Ethyl-2-cyano-2-phenyl-acetate

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

C11H11NO2 cyano-phenyl-acetic acid ethyl ester 4553-07-5... 

Scheme 4.1 Amination of ethyl a-phenyl-a-cyano acetate.

Acetic acid, chloro, tert butyl ester, 55, 94 Acetic acid, cyano-, ethyl ester, 55, 58, 60 Acetic acid, cyano-, methyl ester, 56, 63 Acetic acid, 3,4-dimethoxy-phenyl-, 55,45, 46... 

Yamagata etal. (86CPB516) found that condensation of 2-acetamido(or benzamido)-4,5-dihydrothiophene 3-carbonitriles 61 (R = Me or Ph) with ethyl cyanoacetate in the presence of sodium hydride afforded ethyl a-cyano-4-[2-(methyl or phenyl)thienopyrimidine]acetates 83a. Thiophenes 61 (R = Me or Ph) also reacted with malononitrile in a similar way, to yield the corresponding malononitriles 83b. 

Ethyl 2-cyano-2-(quinazolin-4-yl)acetate (2c), diethyl 2-(quinazolin-4-yl)malonates 2a and b, and 2-phenyl-2-(quinazolin-4-yl)acetonitrile (2d) undergo hydrolytic cleavage under the influence of acids to afford quinazolin-4(3//)-one (3). ... 

Early PG analysis using HPLC techniques was carried out as adsorption chromatography on normal-phase (NP) columns packed with silica or alumina. The nonpolar mobile phase comprizing of organic solvents (hexane, toluene, ethyl acetate, and HOAc) allows separation of PGs which are unstable in aqueous media (e.g., PGH2 on cyano- or phenyl-bonded phases). Usually, the injection medium must be fairly polar to dissolve the PGs. This is achieved by the addition of... 

Ethyl 3-cyano-2-ethoxy-7-methyl-4-phenyl-l,8-naphthyridine-6-carboxamide 415 with dimethylformamide dimethyl acetal produced enamine 416. Subsequent refluxing of the latter with ammonium acetate in ethanol leads to cyclization to form tricyclic naphthyridine 417 (1995H111). 

The 3-imino group of 4-cyano-2-ethyl-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione was acylated with phenyl isocyanate (78MI1). The imino group of l-imino-4-cyano-3-methylthio-l//-pyrido[l,2-cjpyrimidine was alkylated and acylated with methyl iodide and acetic anhydride (75YZ13). Reaction of 3-amino-4-phenyl-4-[2-(A, N-di-n-pro-pylamino)ethyl-4,4 a,5,6,7,8-hexahydro-l //-pyrido[l, 2-c ]pyri midin-l-one with acetic anhydride in pyridine and with sodium nitrite in aqueous acetic acid afforded 3-acetamido and perhydro-l,3-dioxo derivatives, respectively (87USP4680295). 

The coupling of ethyl (4,6-diamino-3,5-dicyano-2-pyridyl)acetate with benzenediazonium chloride in aqueous ethanolic sodium hydroxide solution produces the corresponding phenylhydra-zone, which is cyclized in refluxing acetic acid to give ethyl 2,4-diamino-3-cyano-5-imino-6-phenyl-5,6-dihydropyrido[2,3-a(]pyridazine-8-carboxylate,34 or in refluxing ethanolic sodium hydroxide to give ethyl 2,4-diamino-5-oxo-6-phenyl-5.6-dihydropyrido[2,3-t/]pyridazine-8-car-boxylate35 (see p 14). 

Ethyl 5-cyano-l-phenyl-6-oxo-4-styryl-l,6-dihydropyridazinc-3-carboxylate on refluxing with 30% aqueous ammonia gives ethyl 5-ami no-3,7-diphenyl-4-oxo-3,4-dihydropyrido[3,4-<7]-pyridazine-l-carboxylate (1), whereas refluxing with acetic acid/hydrochloric acid gives ethyl 3,7-diphenyl-4,5-dioxo-3,4,5,6-tctrahydropyrido[3,4-t/]pyridazinc-l-carboxylate (2). 30 Treatment with hot ethanolic sodium hydroxide produces the corresponding carboxylic acid 3.130 According to the obtained products an oxidation step must be involved. 

The scope of the reactions of 5-nitro-3-thienylethyl chloride and acetate with the lithium salt of 2-nitropropane to give (83) (cf. this series, Vol. 2, p. 80) has been investigated. The cyano-group was not found to be sufficiently active, since 4-cyano-2-thienyl-methyl and -ethyl chlorides only gave O-alkylated products by an mechanism. The iSn(AEAE) reaction also occurred between benzenethiolate and 4-nitro-2-thienylmethyl acetate, and a moderate yield of 4-nitro-2-thienylmethyl phenyl sulphide was obtained. 

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