Sodium Dithionite1

Na2S2O4

[7775-14-6]  · Na2O4S2  · Sodium Dithionite  · (MW 174.12)

(versatile reagent for reduction of aldehydes,2 ketones,2-6 unsaturated conjugated ketones,7,8 quinones,9-10 diunsaturated acids,11 azo,12 nitro,13 and nitroso compounds,14,15 imines,16 oximes,17 tropylium salts,18 pyridinium salts,19 pyrazine,20 and vinyl sulfones;21 intramolecular Marschalk cyclizations,22,23 dehalogenation of vic dibromides24 and a-halo ketones,25 Claisen rearrangement of allyloxyanthraquinones26 and for the synthesis of 8-arylaminopurines27,28)

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.29,30

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

Reduction of Aldehydes and Ketones.2

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%),3 and acetophenone to a-hydroxyethylbenzene (94%).2 Reduction of methylcyclohexanones by Na2S2O4 in benzene-water using adogen (commercial mixture of methyl trialkyl C8-C10 ammonium chloride) as a phase-transfer agent afforded good yields of isomeric mixtures of the corresponding methylcyclohexanols.3 Reduction using Na2S2O4 proceeds with stereoselectivity4-6 similar to that obtained with metal hydrides (Sodium Borohydride) and opposite to dissolving metals reductions, e.g. the reductions of 3a-hydroxy-7-keto-5b-cholanic acid to diols (eq 1).

Regiospecific Reduction of Unsaturated Conjugated Ketones.7,8

Exclusive reduction of conjugated carbon-carbon double bonds is achieved with Na2S2O4 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).

Quinones to Hydroquinones.9

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.10 Sodium dithionite reduces anthraquinone to anthrone.

Conjugated Diunsaturated Acids (and Esters) to Monounsaturated Acids (and Esters).11

a,b;g,d-Unsaturated acids are reduced by Na2S2O4 in an alkaline medium (NaOH or NaHCO3) to a mixture of (Z)- and (E)-b,g-unsaturated acids (and esters) (40-75% yield) (eq 5).

Azo to Amine.12

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 Na2S2O4, e.g. 2- and 4-amino-1-naphthols can be prepared from 1-naphthol.

Nitro to Amine.13

Various aromatic nitro compounds are reduced conveniently to the corresponding aniline derivatives with sodium dithionite using dioctyl viologen as an electron-transfer catalyst in a two-phase system (CH2Cl2-H2O), e.g. 1-nitronaphthalene to 1-naphthylamine.

Nitroso to Amine.

Nitroso compounds are reduced to amines by sodium dithionite, e.g. nitrosouracil to diaminouracil (eq 6).14 Reduction of N-nitrosodibenzylamine15 with Na2S2O4 is accompanied by liberation of N2 and rearrangement to dibenzyl. Mixed benzylaryl or diaryl-N-nitrosoamines are reduced to hydrazines (eq 7).

Imines to Amines.

Sodium dithionite in DMF reduces imines16 to N-alkylamines at 110 °C with yields ranging from 40 to 73%. Heating N-cyclohexyldibenzylamine, sodium dithionite, and NaHCO3 in DMF for 30 min at 110 °C gives 73% benzylcyclohexylamine.

Oximes to Amines.17

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).

Cleavage of Oximes.16

Both aldehydes and ketones are regenerated from their oxime derivatives with aqueous sodium dithionite either alone or in the presence of Na2CO3 at 25 °C, e.g. cyclohexanone oxime to cyclohexanone (95%) and benzaldehyde oxime to benzaldehyde (96%).

Reduction of Tropylium and Cyclopropenium Halides.18

Na2S2O4 in acetonitrile at 25 °C reduces the tropylium halides to ditropyl (eq 9) and triphenylcyclopropenium halides to bicyclopropenyl sulfones (eq 10).

Reduction of Pyridinium Salt.19

Sodium dithionite has been extensively used for the reduction of N-methylpyridinium-3-carboxamide to N-methyl-1,4-dihydropyridine-3-carboxamide (eq 11), which is a model of reduced dihydrophosphopyridine nucleotide (DPNH).

Reduction of Pyrazine Derivatives.20

2,3,5,6-Tetraethoxycarbonyl-1,4-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 1-acetate,21 is readily obtained by the reduction of corresponding vinyl sulfone in aqueous ethanol with retention of configuration (eq 13). The mechanism involves the Michael addition of SO2- to the vinylic sulfone, accompanied by protonation and expulsion of SO2 and sulfinate ion to give the alkene.

Intramolecular Marschalk Cyclization.22,23

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).

Dehalogenation of vic-Dibromides, a-Bromo and a-Chloro Ketones.

Vicinal dibromides are debrominated24 with Na2S2O4 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 dehalogenation25 of a-bromo or a-chloro ketones can be effected with Na2S2O4 in aqueous DMF at 25-90 °C in yields of 50-95%. The rate can be enhanced by addition of NaHCO3.25

Claisen Rearrangement of Allyloxyanthraquinone.26

1-Allyloxyanthraquinones rearrange to 1-hydroxy-2-allylanthraquinones in high yields when heated in DMF-H2O containing 1.3-1.8 equiv Na2S2O4. 1,4-Bis(allyloxy)anthraquinone rearranges slowly under these conditions, but more readily if 4 equiv NaOH is added (eq 15).

Synthesis of 8-Arylaminotheophyllines.27,28

Treatment of 5-arylazo-1,3-dimethyl-6-ethoxymethyleneaminouracil with Na2S2O4 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-1,3-dimethyluracils with a mixture of Triethyl Orthoformate and DMF at 180 °C for 5 h.


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Marudai Balasubramanian & James G. Keay

Reilly Industries, Indianapolis, IN, USA



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