Methanesulfonyl fluoride

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

The production of high-purity methanesulfonyl fluoride (19) by reacting methanesulfonyl chloride (18) with sodium fluoride containing 3 parts by weight of water is reported in a patent.19 The reaction takes place at 50 °C for 4 hours while methanesulfonyl fluoride is distilled out of the reaction mixture at 60 Torr. 

Substitution of fluorine for halogen in aromatic and alkyl sulfonyl halides can be carried out with or without using a solvent. An aqueous system such as 70 % aqueous potassium fluoride is also used because the rate of hydrolysis is much slower than the rate of fluorination as reported for the conversion of methanesulfonyl chloride (1) to methanesulfonyl fluoride (2).23... 

A variety of benzyl fluorides 9 were directly prepared in one-step from the corresponding benzyl alcohols 8 by using a combination of methanesulfonyl fluoride and cesium fluoride in the presence of dibenzo-18-crown-6.167 The mesylates formed in situ are thus easily converted to the fluoro derivatives 9. 

This method has been extended to heterocycles bearing a hydroxymethyl-substituted nitrogen. Thus, ethyl l-(hydroxymethyl)pyrazole-4-carboxylate (10) is converted into ethyl 1-(fluoromethyl)pyrazole-4-carboxylate (11) in 76% yield with cesium fluoride/methanesulfonyl fluoride/18-crown-6 system.167 Potassium fluoride did not react at all and tetrabutylammonium fluoride leads to decomposition and formation of coupling products. 

Fig. 1 Possible Reaction Schemes for Amidoxime with Methanesulfonyl Fluoride.

Fig. 3 IR Spectra of Butadiene (BD)-Acrylonitrile(AN)-Acrylamid-oxime (AX) Terpolymer Exposed to Methanesulfonyl Fluoride (MSF) and Dimethyl Methylphosphonate (DMMP) Simulants.

They are prepared from trifluoromethylsulfonyl fluoride and the corresponding aniline. The trifluoromethylsulfonyl fluoride group was prepared by Simons electrochemical fluorination of methanesulfonyl fluoride (Fig. 26) [101]. 

In addition to the unsubstituted sulfene itself, the various substituted sulfenes used in the preparation of thietane 1,1-dioxides are listed in Table 4. Although the usual method for generating the sulfenes is by treatment of a methanesulfonyl chloride with triethylamine, sulfenes have been obtained by the reaction of phenyl-methanesulfonyl fluoride with phenyllithium, by treatment of a-chloro-ethanesulfinic acid with refluxing triethylamine,by treatment of 4-nitro-phenyl or 2-chloro-4-nitrophenyl, esters of arylmethanesulfonic acids with potassium t-butoxide or 2,6-dimethylpyridine, respectively, by treatment of diazoalkanes with sulfur dioxide" (e.g., to give 146) and by thermolysis of a Diels-Alder adduct of sulfene." ... 

Sulfenyl fluorides are extremely unstable and therefore only few perhalosulfenyl fluorides have so far been reported z yjjg formal addition of the elements of methanesulfonyl fluoride to carbon-carbon double bonds has been obtained hy a one-pot reaction with dimethyl(methylthio)sulfonium tetrafluoroborate and triethylammonium tris(hydrofluo-ride). With this system also the addition to double bonds is highly stereoselective, at least... 

Phenyl methanesulfonyl fluoride (PMSF) [329-98-6] M 174.2, m 90-91, 92-93. Purify PMSF by reciystallisation from C6H6, pet ether or CHCVpet ether. [Davies Dick J Chem Soc 483 1932, cf TuUock Coffman / Org Chem 23 2016 I960.] It is a general protease inhibitor (specific for trypsin and chymotiypsin) and is a good substitute for diisopropylphosphoro floridate [Fahmey Gould J Am Chem Soc 85 997 7963]. [Beilstein 11 III 331.]... 

Irreversible inhibitors are effectively esteratic site inhibitors which, like true substrates, react with the hydroxyl group of serine at the catalytic active site. Such inhibitors, sometimes referred to as acid-transferring inhibitors, include the organophosphates, the organo-sulfonates, and the carbamates. All form acyl-enzyme complexes which, unlike substrate-enzyme intermediates, are relatively stable to hydrolysis. Indeed, the phosphorylated enzyme intermediates have half-lives from a few hours to several days (A12), whereas the sulfonated or carbamylated enzyme complexes have much shorter half-lives—several minutes to a few hours. Several strong lines of direct evidence point to the formation of an acyl complex—the isolation of phosphorylated serine from hydrolysates of horse cholinesterase (J2), complex formation and carbamylation (02), and the sulfonation of butyrylcholinesterase by methanesulfonyl fluoride in the presence of tubocurarine and eserine (P6). 

P6. Pavlic, M., The inhibition of butyrylcholinesterase by methanesulfonyl fluoride. Biochim. Biophys. Acta 198, 389-391 (1970). 

Methanesulfonyl fluoride, CH3S02F, and other alkanesulfonyl fluorides were prepared by Davies and Dick, 1932, by refluxing CH3S02C1 over solid ZnF2 or by heating an alkanesulfonyl chloride with 70% KF solution in water (63). 

Dialkylamino-5-aryl-677-l,3,4-thiadiazines cannot be alkylated with methyl iodide. 1,3,4-Thiadiazine hydroiodides are obtained by the reaction of 2-dialkylamino-6//-l,3,4-thiadiazines with methyl iodide in anhydrous ethanol in the presence of dimethyl sulfoxide (DMSO) <1998RJ0417>. The reaction of 2-pyrrolidino- or 2-morpholino-5-phenyl-6/7-l,3,4-thiadiazines with methanesulfonyl fluoride or triethyloxonium tetrafluoroborate affords quaternary 2-dialkylamino-5-phenyl-6/7-l,3,4-thiadiazines 75 in excellent yields (Equation 9) <1998RJ0417>. 

A solution of 4-methoxybenzyl alcohol (122 mg, 1 mmol), methanesulfonyl fluoride (196 mg, 2 mmol, 2 equiv.), tetrabutylammonium fluoride (TBAF, 3 mL of a commercial 1M solution of trihydrate in water, 3 mmol, 3 equiv.), and 1 g of 4-A molecular sieves in 20 mL anhydrous THF is sonicated at 20 C for 2 h using a Sonics Materials Inc. VX-400 probe system (20 kHz, 13 mm probe, 120-W electrical power input). The reaction mixture is then filtered and concentrated under reduced pressure. Purification by preparative circular thin-layer chromatography (Harrison Research Chromatotron with 2 mm silica gel layer) using ethyl acetate/n-hexane 1/1 as eluents yields methoxybenzyl fluoride (99 mg, 65%)... 

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