Ethanol sodium ethoxide production from

Diethyl oxalate (29.2 g, 0.20mol) and 4-bromo-2-nitrotoluene (21.6 g, O.lOmol) were added to a cooled solution of sodium ethoxide prepared from sodium (4.6 g, 0.20 mol) and ethanol (90 ml). The mixture was stirred overnight and then refluxed for 10 min. Water (30 ml) was added and the solution refluxed for 2 h to effect hydrolysis of the pyruvate ester. The solution was cooled and concentrated in vacuo. The precipitate was washed with ether and dried. The salt was dissolved in water (300 ml) and acidified with cone. HC1. The precipitate was collected, washed with water, dried and recrystallizcd from hexane-EtOAc to give 15.2 g of product. 

Vasvari-Debreczy et al. studied the ring closure of the succinates (77) under various conditions, e.g., in Dowtherm A at 250rC,130-133 in a phos-phoryl chloride-polyphosphoric acid mixture1 32-1 34 at 110-120 C, and in ethanolic sodium ethoxide at room temperature.1 33-1 35 The authors expected various cyclic products pyrido[l,2- ]pyrimidines (78) from the Z stereoisomer of 77 and pyridylpyrrolinones (79) or pyrido[l,2-ci](l,3)diaze-pines (80) from the E stereoisomer (Scheme 3). Experiments were carried out... 

In ethanolic sodium ethoxide the pyrido[l,2-a]pyrimidines (78) and the pyridylpyrrolinones (79) were formed in an equilibrium reaction, the pyridyl-pyrrolinones being the preferred product. The pyrido[l,2-c<]pyrimidines (78) were not obtained from the 6-substituted succinates (77 R = 6-OH, 6-Me, or 6-NHAc).13 5... 

CIS- and /rfl j-l,3-Hexadien-5-yne (277 and 278) arc formed as major products, along with small amounts of 2,4-hexadiyne (283), when 275 is heated with potassium /-butoxide in /-butyl alcohol or ethanolic sodium ethoxide. In addition a small amount of 1,2,4,5-hexatetraene (280) was present in the reaction mixture involving sodium ethoxide. l,2-Hexadien-5-yne (276) the product expected from the first isomerization step was not detected, but this is understandable because it was demonstrated in separate experiments that 276 isomerizes much faster than the starting diyne. When 276 is treated with /-BuOK//-BuOH at room temperature, reaction is immediate, producing a mixture of the dienynes 277 and 278 on the other hand, when NaOEt is used, 280 is the exclusive product . ... 

The structures of ebumaminol (155) and larutensine (154) have been confirmed by a synthesis reported by Lounasmaa from the previously available indoloquinolizidine ester 154 (Scheme 8). Successive reduction, acetylation and Fuji oxidation of 156 yielded the enamine 157 which was alkylated with iodoacetic ester followed by NaBH4 reduction to give a mixture of four products. Treatment of two of these, the epimeric esters 158, with ethanolic sodium ethoxide resulted in cyclization to 18-hydroxyebumamonine (159) accompanied by its C(20) epimer. Reduction of 18-hydroxyebumamonine furnished ( )-ebumaminol and 16-epiebumami-nol (160) which on overnight treatment with acid gave ( )-larutensine [114]. 

The final conditions were scaled up with no problems chalcone 8a and guanidine (liberated from its hydrochloride with sodium ethoxide) were heated in dimethyl acetamide while bubbling air through the mixture to form pyrimidine 9a. After complete conversion (16 h), the product was cleaved from the support (20% trifluoroacetic acid in DCM). Pure 4-(2-amino-6-phenyl-pyrimidin-4-yl)bcnzamidc 1 was obtained as its trifluoroacetate salt upon evaporation of the filtrate and recrystallisation of the residue from ethanol/water in 56% overall yield based on the solid phase attached 4-carboxybenzaldehyde 6a. 

Treatment of (2i ,3 )-2-bromo-3-methylpentane with sodium ethoxide in ethanol gives (ii)-3-methylpent-2-ene as the major product. What would be the major product from similar base treatment of (23, 33 )- and 2R,3S)-2-bromo-3-methylpentane Hint Newman projections will be useful here. 

When sodium ethoxide is made from ethanol, dried by distillation from sodium in vacuum, and vacuum-distilled sodium, the product is always yellow. The author believes that he heard the method of obtaining the pure, colourless product in M. Szwarc s laboratory and that it is unpublished the following description is adapted from a Keele thesis. 

A-10. Draw the structures of all the alkenes, including stereoisomers, that can be formed from the E2 elimination of 3-bromo-2,3-dimethylpentane with sodium ethoxide (NaOCH2CH3) in ethanol. Which of these would you expect to be the major product ... 

In an initial step, the sodium derivative of ethyl (3-benzoylphenyl) cyanoacetate is prepared as follows (3-benzoylphenyl)acetonitrile (170 9) 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 about 105° to 115°C and ethanol being continuously distilled. A product precipitates. Toluene (500 cc) is added, and then, after distillation of 50 cc of toluene, the product is allowed to cool. Diethyl ether (600 cc) is added and the mixture is stirred for 1 hour. The crystals which form are filtered off and washed with diethyl ether (600 cc) to give the sodium derivative of ethyl (3-benzoylphenyl)cyanoacetate (131 g). 

