Ethanol, absolute, preparation reactions

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. 

Preparation of Diethyl Allyl (l-Methyl-2-Pentynyl) Malonate A solution of 12.1 g of sodium in 182 ml of absolute ethanol was prepared, and thereto were added 126.6 g of diethyl (l-methyl-2-pentynyl) malonate. Most of the ethanol was then distilled off under reduced pressure, and the residue was cooled and 63.5 g of allyl bromide were slowly added thereto. After completion of the addition, the mixture was refluxed for about 1 hour. The reaction mixture was cooled, treated with about 100 ml of water, and the oily organic layer which formed was removed, washed with water and dried over anhydrous magnesium sulfate. The dried oily organic material was fractionally distilled in vacuo, and diethyl allyl (l-methyl-2-pentynyl) malonate boiling at 105° to 107°C at the pressure of 1 mm of mercury was recovered. 

It is necessary to maintain strictly anhydrous conditions in this reaction. The apparatus should be carefully predried and the absolute ethanol freshly prepared either by the diethyl phtha-late method 2 or by the magnesium ethoxide method.3... 

It may be prepared by the condensation of [2-(phenylsulfinyl) ethyl]- malonic acid diethyl ester with hydrazobenzene in the presence of sodium ethoxide in absolute ethanol. Completion of reaction is achieved by the addition of xylene and subsequent heating at about 130°C whereby the ethanol liberated as a produet of eondensation is removed eompletely. The crude product is extracted with a suitable solvent and finally recrystallized from ethanol. 

A solution of 5.0 g. of shiny K in 72 ml. of carefully dehydrated ethanol is prepared in a round-bottom flask equipped with a reflux condenser and a drying tube. After the evolution of Hg ends, exactly half the solution is decanted and is saturated with HgS (in the absence of atmospheric moisture) in the manner described for NaHS. Excess HgS is removed by brief boilii in a stream of Ng or Hg. The two portions of the solution are then recombined in the original reaction flask. This K S solution is then mixed with 4.1 g. of pure S and boiled for 30 minutes orar e-yellow KgSg crystals separate. These are quickly suction-filtered in a fast Hg or Ng stream, washed with absolute ethanol, and freed of adhering solvent in a vacuum desiccator over PgOg. 

The independent preparation of potassium phthabmide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75 per cent, ethanol) may be avoided in many cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The N-substituted phthalimide (I) is frequently cleav with difficulty this is often facilitated by reaction with hydrazine hydrate to give an intermediate product, which is easily decomposed by hydrochloric acid to 3deld the insoluble hydrazide of phthaUc acid (II) and the primary amine (III) ... 

Girard s reagent P , C5H5NCH2C0NHNH2 C1. In a 1-htre threenecked flask, equipped as in the previous preparation, place 200 ml. of absolute ethyl alcohol, 63 g. (64 -5 ml.) of pure anhydrous pyridine and 98 - 5 g. (84 5 ml.) of ethyl chloroacetate. Heat the mixture under reflux for 2-3 hours until the formation of the quaternary salt is complete acidify a small test-portion with dilute sulphuric acid it should dissolve completely and no odour of ethyl chloroacetate should be apparent. Cool the mixture in ice and salt. Replace the thermometer by a dropping funnel, and add a solution of 40 g. of 100 per cent, hydrazine hydrate in 60 ml. of absolute ethanol all at once. A vigorous exothermic reaction soon develops and is accompanied by vigorous effervescence. The pro duct separates almost immediately. When cold, filter with suction, wash... 

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.)... 

Ir. the second step, the diethylaminoethyl 2-chloro-4-aminobenzoate hydrochloride is prepared by refluxing equimolar proportions of the hydrochloride of (3-diethylaminoethanol in a suitable inert solvent such as a mixture of dry toluene and tetrachloroethane and the hydrochloride of 2-chloro-4-aminobenzoyl chloride until the reaction as indicated by the cessation of hydrogen chloride evolution is complete. The supernatant solvents are decanted from the reaction product which can be conveniently purified by crystallization from absolute ethanol. 

