CARBONYL COMPOUNDS

Introduction
Aldehydes and Ketones are referred to as Carbonyl compounds as both contain the carbonyl
functional group. The saturated aliphatic series are homologous and correspond to a general
molecular formula C n H2n O. Aldehydes possess single hydrogen attached to the carbonyl carbon
whereas Ketones always contain two hydrocarbon groups. Aldehydes are more reactive
therefore easily oxidized and also more susceptible to Nucleophilic addition.

Nomenclature of Aldehydes and Ketones

For Aldehydes, the IUPAC names are obtained by dropping the ending “-e”of the
corresponding alkane and replacing it with suffix “-al” for Aldehydes name. The parent chain
must contain the –CHO group and the –CHO carbon is numbered as carbon 1. For example,

Br
O

O Phenylacetaldehyde
2-Ethyl-4-methylpentanal 2-Bromo-3-methylhexanal

For cyclic aldehydes in which the –CHO group is directly attached to a ring, the suffix -
carbaldehyde is used .

Cyclohexanecarbaldehyde 2-Naphthalenecarbaldehyde

Some few and well-known aldehydes have common names that are recognized by IUPAC

Common names of some simple aldehydes

Formula Common name Systematic name

HCHO Formaldehyde Methanal

CH3CHO Acetaldehyde Ethanal
CH2 = CHCHO Acrolein Propenal
CH3CH = CHCHO Crotonaldehyde 2-Butenal
C6H5CHO Benzaldehyde Benzenecarbaldehyde

1
The IUPAC names for Ketones is also obtained by dropping the ending”-e” of alkanes and
replacing it with suffix”-one”. The parent chain is the longest chain that contains the ketone
group, and the numbering begins at the end nearer the carbonyl carbon.

O
O

O O
Hex-4-ene-2-one
Hexan-3-one Hexane-2,4-dione

Some ketones have also been allowed to maintain their common names by IUPAC

O
O

H3C CH3
O
Acetone Propiophenone
Acetophenone O
Benzophenone

The name acyl group is used when it’s necessary to refer to R – C = O as a substituent and the
name ending – yl/ -oyl is attached instead of ‘e’ of alkane. Thus CH 3 CO is an acetyl group and
C6 H 5 CO is a benzoyl group.
O O O O

C C C C
R H3C H

An acyl group Acetyl Formyl

Benzoyl

2
 H3 C
CH2 O

H2C O

H3C H3C
2-Pentanoyltoluene

1-Butyrylnaphthalene H3C
CH3

O O
2-Propanoylnaphthalene

1-Naphthalen-2-yl-propan-1-one O CH3
O

H3C
2-Butanoylnaphthalene
1-Naphthalen-1-yl-ethanone

If other functional groups are present and the doubly bonded oxygen is considered a substituent
on a parent chain, the prefix Oxo- is used. For example,

O
O O

O O O
Furanyl-2-oxo-benzoate 4-(2-oxo-pentyl)-cyclohexanone
O

O O

S
O O

Methyl-3-oxo-pentanoate 2-(3-Oxo-5-thiophen-2-yl-pentyl)-cyclopenta-2,4-dienone

3
Physical Properties of Carbonyl Compounds
Simple aliphatic Aldehydes and Ketones with exception of methanal are all colourless liquids.
The lower Aldehydes possess rather unpleasant smell whereas Ketones and Benzene
carbaldehyde have pleasant, sweet odour.

Methanal is a gas at room temperature and the rest are liquids. Carbonyl group is polar therefore
Aldehydes and Ketones have a higher boiling points but lower than those of alcohols since
they do not form strong hydrogen bonds with each other.

Lower Aldehydes and Ketones are appreciably soluble in water due to their ability to form
hydrogen bonds with water molecules and the resultant solution is neutral to litmus.

The density of the aliphatic compounds of both series is less than that of water but it increases
with increase in molecular mass.

Synthetic Preparations
1) Oxidation of Alcohols

This reaction is always carried out using Pyridinium chlorochromate (PCC) in dichloromethane
as solvent at room temperature.

PCC

CH2 Cl2
OH O
Citronellol Citronellal

PCC
HO O
CH2 Cl2

4-tert-Butylcyclohexanol 4-tert-Butylcyclohexanone

Oxidization can also be accomplished by dehydrogenation of the alcohol using copper catalyst
heated at about 300o C

Cu
RCH2OH RCHO
o
300 c

2) From Grignard reagent.

