Sodium Dithionite

[7775-14~6J · N~04S2 · Sodium Dithionite · (MW 174.12)

(versatile reagent for reduction of aldehydes, ketones, unsaturated conjugated ketones, '
quinones, diunsaturated acids, azo, nitro, and nitroso compounds, ' imines, oximes,
tropylium salts, pyridinium salts, pyrazine, and vinyl sulfones; ;~ intramolecular Marschalk
cyclizations, , dehalogenation of vic dibromides and a-halo ketones, Claisen rearrangement of
allyloxyanthraquinones and for the synthesis of 8-arylaminopurines ' )

Alternate Name: sodium hydrosulfite.

Physical Data: mp 52 °C (dec). .

Solubility: very sol water; sol alcohol.

Form Supplied in: white or gray-white crystalline powder.

Preparative Methods: by the action of Sulfur Dioxide on Sodium Amalgam in alcoholic solution.

Handling, Storage, and Precautions: flammable; moisture sensitive.

Reduction of Aldehydes and Ketones.

~
Sodium dithionite is an alternative and less expensive reducing agent than metal hydrides. The reactions are
performed in water for soluble substrates, otherwise a 50:50 mixture of water and dioxane or DMF can be used;
sodium bicarbonate is added to keep the reaction mixture basic. Examples are hexanal to 1-hexanol (67%),
benzaldehyde to benzyl alcohol (84%), cyclohexanone to cyclohexanol (80%), and acetophenone to 0.-
· hydroxyethylbenzene (94%). Reduction ofmethylcyclohexanones by N~S204 in benzene-water using adogen .
.(commercial mixture of methyl trialkyl Cg-C 10 ammonium chloride) as a phase-transfer agent afforded good yields
\ of isomeric mixtures of the corresponding methylcyclohexanols. Reduction using N~S204 proceeds with .
I
I

stereoselectivity similar to that obtained with metal hydrides (Sodium Borohydride) and opposite to dissolving
metals reductions, e.g. the reductions of3a.-hydroxy-7-keto-5~-cholanic acid to diols (eq 1).

\
\
 \
..
H

\
+ (1)

N~ 100% 85:15
K,100% 94:6
Na2S204,100% 4:96
NaBH4,100% 6:94

Regiospecific Reduction of Unsaturated Conjugated Ketones. '

Exclusive reduction of conjugated carbon~carbon double bonds 'is achieved with N~S204 to afford the
corresponding saturated carbonyl compound. A two-phase (benzene-water) system using adogen as the phase-
transfer catalyst is used. The isolated carbon-carbon double bond remains unaffected. No alcohols are detectable
(eqs 2-4).

(2)
91%

65%
° (3)

.. (4)
63%

\
Quinones to Hydroquinones.
Most Quinones are reduced by sodium dithionite to hydroquinones. Naphthacenequinone and higher linear
benzologs are exceptional in that they are not reduced by alkaline sodium dithionite. Sodium dithionite reduces
anthraquinone to anthrone.

Conjugated Diunsaturated Acids (and Esters) to

Monounsaturated Acids (and Esters).
a,~;y,8-Unsaturated acids are reduced by N~S204 in an alkaline medium (NaOH or NaHC0 3) to a mixture of (Z)-
and (E)-p,y-unsaturated acids (and esters) (40-75% yield) (eq 5).

NaOH
..

74% 2%

Azo to Amine.
Azobenzene is reduced to aniline by sodium dithionite. This reaction is used to introduce an amino group into a
phenolic compound by first coupling with an aromatic diazonium salt and then reducing the resulting hydroxyazo
derivatives with N~S204' e.g. 2- and 4-amino-I-naphthols can be prepared from I-naphthol.

Nitro to Amine.
Various aromatic nitro compounds are reduced conveniently to the corresponding aniline<krivatives with sodium
dithionite using dioctyl viologen as an electron-transfer catalyst in a two-phase system (CH2CI2-H20), e.g. 1-
nitronaphthalene to 1-naphthylamine.

Nitroso to A"mine.
Nitroso compounds are reduced to amines by sodium dithionite, e.g. nitrosouracil to diaminouracil (eq 6).
Reduction of N-nitrosodibenzylamine with N~S204 is accompanied by liberation ofN2 and rearrangement to
dibenzyl. Mixed benzylaryl or diaryl-N-nitrosoamines are reduced to hydrazines (eq 7).

