Addition of nitriles Thorpe reaction

The method for cyclization of nitriles introduced by Ziegler, Eberle, and Ohlinger106c is suitable particularly for the synthesis of large-ring systems. It involves treatment of dinitriles with sodio-A-methylaniline in an atmosphere of nitrogen  

The reaction is carried out in solution in an ether (diethyl, diisopropyl, or di-n-propyl ether), at a temperature that must not exceed 100°. To induce intramolecular cyclization at the expense of intermolecular polymerization, the dinitrile is added in a continuous but slow stream to the stirred reaction medium (the Ruggli-Ziegler dilution principle). The decisive factors are the stationary concentration and thus the rate of reaction of the reactants high dilution favours intramolecular cyclization and disfavors intermolecular chain formation, and this dilution is achieved by adding the cyclizing material gradually into a relatively small reaction space. 

According to Ziegler and his co-workers,245 the condensing agent is best prepared by the reaction  

The ethylbenzene formed does not interference with subsequent reactions. The condensing agent is sensitive to air, so that all operations must be conducted with an atmosphere of pure nitrogen. For each 0.1 mole of the dinitrile, 1.5 1 of a 0.60-0.67 molar solution of sodio-Y-methylaniline containing a 25% excess of TV-methylaniline is used 246 the solution is heated and stirred under reflux in a nitrogen atmosphere while the dinitrile is run in continuously during 72 h. The subsequent hydrolysis to the cyclic ketone is carried out as indicated in the scheme above. 

Bachman and Barker247 cyclized bis-(2-cyanoethyl)amine in a simple reaction, obtaining a 70% yield of 4-iminopiperidine-3-carbonitrile  

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