Phenylacetonitrile, methylation

This procedure is called chloromethylation and will not only turn 1,3-benzodioxole into a methyl chloride but will work equally well in converting plain old benzene into benzyl chloride. Both are important stepping stones towards the production of X and meth. For example, benzyl chloride is a schedule I controlled substance because it will beget benzaldehyde and phenylacetonitrile (a precursor for phenylacetic acid). 

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. ... 

Essentially the present procedure converted 1-methylgramine to l-methyl-S-indoleacetonitrile," but it failed to convert benzyl-dimethylphenylammonium chloride to phenylacetonitrile. ... 

Phenylacetonitrile is alkylated with secondary butyl bromide and the resultant nitrile is hydrolyzed to 3-methyl-2-phenylvaleric acid. The acid is converted to the acid chioride with thionyl chloride and the acid chloride is in turn reacted with 1-methyl-4-piperidinol. Finally dimethyl sulfate is reacted with the ester. 

Recently, it has been reported that methyl 2-pyridyl sulphoxides (10) and related pyridyl derivatives (11) (see Schepie 25) are good phase transfer catalysts for SN2 reactions of various primary or secondary alkyl halides in a two-phase reaction system and for the alkylation of phenylacetonitrile or phenylacetone with alkyl halides in liquid-liquid two-... 

A. 2-Hydroxyimino-2-phenylacetonitrile. A 1-1., round-bottomed flask is fitted with a mechanical stirrer, a calcium chloride drying tube, a thermometer, and a gas-inlet tube. In the flask are placed 117 g. (1.0 mole) of benzyl cyanide and a solution of 40.0 g. (1.0 mole) of sodium hydroxide in 300 ml. of methanol (Note 1). The resulting solution is stirred and cooled at 0° as methyl nitrite is introduced through the gas-inlet tube, which extends below the surface of the liquid. The methyl nitrite is generated by dropwise addition of a cold solution of 32 ml. of concentrated sulfuric acid in 65 ml. of water from a 100-ml., pressure-equalizing dropping funnel into a 300-ml. Erlenmeyer flask containing a suspension of 83 g. (1.2 moles) of sodium nitrite... 

When phenylacetonitrile is converted to its anion in the presence of excess LDA and then allowed to react with 2-bromo-4-methyl-l-methoxybenzene, the product contains both a benzyl and cyano substituent. Propose a mechanism for this reaction. 

The recombinantly expressed nitrilase from Pseudomonas fluorescens EBC 191 (PFNLase) was applied in a study aimed at understanding the selectivity for amide versus acid formation from a series of substituted 2-phenylacetonitriles, including a-methyl, a-chloro, a-hydroxy and a-acetoxy derivatives. Amide formation increased when the a-substituent was electron deficient and was also affected by chirality of the a- stereogenic center for example, 2-chloro-2-phenylacetonitrile afforded 89% amide while mandelonitrile afforded 11% amide from the (R)-enantiomer but 55% amide was formed from the (5)-enantiomer. Relative amounts of amide and carboxylic acid was also subject to pH and temperature effects [87,88]. 

Phenylacetonitriles can be induced to undergo Michael reactions with unactivated alkenes. For example, propenylarenes, formed in situ from allylarenes, react with phenylacetonitriles to form 3-aryl-l-cyano-2-methyl-l-phenylpropanes (70-98%) [3] by a procedure analogous to 6.4.1.B, Similarly, the nitriles react with alkynes giving allyl cyanides (80-95%) [38]. 

Enantiomers of 2,7-dimethyl-l,6-dioxaspiro[4.5]decane 28 Enantiomers of 2-Ethyl-7-methyl-l,6-dioxaspiro[4.5]decane 29 Enantiomers of 2,8-dimethyl-l,7-dioxaspiro[5.5]undecane 30 5 - Methylh eptan - 2 -ol (Z)-Non-3-en-l-ol 3,7-Dimethyloctan- l-ol Benzaldehyde 2-Phenylethanol Phenylacetonitrile Isobutyl benzoate Isopentyl benzoate Hexadecanoic acid 17-Hydroxyan drost-4-en-3-one (2)-Octadec-9-enoic acid... 

A variety of other carbon nucleophiles have been alkylated with alcohols including malonate esters, nitroaUcanes, ketonitriles [119, 120], barbituric acid [121], cyanoesters [122], arylacetonitriles [123], 4-hydroxycoumarins [124], oxi-ndoles [125], methylpyrimidines [126], indoles [127], and esters [128]. Selected examples are given in Scheme 35. Thus, benzyl alcohol 15 could be alkylated with nitroethane 147, 1,3-dimethylbarbituric acid 148, phenylacetonitrile 149, methyl-pyrimidine 150, and even f-butyl acetate 151 to give the corresponding alkylated products 152-156. 

