Benzyl-cyanide

The quality of the benzyl chloride markedly affects the yield of pure benzyl cyanide. If a poor technical grade is used, the yields will not be more than 60-75 per cent of the theoretical, whereas consistent results of about 85 per cent or more were always obtained when a product was used that boiled over io°. The technical benzyl chloride at hand yielded on distillation about 8 per cent of high-boiling material a technical grade from another source was of unusual purity and boiled over a 2° range for the most part. 

It is advisable to distil off the last portion of alcohol and water in vacuo and also to distil the benzyl cyanide in vacuo, since under ordinary pressures a white solid invariably separates during the distillation. 

One method of purifying the benzyl cyanide is to steam distil it after the alcohol has been first distilled from the reaction mixture. At ordinary pressures, this steam distillation is very slow and, with an ordinary condenser, requires eighteen to twenty hours in order to remove all of the volatile product from a run of 500 g. of benzyl chloride. The distillate separates into two layers the benzyl cyanide layer is removed and distilled. The product obtained in this way is very pure and contains no tarry material, and, after the excess of benzyl chloride has been removed, boils practically constant. This steam distillation is hardly advisable in the laboratory. 

The benzyl cyanide, prepared according to the procedure as outlined, is collected over a 50 range. It varies in appearance from a colorless to a straw-colored liquid and often develops appreciable color upon standing. For a product of special purity, it should be redistilled under diminished pressure and collected over a 1-20 range. For most purposes, such as the preparation of phenylacetic acid or ester, the fraction boiling i35-i4o°/38 mm. is perfectly satisfactory. 

Benzyl cyanide occurs naturally in certain oils.1 The only feasible method of preparing it that has been described in the literature is the one in which alcoholic potassium cyanide and benzyl chloride 2 are employed. The cheaper sodium cyanide is just as satisfactory as the potassium cyanide and therefore is the best material to use. Gomberg has recently prepared benzyl cyanide from benzyl chloride and an aqueous solution of sodium cyanide.3 

When an amide is heated with a dehydrating agent (P2Os, 2 5-PC 1S) it loses water and is converted into a nitrile, e.g. 

as has been described above, amides can be obtained by removal of water from the ammonium salts of acids, nitriles can be prepared directly from ammonium salts in one operation by heating them with a powerful dehydrating agent, e.g. ammonium acetate with P205  

Nitriles can also be obtained by the method of Kolbe alkyl iodides (bromides or chlorides) are heated with alkali cyanide (example, benzyl cyanide), or salts of alkylsulphuric acids are subjected to dry distillation with potassium cyanide  

The preparation of aromatic nitriles from diazo-compounds will be discussed later (p. 291). 

The lower nitriles are colourless liquids, the higher are crystalline solids. The solubility in water decreases progressively with increasing molecular weight. 

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P-Phenylethylamine is conveniently prepared by the hydrogenation under pressure of benzyl cyanide with Raney nickel catalyst (see Section VI,5) in the presence of either a saturated solution of dry ammonia in anhydrous methyl alcohol or of liquid ammonia the latter are added to suppress the formation of the secondary amine, di- P phenylethylamine ... 

Minute amounts of halide have a powerful poisoning effect upon the catalyst it is advisable to distil the benzyl cyanide from Raney nickel. 

By the hydrolysis of nitriles. The nitriles may be easily prepared either from amines by the Sandmeyer reaction (Section IV,66) or by the action of cuprous cyanide upon aryl halides (compare Section IV,163). Benzyl cyanide... 

The hydrolysis of arylacetonitriles may be arrest at the arylacetamide stage by treatment with concentrated hydrochloric acid at about 40° thus benzyl cyanide yields phenylacetamlde ... 

