Sodium ethoxide ethanol solution

Pyrimido[l,2-c]quinoxaline (381) was treated dropwise with 1 N sodium ethoxide-ethanol solution in dimethyl sulfoxide (DMSO) at ambient temperature for 3 hr to give diethyl (4-quinoxalinylamino)methylenemalonate (382) in 39% yield (81EUP30156). 

According to Sheldon et al. (1986), two molecules of the 2,3-dihydropyrazines can form a mixture of the corresponding pyrazine and 1,2,3,4-tetrahydropyrazine by disproportionation. It was also observed by Masuda et al. (1980) that dehydrogenation of 2,3-dimethyl-5,6-dihydropyrazine generated the disproportionation compounds 2,3-dimethyl-1,2,5,6-tetrahydropyrazine and 5-ethyl-2,3-dimethylpyrazine in addition to the desired 2,3-dimethylpyrazine in a sodium ethoxide/ethanol solution. It was then deduced that the carbanion of 2,3-dimethyl-5,6-dihydropyrazine was formed with the base and then reacted with acetaldehyde, present in ethanol in small quantities, to yield the 5-substituted pyrazine. On the basis of this result the authors prepared in high yield a series of nine, 5-substituted, 2,3-dimethylpyr-azines by reaction of 2,3-dimethyl-5,6-dihydropyrazines with six aldehydes and three ketones under the same basic conditions. 

The flask is flushed with dry nitrogen, and 200 ml. (3.40 mols) of anhydrous ethanol is added. Twelve grams (0.522 mol) of clean sodium metal, cut into small pieces, is then rapidly added to the ethanol. Reaction occurs immediately. The flask is closed and the reaction allowed to continue. The reaction mixture is stirred and heated so that the ethanol refluxes. This serves to speed up the reaction and to increase the solubility of the product, sodium ethoxide. The excess ethanol is necessary to keep the sodium ethoxide in solution. 

To a solution of NaOEt prepared from 0.11 g sodium (4.7 mmol) and 10 mL absolute ethanol, cooled in an ice bath, was added in rapid succession 0.88 g methyl 2-chloro-6-hydroxybenzoate (4.7 mmol) and a solution of 1.14 g A-4-methoxyphenylbenzimidyl chloride (4.7 mmol) in 30 mL dry ether. The reaction mixture was shaken vigorously, whereupon a precipitate of sodium chloride began to form. The mixture was allowed to stand at room temperature for 48 h, the solvent was evaporated, and the residue was diluted with water. The resulting oily solid was removed by extraction with ether, the ethereal solution was dried, and the ether was distilled. The crude imido ester was heated in a nitrogen atmosphere at 210-215 C for 70 min, then dissolved in 10.8 mL ethanol the alcoholic solution was diluted with 5.4 mL water and 5.4 mL of a 1 M ethanolic sodium ethoxide. The solution was refluxed for 1.5 h, the alcohol was evaporated on a steam bath, and the aqueous solution was acidified with dilute HCl. The dark oil that formed was separated by decantation, and the crude benzoate of the substituted anthranilic acid was dissolved in 22 mL ethanol. A solution of 7.2 g sodium hydroxide in 7.2 mL water was added, and the mixture was refluxed for 1 h. The alcohol was evaporated, and the solution was then acidified. The brown solid was extracted exhaustively with boiling water to remove the benzoic acid, and the remaining brown solid was recrystallized from aqueous ethanol. The yellow needle-like crystals of A-(4 -methoxyphenyl)-6-chloroanthranilic acid, in a total amount of 0.36 g, was obtained, in a yield of 27.7%, m.p., 139.5-140.5°C (dec). 

Mono and Di-iubstitution Derivatives. The enolic sodium derivative of ethyl acetoacetate (E) is prepared by mixing ethanolic solutions of the ester and of sodium ethoxide. It should not be prepared by the direct action of metallic sodium on the ester, as the reaction is slow and the nascent hydrogen evolved reduces some of the ester to ethyl p4iydroxy- butyrate, CH3CH(OH)CHjCOOEt. 

Substitution Derivatives of Ethyl Malonate, Ethyl malonate resembles ethyl acetoacetate in that it gives rise to mono- and di-substituted derivatives in precisely similar circumstances. Thus when ethanolic solutions of ethyl malonate and of sodium ethoxide are mixed, the sodium derivative (A) of the enol form is produced in solution. On boiling this solution with an alkyl halide, e.g, methyl iodide, the methyl derivative (B) of the keto form is obtained. When this is treated again in ethanolic solution with sodium ethoxide, the... 

Place 30 ml. of ethanol in a 200 ml. conical flask fitted to a reflux water-condenser, and then add 1-4 g. of sodium cut into small pieces. The sodium rapidly dissolves to give a solution of sodium ethoxide, the ethanol boiling under the heat of the reaction. When the sodium has completely dissolved, detach the flask and cool it in ice-water. 

