Methanesulphonyl chloride

As has been mentioned in an earlier section, aqueous chlorination of sulphoxides leads to sulphones. If excess reagents are used, sulphonyl chlorides may be formed directly from sulphoxides in good yields (equation 75)89,90,193. In order for this reaction to be synthetically useful, the sulphoxide used should be symmetrical. The product is presumably formed in a stepwise manner via the sulphinyl chloride [RS(0)C1] and the sulphinic acid [RS(0)0H]. In the case of chloromethyl dichloromethyl sulphoxide, the only sulphonyl chloride formed is chloromethanesulphonyl chloride (equation 76) and this may be readily separated from the other products by distillation90,193. Similarly, oxidation of dichloromethyl methyl sulphoxide and methyl trichloromethyl sulphoxide with chlorine in aqueous acetic acid leads to the formation of methanesulphonyl chloride in 75% and 86% yields respectively. Other species are also produced but these are much more volatile and thus easily removed (equations 77 and 78). In the absence of acetic acid the yields are somewhat reduced. 

Crossed aldol condensation of an anion generated a- to a ketone equivalent with o, /3-unsaturated aldehyde, dehydration and release of the ketone is an effective way of generation of dienones. Corey and Enders found that a-lithiated /V,/V-dirnethylhydrazones undergo 1,2-addition to the aldehydes and ketones to form /1-hydroxy derivatives. Sequential treatment of the intermediate with sodium periodate and methanesulphonyl chloride-triethylamine furnishes , -2,4-dienone derivative (equation 57)94. 

Similar side reactions were observed with 2-methylindole and arenesulphonyl chlorides, but the reaction of 2-substituted indoles with methanesulphonyl chloride gave the expected 1,2-disubstituted indoles (2, R1 = Me). 

Methanesulphonyl chloride [124-63-0] M 114.5. b 55°/llmmm, d 1.474, n 1.452. Distd from P2O5 under vacuum. 

Various methods can be used to prepare dihydro- 1,4-benzoxazines and -benzothiazines (B-78MI22701). A recent approach to the first group of compounds is to react 2-hydroxyacetanilides (279) with 1,2-dibromoethane and sodium hydroxide in acetonitrile containing the phase transfer catalyst Aliquat 336 (Scheme 122) (79S541). 1,1-Dioxides of dihydrobenzo-l,4-thiazines (281) are generated through the cyclization of imines (280) with methanesulphonyl chloride in the presence of triethylamine (79CI(L)26). 

Notes. (1) The handling of methanesulphonyl chloride, which is highly toxic and corrosive, must be carried out in a fume cupboard and protective gloves must be worn. The reaction should also be conducted in a fume cupboard. 

The crude 84-3,20-dioxo-6-chloro-7a-hydroxy-17a-acetoxy-19-nor-pregnene is dissolved in 3 ml of pyridine, mixed at 5°-0°C with 0.3 ml of methanesulphonyl chloride while being stirred, and the mixture is kept for 2 days at 10°C. The reaction product is then poured into dilute sodium bicarbonate solution, dissolved in ether, and the ethereal solution is washed until the washings run neutral, dried and evaporated under vacuum and the 84-3,20-dioxo-6-chloro-7a-mesyloxy-17a-acetoxy-19-norpregnene is obtained. 

Methanesulphonyloxypropyl)phenthiazine-2-sulphonic acid dimethylamide, was obtained by condensing methanesulphonyl chloride in anhydrous pyridine with 10-(3-hydroxypropyl)phenthiazine-2-sulfonic acid dimethylamide. 

In previous investigations by the author (2) and others (3), sulfonyl enaminone derivative of 2-[(2,4,6-trimethyl-3-(4-methyl-phenyl))-phenyl]-5,5-pentamethylene-pyrrolidine-2,4-dione (I) was prepared by reacting with methanesulphonyl chloride as illustrated in Eq. 3 ... 

Reactions of some bismuthonium diacylylides with methanesulphonyl chloride and triethylamine give rise to 1, 3-oxathiolane derivatives, e.g. equation 53 . 

Enamines reaction with methanesulphonyl chloride and its homologues in the presence of triethylamine to yield thietane 1,1-dioxides. Thus 1-morphoIinocyclohexene gives a bicyclic thietane dioxide and 2-methyl-l-pyrrolidinopropene and other enamines derived from aliphatic aldehydes react analogously (equation 1). It is thought that the reactions proceed by way of the unisolable sulphene 1, which adds to the enamine double bond in a stepwise or concerted manner. This question has been much debated (for a critical discussion, see Reference 2, p. 3386) and will not be pursued here. It has been found that there is a lack of stereoselectivity in the addition of sulphene to the conformationally rigid enamines derived from 4-t-butylcyclohexanone . 

