ALDEHYDES & KETONES
(ALKANALS & ALKANONES)
ALDEHYDES & KETONES (ALKANALS & ALKANONES)
: O:
R C H aldehyde
:O:
R C R' ketone
Aldehydes & ketones both contain the carbonyl group.
: O:
C
carbonyl group
q The simplest aldehyde is formaldehyde (CH2O). It is the only aldehyde without an alkyl group attached to the carbonyl C.
: O:
H C H formaldehyde
All other aldehydes, such as acetaldehyde (CH3CHO), have one alkyl group and one H attached to the carbonyl C.
: O:
CH3 C H acetaldehyde
qAll ketones have two alkyl groups attached to the carbonyl C.
: O:
H3C
: O:
CH3
H3C
: O:
CH2CH3
CH3
dimethyl ketone (acetone)
methyl ethyl ketone (MEK)
methyl phenyl ketone (acetophenone)
Aldehydes and Ketones are Electrophiles
q The carbonyl group has a strong dipole. : O: EN(O-C) = (3.5-2.5) = 1.0 (a polar bond) + q The + carbon is an electron acceptor, C (an electrophile). E+ q Good nucleophiles (CH3MgBr) and even fair nucleophiles (NH3) will readily add to the carbonyl group of aldehydes and ketones. tetrahedral
: O:
R C H Nu:
-
Nu:
alkoxide
: O:
3
..
C
sp2
sp
Nu
The weak bond breaks as the Nu:- adds, so that C remains tetravalent ( 5 bonds).
qThe 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. qpKb H:-= -21 and pKb :CH3- = -40! (:CH3- = methide).
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Aldehydes and Ketones are Electrophiles
qAldehydes and ketones are moderately reactive as electrophiles (electron acceptors) among the carboxylic acid derivatives.
:O:
R C
.. O ..
: O:
C R
: O:
R C R
: O:
R C
.. OH ..
N:
acid chloride acid anhydride aldehyde ketone ester carboxylic acid amide nitrile carboxylate
: O:
R C
.. Cl : ..
: O:
R C H
most reactive
:O:
R C
:O:
R C
.. O ..
..
N
H H
:O:
R C
.. _ O: ..
least reactive
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Basicity of Aldehydes and Ketones
q The - oxygen is a weak base (pKb ca. 21) Its non bonded es are protonated by strong acids.
: O:
R C R H
+
Nu:
: O:
HSO4R
: O+
C
H R
R
C
E+
R
: O:
C
qThe + charge is shared with the carbonyl C by resonance forming a carbocation a very good E+. qEven 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 R
HSO4R
: O:
C
: O:
R .. CH3CH2OH ..
C
+
R
5
CH3CH2OH ..
Acidity of Aldehydes and Ketones
qThe -carbon is the carbon bonded to the carbonyl, not the carbonyl carbon itself. qHydrogens bonded to the carbonyl carbon, the -carbon, the -carbon, etc. are not polar and thus are not acidic hydrogens.
H C H
pKa = ca. 55 for -hydrogens in aldehydes and ketones
H H H
:O :
C
-hydrogens pKa = ca. 17 in aldehydes pKa = ca. 19 in ketones H The carbonyl H of an aldehyde is not acidic. It's pKa is ca. 50.
qThe -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 C H C H
:O :
C H OHH
H C H
H C ..
:O :
C H
H H H C
H C
:O :
C H
..
enolate
Boiling Points and Solubility of Aldehydes and Ketones qThe 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. qFormaldehyde 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). qLower molecular weight aldehydes and ketones are water soluble. Acetone, formaldehyde and acetaldehyde are miscible in water.
IUPAC Nomenclature of Aldehydes
Aldehydes: in open chains: alkane+al alkanal
O
4
OH
5
4 3 2
O
1
2
O CH2C H
1
CH3CHBrCH2C H
3 2 1
CH3CHCH2CH2C H
3-bromobutanal
4-hydroxypentanal
2-phenylethanal
qThe 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 C H O C H HO CHO
benzenecarbaldehyde
3-hydroxycyclopentanecarbaldehyde cyclohexanecarbaldehyde
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Functional Group Precedence in Nomenclature
Functional Group Principal Groups Carboxylic Acids Acid Anhydrides Esters Acid Halides Amides Nitriles Aldehydes Ketones Alcohols Phenols Thiols Amines Imines Alkenes Alkynes Alkanes -oic acid carboxylic acid -oic anhydride -carboxylic anhydride -oate -carboxylate -oyl halide -carbonyl halide -amide -carboxamide -nitrile -carbonitrile -al -carbaldehyde -one -ol -ol -thiol -amine -imine -ene -yne -ane alkoxycarbonyl halocarbonyl amido cyano oxo oxo hydroxy hydroxy mercapto amino imino alkenyl alkynyl alkyl carboxy Name as Suffix Name as Prefix
Common Names of Aldehydes
qIn the common system, aldehydes are named from the common names of the corresponding carboxylic acid. qThe ic acid ending is replaced with aldehyde.
