Methanesulfonyl chloride chlorides

Under similar conditions (diethyl ether or THF as solvent) the reaction of lithium alkynylides with methanesulfonyl chloride (CH35O2CI) gave the corresponding alkynyl sulfones in low to moderate yields. 

Direct halogenation of sucrose has also been achieved using a combination of DMF—methanesulfonyl chloride (88), sulfuryl chloride—pyridine (89), carbon tetrachloride—triphenylphosphine—pyridine (90), and thionyl chloride—pyridine—1,1,2-trichloroethane (91). Treatment of sucrose with carbon tetrachloride—triphenylphosphine—pyridine at 70°C for 2 h gave 6,6 -dichloro-6,6 -dideoxysucrose in 92% yield. The greater reactivity of the 6 and 6 primary hydroxyl groups has been associated with a bulky halogenating complex formed from triphenylphosphine dihaUde ((CgH )2P=CX2) and pyridine (90). 

Physical Properties. Methanesulfonyl chloride [124-63-0] (MSG), CH2SO2CI, is a clear Hquid, and is soluble in a wide variety of organic solvents, eg, methanol and acetone (Table 9). 

Chemical Properties. Methanesulfonyl chloride (MSC) is a reactive chemical which allows iatroduction of the mesyl group, CH SO, into a... 

Manufacture. Methanesulfonyl chloride is made commercially either by the chlorination of methyl mercaptan or by the sulfochlorination of methane. The product is available in 99.5% assay purity by Elf Atochem NA in the United States or by Elf Atochem SA in Europe. 

Manufacture. Methanesulfonic acid is made commercially by oxidation of methyl mercaptan by chlorine in aqueous hydrochloric acid to give methanesulfonyl chloride which is then hydrolyzed to MSA. 

The mesylate group, introduced with methanesulfonyl chloride, can be cleaved with lithium aluminum hydride and dissolving metal reduction (Na, /-BuOH, HMPT, NH3, 64% yield). ... 

B. cis-1,2-Gyclohexanedimethanol Dimethanesulfonate. In a 5-1., three-necked, round-bottomed flask, immersed in an ice-salt bath and fitted with a mechanical stirrer and an addition funnel, is plaeed a solution of 111 g. (0.97 mole) of methanesulfonyl chloride in 1.21. of pyridine. While cooling and stirring, a solution of 46.4 g. (0.322 mole) of m-l,2-cyclohexanedimethanol in 250 ml. of pyridine is added dropwise at a rate such that the temperature does not exceed 0° (Note 5). Upon completion of the addition, the mixture is stirred at — 5° to 0° for an additional 2 hours. Two liters of cold 10% hydrochloric acid is introduced at a rate which maintains the reaction mixture below 20° (Note 5). The solid which separates is isolated by suction filtration, washed sequentially with 11. of dilute hydrochloric acid and 21. of water, and air-dried. There is isolated 93-95 g. (96-98%) of the dimethanesulfonate having m.p. 66-67.5°. Reorystallization from methanol gives needles melting at 75-76° (Note 6). 

The difference between the distillation and pot temperatures is closely related to the success of this preparation. If the specified weights of reactants and temperatures are employed a 3 temperature difference should be reached before the yellow intermediate fraction, probably containing methanesulfenyl chloride, chloromethanesulfenyl chloride, and acetic acid, has attained a volume of 10 ml. Toward the end of the distillation the pot temperature may begin to rise owing to the presence in the residue of methanesulfonyl chloride (b.p. 63°/20 mm.,... 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

The azido alcohol is dissolved in a minimal amount of dry pyridine and cooled in an ice bath. Methanesulfonyl chloride (1 ml/g of azido alcohol) is added to the cold solution. The reaction mixture is allowed to stand at 0° for 24 to 72 hr. The reaction mixture is processed by pouring into ice water and either filtering the product, if possible, or by extraction with an organic solvent. Methanol or methanol-ether have been used to recrystallize the crude azido mesylates. 

To the epoxide dissolved in a minimal amount of chloroform or ether is added a corresponding solution of freshly prepared thiocyanic acid (20 fold excess) as described above (acetic acid has also been used as solvent). The resulting solution is allowed to stand at least 70 hr at room temperature. (Some workers have protected the reaction mixture from light during this period). The reaction mixture is worked up by washing first with a 10% solution of sodium carbonate, sodium bicarbonate or potassium bicarbonate, and then water. The remaining ether extract is dried (Na2S04) and evaporated under vacuum. The crude thiocyanatohydrin is crystallized from an appropriate solvent or treated with methanesulfonyl chloride s (see below). 

Treatment of (70a) with methanesulfonyl chloride in pyridine gives rise to vinylcylopropane (73) which can be converted back to the homoallylic alcohol (70a) under conditions similar to those used for converting cyclopropyl carbinol (69a) to the B-homo-7)5-ol (70a). 

