Transcript aldehydes

ALDEHYDES & KETONES
(ALKANALS & ALKANONES)
1
ALDEHYDES & KETONES (ALKANALS & ALKANONES)
: O:
R
:O:
C
H
R
aldehyde
C
R'
ketone
: O:
Aldehydes & ketones both
contain the carbonyl group.
C
carbonyl group
 The simplest aldehyde is formaldehyde (CH2O). It is the only
aldehyde without an alkyl group attached to the carbonyl C.
: O:
H
C
All other aldehydes, such as acetaldehyde
(CH3CHO), have one alkyl group and one
H attached to the carbonyl C.
H
formaldehyde
: O:
CH3
C
H
acetaldehyde
 All ketones have two alkyl groups attached to the carbonyl C.
H3C
: O:
: O:
C
C
CH3
dimethyl ketone
(acetone)
H3C
: O:
CH2CH3
methyl ethyl ketone
(MEK)
C
CH3
methyl phenyl ketone
(acetophenone)
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Aldehydes and Ketones are Electrophiles
Nu:-
 The carbonyl group has a strong dipole.
: O: d
DEN(O-C) = (3.5-2.5) = 1.0 (a polar bond)
d+
C
 The d+ carbon is an electron acceptor,
E+
(an electrophile).
 Good nucleophiles (CH3MgBr) and even fair nucleophiles (NH3)
will readily add to the carbonyl group of aldehydes and ketones.
tetrahedral ..
alkoxide : O :
: O:
R
sp2
C
C
R
H
Nu:
-
sp
3
Nu
R
The weak p bond breaks as the
Nu:- adds, so that C remains
tetravalent ( 5 bonds).
 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).
3
Aldehydes and Ketones are Electrophiles
 Aldehydes and ketones are moderately reactive as electrophiles
(electron acceptors) among the carboxylic acid derivatives.
:O:
R
C
..
O
..
acid chloride
: O:
C
R
C
: O:
R
C
..
OH
..
C N:
C
most
reactive
: O:
R
R
..
Cl
.. :
acid anhydride
C
H
ketone
ester
:O:
R
carboxylic acid
amide
R
R
aldehyde
: O:
R
: O:
: O:
R
C
:O:
nitrile
carboxylate
C
R
C
..
O
..
..
R
H
N
H
.. _
O
..:
least
reactive
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Basicity of Aldehydes and Ketones
Nu:-
 The d- oxygen is a weak base (pKb ca. 21)
Its non bonded e’s are protonated by strong acids.
R
C
H
HSO4-
R
R
C
E+
: O:
: O+
+
+
d
C
H
H
: O:
: O: d
R
R
C
+
R
 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.
: O:
R
C
H
H
H
R
: O:
: O:
+
HSO4R
C
+
R
..
CH3CH2OH
..
R
C
R
+
CH3CH2OH
..
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Acidity of Aldehydes and Ketones
 The a-carbon is the carbon bonded to the carbonyl, not the
carbonyl carbon itself.
 Hydrogens bonded to the carbonyl carbon, the a-carbon, the
b-carbon, etc. are not polar and thus are not acidic hydrogens.
pKa = ca. 55 for
b-hydrogens in
aldehydes
and ketones
H
H
:O :
H
b
C
C
H
a-hydrogens
pKa = ca. 17 in aldehydes
pKa = ca. 19 in ketones
a
C
H
H
The carbonyl H of an
aldehyde is not acidic.
It's pKa is ca. 50.
 The a-hydrogens can be removed by strong bases because the
carbanion that forms is stabilized by resonance with the
adjacent carbonyl oxygen forming an enolate.
H
H
H
b
C
:O :
H
C
H
a
C
H
H
OH-
C
H
H
H
:O :
C
C
..
..
H
H
C
H
H
H
:O :
C
C
enolate
H
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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.
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IUPAC Nomenclature of Aldehydes
Aldehydes: in open chains:
alkane+al  “alkanal”
OH
O
CH3CHBrCH2C H
4
3
2
1
3-bromobutanal
O
O
CH2C H
CH3CHCH2CH2C H
5
4
3
2
2
1
4-hydroxypentanal
1
2-phenylethanal
 The parent chain must contain the CHO- group, and this group is
numbered as carbon 1 (because it is always at a chain end).
