Nitriles from aromatic rings

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. 

Interestingly, when R1 and R2 are hydrogens, the -configurated amino nitriles 1 arc obtained, whereas one or two methoxy substituents on the aromatic ring leads to (S)-diastereomers. This surprising effect is caused by the preferential crystallization of the (R)- or the (.S )-diastereomers, respectively. If the pure diastereomers of 1 are dissolved in methanol, equilibration occurs. On concentration, the optically pure diastereomer again crystallizes from the solution45. 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. 

The typical reaction of alkyl halides, we have seen (Sec. 14.5), is nucleophilic substitution. Halogen is displaced as halide ion by such bases as OH, OR, NH3, CN ", etc., to yield alcohols, ethers, amines, nitriles, etc. Even Friedel-Crafts alkylation is, from the standpoint of the alkyl halide, nucleophilic substitu tion by the basic aromatic ring. 

In 1952, Ritter and Murphy reported cases of intramolecular Ritter behavior resulting in formation of dihydroisoquinolines from reactions of methyleugenol with nitriles such as veratronitrile (equation 30). Such reactions involve nucleophilic attack by the aromatic ring on the nitrilium ion and are enhanced by... 

For electrophilic attack, Markovnikov addition is that in which the positive portion of the reagent adds to the least substituted carbon atom of the double bond undergoing reaction.) This may result from a steric preference for the least-substituted metal alkyl intermediate formed by insertion of olefin into the metal hydride bond . Vinylarenes comprise an exception, where interaction of nickel with the aromatic ring stabilizes the precursor of the branched nitrile, leading primarily to a Markovnikov addition product . 

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