Thiol from alkyl halides

Thiourea is used to prepare thiols from alkyl halides. 

ThiolsJ Preparation of thiols from alkyl halides is readily earned out with a combination of (Me3Si)2S and BU4NF (9 examples, 68-94%). 

The S-alkylation of the sodium salt (72) of thiosaccharin is the basis of a new route to thiols from alkyl halides (Scheme 51). The conversion of alkyl halides (RX) to thiolacetates (RSCOMe), and hence to thiols by saponification, has been shown to be effected by a quaternary ammonium resin with thiolacetate as counterion. Thiolacetates are also available in one step from alcohols in... 

In the known preparation of thiols from alkyl halides and thiourea, the intermediate thiopseudourea (77) is cleaved by aqueous alkali when an activated thiourea is used, heating with ethanol s ces to produce the thiol directly (Scheme 158). The conversion of thiols into alkyl halides is cited above. ... 

Thiols are usually prepared from alkyl halides by Snj2 displacement with a sulfur nucleophile such as hydrosulfide anion, SH. 

Thiol (s), 652, 667-668 disulfides from, 668 electrostatic potential map of, 75 from alkyl halides, 667 hybridization of, 20 naming, 667 odor of, 667 oxidation of, 668 pKa of, 604... 

Thiols are prepared from alkyl halides and sodium hydrosulphide (Na+SH ) by Sn2 reaction. A large excess of Na+SH is used with unhindered alkyl halide to prevent dialkylation (R—S—R). 

Tributyltin hydride, 316 Zinc iodide, 280 From alkyl halides Lithium aluminum hydride-Ceri-um(III) chloride, 159 Palladium catalysts, 230 Sodium cyanoborohydride-Tin(II) chloride, 280 From alkyl sulfonates Lithium triethylborohydride, 153 From thiols... 

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... 

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... 

Sulfides, or thioethers, are sulfur analogues of ethers, and like ethers they can be either symmetrical (R2S) or unsymmetrical (RSR1, where R and R are different). Sulfides can be prepared from alkyl halides by a Williamson-type synthesis with sodium hydrogen sulfide, sodium thiolate or sodium sulfide from alkyl or aryl halides via the Grignard reagent (11) from alkenes by radical-catalysed addition of thiols or by reduction of sulfoxides (Scheme 9).2b... 

Even carbowax (a chemically and thermally stable poly(ethylene glycol), when adsorbed on an inorganic salt with no other solid support, may act as a very efficient gas-solid phase-transfer catalyst. This system has been employed, for example, in the Williamson synthesis of ethers and thioethers, starting from alkyl halides and phenols or thiols in the presence of potassium carbonate as a base Gas-solid PTC shows the advantage that pure products are obtained directly, due to the absence of aqueous and organic solvents. 

Alkyl thiols can be made from alkyl halides by nucleophilic displacement with sulfhydryl ion (Table 6.1, entry 10). 

If the substrate is an alcohol, some dialkyl ethers can be synthesized in a two-phase version of the Williamson synthesis, and thioethers or dithioacetals result from alkylation of thiols, with alkyl halides or CH2CI2 respectively, under similar conditions. The related reaction of equation (2) has been used to make an evaluation of several catalysts, and it has been found that the larger, more symmetrical, quaternary ions are the most efficient. 

Pyrrolethiols, readily obtained from the corresponding thiocyanates by reduction or treatment with alkali, rapidly oxidize to the corresponding disulfides. They are converted into thioethers by reaction with alkyl halides in the presence of base. Both furan- and thiophene-thiols exist predominantly as such rather than in tautomeric thione forms. 

The reaction often works poorly unless an excess of the nucleophile is used because the product thiol can undergo a second S 2 reaction with alkyl halide to give a sulfide as a by-product. To circumvent this problem, thiourea, (NH2J2C=S, is often used as the nucleophile in the preparation of a thiol from an alkyl halide. The reaction occurs by displacement of the halide ion to yield an intermediate alkyl isothiourea salt, which is hydrolyzed by subsequent reaction with aqueous base. 

In 1978 and 1980 the coupling of aryl bromides and iodides with both aliphatic and aromatic thiols was first reported in the presence of NaO-t-Bu and Pd(PPh3)4 (Equation (35)).118,119 In contrast to aryl halide aminations and etherifications, the thiation reactions did not require unusual catalysts. Yet, reactions that form aryl alkyl sulfides from alkyl thiols occurred in modest yields in many cases ... 

Several palladium catalysts for formation of aryl sulfides from aryl halides have been investigated more recently. A combination of Pd2(dba)3 and DPEphos catalyzed the formation of a broad range of diaryl sulfides in the presence of 1 mol.% palladium and NaO-t-Bu base in toluene solvent.12,rThe highest yields of alkyl aryl sulfides were obtained from aryl triflates and n-butyl thiol catalyzed by a combination of palladium acetate and BINAP. However, these reactions contained 10 mol.% catalyst, were long, and required deactivated aryl triflates. A combination of Pd2(dba)3 and DPPF catalyzed the coupling of thiols with resin-bound aryl halides.121... 

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