Preparation of benzyl cyanide. Place 100 g. of powdered, technical sodium cyanide (97-98 per cent. NaCN) (CAUTION) and 90 ml. of water in a 1 litre round-bottomed flask provided with a reflux condenser. Warm on a water bath until the sodium cyanide dissolves. Add, by means of a separatory funnel fitted into the top of the condenser with a grooved cork, a solution of 200 g. (181-5 ml.) of benzyl chloride (Section IV.22) in 200 g. of rectified spirit during 30-45 minutes. Heat the mixture in a water bath for 4 hours, cool, and filter off the precipitated sodium chloride with suction wash with a little alcohol. Distil off as much as possible of the alcohol on a water bath (wrap the flask in a cloth) (Fig. II, 13, 3). Cool the residual liquid, filter if necessary, and separate the layer of crude benzyl cyanide. (Sometimes it is advantageous to extract the nitrile with ether or benzene.) Dry over a little anhydrous magnesium sulphate, and distil under diminished pressure from a Claisen flask, preferably with a fractionating side arm (Figs. II, 24, 2-5). Collect the benzyl cyanide at 102-103°/10 mm. The yield is 160 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°. 

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. 

An example of the application of the Raney nickel catalyst is given in Section IV,35 (p-phenylethylamine from benzyl cyanide). 

A solution of sodamide in liquid ammonia (essentially the amide NHj ion) is a very powerful alkylation catalyst, enabling condensations to be carried out with ease and in good yield which are otherwise either impossible or proceed with difficulty and are accompanied by considerable by-products. Thus 3-alkylpjTidines, otherwise inaccessible, are easily prepared from 3-picoline (see 3-n-amylpyridine in Section V,20). Also benzyl cyanide (I) and cyclohexyX bromide give a- r/ohexylphenylacetonitrile (II) ... 

Hydrolysis of a nitrile to an amide. Warm a solution of 1 g. of the nitrile benzyl cyanide) in 4 ml. of concentrated sulphuric acid to 80-90°, and allow the solution to stand for 5 minutes. Cool and pour the solution cautiously into 40 ml. of cold water. Filter oflT the precipitate stir it with 20 ml. of cold 5 per cent, sodium hydroxide solution and filter again. RecrystaUise the amide from dilute alcohol, and determine its m.p. Examine the solubility behaviour and also the action of warm sodium hydroxide solution upon the amide. 

Finally a general approach to synthesize A -pyrrolines must be mentioned. This is tl acid-catalyzed (NH4CI or catalytic amounts of HBr) and thermally (150°C) induced tea rangement of cyclopropyl imines. These educts may be obtained from commercial cyan> acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1-silyloxy-l-vinylcyclopropancs (p. 7 83) but since it is acid-catalyzed it occurs at much lower temperatures. A -Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

R B Woodward was one of the leading organic chemists of the middle part of the twenti eth century Known pnmanly for his achievements in the synthesis of complex natural products he was awarded the Nobel Pnze in chemistry in 1965 He entered Massachusetts Institute of Tech nology as a 16 year old freshman in 1933 and four years later was awarded the Ph D While a student there he earned out a synthesis of estrone a female sex hormone The early stages of Woodward s estrone synthesis required the conversion of m methoxybenzaldehyde to m methoxy benzyl cyanide which was accomplished in three steps... 

Nearly all uses and appHcations of benzyl chloride are related to reactions of the active haUde substituent. More than two-thirds of benzyl chloride produced is used in the manufacture of benzyl butyl-phthalate, a plasticizer used extensively in vinyl flooring and other flexible poly(vinyl chloride) uses such as food packaging. Other significant uses are the manufacture of benzyl alcohol [100-51-6] and of benzyl chloride-derived quaternary ammonium compounds, each of which consumes more than 10% of the benzyl chloride produced. Smaller volume uses include the manufacture of benzyl cyanide [140-29-4], benzyl esters such as benzyl acetate [140-11-4], butyrate, cinnamate, and saUcylate, benzylamine [100-46-9], and benzyl dimethyl amine [103-83-8], and -benzylphenol [101-53-1]. In the dye industry benzyl chloride is used as an intermediate in the manufacture of triphenylmethane dyes (qv). First generation derivatives of benzyl chloride are processed further to pharmaceutical, perfume, and flavor products. 

Reaetion of several 3-bromobenzoic acids with excess LDA, followed by addition of a benzyl cyanide, gave the product mixtures shown. Suggest a mechanism for the formation of each of these products. 

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