While the sodium ethoxide solution is cooling, prepare a solution of 7 7 g. of finely powdered iodine in 60 ml. of ether. When this solution is ready, add 9 ml. (9 6 g.) of ethyl malonate to the ethanolic sodium ethoxide solution, mix w ell and then allow to stand for 30-60 seconds not longer) then cautiously add the ethereal solution of the iodine, mixing thoroughly during the addition in order to avoid local overheating by the heat of the reaction. (If, after the ethyl malonate has been added to the sodium ethoxide, a considerable delay occurs before the iodine is added, the yield of the final product is markedly decreased.)... 

On being heated with a solution of sodium ethoxide in ethanol compound A (CyHisBr) yielded a mixture of two alkenes B and C each having the molecular formula C7H14 Catalytic hydrogenation of the major isomer B or the minor isomer C gave only 3 ethylpentane Suggest structures for compounds A B and C consistent with these observations... 

Benzhydryloxy ethoxy diphenyl silane (2). To a solution of benzoyl triphenylsilane 1 (2.5 g, 6 9 mmol) in benzene (25 mL) was added a solution of sodium ethoxide in ethanol (2 mL, 0 S mmol). The solution changed colour and after 11 min laded airmst completely. The solution was washed with water and the solvent removed in vacuum. The oily residue was dissolved in hot ethanol (15 mL) and cooled to give 2 (2 1 g, 74%), np 67-75 C Recrystallizatlon from ethanol gave 1 8 g (64%). mp 77-78,C... 

The phenol (Imol) in 5% aqueous NaOH is treated (while cooling) with benzoyl chloride (Imol) and the mixture is stirred in an ice bath until separation of the solid benzoyl derivative is complete. The derivative is filtered off, washed with alkali, then water, and dried (in a vacuum desiccator over NaOH). It is recrystalUsed from ethanol or dilute aqueous ethanol. The benzoylation can also be carried out in dry pyridine at low temperature ca 0°) instead of in NaOH solution, finally pouring the mixture into water and collecting the solid as above. The ester is hydrolysed by refluxing in an alcohol (for example, ethanol, n-butanol) containing two or three equivalents of the alkoxide of the corresponding alcohol (for example sodium ethoxide or sodium n-butoxide) and a few ca 5-10) millilitres of water, for half an hour to three hours. When hydrolysis is complete, an aliquot will remain clear on dilution with four to five times its volume of water. Most of the solvent is distilled off. The residue is diluted with cold water and acidified, and the phenol is steam distilled. The latter is collected from the distillate, dried and either fractionally distilled or recrystalUsed. 

A solution of sodium ethoxide is prepared from sodium (0.1 g) and 10 ml ethanol. This solution is then added to a solution of ethyl 5a-cholestan-3)8-ol 2a-xanthate (0.57 g, 1.12 mmol) in 25 ml ethanol. The reaction flask is... 

To an ethanolic solution of sodium ethoxide prepared by addition of 0.46 g (0.02 mole) of freshly cut sodium metal in 100 mL of absolute ethanol was slowly added 5.10 g (0.02 mole) of ethyl 4-nitrobenzylthioacetate 28 with stirring at 5°C. The mixture was refluxed for about 4 to 6 hours until the reaction was complete (monitored by tic). The resultant mixture was allowed to cool to room temperature and then added into an ice-water mixture. The solution was neutralized with slow addition of dilute aqueous hydrochloric acid (10%). The precipitated solid was removed by filtration, washed with water, and recrystallized from a dimethylformamide-ethanol (T.l) mixture yielding 2.10 g (76 %) of 29 as a light brown crystalline solid, mp 227°C ir (nujol) (neat (1710 cm ms m/z Til (NT). Anal. Calcd. For C13H11NO4S C, 56.31 H, 3.97 N, 5.05 S, 11.55. Found C, 56.36 H, 3.95 N, 5.01 S, 11.49. 

I. 2,5-Dicarbethoxy-1,4-cyclohexanedione (7) A 500-ml, three-necked, round-bottom flask is fitted with a condenser (drying tube) and arranged for magnetic stirring. A solution of sodium ethoxide is prepared in the flask by the addition of sodium (9.2 g, 0.4 g-atom) in small pieces to 90 ml of absolute ethanol. The mixture is heated at reflux for 3 hours (oil bath) to complete the reaction. Diethyl succinate (34.8 g, 0.2 mole) is added to the hot solution in one portion exothermic ) and the mixture is refluxed for 24 hours. (A pink precipitate forms and persists during the reflux.)... 

The quaternary salt is now treated with ethoxide ion in the presence of cinnamalde-hyde so that the ylide reacts in situ as it is produced. A solution of sodium ethoxide is prepared by slowly adding 0.75 g of sodium metal to 100 ml of absolute ethanol in a dry Erlenmeyer flask (hood). In a second flask, the phosphonium chloride is dissolved in 150 ml of absolute ethanol, cinnamaldehyde (2.9 g) is added and the flask is swirled while the ethoxide solution is added a transient orange-red color indicates the formation of the ylide. 

