Sodium Sulfide1

Na2S.9H2O
(nonahydrate)

[1313-84-4]  · H18Na2O9S  · Sodium Sulfide  · (MW 240.18) (anhydrous)

[1313-82-2]  · Na2S  · Sodium Sulfide  · (MW 78.05)

(nucleophile and reducing agent derived from H2S; reagent for the synthesis of thiols,2 thioethers,3 and disulfides;4 reduces aromatic nitro compounds to amines5)

Physical Data: mp ~50 °C (hydrate, loses most of its water below 100 °C); mp 1180 ± 10 °C (pure Na2S); d 1.43 g cm-3 (anhydrous 1.86 g cm-3); E0 (S2- -> S + 2e) +0.48 V.

Solubility: v sol cold and hot water; somewhat sol methanol, ethanol; insol acetone, benzene, ether.

Form Supplied in: colorless or pale yellow crystalline solid. May contain NaSH and small amounts of Na2S2O3, Na2SO3, NaOH, Na2CO3, NaCl, Na2S2O4, and Na2SO4. Also available as essentially anhydrous fused chips of 60% Na2S. The form used in synthesis is not always specified. A pentahydrate is also known.

Analysis of Reagent Purity: titration methods (e.g. iodometric) are available.

Handling, Storage, and Precautions: light (discolors) and air sensitive. Produces H2S on exposure to air. Corrosive; flammable; deliquescent. Refrigerate. Incompatible with oxidizing agents and strong acids. Destructive of mucous membranes, eyes, skin. Absorbed through the skin. Inhalation can be fatal. Use a well-ventilated hood, goggles, and gloves.

Preparation of Na2S2, Na2Sx.

Refluxing sodium sulfide with elemental Sulfur in 95% ethanol or aqueous sodium hydroxide yields solutions of Sodium Disulfide, Na2S3, and Na2Sx.6

Thiols.

Although treatment of halides, epoxides, aziridines, and sulfonate esters with Sodium Hydrogen Sulfide or Potassium Hydrogen Sulfide is usually more advantageous (Na2S often gives the thioether), the use of Na2S2 followed by reduction of the disulfide has found application (eq 1).6b,d Sulfide or disulfide ions can cleave a disulfide to a thiolate ion,7 and nitro aromatic halides have been observed to yield the thiolate under conditions in which Na2S2 may be formed from Na2S.7b Best results are obtained at room temperature with anhydrous Na2S, in DMF or DMSO (eq 2).8a Reduction of the nitro group8b does not occur. What appears to be a direct synthesis of a thiol via Na2S.9H2O occurs in the formation of 6-mercaptopteridine (84% yield) from 6-chloropteridine,9a and 3-aryl-1,2,3,4-thiatriazolium-5-thiolates (30-34% yields) from 5-ethoxy-3-aryl-1,2,3,4-thiatriazolium tetrafluoroborates.9b Na2S cleaves thiocyanates to the thiols.10 Tertiary thiols are obtained from tertiary nitro compounds by treatment with Na2Sx (Na2S + S) in DMSO (eq 3),11 but the reaction is limited to tertiary derivatives. Addition of Methanethiol to acetaldehyde in the presence of Na2S gives the dithiohemiacetal in 38% yield.12

Thioethers (Sulfides).

Symmetrical primary and secondary acyclic thioethers are obtained from the corresponding halide, sulfonate, or sulfate ester.13 Oxiranes and aziridines are also useful substrates but Hydrogen Sulfide, NaSH, and KSH are more commonly used with this class of compound.3 Secondary starting materials may yield some alkene, particularly if Na2S is prepared in situ from H2S and alkali. The yield of di-n-octyl sulfide from n-octyl bromide is increased from 20% to 97% when Na2S is supported on neutral Alumina.14 The use of phase-transfer catalysis is beneficial.15 In the absence of catalyst, the yield of bis(3-penten-2-yl) sulfide from 4-chloro-2-pentene and Na2S.9H2O is 14%; in the presence of polyglycol or Tetra-n-butylammonium Bromide it is 98% and 94%, respectively (eq 4).15a The a-trimethylsilyl sulfide (1) is a source of the useful MeSCH2- synthon (eq 5),16 Bis(trimethylsilyl) Sulfide is available (96% yield) by treatment of Chlorotrimethylsilane with anhydrous Na2S at 240 °C in a sealed tube.17a Treatment of this silyl sulfide17b with Methyllithium yields highly active Li2S that is useful in the synthesis of six- to twelve-membered sulfur heterocycles without the need for high dilution techniques.17c Addition of the sulfide anion to Michael acceptors such as acrylonitrile is another route to acyclic sulfides.18

Cyclic sulfides in small to large ring sizes are readily obtained from dihalides, bissulfonates, or other compounds that are capable of reacting with Na2S at two sites with formation of a ring. The formation of thiiranes19 from 1,2-dihalides and Na2S frequently fails due to polymerization or elimination to the alkene. However, use of a-halo or thiocyanato thiocyanates or disulfides with Na2S can circumvent this limitation (eq 6).19,20 Thietanes are conveniently prepared from 1,3-dihalides and related compounds (eq 7).21 Cyclizations involving mesylates or tosylates are conducted under anhydrous conditions to avoid hydrolysis.22 Even the cyclization of 1,4-dichlorobutane to thiolane gives better yields if fused 60% Na2S is used instead of the nonahydrate.23 Examples of the synthesis of five- and six-membered sulfur heterocycles are shown in eqs 8-10.24-26 The dithiin synthesis in eq 11 demonstrates the ability of sulfide ion to add to an acetylenic bond.27 Macrocyclic sulfides are readily prepared (eq 12).28

