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Reduction of Aldehydes, Ketones, To: (1) Clemmsens Method
Reduction of Aldehydes, Ketones, To: (1) Clemmsens Method
This type of reduction forms one step in the extension of benzenoid systems
via Friedel-Crafts acylations.
The reagent also reduces the olefinic bond in α β–unsaturated ketones,
acids, and esters; and benzyl halides and alcohols are hydrogenolyzed. Strongly
hindered ketones give low yields and sometimes rearrangement products [e.g.
Ph3C-CO-PhPh2C=CPh2]
[2]Wolff-Kishner Method.
The hydrazones of aldehydes and ketones are reduced in vigorous basic
conditions with the evolution of nitrogen, probably as follows:
The standard procedure is the Huang-Minlon modification. The
hydrazone is formed by heating the carbonyl compound with hydrazine hydrate
and potassium hydroxide in di- or tri-ethylene glycol under a water condenser.
After completion of the formation of the hydrazone, the water condenser is
removed so that water liberated in the first reaction is distilled and the
temperature rises to about 200 oC, so bringing about decomposition of the
hydrazone.
A newly developed modification employs potassium t-butoxide as the
base and dimethyl sulphoxide as solvent. Alkoxide bases are very much more
powerful in this solvent than in water or hydroxylic solvents and reaction
occurs at room temperature in high yield. For example, benzophenone gives
about 905 of diphenylmethane:
[3]Mozingo Method.
The carbonyl compounds are converted with ethylene dithiol in the presence of
a Lewis acid into its dithiol-acetal or ketal and this is hydrogenolyzed over
Raney nickel:
[B]TO ALCOHOLS
Carbonyl compounds are reduced to alcohols by the variety of reagents.
Of the three general classes of reductive process, catalytic hydrogenation is
not normally chosen because it is slow, but both hydride-transfer reagents are
employed.
[I]HYDRIDE TRANSFER
The alkali-metal hydrides such as sodium hydride are unsuitable
reducing agents because of their insolubility in organic solvents and their
powerful effects as catalyst for base-catalyzed condensations. The most
commonly used hydride reducing agents are lithium aluminium hydride, sodium
[or potassium] borohydride and lithium borohydride.
[1Lithium aluminium hydride
Lithium aluminium hydride is made by treating lithium hydride with aluminium
trichloride in ether, and is generally used in very dry ether or tetra-hydrofuran
.All hydroxyl-,amino-,and thiol-containing compounds liberate hydrogen
quantitatively from it e.g.,
Each of the four hydrogen atoms in lithium aluminium hydride is
available for the transfer to carbonyl groups. e.g.
each step occurring less rapidly than the proceeding one[As result, the
replacement of two or three hydrogen atoms of aluminium hydride anion by
alkoxy groups give less reactive selective reducing agents;].Finally, hydrolysis
of the aluminum alkoxide give the alcohol.
[2]Sodium borohydride.
Sodium borohydride is much less reactive .It can be used in alcoholic
solvents and even in water ,for it decomposes only enough to make the solution
alkaline, after which it is stable.
[3]Lithium borhydride
Lithium borohydride in more reactive than sodium analogue and reacts
with hydroxylic compounds. It is usually employed in solution in
tetrahydrofuran or diethylene glycol dimethyl ether [diglyme].
These three reagents differ considerable in their reducing power.
Lithium aluminium hydride reduces not only aldehydes and ketone but also
acids, acid chlorides, esters, nitriles, imines, and nitro groups, whereas sodium
borohydride reduces only aldehydes, ketones, imines and acid chlorides.
Lithium borohydride resemble sodium borohydride except that it also
reduces esters and nitriles. None of the reagents normally reduces olefinic,
acetylenic, or N=N bonds, although the first reduces acetylenes containing α-
hydroxy-substituents and reduces azo compounds in the presence of Lewis acid.
Except in simple cases, therefore, sodium borohydride is the reagent of
choice. Typical examples are:
[4]Cannizarro reaction.
Aldehydes which do not have α-CH groups cannot undergo base-catalyzed
condensation. Instead they react with bases by disproportionation involving the
transfer of hydride ion e.g.
Zinc is often used as the electron source in these reductions. For example, α-
hydroxycyclodecanone gives cyclodecanone in about 75% yield when treated
with zinc in mixture of hydrochloric and acetic acid at 75-80 oC
[C] PINACOLS.
In the absence of a proton-donor, electropositive metal reduce ketones
to pinacols via the dimerization of anion-radicals:
The standard procedure employs amalgamated magnesium with benzene a
solvent; the solid magnesium salt of the pinacol is formed and is hydrolyzed to
the pinacol. For example, acetone gives pinacol itself in 45% yield after 2
hours in refluxing benzene
The reaction is generally ineffective for aldehydes because they are too
readily reduced to alcohols. Pinacols may also be formed by photochemical
dimerization