NH2
\ ... (6)
68-81%
NO NH2
OR OH
 • (7)

Imines to Amines.
Sodium dithionite in DMF reduces imines to N-alkylamines at 110°C with yields ranging from 40 to 73%.
Heating N-cyclohexyldibenzylamine, sodium dithionite, and NaHC0 3 in DMF for 30 min at 110°C gives 73%
benzylcyclohexylamine.

Oximes to Amines.
Oximes are readily reduced to amines by sodium dithionite. Substituted phenylethylamines are key intermediates
required for the synthesis of isoquinoline derivatives. They are readily obtained from aryl alkyl ketones by
nitrosation of the alkyl group followed by the reduction of the resulting oxime derivatives by sodium dithionite (eq
8). .l'

o ".
.. Ph~ (8)
NH2

Cleavage of Oximes.
Both aldehydes and ketones are regenerated from their oxime derivatives with aqueous sodium dithionite either
alone or in the presence ofN~C03 at 25°C, e.g. cyclohexanone oxime to cyclohexanone (95%) and benzaldehyde
oxime to benzaldehyde (96%).

Reduction of Tropylium and Cyclopropenium Halides.

N~S204 in acetonitrile at 25°C reduces the tropylium halides to ditropyl (eq 9) and triphenylcyclopropenium
halides to bicyclopropenyl sulfones (eq 10).

2 x-
MeCN
. (9)
 . Ph
R
o\\110 R
Ph Ph
Na2S204 S
R X- ~ ...
(10)

Ph . Ph
R=H,Ph

Reduction of Pyridinium Salt. .

Sodium dithionite has been extensively used for the reduction of N-methylpyridinium-3-carboxamide to N-methyl-
I,4-dihydropyridine-3-carboxamide (eq 11), which is a model of reduced dihydrophosphopyridine nucleotide
(DPNH).

C'ONH 2·
.. (11)

Reduction of Pyrazine Derivatives.

2,3,5,6-Tetraethoxycarbonyl-I ,4-dihydropyrazine is prepared from 2,3,5,6-tetraethoxycarbonylpyrazine using
sodium dithionite as reducing agent (eq 12). It is a more convenient and simpler method than catalytic
hydrogenation and no saponification of esters occurred during this reduction process.

Reduction of Vinyl Sulfone.

An insect phermone, (Z)-8-dodecenyl I-acetate, is readily obtained by the reduction of corresponding vinyl
sulfone in aqueous ethanol with retention of configuration (eq 13). The mechanism involves the Michael additio'n
. of 802- to the vinylic sulfone, accompanied by protonation and expulsion of 802 and slllfinate ion to give the
alkene.

,I
 .. , (13)
57%

(Z) 98%

Intramolecular Marschalk Cyclization.

This cyclization reaction is a key step in the total synthesis of daunomycinone, the aglycon of an anthracycline
antibiotic. Treatment of the anthraquinone derivative with sodium dithionite and sodium hydroxide in dioxane at
25-90 °C gives the anticipated cyclized product in 52% yield (eq 14).

OMe 0 OR

Dehalogenation ofvic-Dibromides, a-Bromo and a-Chloro

Ketones.
Vicinal dibromides are debrominated with N~S204 in DMF (140-145 °C). The yields are moderate to high but
the reaction is not stereospecific. Both meso- and (±)-2,3-dibromobutane give 1:1 mixtures of cis- and trans-2-
butene. The dehalogenation of a-bromo or a-chloro ketones can be effected with N~S204 in aqueous DMF at
25-90 °C in yields of 50-95%. The rate can be enhanced by addition ofNaHC0 3 •

Claisen Rearrangement of Allyloxyanthraquinone.

l-Allyloxyanthraquinones rearrange to I-hydroxy-2-allylanthraquinones in high yields when heated in DMF-H20
containing 1.3-1.8 equiv N~S204. 1,4-Bis(allyloxy)anthraquinone rearranges slowly wider these conditions, but
more readily if 4 equiv NaOH is added (eq 15).
 o O~ o OR
N~S204' NaOH
Dl\AF, H20

72%
.. (15)

o OH

Synthesis of 8-Arylaminotheophyllines.
Treatment of 5-arylazo-l,3-dimethyl-6-ethoxymethyleneaminouracil with N~S204 in formic acid gives 8-
arylaminotheophyllines (eq 16). The key intermediates required for this reaction are prepared by reaction of the
appropriate 6-amino-5-arylazo-l,3-dimethyluracils with a mixture of Triethyl Orthoformate and DMF at 180°C
for 5 h.

.,-
0 0
Me, N· Me,
N ~N Na2S204
.. N
(16)
oAN I
N~Et HC0 2H O~NI
Me "r Me

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~.
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