Transcript Aldehydes and Ketones - Clayton State University

Aldehydes and Ketones
Introduction: Types of Carbonyl
Compounds
Carbonyl Reactivity
Carbonyl Structure
Carbonyl carbon is sp2 hybridized, like an alkene
Carbonyl Geometry/Bond Properties
• The double bond between C and O is shorter and stronger than a single bond.
• Due to EN of O, electron density moves from C to O, leaving a partial positive
charge on the carbonyl carbon.
2 Major Pathways for Nucleophilic
Addition
Examples of First Major Pathway
Second Major Pathway: Imine
Formation
Reactions with CA Derivatives
Esterification
Alpha Substitution Rxns (Ch. 22)
Carbonyl Condensation Rxns
Treatment of acetaldehydes with strong base leads to formation of aldol
Mechanism of Carbonyl Condensation
Nucleophilic Addition Reactions
Aldehydes and Ketones
• Aldehydes (RCHO) and ketones (R2CO) are characterized by the
carbonyl functional group (C=O)
• The compounds occur widely in nature as intermediates in
metabolism and biosynthesis
Functional Group Priority
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Carboxylic Acids (3 O bonds, 1 OH)
Esters (3 O bonds, 1 OR)
Amides
Nitriles
Aldehydes (2 O bonds, 1H)
Ketones (2 O bonds)
Alcohols (1 O bond, 1 OH)
Amines
Alkenes, Alkynes
Alkanes
Ethers
Halides
O
OH
OH
2-ethyl-4-hydroxybutanoic acid
The parent will be determined based on the highest priority functional group.
Naming Aldehydes and Ketones
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
Naming Aldehydes
O
H3C
O
H
pentanal
O
Cl
H3C
H
H
5-chloropentanal
CH3
H
CH3
O
2-ethylbutanal
O
H
Cl
Cl
m-chloro-benzaldehyde
5-chloro-2-methylbenzaldehyde
CH3
O
H
CH3
H3C
O
H
CH3
3,4-dimethylhexanal
O
CH3
5-methoxy-2-methylbenzaldehyde
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
Ketones with Common Names
• IUPAC retains well-used but unsystematic
names for a few ketones
Naming Ketones
O
O
O
H3C
Cl
CH3
Cl
CH3
2-pentanone
CH3
1-chloro-3-pentanone
5-chloro-2-pentanone
O
F
O
CH3
H3C
CH3
4-ethylcyclohexanone
CH3
2-fluoro-5-methyl-4-octanone
Naming Ketones
O
O
O
O
Cl
butan-2-one
3,5-dimethylheptan-4-one
3-chloro-5-ethylheptan-4-one
O
O
O
but-3-en-2-one
OH
O
4-hydroxybutan-2-one
octane-2,7-dione
3-methylcyclopentanone
Cl
O
O
O
Cl
Br
7-bromo-3-chloro-4-methylcyclooctanone
cyclohex-2-en-1-one
3-chloro-5-ethyloct-7-en-1-yn-4-one
Ketones and Aldehydes as Substituents
• The R–C=O as a substituent is an acyl group, used with the
suffix -yl from the root of the carboxylic acid
– CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl
• 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
(lower priority functional group)
Ketones/Aldehydes as minor FGs,
benzaldehydes
O
H
O
O
O
O
OH
H
O
O
O
3-oxopentanal
3,4-dioxopentanal
3,4-dioxopentanoic acid
O
O
O
Cl
H
H
OH
H
O
benzaldehyde
O
H
O
3-chlorobenzaldehyde
O
O
H
3-oxopropanoic acid
O
2-formylbenzoic acid
O
O
H
methyl 3-oxopropanoate
O
O
methyl 3-oxobutanoate
Solubility of Ketones and Aldehydes



Good solvent for alcohols
Lone pair of electrons on oxygen of carbonyl can accept a
hydrogen bond from O—H or N—H.
Acetone and acetaldehyde are miscible in water.
