Ethyl malonate reactions

It follows therefore that ethyl malonate can be used (just as ethyl aceto- acetate) to prepare any mono or di-substituted acetic acid the limitations are identical, namely the substituents must necessarily be alkyl groups (or aryl-alkyl groups such as CjHjCHj), and tri-substituted acetic acids cannot be prepared. Ethyl malonate undergoes no reaction equivalent to the ketonic hydrolysis of ethyl acetoacetate, and the concentration of the alkali used for the hydrolysis is therefore not important. 

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.)... 

The Michael Addition Reaction consists in the addition of the sodio-derivative of ethyl acetoacetate, ethyl malonate or ethyl cyanoacetate to an olefine group... 

Assemble a 250 ml. three-necked flask, fitted with a stirrer, a reflux condenser and a dropping-funnel, as in Fig. 22(A) and (j), p. 43, or Fig. 23(c), p. 46 (or a two-necked flask, with the funnel fitted by a grooved cork (p. 255) to the top of the condenser). Place 40 ml. of ethanol in the flask, and then add 2-3 g. of sodium cut into small pieces. When all the sodium has dissolved, heat the stirred solution on the water-bath, and run in from the funnel 17 g. (17 ml.) of ethyl malonate and then (more slowly) io-2 g. (12 ml.) of mesityl oxide, the reaction-mixture meanwhile forming a thick slurry. Boil the stirred mixture under reflux for i hour, and then add a solution of 10 g. of sodium hydroxide in 50 ml. of water, and continue boiling the pale honey-coloured solution for ij hours more. 

CHjClCOONa + KCN —> CHj(CN)COONa + KCl Upon warming the crude sodium cyanoacetate with ethyl alcohol and sulphuric acid, ethyl malonate is produced. Two mechanisms of the reaction have been proposed —... 

Equip a 3 litre three-necked flask with a thermometer, a mercury-sealed mechanical stirrer and a double-surface reflux condenser. It is important that all the apparatus be thoroughly dry. Place 212 g. of trimethylene dibromide (Section 111,35) and 160 g. of ethyl malonate (Section 111,153) (dried over anhydrous calcium sulphate) in the flask. By means of a separatory funnel, supported in a retort ring and fitted into the top of the condenser with a grooved cork, add with stirring a solution of 46 g. of sodium in 800 ml. of super dry ethyl alcohol (Section 11,47,5) (I) at such a rate that the temperature of the reaction mixture is maintained at 60-65° (50-60 minutes). When the addition is complete, allow the mixture to stand until the temperature falls to 50-55°, and then heat on a water bath until a few drops of the liquid when added to water are no longer alkaline to phenolphthalein (about 2 hours). Add sufficient water to dissolve the precipitate of sodium bromide, and remove the alcohol by distillation from a water bath. Arrange the flask for steam distillation (Fig. this merely involves... 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

In a 2 litre round-bottomed flask, fitted with a double surface reflux condenser, place 11-5 g. of clean sodium. Add 250 ml. of absolute alcohol in one portion if the reaction is unduly vigorous, immerse the flask momentarily in ice. When all the sodium has reacted, add 80 g. (76 ml.) of ethyl malonate (Section 111,153), followed by a solution of 30 g. of dry urea in 250 ml. of hot (ca. 70°) absolute alcohol. Shake the mixture well, fit a calcium chloride (or cotton wool) guard tube to the top... 

Quinone monoacetals such as 2-methoxyben2oquinonemonoacetal [64701-03-7] (66) show regiospeciftc addition of active methylene compounds (66), yielding 83% (67) and 63% (68) on reactions with ethyl malonate. 

One-part urethane sealants (Table 3) are more compHcated to formulate on account of an undesirable side reaction between the prepolymer s isocyanate end and water vapor which generates carbon dioxide. If this occurs, the sealant may develop voids or bubbles. One way to avoid this reaction is to block the isocyanate end with phenol and use a diketamine to initiate cure. Once exposed to moisture, the diketamine forms a diamine and a ketone. The diamine reacts with the isocyanate end on the prepolymer, creating a cross-link (10). Other blocking agents, such as ethyl malonate, are also used (11). Catalysts commonly used in urethane formulations are tin carboxylates and bismuth salts. Mercury salt catalysts were popular in early formulations, but have been replaced by tin and bismuth compounds. 

These compounds yield, on hydrolysis, the free acids, which, like all acids containing two carbo.xyl groups attached to the same carbon atom, lose COj on heating. Thus, ethyl malonic acid yields butyric acid. In this way the synthesis of monobasic acids may be readily effected. Malonic ester, moreover, may be used in the preparation of cyclic compounds as well as of tetrabasic and also dibasic acids of the malonic acid series ( Perkin). To give one illustration malonic ester, and ethylene bromide in presence of sodium alcoholate, yield triniethyleiic dicarbo.xylic ester and tetramethylene tetracarbo.xylic ester. The first reaction takes place in two steps,... 

