Anisyl chloride

In a 2-1. three-necked round-bottomed flask, fitted with an efficient sealed stirrer and a reflux condenser capped by a drying tube, are placed the dried anisyl chloride (Notes 2 and 3), 73.6 g. (1.5 moles) of finely powdered sodium cyanide, 10 g. of sodium iodide, and 500 ml. of dry acetone (Note 4). The heterogeneous reaction mixture is heated under reflux with -sngorous stirring for 16-20 hours, then cooled and filtered with suction. The solid on the filter is washed with 200 ml. of acetone and discarded (Note 5). The combined filtrates are distilled to remove the acetone. The residual oil is taken up in 300 ml. of benzene and washed with three 100-ml. portions of hot water. The benzene solution is dried over anhydrous sodium sulfate for about 15 minutes, and the solvent is removed by distillation at the reduced pressure of the water aspirator (Note 6). The residual -methoxyphenyl-acetonitrile is purified by distillation under reduced pressure through an 8-in. Vigreux column b.p. 94—97°/0.3 mm. 1.5285-1.5291. The yield is 109-119 g., or 74-81% based on anisyl alcohol (Notes 7 and 8). 

The crude anisyl chloride is unstable. It should be used the same day it is made. 

This method is particularly applicable to the more reactive benzyl halides which are easily hydrolyzed in the aqueous media usually employed for the metathetical reaction with alkali cyanides. For example, anisyl chloride treated with sodium cyanide in aqueous dioxane gives, as a by-product, 5-10% of anisyl alcohol as determined by infrared analysis. The use of anhydrous acetone not only prevents hydrolysis to the alcohol but also decreases the formation of isonitriles. This method was also applied successfully by the submitters to the preparation of -chlo-rophenylacetonitrile in 74% yield. 

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 compound is usually made and used in situ. A 5 g sample was allowed to sit in a screw top vial for a couple of days, one morning it was found to have blown a hole in the lid and extruded a 20 ml plume of polymeric foam [1], An attempt to dry anisyl chloride over molecular sieves pressurised the container, presumably with hydrogen chloride evolved during polymerisation [2],... 

Benzylbenzo[i>]thiophene13z and 2-p-methoxybenzylbenzo[i>]-thiophene and its 3-ethyl derivative 464 may be prepared by treating 2-benzo[6]thienyllithium or its 3-ethyl derivative with benzyl chloride or anisyl chloride, respectively. Various p-methoxybenzyl-benzo [6]thiophenes may be prepared by Friedel-Crafts reactions between the appropriate benzo[6]thiophene and anisyl chloride.464... 

Aryl chlorides are more reluctant to participate in amination than most other aryl halides/pseudohalides. To tackle this problem, Caddick et al. examined the effect of palladium-N-heterocyclic carbenes as catalysts in rapid microwave-promoted reactions [87]. Para-tolyl and -anisyl chloride were reacted with aromatic and aliphatic amines in mostly good yields within 6 minutes of heating at 160 °C. Reactions using anisyl, tolyl or phenyl chlorides and aliphatic amines have also been reported by Maes et al. using a phosphine ligand and a strong base, which creates the desired products after 10 minutes of heating at 110-200 °C [88]. 

Aluminum chloride Aluminum lithium hydride Ammonia solution Ammonium hydroxide Ammonium persulfate Anisyl chloride Aqua regia... 

Amyl bromide [Pentane, 1-bromo-], 82 Aniline [Benzenamine], 122 Anilines, o-alkylation of, 15 Anisole [Benzene, methoxy-j, 48 Anisyl chloride [Benzene, l-(chloromethyl)-... 

Another approach for the total synthesis of anisomycin derivatives from (+)-tartaric acid has been reported via the N -benzyl tartarimide (95) (Scheme 11) [89]. Thus, (+)-tartaric acid was refluxed with benzyl amine in a xylene solution to give 95, which was subjected to reaction with the Grignard reagent of anisyl chloride in THF to give the keto-amide 96 in 55% yield. 

Scheme 11 a BnNH2, xylene, reflux, 3 h with continuous water removal b Mg, anisyl chloride, THE, rt, 30 min then added N-benzyl tartarimide, rt, overnight, 55% c LiAlH4, THE, reflux, 6h d AC2O, 20 min e EtOH, HCl, 5% Pd-C, H2, 3h f P2O5, CHCI3, 10 min, evaporation then added MeOH, 20% KOH in EtOH, 30 min g glacial acetic acid, reflux, 90 min, evaporation then 1 N NaOH, reflux, 2 h... 

Methoxyhenzyl chloride (anisyl chloride) [824-94-2] M 156.6, m -1", h 76"/0.1mm, 95"/5mm, 110"/10mm, 117-117/5"/14mm, 117"/18mm, df 1.15491, ng 1.55478. Purify 4-anisyl chloride by fiactional distillation under vacuum, and the middle fraction is redistilled at 10" mm at room temperature by intermittent cooling of the receiver in licpiid N2, and the middle fraction is collected. [Mohammed Kosower JAm Chem Soc 93 2709 7977, Beilstein 6 TV 2137.]... 

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