Sodium amide with ethers

The reaction of cyclooctanone with diethyl oxalate, followed by decarbonylation of the resulting glyoxylate, has been reported to yield 32% of 2-carbethoxycyclooctanone.2 The reaction of cyclooctanone with sodium amide in ether, followed by the... 

Treatment of the bis-ylide generated from bis 2-[(triphenylphosphonio)methyl]phenyl ether and sodium amide with oxygen gives dibenz[A./]oxepin (3) in 50% yield.98 99... 

The benzylation of diphenylacetonitrile with benzyl chloride to form a,o ,j8-triphenylpropionitrile has been previously effected in 83% yield by sodium ethoxide in ethanol,3 in 67% yield by methylmagnesium iodide in ether,4 and in unreported yield by sodium amide in ether.5... 

Sodium hydrazide, R NNIdNa. Mol. wt. 54.04. The reagent is a crystalline yellow solid which explodes at temperatures above 70° or in the presence of oxygen. It is prepared by reaction of sodium amide with anhydrous hydrazine under nitrogen at 0°, for most purposes as a suspension in ether, diisopropyl ether, benzene, or a mixture of these solvents. ... 

The following compound reacts with sodium amide in ether to give a product with the molecular formula C10H14N2. Suggest a structure for this product. 

Hydrolysis of a substituted amide. A. With 10 per cent, sulphuric acid. Reflux 1 g. of the compound (e.g., acetanilide) with 20 ml. of 10 per cent, sulphuric acid for 1-2 hours. Distil the reaction mixture and collect 10 ml. of distillate this will contain any volatile organic acids which may be present. Cool the residue, render it alkaline with 20 per cent, sodium hydroxide solution, cool, and extract with ether. Distil off the ether and examine the ether-soluble residue for an amine. 

Cumulenic ethers with the 4-positions blocked by alkyl groups can be obtained from bis-ethers, R0-CH2C=C-C(R )(r2)0R, and sodium amide in liquid NHj, applying the... 

A suspension of sodium amide in 500 ml of anhydrous liquid artmonia was prepared from 18 g of sodium (see Chapter II, Exp. 11). To the suspension was added in 10 min with swirling a mixture of 0.30 mol of 1-chloro-l-ethynylcyclohexane (see VIII-2, Exp. 27) and 50 ml of diethyl ether. The reaction was very vigorous and a thick suspension was formed. The greater part of the ammonia was evaporated by placing the flask in a water bath at 50°C. After addition of 500 ml of ice-water the product was extracted three times with diethyl ether. The ethereal extracts were dried over anhydrous KjCOj and subsequently concentrated in a water-pum vacuum. Distillation of the residue afforded the amine, b.p. 54°C/15 mmHg, n 1.4345, in 87% yield. 

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). 

POCI3 was added to a solution of amide 62 (0.075g, 0.02 mmol) in toluene (5 mL). The reaction mixture was heated to 110 °C with stirring for 5 h, then cooled to rt. A solution of 2 N NaOH (10 mL) was added and the mixture was extracted with ether (3 x 15 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was then purified by flash chromatography on silica gel (40% Ethyl acetate/hexanes) to afford the 68 mg (95%) of the title compound as... 

A mixture of 100 g (0.6 mole) of 1-morpholino-l-cyclohexene, 28.8 g (0,4 mole) of /3-propiolactone, and 100 ml of chlorobenzene is placed in a 500-ml round-bottom flask fitted with a condenser (drying tube). The mixture is refluxed for 4 hours. The solvent and excess enamine are removed by distillation at aspirator pressure. (The residue may be distilled to afford the pure morpholide, bp 187-18871 rnm, 1.5090.) Basic hydrolysis may be carried out on the undistilled morpholide. To the crude amide is added 400 ml of 10% sodium hydroxide solution. The mixture is cautiously brought to reflux, and refluxing is continued for 2 hours. The cooled reaction mixture is made acidic (pH 4) and is extracted three times with ether. The combined ether extracts are washed twice with 5 % hydrochloric acid solution and twice with water. The ethereal solution is dried (sodium sulfate), then filtered, and the solvent is removed (rotary evaporator). The residue may be recrystallized from petroleum ether-benzene, mp 64°. 