Benzyl-4,4,6-trimethyl-5,6-dihydro-l, -3(4H)-oxazine, from 2-methyl-2,4-pentanediol and phenylacetonitrile, 51,27... 

There are no reported examples of the reaction of the quinolizinium ion or its angular benzo derivatives with active methyl and methylene compounds. The linear benzo[6]quin-olizinium (3) bromide and some of its derivatives have been found to react with acetone, acetophenone and phenylacetonitrile in the presence of hydroxide ion (59JA1938). On the basis of 1HNMR data obtained later (67JOC733), it is clear that the reaction product of... 

In another investigation, linalool (Fig. 8.1) was detected in relatively low concentration in the solvent-extracted volatiles of fresh papaya pulp from Sri Lanka [41]. The authors attributed the characteristic sweaty note of this papaya fruit mainly to methyl butanoate. Phenylacetonitrile was also found in high amounts (17.7%), which, according to the authors, combined with lesser concentrations of benzyl isothiocyanate (1.5%) can play a role in the aroma of papaya. 

Condensation of the sodium salt of phenylacetonitrile with 1,3-dibromobulane gives an isomeric mixture of l-cyano-2-methyl-1-phenylcyclobutanes 21 and 22.30 The effects of solvents on this cyclization reaction have been studied. While solvents of low dielectric constants seem to favor the formation of 21, the ratio of 21 to 22 was found to be almost 1 1 in dipolar aprotic solvents, as can be seen in the following table.30... 

The procedure given above is an adaptation of the methylation method first used by Sommelet and Ferrand3 and developed more fully by Clarke, Gillespie, and Weisshaus.2 /3-Phenylethyldi-methylamine has been prepared from /9-phenylethylamine by alkylation with dimethyl sulfate 4 by the reaction of fi-phenyl-ethylamine and of N-methyl- S-phenylethylamine with formaldehyde 6 by catalytic reduction of phenylacetonitrile in the presence of dimethylamine 3 by the reaction of dimethylamine with /3-phenylethyl chloride 7 8 9 and with /3-phenylethyl bromide 9 and by the reaction of phenylacetaldehyde with dimethylamine.10... 

The reaction between phenylacetonitriles and methyl formate is similar in nature and yields 4-cyanoisocoumarins (53JIC103). 

Novel 3-aryl-2-imino-4-methyl-2,5-dihydrofurans have also been efficiently synthesised using focused microwave heating by a one-pot condensation from a-ketols and substituted phenylacetonitrile in the presence of sodium ethoxide in ethanol (Scheme 3.2)4. 

In comparison, the l,3-dialkylimidazolium-2-carboxylate isolated by Tommasi et al. [27, 40] was revealed to be a more versatile catalyst that allowed the synthesis of benzoylacetic acid from benzophenone and C02 in good yield and under mild conditions (isolated yield 81%). The presence of tetrafluoroborate- or tetraphenyl-borate sodium salts in the reaction was essential, as this allowed the formation of the related 1,3-dialkylimidazolium tetrafluoroborate or tetraphenylborate and the concomitant quantitative trans-carboxylation to sodium benzoylacetate. Likewise, compounds such as acetone, cyclohexanone, and phenylacetonitrile could also be converted with this system to afford the corresponding carboxylate salts (methyl a-cyanophenylacetate) (Scheme 5.8). Following the same general procedure, acetone was carboxylated, being simultaneously the cosolvent and reagent. 

Phenylacetonitrile Thionyl chloride Sodium amide l-Methyl-4-piperidinol... 

To check the. general applicability of activation by alkali, Paty (44) extended the investigation to several functional groups. The addition of small amounts of sodium hydroxide considerably reduced the time for reduction of 2-methyl-2-butene, phenylacetonitrile, and anethole. Larger amounts of alkali, in the case of phenylacetonitrile and in the case of anethole, increased the time for complete hydrogenation. Paty considers that the activating effect is due to the action of sodium hydroxide on the residual aluminum or nickel-aluminum alloy in the catalyst. 

This reaction gives high product yields and works with a methylbenzyl-cyanide, 9-methylfluorenide anions as well as with the anion of a-meth-ylphenylacetic ester or propiophenone. No reaction is however found with the non methylated anions of phenylacetonitrile, fluorene, phenylacetic ester or acetophenone. The postulated mechanism implies an hydrogen abstraction from an anion leading to a radical anion intermediate ... 

In the temperature range of 1050-1700 K, similar to pyrrole, the main thermal reactions of indole are isomerization to produce 2-phenylacetonitrile 8, and 2-methyl- 9 and 3-methyl- 10 benzenecarbonitriles as a result of the pyrrole ring opening under shock heating (Scheme 4) <1997PCA7787>. 

---