A solution of 151 grams of 1-(3, 4 -dimethoxyphenyl)-2-propanone oxime in 200 cc of absolute ethanol is treated with 5 grams of Raney nickel catalyst and ammonia in an autoclave at about 25 atm of pressure and at 75 -100°C. The reduction is complete in about one-half hour and the reaction mixture is filtered and fractionated under reduced pressure to recover the a-methylhomoveratrylamine formed by the reduction. a-Methylhomoveratryl-amine thus prepared boiled at 163°-165°C at 18 mm pressure. 

Preparation of Diethyl (1-Methyl-2-Pentynyl) Malonate To a solution of 2B.6 g of sodium in 430 ml of absolute ethanol were added 200 g of diethyl malonate. About half of the alcohol was removed by distillation in vacuo, and thereafter a solution of 200 g of 2-bromo-3-hexyne in 100 ml of anhydrous ether was added slowly to the reaction mixture. 

C) Preparation of 6-Allyl-7-Hydroxy-4,8-Dimethylcoumarin 7-Allyloxy-4,8-dimethyl-coumarin (195.0 g, 0.84 mol) was heated (oil bath) to 215 4°C (reaction mixture temperature) for 3 hours and was then poured into absolute alcohol (ca 1.5 liters). Activated carbon (Norite) (19.5 g) was added, and the solution was heated to boiling, filtered, and diluted with excess water (ca 12 liters). The product was collected by filtration and partially dried at 70°C for 6 hours. 6-Allyl-7-hydroxy-4,8-dimethylcoumarin was obtained as pale yellow microcrystalline prisms, MP 166° to 168°C, by two recrystallizations from aqueous ethanol of a portion of the partially dried solid. The remaining partially dried solid was used in the next step. 

E. Quench and purification. While the butyllithium addition is taking place, an acidic ethanol quench solution is prepared in a 3-L, two-necked, round-bottomed flask, equipped with a mechanical stirrer and a 250-mL, pressure-equalizing dropping funnel. The flask is charged with 1 L of absolute ethanol and the funnel with 250 mL of acetyl chloride. The ethanol is stirred rapidly and the flask is cooled with an ice bath as the acetyl chloride is added over a 30-40-min period and then the cooling bath is removed and stirring is continued for 20-30 min. After the main reaction mixture has been stirred for 30 min at room temperature, it is cooled with a dry ice-acetone bath. The acidic ethanol solution is cooled with an ice bath and the cold, main reaction mixture is quenched by addition (via a double-ended needle) into the rapidly stirred, cold, acidic ethanol solution over a 3 to 3.5 hr period (Note 16). 

A. Z,5-DicaThelhoxy-l,4-cyclohexanedione. A solution of sodium ethoxide is prepared by adding small pieces of sodium (92 g., 4 g. atoms) as rapidly as possible to 900 ml. of commercial absolute ethanol contained in a 3-1., three-necked, round-bottomed flask equipped with two stoppers and a reflux condenser fitted with a drying tube packed with calcium chloride and soda lime. The reaction is completed by heating the mixture under reflux for 3-4 hours (Note 1). To the hot solution is added diethyl succinate (348.4 g., 2 moles) (Note 2) in one portion Caution Exothermic reaction), and the mixture is heated under reflux by maintaining the original bath temperature for 24 hours. A thick pink-colored precipitate is formed almost immediately and remains throughout the reaction. 

Diphenyl telluropyran-4-one (typicalprocedure)7° 120 mL (0.12 mol) of a 1.0 M solution of lithium triethylborohydride in tetrahydrofuran are added to 7.65 g (60 mmol) of powdered tellurium under nitrogen, and the mixture stirred at 20°C for 4 h. A solution of sodium ethoxide (prepared from 5.52 g (0.24 mol) of sodium and 240 mL of absolute alcohol) is added to the dilithium telluride, 13.8 g (60 mmol) of bis(phenylethynyl) ketone are dissolved in a mixture of 150 mL of tetrahydrofuran and 150 mL of 1 M sodium ethoxide in ethanol this solution is poured as quickly as possible into the deep-purple-coloured dilithium telluride soluhon. The flask containing the reaction mixture is immediately placed in a water bath at 50°C and the temperature slowly increased over 30 min until ethanol begins to condense on the side of the flask. The water bath is removed and the mixture is stirred overnight at 20°C. Dichloromethane (400 mL) is then added, the resultant mixture is washed with 800 mL of water, and the organic phase is separated and concentrated to an oil. The oil is dissolved in 600 mL of dichloromethane, and the solution is filtered through a pad of sand. The filtrate is washed with 200 mL of 2% aqueous sodium chloride soluhon, dried with anhydrous sodium sulphate, filtered and evaporated. The brownish solid residue is triturated with 20 mL of butanenitrile and the fine yellow solid is collected by filtration yield 10.9 g (51%) m.p. 126-129°C (from acetonitrile). 

