Methylthiomethyl chloride

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by methylthiomethyl chloride is efficient if catalyzed by iodide ion.9 Alcohols are also converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride10 or with benzoyl peroxide and dimethyl sulfide.11 The latter two methods involve the generation of the methylthiomethylium ion by ionization of an acyloxysulfonium ion (Pummerer reaction). 

Preparation7 The reagent is prepared by the reaction of methylthiomethyl chloride with triethyl phosphite (110°, 6 hrs.). 

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. 

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). 

Methylthiomethyl p-tolyl sulfone, 192 Potassium ruthenate, 259 Trimethylsilyl chlorochromate, 327 a-Substituted ketones (see also Halo carbonyl compounds, Hydroxy aldehydes and ketones) a-Acetoxy ketones Benzeneselenenyl chloride-Silver acetate, 27... 

Very occasionally, solvents other than benzene, such as toluene,23 CH2CI224 or DME,25 have been used. It must be mentioned that the use of polar solvents tends to promote the formation of methylthiomethyl ethers in oxidations with activated DM SO.26 So far, pyridinium trifluoroacetate27 is the acid most commonly used, while phosphoric28 and dichloroacetic acid18 are being used less often. Acids rarely used include pyridinium tosylate,29 pyridinium phosphate30 and pyridinium chloride,31 which are normally employed in the presence of excess of pyridine. 

Methylthiomethylesters.1 Treatment of DMSO with n-butyllithium followed by tri-n-butylborane affords the ate complex CH3S(0)CH2BBu3Li+(l), which converts acid chlorides into methylthiomethyl esters. 

Methylthiomethyl ethers, like most 0,5-acetals, are stable to aqueous acid, but they can be removed under essentially neutral conditions in the presence of heavy metal catalysts with a high affinity for sulfur such as mercury(Il) or silver ), Typically, the substrate is treated with mercury(II) chloride in acetoni-trile-H20 (4 1) at room temperature or slightly above.586 With acid-sensitive... 

Aldehydes Alkyidimesitylborane. Chloro-methyltrimethylsilane. Diethyl[(2-tetrahy-dropyranyloxy)methylphosphonate. N,N-Dimethylchloromethyleniminum chloride. Dimelhyl(methylthio)sulfonium tetrafluom-borate. Methoxy(phenylthio)methyllithium. Methylthiomethyl p-tolyl sulfone. 1-Phen-ylthio-1 -trimethylsilylethylene. Tetrakis-(Iriphcnylphosphine)palladium. Thexyl-chloroborane-Dimethyl sulfide. 

A methylthiomethyl (MTM) group is removed by acid or can be cleaved by mild treatment with aqueous silver or mercury salts (neutral mercuric chloride) to which most other ethers are stable as a result, the selective deprotection of polyfunctional molecules becomes possible using MTM ethers for the hydroxy groups. 

The new oxidation process has one important limitation. Allylic or benzylic alcohols are not oxidized but instead replacement of hydroxyl by chlorine is observed. Still another reaction may occur in polar media thus, methylthiomethyl ether formation becomes pronounced when methylene chloride-dimethyl sulfoxide is used as solvent. 

Use of the chiral carbon pool for cyclopentenone preparation is also known. The fungal metabolite terrein [88] was selectively monoacetylated and then reduced with chromous chloride to enone [89]. Acetylation and olefin cleavage with ruthenium tetroxide aiwi sodium periodate led to aldehyde [90], which was readily decarbonylated to [65] (51). An alternative route (52) began with the less common S,S-tartaric acid [91], converted in four steps to diiodide [92]. Dialkylation of methyl methylthiomethyl sulfoxide with [92] gave the cyclopentane derivative [93]. Treatment of [93]... 

Methyl methylthiomethyl sulfone and methylthiomethyl p-tosyl sulfone have been monoalkylated, benzylated or alkylsilylated with 1.5 equiv. of the electrophile in the presence of aqueous sodium hydroxide and trioctylmethylammonium chloride (TOMAC). Without doubt the organometallic is less reactive than the one derived from the corresponding sulfoxide since the reaction is rather slow with... 

Appropriate alkyl iodides or bromides were reacted with 57 and 2-epi-Sl in the presence of Ag20 in CH3CN with yields ranging from 36 to 77% (74, Scheme 10) [34, 51]. However, with these conditions preparation of branched alkyl ethers was unsuccessful [51]. Reacting 57 with chloromethyl methyl ether, diisopropylethy-lamine, and catalytic DMAP in CH2CI2 afforded 75 in a 72% yield and was the first 1 derivative reported to have increased affinity at the KOP receptor relative to 1. [41, 52]. Based on the successful increase in affinity of derivative 75, additional simple alkoxymethyl ethers were obtained using appropriate alkyoxymethyl chloride with diisopropylethylamine in DMF (76-78). However, more complex alkoxymethyl derivatives were synthesized from the common methylthiomethyl ether intermediate (79), which was obtained from reaction of 57 with acetic acid, acetic anhydride, and dimethylsulfoxide (DMSO) [52]. Compound 79 was then... 

MMTS MsOH NBS NHMDS NMP NMR PPb Ph Pr PTC rt TBDMS Tf THF THP TLC TMEDA TMS TMSOTf Tol TOMAC Ts TsOH UDP methyl methylthiomethyl sulfoxide (=FAMSO) methanesulfonic acid N-bromosuccinimide sodium hexamethyldisililazide /V-methyl-2-pyrrolidone nuclear magnetic resonance parts per billion phenyl propyl Phase transfer catalysis room temperature t-butyldimethylsilyl triflatc (trifluoromethanesulfonate) tetrahydrofuran 2-tetrahydro-2//-pyran-2-yl thin-layer chromatography /V./V./V /V -tetramethylethylenediamine trimethylsilyl trimethylsilyl triflate p-tolyl trioctylmethylammonium chloride tosyl p-toluenesulfonic acid ultrasonically dispersed potassium... 

Methylthiomethyl esters have been prepared by reaction of triethylammonium salts of carboxylic acids with chlorodimethylsulfonium chloride or by reaction of the potassium salts of carboxylic acids with chloromethyl methyl sulfide in the presence of sodium iodide and 18-crown-6. ... 

A soln. of N-chlorosuccinimide in dry methylene chloride added at -20° to a stirred soln. of the equivalent amount of 4-diloro-2-(methylthiomethyl)aniline in the same solvent, and after 2 hrs. treated with a slight excess of aq. NaOH -> product. Y 95%. F. e. s. P. K. Claus, P. Hofbauer, and W. Rieder, Tetrah. Let. 1974, 3319. 

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