Acetonitrile methoxyphenyl

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). 

There is also substantial stabilization of [4+] by electron delocalization from the cyclic a-vinyl group. This is shown by a comparison of the thermodynamic driving force (p Tr lies between —7.8 and —8.5) and absolute rate constant (ks = 1 -6 x 107 s 1) for the reaction of [4+] in 25% acetonitrile in water with the corresponding parameters for reaction of the resonance-stabilized l-(4-methoxyphenyl)ethyl carbocation in water (p Tr = — 9.4and s= 1 x 108 s Table 5). 

The photo-oxidation of the aryl-substituted cycloheptatrienes 7-(/ -methoxy-phenyl)cycloheptatriene and 7-, 1- and 3-(/ -dimethylaminophenyl)cycloheptatrienes to the corresponding radical cations in de-aerated acetonitrile solution was accomplished by electron transfer to the electronically excited acceptors 9,10-dicyanoanthracene, iV-methylquinolinium perchlorate, iV-methylacridinium perchlorate and l,T-dimethyl-4,4-bipyridinium dichloride. In the case of l- p-methoxyphenyl)cycloheptatriene (62), deprotonation of the radical cation occurs successfully, compared with back electron transfer, to give a cycloheptatrienyl radical (63) which undergoes a self-reaction forming a bitropyl. If the photooxidation is done in air-saturated acetonitrile solution containing HBF4 and one of the acceptors, the tropylium cation is formed. Back electron transfer dominates in the / -dimethylaminocycloheptatrienes and the formation of the cycloheptatrienyl radical is prevented. 

Vaughn SF, Boydston RA, MaUory-Smith CA (1996) Isolation and identification of (3-methoxyphenyl)acetonitrile as a phytotoxin from meadowfoam Limnanthes alba) seedmeal. J Chem Ecol 22 1939-1949... 

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

NUCLEOPHILIC AROMATIC SUBSTITUTION OF (2-METHOXYPHENYL)-ACETONITRILE WITH ISOBUTYRONITRILE... 

Nitrenium ions can be viewed as products from two-electron oxidation of amines (Fig. 13.13) followed by loss of a proton. Thus they need to be considered as intermediates in the oxidation of amines. In two early studies, diarylnitrenium ions were shown to have formed in the oxidation of diarylamines. Svanholm and Parker carried out cyclic voltammetry on A,A-di-(2,4-methoxyphenyl)amine (25) in acetonitrile with alumina added to suppress any adventitious nucleophiles. The voltam-mogram revealed two sequential oxidation processes (1) formation of the cation radical 26, and (2) either the nitrenium ion 27 or its conjugate acid. In strongly acidic solution the latter was sufficiently stable that its absorption spectrum could be recorded. 

Fluoro-l-(4-methoxyphenyl)-3-(phenylselanyl)propane is obtained in 53 % yield in a one-pot synthesis by reaction of 3-(4-methoxyphenyl)prop-l-ene with benzeneselenenic chloride and silver(I) fluoride in acetonitrile at room temperature for 18 hours.37... 

Evans and co-workers159 reported that 5-p-methoxyphenyl-3-phenyl-1,2,4-oxadiazole fluoresces in acetonitrile as solvent and was quenched by olefins. 

In this respect, it is of interest that the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile proceeds with retention of ( )-olefin geometry in acetonitrile from the first excited singlet state of the anisole chromophore [160] (Scheme 40). The ortho adduct undergoes further... 

The resulting reaction solution was poured into 200 ml of ice water, and the toluene phase was separated off and washed twice with water. The required amount of hydrochloric acid was added to the toluene solution, the toluene was distilled off under reduced pressure and the residue, which remained was recrystallized from acetone to give l,7-bis-(2-methoxyphenyl)-3-methylaza-7-cyanononadecane hydrochloride or a-dodecyl-3-methoxy-a-[3-[[2-(3-methoxyphenyl)ethyl] methyl amino] propyl] benzene-acetonitrile (anipamil) ... 

Pyridine may react as a nucleophile with radical cations to pyridinium salts, as in the electrolysis of anthracene in acetonitrile-pyridine which yields a bis-pyridinium-adduct 283 With tris (p-methoxyphenyl)ethylene a tripositive tripyridinium cation is formed (Eq. (124) ) 284 ... 