When Grignard reagent reacts with cyanide compounds and on hydrolysis, ketones are
obtained.

4
 RMgBr 2H2O RCOR' + MgBrOH + NH3
R'CN RC NMgBr
dry ether dil.HCl
R'

3) Decarboxylation method of Calcium salts

heat
(CH3COO)2Ca + (HCOO)2Ca 2CH3CHO + 2CaCO3

heat
(CH3COO)2Ca CH3COCH3 + CaCO3

4) Ozonolysis of Alkenes

R R"
(i) O3/CCl4
C C RCOR' + R''COR'''
(ii) H2O/ Zn
R' R'''

(i) O3 /CCl4 CH3CHO

CH3CH CHCH3
(ii) H2O/ Zn

1. O3
O
2. Zn, CH3CO2H
O
1-Methylcyclohexene 6-oxoheptanal

O O

O
CH2 O
1. O3
+ C
H H
CH3 2. Zn/H3O+

2-(2-Methyl-allyl)-cyclohexanone 2-(2-Oxo-propyl)-cyclohexanone

5) Hydration of Alkynes

H3O+
RC CR RCOCH2R
HgSO4

Hydration of terminal alkynes still produces methyl ketones

O
+
H3O

HgSO4
1-Hexyne 2-Hexanone

5
6) Reduction of certain carboxylic acids produce aldehydes

The reduction of esters by diisobutylaluminum hydride (DIBAH), for instance is normally

carried out at -78o C (dry ice temperature) in toluene solution, to prevent reaction with the
aldehyde product.
O
1. DIBAH, toluene, -78oC O
O
+
2. H3O
Propanal
Methyl propanoate
H

where DIBAH = (CH3)2CHCH2 Al

CH2CH(CH3)2

Acid chlorides can be reduced using lithium tri-tert-butoxyaluminum hydride (LtBAH) to

aldehydes.
O O
LiAlH(Ot-Bu)3

R Cl R H

LtBAH = LiAl [OC(CH 3 )3 ]3 H

7) Gilman Synthesis

Ketones can also prepared from certain carboxylic acid derivatives. A reaction of acid
chloride and a Gilman diorganocopper reagent yields a ketone.
O
O
- +
(CH3 )2Cu Li

Ether
Cl
2-Hexanone
Pentanoyl chloride

8) From methyl benzene

Oxidation of toluene with chromyl chloride yields benzaldehyde

O
CrO2Cl2

Toluene Benzaldehyde
6
 9) Acylation method

COR
RCOCl

AlCl3

Cl
Cl
O-
CH3COCl -
N+ O
AlCl3 N+
O
2-Nitrochlorobenzene O O
p-Chloro-m-nitroacetophenone
Question:

Show the reaction steps indicating the reagents and reaction conditions for synthesizing 1-
Phenylethanol from benzene.

HO

from

Phenylethanol

Reactions of Carbonyl compounds

In carbonyl compounds, the carbonyl carbon has a partial positive charge because it is bonded
to a more electronegative oxygen atom therefore it is attacked by a Nucleophile.

The susceptibility of the carbonyl carbon to Nucleophilic attack is reduced by its attachment to
electron-releasing alkyl or aryl groups which reduces the degree of positive charge on the
carbon.

Steric hindrance by the hydrocarbon groups impedes the approach of the attacking Nucleophile
and reduces the reactivity.

Some of the Nucleophilic addition reactions include;

1. Addition of water: Hydration

Aldehydes and ketones react with water to form 1, 1- diols or geminal (gem) diols. The
hydration reaction is reversible.

7
 OH
CH3
+ H2O C
H3C OH
O
Acetone (99.9%) Acetone hydrate (0.1%)

OH
O OH
+ H2O C
C H H
H H
Formaldehyde hydarte (99.9%)
Formaldehyde (0.1%)

The position of the equilibrium between a gem diol and an aldehyde or a ketone depends
on the structure of the carbonyl compound. The equilibrium generally favors the carbonyl
compounds for steric reasons, but the gem diol is favored for a few simple aldehydes.

The nucleophilic hydration is slow under neutral conditions but is catalyzed by both base
and acid.

