Ethyl /3-toluenesulfonate

From benzylmagnesium chloride and ethyl />-toluenesulfon-ate. Gilman and Beaber, J. Am. Chem. Soc. 47, 518 (1925). 

N -Ethyl-jK-toluidine has been obtained by passing m-toluidine and ethyl alcohol over a catalyst at high temperatures,1 and by the use of ethyl />-toluenesulfonate 2 as an alkylating agent. The present method of purification is a modification of a general procedure for secondary amines developed by Diepolder.3... 

Phenetole 703 Phenol (19 g, 0.2 mole) is dissolved in 3N-sodium hydroxide solution (0.2mole of NaOH), treated with ethyl / -toluenesulfonate (40 g), and heated and stirred under reflux on a boiling water-bath. Further 6N-sodium hydroxide solution (10 ml) was added and the whole heated for a further 30 min. After cooling, the upper, organic, layer was taken up in ether, washed with dilute sodium hydroxide solution, dried, and evaporated. The residue, distilled in a vacuum, gave the ethyl ether (19.2 g, 78.7%), //D20 1.5075. 

The desired sulfonate ester is usually prepared by reaction of the alcohol in pyridine with the appropriate sulfonyl chloride, that is, methanesulfonyl chloride (mesyl chloride) for a mesylate, y)-toluenesulfonyl chloride (tosyl chloride) for a tosylate, or trifluoromethane-sulfonyl chloride [or trifluoromethanesulfonic anhydride (triflic anhydride)] for a triflate. Pyridine (C5H5N, pyr) serves as the solvent and to neutralize the HCI formed. Ethanol, for example, reacts with methanesulfonyl chloride to form ethyl methanesulfonate and with yj-toluenesulfonyl chloride to form ethyl /-toluenesulfonate ... 

Direct, acid catalyzed esterification of acryhc acid is the main route for the manufacture of higher alkyl esters. The most important higher alkyl acrylate is 2-ethyIhexyi acrylate prepared from the available 0x0 alcohol 2-ethyl-1-hexanol (see Alcohols, higher aliphatic). The most common catalysts are sulfuric or toluenesulfonic acid and sulfonic acid functional cation-exchange resins. Solvents are used as entraining agents for the removal of water of reaction. The product is washed with base to remove unreacted acryhc acid and catalyst and then purified by distillation. The esters are obtained in 80—90% yield and in exceUent purity. 

Mixtures of /V-alkylanilines can usually be separated by fractional distillation. Mixtures of the methyl or ethyl derivatives have also reportedly been separated by converting the V/-ethyl or the /V-methyl derivative to the nonvolatile salt with -toluenesulfonic acid (12) or phthaUc anhydride (13), followed by distillation. 

All lation. In alkylation, the dialkyl sulfates react much faster than do the alkyl haHdes, because the monoalkyl sulfate anion (ROSO ) is more effective as a leaving group than a haHde ion. The high rate is most apparent with small primary alkyl groups, eg, methyl and ethyl. Some leaving groups, such as the fluorinated sulfonate anion, eg, the triflate anion, CF SO, react even faster in ester form (4). Against phenoxide anion, the reaction rate is methyl triflate [333-27-7] dimethyl sulfate methyl toluenesulfonate [23373-38-8] (5). Dialkyl sulfates, as compared to alkyl chlorides, lack chloride ions in their products chloride corrodes and requires the use of a gas instead of a Hquid. The lower sulfates are much less expensive than lower bromides or iodides, and they also alkylate quickly. 

Reaction of carboxylate ion with nitrophenyl sulfites gives the carboxylate -nitrophenyl esters. If the -nitrophenyl sulfite is unsymmethcal (02NCgH40S(0)0R, where R is ethyl or phenyl), carboxylate attacks the -nitrophenyl side (69). Some amino acids react with methyl and benzyl sulfites in the presence of -toluenesulfonic acid to give methyl and benzyl esters of the amino acids as -toluenesulfonate salts (70). With alcohols, the conversion of henzil to a monoacetal upon addition of sulfuric acid to the henzil in methanol and dimethyl sulfite proceeds in high yield (71). 

