Absolute methanol

When a solution of a diazonium compound in absolute methanol is boiled, the chief product is the corresponding methyl ether, henzenediiizonium hydrogen sulphate thus giying methyl phenyl etlier or anisole ... 

In view of the high cost of methyl iodide in the above preparation of anisole, and the fact that, unless absolute methanol is used, the ready hydrolysis of the methyl iodide may cause a low yield of the ether, the preparation of anisole may be ad antageously replaced by that of phenetole. I he reaction is not of course a methylation, but is nevertheless of the same type as that used in the preparation of anisole. 

If the ester does not yield a benzylamide by this procedure, convert it into the methyl ester by refiuxing 1 g. for 30 minutes with 5 ml. of absolute methanol in which about 01 g. of sodium has been dissolved. Remove the methanol by distillation and treat the residual ester as above. 

Sebacic acid. Dissolve 40 g. of methyl hydrogen adipate in 100 ml. of absolute methanol to which 01 g. of sodium has been added. Pass a current of about 2 0 amps, until the pH of the solution is about 8 (ca. 5 hours) test with B.D.H. narrow-range indicator paper. Transfer the contents of the electrolysis cell to a 500 ml. round-bottomed flask, render neutral with a little acetic acid, and distil off the methanol on a water... 

Reflux 6 8 g. of the dimethyl ester with a solution of 3 2 g. of sodium hydroxide in 150 ml. of 80 per cent, methanol for 2 hours on a water bath. When cold, filter oflF the solid and wash it with a little cold methanol. Dissolve the solid in 350 ml. of warm water, add concentrated hydrochloric acid to the solution at 60° until acidic to litmus, filter off the precipitated acid, wash with a little water and dry at 100°. The resulting hexadecane-1 16 dicarboxylic acid, m.p. 122°, weighs 5-3 g. Recrystallisation from absolute methanol raises the m.p. to 124 -5°. 

Myristic acid from hexanoic acid and methyl hydrogen sebacate). Dissolve 23 -2 g. of redistilled hexanoic acid (re caproic acid), b.p. 204-6-205-5°/760 mm., and 21-6 g. of methyl hydrogen sebacate in 200 ml. of absolute methanol to which 0 13 g. of sodium has been added. Electrolyse at 2 0 amps., whilst maintaining the temperature between 30° and 40°, until the pH is about 8 0 (ca. 6 hours). Neutralise the contents of the electrolysis cell with a little acetic acid and distil off the methyl alcohol on a water bath. Dissolve the residue in 200 ml. of ether, wash with three 50 ml. portions of saturated sodium bicarbonate solution, once with water, dry with anhydrous magnesium sulphate, and distil with the aid of a fractionating column (see under Methyl hydrogen adipate). Collect the re-decane at 60°/10 mm. (3 0 g.), the methyl myristate at 158-160°/ 10 mm. (12 5g.) and dimethyl hexadecane-1 16-dicarboxylate at 215-230°/ 7 mm. (1 -5 g.)... 

Methylation with diazomethane may be carried out as follows (FUME CUPBOARD )-. Dissolve 2-3 g. of the compound (say, a phenol or a carboxylic acid) in a little anhydrous ether or absolute methanol, cool in ice, and add the ethereal solution of diazomethane in small portions until gas evolution ceases and the solution acquires a pale yellow colour. Test the coloured solution for the presence of excess of diazomethane by removing a few drops into a test-tube and introducing a glass rod moistened with glacial acetic acid immediate evolution of gas should... 

A commercial grade of methanol was used absolute methanol did not result in an increased yield. 

Acriflavine [8048-52-0] M 196.2, pK >12. Treated twice with freshly ppted AgOH to remove proflavine, then recrystd from absolute methanol [Wen and Hsu J Phys Chem 66 1353 1962]. 

To a solution of methyl 3-oxobutanoate 127 (580 mg, 5 mmol) and l-methyl-2-methylthio-l//-imidazole-5-carboxaldehye 128 (390 mg, 2.5 mmol) in 5 mL of absolute methanol was added a solution of ammonium hydroxide (25%, 0.4 mL). The reaction was heated at reflux overnight before cooling to room temperature and removing the solvent. The crude product was purified by preparative TLC to afford 526 mg of dimethyl l,4-dihydro-2,6-dimethyl-4-(l-methyl-2-methylthio-5-imidazolyl)-3,5-pyridine-dicarboxylate 129 (60%) as a solid, mp = 200-201 °C (MeOH). 

Equimolar amounts (0.5 mmol) of 130 and 95 in 5 mL of absolute methanol were heated at 100°C for 24 h. The reaction was cooled to room temperature and the solvent removed. The crude product was recrystallized from methanol to afford 131 in 98% yield (mp = 125-126°C). 

Other workers have obtained higher yields of phenylethanol is absolute methanol the 90% yield reported above was probably due to traces of residual acid remaining from the catalyst preparation. Note that hydrogenolysis with this catalyst can be prevented completely by traces of base addition of base is often a useful means of preventing or minimizing unwanted hydrogenolysis in a variety of systems. 