The base catalyzed hydration follows the mechanism below:

O

OH

1. The nucleophilic hydroxide ion

addds to the aldehyde or ketone and
forms a tetrahedral alkoxide ion intermediate 1

O
H H
C O
OH

2. The alkoxide ion is protonated by water

to give the gem diol product and 2
regenerate the hydroxide ion catalyst

OH

C
OH
Gem diol

8
The acid catalyzed hydration follows the mechanism below:

H H
C
O

H
1. Acid catalyst protonates the basic carbonyl
carbon atom making the aldehyde or ketone a
better acceptor for nucleophilic addition 1

OH

C
H

O
H

2. Addition of water to the protonated

carbonyl compound gives a protonated 2
gem diol intermediate
OH
OH2
C H
O

3
3. Deprotonation of the intermediate by
reaction with water yields the neutral
gem diol and regenerates the acid catalyst
OH
+ H3 O+
C
OH
Note: The hydration reaction is typical reaction of carbonyl compounds with nucleophile
H – Y, where the Y atom is electronegative and can stabilize the negative charge (oxygen,
Sulphur, halogen, for instance). In such cases, the nucleophilic addition is reversible, with
the equilibrium generally favoring the carbonyl reactant rather than the tetrahedral
addition product. In other words, treatment of an aldehyde or ketone with CH 3 OH, H 2O,
HBr, HCl or H 2 SO4 does not normally lead to a stable alcohol addition product.

9
2. Addition of Hydrogen cyanide:

Aldehydes and unhindered ketones undergo nucleophilic addition reactions with HCN to
form cyanohydrins, RCH (OH) CN. Cyanohydrins formation is a form of a protic acid
(H-Y) addition reaction to carbonyl compounds. This is because the equilibrium constants
are favorable.

O OH
HCN
C C
CN

Hydrogen cyanide is usually prepared during a reaction of dilute sulphuric acid on alkali metal
cyanide.
OH
HCN
CH3CHO CH3C CN

Mechanism
OH
+
H
CH3CHO CH3CH CH3 CHCN

OH
CN

Cyanohydrin formation is important because of the further chemistry that can be carried out
on the product. For example, a nitrile (RCN) can be reduced with LiAlH 4 to yield primary
amines (RCH 2 NH 2 ) and can be hydrolyzed by hot aqueous acid to yield a carboxylic acid.
Thus, cyanohydrin formation provides a method for transforming an aldehyde or ketone into
a different functional group.

10
 H2N
1.
LiAlH4,
THF
N
2. H2O
O OH
HCN 2-Amino-1-phenylethanol

OH
Benzaldehyde Mandelonitrile O
H 3O +
Heat OH

OH
Mandelic acid

Question: Using equations indicating the necessary conditions show how ethene can be
converted to 2-hydroxypropanoic acid.

3. Addition of saturated sodium hydrogen sulphite solution

The reaction occurs readily with most aldehydes and some ketones especially methyl
ketones or less hindered ketones to form white solids of aldehydes or ketones hydrogen
sulphite.

Formation of Bisulphite Compound

Most aldehydes, methyl ketones, and unhindered cyclic ketones add on sodium hydrogen
sulphite (concentrated aqueous solution) to form bisulphite addition compounds. No
catalyst is required in this reaction because sulphite is an efficient nucleophilic agent.

These bisulphite compounds are hydroxysulphonic acid salts, since Sulphur atom is
directly attached to the carbon atoms. Bisulphite compounds are usually crystalline solids,
insoluble in excess concentrated sodium hydrogen sulphite solution. Since they regenerate
the carbonyl compound when treated with dilute acid or sodium carbonate solution, their
formation affords a convenient means of separating carbonyl compounds from non-
carbonyl compounds

11
 R OH
R
NaHSO3 C
C O
R' R' SO3Na

Aldehyde or Ketone hydrogen sulphite

OH
NaHSO3
CH3CHO CH3C SO3Na

H
Mechanism

HSO3- + OH- SO3 2- + H2O

O O
H3C H
C + SO32- C
H3C H
SO3Na
O O
S
HSO3-
O
OH
H
+ SO32-
C
H3C SO3Na

The position of equilibrium lies largely to the right for most aldehydes and to the left for
most ketones. The reaction occurs by nucleophilic attack of a lone pair of S-atom on the
carbonyl group. This leaves a positively charged Sulphur atom but a simple proton transfer
leads to the product.

The product is the salt of sulphonic acid that reflects the greater nucleophilicity of Sulphur
rather than oxygen in the attacking anion. The effective nucleophile is SO 3 2- rather than
HSO 3 - (shown in mechanism above), as though the latter will be present in higher relative
concentration the former is a much more effective nucleophile.