Step B 3-Carbethoxy-4-Hydroxy-8-Trifluoromethylquinoline - A mixture of 113 grams of crude ortho-trifluoromethylanilinomethylene ethyl malonate from Step A, and 115 cc of phenyl oxide was heated rapidly under an inert atmosphere. At about 195°C, the ethanol formed began to distill off. At the end of about 30 minutes, the interior temperature reached 250°C and the reaction mixture was heated to reflux. Reflux was maintained for 1 hour and the mixture was then cooled, 25 cc of acetone were added and the mixture was allowed to crystallize. The mixture was filtered and the crystals thus formed were washed and dried to obtain 71.5 grams of 3-carbethoxy-4-hydroxy-8-trifluoromethylquino-line with a melting point of 210° to 214°C, which was used as is for the following stage. 

In a 2-1. round-bottomed flask fitted with a reflux condenser protected by a calcium chloride tube 11.5 g. (0.5 gram atom) of finely cut sodium is dissolved in 250 cc. of absolute alcohol. To this solution is added 80 g. (0.50 mole) of ethyl malonate followed by 30 g. (0.50 mole) of dry urea dissolved in 250 cc. of hot (70°) absolute alcohol. After being well shaken the mixture is refluxed for seven hours on an oil bath heated to 1 io°. A white solid separates rapidly. After the reaction is completed, 500 cc. of hot (50°) water is added and then enough hydrochloric acid (sp. gr. 1.18) to make the solution acidic (about 45 cc.). The resulting dear solution is filtered and cooled in an ice bath overnight. The white product is collected on a Buchner funnel, washed with 50 cc. of cold water, and then dried in an oven at 105-1 io° for three to four hours. The yield of barbituric acid is 46-50 g. (72-78 per cent of the theoretical amount). 

Bose et al. [18] reported that the Knoevenagel reaction between salicylaldehyde 27 and ethyl malonate 28 in the presence of piperidine gave a high yield of 3-carbethox-ycoumarin 29 in 3 min in an open vessel in a MW oven (Scheme 4.15). 

Recently Bogdal [48] observed, using kinetic studies, greater MW rate enhancements when the Knoevenagel reaction of salicylaldehyde with ethyl malonate (vide supra, Scheme 4.15) was performed in toluene than when ethanol was used as the solvent. The calculated rate constants in toluene solution were more than three times higher under MW irradiation than under conventional conditions, whereas the rate constants of the reaction in ethanol were the same, within experimental error, under both heating methods. 

The steam distillation separates ethyl malonate and ethyl 1,1-cyclobutanedicarboxylate from ethyl pentane-1,1,5,5-tetra-carboxylate, formed in a side reaction between malonic ester (2... 

Potassium 4-chloro-3,5-dinitrobenzene-sulfonate, 31, 46 Potassium cyanate, 31, 9 Potassium cyanide, 30,84 32,31,63 37,47 Potassium ethyl malonate, 37, 34 Potassium ethyl xanthate, 30, 56 Potassium fluoride, 36, 40 Potassium iodide, 30, 34 31, 31, 66 Potassium metal, 37, 29, 30 Potassium methyl sulfate, 31, 73 Potassium nitrate, 31, 46 Potassium 1-nitropropylnitronate, 37, 24 Potassium oxalate, 34, 83 Potassium permanganate, 30, 87 31, 59 Potassium sulfide, 32, 103 Potassium thiobenzoate, 32, 101 Potassium thiocyanate, 32, 39, 40 Prins reaction, 33, 72 Propane, 1, 3-dibromo-2, 2-Ws-(bromo-methyl)-, 31, 82... 

An ethanolic solution of diethyl thieno[2,3-/ -l,4-thiazepin-5(2//)-yli-dene malonate (515) was refluxed in the presence of sodium ethylate. The reaction mixture was then evaporated, and the residue was treated with water to give (thieno[2,3-/]-l,4-thiazepin-5-ylidene) acetate (1640) (86EUP183994). 

A reaction of bromobenzene with ethyl malonate in the presence of sodamide affords homophthalimide [103], This fascinating reaction involves sequential elimination, addition, intramolecular acylation, fragmentation, and addition. Excellent polarity alternation along the chains of atoms in various intermediates allows so many steps to proceed efficiently. 

The results in Table 2 show that the pyridine is less active than any of the X zeolites and Ge faujasite except the lithium form which shows slightly lower activity, whereas all Y zeolites show lower activity than pyridine. Piperidine, however, is more active than any of the zeolite samples studied here. From this comparison, it appears that, most of the basic sites of the zeolites must have pK<10.3. However, the fact that zeolites are also active for catalyzing the condensation of benzaldehyde with ethyl malonate, indicate that these samples have some basic sites with pK< 13.3. On a quantitative bases, and comparing the activity of zeolites for condensation with ethyl cyanoacetate, ethyl acetoacetate and ethyl malonate (Fig. 2), we can conclude that most of the basic sites of the zeolite have pK<9.0 with a sensible amount with 9.0basic strength of different solid base catalysts. 

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