Type (ii) cyclizations are more common. Thus, acid derivatives of pyrrolo[l,2-f>]-[l,2,5]benzothiadiazepine 5,5-dioxide 346 and 347 have been prepared from amino sulfonyl pyrrole 345 with acetal (2006JMC5840) or the semiacetal (1994JHC867) of ethyl glyoxalate or ethyl 2,2-diethoxy propionate (1996FES425) in the presence of PTSA catalyst in boiling absolute ethanol by a Pictet-Spengler type of reaction (Scheme 73). 

Preparation of nitrile acetates from oximes with sodium acetate and acetic anhydride. Pentaacetyl-v-glucononitrile. If only the nitrile is needed, isolation of the oxime can be avoided. One hundred grams of anhydijous n-glucose was dissolved in 50 ml. of warm water, and maintaining the temperature at 60°, a solution of 28 g. of hydro-xylamine in 700 ml. of ethanol was added sufficiently slowly that no precipitation took place. After one hour at 65°, the reaction mixture was concentrated under reduced pressure to a thick sirup. The residue was mixed with absolute ethanol, the ethanol evaporated and the operation repeated in order to eliminate all water. One hundred and twenty grams of anhydrous sodium acetate and 700 ml. of acetic anhydride were added to the sirup, and the mixture was slowly and cautiously warmed in a water bath to 95°. It was advisable to agitate the flask continuously and to watch the... 

The analogous reaction to that described in Equation (42) using paraformaldehyde in equimolar amount to dimedone (instead of a large excess) was irradiated for 3 min to yield pyrimido[4,5- ]quinoline-4,6-dione 591 via formation of intermediate adduct 590 <2006TL27>. The 5-aryl-5,6,7,8,9,10-hexahydropyrimido[4,5-/ ]quinolines 592 were also prepared by the cyclocondensation reaction of 6-aminopyrimidine 460 with dimedone and 4-sub-stituted benzaldehydes by boiling in absolute ethanol for 30 min <1998JHC231>. 

A solution of sodium ethoxide is prepared under nitrogen from 70 g. (3.04 gram atoms) of sodium and 2-1. of absolute ethanol (Note 1) in a 3-1. three-necked flask which is equipped with mechanical stirrer, efficient reflux condenser, dropping funnel, and a thermometer which dips below the level of the liquid in the flask. Chloropicrin (100 g., 0.61 mole) (Note 2) is placed in the dropping funnel, and the stirred solution is heated to 58-60° with a water bath. The chloropicrin is added at a rate of 30-35 drops per minute until the reaction becomes self-sustaining (about 20 minutes), at which point the water bath is removed and the balance of the chloropicrin is added at a rate sufficient to maintain the temperature at 58-60° (Note 3). When the addition, which requires nearly 2 hours, is complete, the stirrer is stopped and the mixture is allowed to stand overnight. 

The apparatus used is shown in Fig. 2 (Note 1). A solution of sodium ethoxide prepared by dissolving 2.5 g. of clean sodium metal (0.11 gram atom) in 230 g. (292 ml., 5 moles) of absolute ethanol under anhydrous conditions is added to the reaction tube C. The tube C thus charged is weighed, and placed in position with the gas inlet tube, fitted with fritted-glass dispersion cylinder D, extending nearly to the bottom. Several inches of ethanol is placed in the tube G, which serves as a flow indicator. The... 

To a freshly prepared solution of 3 moles of sodium ethoxide in 1200 ml of absolute ethanol is added dropwise benzotrichloride until 195 gm (1.0 mole) has been added. The reaction mixture is stirred for 5-6 hr without heating and then refluxed for 11 hr. The salt is filtered off, washed with ether, and the combined ether washings and filtrate are concentrated. Distillation of the residue affords 50 gm (22 %), b.p. 108°-112°C (13 mm). The yield is poor, and further work is required to ascertain the optimum conditions for this reaction. Whether other products are produced in the reaction was not reported in this earlier investigation. 

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