The attacking anion is already present in solution as such no base catalysis is required, and
SO 3 2- is a sufficiently powerful nucleophile not to require activation by protonation of the
carbonyl group. So no acid catalysis is required either.

12
 The nucleophile is a large one, however, and the equilibrium constant (K) values for
product formation are normally considerably smaller than those for cyanohydrin formation
with the same carbonyl compound.

The products are useful for two reasons. They are usually crystalline and so can be used
to purify liquid aldehydes by recrystallization. This is of value only because this reaction
is reversible. The bisulphite compounds are made by mixing the aldehyde or ketone with
saturated aqueous sodium bisulphite in an ice bath, shaking, and crystallizing.

After purification the bisulphite addition compound can be hydrolyzed back to the
aldehyde in dilute aqueous acid or base.
O OH
Stir together in ice-bath SO3Na
CH3 CH2CH + NaHSO3 C
3 H CH C
2 H
Dilute acid or base
The reversibility of the reaction makes bisulphite compounds useful intermediates in the
synthesis of other adducts from aldehydes and ketones. For example, one practical method
for making cyanohydrins involves bisulphite compounds.

Acetone on reacting first with sodium bisulphite and then with sodium cyanide gives a
good yield (70%) of the cyanohydrin.
O OH
CN
1. NaHSO3
C C
2. NaCN H3C CH3
Acetone
Cyanohydrin

4. Nucleophilic addition of Amines: - Condensation reaction yielding Imines and

Enamines.

In this reaction, carbonyl compounds react with derivatives of ammonia of general form
X-NH 2, in presence of an acid catalyst, to release water molecules. The final products are
usually solids which are easily isolated and purified by recrystallization.

Primary amines, RNH 2 add to carbonyl compounds to form imines, R 2 C = N – X.

Meanwhile, secondary amines react to form enamine, R 2 N – C(R) = CR2

13
 O

C H
C

RNH2 R2NH

R
R
R N
N
+ H2O
+ H 2O C
C H C
C

An enamine
An imine

Formation of imines follows the steps below:

Mechanism
OH
NH2R O +
H shift
O C C
C NHR
NH2R Carbinolamine
Ketone/aldehyde

H 3O +
R
N R H
N OH2
- H+ OH2 - H2O
C
C C
NHR
Imine Iminium ion

Formation of enamine follows similar mechanism up to iminium ion, and the lost proton
takes place from the alpha carbon atom as shown below

14
 Mechanism
OH
NHR2 O H+ shift CH
O C CH
C
C NR2
NHR2 Carbinolamine
Ketone/aldehyde

H3 O+
R
R
N R R
N OH2
- H+ - H2 O
C CH

C
C C
C NR2

OH2
H
Enamine

Some of the addition reagents include:

a) With Hydroxylamine, NH2 OH

The white solid formed is Aldehyde or Ketone oxime.

NH2OH
RCOR' RC NOH + H2O
R'

NH2OH CH3CH NOH + H2O

CH3CHO
ethanal oxime

Question: Write the mechanism of the reaction above and show how the product
formed can be converted to:

(i) CH3CH2NH2

(ii) CH3COOH

b) With hydrazine, NH2 NH2

The product is hydrazone which in excess yield azine.

15
 NH2NH2 RCHO RCH NN CHR + H2O
RCHO RCH NNH2

+ H2O
A reaction of carbonyl compound with hydrazine in the presence of a base, KOH, forms an
alkane in the Wolff- Kishner reaction.
O
NH2NH2 RCH2R'
C
KOH
R R'
O
NH2 NH2
CH H3C
KOH

Cyclopropanecarbaldehyde Methylcyclopropane

NH2NH2
KOH
O
Propiophenone
Propylbenzene

16
 Mechanism
O
H+
+ NH2NH2 C N
C
N
H
H

OH

N N
HN
H N N H
N

C C
C
H O
H
H
OH

H
H H
H 2O
C C

c) With Phenyl hydrazine C 6 H5 NHNH2

Carbonyl compounds generate phenyl hydrazone derivatives which are low melting point
solids. The reaction occurs with or without an acid.
O R
H+
C + NH2NHC6H5 C NNHC6H5
R R'
R' Phenylhydrazone

d) With 2,4-dinitrophenylhydrazine

2, 4-dinitrophenylhydrazine is utilized in Brady’s reagent for detection of a carbonyl

functional group. Yellow or orange solid crystallizes out in the form of 2, 4-
dinitrophenylhydrazone.

