4) Hydroboration–oxidation of alkynes.

Borane (BH3) adds to alkynes to form

alkenes, which undergo oxidation with H2O2 and NaOH (alkaline peroxide), yielding
an enol. The addition of borane is an anti-Markownikoff addition. Terminal alkynes
form aldehydes, whereas internal alkynes give ketones as final product.
Example:

There are two other interesting reactions that give aldehydes or ketones as
products, but these are less important as synthetic methods: ozonolysis of alkenes
and periodate cleavage of glycols. Ozonolysis and periodate cleavage are reactions
that break carbon–carbon bonds. Because an important aspect of organic synthesis
is the making of carbon–carbon bonds, the use of these reactions in effect wastes
some of the effort that goes into making the alkene or glycol starting materials.
Nevertheless, these reactions can be used synthetically in certain cases.
Reactions involving carboxylic acids and their derivatives will be discussed in
subsequent sections.

REACTIONS OF ALDEHYDES AND KETONES

The carbonyl group C=O governs the chemistry of aldehydes and ketones in two
ways:
 by providing a site for nucleophilic addition, and
 by increasing the acidity of the hydrogen atoms attached to the alpha carbon.
The reactions can be divided into two
main categories:
a) – Reactions of the carbonyl group
b) – Reactions involving the -carbon.

Since the important step in the reactions of carbonyls is the formation of a bond to
the electron-deficient (acidic) carbonyl carbon, they are most susceptible to be
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attacked by electron-rich, nucleophilic reagents, that is, by bases! The typical
reaction of aldehydes and ketones is nucleophilic addition. With the exception of
oxidation of aldehydes, the reactions of aldehydes and ketones is therefore
dominated by nucleophilic addition.

Mechanism of nucleophilic addition:

In case a weak nucleophile is reacting, an acid catalyst is used to initiate the

reaction. The carbonyl oxygen is protonated to form an oxonium cation, thereby
enhancing the electrophilicity of the carbonyl carbon.

The nucleophile can then easily attack the carbonyl carbon.

Aldehydes are typically more reactive than ketones due to the following factors.
1  Aldehydes are less hindered than ketones (a hydrogen atom is smaller than any
other organic group).
2  The carbonyl carbon in aldehydes generally has more partial positive charge
than in ketones due to the electron-donating nature of alkyl groups. Aldehydes only
have one e-donor group while ketones have two.

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OXIDATION
The most common and characteristic oxidation reaction is the conversion of
aldehydes to carboxylic acids. RCHO + [O] RCOOH. There are several
different methods of accomplishing this transformation, the most common of which
is the use of oxidizing agents such as acidified dichromate (Cr2O72-) or
permanganate (MnO4-).

Even oxygen in air will slowly oxidize aldehydes to acids or peracids. Useful tests for
aldehydes take advantage of this ease of oxidation by using mild oxidizing agents
such as Tollens', Benedict's, and/or Fehling's reagent. When an aldehyde is heated
with Benedict’s or Fehling’s solution or treated with a Clini-test tablet (all of which
contain Cu2+ complex ion), a red precipitate of copper (I) oxide (Cu2O) is formed.

This is actually the test for glucose

(sugar) in urine, since glucose is an
aldehyde.

The presence of aldehydes with the Tollen’s reagent, which contains Ag+ complex
ion, causes the formation of a bright, shiny mirror inside the test tube; hence the
name “silver mirror test”. -Hydroxyketones also give a positive Tollen’s test, but not
simple ketones.

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Saturated ketones are generally inert to oxidation conditions that convert aldehydes
to carboxylic acids. Nevertheless, under vigorous acid-catalysed oxidations with
nitric or chromic acids ketones may undergo carbon-carbon bond cleavage at the
carbonyl group.