The assertion of W. L. F. Armarego [in Advances in Heterocyclic Chemistry (A. R. Katritzky, ed.), Vol. 1, pp. 282-283. Academic Press, New York, 1963], attempts made to prepare l,2-dimethyl-l,4-dihydroquinazo-lines from o-methylaminobenzyl chloride hydrochloride and acetonitrile in the presence of stannic chloride gave l,2-dimethyl-4(lH)-quinazolinone [M. Lora-Tamayo, R. Madronero, and G. G. Munoz, Ber. 94, 208 (1961)] , is mistaken. This type of reaction has permitted the preparation, for the first time, not only of l-methyl-2-phenyl-, l-methyl-2-(o-nitrophenyl)-, and l-methyl-2-(p-methoxyphenyl)-l,4-dihydroquinazolines, but also of 1,2-dimethyl-l,4-dihydroquinazoline. The stability of these compounds depends in a great measure on the substituent on position 2. Contrary to the statement of Armarego, the infrared spectrum of the tin complex has not been recorded by us. 

Enamine (342 Ar = 3-methoxyphenyl) reacts with Nal in acetonitrile at 80 °C giving the pyrano-pyridine derivative (87) (40% yield) <89JCS(Pl)il77> and this represents an example of a transformation of the general type (295) -> (290). 

Bis[4-methoxyphenyl] tellurium trichloroacetimidc was similarly reduced by thiourea in acetonitrile. Bis[4-methoxyphenyl] tellurium was isolated in 92% yield3. 

A palladium(O) catalyzed reaction in acetonitrile converted bis[4-methoxyphenyl] tellurium to 4,4 -dimethoxybiphenyl in quantitative yield4. 

Diphenyl ditellurium in acetonitrile reacted at 125° with carbon monoxide at 100 atm in the presence of octacarbonyldicobalt to give phenyl tellurohenzoate in 52% yield. Carbon monoxide at only one atmosphere and 0° effected the same conversion when benzoyl(tetracarbonyl)cobalt was used instead of octacarbonyldicobalt. Addition of triphenylphosphane to the reaction mixture prevented the formation of phenyl telluroben-zoate. Attempts to carry out this carbonylation catalytically with respect to the cobalt compound failed. Bis[4-methoxyphenyl] ditellurium and didodecyl ditellurium did not produce any tellurocarboxylic esters under these conditions2. 

Diaryl tellurium dichlorides, obtainable from aromatic compounds and tellurium tetrachloride, react with excess bromine or iodine in refluxing DMF or acetonitrile in the presence of a metal fluoride to give aryl halides in low yields. The reactions with chlorinating agents are very sluggish. The reaction of bromine and bis[4-methoxyphenyl] tellurium dichloride formed 2,4-dibromomethoxybenzene in 76% yield. Reactions of these tellurium dichlorides with copper(I) cyanide in DMF produced aryl cyanides in yields of less than 8%3. 

Dialkyl, diaryl, alkyl aryl, and heterocyclic tellurium oxides are known. Most of these compounds are white solids that are soluble in sodium hydroxide. Diorgano tellurium oxides appear to be oxidized by atmospheric oxygen. Their exposure to air should be minimized5. The protonation constant of dimethyl tellurium oxide in water was found to be 6 (pKa)6,7, and of bis[4-methoxyphenyl] tellurium oxide in acetonitrile 14.9s. The barrier to inversion for dihydrogen tellurium oxide (H2Te = 0), the parent compound of diorgano tellurium oxides, was determined as 92.4 kJ/mol (22.0 kcal/mol) by extended Hiickel calculations9. 

Dimethyl-l,3-dioxo-2-cyclohexyl 5,5-Dimethyl-l,3-dioxo-2,2-cyclohcxyhdene 4-Methoxyphenyl Tellurium1 1.9 g (4.5 mmol) of 4-methoxyphenyl benzenesulfonylimino tellurium chloride and 1.26 g (9 mmol) of 5,5-dimcthyl-1.3-dioxocyclohexane are suspended in 50 ml of benzene. A solution of 0.46 g (0.6 ml 4.5 mmol) of triethylamine in 10m/of benzene is added dropwise to the stirred suspension and the mixture is allowed to stand for 1 day. The precipitate is filtered off, washed with cold acetonitrile, then with water, and dried in the air yield 1.8 g (79%) m.p. 132° (from acetonitrile). 

A mixture of l-(5-chloro-2-methoxyphenyl)piperazine (28.64 g), K2CO3 (44.6 g) and N-(3-bromopropyl)phthalimide (33.65 g) were dissolved in 250ml acetonitrile and refluxed 8 hours. The mixture was cooled, poured into 800 ml water, filtered, recrystallized in methyl alcohol, and the product isolated in 91% yield, mp = 131-133 °C. 

Kaiser DG, Glenn EM (1972) Correlation of plasma 4,5-bis(p-methoxyphenyl)-2-phenyl-pyrrole-3-acetonitrile levels with biological activity. J Pharm Sci 61 1908-1911... 

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