Aldehydes and Ketones
Preparation of Aldehydes — Oxidation of primary alcohols – O RCH
C 5H5 NH CrO 3Cl
C 5H5 NH CrO 3 Cl is pyridinium chlorochromate, PCC The aldehyde that is the product is very easily oxidized to a carboxylic acid, RCOOH. Preparation of Ketones — Oxidation of secondary alcohols –
H R1 C R2 OH
K 2C r 2O 7
Unlike aldehydes, ketones are not easily oxidized.
HgSO 4 H2O H H C C R H O
An enol initially forms in this reaction. Terminal alkynes. this reaction is most useful when R1 = R2 .or when the alkyne has a terminal triple bond. but it tautomerizes to the more stable ketone. following Markovnikov’s rule.. give methyl ketones rather than aldehydes.. HgSO 4 H2O H C R2 + R1 C O C H R2
Owing to the formation of mixtures if R1 ≠ R2.Hydration of an alkyne –
.. H C C R H2SO 4. .
it is likely to be a site of electrophilic attack. as a substituent. In ketones. only carbons are bonded to the carbonyl carbon. Since ordinary carbanions (R: −) and hydride ions (H: −) are very poor leaving groups (unlike halide ions. In aldehydes at least one hydrogen is joined to the carbonyl carbon (formaldehyde has two).Friedel-Crafts acylation for aryl ketones –
O H + R C Cl AlC l3 O C R
The aromatic ring cannot have. an amino group or a meta director.
Structural Features of Aldehydes and Ketones Both contain the carbonyl δ+ δ− group and only carbons or hydrogens bonded to this sp 2 orbitals C O π group. X−) nucleophilic substitution does not usually occur at the carbonyl carbon of aldehydes or ketones. And. Since the carbon has a partial positive charge it is likely to be a site that is attacked by nucleophiles.
. since the oxygen bears a partial negative charge.
R1 Nu:R2 C O
C O + R1:
Benedict's test: R C (not Ar) O H + 2 CuO complexed with citrate or tartarate. etc. in solution RCOH O + Cu2O red precipitate
Ketones RCH2 C CH2R' O
hot KMnO 4 O O or hot HNO 3 Vigorous conditions RCH2COH + R'COH required for reaction.Reactions of Aldehydes and Ketones — Oxidation — Aldehydes are easily oxidized to carboxylic acids. ketones are not.+ Ago (Ar) O
Fehling's test. R C (Ar) O OH
Tollen's test for aldehydes: R C (Ar) O H + Ag(NH3)2
Aldehydes R C (Ar) O O 2 or CrO 3 or K 2Cr2O 7 H or KMnO 4. O O
Nucleophilic Additions — :Nu or :Nu .
. aryl.is a generic nucleophile.
R. H :NuC O R' δ+ δ− R R Nu δ−
C O δ− R' becoming tetrahedral: sp2 sp3 R Nu C O H+ R R' Nu C OH
Since there is an increase in crowding on going from reactant to transition state (~120o to ~109o). R' = alkyl. some steric effects might be expected. This is one reason aldehydes (less crowded) are more reactive than ketones.
when acid catalysis is employed one should usually be careful to avoid completely converting the nucleophile to its conjugate acid (which would be much less nucleophilic). In most cases the equilibrium greatly favors the carbonyl compound. Nucleophilic Addition of Water: Hydration —
acid or base catalyst
C OH OH
The product here is known as a geminal diol.Nucleophilic additions may be acid catalyzed —
R C O R' + H
R C O H
R C O H
R' R' More easily attacked by nucleophile than unprotonated carbonyl. Formaldehyde and chloral (trichloroacetaldehyde) are two common exceptions.
the nucleophile will be much weaker – water. In acidic catalysis. But the substrate has been activated by protonation and is more susceptible to attack.
.The mechanism for this reaction under basic conditions is as follows –
HO C O H O H
HO C O H + O H
In this case – basic catalysis – a powerful nucleophile attacks the substrate. as we shall see below.
