Alcohols methoxide solutions

By oxidizing benzoin in methyl alcoholic sodium methoxide solution by the addition of iodine. Corson and McAllister, J. Am. Chem. Soc. 51, 2822 (1929). 

The sodium methoxide solution is prepared as follows- 203 g. of methyl alcohol, available from Fisher Scientific Company, is placed in a 500-ml., two-necked flask under an inert atmosphere. The flask is equipped with a magnetic stirring bar and a reflux condenser provided with a calcium sulfate drying tube. Freshly cut, clean sodium (23 g., 1 mole) is added in small pieces at such a rate that reflux is maintained. The mixture is stirred until all the sodium has reacted. 

Identification Place about 150 mg of melted sample into a 16- x 125-mm tube equipped with a screw cap having a Teflon liner, and add 4 mL of absolute methanol, 4 drops of a 25% sodium methoxide solution in absolute methanol, and a boiling chip. Cap the tube, reflux for 15 min, and cool to room temperature. Extract as follows Add 8 drops of a 15% potassium acid sulfate solution, 4 mL of water, and 4 mL of n-hexane cap the tube shake for 1 min and centrifuge for 30 to 60 s. Decant and discard the M-hexane layer, and repeat the extraction with three additional 4-mL portions of M-hexane, discarding each extract. Transfer the aqueous alcoholic phase from the tube into a 50-mL round-bottom, glass-stoppered flask place the flask in a water bath at 50° to 55° and evaporate to near dryness (about 0.5 mL of residue) in a rotary film evaporator under full water aspirator vacuum. 

AIM sodium methoxide solution was prepared by adding Na (12.5 mmol) to 12.5 ml methyl alcohol with cooling, tosyl hydrazone (12.25 mmol) added, and the mixture stirred until all solids were dissolved. After stirring an additional 15 minutes the mixture was concentrated and the product ground to a fine powder. Elemental analysis, IR, and H-NMR provided. 

Mannitol from hexa-O-acetylmannitol 71 Anhydrous methanol (20 ml) is poured on hexa-O-acetylmannitol (8 g), the mixture is warmed on a water-bath, and 0.1n sodium methoxide solution (2 ml) is added. Mannitol begins to separate in 3 min. The mixture is evaporated to dryness under reduced pressure, the residue is dissolved in water (5 ml), and to this hot solution anhydrous alcohol (25 ml) is added. On cooling, the mannitol (2.7 g, 80.5 % m.p. 165°) separates. 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

The alcoholysis reaction may be carried out either batchwise or continuously by treating the triglyceride with an excess of methanol for 30—60 min in a well-agitated reactor. The reactants are then allowed to settle and the glycerol [56-81-5] is recovered in methanol solution in the lower layer. The sodium methoxide and excess methanol are removed from the methyl ester, which then maybe fed directiy to the hydrogenolysis process. Alternatively, the ester may be distilled to remove unreacted material and other impurities, or fractionated into different cuts. Practionation of either the methyl ester or of the product following hydrogenolysis provides alcohols that have narrow carbon-chain distributions. 

The reaction is driven to completion by distilling the lower boiling alcohol. Metal methoxides are frequentiy insoluble and caimot be employed as starting materials in this reaction by the same token, they can be convenientiy prepared from solutions of higher alkoxides by precipitation with methanol. Alcoholysis also gives mixed metal alkoxides ... 

The estimation of alkoxy groups is not such a simple task. One method (26,68) involves hydrolysis and oxidation of the Hberated alcohol with excess standard potassium dichromate solution. The excess may then be estimated iodometrically. This method is suitable only for methoxides, ethoxides, and isopropoxides quantitative conversion to carbon dioxide, acetic acid, and acetone, respectively, takes place. An alternative method for ethoxides is oxidation followed by distillation, and titration of the Hberated acetic acid. 

