1H, 13C and 15N NMR of spiro acridines integrated with pyrrole scaffolds

Acridines are important organic compounds with potent biological properties, which are in focus of our long‐ term research. The hydrazide–hydrazone fragment CH═N─NH─CO represents a significant structural unit with a wide range of biological activities such as antitumor, antimicrobial, anti‐inflammatory, and antituberculotic. The use of acridine derivatives in the synthesis of hydrazide–hydrazones has seemed favorable to us because of their interesting antiviral, antibacterial, and antitumor properties. In connection with our ongoing studies on the new acridine derivatives, we decided to prepare compounds containing both hydrazide–hydrazone and acridine substructures for utilization in the synthesis of heterocycles. Originally, we intended to obtain novel compounds 3 (Scheme 1) from starting N′‐[(E)‐acridin‐9‐ylmethylidene]‐2‐ cyanoacetohydrazide (2a). We have found, however, that 2a rapidly reacted with another molecule of acridin‐9‐ carbaldehyde (1a) via methylene carbon forming a non‐isolated intermediate 4a and eventually a spiro compound 5a due to spontaneous spirocyclization. As it was previously reported, we again observed a particular susceptibility of acridine C‐9 carbon to the nucleophilic attack enabling subsequent formation of a five‐membered spiro ring. Owing to a rapid reaction of the hydrazide 2a with aldehyde 1a, further derivatization of 2a was not possible. Inspired by this reaction course, we changed the strategy and attempted a reaction of substituted benzaldehydes 1b–i with 2‐cyanoacetohydrazide affording acylhydrazones 2b–i. Their subsequent reaction with the aldehyde 1a provided non‐isolable intermediates 4b–i, which again rapidly spirocyclized to 1‐[(E)‐ (phenylmethylidene)amino]‐5‐oxo‐1,5‐dihydro‐10′H‐ spiro[acridine‐9′,2‐pyrrole]‐4‐carbonitriles 5b–i (Scheme 2). In our work, we synthesized altogether nine derivatives of 5, of which five derivatives, 5b,d,e,g,i, have been described previously. Although H and C nuclear magnetic resonance (NMR) data for the compounds 5b,d,e,g,i were already published in papers, 17] reporting also their biological activity, the data were