Methanesulfonic acid, reaction with

Compound 160 was transformed to chloride 161 by treatment with thionyl chloride and methanesulfonic acid. Reaction of 161 and 158 led to the formation of 162, which was separated as a single diastereomer by transformation to oxalate and subsequent crystallization. Finally, reduction of 162 with NaBH4 gave Emtricitabine (8) which was isolated as hydrochloride. 

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]. 

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). 

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). 

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. 

A variety of media have been used for the Wallach fluorination reaction anhydrous hydrogen fluoride alone or with cosolvents such as methylene chloride, benzene, or tetrahydrofuran and hydrogen fluoride-pyridine alone or with co solvents such as benzene, glyme, or acetic acid [42,43, 46 50] Solutions of cesium fluoride, tetraethylammonium fluoride, or tetrabutylammonium fluoride in strong acids such as methanesulfonic acid or trifiuoroacetic acid with numerous cosolvents have also been studied [48, 49]... 

After cooling, the reaction mixture is agitated (with a mixture of (water (40 cc) and a normal solution of methanesulfonic acid (70 cc), the xylene layer is removed and the acid liquors are (washed (with ether (200 cc). The aqueous phase is then made alkaline (with sodium hydroxide (d = 1.33 10 cc) and the liberated base Is extracted (with ether. The ethereal solution is dried over anhydrous potassium carbonate and concentrated at normal pressure. On distillation of the residue under reduced pressure 3-(3-methoxy-10-phenthi-azinyl)-2-methyl-1-dimethylaminopropane (11.3 g) is obtained, MP 103°C, BP 182° to 191°C/0.15 mm Hg. The hydrochloride prepared in isopropanol melts at about 90°C. 

Preparation of 7-(N,N -Dicarbobenzyloxyhydrazino)-6-Demethyttetracydine A 1.0 g portion of O-demethyltetracycline was dissolved in a mixture of 9.6 ml of tetrahydrofuran and 10.4 ml of methanesulfonic acid at -10°C. The mixture was allowed to warm to 0°C. A solution of 0.86 g of dibenzyl azodicarboxylate in 0.5 ml of tetrahydrofuran was added dropwise and the mixture was stirred for 2 hours while the temperature was maintained at 0°C. The reaction mixture was added to ether. The product was filtered off, washed with ether and then dried. The 7-(N,N -dicarbobenzyloxyhydrazino)-6-demethyltetracycline was identified by paper chromatography. 

Twenty-two grams (0.45 mole) of 70% hydrogen peroxide (Note 1) is added dropwise with efficient agitation to a slurry or partial solution of 36.6 g. (0.30 mole) of benzoic acid (Note 2) in 86.5 g. (0.90 mole) of methanesulfonic acid (Note 3) in a 500-ml. tail-form beaker. The reaction temperature is maintained at 25-30° by means of an ice-water bath. The reaction is exothermic during the hydrogen peroxide addition, which requires approximately 30 minutes. During this period the benzoic acid completely dissolves. 

However, when an electron-withdrawing group, e.g., a trifluoromethyl group, is attached to the anilines this procedure is not applicable. A way to circumvent this problem was enlightened by Glasnov et al. [53] who treated the malondianilide 14 with Eaton s reagent, a 7.7% solution of phosphorus pen-toxide in methanesulfonic acid (a. Scheme 6) [54]. This reaction is, however, sensitive to time, temperature, and concentration. More reactive malondian-... 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

Antydrides are also abtained by the reaction of carboxylic acids with N, A -oxa-lyldiimidazole in the presence of methanesulfonic acid.[2] 3... 

Figure 15.5 A trityl-protected pyrrolidine derivative of Cgg can be prepared by the reaction of N-trityl-oxazolidinone with a fullerene. Deprotection of the trityl group using methanesulfonic acid gives the secondary amine, which can be used in further conjugation reactions.

In a similar fashion, 2-cumyladamantane (12, R = Ph) is formed in nearly quantitative yield upon treatment of the easily synthesized 2-cumyl-2-adaman-tanol (11, R = Ph)154 with triethylsilane and methanesulfonic acid in dichloromethane at —78°.155 The high yield of a single very strained hydrocarbon product in each reaction is quite surprising in view of the very complex interconversions of carbocations known to take place from the alcohol precursors.140,151 152 156... 

A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2-10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0° (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3, use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2, attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(/ -nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126129 Triethylsilane may be used as the silane.143... 

BUTANAL, l-d—2-METHYL-, 51, 31 erythro-2,3-Butanediol monomesylate, by reaction of trans-2-butene oxide with methanesulfonic acid, 51, 11 3,5,1,7-[1,2,3,4]Butanetetrayl-naphthalene, decahydro-, 53, 30... 

A nucleophilic attack at an allene system of the type of 417 was described for the first time by Cainelli et al. [172], namely at 444 with the chloride ion as the nucleophile (Scheme 6.91). After the treatment of the mesylate 443 with triethylamine in the presence of lithium, sodium or tetrabutylammonium chloride, mixtures of the vinyl chlorides 445 and 447 were isolated in high yields. Since the reaction did not proceed in the absence of triethylamine, the first step should be a /3-elimination of methanesulfonic acid from 443 to generate 444, which would accept a chloride ion at the central allene carbon atom. A proton transfer to either allyl terminus of the anion thus formed (446) would lead to the products 445 and 447. 

Akermark et al. reported the palladium(II)-mediated intramolecular oxidative cyclization of diphenylamines 567 to carbazoles 568 (355). Many substituents are tolerated in this oxidative cyclization, which represents the best procedure for the cyclization of the diphenylamines to carbazole derivatives. However, stoichiometric amounts of palladium(II) acetate are required for the cyclization of diphenylamines containing electron-releasing or moderately electron-attracting substituents. For the cyclization of diphenylamines containing electron-attracting substituents an over-stoichiometric amount of palladium(II) acetate is required. Moreover, the cyclization is catalyzed by TFA or methanesulfonic acid (355). We demonstrated that this reaction becomes catalytic with palladium through a reoxidation of palladium(O) to palladium(II) using cupric acetate (10,544—547). Since then, several alternative palladium-catalyzed carbazole constructions have been reported (548-556) (Scheme 5.23). 

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