Hydrolysis of the acetate ester with alkali, e.g., sodium methoxide in methanol, affords the free alcohol, 16/3-methyl-1,4,9( 11 )-pregnatriene-17o, 21-diol-3,20-dione. To a suspension of 3 grams of 16/3-methyl-1,4,9(11)-pregnatriene-17o,21-diol-3,20-dione-21-acetate in 40 ml of acetone is added at 0°C with stirring 2 grams of N-chlorosuccinimide and then 7 ml of a perchloric acid solution prepared by dissolving 0.548 ml of 70% perchloric acid in 33 ml of water. The resulting reaction mixture is stirred at 0°C for about 4 hours 45 minutes. 

In 450 cc of methanol is added 47 grams of sodium metal and the mixture allowed to completely react to form a methanol solution of sodium methoxide. The methanol solution of sodium methoxide is then cooled to 60°C and 68 grams of thiourea which has been thoroughly dried is added with stirring until a uniform solution is formed. Thereafter, 157 grams of diethyl allyl-(1-methylbutyl)malonate is added to the solution of the sodio derivative of thiourea at a temperature of 55°C and the condensation reaction mixture maintained at the said temperature for 24 hours. Methyl alcohol is removed under vacuum during the course of the reaction while maintaining a temperature of 55°C. 

Z)-2-Butenylpotassium is generated from 4.5 mL (50 mmol) of (Z)-2-butene, 2.8 g (25 mmol) or /-BuOK. and 10.8 mL (25 mmol) oT 2.3 M butyllithium in THF for 15 min at —45 JC. This solution is cooled to — 78 C and 30 mmol of a 1 M solution of methoxy(diisopinocampheyl)borane in diethyl elher is added dropwise. The mixture is stirred for 30 min at — 78 °C, then is treated with 4mL (33 mmol) of boron trifluoride-diethyl ctherate complex this removes methoxide from the intermediate ate complex. This solution is immediatelv treated with 35 mmol of an afdchyde. Isolated yields of homoallylic alcohols are 63-79%. 

C. 3-n-Heplyl-5-cyanocytosine. In a 250-ml. Erlenmeyer flask are placed 33.8 g. (0.145 mole) of 3-w-heptylureidomethylenemalononitrile and 70 ml. of methanol then 8.5 g. (0.16 mole) of sodium methoxide (Note 6) is added carefully in small portions (Note 7). The resulting solution is allowed to stand at room temperature for 3 days in the stoppered flask. The contents of the flask are dissolved in 300 ml. of cold water in an 800-ml. beaker, and the solution is stirred as 11 ml. of glacial acetic acid is added. The precipitated solid is collected by suction filtration on a Buchner funnel and washed with three 40-ml. portions of distilled water. The undried product is dissolved in 600 ml. of hot ethyl alcohol then the solution is filtered into a 1-1. flask by gravity through a fluted filter paper, concentrated on the steam bath to 200 ml., and cooled in the refrigerator for 4 hours. The 3-w-heptyl-5-cyanocytosine crystallizes in white needles, melts at 192-197° (Note 8), and amounts to 29.7-31.1 g. (88-92%) (Note 9). 

The least powerful method of reduction, boiling nitrobenzene with sodium methoxide in solution in methyl alcohol, provides azoxybenzene in excellent yield (Zinin) the methoxide is converted into formate. (Write the equation.)... 

To 350 cc. of anhydrous methyl alcohol contained in a i-l. three-necked, round-bottomed flask, to which is attached a reflux condenser protected by a drying tube, is added 20 g. (0.87 gram atom) of sodium (Note 1) in large pieces. The reaction is kept under control by cooling the flask in a pan of ice water. To the resulting solution of sodium methoxide is added a solution (Note 2) of 61 g. of hydroxylamine hydrochloride... 

For solutions of the methoxide ion in methanol [17], (p = 0.76 was obtained (More O Ferrall, 1969). This result was later slightly modified to (p = 0.74 (Gold and Grist, 1971) and a value for the solvated proton in methanol [18], (p = 0.625, was also measured. The result for deuterium fractionation was deduced as (p = 0.7 from observations of tritium fractionation (Al-Rawi ei al., 1979) and tp = 0.74 has been obtained more recently (Baltzer and Bergman, 1982). Values for several alkoxide ions in alcohol were used to reach conclusions about the solvation of the alkoxide ions [19] in these solutions (Gold et al., 1982). 

---