In contrast to the behavior of homoallylic alcohol (70a) when treated with methanesulfonyl chloride is pyridine, heating A -19-methanesulfonate (68b) in pyridine gives the 5)5,19-cyclo-6-ene (72). Vinylcyclopropane (72) is inert to the conditions used for converting vinylcyclopropane (73) to the A ° -B-homo-7)5-ol (70a). The latter results are only consistent with the existence of two discrete isomeric carbonium ion intermediates which give rise to isomeric elimination products. °... 

On the basis of these findings, the reaction of acyl imines with methanesulfony 1 chloride-triethylamine is not expected to proceed via a sulfene intermediate as previously proposed [99]. Again, a carbanion intermediate accounts nicely for the experimental facts. The electrophihcity of the hetero-l,3-diene is exdemely high, therefore the carbanion, formed on reaction of triethylamme with methanesulfonyl chloride, should undergo nucleophilic attack at C-4 of the hetero-1,3-diene faster than sulfene formabon by chloride elimination. 

The reaction with methanesulfonyl chloride in the presence of a proton abstracter like triethyl amine gave not the enamine, but a cyclic amino-sulfone (64). 

Alkyl sulfonyl chlorides, having an a-hydrogen atom, react with enamines derived from aldehydes and cyclic ketones in the presence of triethylamine to give cyclic sulfones. Thus the enamine (22) gave the four-membered cyclic aminosulfone (143) on reaction with methanesulfonyl chloride (95). 

In a similar manner the enamine (113) reacted with methanesulfonyl chloride (96) to give the cyclic sulfone (144). 

Methanesulfonyl chloride reacts with enamino ketones (104), (e.g., 151) to give good yields of the enol sulfones (e.g., 152). The analogy with ketene addition to form a-pyrones (Section IV.A) is obvious. 

Dienamines undergo 1,4 cycloaddition with sulfenes as well as 1,2 cycloaddition. For example, l-(N,N-diethylamino)butadiene (111), when treated with sulfene (generated from methanesulfonyl chloride and triethyl-amine), produces 1,4 cycloadduct 116 in an 18 % yield and di-1,2-cycloadduct 117 in a 60 % yield (160). Cycloadduct 116 was shown not to be the precursor for 117 by treating 116 with excess sulfene and recovering the starting material unchanged (160). This reaction probably takes place by way of zwitterion 115, which can close in either a 1,4 or 3,4 manner to form cycloadducts 116 and 118, respectively. The 3,4 cycloaddition would then be followed by a 1,2 cycloaddition of a second mole of sulfene to form 117. Cycloadduct 117 must form in the 3,4 cycloaddition followed by a 1,2-cycloaddition sequence rather than the reverse sequence since sulfenes undergo cycloaddition only in the presence of an electron-rich olefinic center (159). Such a center is present as an enamine in 118, but it is not present in 119. 

Stable sulfenes have been isolated by treating methanesulfonyl chloride, with triethylamine or trimethylamine in acetonitrile solvent at -40°C (165,166). These stable sulfenes undergo 1,2 cycloaddition with enamines to form the expected thietanes (trimethylenesulfones). 

Reactions of vinylogous amides with methanesulfonyl chloride also led to the formation of six-membered rings. Here the initial attack on oxygen produces a zwitterionic intermediate which can collapse to an enol sulfonic acid lactone (383,469). 

The formation of four-membered-ring sulfones and a-sulfonyl amides has also been applied to the reaction of methanesulfonyl chloride with ketene aminals and acetals (470-473). 

The oxygen atom at 21 is similarly an expendable group. Reaction of 241 (obtained from 185 by the usual procedure for introduction of the 9a-fluoro group) with methanesulfonyl chloride affords the 21 mesylate (242a). Replacement of the leaving group at 21 with iodine by means of potassium iodide in acetone followed by reduction of the halogen with zinc in acetic acid leads to fluorometholone (243). ... 

Activity is also retained when the hydroxyl group at the 21 position is replaced by chlorine. Reaction of corticoid 44 with methanesulfonyl chloride proceeds preferentially at the 21-hydroxyl (45) due to the hindered nature of the 11-alcohol. Replacement of the mesylate by means of lithium chloride in DMF affords clobetasol propionate (46) a similar sequence starting with the 17- butyrate ester 47, via mesylate 48, should give clobetasone butyrate, (49) [11]. 

Nitrn-l-propene Preparation is accomphshed by dehydration of l-nitro-2-propanol with methanesuLfonyl chloride and triethylamine (30% ieldi, acetic... 

Dehydro-6a-methyl-9a-fluorohydrocortisone Methanesulfonyl chloride Sodium iodide Sodium thiosulfate... 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

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