Aldehydes: attached to rings:
ring+carbaldehyde  “ringcarbaldehyde”
O
O
C H
C H
benzenecarbaldehyde
HO
CHO
3-hydroxycyclopentanecarbaldehyde
cyclohexanecarbaldehyde
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Functional Group Precedence in Nomenclature
Functional Group
Name as Suffix
Name as Prefix
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
Principal Groups
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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’.
Structure
IUPAC
name
HCO2H
methanoic acid
CH3CO2H
ethanoic acid
CH3CH2CO2H
propanoic acid
CH3(CH2)2CO2H
butanoic acid
CH3(CH2)3CO2H
pentanoic acid
CH3(CH2)4CO2H
hexanoic acid
Common name
Structure
IUPAC
Common name
formic acid
acetic acid
propionic acid
butyric acid
valeric acid
caproic acid
HCHO
methanal
CH3CHO
ethanal
CH3CH2CHO
propanal
CH3(CH2)2CHO
butanal
CH3(CH2)3CHO
pentanal
CH3(CH2)4CHO
hexanal
formaldehyde
acetaldehyde
propionaldehyde
butyraldehyde
valeraldehyde
caproaldehyde
 Substituents locations are given using Greek letters (a, b, , d, , .)
beginning with the carbon next to the carbonyl carbon, the a-carbon.
O
CH3CHBrCH2C H
 b a
b-bromobutyraldehyde
OH
O
O
CH3CHCH2CH2C H
d  b a
-hydroxyvaleraldehyde
CH2C H
a
a-phenylacetaldehyde
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IUPAC Nomenclature of Ketones
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’.
O4 5
1 2
CH3 CHCCHCH3
O
CH3 CCH2 CH3
1 2 3 4
2-butanone
Cl
CH3
2-chloro-4-methyl-3-pentanone
O
C CH2 CH2 CH3
1 2 3 4
1-phenyl-1-butanone
 Ketones are just below aldehydes in nomenclature priority.
 A ketone group is named as an ‘oxo’ substituent in an aldehyde.
O
CH3CH2CCH2CHO
5 4 32 1
3-oxopentanal
H3C
4
1
O
An olefinic ketone is named
2
3
as an ‘enone’, literally:
4-methyl-2-cyclohexen-1-one
“#-alken-#-one”.
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Common Names of Ketones
:O:
R
C
R'
alkyl alkyl ketone
 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 (a, b, , d, , .) beginning with the a-carbon.
O
CH3
CH3CCH2CHCH3
b a O
CH3CHCCHCH3
Cl
C CH2CH2CH2
a b 
CH3
methyl isobutyl ketone
a-chloroethyl isopropyl ketone
(MIBK)
Some historic
names persist:
O
OCH3
-methoxypropyl phenyl ketone
O
O
O
C CH3
C
C H
acetophenone
benzophenone
benzaldehyde
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Nomenclature Practice
 Name these in IUPAC and, where possible, common nomenclature.
O
CH2
C
O
F
CH3
C
(I) 1-phenyl-2-propanone
O
C
H
H
(I) 4-fluorocyclohexane-1-carbaldehyde
(I) 3-cylcopentene-1-carbaldehyde
(c) methyl benzyl ketone
 Draw the structures of the following compounds.
butanedial
bromomethyl b-bromoethyl ketone 2,4-pentanedione
O
O
O
HCCH2CH2CH
BrCH2
C
O
CH2CH2Br
H3C
C
O
 And these:
CH3CH
CH
C
(I) 2-butenal
O
CH2
C
CH3
O
H
CH2
CH
C
CH3
(I) 3-buten-2-one
(c) methyl vinyl ketone
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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
HOCH2
2.
CH2OH
PCC in CH2Cl2
O
O
HC
CH
Dry ice
(solid CO2)
sublimes at
–78°C.
Reduction of acid chlorides,esters, and nitriles.
: O:
acid chloride
R
C
..
Cl
.. :
-78°C
1equiv.
R
: O:
ester
nitrile
R
R
C
C
: O:
..
..
OR
N:
1 DIBAH
+
2 H3O
C
aldehyde
H
Only 1 equivalent
of very cold DIBAH
is used to avoid
further reduction of
the aldehyde to an
alcohol.
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Preparation of Aldehydes (2 Methods)