An ethanolic solution of sodium ethoxide is prepared by reacting 3 g of sodium with 300 ml of absolute ethanol. 30 g of estradiol are dissolved in the resultant solution and there are then added thereto, with stirring, 30 ml of n-propyl bromide. Reaction is continued for 3 hours with stirring at 60°C and then the reaction mixture is concentrated under vacuum at 30°C to about 50 ml. The residue is taken up in 500 ml of benzene and then washed twice with 250 ml of a 0.25 N solution of sodium hydroxide and then with distilled water to neutrality. The solution is then dried over sodium sulphate and concentrated to give 32 g of crude product (yield 93%), which on recrystallization from 100 ml of methanol gives 31 g (yield 89%) of pure product MP 100°-101°C. 

The extent of C-alkylation as a side reaction in etherification varies about 1% of allyl 2-allylphenyl ether is formed when phenol is used in the acetone and potassium carbonate method with allyl bromide with cinnamyl bromide or 7,7-dimethylallyl bromide the extent of C-alkylar tion is greater.16 A complicated mixture of C- and O-alkylation products results from the treatment of phenol with 4-bromo-2-hexene and 4-chloro-2-hexene. 9 4-Hexenylresordnol has been obtained in about 40% yield from the reaction of l-bromo-2-hexene, resorcinol, and potassium carbonate in boiling acetone.99 An appreciable amount of C-alkylation occurs when 2,6-dimethyIphenol is treated with allyl bromide and sodium ethoxide in ethanol.70 Since, in general, the ampunt of C-alkylation is greatly increased by carrying out the alkylation on the sodium salt of the phenol in benzene,16 this method is unsuitable for the preparar tion of allyl aryl ethers. 

What product would be expected from the elimination reaction of (l/ ,25j-l-bromo-1,2-diphenylpropane using sodium ethoxide in ethanol as the solvent ... 

Tellurium Tetraethoxide2 188.3 g (0.5 mol) of diammonium hexachlorotellurate are suspended in 500 ml of absolute ethanol and a cooled solution of sodium ethoxide, prepared by careful addition of 50 g (2.17 mol) of sodium in small pieces to 400 ml of ethanol, is added dropwise. The mixture is healed under reflux until evolution of ammonia has ceased, filtered to remove sodium chloride, and ethanol is distilled from the filtrate. The residue is distilled under vacuum to give the product as a colorless oil b.p. 10770.3 torr. 

Diethyl malonate adds to diethyl fumarate in a conjugate addition reaction promoted by sodium ethoxide in dry ethanol to give a tetraester, Diethyl fumarate is an excellent Michael acceptor because two ester groups withdraw electrons from the alkene, The mechanism involves deprotonation of the malonate, conjugate addition, and reprotonation of the product enolate by ethanol solvent, In this reaction two ester groups stabilize the enolate and two more promote conjugate addition. 

N,N, N",N "-Tetra(p-toluenesulfonyl) Derivative of f 13]aneNA. Two equivalents of sodium ethoxide (3.02 g in 66 mL of ethanol) are added to SO g of the tosylated linear tetraamine in 200 mL of boiling ethanol. After the solution is boiled for 20 minutes, the ethanol is removed by rotary evaporating to dryness to yield the disodium salt of the tosylated linear tetraamine. The sodium salt is dissolved in 660 mL of dimethylformamide (0.1 M) and transferred to a 2-L, three-necked flask equipped with an addition funnel and a thermometer. The mixture is heated to 110°, and 1 equiv of 1,3-dibromopropane (14 g in 330 mL of DMF, 0.2 M) is added dropwise over a period of 1 hour while the solution is stirred vigorously. The volume of DMF is reduced to one-fourth the initial volume. The solution is slowly added to a volume of water equal to 1 times that of the initial DMF volume. This yields a tacky off-white precipitate. The product is recrystallized from hot benzene. A white product is precipitated by reducing the volume of the benzene to about 150-mL, adding ethanol to the solution, and then letting it stand at room temperature for 1 hour. Yield 40%. 

The optimal base for closure to epoxide 2 is sodium ethoxide in ethanol, as potassium hydroxide in ethanol, sodium or potassium carbonate in ethanol, or benzyllrimethylammonium hydroxide in ethanol resulted in the formation of a complex mixture of decomposition products arising mainly from deprotonation at carbon. 

Enamines undergo the Michael addition reaction to give the least substituted product in contrast to the highly substituted product obtained from enolate derived from unsymmet-rical ketone by Sodium ethoxide (NaOEt) in ethanol (EtOH). 

In a modified Claisen flask set up for distillation are placed 14.4 g. (0.1 mole) of ethyl caproate and 3.4 g. (0.05 mole) of dry sodium ethoxide, and the contents are heated to 90-95° under a pressure of 75-80 mm. for 7-8 hours. Under these conditions ethanol is removed from the reaction mixture at an even rate. After cooling the product is treated with 10 g. of 30% aqueous acetic acid and shaken until the sodium salt is decomposed. The reaction mixture is extracted with 25 ml. of benzene, and the extract is washed with water, dried over sodium sulfate, and distilled. Ethyl a-caproylcaproate, b.p. 132-133°/5 mm., 1.4351, is obtained in 80% yield. 

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