Ethyl 2-phenylacetate

Place 75 g. (74 ml.) of benzyl cyanide (Section IV,160), 125 g. (153 ml.) of rectified spirit and 150 g. (68 ml.) of concentrated sulphuric acid in a 750 ml. round-bottomed flask, fitted with an efficient refiux condenser. Reflux the mixture, which soon separates into two layers, gently for 8 hours, cool and pour into 350 ml. of water. Separate the upper layer. Dissolve it in about 75 ml. of ether (1) in order to facilitate the separation of the layers in the subsequent washing process. Wash the ethereal solution carefully with concentrated sodium bicarbonate solution until effervescence ceases and then with water. Dry over 10 g. of anhydrous magnesium sulphate for at least 30 minutes. Remove the solvent with the aid of the apparatus shown in Fig. II, 13, 4 and distil from an air bath (Fig. II, 6, 3). The ethyl phenylacetate passes over at 225-229° (mainly 228°) as a colourless liquid the yield is 90 g. Alternatively, the residue after removal of the ether may be distilled in a Claisen flask under diminished pressime (Fig. II, 20, 1) collect the ester at 116-118°/20 mm. 

In a 3-I. round-bottom flask, fitted with an efficient reflux condenser, are mixed 750 g. of 95 per cent alcohol, 750 g. of concentrated sulfuric acid and 450 g. of benzyl cyanide. The mixture, which soon separates into two layers, is heated to boiling over a low flame, for six to seven hours, cooled and poured into 2 1. of water, and the upper layer is separated. This is washed with a little 10 per cent sodium carbonate solution to remove small amounts of phenylacetic acid which may have been formed, and then distilled in vacuo. A small amount of water goes over first and then a pure product boiling i32-i38°/32 mm. (r2o-i25°/i7-i8 mm.). The yield varies in general between 525 and 550 g. (83-87 per cent of the theoretical amount). 

The benzyl cyanide can be most conveniently prepared according to the directions in preparation III (p. 9) the product which boils over a 50 range should be used. 

In washing the layer of ethyl phenylacetate with sodium carbonate it js sometimes advisable to add a certain amount of sodium chloride so that the ester will separate more readily. 

The product obtained is water-clear and practically colorless. Although the product is collected over a 5° range, most of the 

The boiling point of ethyl phenyl acetate is near that of benzyl cyanide. However, a Kjeldahl analysis of the product shows that only a trace of nitrogen compounds is present. 

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Successful results have been obtained (Renfrew and Chaney, 1946) with ethyl formate methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and iso-amyl acetat ethyleneglycol diacetate ethyl monochloro- and trichloro-acetates methyl, n-propyl, n-octyl and n-dodecyl propionates ethyl butyrate n-butyl and n-amyl valerates ethyl laurate ethyl lactate ethyl acetoacetate diethyl carbonate dimethyl and diethyl oxalates diethyl malonate diethyl adipate di-n-butyl tartrate ethyl phenylacetate methyl and ethyl benzoates methyl and ethyl salicylates diethyl and di-n-butyl phthalates. The method fails for vinyl acetate, ieri.-butyl acetate, n-octadecyl propionate, ethyl and >i-butyl stearate, phenyl, benzyl- and guaicol-acetate, methyl and ethyl cinnamate, diethyl sulphate and ethyl p-aminobenzoate. 

One synthesis of phenobarbital begins with ethyl phenylacetate and diethyl car bonate Using these starting materials and any necessary organic or inorganic reagents devise a synthesis of phenobarbital (Hint See the sample solution to Problem 21 3a )... 

Ethyl phenylacetate and (2-bromoethyl)benzene as supplied by Eastman Organic Chemicals were used without further purification. 

The method described is successfully used for the alkylation and aralkylation of ethyl and /-butyl phenylacetate.3 The alkylation of ethyl phenylacetate with methyl iodide, M-butyl bromide, benzyl chloride, and a-phenylethyl chloride affords the corresponding pure monoalkylation products in 69%, 91%, 85%, and 70% (erythro isomer) yields, respectively. The alkylation of /-butyl phenylacetate with methyl iodide, M-butyl bromide, a-phenylethyl chloride, and /3-phenylethyl bromide gives the corresponding pure monoalkylated products in 83%, 86%, 72-73%, and 76% yields, respectively. 

Certain of the monoalkylated ethyl phenylacetates have been further alkylated with alkyl and aralkyl halides to produce the corresponding disuhstituted phenylacetic esters.4 Ethyl 2-phenyl-propanoate has been alkylated by methyl iodide to give pure ethyl 2-methyl-2-pheny]propanoate in 81% yield. Similarly, the alkylations of ethyl 2-phenylhexanoate with methyl iodide, M-butyl bromide, and benzyl chloride gave the corresponding pure dialkylated products in 73%, 92%, and 72% yields, respectively. 

Butylation of ethyl phenylacetate, /-butyl phenylacetate, and ethyl 2-phenylhexanoate has also been accomplished with M-butyl bromide and sodium hydride in refluxing monoglyme in 64%, 66%, and 56% yields, respectively.6 In contrast to the sodium amide reactions above, however, careful fractionation of the crude products was required to obtain pure products. 

Bromoethyl)benzene, reaction with ethyl phenylacetate, 47, 72 ic-Bromofluorides from olefins, 46,12 Bromofluorination of olefins, 46, 39... 

Ethyl phenylacetate, reaction with (2-bromoethyl)benzene, 47, 72 Ethyl 2-phenylhexanoate, 47, 74 Ethyl 2-phenylpropionate, 47, 74 Exchange of oxygen by sulfur in preparation of chloromethylphospho-nothioic dichlonde, 46, 21 Extractor, stirred in isolation of 3-hydroxyglutaromtnle, 46, 49... 

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... 

Ethyl Oxomalonate, 4,27 Ethyl Phenylacetate, 2, 27 Ethyl Propane-i, i, 2, 3-tetracar-boxylate, 4, 20, 77 Ethyl succinate, 6, 10 Ethyl sulfate, 4, 60... 

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... 

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