REDUCTION
Reduction of carbonyl compounds, either to alcohols or to hydrocarbons, may take
place by different mechanisms. For example, hydrogenation (Pt, Pd, Ni or Ru
catalysts), reaction with diborane, and reduction by lithium, sodium or potassium
in hydroxylic or amine solvents have all been reported to convert carbonyl
compounds into alcohols. However, the complex metal hydrides are generally
preferred for such transformations because they give cleaner products in high yield.

 Addition of a hydride anion (H-) to an aldehyde or ketone would produce an

alkoxide anion, which on protonation should yield the corresponding alcohol.
Aldehydes would give 1º alcohols and ketones would give 2º alcohols.

Two practical sources of hydride ion are the complex metal hydrides lithium
aluminum hydride (LiAlH4) and sodium borohydride (NaBH4). These are both white
(or near white) solids. LiAlH4 is far more reactive, reacting violently with water,
alcohols and other acidic groups with the evolution of hydrogen gas.
LiAlH4 and NaBH4 act in a fashion similar to Grignard reagents. The hydride ion H-
acts as the nucleophilic reagent adding to the carbonyl carbon atom of an aldehyde
or a ketone.

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Example:

In the above example, it is shown that all four hydrogens of the complex metal
hydrides may function as hydride anion equivalents which bond to the carbonyl
carbon atom. In the LiAlH4 reduction, the resulting alkoxide salts are insoluble and
need to be hydrolyzed (with care) before the alcohol product can be isolated. In the
borohydride reduction the hydroxylic solvent system achieves this hydrolysis
automatically. The Li, Na, B and Al end up as soluble inorganic salts.
Some functional groups which may be reduced by LiAlH4 are unreactive with NaBH4
(e.g., alkyl halides R-X, nitro groups -NO2). Therefore NaBH4 may be used to reduce
C=O bonds in the presence of such groups.
The reductive conversion of a carbonyl group to a methylene group requires
complete removal of the oxygen, and is called deoxygenation. This can be achieved
in different ways.
 Wollf-Kishner reduction: In the context of complex molecule synthesis, it is
frequently employed to remove a carbonyl function after it has served its synthetic
purpose of activating an intermediate. An aldehyde or a ketone reacts with excess
hydrazine to generate a hydrazone derivative, which on heating with base gives the
corresponding hydrocarbon.
Example:

DEG = diethylene glycol

The Wollf-Kishner reduction requires highly basic conditions, and is therefore
unsuitable for base sensitive substrate. In some cases, formation of the required
hydrazone will not occur at sterically hindered carbonyl groups, preventing the
reaction.
 Clemmensen reduction: This alternative method is most commonly used to
convert acylbenzenes, from Friedel-Crafts acylation, to alkylbenzenes. It also works
with aldehydes and ketones that are not sensitive to acid. The carbonyl compound
is heated with excess amalgamated zinc, Zn (Hg), and conc. HCl. The reduction
occurs by a complex mechanism on the surface of the Zn.

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Example:

ADDITION OF CARBON NUCLEOPHILES

Carbon nucleophiles are generally found in organometallic reagents. The two most
commonly used of such are Grignard and organolithium reagents.

They are powerful nucleophiles and strong bases, so they readily bond, essentially
irreversibly, to the carbonyl carbon.
Aldehydes and ketones will therefore react with an organometallic reagent to give an
alkoxide salt of lithium or halomagnesium. In the second step, weak hydrolysis of
the alkoxide salt yields an alcohol.
Step 1:

halomagnesium alkoxide
Lewis acid-base interaction
between basic carbonyl oxygen
and Mg makes the carbonyl carbon
more reactive toward the alkyl group.
Step 2:

alcohol
- The addition of organometallic to aldehydes or ketones is an important synthetic
method available to chemists, because it permits simple starting compounds to be
joined to form more complex structures.
- It is an efficient method of carbon chain elongation.
- It is a good method of synthesizing primary (from formaldehyde), secondary (from
aldehydes), and tertiary alcohols (from ketones).

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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. 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

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