Structure HCO2H CH3CO2H CH3CH2CO2H CH3(CH2)2CO2H CH3(CH2)3CO2H CH3(CH2)4CO2H IUPAC name Common name Structure HCHO CH3CHO CH3CH2CHO CH3(CH2)2CHO CH3(CH2)3CHO CH3(CH2)4CHO IUPAC methanal ethanal propanal butanal pentanal hexanal Common name
methanoic acid ethanoic acid propanoic acid butanoic acid pentanoic acid hexanoic acid
formic acid acetic acid propionic acid butyric acid valeric acid caproic acid
formaldehyde acetaldehyde propionaldehyde butyraldehyde valeraldehyde caproaldehyde
qSubstituents locations are given using Greek letters (, , , , , .) beginning with the carbon next to the carbonyl carbon, the -carbon.
O CH3CHBrCH2C H OH O O CH2C H CH3CHCH2CH2C H
-bromobutyraldehyde
-hydroxyvaleraldehyde
-phenylacetaldehyde
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IUPAC Nomenclature of Ketones
Ketones: in both open chains and rings: alkane+one alkanone qThe 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.
O CH3 CCH2 CH3
1 2 3 4
O4 5 CH3 CHCCHCH3
1 2
O C CH2 CH2 CH3 3 4 1 2
Cl
CH3
2-butanone
2-chloro-4-methyl-3-pentanone
1-phenyl-1-butanone
qKetones are just below aldehydes in nomenclature priority. qA ketone group is named as an oxo substituent in an aldehyde.
O CH3CH2CCH2CHO 5 4 3 2 1
3-oxopentanal
An olefinic ketone is named 2 3 as an enone, literally: 4-methyl-2-cyclohexen-1-one #-alken-#-one.
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H3C
Common Names of Ketones
qThe two alkyl groups attached to the carbonyl are named and the word ketoneis added as a R C R' separate word. It is literally alkyl alkyl ketone. qThe alkyl groups are listed alphabetically or in order of increasing size. alkyl alkyl ketone qAs with aldehydes, substituents locations are given in common names using Greek letters ( , , , , , .) beginning with the -carbon.
O
CH3
:O:
CH3CCH2CHCH3
O CH3CHCCHCH3
OCH3
methyl isobutyl ketone -chloroethyl isopropyl ketone (MIBK)
O
Cl
CH3
C CH2CH2CH2
O C
-methoxypropyl phenyl ketone O
C H
Some historic names persist:
C CH3
acetophenone
benzophenone
benzaldehyde
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Nomenclature Practice
qName these in IUPAC and, where possible, common nomenclature.
O CH2 C CH3 F O C H O C H
(I) 1-phenyl-2-propanone (c) methyl benzyl ketone
(I) 4-fluorocyclohexane-1-carbaldehyde (I) 3-cylcopentene-1-carbaldehyde
qDraw the structures of the following compounds. butanedial bromomethyl -bromoethyl ketone 2,4-pentanedione
O O
BrCH2 O C CH2CH2Br
H3C O C CH2 O O C CH3
HCCH2CH2CH
qAnd these:
CH3CH CH
O C H
CH2 CH
CH3
(I) 2-butenal
(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 CH2OH PCC in CH2Cl2
O HC
O CH
2.Reduction of acid chlorides,esters, and nitriles.
: O:
Dry ice (solid CO2) sublimes at 78
acid chloride ester nitrile
.. Cl : ..
..
-78C 1equiv.
R 1 DIBAH + 2 H3O
: O:
C H aldehyde
: O:
R C
OR ..
N:
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)
qRecall that 1 alcohols are readily oxidized to carboxylic acids by most oxidants in aqueous media.
moderate to strong oxidation
(Cr+6, HNO3, KMnO4, etc.)
: O:
R C H aldehyde moderate to strong oxidation R
: O:
C
OH
mild oxidation
CrO3 in N or PCC in CH2Cl2
1 alcohol
Jones reagent CrO3 in H2SO4
OH ..
