Phenylacetate,

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. 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

The production of a-phenylcinnamic acid by heating benzaldehyde with acetic anhydride and sodium phenylacetate ... 

Here the phenylacetic anhydride, possessing more reactive a-hydrogen atoms, condenses with benzaldehyde to give a-phenylcinnamic acid. The preparation of the latter is an example of the Oglialoro modiflcation of the Perkin reaction. 

The preparation of a-phenylclnnamlc acid from benzaldehyde, phenylacetic acid, acetic anhydride and triethylamine is described. Presumably equilibria are set up between phenylacetic acid and acetic anhydride to form phenylacetic anhydride, a mixed anhydride or both ... 

The dibenzyl ketone has a very high b.p. (ca. 200°/21 mm.) and this remains in the flask when the unsymmetrical ketone has been removed by distillation. The dialkyl ketone has a comparatively low b.p. and is therefore easily removed by fractionation under normal pressure acetone is most simply separated by washing with water. In this way methyl benzyl ketone (R = CHj), ethyl benzyl ketone (R = CHgCH,) and n-propyl benzyl ketone (R = CHjCHjCH,) are prepared. By using hydrocinnamic acid in place of phenylacetic acid ... 

Ethyl benzyl ketone. Use 204 g. of phenylacetic acid (m.p. 77°) and 333 g. (335 -5 ml.) of propionic acid (b.p. 139-141°), but omit the extraction with benzene when working up the distillate. Distil the dried... 

Phenylacetic acid. Use 5 0 g. of magnesium, 25 g, (23 ml.) of redistilled benzyl chloride (Section IV,22) and 75 ml. of sodium-dried ether. Allow the reaction mixture to warm to 15° and then decompose it with dilute hydrochloric or sulphuric acid. Filter off the crude acid and recrystallize it from water. The yield of pure phenylacetic acid, m.p. 76-77°, is 11 g. 

Phenylacetic acid is appreciably soluble in water, so that the yield is poor it may be improved by evaporating the filtrates to a small volume and extracting with ether. 

Place 25 g. of phenylacetic acid (Section IV,160) in a 500 ml. round-bottomed flask, cool the latter in running water and add 250 ml. of fuming nitric acid, rather slowly at first and then more rapidly. The addition occupies about 15 minutes. Attach a condenser to the flask, reflux the solution for 1 hour, and pour into about 500 ml. of cold water. When cold, filter the crude 2 4-dinitrophenylacetic acid at the pump and wash it with cold water the resulting acid, after drying at 100°, is almost pure (m.p. 181°) and weighs 31 g. Recrystallise it from 300 ml, of 20 per cent, alcohol. Collect the first main crop (25 g.), and allow the mother liquor to stand overnight when a further 2 g. of pure acid is obtained dry at 100°, The yield of pure 2 4-dinitrophenylacetic acid, m.p. 183°, is 27 g. 

This product is sufficiently pure for the preparation of phenylacetic acid and its ethyl ester, but it contains some benzyl tso-cyanide and usually develops an appreciable colour on standing. The following procedure removes the iso-cyanide and gives a stable water-white compound. Shake the once-distilled benzyl cyanide vigorously for 5 minutes with an equal volume of warm (60°) 60 per cent, sulphuric acid (prepared by adding 55 ml. of concentrated sulphuric acid to 100 ml. of water). Separate the benzyl cyanide, wash it with an equal volume of sa+urated sodium bicarbonate solution and then with an equal volume of half-saturated sodium chloride solution- Dry with anhydrous magnesium sulphate and distil under reduced pressure. The loss in washing is very small (compare n-Butyl Cyanide, Section 111,113, in which concentrated hydrochloric acid is employed). 

Hydrolysis of benzyl cyanide to phenylacetic acid. Into a 500 ml. round-bottomed flask, provided with a reflux condenser, place 100 ml. 

Hydrolysis of benzyl cyanide to phenylacetamide. In a 1500 ml. three-necked flask, provided with a thermometer, reflux condenser and efficient mechanical stirrer, place 100 g. (98 ml.) of benzyl]cyanide and 400 ml. of concentrated hydrochloric acid. Immerse the flask in a water bath at 40°. and stir the mixture vigorously the benzyl cyanide passes into solution within 20-40 minutes and the temperature of the reaction mixture rises to about 50°, Continue the stirring for an additional 20-30 minutes after the mixture is homogeneous. Replace the warm water in the bath by tap water at 15°, replace the thermometer by a dropping funnel charged with 400 ml. of cold distilled water, and add the latter with stirring crystals commence to separate after about 50-75 ml. have been introduced. When all the water has been run in, cool the mixture externally with ice water for 30 minutes (1), and collect the crude phenylacetamide by filtration at the pump. Remove traces of phenylacetic acid by stirring the wet sohd for about 30 minutes with two 50 ml. portions of cold water dry the crystals at 50-80°. The yield of phenylacetamide, m.p. 154-155°, is 95 g. RecrystaUisation from benzene or rectified spirit raises the m.p. to 156°. 

The suspension of phenylacetamide may be further hydrolysed to phenylacetic acid by refluxing with stirring until the solid dissolves. The mixture becomes turbid after 30 minutes and the product begins to separate as an oil refluxing is continued for 6 hours, the mixture is cooled first with tap water and then by an ice-water bath for about 4 hours. The crude phenylacetic acid is filtered at the pump, washed with two 50 ml. portions of cold water, and dried in a desiccator. The resulting crude acid melts at 69- 70° it may be purified by recrystallisation from light p>etroleum (b.p. 40-60°) or, better, by vacuum distillation. 

Place 75 g. (74 ml.) of benzyl cyanide (Section IV,160), 125 g. (153 ml.) of rectifled spirit and 150 g. (68 ml.) of concentrated sulphuric acid in a 750 ml. round-bottomed flask, fitted with an efficient reflux condenser. Reflux the mixture, which soon separates into Wo layers, gently for 8 hoius, 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 anh3 drous 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, 5, 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 pressm (Fig. II, 20, 1) collect the ester at 116-lI8°/20 mm. 

Reflux a mixture of 15 g. of homoanisamide, 30 g. of potassium hydroxide and 300 ml. of ethanol on a water bath for 5 hours. Dilute with 750 ml. of water, evaporate to 75 ml. and acidify to Congo red. Collect the acid and recrystallise it from ethyl alcohol. The yield of p-methoxy-phenylacetic acid, m.p. 86-87°, is 13 g. 

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

The mechanism of the reaction la not known with certainty. It is known from studies utilising as tracer that no change in the carbon skeleton occurs during the reaction, and also that unsaturated hydrocarbons can undergo reactions very similar to those of ketones thus both styiene and phenyl-acetylene can react with sulphur and morpholine to produce phenylaceto-thiomorphoUde, hydrolysis of which yields phenylacetic acid ... 

Upon prolonged standing or, more rapidly, upon refluxing for 4-18 hours, the sodium atom migrates and benzyl-sodium is formed, as is proved by the production of phenylacetic acid in good yield upon carbonation. 

Acids. Acetic acid re-Caproic acid Benzoic acid Phenylacetic acid Succinic acid Adipic acid Anthranihc acid. 

PHENYLACETIC AGIO Very important fragrance chemical. Only recently was it banned by the DEA. Fragrance companies still can t believe they cannot openly sell it. It makes up 15% of jasmine oil (very expensive). 

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