7. The Wittig Reaction [reactions of carbonyl compounds cont.

…]
This involves the synthesis of alkene by reacting ylides and the carbonyl compound. The
advantage of the Wittig reaction is that the location of the double bond is absolutely fixed, in
contrast to the mixtures often produced by alcohol dehydration.
Ylide formation
Ylides can be synthesized from an alkyl halide and a trialkyl phosphine.
1) SN2 reaction

2) Deprotonation
 3) Formation of the alkene

1) Nucleophilic attack on the carbonyl

2) Formation of a 4 membered ring

8. Formation of Acetals and Ketals from carbonyl compounds
• Water adds rapidly to the carbonyl function of aldehydes and ketones to form diols,
referred to as hydrate (dihydroxy compound/geminal (gem diol).
R
R
C O + H 2O R1 C OH C C

R OH OH
OH
G e m in a l d io l V ic in a l d io l

▪ One equivalent of an alcohol, in the presence of an acid catalyst, adds reversibly to

aldehydes and ketones to form a hydroxy ether called a hemiacetal (R2COHOR')
(hemi, Greek, half). This reaction can continue by adding another equivalent of an
alcohol to form a diether called an acetal R2C(OR')2.

• Acetals are geminal-diether derivatives of aldehydes or ketones, formed by reaction

with two equivalents (or an excess amount) of an alcohol and elimination of water.
 Mechanism for Hemiacetal and Acetal Formation
1) The acid catalyst 4) The OH group of the
protonates the carbonyl hemiacetal is protonated
oxygen, making the making it into a good leaving
carbonyl carbon more group.
electrophilic.
5) Lone pair electrons on
the ether oxygen reforms
the C=O bond causing the
2) An alcohol undergoes elimination of water and
nucleophilic addition to producing an oxonium ion.
the carbonyl producing a
6) A second alcohol
protonated hemiacetal.
undergoes nucleophilic
addition to oxonium ion
producing a protonated
acetal.

3) Water acts as base to

cause a deprotonation 7) Water acts as a base
and causes a
creating a hemiacetal and
deprotonation, creating
hydronium.
the product acetal.
• Molecules which have both an alcohol and a carbonyl can undergo an intramolecular
reaction to form a cyclic hemiacetal.

• Because sugars often contain alcohol and carbonyl functional groups, intramolecular
hemiacetal formation is common in carbohydrate chemistry
NB: An acid catalyst must be used during
this reaction because alcohols are weak
nucleophiles and would add very slowly
under neutral conditions. Under acidic
conditions, the oxygen of the carbonyl
becomes protonated, increasing the
electrophilicity of the carbonyl carbon,
speeding up the reaction.
9. Tollens' reagent/Tollens test
Tollens' reagent is a chemical reagent used to distinguish between aldehydes and
ketone functional groups along with some alpha-hydroxy ketones which can tautomerize
into aldehydes. It exploits the fact that aldehydes are readily oxidized, whereas ketones
are not. The reagent consists of a solution of silver nitrate, ammonia and sodium
hydroxide
Tollens’ reagent is prepared using a two-step procedure
Step 1: Aqueous silver nitrate is mixed with aqueous sodium hydroxide.
2AgNO3 + 2NaOH → Ag2O (brown ppt) + 2NaNO3 + H2O
Step 2: Aqueous ammonia is added drop-wise until the precipitated silver oxide
completely dissolves.
Ag2O (brown ppt) + 4NH3 + 2NaNO3 + H2O → 2[Ag(NH3)2]NO3 + 2NaOH
i.e. it contains the [Ag(NH3)2]+ complex.
During the reaction:
(i) The aldehyde is oxidized by the Tollens reagent and forms a carboxylic acid.
(ii) The silver ions present in the Tollens reagent are reduced into metallic silver. The
silver form a silver mirror on the test tube which leaves a shiny appearance inside the
test-tube, indicating a positive result.
Tollens’ test cannot distinguish between an aldehyde and an α-hydroxy ketone.
The alpha hydroxyl ketones give positive Tollens' Test because they tautomerize to give
alpha hydroxyl aldehydes. For example, 1-hydroxy-2-propanone, tautomerizes to 2-
hydroxypropanal as illustrated below.
 10. Benedict’s reagent/Benedict’s solution/Benedict’s test
▪ Benedict’s solution is a deep-blue alkaline chemical reagent used to test for the presence of the
aldehyde functional group -CHO which consists of copper sulfate pentahydrate (CuSO4. 5H2O), sodium
carbonate (Na2CO3), sodium citrate (Na3C6H5O7) and distilled water.
▪ Sodium carbonate renders alkaline conditions which are required for the redox reaction, while sodium
citrate is a complexing agent which complexes with the copper (II) ions to avoid degradation into copper
(I) ions during storage.
▪ When exposed to reducing sugars Benedict’s test is performed by heating the reducing sugar solution
with Benedict‘s reagent. The presence of the alkaline sodium carbonate converts the sugar into a strong
reducing agent called enediols
 11. Fehling’s Test

For Fehling’s solution, the starting reagents are; bright blue copper(II) sulfate, sodium hydroxide, and
potassium sodium tartrate (otherwise known as Rochelle’s salt). The purpose behind using the
tartrate is that it coordinates to the copper(II) and helps prevent it from crashing out of solution.

In Fehling’s solution the reaction between copper(II) ions and aldehyde is represented as;

When tartrate is added:

RCHO + 2 Cu(C4H4O6)22− + 5 OH− → RCOO− + Cu2O + 4 C4H4O62− + 3 H2O

Glucose found to be in urine is an indication of diabetes mellites.

 12. Haloform Reaction e.g. iodoform reaction
When Iodine and sodium hydroxide are added to a compound that contains either a methyl
ketone or an alcohol with a methyl group in the alpha position, a pale yellow precipitate forms.
The base (hydroxide ion) takes out the alpha hydrogen producing enolate. Then, the
reaction between the enolate and the halogen occurs, leading to the formation of the
halogenated ketone. The process is repeated twice to yield a tri-halogenated ketone.
The hydroxide ion acts as a nucleophile and attacks the electrophilic carbon which is
doubly bonded to oxygen.
13. The Cannizzaro Reaction
• A characteristic reaction of aldehydes without α- hydrogens is the self oxidation-
reduction they undergo in the presence of strong base. Example:

NB: If the aldehyde has α hydrogens,

other reactions usually occur more rapidly.
 14. Aldol condensation
An aldol condensation is a condensation reaction in which an enol or an enolate ion reacts with
a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone, followed
by dehydration to give a conjugated α, β – unsaturated ketone also known as enone. When
similar carbonyl compound undergoes aldol condensation, it is referred to as simple aldol
condensation
The general reaction of aldol condensation

NaOH

Heat
 Crossed aldol condensation
• Crossed aldol condensation occurs when two dissimilar carbonyl compounds (each
containing alpha hydrogens) undergo the condensation reaction together. In such
reactions, up to four different products may be formed.
• Either carbonyl compound can act as the nucleophile and self-condensation is
possible.
• The mechanism: the strong base
(base-catalyzed aldol reaction)
acquires a proton from the alpha-
carbon and generates the enolate.
• The enolate is then used as
a nucleophile to attack the aldehyde
in an SN2 fashion.
• A proton transfer occurs forming
the beta -hydroxyketone
intermediate.
• Another OH- acquires an alpha-
proton upon additional heating, and
starts the dehydration, the OH is
eliminated, forming the final
product.