Methylthiomethyl

Methylthiomethyl ethers are quite stable to acidic conditions. Most ethers and 1,3-dithianes are stable to the neutral mercuric chloride used to remove the MTM group. One problem with the MTM group is that it is sometimes difficult to introduce. 

Some of the methods used to cleave methylthiomethyl (MTM) ethers should also be applicable to the cleavage of tetrahydrothiofuranyl ethers. 

HgCl2, CH3CN-H2O, reflux, 10 h, 90-95% yield. Aiyl methylthiomethyl ethers are stable to the conditions used to hydrolyze primary alkyl MTM ethers (e.g., HgCl2/CH3CN-H20, 25°, 6 h). They are moderately stable to acidic conditions (95% recovered from HOAC/THF-H2O, 25°, 4 h). 

CH3CN H20 (4 1), HgCl2, 24 h, 90-94% yield. The methylthiomethyl ether group can be removed in the presence of the phenylthiomethyl ether. ... 

A 1,3-dithiane is stable to the conditions (HgCl2, CaC03, CH3CN-H2O, 25°, 1-2 h) used to cleave a methylthiomethyl (MTM) ether (i.e., a mono-thio acetal). ... 

Methylthiomethyl Ester (MTM Ester) RCOOCH2SCH3 (Chart 6) Formation... 

Methoxymethyl, 27 Methylthiomethyl, 33 (Phenyldimethylsilyl)methoxymethyl, 35 Benzyloxymethyl, 36 p-Methoxybenzyloxymethyl, 37 p-Nitrobenzyloxymethyl, 38 o-Nitrobenzyloxymethyl, 38 (4-Methoxyphenoxy)methyl, 38 Guaiacolmethyl, 39 /-Butoxymethyl, 39 4-Pentenyloxymethyl, 40 Siloxymethyl, 41... 

Methoxymethyl. 257 Benzyloxymethyl, 258 Methoxyethoxymethyl, 258 2-(Trimethylsilyl)ethoxymethyl, 259 Methylthiomethyl, 259 Phenylthiomethyl, 259 Azidomethyl, 260 Cyanomethyl, 260 2,2-Dichloro-1,1-difluoroethyl, 260 2-Chloroethyl, 261 2-Bromoethyl, 261 Tetrahydropyranyl, 261 1-Ethoxyethyl, 261 Phenacyl, 262... 

Fluorenylmethyl, 387 Methoxymethyl, 388 Methylthiomethyl, 389 Tetrahydropyranyl, 390 Tetrahydrofuranyl, 390 Methoxyethoxymethyl, 390 2-(Trimethylsilyl)ethoxymethyl, 391 Benzyloxymethyl, 391 Pivaloyloxymethyl, 391 Phenylacetoxymethyl, 392 Triisopropylsilylmethyl, 392 Cyanomethyl, 392 Acetol, 393 Phenacyl, 393... 

A. Ethyl 4-Amino-3-(methylthiomethyl)benzoate [Benzoic acid, 4-amino-3-[(methylthio)methyl]-]. A 1-1., three-necked, round-bottomed flask is fitted with a mechanical stirrer, a condenser topped with a gas-inlet tube, and a two-neckcd adapter holding a low-temperature thermometer and a 100-ml., pressure-equalizing dropping funnel. The flask is charged with 10.50 g. (0.10 mole) of ethyl p-aminobenzoate [Benzocaine Benzoic acid, 4-amino-, ethyl ester] (Note 1), 300 ml. of acetonitrile, and 100 ml. of dichloromethane, is flushed with nitrogen, and is then immersed in a 40% aqueous methanol-dry ice bath maintained between... 

The cooling bath is then replaced by a steam bath, and the reaction mixture is refluxed for 16 hours. It is then cooled, transferred to a one-necked, 1-1., round-bottomed flask, and concentrated to dryness on a rotary evaporator. The dark residue is dissolved in a mixture of 200 ml. of water, 200 ml. of dichloromethane, and 20 ml. of triethylamine, and the aqueous phase is separated and washed with two 200-ml. portions of dichloromethane. The organic phases are combined and washed with 300 ml. of saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Removal of the solvent on a rotary evaporator gives a red oil, which solidifies on storage at 0-5° (Note 5). Recrystallization of this solid from 40 ml. of absolute ethanol gives 7.6-8.4 g. (34-37%) of ethyl 4-amino-3-(methylthiomethyl)-benzoate, m.p. 83-85°. A second crop of l.l-2.5g. of crystalline material, m.p. 78-83°, may be obtained by concentration of the mother liquors (Note 6). 

B. Ethyl l-Amino-S-methylbenzoate. A 1-1., three-nocked, round-bottomed flask equipped with a mechanical stirrer, a condenser, and a nitrogen-inlet tube is charged with 11.25 g. (0.050 mole) of ethyl 4-amino-3-(methylthiomethyl)benzoate, 300 ml. of absolute ethanol, and 17 teaspoons (ca. 50 g.) of W-2 Raney nickel (Note 7). The reaction mixture is stirred at 25° for one hour, then stirring is discontinued, and the ethanolic solution is decanted from the catalyst (Note 8). The catalyst is then washed with one 300-ml. portion of absolute ethanol and one 500-ml. portion of dichloromethane, the solvent being removed... 

The anions of alkyl alkylthiomethyl sulphoxides have found a much broader application. Methyl methylthiomethyl sulphoxide 324 was first introduced by Ogura and Tsuchihashi in 1971412 and ethyl ethylthiomethyl sulphoxide 325 was synthesized by Schlessinger and coworkers in 1973413. Ogura and Tsuchihashi performed alkylation of 324 and obtained a series of substituted dithioacetal monoxides 326 which were then hydrolysed to the corresponding aldehydes (equation 181 Table 17)412. 

TABLE 17. Alkylation of the methyl methylthiomethyl sulphoxide anion 324... 

Dithioacetal monoxide anions react with carbonyl compounds in a similar way affording the corresponding a-hydroxy aldehyde dithioacetal oxides 428. Ogura and Tsuchihashi, who performed this reaction for the first time using the anion of methyl methylthiomethyl sulphoxide 324, obtained in this way a series of a-hydroxyaldehydes 429504 (equation 257). 

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