUPAC name Common name Structure IUPAC Common name
HCO2H methanoic acid HCHO methanal
CH3CO2H ethanoic acid CH3CHO ethanal
CH3CH2CO2H propanoic acid CH3CH2CHO propanal
CH3(CH2)2CO2H butanoic acid CH3(CH2)2CHO butanal
CH3(CH2)3CO2H pentanoic acid CH3(CH2)3CHO pentanal
CH3(CH2)4CO2H hexanoic acid CH3(CH2)4CHO hexanal
formic acid
acetic acid
propionic acid
butyric acid
valeric acid
caproic acid
formaldehyde
acetaldehyde
propionaldehyde
butyraldehyde
valeraldehyde
caproaldehyde
-bromobutyraldehyde -hydroxyvaleraldehyde -phenylacetaldehyde
CH3CHBrCH2C
O
H CH3CHCH2CH2C
O
H
OH
CH2C
O
H
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IUPAC Nomenclature of Ketones
Ketones are just below aldehydes in nomenclature priority. A ketone group is named as an ‘oxo’ substituent in an aldehyde.
Ketones: in both open chains and rings:
alkane+one “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’.
CH3CCH2CH3
OCH3CHCCHCH3
O
Cl CH3
C CH2CH2CH3
O
1 2 3 4
2-butanone 2-chloro-4-methyl-3-pentanone
1 2 4 5
1 2 3 4
1-phenyl-1-butanone
12345
3-oxopentanal
An olefinic ketone is named as an ‘enone’, literally: “#-alken-#-one”.
1
23
4
4-methyl-2-cyclohexen-1-one
CH3CH2CCH2CHO
O
OH3C
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Common Names of Ketones
The two alkyl groups attached to the carbonyl are named and the word ‘ketone’ is added as a separate word. It is literally ‘alkyl alkyl ketone’.
The alkyl groups are listed alphabetically or in order of increasing size.
As with aldehydes, substituents locations are given in common names using Greek letters (, , , , , .) beginning with the -carbon.
: :
R C
O
R'
alkyl alkyl ketone
methyl isobutyl ketone (MIBK)
-chloroethyl isopropyl ketone -methoxypropyl phenyl ketone
C CH3
O
C H
O
C
O
acetophenone benzophenone benzaldehyde
Some historic names persist:
CH3CHCCHCH3
O
Cl CH3
C CH2CH2CH2
OOCH3
CH3CCH2CHCH3
O CH3
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Nomenclature Practice
Name these in IUPAC and, where possible, common nomenclature.
CH2 C
O
CH3
F
C
O
H C
O
H
(I) 1-phenyl-2-propanone
(c) methyl benzyl ketone
(I) 4-fluorocyclohexane-1-carbaldehyde
(I) 3-cylcopentene-1-carbaldehyde
Draw the structures of the following compounds.
butanedial bromomethyl -bromoethyl ketone 2,4-pentanedione
And these:
(I) 2-butenal (I) 3-buten-2-one(c) methyl vinyl ketone
HCCH2CH2CH
OO
C
O
CH2CH2BrBrCH2
C
O
H3C CH2 C
O
CH3
CH3CH CH C
O
H
C
O
CH3 CH2 CH
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Preparation of Aldehydes (2 Methods)
1. Mild oxidation of 1° Alcohols: (with anhydrous oxidants, PCC in CHCl2 or Collins reagent (CrO3 in pyridine). 1,3-cyclobutanedicarbaldehyde
2. Reduction of acid chlorides,esters, and nitriles.
1 DIBAH
2 H3O+
: :
R C
O
H
aldehyde
C
O
R Cl
: :
:....
C
O
R OR
: :
..
..
R C N:
-78°C1equiv.
acid chloride
ester
nitrile
Only 1 equivalent of very cold DIBAH is used to avoid further reduction of the aldehyde to an alcohol.
Dry ice (solid CO2) sublimes at
–78°C.
HOCH2 CH2OHPCC in CH2Cl2
HC CH
OO
15
1 LiAlH4
2 H3O+
Preparation of Aldehydes (2 Methods)
Recall that 1° alcohols are readily oxidized to carboxylic acids by most oxidants in aqueous media.
moderate tostrong oxidation
In non aqueous media, moderate to strong oxidants become mild, oxidizing 1° alcohols only as far as the aldehyde.
PCC in CH2Cl2
CrO3 in N
or
: :
R C
O
H
aldehyde
R OH
1° alcohol
mild oxidationC
O
R OH
: :
..
..
carboxylic acid
moderate tostrong oxidation
Jones reagentCrO3 in H2SO4
Carboxylic acids can be reduced to 1° alcohols with LiAlH4, but no reagent has been found that will stop the reduction at the aldehyde.
(Cr+6, HNO3, KMnO4, etc.)
16
Preparation of Aldehydes (2 Methods)
Carboxylic acids are difficult to reduce and any reducing agent strong enough to reduce them, e.g., LiAlH4, will not stop at the aldehyde but always produces the 1° alcohol.
Several ‘derivatives’ of carboxylic acids can be reduced to aldehydes under carefully controlled conditions.
Acid chlorides, esters, and nitriles are reduced to aldehydes using very cold conditions (-78°C) and only 1 equivalent of a mild reducing agent, ‘diisobutylaluminum hydride’ = DIBAH (usually in toluene).
