Chloro thioether

Also in this case, the use of the chloro thioether 479 allowed the introduction of two different electrophiles in a sequential process. Using lithium naphthalene (the stoichiometric version of the arene-promoted lithiation) in THF at — 78°C, only a chlorine-lithium exchange occurred, so the first electrophile R R CO was introduced (—78 to —50°C). Then the second lithiation (sulfur-lithium exchange) takes place under catalytic conditions (naphthalene) and the second electrophile R R CO was introduced. After final hydrolysis, differently substituted 1,5-diols 476 were isolated (Scheme 134) °. 

Take up the (3-chloro thioether, prepared in step 2, in dry DMF (150 mL) and carefully transfer the solution to a pressure-equalising addition funnel (250 mL). Add 3-thiapentane-1,5-dithiol (5.09 g, 33 mmol) to this solution. 

Addition to Alkenes. Phthalimidosulfenyl chloride can be added to alkenes to yield a-chloro thioethers which, after treatment with lithium aluminum hydride, produce episulfides (eq 4). Sodium borohydride is unsuccessful in transforming the alkene adduct to the episulhde. The alkene addition is stereospecifically trans and proceeds through a thiiranium ion intermediate, the opening of which is governed predominantly by steric factors and usually gives a predominance of the anti-Markovnikov addition product. As in the addition of phthalimidosulfenyl chloride to alkynes, the phthalimido group can also be displaced with... 

Miscellaneous Transformations. Cyanotrimethylsilane effects the transformation of acyl chlorides to acyl cyanides, a-chloro ethers and a-chloro thioethers to a-cyano ethers and a-cyano thioethers (eq 19), t-butyl chlorides to nitriles (eqs 20 and 21), 1,3,5-trisubstituted hexahydro-l,3,5-triazines to amino-acetonitriles, the cyanation of allylic carbonates and acetates (eqs 22 and 23), and the formation of aryl thiocyanates from aryl sulfonyl chlorides and sulfinates. The reagent has been used effectively in peptide synthesis and in a range of other synthetic applications. " ... 

Treatment of thioethers with xenon difluoride, or a-chloro thioethers with potassium fluoride/crown ether, had been reported to give a-fluoro thioethers. McCarthy and... 

Several procedures exist for the synthesis of a-chloro thioethers and sulfoxides. The solid iodobenzene dichloiide [phenyliodine(III) dichloride] reagent is a convenient source of positive chlorine, and the lipophilic iodobenzene by-product can be recycled. Colonna and cowoikers have reported reactions of sulfoxides with iodobenzene dichloride and investigated the stereochemistry of a-chloro sulfoxides obtained und various conditions. ... 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

The 2- and 4-alkylthioquinazolines are formed by the second or third of the above methods as appropriate. For example, quinazoline-2(l//)-thione and methyl iodide/alkali give the thioether (883) and the 4-thioether is made similarly (62JCS3129) 2,4-dichloroquinazoline and sodium p-chlorothiophenate give 2-chloro-4-p-chlorophenylthio-(884 R = C1) or 2,4-bis-p-chlorophenylthio-quinazoline (884 R = SC6H4C1) according to conditions (48JCS1766). 

The diarsine and arsine/phosphine analogues of dppm have been used to prepare bridged diplatinum(I) complexes, in both cases with terminal chloro ligands.116,117 Both complexes react with carbon monoxide to produce carbonyl-bridged species. The mixed thio/phosphine ligand Ph2PCH2SMe (PS) also forms a diplatinum(I) complex by conproportionation of its dichloroplat-inum(II) complex with [Pt(dba)2].118 This dimer reacts with carbon monoxide to produce an unsupported dimer [PtCl(PS)(CO)]2 with the thioether arm of the Ph2PCH2SMe unbound. 

The profitable conversion of thiouronium salts into dialkyl thioethers (see Section 4.1) is less successful for synthesis of diaryl thioethers. For example, l-chloro-4-nitrobenzene reacts with bis-thiouronium salts of the type (H2N)2CS(CH2) SC(NH2)2+ under soliddiquid and liquidrliquid conditions to produce the desired bis-thioethers, ArS(CH2) SAr, (20-35%), together with the diaryl sulphide, Ar2S (5-15%). Higher yields of the diaryl sulphide are observed under liquiddiquid conditions whereas, under solidiliquid conditions, the diaryl disulphide, (ArS)2, (20%) is also formed [56], Diaryl disulphides are the sole products (>65%) from the stoichiometric reaction of aryl diazonium salts with benzyltriethylammonium tetrathiomolybdate [57],... 

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

The general scheme is sufficiently flexible to permit the interchange of the order of some of the steps. Thus alkylation of aniline thioether (30-3) with 3-chloro-l-diethylaminopropane leads to the intermediate (31-1). Ring closure as above by nucleophilic aromatic displacement leads to the antipsychotic dmg chlorproethazine (31-2) [32]. 

Thiols react with l-chloro-2,4-dinitrobenzene in alkaline solution to yield crystalline thioethers (2,4-dinitrophenyl sulphides) (1). These sulphides (1) can be readily oxidised in glacial acetic acid solution by potassium permanganate to the corresponding sulphones (2) the latter exhibit a wide range of melting points and are therefore particularly valuable for the characterisation of thiols. (See also Expt 5.208.)... 

Preparation of 2,4-dinitrophenyl sulphides. Dissolve about 0.5 g (or 0.005 mol) of the thiol in 10-15 ml of rectified spirit (or in the minimum volume necessary for solution warming is permissible) and add 2 ml of 10 per cent sodium hydroxide solution. Mix the resulting solution with a solution of 1 g of l-chloro-2,4-dinitrobenzene (CAUTION see Section 9.6.21, p. 1276) in 5 ml of rectified spirit. Reaction may occur immediately with precipitation of the thioether. In any case reflux the mixture for 10 minutes on a water bath in order to ensure the completeness of the reaction. Filter the hot solution rapidly allow the solution to cool when the sulphide will crystallise out. Recrystallise from ethanol. 

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