Ethyl phenylmalonate

In a 2-1. three-necked flask fitted with a mercury-sealed stirrer, reflux condenser, and dropping funnel is placed 500 cc. of absolute ethyl alcohol (Note i), and 23 g. (i gram atom) of cleanly cut sodium is added in portions. When the sodium has dissolved the solution is cooled to 60°, and 146 g. (i mole) of ethyl oxalate (Org. Syn. Coll. Vol. i, 256) (Note 2) is added in a rapid stream through the funnel with vigorous stirring. This is washed down with a small quantity of absolute alcohol, and is followed immediately by the addition of 175 g. (1.06 moles) of ethyl phenylace-tate (Org. Syn. Coll. Vol. i, 265) (Note 2). Stirring is discontinued at once, the reaction flask is lowered from the stirrer, and a 2-1. beaker is made ready. Within four to six minutes after the ethyl phenylacetate has been added crystallization sets in. The contents of the flask are transferred immediately to the beaker at the first sign of crystallization, which is nearly Instantaneous. 

The nearly solid paste of the sodium derivative is allowed to cool to room temperature and then stirred thoroughly with 800 cc. of dry ether. The solid is collected by suction and washed repeatedly with dry ether. The phenyloxaloacetic ester is liberated from the sodium salt with dilute sulfuric add (29 cc. 

A high grade of absolute alcohol is essential. Ordinary absolute alcohol may be treated with about 5 per cent of its weight of sodium and distilled directly into the reaction flask. 

To insure absolutely dry and neutral reagents the ethyl oxalate and ethyl phenylacetate were sheiken with anhydrous potassium carbonate and distilled carefully under reduced pressure, after a preliminary heating under atmospheric pressure until their boiling points were reached. 

The procedure is based upon the standard method of Wis-licenus. Ethyl phenylmalonate has also been obtained from benzyl cyanide and ethyl carbonate. Phenylmalonic acid has been prepared by carbonation of the enolate of phenylacetic acid.  

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Ethyl phenylethylmalonate. In a dry 500 ml. round-bottomed flask, fitted with a reflux condenser and guard tube, prepare a solution of sodium ethoxide from 7 0 g. of clean sodium and 150 ml. of super dry ethyl alcohol in the usual manner add 1 5 ml. of pure ethyl acetate (dried over anhydrous calcium sulphate) to the solution at 60° and maintain this temperature for 30 minutes. Meanwhile equip a 1 litre threenecked flask with a dropping funnel, a mercury-sealed mechanical stirrer and a double surface reflux condenser the apparatus must be perfectly dry and guard tubes should be inserted in the funnel and condenser respectively. Place a mixture of 74 g. of ethyl phenylmalonate and 60 g. of ethyl iodide in the flask. Heat the apparatus in a bath at 80° and add the sodium ethoxide solution, with stirring, at such a rate that a drop of the reaction mixture when mixed with a drop of phenolphthalein indieator is never more than faintly pink. The addition occupies 2-2 -5 hoius continue the stirring for a fiuther 1 hour at 80°. Allow the flask to cool, equip it for distillation under reduced pressure (water pump) and distil off the alcohol. Add 100 ml. of water to the residue in the flask and extract the ester with three 100 ml. portions of benzene. Dry the combined extracts with anhydrous magnesium sulphate, distil off the benzene at atmospheric pressure and the residue under diminished pressure. C ollect the ethyl phenylethylmalonate at 159-160°/8 mm. The yield is 72 g. 

Ethyl Phenylmalonate (16, 33) By condensing ethyl phenylacetate with ethyl carbonate using a sodium-potassium alloy. Skinner, J. Am. Chem. Soc. 59, 322... 

Ethyl pentadecylate, 16, 37 Ethyl pentanehexacarboxylate, 10, 59 Ethyl phenylacetate, 16, 33 Ethyl -phenylacetoacetate, 18, 36 Ethyl -y-phenylbctyrate, 18, 25, 26 Ethyl phenylcyanopyruvate, 11, 40 Ethyl /J-phenylethyl ketone, 16, 49 Ethyl phenylmalonate, 16, 33 18, 84 Ethyl phenyloxaloacetate, 16, 33 Ethyl phthalimidomalonate, 14, 58 Ethyl pjmelate, 11, 42 17, 91 Ethyl propanetetracarboxylate, 10, 58 Ethyl propionate, 17, 34 Ethyl tso-propylmalonate, 11, 20, 21 Ethyl salicylate, 10, 51 11, 43 Ethyl sebacate, 14, 20 Ethyl sodium phthalimidomalonate, 14, 58... 

Ethyl phenylmalonate. In a 1-litre flask, equipped with a dropping funnel, mercury-sealed stirrer and reflux condenser, place 11-5 g. of dean sodium pieces (see Section III,7, Note 1) add 250 ml. of superdry ethyl alcohol (Section 11,47,5) aud allow the vigorous reaction to... 

Ethyl phenylmalonate, 1003 Ethylphenylnitrosamine, 570 Ethyl phenyloxalacetate, 1003,1004 Ethyl n-propylacetoacetate, 475, 481 Ethyl propane-1 1 2 3-tetracarboxy-late, 912, 913... 

Dowtherm gives 3-ethoxycarbonyl-4//-pyrazino[l,2-a]pyrimidin-4-one (275) in good yield. Ethyl phenylcyanoacetate also condenses with the starting pyrazine to give 2-hydroxy-4-imino-3-phenyl-4H-pyrazino[l,2-a]pyrimidine (276). Condensation of (274) with ethyl phenylmalonate gives zwitterion (277) (68JMC1045). 

Kanetsuna and Nonaka [264,370] compared the stereochemistry of diethyl 2,3-diphenylsuccinate formed in the oxidation of (1) ethyl phenylacetate (in the presence of iodide ion), (2) its sodium salt, and (3) ethyl phenylmalonate [Eq. (58)]. A phenylethox-... 

Arboricine was shown to be l,2-dihydro-4-hydroxy-l-methyl-2-oxo-3-phe-nylquinoline (10) or its diketo tautomer. It was synthesized by condensation of ethyl phenylmalonate with A-methylaniline (9). The formation of 10 during the alkaline hydrolysis of 1 probably takes place through the intermediate A -meth-yl-A -phenylacetylanthranilamide with loss of ammonia. 

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