A simple one-pot synthesis of the bicyclobutanes (178 R = H, = R" = H or Me R = Me, R = H, R = Pr ) (> 50%) from (177) has been reported. Sequential treatment of (177) in THF at 0°C with one equivalent each of BuLi, methanesulphonyl chloride, and then BuLi again, to give (17 ), may be accomplished in 10 minutes. Terminal 7-epoxy-sulphones, on treatment with two equivalents of MeMgl, give c/s-3-phenylsulphonylcyclo-butanols thus (179) yields (180). This reaction contrasts with that of (179) with MeLi or with LiNPr 2, which gives derivatives of cyclopropyl-methanol. 

Phase-transfer catalysis has become highly useful in the synthesis of azetidinones. It facilitates the one-pot synthesis of azetidinones from 0 -amino-acids and acid chlorides such as (13). It also promotes the reaction of i8-amino-acids and methanesulphonyl chloride to form azetidinones. ... 

A very convenient method for the synthesis of (158) consists in the side-chain bromination of 2-thienyl ethyl ketone followed by reaction with sodium methoxide in methanol and with methanesulphonyl chloride in pyridine, which gave (157) in 88% yield. Treatment of (157) with calcium carbonate led to 1,2-rearrangement of the thienyl group to give (158). Metal complexes of s> -thiophen-2-aldoxime, thiophen-2-carbaldehyde 2-benzothiazolylhydrazone, and thiophen-2-carbaldehyde thiosemicarba-zone have been studied. 

Reactions of Vinylthiophens and Related Compounds. - 2-Aroyl-5-vinyl-thiophens react with triphenylphosphine, palladium chloride, and carbon monoxide to give 2-(5-aroyl-2-thienyl)propionic acid. Cycloaddition of sulphene, from methanesulphonyl chloride and triethylamine, to 2-(a-dimethylaminovinyl)thiophen gave (160). The synthesis of some substituted 3-(2-thienyl)acryloylamino-acids has been described. Some reactions of 3-chloro-j8-(2-thienyl)vinylphosphonic acid dichlorides have been studied, ... 

AI3-52234 Chloromethyl sulfone EINECS 204-706-1 HSDB 5605 Mesyl chloride Methanesulfonic acid chloride Methanesulfonyl chloride Methanesulfuryl chloride Methanesulphonyl chloride Methyl sulfochloride Methylsulfonyl chloride NSC 16039 UN3246. Liquid bp = 162, bpii = 55 d = 1.4805 insoluble in H2O, soluble in EtOH, EtzO. 

Turning now to the neutral benzene and methanesulphonyl chlorides 79 and 80, Table 14 explores the difference between the heats of formation of gaseous benzene and methane derivatives with other electronegative and -withdrawing substituents. The desired difference is seen to hover around 31 + 2 kcal mol-1. We cannot think of any way of rationalizing the difference of only 15 kcal mol-1 for 79 and 80 and do not know which... 

We now turn to methanesulphonyl chloride, 80. Recall the above 31 kcalmol-1 difference of heats of formation of comparable PhX and MeX derivatives. This is for gaseous species. For liquid species, we recall the simple but accurate (generally 1 kcalmol-1) formula derived by Chickos, Hesse, Liebman and Panshin54 ... 

We also recall from GN s study that the heat of formation of liquid n-dodecanesulphonyl chloride (19) is —170 kcal mol - L Ideally we would like to synthesize methanesulphonyl chloride from 19. Consider the hypothetical reaction 50 ... 

Aryl sulphonyl chlorides may also be synthesized from the sulphinyl chloride, by oxidation with chlorine, in 80% yield573 (equation 146) or dimethyl sulphoxide574. Sulphinate esters may also be utilized as the precursor to sulphonyl halide via oxidative halogenation. For example, methyl methanesulphinate is converted to methanesulphonyl chloride in excellent yield at 0°C568. 

Phosphines have been used to trap sulphenes produced by dehydrochlorination of methanesulphonyl chlorides. The reaction of tetrazolo-pyridine with triphenylphosphine to give an iminophosphorane was shown, by kinetic measurements, not to involve a nitrene intermediate, but rather to involve reaction of the phosphine with the azide (12). The reaction... 

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