..
carboxylic acid
1 LiAlH4 + 2 H3O
qIn non aqueous media, moderate to strong oxidants become mild, oxidizing 1 alcohols only as far as the aldehyde. qCarboxylic acids can be reduced to 1 alcohols with LiAlH4, but no reagent has been found that will stop the reduction at the aldehyde.
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Preparation of Aldehydes (2 Methods)
qCarboxylic 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. qSeveral derivatives of carboxylic acids can be reduced to aldehydes under carefully controlled conditions. qAcid chlorides, esters, and nitriles are reduced to aldehydes using very cold conditions (-78C) and only 1 equivalent of a mild reducing agent, diisobutylaluminum hydride = DIBAH (usually in toluene).
CH3 CH3CHCH2 H Al CH3 CH2CHCH3 CH3 CH3CHCH2 _
H Al H H aluminum hydride
+ Al
CH3 CH2CHCH3
H:
diisobutyl aluminum hydride (DIBAH)
qDIBAH is weaker than LiAlH4. DIBAH is neutral; LiAlH4 is ionic. qDIBAH is similar to AlH3 but is hindered by its bulky isobutyl groups. qOnly one mole of H:-is released per mole of DIBAH. q
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Preparation of Aldehydes (2 Methods)
qStudy the following examples and note which groups are displaced by the hydride (H:-) from DIBAH.
O CH3CH2 C O CH3 methyl propanoate O CH3CH2 C Cl propanoyl chloride toluene 1. DIBAH -78C 2. H3O _
+
propanal CH3CH2
O C H + CH3OH CH3CH2C N
HCl
_ NH 3
propanenitrile
qWrite equations showing the preparation of: a)pentanal from 1-pentanol b)butanal from an ester
CH3CH2CH2CH2CH2OH
O
PCC in CH2Cl2 or CrO3 in N
CH3CH2CH2CH2CH
O CH3CH2CH2CH
c)benzaldehyde from a nitrile
C N
-78C 1equiv. 1 DIBAH + 2 H3O
CH3CH2CH2COCH3
-78C 1equiv.
O C H
1 DIBAH + 2 H3O
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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.
PCC (CH3 )3 C OH or Jones reagent
(CH3 )3 C
4-t-butylcyclohexanone
2.Friedel Crafts Acylation of Aromatics: yields ketones when an acid chloride is used as the electrophile.
O C
O HO + CH3CH2 C Cl AlCl3 EAS
HO
CH2CH3
propanoyl chloride
1-(4-hydroxyphenyl)propanone
3.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
H CH H
CH3 (CH2)3 C
2-octanone
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Preparation of Ketones (4 Methods)
4.Acid Chlorides + Lithium Dialkyl Copper (Gilman Reagent): produces ketones. qThe 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). qCarboxylic 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 + (CH3)2 Cu- Li+ dimethyl copper lithium Gilman reagent - 78C ether
O CH3 (CH2)4 C CH3
hexanoyl chloride
2-heptanone
qRecall 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 C
.. Cl : ..
CH3MgBr
: O:
R C CH3 ketone
CH3MgBr
R
:O:
C CH3
+ 2 H3O
..
:O
CH3
acid chloride
alkoxide CH3
3 alcohol CH3
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Preparation of Ketones Problems
qWrite equations to show how the following transformations can be carried out. Show all reagents and intermediate products.
a)3-hexyne 3-hexanone
CH3CH2C CCH2CH3
OH CH3CH2C CCH2CH3 H
+
O CH3CH2C 3-hexanone
O C
H CCH2CH3 H
O C CH3
3-hexyne
Hg , H3O
+2
b)benzene m-bromoacetophenone
: O:
H3C
.. Cl : ..
AlCl3
CH3
FeBr3 Br2
Br
c)bromobenzene acetophenone
Br Mg in ether
acetyl chloride
HBr
acetophenone
: O: MgBr
H C CH3
:O:
CH CH3
H3O+
..
: OH
CH CH3 Cr+6, H+
O C CH3
..
m-bromoacetophenone
d)1-methylcyclohexene 2-methylcyclohexanone
CH3
1 BH3, THF 2 NaOH, H2O2, pH8 CH3 OH
acetophenone
Cr , H
+6
CH3 O
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Preparation of Ketones Problems
qRecall 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 CH3 F
o- and pdirecting Br
m-directing O CH O C OH SO3H NO2
Reactivity
Reactivity
OH
O NH C CH3 activators
Cl deactivators
O COCH3
O C CH3
C N
N+R3
deactivators
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