Addition of Ylides (Wittig reaction): In 1954, Georg Wittig, working at the

University of Tübingen in Germany, reported a method of synthesizing alkenes from

carbonyl compounds, using phosphorus ylides. A ylide is a compound in which a
carbanion is directly bonded to a heteroatom.
The ylides are another class of nucleophilic organic reagents that add rapidly to the
carbonyl function of aldehydes and ketones.
In this method a phosphorus ylide is added to the carbonyl, leading to the
formation of a 4-membered ring oxaphosphetane, which rearranges to an alkene
and a triphenylphosphine oxide. The net outcome is the replacement of the
carbonyl oxygen by a CRR’ group.

An ylide is a neutral molecule with adjacent positive and negative charges. It is

formed by the reaction of triphenylphosphine with a primary or secondary alkyl
halide to produce a phosphonium salt, which is then deprotonated by a strong base
to yield the ylide.

Mechanism of Wittig reaction

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Example:

ADDITION OF OXYGEN NUCLEOPHILES

 Addition of Water: Adding water to an aldehyde or a ketone gives a product
called a “hydrate” or a “gem-diol” (germinal diol; i.e. two –OH on the same C). The
reaction is both acid- and base-catalysed.
Under acidic conditions, the reaction occurs in three (3) steps: protonation, addition
and deprotonation.

Under basic conditions, it is a two (2) step reaction: addition, followed by

protonation. OH- being a more reactive nucleophile than H2O, addition occurs
directly.

Independent of whether the reaction is acid or base catalysed, the regioselectivity is

the same.
The addition of water to aldehydes and ketones is a reversible reaction. Whether the
equilibrium is more to the right of equation or to the left depends on the
substituents attached to the carbonyl carbon. If alkyl or aryl groups are present,
the equilibrium will be more to the left, i.e. the free carbonyl is favoured.

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<1 % chloral > 99% chloral hydrate

In formaldehyde, the weaker -component of the carbonyl double bond relative to

other aldehydes or ketones, and the small size of the H-substituents favour
addition. In the case of chloral, the equilibrium is more to the right due to the
electron-withdrawing (-I) effect of the -CCl3 group. It destabilises the partial positive
charge on the carbonyl carbon more than it does on the same carbon in the hydrate
form.
Therefore, electron-withdrawing groups attached to the carbonyl carbon make
addition more favourable, and equilibrium will be more to the right. Electron-
donating groups, conjugation with the carbonyl group and larger sized substituents
will all contribute to make addition less favourable.

 Addition of Alcohols: Alcohols react with aldehydes and ketones to form

hemiacetals. This reaction can be acid or base-catalysed.

When an aldehyde or a ketone is dissolved in an alcohol solution, the free carbonyl

compound is in equilibrium with its hemiacetal derivative. Typically the equilibrium
strongly favours the free aldehyde or ketone except when the aldehyde or ketone
can react intramolecularly (i.e. within the same molecule).

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If a 5- or 6-membered ring is formed then the cyclic hemiacetal is the major species
in the equilibrium. Acylic hemiacetals are generally not stable, however, cyclic 5-
and 6-membered ring hemiacetals are stable.
Example:

Carbohydrates, or sugars are usually composed of a linear (unbranched) chain of C

atoms with several alcohol functional groups and an aldehyde or ketone group. In
solution carbohydrates exist as an equilibrium mixture of open chain polyhydroxy-
aldehyde and cyclic hemiacetal compounds.
An example is (+)-Glucose:

In the presence of excess alcohol and an acid catalyst, aldehydes and ketones will
form acetals. Formation of the acetal proceeds via the corresponding hemiacetal.
Hemiacetals react further with alcohols to form acetals only under acidic
conditions.

Under acidic conditions, some of the alcohol becomes protonated. The hemiacetal
OH oxygen abstracts a proton from the protonated alcohol. Loss of water gives a
resonance-stabilized alkoxy carbocation. Nucleophilic attack by the alcohol on the

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carbocation occurs and deprotonation by a further alcohol molecule produces the
acetal.

Acetaldehyde forms a cyclic trimer, called paraldehyde, when treated with acid.
Paraldehyde depresses the central nervous system. It is used as a hypnotic, a sleep
inducer. It is also used in the treatment of alcoholism.
In therapeutic doses, paraldehyde is
nontoxic, it does not depress heart
action or respiration. Its
disadvantages are its unpleasant
odour and taste.

The importance of acetals as carbonyl derivatives lies chiefly in their stability and
lack of reactivity in neutral to strongly basic environments. As long as they are not
treated by acids, especially aqueous acid, acetals exhibit all the lack of reactivity
associated with ethers in general. The reversibility of acetal formation along with
the relative inertness of the acetal linkage (RO-C-OR) make acetals useful as
protecting groups.
Protecting groups are functional groups which may be introduced in a molecule by
converting another functional group in a reversible reaction. If the protecting group
is more inert than the original functional group, then other reactions may be
carried out with this molecule without worrying about altering or destroying the
protecting group. When the other desired reactions are completed, the original
group may be restored by carrying out the reverse of the reaction which introduced
the protecting group.

Cyclic acetals are often used as protecting groups. They are stable to most reagents
except aqueous acid.

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Example: An ester is reduced in the presence of a ketone, protected as an acetal.

ADDITION OF SULPHUR NUCLEOPHILES

Thiols, which are sulphur analogues of alcohols, react with aldehydes and ketones
in the presence of acid to give thioacetals. The reaction can also be carried out in
the presence of a Lewis acid such as BF3.

Example:
The relatively hindered ketone is treated with excess ethanedithiol, which also acts
as the solvent, and the Lewis acid BF3 as catalyst to obtain a good yield of the bis-
thioacetal.

Thioacetals are generally more difficult to hydrolyse than are acetals. They can be
converted to CH2 groups by hydrogenation, using a catalyst such as Raney nickel.
This reaction sequence provides a way to remove an aldehyde or ketone carbonyl
oxygen.

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