CH3CHCH2
CH3
CH2CHCH3
CH3
Al
H
CH3CHCH2
CH3
CH2CHCH3
CH3
Al+ H:
_
diisobutyl aluminum hydride (DIBAH)
+
DIBAH is weaker than LiAlH4. DIBAH is neutral; LiAlH4 is ionic.
DIBAH is similar to AlH3 but is hindered by its bulky isobutyl groups.
Only one mole of H:- is released per mole of DIBAH.
Al
H
H H
aluminumhydride
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1.
2. H3O+
DIBAH -78ºCtoluene
CH3CH2 C
O
H + CH3OH
CH3CH2 C
O
Cl
propanoyl chloride
CH3CH2 C
O
O CH3
methyl propanoateCH3CH2C N
propanenitrileNH3
_HCl
_
propanal
Preparation of Aldehydes (2 Methods)
Study the following examples and note which groups are displaced by the hydride (H:-) from DIBAH.
Write equations showing the preparation of:
a) pentanal from 1-pentanol
b) butanal from an ester
c) benzaldehyde from a nitrile
CH3CH2CH2CH2CH2OH
PCC in CH2Cl2or
CrO3 in N
CH3CH2CH2CH
O
1 DIBAH
2 H3O+
-78°C1equiv.
C N
1 DIBAH
2 H3O+
-78°C1equiv.
C
O
H
CH3CH2CH2CH2CH
O
CH3CH2CH2COCH3
O
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Preparation of Ketones (4 Methods)
1. Oxidation of 2° Alcohols: with mild (anhydrous) oxidants, moderate, or strong oxidants, e.g., H2CrO4, HNO3, KMnO4, NaOCl, etc.
OH(CH3 )3 CPCC
or Jones reagent
O(CH3 )3 C
4-t-butylcyclohexanone
2. Friedel Crafts Acylation of Aromatics: yields ketones when an acid chloride is used as the electrophile.
HO CH3CH2 C
O
Cl+AlCl3
EASpropanoyl chloride 1-(4-hydroxyphenyl)propanone
3. Hydration of Alkynes: with Hg+2 and H3O+ yields an enol, that ‘tautomerizes’ to a ketone.
CH3 (CH2)3 C CH
Hg(OAc)2
H3O+
1-hexyne
CH3 (CH2)3 C CH
H
OH
an enol
CH3 (CH2)3 C CH
H
O H
2-octanone
CHO
O
CH2CH3
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Preparation of Ketones (4 Methods)
4. Acid Chlorides + Lithium Dialkyl Copper (Gilman Reagent): produces ketones.
The reaction is unique to these two reagents and the mechanism is uncertain. As with DIBAH for aldehyde reductions, a low temperature (-78 C) solvent (ether) is used to prevent further alkyl addition to the ketone to form an alcohol. (Acid chlorides are very good electrophiles).
Carboxylic acids, esters, anhydrides and amides are not reduced by diorganocopper reagents. They are not as reactive as acid chlorides.
CH3 (CH2)4 C
O
Cl
hexanoyl chloride
+ (CH3)2 Cu- Li+
dimethyl copper lithiumGilman reagent
78ºC
ether
-
CH3 (CH2)4 C
O
CH3
2-heptanone
Recall that a stronger reducing reagent, such as a Grignard (RMgBr) will also reduce an acid chloride to a ketone, but reduction cannot be stopped here. The ketone is further reduced to an alcohol.
C
O
R Cl
: :
:....
CH3MgBr
acid chlorideC
O
R CH3
: :CH3MgBr
ketone
C
O
R CH3
:
CH3
..:
2 H3O+
alkoxide 3° alcohol
C
O
R CH3
:
CH3
..H
20
Preparation of Ketones Problems
Write equations to show how the following transformations can be carried out. Show all reagents and intermediate products.
a) 3-hexyne 3-hexanone
b) benzene m-bromoacetophenone
c) bromobenzene acetophenone
d) 1-methylcyclohexene 2-methylcyclohexanone
CH3CH2C CCH2CH3
3-hexyne Hg+2, H3O+
AlCl3C
O
H3C Cl
: :
:....
acetyl chloride
+Br2
FeBr3 C
OBr
+
CH3
HBr
m-bromoacetophenone
Br MgBr
CH3CH2C CCH2CH3
O
H
H
3-hexanone
CH3CH2C CCH2CH3
OH
H
C
O
CH3
acetophenone
Mg in ether
C
O
H CH3
: :
CH
O: :..
CH3 H3O
+ CH
OH:..
CH3
C
O
CH3
acetophenone
Cr+6, H+
CH3 BH3, THFNaOH, H2O2, pH8
12
CH3
OH
Cr+6, H+CH3
O
21
NH2
OH
CH3OCH3 F
Cl
Br
I
C OH
O
C CH3
O
C H
O
NH C CH3
O
SO3H NO2
N+R3C N
COCH3
OH
Reactivity Reactivity
o- and p- directing
activators
o- and p- directing
deactivatorsdeactivators
m-directing
Preparation of Ketones Problems
Recall the effects of substituents on aromatic rings. They affect both the reactivity of aromatics and the position at which Electrophilic Aromatic Substitution (EAS) will occur.