Thioethers from alkyl halides

The fact that sulphur dioxide possesses a dipole moment and is triangular in shape lends support to the view that the contribution of the tetravalcnt structure is very small. A direct indication of the existence of the positively charged trivalent state lies in the existence of the sulphonium compounds (RgS) Cl which are formed readily from thioethers and alkyl halides and behave in solution as strong electrolytes containing the (RsS)" ion. 

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... 

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. 

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. 

A superior and relatively versatile procedure for the synthesis of unsymmetrical dialkyl thioethers, which avoids the unattractive direct use of thiols, utilizes the stable l-alkylthioethaniminium halides, which are readily obtained from thioacet-amidc [32] (Scheme 4.4). The reaction has also been used for the synthesis of alkyl aryl thioethers from activated aryl halides [33], but it cannot be used for the synthesis of cyclic thioethers, as polymeric sulphides are formed from a,co-dihaloalkanes. A similar sequence to that which leads to the thioethers has been used for the synthesis of S-alkyl thioesters [34] (see 4.1.26). 

Therefore, it is possible to convert a variety of primary and secondary alkyl halides to alcohol, ethers, thiols, thioethers, esters, amines, and azides (Following fig.). Alkyl iodides and alkyl chlorides can also be synthesised from other alkyl halides. 

The reactions of lithiophosphide reagents with alkyl halides or sulphonate esters have continued to find wide application in the synthesis of new phosphines. A series of phosphino-ethers, e.g., (22), has been prepared from the reactions of chloromethyl-substituted ethers with lithium diphenylphosphide. " A one-step synthesis of macrocyclic phosphino-ethers and -thioethers (23) is afforded by the reactions of dilithio-organophosphides with bis(j8-chloroethyl)-ethers and -thioethers derived from ethane-1,2-diol and ethane-1,2-dithiol, respectively. " A new family of water soluble phosphonio-phosphine ligands (24) has been prepared by the reaction of a,o)-dihaloalkanes with one mole of lithium diphenylphosphide, followed by quatemisation of the intermediate w-haloalkylphosphine with trimethylphosphine. The new ligand system (25) has been prepared by the reaction of chloromethylbenzene-chromium tricarbonyl with... 

From the alkyl 2,4-dinitrophenyl thioether (prepared from the alkyl halide as above) in glacial acetic acid, with aqueous potassium permanganate. 

The thiolactams can be alkylated on sulfur by treatment with alkyl halides and base under aqueous or nonaqueous conditions, for example, (99 X = S) is converted into (100) (Scheme 16) <82CPBil4l>. The thioether (100) can be obtained directly from the lactam (99, X = O) on reaction with dimethylaminoethane thiol in the presence of either titanium tetracUoride or silicon tetrachloride other Lewis acids were ineffective <82CPB1473>. 

Cobalt has attracted attention in recent years as a cost-effective and sustainable alternative to palladium or nickel. As indicated earlier, functionalized arylzinc reagents can be prepared from aryl halides and sulfonates by zinc insertion in the presence of catalytic amounts of CoBtj [50, 51, 210). Interestingly, the presence of this cobalt salt suffices to catalyze in situ the cross-coupling of the arylzincs thus produced with aryl, alkyl, and heteroaryl electrophiles such as organic halides [211-214] or thioethers, as exemplified with the formation of 286 [214] (Scheme 4.63). 

The resulting thiolate anion is then capable of displacing halogen from a second equivalent of alkyl halide. This produces the corresponding thioether (dibutyl sulfide, Equation 8.59). In practice, thiol synthesis via the Sn2 process is best undertaken using a large excess of hydrosulfide anion so that the relative concentration of thiolate anion is minimized and thioether formation (Equation 8.59) is repressed. However, even under the best of circumstances, elimination competes with substitution. Alkenes can even be the major product and with tertiary alkyl halides, it is common to find that only alkenes result. 

Alkyl thiocyanates have also been prepared from thioethers with cyanogen bromide and via the reaction of polymer-based quaternary ammonium salts with alkyl halides. Enethiocyanates have been prepared by Markovnikov addition of in situ generated thiocyanic acid to alk-l-ynes, and via the reaction of epoxy-ketones with Ph3P(SCN)2. ... 

Use of the methylsulphinyl carbanion as base is recommended for the synthesis of ethers from alcohols and alkyl halides. The catalysed formation of dimethyl ether from hydrogen and carbon dioxide has been reported. Carey has described the use of the silicon-modified organolithium reagent (73) in the preparation of vinyl thioethers (Scheme 151). In order to extend the scope of this reaction to include vinyl ethers themselves, an attempt was made to metalate trimethylsilylmethyl ether use of n-buty 1-lithium resulted in nucleophilic attack on silicon, whereas t-butyl-lithium abstracted the wrong proton, as shown in Scheme 151. 

The oxidative cleavage of ethers to give carbonyl compounds has been demonstrated using UFe (readily available deficient in U) as oxidant. The reaction is regiospecific with methyl ethers (89 90). Phenyl thioethers have also been shown to undergo oxidative cleavage via a-chlorination (Scheme 41) giving, as shown, a route from alkenes or alkyl halides to aldehydes. 

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. 

A variety of discotics can be prepared from the tetrabromopyrene 59 as shown in Scheme 4.17. Thus, the Suzuki coupling between 59 and commercially available methoxyphenylboronic acid or 1-fluorophenylboronic acid yields tefiaphenyl derivatives 64 and 67, respectively. Demethylation of 64 with HBr yields 1,3,6,8-tetrakis(4-hydroxyphenyl)-pyrene 65 which can be alkylated with different alkyl halides to tetraethers 66. Similarly, esterification of the tetraphenol with acid chloride or benzoic acid affords tetraesters 66 (R = COR) or benzoate 66 (R = CORiR), respectively [111]. Replacement of fluoro atoms with alkylthiolates generates nonmesomorphic tetra-thioethers of pyrene 68. 

This reaction is analogous to 10-16. Primary and secondary alcohols can be converted to alkyl aryl sulfides (ROH RSAr) in high yields by treatment with BU3P and an V-(arylthio)succinimide in benzene. Thioethers RSR can be prepared from an alcohol ROH and a halide R Cl by treatment with tetra-methylthiourea Me2NC(=S)NMe2 followed by NaH. ... 

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