The crude ketal from the Birch reduction is dissolved in a mixture of 700 ml ethyl acetate, 1260 ml absolute ethanol and 31.5 ml water. To this solution is added 198 ml of 0.01 Mp-toluenesulfonic acid in absolute ethanol. (Methanol cannot be substituted for the ethanol nor can denatured ethanol containing methanol be used. In the presence of methanol, the diethyl ketal forms the mixed methyl ethyl ketal at C-17 and this mixed ketal hydrolyzes at a much slower rate than does the diethyl ketal.) The mixture is stirred at room temperature under nitrogen for 10 min and 56 ml of 10% potassium bicarbonate solution is added to neutralize the toluenesulfonic acid. The organic solvents are removed in a rotary vacuum evaporator and water is added as the organic solvents distill. When all of the organic solvents have been distilled, the granular precipitate of 1,4-dihydroestrone 3- methyl ether is collected on a filter and washed well with cold water. The solid is sucked dry and is dissolved in 800 ml of methyl ethyl ketone. To this solution is added 1600 ml of 1 1 methanol-water mixture and the resulting mixture is cooled in an ice bath for 1 hr. The solid is collected, rinsed with cold methanol-water (1 1), air-dried, and finally dried in a vacuum oven at 60° yield, 71.5 g (81 % based on estrone methyl ether actually carried into the Birch reduction as the ketal) mp 139-141°, reported mp 141-141.5°. The material has an enol ether assay of 99%, a residual aromatics content of 0.6% and a 19-norandrost-5(10)-ene-3,17-dione content of 0.5% (from hydrolysis of the 3-enol ether). It contains less than 0.1 % of 17-ol and only a trace of ketal formed by addition of ethanol to the 3-enol ether. 

Ji-Methoxy-ll, 11-ethylenedioxy-lS-methylestra-1,3,5(lO)-tnene. A solution of (+)3-methoxy-18-methylestra-l,3,5(10)-trien-17-one (5 g) dissolved in ethylene glycol (5 ml) and ethyl orthoformate (10 ml) containing />-toluenesulfonic acid (0.3 g) is heated under reflux for 2 hr in a nitrogen atmosphere. The resulting solution is diluted with methylene chloride and washed with dilute sodium bicarbonate and water. The organic phase is dried over sodium sulfate and evaporated to dryness in the presence of a trace of pyridine. Trituration of the residue with petroleum ether yields 4.7 g (82 %) of the pure ketal. 

Androst-4-ene-3,l7-dione 3-Ethylene Thioketal A solution of androst-4-ene-3,17-dione (1.42 g, 5 mmoles) in acetic acid (20 ml) is treated with ethanedithiol (0.47 g, 5 mmoles) and a solution of 0.45 of p-toluenesulfonic acid monohydrate in acetic acid (5 ml). After 1 hr at room temperature, the pale yellow solution is poured into water and the resulting suspension is extracted with chloroform. The chloroform solution is washed with water, 5 % sodium hydroxide solution and water, dried (Na2S04) and evaporated. Chromatography of the resulting oil (1.93 g) over silica gel yields androst-4-ene-3,17-dione bisethylene thioketal, mp 173-175° [0.16 g, eluted with petroleum ether-benzene (1 2)] and androst-4-ene-3,17-dione 3-ethylene thioketal, mp 173-176° [1.38 g (76%), eluted with benzene-ethyl acetate (19 1)]. 

A solution was made of N-benzyl-L-tyrosine (5.7 g, 20 mmols) and N-methylmorphollne (2,04 g, 20 mmols) In 60 ml of THF, at -15°C, and to it was added ethyl chloroformate (2,08 g, 20 mmols), After 12 minutes, p-aminobenzoic acid (2.74 g, 20 mmols) dissolved in 25 ml of THF and 0.38 g of p-toluenesulfonic acid (2 mmols) were added, and the temperature allowed to rise to 5°C. After 2 hours and forty minutes, the mixture was poured into 1 liter of 0,1 N cold HCI, stirred one-half hour, filtered and dried, to give 8,7 g, MP 192°-223°C. The product was recrystallized from 90 ml methanol and 40 ml water, to give 6 g (74%) of product, N-benzoyl-L-tyrosyl-p-amlnobenzoic acid, MP 240°-242°C. 

The lactone is prepared as follows A solution of 5 parts of 17a-carboxyethyl-17/3-hydroxy-androst-4-en-3-one lactone and 5 parts of chloranil in 400 parts of xylene containing a trace of p-toluenesulfonic acid is heated at the boiling point of the solvent under reflux overnight. The solution is then cooled and filtered through approximately 200 parts of silica gel. The gel is successively washed with 5%, 10%, and 15% ethyl acetate-benzene... 

Ethyl p-toluenesulfonate Bretylium tosylate N-ethyl o-toluidine Crotamiton Ethyl undecylenate lophendylate Ethyl urethane Mebuta mate 170 -Ethynyl estradiol Quinestrol... 

Glycine ethyl ester hydrochloride, 14, 46 16, 86 17, 92 Grignard reaction in -butyl ether, 11, 84 with acetaldehyde, 12, 48 with butyl p-toluenesulfonate, 10, 4 with carbon dioxide, 11, 80 with dimethyl sulfate, 11, 66 with ethyl carbonate, 11, 98... 

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