Recall that 1° alcohols are readily oxidized to carboxylic acids by most
oxidants in aqueous media.
moderate to
strong oxidation
(Cr+6, HNO3, KMnO4, etc.)
R
OH
1° alcohol
mild oxidation
CrO3 in N
or
PCC in CH2Cl2
R
C
: O:
moderate to
strong oxidation
: O:
H
aldehyde
R
Jones reagent
CrO3 in H2SO4
C
..
OH
..
carboxylic acid
1 LiAlH4
+
2 H3O

In non aqueous media, moderate to strong oxidants become mild,
oxidizing 1° alcohols only as far as the aldehyde.

Carboxylic acids can be reduced to 1° alcohols with LiAlH4, but no
reagent has been found that will stop the reduction at the aldehyde.
15
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).
CH3
H
CH3CHCH2
Al
CH3
CH3
CH2CHCH3
CH3CHCH2
+
Al
diisobutyl aluminum hydride (DIBAH)



CH3
CH2CHCH3
+
H:
_
H
Al
H
H
aluminum
hydride
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.
16
Preparation of Aldehydes (2 Methods)

Study the following examples and note which groups are displaced by
the hydride (H:-) from DIBAH.
O
CH3CH2 C O CH3
methyl propanoate
toluene
1. DIBAH -78ºC
propanal
CH3CH2
+
O
C
H
+
CH3OH
2. H3O
O
_
_
HCl
NH3
CH3CH2C
propanenitrile
CH3CH2 C Cl
propanoyl chloride

a)
Write equations showing the preparation of:
pentanal from 1-pentanol
CH3CH2CH2CH2CH2OH
b)
c)
butanal from an ester
C
N
CH3CH2CH2CH2CH
CrO3 in N
-78°C
1equiv.
CH3CH2CH2COCH3
-78°C
1equiv.
1 DIBAH
+
2 H3O
O
C
O
PCC in CH2Cl2
or
O
benzaldehyde from a nitrile
N
1 DIBAH
+
2 H3O
O
CH3CH2CH2CH
H
17
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.
(CH3 )3 C
PCC
(CH3 )3 C
OH
or Jones reagent
2.
O
4-t-butylcyclohexanone
Friedel Crafts Acylation of Aromatics: yields ketones when an acid
chloride is used as the electrophile.
O
O
+
HO
CH3CH2 C
AlCl3
propanoyl chloride
3.
HO
Cl
EAS
C
CH2CH3
1-(4-hydroxyphenyl)propanone
Hydration of Alkynes: with Hg+2 and H3O+ yields an enol, that
‘tautomerizes’ to a ketone.
Hg(OAc)2
CH3 (CH2)3 C
1-hexyne
CH
+
H3O
O
CH3 (CH2)3 C
an enol
H
CH
H
O
CH3 (CH2)3 C
2-octanone
H
CH
H
18
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.
O
CH3 (CH2)4 C
Cl
dimethyl copper lithium
Gilman reagent
hexanoyl chloride

O
ether
CH3 (CH2)4 C
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. ..
: O:
R
(CH3)2 Cu- Li+
+
- 78ºC
C
..
Cl
.. :
acid chloride
..
CH3MgBr
R
C
:O
:O:
: O:
CH3MgBr
CH3
ketone
R
C
alkoxide CH3
+
2 H3O
CH3
R
C
3° alcohol CH3
H
CH3
19
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
CH3CH2C
CCH2CH3
CH3CH2C
+2
+
H
: O:
3-hexanone
H3C
..
Cl
.. :
C
O
C
AlCl3
MgBr
H
C
Br
CH
CH3
1 BH3, THF
2 NaOH, H2O2, pH8
CH3
OH
CCH2CH3
H
O
C
CH3
+
HBr
m-bromoacetophenone
..
:OH
H3O+
CH
CH3
CH3 Cr+6, H+
+6
+
O
C
CH3
acetophenone
1-methylcyclohexene  2-methylcyclohexanone
CH3
H
CH3
acetophenone
bromobenzene  acetophenone ..
: O:
: O:
Br
Mg in ether
FeBr3
Br2
acetyl chloride
d)
CH3CH2C
benzene  m-bromoacetophenone
+
c)
CCH2CH3
Hg , H3O
3-hexyne
b)
O
OH
CH3
Cr , H
O
20
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.
o- and pdirecting
NH2
OCH3
o- and pdirecting
F
CH3
m-directing
Br
O
O
CH
C OH
O
NH C CH3
activators
NO2
Reactivity
Reactivity
OH
SO3H
H
Cl
deactivators
I
O
O
COCH3
C CH3
C N
+
N R3
deactivators
21