Methanesulfonyl chloride, reaction with

The stereoisomeric bicyclic amino alcohols (218) and (219) each undergo in tetrahy-drofuran solvent ready acetylation with acetyl chloride and ready mesyiation with methanesulfonyl chloride. Reaction of the endo isomer (219) very probabiy proceeds via the intramolecular 5-exo-Trig pathway, similar intermediates being formed in... 

Section 7.8). Other classes of derivatives are thus most conveniently prepared from the sulfonyl chloride. Reaction with an alcohol leads to formation of a sulfonate ester. Two common sulfonyl chloride reagents employed to make sulfonate esters from alcohols arep-toluenesulfonyl chloride, known as tosyl chloride, and methanesulfonyl chloride, known as mesyl chloride (see Section 6.1.4). Note the nomenclature tosyl and mesyl for these groups, which may be abbreviated to Ts and Ms respectively. 

Almotnptan (5, LAS-31416) was discovered and developed by Almirall in Spain. The U.S. marketing rights were licensed to Pharmacia and then to Janssen. The synthesis commenced with the reaction of (p-nitrophenyl)-methanesulfonyl chloride (57) with pyrrolidine, followed by hydrogenation of the nitro group to give aniline 58 (Scheme 21). The hydrazine 59 was prepared by diazotization of 58 followed by reduction of the resulting diazonium salt with stannous chloride. Hydrazine 59 was treated with 4-chlorobutanal diethyl acetal in aqueous HCl and hydrazone 60 precipitated and was... 

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. 

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. 

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 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). 

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). 

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. 

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]. 

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. 

After finding the right combination for the diamine linkers, Yus et al. tried to determine whether it was compulsory to use two isoborneol-10-sulfonamide moieties. In this context, these authors have prepared the ligand depicted in Scheme 4.24 by reaction of the best amine linker, trani-cyclohexane-1,2-diamine, with camphorsulfonyl chloride and then with methanesulfonyl chloride, followed by reduction with AlH(i-Bu)2 and then hydrolysis.When this new ligand was involved in the enantioselective addition of ZnEt2 to acetophenone, the expected tertiary alcohol was obtained in excellent yield and enantioselectivity of 96% ee, as shown in Scheme 4.24. According to this result, the authors concluded that the second isoborneol unit seemed not to be necessary to obtain a high enantioselectivity. 

It is of interest that there exists a considerable amount of flexibility as to the substituent at C-21 in the acetonide series. For example, formation of the acetonide from 241 affords intermediate 242. Reaction with methanesulfonyl chloride gives the corresponding mesylate (243). Displacement... 

R)-Cyanohydrins react with toluenesulfonyl chloride, methanesulfonyl chloride or 4-nitrobenzenesulfonyl chloride without loss of stereochemical purity, and the 2-sulfonyloxy-nitrile reacts with a variety of Sn2 reactions to give a variety of products, such as 2-fluoro nitrile [64], 2-azidonitrile [65] and /V- p h t h a I o yl - p rot e c te d 2-aminonitrile [66], 2-acetoxy nitrile [66], and 2-mercapto nitrile [67]. Hydrogenation of 2-sulfonyloxynitriles with LiAIH4 in good chemical yields and high ee afforded 2-monosubstituted (S)-aziridines [68]. 

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