A suspension of 37.3 g (0.1 mol) of 7/3-amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride dioxanate in 500 ml methylene chloride is stirred for 15 minutes at room temperature under an argon atmosphere and treated with 57.2 ml (0.23 mol) of bis-(trimethylsilyl)-acetamide. After 45 minutes the faintly yellow slightly turbid solution is cooled to 0°C and treated within 10 minutes with 31.2 g (0.15 mol) of D-Ct-amino-Ct-d, 4-cyclohexadienyl (acetyl chloride hydrochloride. Thirty minutes thereafter 15 ml (about 0.21 mol) of propylene oxide is added and the mixture is further stirred for 1 hour at 0°C. A cooled mixture of 20 ml of absolute methanol in 200 ml of methylene chloride is added within 30 minutes, after another 30 minutes the precipitate is filtered off under exclusion of moisture, washed with methylene chloride and dried under reduced pressure at room temperature. The obtained hygroscopic crystals of the hydrochloride of 7j3-[D-a-(1,4-cyclohexadienyl)acetylamino] -... 

To a refluxing solu tion of 100 g of allyl urea and 600 ml of absolute methanol there was added with stirring a suspension of 319 g of mercuric acetate and 600 ml of absolute methanol and 60 ml of glacial acetate acid complete solution resulted. After 6 hours of refluxing, the solution was cooled and clarified by filtration. To this solution there were added 50 g of sodium chloride and 240 ml of water. After a short time a heavy white precipitate settled out. This precipitate, which wes3-chloromercuri-2-methoxy-propylurea, was filtered, washed and dried. 

The free base was then dissoived in absolute methanol, and the resulting solution was then adjusted to an acid pH value with an ethereal hydrochloric acid solution. The acidified solution was purified with charcoal and then dry ether was added thereto until crystallization took place. The hydrochloride, prepared in this customary manner, had a melting point of 305°C according to U.S. Patent 3,202,660. 

A small amount of undissolved material collected on the filter and it was washed with chloroform. The chloroform solution (filtrate plus washings) was washed three times with ice-water, twice with ice-cold 3N sulfuric acid, twice with ice-cold saturated aqueous sodium bicarbonate solution, twice with ice-water, and then dried over anhydrous sodium sulfate. The chloroform was removed under reduced pressure at a bath temperature of about 40°C, leaving a yellow, somewhat gummy residue. This yellow residue was dissolved in absolute methanol which was then evaporated at reduced pressure at about 40°C, and the residue was then held for 2 hours at 0.5 to 2.0 mm pressure and a bath temperature of about 50°C. There was thus obtained 1.69 g of T(2,3,5-tri-0-acetyl-(3-D-arabinofuranosyl)-4-thiouracil. 

B) Preparation of 1-0-D-Arabinofuranosylcytosine In a glass liner, a mixture of 1.16 g (3.0 mmol) of 1-(2,3,5-tri-0-acetyl-(3-D-arabinofuranosyl)-4-thiouracil prepared in (A) and about 60 ml of absolute methanol which had been saturated with anhydrous ammonia at 0°C was heated in a steel bomb at 98° to 105°C for 35 hours. After cooling to about 25°C and venting the bomb, the dark solution was filtered into a round-bottom flask. The methanol and excess ammonia were then removed under reduced pressure at about 25°C. The residual syrup was dissolved in absolute methanol, and the methanol was removed under reduced pressure at a bath temperature of about 40°C. This procedure of dissolving in absolute methanol and removing the solvent was repeated, and the residue was held under reduced pressure at a bath temperature of 45°C for 12 hours. 

The resulting semisoiid was triturated thoroughly with absolute methanol, and the resulting suspension was chilled at 0°C. A pale tan solid that separated was collected on a filter and washed repeatedly with methanol. After washing with anhydrous ether, there was obtained 430 mg of 1-(3-D-arabinofuranosylcytosine. 

The pale yellow product was dissolved in warm, absolute methanol, and the solution after mixing with decolorizing charcoal was filtered through a bed of filter aid. The filter bed was washed with warm absolute methanol, and the combined methanolic filtrate and... 

A mixture of 103.6 grams (0.6 mol) of the freshly prepared potassium enolate of ethyl fluoromalonaldehydate, 83.4 grams (0.3 mol) of S-methylisothiouronium sulfate and 32.5 grams (0.6 mol) of sodium methoxide was refluxed with stirring in 1,500 ml of absolute methanol. At first the reactants dissolved to a great extent, but very shortly thereafter precipitation occurred. The reaction mixture was refluxed for 2 hours and at the end of this time was evaporated to dryness in vacuo. The residue was treated with 280 ml of water incomplete dissolution was observed. 

Bi Methylation of 8-Hydroxypsoralen 115 mg of 8-hydroxypsoralen was dissolved in 10 ml absolute methanol, an excess of diazomethane dissolved in ether was added and the mixture allowed to stand at room temperature with occasional stirring for 3 hours. The next day the reaction mixture was reduced in volume to 3 ml by evaporation on the steam bath and the concentrate was held in a refrigerator overnight. The next day, fine needles (80 mg) of 8-methoxypsoralen were filtered from the solution. The compound had a MP of 145° to 146°C and was obtained in a yield of 65% of theory. 

Sodium methylete is mede by dropping 11.7 g of sodium strips into 199 ml of absolute methanol in a 1-liter three-necked flask. 93.9 g of o-benzylphenol ere dissolved in 200 ml of dry toluene end added to the sodium methylete solution. The solution is distilled until the boiling point of toluene is reached. At the end of the distillation, enough toluene is added to restore the original volume of solvent. 

This was dissolved in 550 ml of absolute benzene and the so-formed solution added to a mixture of 248 ml of absolute methanol and 550 ml of absolute benzene. After the exothermic reaction had terminated, the reaction mixture was boiled for a further 20 hours, then concentrated in vacuo and the product, 4-methylbenzoic acid methyl ester, isolated by conventional means. It could be purified by distillation, and the purified product boiled at 91°C/9 mm Hg, MP 32°C. 

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