Phenyl ethyl malonic acid diethyl ester

Phenyl ethyl malonic acid diethyl ester Methylurea... 

C]phenyl ethyl malonic acid diethyl ester and, finally, the condensation of this ester with urea. 

In order to label in the 2 position, [ " C]nrea is condensed with ethyl phenyl malonic acid diethyl ester, according to the plan in Fig. 1. 

C]benzyl alcohol [7- " C]benzyl chloride [l- Clphenyl acetic acid ethyl ester [2- " C]phenyl malonic acid diethyl ester... 

Diethyl phenyl ethyl malonate. 1 mole of benzyl cyanide is added dropwise to a solution of 1 mole of ethyl carbonate in 2 liters of anhydrous ethanol containing 5 g of clean sodium metal. This mixture is refluxed (preferably on a steam bath) for 5 hours. It is then cooled and to it is added a cooled mixture of 40 g of sulfuric acid in 100 ml of anhydrous ethanol. This alcoholic solution is refluxed for 5 hours, cooled, neutralized with sodium ethylate (use external indicator). The mixture is evaporated to half bulk, filtered from the sodium sulphate and to it is added 1 mole of clean metallic sodium. Reflux while adding 1 mole of ethyl bromide dropwise. Heat for another 2 hours after the addition is completed. Remove the alcohol by distillation and dissolve the remaining residue in water. Extract the substance from the water with benzene and after drying, the benzene is recovered and the ester should be purified by distilling in vacuo. 

Nitro compounds, ar. Nitrobenzene, m-Dinitrobenzene o-Nitrophenol N-Nitramines Oxonium fluoroborate Trialky loxonium salt Trialky loxonium fluoroborate Pyrylium fluoroborate Carboxylic acid esters HCOOC Hs, p-Nitro-phenyl formate Isopropenyl acetate Salicylic acid esters Ethyl cyanoacetate Chloroformic acid esters Ethyl chloroformate, ClCOOC Hg-i Methyl trichloroacetate Diethyl oxalate Ethyl malonate... 

The Claisen condensation of diethyl oxalate with esters of fatty acids (cf. method 211) produces a-ethoxalyl esters which are thermally de-carbonylated to alkylmalonic esters. The over-all yields range from 78% to 91% for the conversion of fatry esters up to ethyl stearate. Phenyl-malonic ester is made in 85% yield. Powdered glass is sometimes used... 

From 3(5)-hydroxypyrazoles. 5-Hydroxy-l-phenyl-lH-pyrazole-4-carboxylic acid ethyl ester 303, derived from diethyl (ethoxymethylene)-malonate and phenylhydrazine hydrochloride, when methylated with dimethyl sulfate in aqueous sodium hydroxide solution afforded pyrazole 304 together with pyrazol-3-one 305 in 16% and 33% yield, respectively (95JHC1341) (Scheme 68). 

Phenobarbital is prepared by treating benzyl ehloride with sodium eyanide when benzyl eyanide (or a-phenyl acetonitrile) is formed with the elimination of a moleeule of sodium chloride. Benzyl cyanide, first on hydrolysis yields phenyl aeetic acid which on subsequent esterification with ethanol forms the eorresponding ester as ethyl phenyl acetate. This on reaction with diethyl oxalate in the persence of absolute ethanol and sodium metal gives diethyl phenyl oxalo acetate which on distillation at 180°C results into phenyl malonic ester. When it is treated with ethyl bromide and sodium ethoxide, the lonely active hydrogen atom gets replaced with an ethyl group thus forming ethyl phenyl malonic ester. Lastly, this on condensation with urea loses two molecules of ethanol and finally forms the desired compound phenobarbital. 

Diesters also react smoothly with the urea derivatives, which undergo displacement of the alkoxy groups to create amide bonds. Barbituric acid can be made this way by reaction of diethyl malonate (9.122, R=R =H) with urea (Scheme 9.64). An important family of pharmaceutical agents results from the use of substituted malonic esters. Thus, with a phenyl and an ethyl substituent the important hypnotic agent, phenobarbital (9.123) is produced. Veronal, which is another important hypnotic, is prepared from diethyl-substituted malonates. 

The question of where carbanions will attack 2,4-dichloronitrobenzene is addressed. Experimental evidence is presented that such carbon acids as alkylsubstituted phenyl-acetonitriles and ethylmalonate ester which contain a methine group prefer nucleophilic aromatic substitution in the para-pos X on whereas active methylene compounds like desoxybenzoin, diethyl malonate, ethyl cyanoacetate and phenylacetonitrile prefer attack at the ortho-cYAoiine. A variety of conditions was used including strong base in DMSO but most of the cases are phase transfer alkylation conditions. 

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