Methyl thioether

CF3COOH, 2.5% phenol, 30°, 2 h, 65% yield. Zervas and co-workers tried many conditions for the acid-catalyzed formation and removal of the 5-diphenyl methyl, 5-4,4 -dimethoxydiphenylmethyl, and 5-tripheny I methyl thioethers. The best conditions for the 5-diphenylmethyl thioether are shown above. Phenol or anisole act as cation scavengers. 

II. 5-Bis(4-methoxyphenyl)methyl Thioether RSCH(C6H4-4-OCH3)2 (Chart 7)... 

Diphenyl-5-methoxythiazyne, benzene, 30° was used to prepare the methyl thioether. ... 

Na/NH3, >54% yield. Methyl thioether cleavage of BOC-protected methionine. ... 

Halogenated compounds containing CH2C1 Methyl thioethers... 

However, more recent work has shown that the reaction of thioglycollic acid (HSCH2COOH) with methylcobalamin to give the methyl thioether requires oxygen and shows an induction period [which can be reduced by increasing the pH, the thiol concentration, or the partial pressure of O2, and eliminated by the addition of the Co(II) complex], followed by a steady-state reaction [ whose rate increases with pH, the concentration of the CH3C0 and Co(II) complexes and the partial pressure of O2, but is independent of thiol concentration]. Neither the induction period nor the steady-state... 

It has been demonstrated that the MCR enzyme is active only if the metal center of coenzyme F430 is in the Ni1 form.1857 The natural substrate Me-CoM or simple methyl thioethers, however, do not react with Ni1 F430, which has lead to the proposal of a catalytic mechanism in which the addition of a thiyl radical to the S atom of the thioether giving a sulfuranyl radical intermediate is... 

The readily available benzotriazolyl derivative of dimethyl sulfide, compound 821, can be alkylated on a-carbon in a stepwise manner to provide (a,a-disubstituted)alkyl thioethers 823 (Scheme 131). Hydrolysis of these thioethers under mild conditions (5% H2S04 at room temperature) furnishes ketones 824 in high yields. The anion derived from mono substituted (benzotriazol-l-yl)methyl thioether 822 adds to butyl acrylate to give intermediate 826 that can be hydrolyzed to y-ketoester 825. In another example of reactivity of a-(benzotriazol-l-yl)alkyl thioethers, treatment of thioether 822 with BunLi followed by phenyl isocyanate converts it into a-ketoanilide 828, via intermediate adduct 827 <1998JOC2110>. 

Investigations by Vermeer and co-workers have shown that 3-substituted allenyl methyl thioethers 309 can be prepared by regioselective addition of an alkyl silver species to the terminal C=C bond of enyne sulfides 308 (Scheme 8.83) [172], Remarkably, this method can also be applied to the preparation of several allenyl-phosphines starting from the corresponding phosphorus-substituted alkynes. 

In contrast with the reactions involving sulphide or hydrogen sulphide anions, aryl alkyl thioethers and unsymmetrical dialkyl thioethers (Table 4.3) are obtained conveniently by the analogous nucleophilic substitution reactions between haloalkanes and aryl or alkylthiols under mildly basic conditions in the presence of a quaternary ammonium salt [9-15] or polymer-supported quaternary ammonium salt [16]. Dimethyl carbonate is a very effective agent in the formation of methyl thioethers (4.1.4.B) [17]. 

Direct sulphanylation of activated methylene groups to form methyl thioethers is possible under basic conditions, when the stabilized carbanion reacts with 5-methyl methanethiosulphonate. The reaction has been applied successfully in, for example, reactions with p-keto sulphoxides [59] and a-sulphonyl acetic esters [60] (Scheme 4.13). 

The activated methylene compound (2 mmol), TEBA-Cl (46 mg, 0.2 mmol) and powdered K2C03 (0.55 g) in CH2Cl2 or PhH (10 ml) are stirred at room temperature for ca. 1 h. MeSS02Me (0.25 g, 2 mmol) in CH2C12 (3 ml) is added, and the mixture is stirred for 2-6 h and then filtered. The solid is washed with CH2C12 (20 ml) and the combined solutions are washed with H20 (2 x 20 ml), dried (MgS04), and evaporated to yield the methyl thioether ( a 1 1 mixture of CH2C12 and PhH is preferred for the p-keto sulphoxides). 

Methylthiomethyl has been used as the protecting group in the total synthesis of neoechinulin A (80TL2817). Cyclo(L-Ala-Gly) was treated with sodium hydride in DMF and N-alkylated with chloromethyl methyl thioether at room temperature, to give the bis(methylthiomethyl) derivative. After further chemical transformations, deprotection was achieved by treatment with methyl iodide in the presence of NaHC03 at 40°C for 3 days, followed by heating in dioxane at 100°C for 1 h. 

The frequently observed bioisosteric relation of benzene and thiophene applies to the clonidine series as well. Reaction of the thiophenyl thiourea (85-1), in which the amine group is flanked by substituents as in the prototype, with methyl iodide and a base gives the corresponding methyl thioether (85-2). Treatment of that intermediate with ethylene diamine leads to the formation of an imidazoline ring and the antihypertensive agent, tiamenidine (85-3) [90], shown as its imino tautomer. 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

Because of their structural and spectroscopic analogies with the hemo-chromes Fe(P)L2, e.g. the protoporphyrin derivative 3 (L, L = Py or 1-Meim), the corresponding 4d and 5d homologs are named ruthenochromes or osmo-chromes . The hemochromes derive their name from the cytochromes, the widespread electron-carrying heme proteins. Cytochrome b (coordination type F, M = Fe) has two imidazole donors from histidine side chains at the central iron, cytochrome c (coordination type G, M = Fe) an imidazole and a methyl-thioether function from a methionine. F is an axially symmetrical, G an axially unsymmetrical system. 

A wide range of variously substituted thiochromans has been obtained from the readily accessible ot-(benzotriazo-lyl)methyl thioethers by their Lewis acid-catalyzed reaction with styrenes. Initial loss of the benzotriazole unit generates a thionium cation which undergoes an efficient cationic cycloaddition to the alkene. The reaction, which generally proceeds with high diastereoselectivity, is considered to occur in a stepwise manner rather than as a concerted [4++2] process (Scheme 174) <2001JOC5595>. 

Trifluoromethylthio-substituted heteroaromatic systems are available by a multistep procedure, namely photochlorination of the corresponding methyl thioether and subsequent halogen exchange on treatment with antimony trifluoride (52ZOB2216 54ZOB887) (Scheme 18). 

Ni site coordinated throngh both the thiolate and the methyl thioether snlfur atoms, and four N-donors, respectively. 

As interpreted in Scheme 12, a sterically shielded, bifhnctional model snbstrate containing a methyl thioether and snlfhydryl fhnctional group could form a five-membered... 

The oxidation of thioethers on TS-1, Ti-P and Ti,Al-P produced corresponding sulfoxides and, more slowly, sulfones by consecutive oxidation [144—149]. AUyl methyl thioether was oxidized selechvely on sulfur, with no reaction of the double bond [148]. The kinetic law was obtained for the oxidation of dibutylsulfoxide on Ti,Al-P [147]. 

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