Methanesulfonate

Conversion of an Alcohol into a Mesylate (an Alkyl Methanesulfonate) 

The alcohol oxygen attacks the sulfur The intermediate loses atom of the sulfonyl chloride. a chloride ion. 

Show how you would prepare the following compounds from the appropriate sulfonyl chlorides. 

Suggest an experiment using an isotopically labeled alcohol that would prove that the for- Review Problem 11.10 mation of an alkyl sulfonate does not cause cleavage at the C—O bond of the alcohol. 

Alcohols react with phosphoric acid to yield alkyl phosphates  

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Alkenylation of cyclopentenone with the alkenylstannane 719 has been used for the introduction of an a,>-chain into a prostaglandin derivative[590]. Even the vinyl mesylate (methanesulfonate) 720 can be used for coupling with alkenylstannanes[59l]. 

A mixture of methanesulfonic acid and P Oj used either neat or diluted with sulfolane or CH2CI2 is a strongly acidic system. It has been used to control the rcgiosclcctivity in cydization of unsymmetrical ketones. Use of the neal reagent favours reaction into the less substituted branch whereas diluted solutions favour the more substituted branch[3]. 

Optically pure (S) (+) 2 butanol was converted to its methanesulfonate ester according to the reaction shown... 

Nearly all commercial acetylations are realized using acid catalysts. Catalytic acetylation of alcohols can be carried out using mineral acids, eg, perchloric acid [7601-90-3], phosphoric acid [7664-38-2], sulfuric acid [7664-93-9], benzenesulfonic acid [98-11-3], or methanesulfonic acid [75-75-2], as the catalyst. Certain acid-reacting ion-exchange resins may also be used, but these tend to decompose in hot acetic acid. Mordenite [12445-20-4], a decationized Y-zeohte, is a useful acetylation catalyst (28) and aluminum chloride [7446-70-0], catalyzes / -butanol [71-36-3] acetylation (29). 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

Methanesulfonic and ben2enesulfonic anhydrides are the most frequently used anhydrides ia Friedel-Crafts sulfonylation reactions ... 

Petfluotoalkanesulfonic acids also show high acidity. The parent trifluoromethanesulfonic acid (triflic acid), CF SO H, is commercially prepared by electrochemical fluorination of methanesulfonic acid (214). It has an value of —14.1 (215,216). The higher homologues show slightly decreasing acidities. 

NaOH solution is added dropwise to an aqueous suspension of this ester at 40—70°C over 1 h and the reaction mixture kept for 2 h to give 86.6% DHNA of 98.7% purity (74), which is then esterified with (CgH O) to obtain PDNA. The esterification process is dramatically improved by adding a small amount of inorganic or organic acid, preferably methanesulfonic acid, benzene sulfonic acid, or naphthalene sulfonic acid subsequent isolation and crystallisation gives a pure product (75). 

The unique chemical behavior of KO2 is a result of its dual character as a radical anion and a strong oxidizing agent (68). The reactivity and solubiHty of KO2 is gready enhanced by a crown ether (69). Its usefiilness in furnishing oxygen anions is demonstrated by its appHcations in SN2-type reactions to displace methanesulfonate and bromine groups (70,71), the oxidation of benzyHc methylene compounds to ketones (72), and the syntheses of a-hydroxyketones from ketones (73). 

The choice of catalyst is based primarily on economic effects and product purity requirements. More recentiy, the handling of waste associated with the choice of catalyst has become an important factor in the economic evaluation. Catalysts that produce less waste and more easily handled waste by-products are strongly preferred by alkylphenol producers. Some commonly used catalysts are sulfuric acid, boron trifluoride, aluminum phenoxide, methanesulfonic acid, toluene—xylene sulfonic acid, cationic-exchange resin, acidic clays, and modified zeoHtes. 

The deterruination of amino acids in proteins requires pretreatment by either acid or alkaline hydrolysis. However, L-tryptophan is decomposed by acid, and the racemi2ation of several amino acids takes place during alkaline hydrolysis. Moreover, it is very difficult to confirm the presence of cysteine in either case. The use of methanesulfonic acid (18) and mercaptoethanesulfonic acid (19) as the protein hydroly2ing reagent to prevent decomposition of L-tryptophan and L-cysteine is recommended. En2ymatic hydrolysis of proteins has been studied (20). 

