Carbon Disulfide1

CS2

[75-15-0]  · CS2  · Carbon Disulfide  · (MW 76.14)

(starting material for the synthesis of various sulfur and heterocyclic compounds;1 protecting group for secondary amines2)

Physical Data: mp -111.6 °C; bp 46.3 °C; d 1.26 g cm-3; flashpoint -30 °C; fire point 102 °C.

Solubility: sol alcohol, ether, THF, benzene, CCl4, CHCl3; insol cold H2O.

Form Supplied in: colorless liquid; discolors to yellow under influence of light.

Handling, Storage, and Precautions: should be stored in brown bottles in absence of light. CS2 forms explosive mixtures with air (explosion limit 1-60 vol %). CS2 is teratogenic. Constant inhalation or constant resorption through the skin cause chronic symptoms of poisoning, e.g. sight defects and headache. Inhalation of concentrated CS2 vapor can be lethal. Use in a fume hood.

Reactions with Organometallic Compounds.

Grignard Reagents.

Treatment of CS2 with Grignard reagents RMgX (1) leads to dithioesters (2) (eq 1).

If THF is used as solvent, dithioesters can be obtained in 60-85% yield.3 This method fails when t-alkyl- or cyclohexylmagnesium halides are used. With diethyl ether as solvent, the dithioesters are obtained in poor yields.4 The reaction of CS2 with an allylic Grignard reagent followed by methylation affords the dithioesters (3), bearing an inverted allylic chain as expected.5 Treatment of (3) with first Lithium Diisopropylamide, then with Iodomethane, leads to an isoprenic ketene dithioacetal (4) (eq 2).

It is also possible to prepare various ketene dithioacetals in a one-pot synthesis with Grignard reagents and CS2 as starting materials.6

Organocopper Reagents.

When catalytic amounts of Copper(I) Bromide are used, the reaction of CS2 with Grignard reagents leads to dithioesters in 80-100% yield (eq 3).7

The organocopper(I) compound (5) is the reacting species.7a With this method, halides containing bulky groups can also be converted to dithioesters.

Reactions with Alcohols.

Treatment of alcohols with sodium hydroxide and CS2 and subsequent reaction with an alkyl halide, usually methyl iodide, leads to O-alkyl S-methyl dithiocarbonates which can be pyrolyzed to alkenes (Tschugaeff reaction) (eq 4).8

Formation of the metal salt of the alcohol can be difficult.9 If Sodium Methylsulfinylmethylide in DMSO is used as base, the dithiocarbonates can be prepared in good yields.10 The decomposition temperature is lowered when pyrolysis is also carried out in DMSO.11

Vicinal diols react with CS2 under basic conditions, to give the corresponding bis-dithiocarbonates. Reduction with Tri-n-butylstannane in toluene12 gives high yields of the alkenes.

Recently, a variety of reducing agents has been developed to convert dithiocarbonates derived from alcohols, especially secondary ones, to alkanes. The hydroxy function can be selectively replaced by hydrogen under mild conditions, with tri-n-butylstannane,13a tri-n-butylstannane/Triethylborane,13b or Tris(trimethylsilyl)silane/Azobisisobutyronitrile13c as radical-based reducing agents.

Reaction with Amines.

Primary Amines.

Treatment of primary amines with base and CS2 leads to isothiocyanates via the dithiocarbamate derivatives.14 Alkyl or aryl amines which do not contain groups that react with butyllithium, can be converted in 55-99% yield to the corresponding isothiocyanates. The amines are treated with an equimolar amount of n-Butyllithium and CS2 to give the lithium dithiocarbamate (6). Subsequent reaction with n-butyllithium and CS2 forms the complex (7). Loss of Li2CS3 leads to an isocyanate (eq 5).15

Diamines.

Aliphatic diamines react with CS2 to give betaines (8). After pyrolysis of (8), cyclic thiourea derivatives are obtained (eq 6).16

In the same way, 1,2-diarylamines and their hetero analogs can be converted to heterocyclic compounds.17

Secondary Amines.

Treatment of secondary amines with base and CS2 leads to the corresponding dithiocarbamates.18 Dithiocarbamates of functionalized secondary amines form heterocyclic compounds.19 For example, monoalkylaminobutynes (9) react readily with CS2 to give 4-methyl-3-alkyl-5-methylenethiazolidine-2-thiones (10) (eq 7).20

Protecting Group.

As mentioned above, under basic conditions, secondary amines form with CS2 dithiocarbamates. Subsequent reaction with an organometallic base and one equivalent of electrophile gives, in good yields, the secondary amines substituted in the a-position (eq 8).2,21

The natural reactivity at a-position is umpoled.22 This is a simple and versatile method for nucleophilic aminoalkylation23 in a one-pot procedure. The reaction can be applied to numerous aliphatic and aromatic secondary amines.

Reactions with Enolizable Hydrogen Compounds.

Enamines.

Reactions of enamines with CS2 afford several heterocycles.24 Treatment of cyclic enamines with CS2 leads to 1,4-dipoles (11) (eq 9).

In the absence of moisture the 1,4-dipoles (11) can be stored for several days at 0 °C. Further reactions with electrophiles lead to various heterocycles.25

Carbonyl Compounds.

In the case of aldehydes, only self-condensation products are obtained, whereas aliphatic ketones usually form the corresponding dithiocarboxylates or a-ketoketene dithioacetals.26 If cyclic ketones are used, occurrence of carbon-carbon cleavage or formation of a-ketoketene acetals depend on the steric demands of the base. Treatment of cyclohexanone with lithium 4-methyl-2,6-di-t-butylphenoxide (12) (readily obtained by treatment of the phenol with n-butyllithium) and CS2, followed by methylation, leads via the dithiocarboxylate ion (13) to the a-ketoketene dithioacetal (14) (eq 10).27

If the reaction is carried out with lithium methoxide as base, 1,1-dithiodicarboxylic acid ester (15) is formed (eq 11).28

This carbon-carbon cleavage in cyclic ketones corresponds to an inverse Dieckmann-type reaction. Bulkier alkoxides like ethoxide or isopropoxide afford only a-ketoketene dithioacetals.27


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Christine Schmitt

Justus-Liebig-Universität, Giessen, Germany



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