Sodium sulfide, reaction with alkyl halides

Sodium hydrogen sulfide can be used for the preparation of thiols (19) by reaction with alkyl halides. A large excess of sodium hydrogen sulfide must be employed to avoid formation of the dialkyl sulfide (Scheme 17) (see Chapter 4, p. 41). 

The alkyl phenyl sulfone precursors for the olefination may be prepared by the reaction of alkyl halides with sodium benzenethiolate, followed by oxidation of the alkyl phenyl sulfides formed with mCPBA. Alternatively, displacement of an alkyl bromide or iodide with the less nucleophilic sodium benzenesulfmate PhS02Na leads directly to the alkyl phenyl sulfone. 

Hydrogen sulfide also reacts by nucleophilic substitution with alkyl halides and alcohols under appropriate conditions to form thiols (Scheme 10) (see Chapter 4, p. 42). The reaction with an alkyl halide is generally facilitated by using sodium hydrogen sulfide (NaSH) rather than hydrogen sulfide since NaSH is a much better nucleophile. Hydrogen sulfide also adds to ketones to give gem-dithiols (13) (Scheme 11). 

In the presence of sodium hydroxide, thiols react with alkyl halides to form the sulfides (20) the reaction occurs via the sodium thiolate and is analogous to the well-known Williamson synthesis of ethers and can also be applied to obtain unsymmetrical sulfides (Scheme 18). Symmetrical sulfides may be prepared directly by condensation of sodium sulfide with alkyl halides (Scheme 18). These reactions are of the SN2 type, and consequently the optimum yields of sulfides are realised using primary alkyl halides. 

Sulfides. Symmetrical sulfides can be prepared in high yield from the reaction of alkyl halides and sodium sulfide in water with this phase-transfer catalyst. Unsymmetrical sulfides are prepared from alkyl halides and sodium mercap-tides. Secondary alkyl halides react more slowly than primary halides bromides are more reactive than chlorides. ... 

Symmetrical thioethers can also be prepared by treatment of an alkyl halide with sodium sulfide,769 in a reaction similar to 0-30. 

Thiols can be prepared by SN2 reactions of sodium hydrosulfide with unhindered alkyl halides. The thiol product is still nucleophilic, so a large excess of hydrosulfide is used to prevent the product from undergoing a second alkylation to give a sulfide (R—S—R). 

Sodium sulfhydride (NaSH) is a much better reagent for the formation of thiols (mercaptans) from alkyl halides than H2S and is used much more often. It is easily prepared by bubbling H2S into an alkaline solution, but hydrosulfide on a supported polymer resin has also been used. " The reaction is most useful for primary halides. Secondary substrates give much lower yields, and the reaction fails completely for tertiary halides because elimination predominates. Sulfuric and sulfonic esters can be used instead of halides. Thioethers (RSR) are often side products. The conversion can also be accomplished under neutral conditions by treatment of a primary halide with F and a tin sulfide, such as PhsSnSSnPhs. An indirect method for the preparation of a thiol is the reaction of an alkyl halide with thiourea to give an isothiuronium salt (119), and subsequent treatment with alkali or a... 

The reduction of alkyl tellurium tri halides is a convenient method for the preparation of the corresponding dialkyl ditellurium when the trihalides can be obtained by reactions other than the halogenolysis of the dialkyl ditellurium. Addition of tellurium tetrachloride to olefins and condensation with ketones produces alkyl tellurium trichlorides. Sodium sulfide nonahydrate" and sodium or potassium disulfite were used as reducing agents. 

Several thiols occur naturally for example, skunk secretion contains 3-methyll-butanethiol and cut onions evolve 1-propanethiol, and the thiol group of the natural amino acid cysteine plays a vital role in the biochemistry of proteins and enzymes (see Introduction, p. 2). Primary and secondary thiols may be prepared from alkyl halides (RX) by reaction with excess sodium thiolate (SN2 nucleophilic substitution by HST) or via the Grignard reagent and reaction with sulfur. Tertiary thiols can be obtained in good yields by addition of hydrogen sulfide to a suitable alkene. Thiols can also be prepared by reduction of sulfonyl chlorides (Scheme l).la,2a... 