A mixture of 100 g of 5,5-dimethylacridan, 20 g of pulyerized sodium amide and 6.5 g of 1 -chloro-3-dimethylaminopropane in 50 ml of xylene is heated at reflux with stirring for one hour. To the cooled reaction mixture is added one yolume of water. The organic layer is separated and extracted several times with diluted lactic acid. The acidic extracts are combined, washed with ether and neutralized by alkali. The crude 10-(3 -dimethylaminopropvl)-5,5-dimethylacridan is isolated by ether extraction and purified by distillation in a high vacuum. The yield is 6,4 g BP 170°-1 B0°C/0.005 mm. n = 1.5990. 

A 500 cc flask equipped with a mechanical stirrer, reflux condenser and a soda-lime tube was filled with 230 cc of absolute xylene, 27.5 g of 1-methyl-3-bromomethylpiperidine, 53.3 g of phenothiazine and 14.2 g of finely powdered sodium amide, and the solution was heated under reflux for 6 hours. After cooling water was added and the batch was extracted with ether. 

Benzyl cyanide is first reacted with 2-butylbromide in the presence of sodium amide to give 2-phenyl-3-methylvaleronitrile which is hydrolyzed by sulfuric acid to give 3-methyl-2-phenyl-pentanoic acid. 24 g of 2-phenyl-3-methyl-pentanoic acid are heated for one hour at 175° to 185°C with 30 g of 2-diethylaminoethanol and 0.5 g of sodium methylate. The excess diethyl-aminoethanol is removed in vacuo, the residue is dissolved in 300 cc of 2 N-acetic acid, the acid solution is shaken with ether and made alkaline with concentrated potassium carbonate solution and ice. The ether solution Is washed with water, dried with sodium sulfate and evaporated. The residue is distilled under high vacuum, yielding 20 to 21 g of the basic ester (60% of the theoretical) is obtained, the ester boiling at 98° to 100°C at a pressure of 0.03 mm. The hydrochloride of the ester melts at 112° to 113°C and the methobromide at 100° to 101°C. 

A suspension of sodium amide2 (0.1 mole) in liquid ammonia is prepared in a 500-ml. three-necked, round-bottomed flask fitted with a West condenser, a ball and socket glass mechanical stirrer (Note 1), and a dropping funnel. In the preparation of this reagent a small piece of clean sodium metal is added to 350 ml. of commercial anhydrous liquid ammonia. After the appearance of a blue color, a few crystals of hydrated ferric nitrate are added, whereupon the blue color is discharged. The remainder of the 2.3 g. (0.1 mole) of sodium (Note 2) is then rapidly added as small pieces. After all the sodium has been converted to sodium amide (Note 3), a solution of 16.4 g. (0.1 mole) of ethyl phenyl-acetate (Note 4) in 35 ml. of anhydrous ethyl ether is added dropwise over a 2-minute period, and the mixture is stirred for 20 minutes. To the dark green suspension is added over an 8-minute period a solution of 18.5 g. (0.1 mole) of (2-bromo-... 

Silver fluoborate, reaction with ethyl bromide in ether, 46, 114 Silver nitrate, complexing with phenyl-acetylene, 46, 40 Silver oxide, 46, 83 Silver thiocyanate, 45, 71 Sodium amide, in alkylation of ethyl phenylacetate w ith (2-bromo-ethyl)benzene, 47, 72 in condensation of 2,4-pentanedione and 1 bromobutane to give 2,4-nonanedione, 47, 92 Sodium 2 ammobenzenesulfinate, from reduction of 2 mtrobenzenesul-finic acid, 47, 5... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

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