Under acidic conditions the following mechanism applies –
H O H H C O C O H
H O H C O H H O H H O H O H H C O H
H O H
H O C O H
Acetal Formation — Under acidic conditions an aldehyde or ketone will react with an alcohol to form a hemiacetal. in turn. will react with more alcohol to form an acetal.
H ROH H ROH
OR + H2O
. The hemiacetal.
The mechanism is as follows –
R O H H C O C O H
R O H C O H R O H R O R O H H C O H
R O H
R O C O H
hemiacetal OK. Now we have to get from the hemiacetal to the acetal.
For example if you wanted to convert a ketoacid to a ketoalcohol you could do the following: (1) convert the keto group to an acetal. (2) reduce the acid with LiAlH4.R O R O C O H H
H R O H C O
R O H
H R O C H O R H O H
R O C O
H O R
R O C acetal O R H O R H
Acetals are used to “protect” the carbonyl groups of aldehydes and ketones when one wants to have some other part of the molecule react without affecting the aldehyde or ketone functional group. and (3) regenerate the keto group from the acetal. They can be used this way because they are fairly unreactive and the carbonyl functional group can be regenerated from the acetal.
. In the Grignard Synthesis smaller molecules —> larger molecules. Formation of Grignard reagent —
R-X or Ar-X
anhydrous C2H5OC2H5 or O
R-Mg-X or Ar-Mg-X
X = I. Br.Addition of Grignard Reagents — A powerful method for synthesis of alcohols.
Grignards react with aldehydes and ketones to give alcohols —
H RMgX or ArMgX + C O H formaldehyde R' + C O H aldehyde H H2O H3O + H C OH 1o alcohol R R' H2O H3O + H C OH 2o alcohol R R' H2O + H3O R'' C OH 3o alcohol R
R' + C O R'' ketone
A pseudo-mechanism for this reaction —
δ− δ+ R Mg X C O δ+ δ− H2O Mg X
C O Mg X
magnesium salt of an alcohol R C O H + Mg(OH)X
See. In the scheme below. but methyl bromide is not convenient to handle. In practice. for example: http://www.gov/docs/ozone/mbr/mbrqa.Synthesize 2-phenyl-2-butanol using a Grignard synthesis — The figure below shows three possible routes by which this synthesis can be accomplished. [Large quantities of methyl bromide are used as a soil and grain fumigant.html]
. the route chosen would likely depend on the starting materials that may be at hand in the laboratory (all of these compounds could be purchased). so it is a gas at room temperature.epa. CH3MgBr could be made from CH3Br and Mg. Its use is quite controversial since it is somewhat toxic and an ozone depleting chemical. It boils at 4oC.
OH CH3CH2 C CH3
O H3CC + CH3CH2MgBr Mg anhydrous ether Mg +
O CH3CH2CCH3 MgBr
anhydrous ether Br
O CH3CH2 C + CH3MgBr
not commonly available
.It is possible to extend the Grignard synthesis to make quite complex alcohols from simple ones (you don’t win the Nobel prize for nothing). The basic scheme is as follows –
alcohol 1 alkyl halide alcohol 2 Grignard reagent aldehyde or ketone more complicated alcohol which may become alcohol 1 or 2 in a subsequent Grignard synthesis.
KOH heat H CH3CH2CH2 C COO.Formation of Cyanohydrins — R C O + K -C N R'
R R' C CN OH
These compounds can be hydrolyzed by base or acid to give α-hydroxyacids or α. respectively.
H CH3CH2CH2 C CN OH H2O.β-unsaturated acids.K+ HCl H2O OH CH3CH2CH2 H3O+ H2O heat H CH3CH2CH C COOH
H C COOH OH + KCl
2.4-DNPs.Addition of Ammonia and Its Derivatives —
C O + R NH2 a primary amine weak acid catalyst C N an imine R C N Oximes. and semicarbazones are used as derivatives in identifying aldehydes and ketones.4-dinitrophenylhydrazone
weak acid NH2OH catalyst hydroxylamine O2 N
an oxime OH
weak acid catalyst
O 2N NH NO 2