Quinoxaline-2-thione is readily converted into 2-hydrazinoqmnoxaline on treatment with hydrazine hydrate, and 3-hydrazinoquinoxaline-2-thione is readily hydrolyzed (2.5 M HCl at 70°) to quinoxaline-2,3-dione. The sodium salt of quinoxaline-2-thione has been S-alkylated with a wide range of alkyl halides to give 2-quinoxalinyl sulfides,but attempts to carry out a parallel reaction with p-nitrochlorobenzene failed. p-Nitrophenyl-2-quinoxalinyl sulfide (5) can however be prepared by reaction of 2-chloroquinoxaline with the sodium salt of p-nitro-benzenethiol. ... 

Sulfides (thioethers) can be obtained by replacing the halogen of alkyl and suitable aryl halides in a reaction with sodium sulfide, this being analogous to the preparation of thiols and disulfides. The reaction is usually carried out... 

Preparation of the lower dialkyl sulfides by the following general procedure has been described by McAllan and his co-workers 286 Sodium sulfide nonahydrate (1.5 moles) is dissolved in water (250 ml) in a three-necked flask fitted with a reflux condenser, dropping funnel, and stirrer, then the alkyl halide (2 moles) is added slowly with vigorous stirring. When the very exothermic reaction ceases, the mixture is heated under reflux for a further 3 h and the sulfide is distilled over in steam, separated, washed with water, 10% sodium hydroxide solution, and again water, dried over calcium chloride, and distilled. In this way were obtained dimethyl (b.p. 37.3°), diethyl (b.p. 92°),287 diisopropyl (b.p. 119.8°), dipropyl (b.p. 142.8°),288 and bis-(2-cyanovinyl) sulfide (m.p. 142-143°, from ethyl acetate-cyclohexane).289... 

Disulfides, such as the diallyl disulfide shown in Rgure 8.24, can be obtained by the reaction of sodium disulfide (NaiSi), itself prepared by the dissolution of an equivalent of sulfur in a concenctrated sodium sulfide (Na2S) solution, with the corresponding alkyl halide. Reduction of the disulfide (e.g., with zinc dust in acetic acid) results in cleavage of the sulfur-sulfur bond and thiol formation (Scheme 8.105). Alternatively, as might be expected, thiols are rather easily oxidized (e.g., by hypohalites [NaOCl]) and the products are disulfides (Equation 8.60). 

Symmetrical dialkyl sulfides have been prepared in high yield by the reaction of sodium or potassium sulfide with a primary or secondary halide under phase transfer conditions. Both quaternary ions [1] and crown ethers [2] have been successfully utilized in this reaction. It was found that at 70 several different alkyl halides would condense with 0.6 to 1.0 equivalent of sodium sulfide to give generally excellent yields of symmetrical thioethers according to equation 13.1. Even the highly... 

Therefore, it is not necessary to prepare the thiolate in a separate reaction with a sttong base, as is required in the reaction of alcohols with sodium hydride. Sulfides are usually prepared by adding the alkyl halide to a basic alcoholic solution of the thiol. 

The reaction of activated alkyl or aryl halides with sodium sulfide yields disulfides. 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

The preparation of N-alkoxy derivatives (i.e., type V) is somewhat more difficult They can be prepared by treatment of the sodium salt of 2-mercaptopyridine-N-oxide with 1 molar equivalent of the suitable alkyl halide in DMF at 80°C. ° By using this coupling reaction, alkylation occurs at sulfur rather than at oxygen, and the reaction affords pyridyl sulfides as the major product. In such cases, the Mitsonobu method using diethyl azodicarboxylate and triphenylphosphine may provide a solution (Scheme 8). ... 

---