Thorpe-Ziegler ring closure

The use ort/io-cyanoanilines provides an effective means to prepare 4-aminoquinolines by base-catalyzed ring closure onto the cyano group <97BCJ 1697>. In one example the use of DMSO/KO-r-Bu offers a mild base system for the Thorpe-Ziegler reaction <97H(45)483>. 

A second route to 78 was first attempted from 79 0,91 Unlike 75 above, 79 did not cyclize in the Dieckmann reaction, so it was converted to the corresponding dinitrile 80 for Ziegler-Thorpe ring closure. This cyclization was successful, and exposure of the resulting enamino nitrile to acid hydrolysis and then Jones oxidation yielded ketolactone 81. In this case the carbene insertion failed. These differences in the fates of closely related carbenes presumably reflect changes in dynamic conformation as a function of specific structure. In contrast to the carbene insertion, the thermal reaction in the presence of palladium-on-carbon used previously on 77 did succeed with 81, giving directly a modest yield of 78. 

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