Preparing Aldehydes and Ketones
• Preparing Aldehydes
• Oxidize primary alcohols using PCC (in dichloromethane)
• Alkenes with a vinylic hydrogen can undergo oxidative cleavage
when treated with ozone, yielding aldehydes
• Reduce an ester with diisobutylaluminum hydride (DIBAH)
– Like LiAlH4
Preparing Ketones
• Oxidize a 2° alcohol (See chapter on alcohols)
Ketones from Ozonolysis
• Ozonolysis of alkenes yields ketones if one of the unsaturated
carbon atoms is disubstituted
Aryl Ketones by Acylation
• Friedel–Crafts acylation of an aromatic ring with an acid chloride in the
presence of AlCl3 catalyst
O
+
Cl
AlCl3
Heat
O
Limitations of FC Acylation
• Does not occur on rings with electron-withdrawing substituents or basic
amino groups
NH2
O
+
Cl
AlCl3
Heat
No Rxn
Mechanism of FC Acylation
Not subject to rearrangement like FC alkylation.
Mercury catalyzed hydration of terminal alkyne
•
•
•
•
Hydration of terminal alkynes in the presence of Hg2+
Markovnikov addition
Produces enol that tautomerizes to ketone
Works best with terminal alkyne
Oxidation of Aldehydes
• CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids
efficiently
• Silver oxide, Ag2O, in aqueous ammonia (Tollens’ reagent)
oxidizes aldehydes
Oxidation of Ketones
•
•
•
•
Ketones oxidize with difficulty
Undergo slow cleavage with hot, alkaline KMnO4
C–C bond next to C=O is broken to give carboxylic acids
Reaction is practical for cleaving symmetrical ketones
Nucleophilic Addition Reactions
of Aldehydes and Ketones
• Nu- approaches 75°
to the plane of C=O
and adds to C
• A tetrahedral
alkoxide ion
intermediate is
produced
Nucleophiles
• Nucleophiles can be negatively charged ( :Nu) or neutral (
:Nu) at the reaction site
• The overall charge on the nucleophilic species is not
considered
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)
• Aldehydes have one large substituent bonded to the C=O:
ketones have two
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
Reactivity of Aromatic Aldehydes
• Less reactive in nucleophilic addition reactions than aliphatic
aldehydes
• Electron-donating resonance effect of aromatic ring makes C=O
less reactive electrophile than the carbonyl group of an aliphatic
aldehyde
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
Hydration of Aldehydes
• Aldehyde hydrate is oxidized to a carboxylic acid by usual
reagents for alcohols
• Relatively unreactive under neutral conditions, but can be
catalyzed by acid or base.
Hydration of Carbonyls
Acid catalyzed

Hydration occurs through the nucleophilic addition mechanism, with water (in
acid) or hydroxide (in base) serving as the nucleophile.
Base catalyzed
• The hydroxide ion attacks the carbonyl group.
• Protonation of the intermediate gives the hydrate.
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 (unstable alcohol)
Nucleophilic Addition of HCN: Cyanohydrin
Formation
• Aldehydes and unhindered ketones react with HCN to yield
cyanohydrins, RCH(OH)CN
• 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
Nucleophilic Addition of Grignard Reagents and
Hydride Reagents: Alcohol Formation
• Treatment of aldehydes or ketones with Grignard reagents
yields an alcohol
– Nucleophilic addition of a carbanion. A carbon–magnesium
bond is strongly polarized, so a Grignard reagent reacts for all
practical purposes as R:  MgX+.
