Methedology Development On The Synthesis Of Aminonaphthoquinone And Benzodiazepine-fused Naphthoquinone Derivatives

2-(Nitroaryl)amino-1,4-naphthoquinones failed to be obtained through the classical routes due to the strongly electron-withdrawing nitro group, which deactivating the nucleophilic ability of the nitro anilines. Synthesis of 2,3-diamino-1,4-naphthoquinones via the coupling reaction of mono-aminonaphthoquinones with amines are limited because of the deactivating effect of an amino substituent to nucleophilic addition of a second amino group.The transition metal catalyzed amination of aryl halides has been developed rapidly in the past few years and has been proven to be a powerful method for the synthesis of various substituted amines. Considering the major effect of the use of palladium complexes in related C-N bond formation processes discussed in the literature,it seemed reasonable that the amination of 2-amino-3-chloro-1,4-naphthoquinones could be accomplished by using a palladium catalyzed amination reaction.The PdCl2(dppf)/DPPF catalyst combined with t-BuONa in toluene proved to be efficient both for the coupling of nitro substituted aryl amines with 2,3-dichloro-1,4-naphthoquinone and for the coupling of monoaminonaphthoquinones with amines. A variety of 2-[(nitroaryl)amino]-3-chloro- naphthoquinones and diaminonaphthoquinones,some unavailable by any other procedure,are now available by a simple and mild method.Reaction of 2,3-diamino-naphthoquinones with aldehydes in the presence of BF3·Et2O gives novel 4,5-dihydro-1H-1,4-naphthoquino[b]-benzo[e][1,4]diazepine derivatives in good yields. We speculate that the reaction takes place through a Pictet-Spengler cyclization mechanism. Although new application of Pictet-Spengler reaction in the preparation of seven-membered heterocyclic ring system has been reported,application of this reaction to aromatic amines linked to an activated aromatic nucleus was not as well documented.