For deterrnination of tryptophan, 4 M methanesulfonic acid hydrolysis is employed (18). For cystine, the protein is reduced with 2-mercaptoethanol, the resultant cysteine residue is carboxymethylated with iodoacetic acid, and then the protein sample is hydroly2ed. Also, a one-pot method with mercaptoethanesulfonic acid has been developed for tryptophan and cystine (19). 

Sulfonic acids are such strong acids that in general they can be considered greater than 99% ionized. The piC value for sulfuric acid is —2.8 as compared to the piC values of —1.92, —1.68, and —2.8 for methanesulfonic acid, ethanesulfonic acid, and benzene sulfonic acid, respectively (3). Trifluoromethanesulfonic acid [1493-13-6] has a piC of less than —2.8, making it one of the strongest acids known (4,5). Trifluoromethanesulfonic acid is also one of the most robust sulfonic acids. Heating this material to 350°C causes no thermal breakdown (6). 

A method suitable for analysis of sulfur dioxide in ambient air and sensitive to 0.003—5 ppm involves aspirating a measured air sample through a solution of potassium or sodium tetrachloromercurate, with the resultant formation of a dichlorosulfitomercurate. Ethylenediaminetetraacetic acid (EDTA) disodium salt is added to this solution to complex heavy metals which can interfere by oxidation of the sulfur dioxide. The sample is also treated with 0.6 wt % sulfamic acid to destroy any nitrite anions. Then the sample is treated with formaldehyde and specially purified acid-bleached rosaniline containing phosphoric acid to control pH. This reacts with the dichlorosulfitomercurate to form an intensely colored rosaniline—methanesulfonic acid. The pH of the solution is adjusted to 1.6 0.1 with phosphoric acid, and the absorbance is read spectrophotometricaHy at 548 nm (273). 

Physical Properties. Methanesulfonic acid [75-75-2] (MSA), CH SO H, is a clear, colorless, strong organic acid available in bulk quantities from Elf Atochem North America as a 70% solution and on an anhydrous basis (100%). MSA is soluble in water and in many organic solvents. Its physical properties ate described in Table 10. 

The metal salts of MSA are highly soluble in water as well as in some organic solvents, making MSA usefijl in electroplating operations. For example, lead sulfate is insoluble in water, whereas lead methanesulfonate (lead mesylate) is water soluble. 

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. 

Its production was 621 t and the average price 0.75/kg in 1987. Direct YeUow 44 (64) is prepared by phosgenation of an equimolar mixture of metanilic acid coupled to o-anisidinomethanesulfonic acid (with subsequent hydrolysis of the methanesulfonic acid group) and nitro aniline coupled to sahcychc acid (with subsequent reduction of the nitro group). 

Zinc chloride is a Lewis acid catalyst that promotes cellulose esterification. However, because of the large quantities required, this type of catalyst would be uneconomical for commercial use. Other compounds such as titanium alkoxides, eg, tetrabutoxytitanium (80), sulfate salts containing cadmium, aluminum, and ammonium ions (81), sulfamic acid, and ammonium sulfate (82) have been reported as catalysts for cellulose acetate production. In general, they require reaction temperatures above 50°C for complete esterification. Relatively small amounts (<0.5%) of sulfuric acid combined with phosphoric acid (83), sulfonic acids, eg, methanesulfonic, or alkyl phosphites (84) have been reported as good acetylation catalysts, especially at reaction temperatures above 90°C. 

The newest fin baths, fin—lead baths, and lead baths recendy entering the market, are based on methanesulfonates. The higher makeup cost of tin methanesulfonate baths, about 1.6 times the cost of duoborate baths, may be justified where restrictions on duoborates and boric acid ia wastes exist. 

In laboratory preparations, sulfuric acid and hydrochloric acid have classically been used as esterification catalysts. However, formation of alkyl chlorides or dehydration, isomerization, or polymerization side reactions may result. Sulfonic acids, such as benzenesulfonic acid, toluenesulfonic acid, or methanesulfonic acid, are widely used in plant operations because of their less corrosive nature. Phosphoric acid is sometimes employed, but it leads to rather slow reactions. Soluble or supported metal salts minimize side reactions but usually require higher temperatures than strong acids. 

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