SYNTHESIS OF 2,9-DI(HALOPHENYL)SUBSTITUTED POLYAZAPOLYCYCLES OF THE PERHYDROTETRACENE SERIES

Abstract

Saturated N-containing polycycles occupy a special place among the wide variety of heterocyclic compounds, which is largely due to their prospects for practical application. Catalysis methods open up wide possibilities in the synthesis of functionally substituted azapolycycles. Catalytic heterocyclization reactions make it possible to selectively design complex organic compounds under mild conditions and represent a powerful tool for the targeted synthesis of heteropolycycles of a given molecular structure based on simple and affordable starting reagents. One of the effective "building blocks" is trans-1,2-diaminocyclohexane. The world literature presents approaches to the synthesis of both N,N'-disubstituted derivatives of trans-1,2-diaminocyclohexane and its cyclic adducts, including poly- and macroheterocycles. Compounds containing a trans-1,2 diaminocyclohexane fragment in their structure have antitumor activity and antiproliferative effects, and are of interest as N-containing chiral ligands, bifunctional organocatalysts, and catalysts for enantioselective transforma tions. Based on trans-1,6,7,12-tetraazaperhydrotetracene obtained from trans-1,2-diaminocyclohexane and glyoxal, hexaazaperhydrodibenzotetracenes with a wide range of functional substituents can be synthesized. In this work, we have proposed a single-reactor method for the synthesis of 2,9-di(halophenyl)substituted (3bR*,7aR*,10bR*,14aR*-cis-14c,14d)-octadecahydro-1H,8H-2,3a,7b,9,10a,14b-hexaazadibenzo[fg,op]tetracenes by the reaction of multicomponent condensation of trans-1,6,7,12-tetraazaperhydrotetracene with N,N,N',N' tetramethylmethanediamine and halogenanilines in the presence of a Ni(II) hexahydrate chloride catalyst. The structures of the synthesized perhydro hexaazadibenzotetracenes were established based on NMR data using 2D techniques (COSY, NOESY, HSQC, HMBC) and confirmed by registration of molecular peaks in high-resolution mass spectra (HRMS) using a mass analyzer (TOF) with electrospray ionization (ESI). The developed approach made it possible to obtain perhydrotetracenes with R*,R*,R*,R*-relative configuration of chiral centers at carbon atoms C3b, C7a, C10b, C14a and with cis-junction of piperazine rings at the C14c–C14d bond.