17
 H+
RC NN + H2O
RCOR' + NH2NH
H
NO2 R'

Aldehyde or Ketone
2,4-dinitrophenylhydrazone

NO2

e) With semicarbazide, NH2 NHCONH2 forming semicarbazone

RCOR' + H2NNHCONH2 RC NNHCONH2 + H2O

R'
semicarbazone

5. Carbonyl condensation: Aldol Reaction.

A useful carbon-carbon bond-forming reaction known as the Aldol Reaction is another

example of electrophilic substitution at the alpha carbon in enolate anions. This reaction
requires the formation of an enolate so at least one of the reactants must have an α-
hydrogen. Due to the carbanion like nature of enolates, they can add to carbonyls through
nucleophilic addition much like Grignard reagents.

The aldol reaction takes advantage of a carbonyl compound’s ability to undergo both alpha
substitution and nucleophilic addition reactions. The fundamental transformation in the
aldol reaction is a dimerization of an aldehyde (or ketone) to form a beta-hydroxy aldehyde
(or ketone). A C-C bond is formed between the alpha carbon of one reactant molecule and
the carbonyl carbon of a second reactant molecule. In the reaction’s product, the formed
C-C bond links a carbon in the alpha position and a carbon in the beta position away from
the carbonyl.

OH
O
O H
H Base
H H C C
C
C C
C + C C O

beta-Hydroxycarbonyl
Examples,

18
 H CH3
O
NaOH
2 O OH
C
H3C H 3-Hydroxybutanal
Ethanal
O

NaOH
2

O OH
Acetone 4-Hydroxy-4-methyl-2-pentanone

Mechanism O
O O

H C
C C
C C C
B

Enolate
Aldehyde/Ketone
O
O
C C
C O C O

C
C Tetrahedral alkoxide intermediate

H B
C
C O
HO C

3-Hydroxycarbonyl (Aldol product)

Stereochemical Ramifications of the Aldol reaction

Aldehydes condensation reactions yield aldol products with two chiral centers whereas
ketone condensation yields aldol products with only one chiral center.

19
 OH O
O O
R
R CH C
C C C
H + C CH H
H2 H H2
2HC
R
R Aldehyde reactants Aldol product with two chiral carbons

O R
O
H2C O
R
R C R
+ R C
C C HO C C R
H2 C C
H2 H2 H2C CH C
H2 H2

R R
Symmetrical Ketone reactants
Aldol product with one chiral carbon

6. Cannizzaro reaction

Aldehydes without at least one-α-hydrogen atom react with sodium hydroxide solution
to undergo self-oxidation and reduction reaction.

This reaction is limited to aromatic and aliphatic compounds in which the carbonyl
carbon is attached to tertiary alkyl carbon atom.

reduction

2C6H5CHO C6H5COONa + C6H5CH2OH

oxidation

2 NaOH(aq)
C RCH2 OH + RCOOH
R H

R = Aryl group or tertiary alkyl group

20
Mechanism

First step

Second step

Third step

21
7. Oxidation reaction

Aldehydes are oxidized to carboxylic acids by oxidizing agents such as acidified

potassium dichromate solution, acidified chromium (VI) oxide solution or hot nitric
acid. The oxidation occurs at room temperature and gives good yield.

Ketones are resistant to oxidation by common oxidizing agents.

Cr2 O72-/ H+
RCHO RCOOH
Heat
O
+
CrO3 , H3 O

O Acetone, 0o C
OH
Pentanal Pentanoic acid
Since the reaction takes place in acidic condition, some sensitive molecules undergo
side reactions. An oxidation of such molecules can be carried out using a solution of
Silver oxide, Ag2 O, in aqueous ammonia, the so- called Tollens’ reagent. Aldehydes
are oxidized by Tollens’ reagent in high yield without harming carbon- carbon double
bonds or other acid- sensitive functional groups in a molecule.
O HO
Ag2O
NH4OH, H2O
O
Benzaldehyde Benzoic acid
Aldehydes are oxidized through 1, 1-diols or hydrates, which are formed by a reversible
nucleophilic addition of water to the carbonyl group.

OH O
O
R H CrO3
H2O C
C
C H3O+ R OH
R H
OH
An aldehyde A carboxylic acid
A hydrate
Ketones are inert to most oxidizing agents, but undergo a slow cleavage reaction when
treated with hot alkaline KMnO 4 . The C – C bond next to the carbonyl carbon is broken
and carboxylic acids are produced. The reaction is useful primarily for symmetrical
ketones such as cyclohexanone because product mixtures are formed from
unsymmetrical ketones.

