Phenylacetonitrile, hydrolysis

This method is an adaptation of that of Dengel. -Methoxy-phenylacetonitrile can also be prepared by the metathetical reaction of anisyl chloride with alkali cyanides in a variety of aqueous solvent mixtures by the nitration of phenylaceto-nitrile, followed by reduction, diazotization, hydrolysis, and methylation 1 by the reduction of ct-benzoxy- -methoxy-phenylacetonitrile (prepared from anisaldehyde, sodium cyanide, and benzoyl chloride) and by the reaction of acetic anhydride with the oxime of -methoxyphenylpyruvic acid. ... 

This procedure is an adaption of one described by Hauser and Chambers. Previous preparations include the benzylation of diethyl phenylmalonate followed by hydrolysis, the benzylation of phenylacetonitrile followed by hydrolysis, the benzylation of phenylacetic acid through the Ivanov reagent, and the reduction of oi-phenylcinnamic acid using sodium amalgam. ... 

Girgensohnia spp. G. diptera Bge. contains N-methylpiperidine and dipterine, CHH14N2, m.p. 87-8°, [a]D 0° hydrochloride, m.p. 177-8°, picrate, m.p. 189-190°, and picrolonate, m.p. 242-3°, which was later shown to be N-methyltryptamine.i G. oppositiflora Pall, contains N-methylpiperidine and girgensonine, C13H13ON2, m.p. 147-8°, [aJjj 0°. The latter forms a hydrochloride, m.p. 145-8°, and a picrolonate, m.p. 192-4°, and on hydrolysis by alkali yields piperidine, hydrocyanic acid and p-hydroxybenzaldehyde, indicating that it is N-piperidyl-p-hydroxy-phenylacetonitrile, and this has been confirmed by comparison with a synthetic specimen. ( (1) Juraschevski and Stepanova, J. Gen. Chem. Russ., 1939, 9, 2203 Juraschevski, ibid., 1940, 10, 1781. (2) Juraschevski and Stepanova, ibid., 1946, 16, 141). 

Attachment of a basic amino group to the side chain leads to a compound with antiparkinsonian activity. Alkylation of the carbanion from phenylacetonitrile with 2-chlorotriethylamine affords the product, 36. Conjugate addition of the anion from this to acrylonitrile gives the glutarodinitrile (37). Partial hydrolysis of this in a mixture of sulfuric and acetic acid leads to phenglutarimide (38). ... 

Glutarimides may be regarded as oxidized piperidines, and many drugs containing this moiety are sedatives and anticonvulsants. A spiro derivative, alonimid (105) is such a sedative-hypnotic agent. It can be prepared by K t-butoxide catalyzed biscyano-ethylation of phenylacetonitrile, leading to 101. Alkaline hydrolysis produces tricarboxylic acid 102 which is smoothly Converted to the glutaric acid anhydride (103) with acetic anhydride. Friedel-Crafts... 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

In a related reaction arylacetonitriles are nitrated to the corresponding a-nitronitriles, which on alkaline hydrolysis and subsequent acidification, yield arylnitromethanes. This method has been used to convert phenylacetonitrile to phenylnitromethane in 70 % overall yield without the need for intermediate purification. 

Barbier-type reaction conditions ) in THF at —30°C (—78°C for phenylacetonitrile) yielding, after hydrolysis, the expected compounds 20 (Scheme 8) . ... 

Fig. 7.9. Partial hydrolysis of phenylacetonitrile (A) under basic conditions to give the primary carboxylic acid amide B, and the possibility of hydrolyzing the latter to yield phenylacetic acid (C).

The total hydrolysis of phenylacetonitrile (Formula A in Figure 7.9) to phenylacetic acid (C) can be performed in one or two steps and both under acidic (following the mechanism in Figure 7.8) and basic conditions. In the latter case, the nucleophilic addition of a hydroxide ion to the nitrile carbon atom is the rate-determining step. This is how the imidic acid anion D is formed. Protonation (—> F), deprotonation (—> E) and reprotonation yield the amide B, which one can isolate or further hydrolyse under harsher conditions via the usual BAC2 mechanism (cf. Figure 6.24). 

Ozonolysis of vinylpyrazine in methanol at — 30° furnishes pyrazine aldehyde in 73% yield.196 Vinylpyrazine undergoes a variety of addition reactions and pyrazylethyl derivatives of amines, ketones, ethyl phenyl acetate, phenylacetonitrile, and acetamide have been obtained.197-199 2-(2-Pyrazylethyl)cyclohexanone (42) has been prepared both by the condensation of vinylpyrazine with cyclohexanone in the presence of sodium metal and by interaction of vinylpyrazine with the pyrrolidine enamine of cyclohexanone followed by hydrolysis.200... 

Oxidative decyanation of phenyl-3-pyridazinylacetonitriles, by passing a brisk stream of oxygen into an aqueous sodium hydroxide/DMSO solution of the substrate containing tri-ethylbenzylammonium chloride, is a convenient method for the synthesis of phenyl 3-pyridazinyl ketones (Scheme 55). Modified reaction conditions allow the one pot conversion of a-(6-chloro-pyridazin-3-yl)phenylacetonitrile into ketones with concomitant hydrolysis or methoxylation of the chloro substituent the direct one pot preparation of 3,6-dibenzoylpyridazine from 3,6-dichloro-pyridazine is achieved in 48% yield <93JHC1685>. 

Dilute sulfuric acid is used for hydrolysis of phenylacetonitrile (benzyl cyanide) to phenylacetic acid 626... 

For example, dropping a mixture of benzyl cyanide and methyl or ethyl nitrate into a cooled alkoxide solution leads to an 80% yield of 2- a-nitro-2-phenylacetonitrile, which gives phenylnitromethane on hydrolysis and decarboxylation.155,156 Ethyl phenylacetate also gives phenylnitromethane analogously and in the same yield.157 Further examples are described by Wislicenus and Wren.158 Wieland et al.159 have converted cyclohexane by this method into the potassium salt of 2-aa-nitrocyclohexanone in about 40% yield, and cyclo-pentanone almost quantitatively into the dipotassium salt of 2,5-di-fla-nitrocyclopentanone. 

Nitrile enolates can also react with carbonyl derivatives such as oxalate, which serves as a carboxyl surrogate. Reaction of 2-phenylacetonitrile and diethyl oxalate, in the presence of sodium amide, gave 4.99. " Catalytic hydrogenation of the cyano group and hydrolysis led to ethyl 2-phenyl-3-aminopropanoate, 4.100. In this case also, the nitrile moiety was an amine surrogate. Other a-aryl acetonitrile derivatives... 

Phenylacetonitrile (benzyl cyanide) was the first compound reported to undergo phase transfer alkylation and is probably the most abundantly studied example of this procedure [ 1 ]. It is a good substrate for study because it is reasonably acidic, but not readily alkylated by aqueous sodium hydroxide in the absence of catalyst at any synthetically useful rate. It has the further advantage that it can be mono-or dialkylated depending on conditions and it, like most nitriles, is not prone to rapid hydrolysis. It is a versatile synthetic intermediate, however, in the sense that the nitrile function can be hydrolyzed, reduced, or added to by organometallics after an alkylation has been carried out. 

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