This ester (70 g) and diethyl carbonate (250 mg) were stirred at 90°C to 100°C while a solution of sodium ethoxide [from sodium (7.8 g) and ethanol (1 54 ml)] was added over 1 hr. During addition, ethanol was allowed to distill and after addition distillation was continued until the column heat temperature reached 124°C. After cooling the solution to 90°C, dimethyl sulfate (33 ml) was followed by a further 85 ml of diethyl carbonate. This solution was stirred and refluxed for 1 hr and then, when Ice cool, was diluted with water and acetic acid (10 ml). The malonate was isolated in ether and fractionally distilled to yield a fraction boiling at 148°C to 153°C/0.075 mm, identified as the alpha-methyl malonate. This was hydrolyzed by refluxing for 1 hr at 2.5N sodium hydroxide (350 ml) and alcohol (175 ml), excess alcohol was distilled and the residual suspension of sodium salt was acidified with hydrochloric acid to give a precipitate of the alpha-methyl malonic acid. This was decarboxylated by heating at 180°C to 200°Cfor 30 minutes and recrystallized from petroleum ether (BP 80°C to 100°C) to give 2-(2-fluoro-4-biphenylyl)propionic acid, MP 110°C to 111°C. 

In an initial step, the sodium derivative of ethyl (3-benzoylphenyl)cyanoecetate is prepared as follows (3-benzoylphenyl)acetonitrile (170 g) is dissolved in ethyl carbonate (900 g). There is added, over a period of 2 hours, a sodium ethoxide solution [prepared from sodium (17.7 g) and anhydrous ethanol (400 cc)], the reaction mixture being heated at... 

A. 2-Methyl-4-eihoxalylcyclopenlane-l,3,5-trione. A solution of sodium ethoxide is prepared in a 2-1. three-necked, round-bottomed flask fitted with a mercury-sealed stirrer, a reflux condenser carrying a drying tube, and a stopper by the addition of 69.0 g. (3 moles) of sodium to 950 ml. of absolute ethanol. The solution is cooled to 0-5° in an ice bath and stirred. The stopper is replaced by a dropping funnel, and a cold mixture (5-15°) of 108 g. (1.50 moles) of freshly distilled 2-butanone and 482 g. (3.30 moles) of diethyl oxalate (Note 1) is added gradually over a... 

Dimethyl 4-ethoxy-2,7-dimethyl-4,5-dihydro-l 7/-azepine-3,6-dicarboxylate (1) with sodium ethoxide in refluxing diethyl ether, or on standing at room temperature in carbon tetrachloride solution, readily loses ethanol to yield dimethyl 2,7-dimethyl-4//-azepine-3,6-dicar-boxylate (2).29 The 4-methoxy derivative is also unstable and on warming at 100 C under reduced pressure loses methanol to yield the same product (44%).120... 

The sodium ethoxide solution is preptired from the reaction of 9.2 g. (0.40 mole) of sodium with 11. of absolute ethanol and is standardized by titration with aqueous 0.1 N hydrochloric acid. The appropriate volume of the solution to give 0.280 mole of base is used. 

It is important to maintain strictly anhydrous conditions throughout this reaction. The equipment should be carefully predried and the absolute ethanol freshly prepared (preferably by the magnesium ethoxide method2) and distilled directly into the reaction flask. If the volume of ethanol is less than 2.5 1. the sodium ethoxide may not remain in solution. It is convenient to employ a three-necked flask carrying two condensers for this operation and to add the sodium through the third neck, which is otherwise kept stoppered. 

For the preparation of methyl orthoformate, solid sodium methoxide, methanol and chloroform were mixed together. The mixture boiled violently and then exploded [1]. The analogous preparation of ethyl orthoformate [2] involves the slow addition of sodium or sodium ethoxide solution to a chloroform-ethanol mixture. The explosion was caused by the addition of the solid sodium methoxide as one portion. See Sodium, etc., above... 

An alcoholic solution of sodium ethoxide is prepared in a 1-1. round-bottomed flask from 15.5 g. (0.67 gram atom) of sodium and 300 ml. of absolute ethanol (Note 1). One hundred thirty-three grams (0.64 mole) of phenylmethylglycidic ester (p. 82) is then added to this solution slowly and with shaking. The flask is then cooled externally to 15°, and 15 ml. of water is slowly added considerable heat is evolved, and the sodium salt soon begins to separate. After the mixture has stood overnight, the salt is filtered by suction and rinsed with one 50-ml. portion of alcohol and a similar amount of ether. The dried salt weighs 102-108 g. (80-85%) and melts at 255-256° with decomposition. 

The phosphonyl adduct 300 reacted with a dilute solution of anhydrous hydrogen chloride in ethanol or with sodium ethoxide to afford an essentially quantitative yield of the P-N cleaved product 304 with inversion of configuration. Addition of sodium ethoxide to a solution of 304 in methanol resulted in the formation of enantiomerically pure (+)-(.V)-ethyl methyl phenylphosphonate (305). It also reacted quantitatively with methylmagnesium iodide at room temperature to give the product of P-S bond cleavage 306, which upon acid catalyzed methanolysis afforded enantiomerically pure (+)-(R)- methyl methylphenylphosphinate (307) (Scheme 72) [108],... 

Addition of sodium hydride (NaH) to ethanol produces a solution of sodium ethoxide (CH3CH2ONa) in ethanol. 

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