O O
O
1. KMnO4 , H2O, NaOH + C
CH3 CCH2CH3 C
H OH H3CH2C OH
2-Butanone 2. H3O+
Formic acid Propanoic acid

22
 1. KMnO4, H2O, NaOH COOH
O
2. H3 O+
COOH
Cyclohexanone
Hexanedioc acid
8. Reduction reaction

Aldehydes are reduced to Primary alcohol while Ketones are reduced to Secondary
Alcohol. Reducing agents commonly used are LiAlH 4 / dry ether, Hydrogen /Nickel at
150OC, Amalgamated Zinc and concentrated hydrochloric acid, NaBH 4 / Water.

O
HO
NaBH4 , CH3 OH

Benzaldehyde Phenylmethanol
O
OH
1. LiAlH4
2. H2 O
Butan-2-one
Butan-2-ol
Mechanism

Li+ H
H H
O Al Li OH
H
O H+
C H
R C
R R' R H
C
H H

(R' = Alkyl or Hydrogen)

23
 O

Zn(Hg), Conc. HCl R

R

Where R = H or alkyl

Reduction can also be done using excess hydrazine, hot glycerol and later in a basic
medium.

9. α- Halogenation of Carbonyl compounds

a) Acid- catalyzed α-Halogenation

Halogenation of an aldehyde or ketone results in the replacement of one α-

hydrogen by halogen.
Br

HOAc
Br
Br2 + Br o
25 C
O
O
p-Bromoacetophenone 1-(4-bromophenyl)-2-bromoethanone
Cl

H3 O+
O + Cl2 O

Cyclohexanone 2-Chlorocyclohexanone

Enols are reactive intermediates in these reactions,

O
HO
H3O+
C
CH
C C

enol
aldehyde or ketone
Like other alkenes, enols react with halogens; but unlike ordinarily, enols add only one
halogen atom. After the first halogen addition to the double bond, the resulting
carbocation intermediate loses a proton instead of adding the second halogen. (Addition

24
 of the second halogen would form a tetrahedral addition intermediate which, in this
case, is relatively unstable

HO H
H
C C
O C Br-
O
C Br
C
C
Br Br

Br

C Br
C
+ HBr

Because only one halogen is introduced at a given α- carbon in acidic solution, it

follows that introduction of a second halogen is much slower than introduction of the
first. The slower reaction is probably a consequence of the stability of the carbocation
intermediate that is formed by reaction of the halogen with the halogenated enol. This
carbocation is destabilized by the electron- attracting polar effect of two halogens.

Br Br HO Br

C Br
HO

C C
carbocation intermediate is
Br destabilized by the polar effect
of two bromines
Halogenated enol

If the rate- limiting transition state resembles this carbocation, then the transition state
should have very high energy and the rate should be small.

b) Halogenation of Aldehydes and Ketones in Base: The Haloform Reaction.

When halogenation of carbonyls proceeds in basic condition, all α- hydrogens are

substituted by halogen.

25
 CH3 O O

H3C NaOH, 0o C C + 3NaBr + 3H2O

+ 3NaOH + Br2
H2O/ Dioxane (H3C)3C
CH3 CBr3
CH3

Methyltert-butyl ketone

The trihalo carbonyl compound formed is not stable under the reaction conditions. It
reacts further to give, after acidification of the reaction mixture, a carboxylic acid and
a Haloform. (A haloform is a trihalomethane- that is, a compound of the form HCX3,
where X = halogen.)
O
O
OH H3 O+ + HCBr3
C C
(H3C)3C OH Bomoform
Br3C C(CH3 )3

The conversion of acetaldehyde or a methyl ketone into a carboxylic and a haloform by

halogen in a base, followed by acidification, exemplified above, is called the haloform
reaction. Notice that, in a haloform reaction, a carbon- carbon bond is broken.

The mechanism of the haloform reaction involves the formation of an enolate ion as a
reactive intermediate.
O
O

C + OH C + H2O
R CH2
R CH3
enolate ion
The enolate ion reacts as a nucleophile with halogen to give an α- halo carbonyl
compound .

O O
+ Br_
+ Br Br
C C
R CH2 R CH2Br

However, halogenation does not stop there, because the enolate ion of the α- halo ketone
is formed even more rapidly than the enolate ion of the starting ketone. The reason is
that the polar effect of the halogen stabilizes the enolate ion and, by Hammond’s
postulate, the transition state for enolate ion formation. Consequently a second
bromination occurs.