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
Hydride Addition
• Convert C=O to CH-OH
• LiAlH4 and NaBH4 react as donors of hydride ion
• Protonation after addition yields the alcohol
Nucleophilic Addition of Amines: Imine and Enamine
Formation
• RNH2 adds to R’2C=O to form imines, R’2C=NR
(after loss of HOH)
• R2NH yields enamines, R2NCR=CR2 (after loss
of HOH) (ene + amine = unsaturated amine)
Mechanism of Formation of Imines
• Primary amine adds to
C=O
• Proton is lost from N
and adds to O to yield
an amino alcohol
(carbinolamine)
• Protonation of OH
converts it 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
• Optimum pH = 4.5
Imine Formation Reactions
O
+
NH2
N
+
+
H3O
Enamine Formation
• After addition of
R2NH and loss of
water, proton is lost
from adjacent carbon
The Wolff–Kishner Reaction: Convert ketone to alkane
• Treatment of an
aldehyde or ketone
with hydrazine,
H2NNH2, and KOH
converts the
compound to an
alkane
• Can be conducted
near room
temperature using
dimethyl sulfoxide as
solvent
• Works well with both
alkyl and aryl ketones
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
Addition of alcohol to aldehydes and ketones
H
O
O
R
+
H
O
R
H , RO-H
H
+
H
O
R
R
Hemiacetal
intermediate
acetal
R
+
H-O-H
O
O
O
R
R
H
H
R
O
R
H
O
R
+
R
R
H+, RO-H
O
R
R
R
+
H-O-H
O
O
R
Hemiketal
intermediate
R
ketal
 Hemiacetal is unstable, hard to isolate.
 With excess alcohol and an acid catalyst, a stable acetal is formed.
 Note the bidirectional arrows
Mechanism of Acetal Formation
Mechanism of Acetal Formation
Acetals as Protecting Groups
• Acetals can serve as protecting groups for aldehydes and ketones
• Aldehydes more reactive than ketones
• It is convenient to use a diol to form a cyclic acetal (the reaction goes even
more readily)
Nucleophilic Addition of
Phosphorus Ylides: The Wittig Reaction
• The sequence converts C=O 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 fourmembered ring to yield alkene and triphenylphosphine oxide,
(Ph)3P=O
• Formation of the ylide is shown below
Mechanism of the Wittig Reaction
Product of Wittig Rxn




The Wittig reaction converts the carbonyl group into a new C═C double
bond where no bond existed before.
A phosphorus ylide is used as the nucleophile in the reaction.
Ylide usually CH2 or monosubstituted, but not disubstituted.
Unstabilized ylide tends to favor Z-alkene.
O
(Ph)3P+-CHCH3
H
THF
Z-alkene
+
(Ph)3P=O
Conjugate Nucleophilic Addition to
b-Unsaturated Aldehydes and Ketones
• A nucleophile can
add to the C=C
double bond of an
,b-unsaturated
aldehyde or
ketone (conjugate
addition, or 1,4
addition)
• The initial product
is a resonancestabilized enolate
ion, which is then
protonated
Conjugate Addition of Amines
• Primary and secondary amines add to , b-unsaturated
aldehydes and ketones to yield b-amino aldehydes and ketones
Conjugate Addition of Alkyl Groups: Organocopper
Reactions
• Reaction of an ,b-unsaturated ketone with a lithium
diorganocopper reagent
• Diorganocopper (Gilman) reagents form 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
Mechanism of Alkyl Conjugate
Addition: Organocopper Reactions
• Conjugate nucleophilic addition of a diorganocopper anion,
R2Cu, to an enone
• Transfer of an R group and elimination of a neutral
organocopper species, RCu
Spectroscopy of Aldehydes and Ketones
• Infrared Spectroscopy
• Aldehydes and ketones show a strong C=O peak 1660 to 1770
cm1
• aldehydes show two characteristic C–H absorptions in the 2720
to 2820 cm1 range.
C=O Peak Position in the IR Spectrum
• The precise position of the peak reveals the
exact nature of the carbonyl group
NMR Spectra of Aldehydes
• Aldehyde proton signals are near  10 in 1H NMR - distinctive
spin–spin coupling with protons on the neighboring carbon, J 
3 Hz
13C
NMR of C=O
• C=O signal is at  190 to  215
• No other kinds of carbons absorb in this range
Mass Spectrometry – McLafferty Rearrangement
• Aliphatic aldehydes and ketones that have
hydrogens on their gamma () carbon atoms
rearrange as shown
Mass Spectroscopy: -Cleavage
• Cleavage of the bond between the carbonyl
group and the  carbon
• Yields a neutral radical and an oxygencontaining cation