Benzyl cyanide, hydrolysis

Reduction of the complex on Raney nickel yielded benzylamine, N-methyl-benzylamine, and N,N-dimethylbenzylamine but no / -phenylbenzylamine, a reduction product resulting under the same reaction conditions from benzyl cyanide. Hydrolysis with dilute sulfuric acid in acetic acid yielded benzylamine only, and oxidation of the complex with potassium permanganate gave 4.2 moles of benzoic acid per mole of complex. The bromide anion can be exchanged metathetically with various other anions such as perchlorate, iodide, and thiocyanate. When heated at 100° C. in vacuum, the complex lost one mole of benzyl bromide and yielded only one dicyanotetrakis(benzylisonitrile)iron(II) complex. 

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 ... 

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°. 

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. 

Another method of preparing ,to-diarylated alkanoic acids utilizes the condensation of 5-(w-phenylalkyl) substituted 2-thiophenealde-hydes (224) with benzyl cyanides and hydrolysis and desulfurization of the acids obtained (225). In this way, a,o-diphenylcaprylic acid has been prepared. ... 

Similarly, Pd/tppts was used by Hoechst (Kohlpainter and Beller, 1997) as the catalyst in the synthesis of phenylacetic acid by biphasic carbonylation of benzyl chloride (Fig. 2.29). The new process replaces a classical synthesis by reaction of benzyl chloride with sodium cyanide, followed by hydrolysis of the resulting benzyl cyanide. Although the new process produces one equivalent of sodium chloride, this is substantially less salt production than in the original process. Moreover, sodium cyanide is about seven times as expensive per kg as carbon monoxide. 

Benzyl cyanide is always lost by evaporation in the rather violent hydrolysis described above this can be avoided by boiling the benzyl cyanide (40 g.) under a reflux condenser for forty-five minutes with a mixture of water, concentrated sulphuric acid, and glacial acetic acid (40 c.c. of each). After cooling, the product is poured into water. 

When only small quantities of the acid are required, the following modified procedure is of value. One hundred grams of benzyl cyanide are added to a mixture containing ioo cc. of water, ioo cc. of concentrated sulfuric acid, and ioo cc. of glacial acetic acid. After this has been heated for forty-five minutes under a reflux condenser, the hydrolysis is practically complete. The reaction mixture is then poured into water, and the phenylacetic acid isolated in the usual manner. 

The standard method of preparation of phenylacetic acid is by the hydrolysis of benzyl cyanide with either alkali1 or acid.2 The acid hydrolysis runs by far the more smoothly and so was the only one studied. There are numerous other ways in which phenylacetic acid has been formed, but none of them is of practical importance for its preparation. These methods include the following the action of water on phenyl ketene 3 the... 

In a 2-1. round-bottom flask, fitted with a stopper holding a dropping funnel and a mechanical stirrer, is placed a mixture of 275 cc. of concentrated nitric acid (sp. gr. 1.42) and 275 cc. of concentrated sulfuric acid (sp. gr. 1.84). This is cooled to io° in a freezing mixture, and 100 g. of benzyl cyanide (free from alcohol and water) are run in slowly, at such a rate that the temperature remains at about io° and does not exceed 20°. After all the benzyl cyanide has been added (about one hour), the ice bath is removed, the mixture is stirred for an hour and then poured on to 1200 g. of crushed ice. A pasty mass slowly separates more than half of this mass is -nitrobenzyl cyanide, the other constituents being o-nitrobenzyl cyanide, and a variable amount of an oil which resists hydrolysis apparently no dinitro compounds are formed. The mass is filtered on a porcelain funnel with suction, pressed well to remove as much oil as possible, and dissolved in 500 cc. of boiling alcohol (95 per cent). On cooling, -nitrobenzyl cyanide crystallizes the mother liquor, on distillation, gives an impure alcohol which can be used for the next run. Recrystallization from 550 cc. of 80 per cent alcohol (sp. gr. 0.86 to 0.87) yields 70 to 75 g. (50-54 per cent) of a product which melts at 115-116°. 

Fig. 11.12. Metabolic scheme for reaction of benzyl cyanide (11.80) to mandelonitrile (11.81) as a crossroads to benzoic acid (11.83) via oxidative denitrilation, and to mandelic acid (11.82) as a minor metabolite produced by hydrolysis of the CN group [118][122]...