26
 O

C Br O O
R CH
Br Br
C C + Br
H R CHBr R CHBr2

OH + H 2O

The Dihalo carbonyl compound brominates again even more rapidly.

O
O
Br2 + Br + H 2O
C
C
OH R CBr3
R CHBr2

A carbon- carbon bond is broken when the trihalo carbonyl compound undergoes a
nucleophilic acyl substitution reaction.
O
O

C R
C
R CBr3 CBr3
HO

OH

O O

H CBr3 + CBr3
C + C
R O R OH trihalomethyl
anion

The leaving group in this reaction is a trihalomethyl anion. Usually carbanions are too
basic to serve as leaving group; but trihalomethyl anions are much less basic than
ordinary carbanions. However, the basicity of trihalomethyl anions, although low
enough for them to act as leaving groups, is high enough for them to react irreversibly
with the carboxylic acid byproduct as shown above. This acid -base reaction drives the
overall haloform reaction to completion.

Occasionally, the haloform reaction can be used to prepare carboxylic acids from
readily available methyl ketones. This reaction can be used as a qualitative test for
methyl ketones, called the Iodoform test. In iodoform test, a compound of unknown
structure is mixed with alkaline iodine. A yellow precipitate of iodoform is taken as
evidence for a methyl ketones or acetaldehyde (the methyl aldehyde).

27
 Alcohols of the form shown below also give a positive iodoform test because they are
oxidized to methyl ketones (or acetaldehydes, in the case of ethanol) by basic iodine
solution.
O
OH
I2, base
C
CH
R CH3
R CH3
undergoes the
iodoform reaction

10. Addition of Grignard reagent

Aldehydes generate secondary alcohol except formaldehyde while Ketones generate

tertiary alcohol.

R'MgX H2O RCHR' + Mg (OH)X

RCHO RCHR'
dry ether dil. HCl
OMgX OH

R'MgX H2O
HCHO R'CH2OMgX RCH2OH
dry ether dil.HCl

This reaction is irreversible because the carbanion is too poor a leaving group to be
expelled in a reversible, compared to nucleophilic addition of water and HCN to carbonyl
compounds.

Generally,

O OH
R
R''MgCl R
OMgCl H3O+
C C
R R' C
R' R''
R' R''

Mechanism
MgX
MgX
O
O O
R
MgX R- R-
C C
C

OH
H3O+
C

28
11. Reactions of Carbonyls with Phosphorous pentachloride

Carbonyl compounds generate dichloride.

O Cl
PCl5 H
C C
R H R Cl

O Cl
PCl5 R R''
C C
R R'
Cl
O
PCl5
Cl

Acetophenone Cl
1,1-Dichloro-1-phenylethane
Mechanism

PCl5 exists as [PCl4 ] +[PCl6 ]-

29
12. Nucleophilic addition of Alcohols: Acetal formation

Reaction of carbonyl compounds with 2 equivalents of an alcohol in the presence of acid

catalyst yields acetals, R2 C(OR’)2 , sometimes referred to as ketals if is derived from
ketones.

O
2 CH3OH
O + H2 O
HCl catalyst
O
Cyclohexanone Cyclohexanone dimethyl acetal

This reaction initially yields a hydroxy ether called a hemiacetal, analogous to the gem
diol formed by addition of water. Hemiacetals are formed reversibly with the equilibrium
normally favouring the carbonyl compounds. Protonation of the –OH group in the
presence of acid, followed by an E1- like loss of water, leads to an oxonium ion, R 2 C =
OR+, which undergoes a second nucleophilic addition of alcohol to form the Acetal.
H OH
O
O
H A C
C C

A protonated carbonyl group

A neutral carbonyl group is strongly electrophilic because
is moderately of the positive charge on carbon
electrophilic because of
the polarity of the C - O

R H
Mechanism
OH OH O
O OH
O
+ H Cl C C H H
C C
ROH
OR
Hemiacetal

HCl

R
OR O
OH2
OR ROH
C C
H2O C
H3O+ + H
C O
OR OR
Acetal
R

Acetal can act as protecting groups for carbonyl compounds analogous to trimethylsilyl
ether protection of alcohols. Sometimes one functional group within the molecule can
interfere with the intended chemistry elsewhere in a complex molecule.