Aryl sulfides are obtained by SNAr-type reactions of sulfide ion with activated aryl halides;3 a nitro group also may be displaced,29a even in preference to halogen.29b Phase transfer catalysts, including crown ethers, are useful (eq 13).30 The yields in the substitution reaction are sensitive to the medium. The yield of sulfide from 4-chlorobenzonitrile is 99% in DMF but only 14% in toluene.30 In ethanol, 2,4-dinitrochlorobenzene yields the sulfide (79%) with Na2S.9H2O and the disulfide when the same reaction is done in the presence of elemental sulfur.31 It should be noted that nitro groups may be reduced by sulfide or polysulfide ions.5

Di- and Polysulfides.

These are derived from Na2S2 (or Li2S2, Na2Sx) and halides (or their equivalents) (eq 14)4,6a,c-e,32,33 or aryl diazonium salts (eq 1).6b With some substrates, especially those that contain sulfur, Na2S itself may be used (eq 15).33

Reductions.

Sodium sulfide and polysulfides are better reducing agents than H2S and have been widely used in the reduction of aromatic nitro groups to amino groups (the Zinin reaction).5,6c,f,7c,34 The reduction can be selective for one nitro group of several. In the reduction shown in eq 16, Na2S reduces the o-nitro group whereas Tin(II) Chloride reduces the p-nitro group.34a The Zinin reaction is especially useful in the presence of groups sensitive to acid that preclude the use of a metal-acid reducing reagent. Aliphatic nitro groups are unreactive (eq 17),35 although elimination of nitrous acid has been observed with tertiary aliphatic derivatives. Differences are observed depending on whether Na2S.9H2O or anhydrous Na2S is used. Treatment of p-nitrotoluene with Na2Sx-NaOH results in a remarkable oxidation-reduction reaction (eq 18).6c,36 Partial reduction of 2,2-dinitrobiphenyl by Na2S gives a benzocinnoline (eq 19),37a whereas Na2Sx gives the monoamino derivative.37b Refluxing 2-nitro-4,5-dimethoxybenzophenone with methanolic sodium sulfide yields the anthranil (2) (eq 20).37c A quinone dioxime is reduced to the diamine by Na2S.9H2O,38 and nitrite esters are reduced to alcohols.39 In b-nitrostyrenes, the nitro group is replaced by hydrogen on treatment with Na2S.9H2O-PhSH.40 Other functionalities that are reduced by Na2S are as follows (product in parentheses): nitroxide (amine),41 chlorosulfonyl (sulfinic acid),42 disulfide (thiol),20,43 a-halo (with SnCl2) and a-phenylthio ketones (ketone),44 aldehydes (alcohols; requires Na2S-Al2O3 which does not reduce nitro groups, ketones, or esters) (eq 21),45 carbon-Hg bonds (hydrocarbon) (elimination may be a serious side reaction) (eq 22),46 tetravalent tellurium- and selenium-halogen bonds (divalent tellurides, selenides) (eq 23).47

Miscellaneous.

Na2S has been used in the synthesis of thiocarbonyl compounds, but H2S is more widely applicable. A combination of Na2S.9H2O and H2S with a phase-transfer catalyst converts nitriles to thioamides (46-98% yields),48 and the combination of Na2S with Phosphorus(V) Sulfide, which performs the same transformation, is notable in that a nitro group is not reduced (eq 24).49 A convenient isothiazole synthesis uses thioenaminones obtained by addition of Na2S.9H2O to ArC(Cl)=CHCH=+NMe2 ClO4-.50 A cyclopropenethione is obtained by addition of Na2S to a chlorocyclopropenium salt,51a a thioester by addition to a dialkoxy carbocation,51b and 4H-thiopyran-4-thiones by addition to 6a-thiathiophthenes.51c The usefulness of 2-Chloroacrylonitrile as a dienophile is enhanced by the conversion of the chloro nitrile adducts to ketones by Na2S.9H2O, which is superior to KOH (eq 25).52 A thioketone is presumed to be an intermediate. This renders 2-chloroacrylonitrile into a dienophilic ketene equivalent. An improved synthesis of Sodium Trithiocarbonate utilizes a phase-transfer catalyst in the reaction of Na2S.9H2O with CS2.53 Sodium sulfide also has been used to effect elimination reactions from 1,2-dihalides (anti),54 1,2-dinitro compounds,55a b-halo tellurium(IV) derivatives (anti),55b and b-nitro sulfones,55c and to assist in hydration of alkynes.56 Carboxylic acids protected as their cyanomethyl57a or 4-chlorobutyl57b esters are readily deprotected by treatment with Na2S, thus avoiding strongly acidic or basic conditions (eq 26).

Related Reagents.

Hydrogen Selenide; Hydrogen Sulfide; Hydrogen Telluride; Potassium Hydrogen Sulfide; Sodium Hydrogen Sulfide.


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Donald C. Dittmer

Syracuse University, NY, USA



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