There are a few data in the literature to suggest that the hydrolysis of aliphatic nitriles occurs in mammals, but only as a minor or even undetectable pathway in competition with oxidative denitrilation. For example, benzyl cyanide (11.80, Fig. 11.12) undergoes cytochrome P450 catalyzed hydroxy-lation to mandelonitrile (11.81), from which cyanide and benzaldehyde are produced, the latter being oxidized to benzoic acid (11.83) [118]. However, a careful metabolic study of mandelonitrile has shown that, in the rat, this pathway accounts for ca. 90% and not 100% of the dose [122], Only ca. 10% of orally administered benzyl cyanide was converted to mandelic acid (11.82, Fig. 11.12) by hydrolysis of the CN group. 

Alkaline nitration with alkoxide bases and nitrate esters was first explored by Endres and Wislicenus who synthesized phenylnitromethane by treating ethyl phenylacetate with potassium ethoxide in ethanol, followed by addition of ethyl nitrate and hydrolysis-decarboxylation of the resulting a-nitroester with aqueous acid. Phenylnitromethane is synthesized in a similar way via alkaline nitration of benzyl cyanide, followed by treatment of the resulting a -nitronitrile with aqueous base. ° Wieland and co-workers used alkali metal alkoxides and nitrate esters for the nitration of cyclic ketones but the yields and purity of product are often poor. ° ... 

The common route to phenylacetic acid is conversion of benzyl chloride into benzyl cyanide by reaction with sodium cyanide, followed by hydrolysis. 

Benzylamine, 394, 560, 569 Benzylaniline. 572 Benzyl chloride, 517, 534, 538, 539 Benzyl cyanide, 752, 761 hydrolysis to acid, 761 hydrolysis to phenylacetamide, 762 Benzylidene derivatives, 345, 653 Benzyl magnesium chloride, 517 Benzyl phthalimide, 560, 569 Benzyl-sodium, 933 -Benzyl-iso-thiuronium cliloride, 965, 966... 

Phenylcoumarins are conveniently prepared by the Knoevenagel condensation of salicylaldehyde with a benzyl cyanide, in the presence of base such as sodium hydroxide or piperidine, followed by acid hydrolysis of the resultant imine. A second convenient synthesis is via condensation of 2-methoxybenzaldehyde with benzyl cyanide and cyclization of the 2-methoxy-a-phenylcinnamic nitrile in pyridine (Scheme 12). 

Phenylacetic acid. Into a 500-ml round-bottomed flask, provided with a reflux condenser, place 100 ml of water, 100 ml of concentrated sulphuric acid and 100 ml of glacial acetic arid add lOOg (98 ml, 0.85 mol) of benzyl cyanide. Heat under reflux for 45-60 minutes hydrolysis is then complete. Pour the mixture into 2-3 volumes of water with stirring. Filter the crude arid at the pump. Melt the crude material under water, and wash it two or three times with small volumes of hot water the acid solidifies on cooling. Test a small portion for the presence of phenylacetamide (m.p. 155 °C) by dissolving in sodium carbonate solution. If a clear solution results, phenylacetamide is absent if the solution is not clear, shake the whole of the crude product with excess of sodium carbonate solution, filter and precipitate the phenylacetic arid from the clear filtrate by the addition of dilute sulphuric arid. Filter off the phenylacetic acid and recrystallise it from hot water or, better, light petroleum (b.p. 40-60 °C). The yield of pure acid, 77 °C, is 50 g (43%). Small quantities of acid may be recovered from the mother-liquors by extraction with ether, but this is rarely worth while. Alternatively the acid may be purified by distillation under reduced pressure, b.p. 140-150 °C/20mmHg. The p.m.r. spectrum should be recorded and compared with that shown in Fig. 3.47. The 13C-n.m.r. spectrum is shown in Fig. 3.55. 

Phenylethylamine has been made by a number of reactions, many of which are unsuitable for preparative purposes. Only the most important methods, from a preparative point of view, are given here. The present method is adapted from that of Adkins,1 which in turn was based upon those of Mignonac,2 von Braun and coworkers,3 and Mailhe.4 Benzyl cyanide has been converted to the amine by catalytic reduction with palladium on charcoal,5 with palladium on barium sulfate,6 and with Adams catalyst 7 by chemical reduction with sodium and alcohol,8 and with zinc dust and mineral acids.9 Hydrocinnamic acid has been converted to the azide and thence by the Curtius rearrangement to /3-phenyl-ethylamine 10 also the Hofmann degradation of hydrocinnamide has been used successfully.11 /3-Nitrostyrene,12 phenylthioaceta-mide,13 and the benzoyl derivative of mandelonitrile 14 all yield /3-phenylethylamine upon reduction. The amine has also been prepared by cleavage of N- (/3-phenylethyl) -phthalimide 15 with hydrazine by the Delepine synthesis from /3-phenylethyl iodide and hexamethylenetetramine 16 by the hydrolysis of the corre-... 

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