30
For example,
O

O ??
HO

O 5-Hydroxy-2-pentanone
Ethyl 4- oxopentanoate

By protecting the keto group as an acetal, the problem can be solved. Like other ethers,
acetals are unreactive to bases, reducing agents, Grignard reagents, and catalytic reduction
conditions, but are cleaved by acid. The protective acetal group can be removed by
treatment with aqueous acid.

O
O OCH2 CH3
O

HOCH2CH2 OH C
O + H 2O
Acid catalys O
O
Ethyl-4-oxopentanoate
1. LiAlH4
2. H3O+
Cannot be
done directly

H3O+ O + CH3CH2OH
HO O
CH2OH
5-Hydroxy-2-pentanone
+

HO
OH
Ethylene glycol

In practice, it’s convenient to use 1 equivalent of a diol such as ethylene glycol as the
alcohol and to form a cyclic acetal.

Acetals and hemiacetals groups are particularly common in carbohydrates chemistry.

Glucose, for instance, is a polyhydroxy aldehyde that undergoes an internal nucleophilic
addition reaction and exists primarily as a cyclic hemiacetal.

31
 H OH
HO OH HO
H O
HO
O HO OH
H OH
HO OH
H H
Glucose
Glucose - cyclic hemiacetal

13. Nucleophilic addition of Phosphorus Ylides: The Wittig Reaction

Carbonyl compounds are converted to alkenes by means of a nucleophilic addition called the
Wittig reaction. The reaction is useful in laboratory and drug manufacture.

In this reaction, a phosphorus ylide, R2C P(C6H5)3 , also called phosphorane and
sometimes written in the resonance form R2C P(C6H5)3 adds to an aldehyde or ketone to
yield a dipolar intermediate called a betaine. A betaine- pronounced bay-ta-een- is a neutral,
dipolar compound with nonadjacent charges.) The betaine intermediate is not isolated, rather,
it spontaneously decomposes through a four- membered ring to yield alkene plus
triphenylphosphine oxide, (Ph)3 P = O. The net result is replacement of the carbonyl oxygen
atom by the R2 C = group originally bonded to phosphorus.

P(Ph)3

O
C PH(Ph)3 O P(Ph)3
R''' R'' O R''
C R R''
R R' C C C
C R'''
R' R'''
R R'

R R'''

C C + (Ph)3 P = O

R' R''

The phosphorus ylides required for Wittig reaction are easily S N2 reaction of primary (and
some secondary) alkyl halides with triphenylphosphine P(Ph)3 , followed by treatment with
base.

32
 CH3
P
SN 2
P
+ H3C Br
Br-
Bromomethane

Triphenylphosphine
BuLi (Butyllithium)
Methyltriphenyl-
phosphonium bromide

CH2

Methylenetriphenyl-
phosphorane

The Wittig reaction is extremely general, and a great many monosubstituted, disubstituted,
and trisubstituted alkenes can be prepared from the appropriate carbonyls and ylides.

Distinguishing between Aldehydes and Ketones

Aldehydes can be differentiated from Ketones by various reagents that are oxidizing agent’s
i.e.

a) Ammoniacal Silver nitrate solution.

The reagent consists of silver nitrate in presence of excess ammonia solution.

Aldehydes react with ammoniacal silver nitrate form a silver mirror alongside a clean
test tube on warming whereas no observable change for Ketones.

Ethanal reacts almost immediately.

RCHO + 2Ag(NH3)2OH RCOONH4 + 2Ag + H2O +3NH3

b) Fehling’s test.

Aliphatic Aldehydes reduce copper (II) ions to reddish-brown copper (I) oxide on
heating.

RCHO + 2Cu2+ + NaOH + H2O RCOONa + Cu2O + 4H+

Ketones and aromatic Aldehydes give no observable change.

33
Reactions of Aromatic Aldehydes and Ketones involving substitution in Ring and
side reactions.

Carbonyl group is deactivating group therefore the reaction involving the benzene ring
generate meta-derivative product.
Br

O
Br2

FeBr3
O
Acetophenone m-Bromoacetophenone

O
Conc. HNO3
- O
O
Conc. H2SO4 +
N

Benzaldehyde
O
m-nitrobenzaldehyde

Zn(Hg), Conc. HCl

OR NH2NH2, Base,
O glycerol. Heat
Propiophenone Propylbenzene

O O
10% NaOH
2

Acetophenone

1,3-Diphenyl-2-butene-1-one

34