Phosphorus–nitrogen compounds Part 55. Syntheses of 4-methoxybenzylspiro(N/N)cyclotriphosphazenes: chemical, structural and biological properties

Abstract: The NP ring of hexachlorocyclotriphosphazene, NPCl (1) (HCCP; trimer), was used significantly as a scaffold for the syntheses of inorganic–organic-based hybrid cyclotriphosphazenes, as it is a highly robust skeleton among inorganic phosphorus–nitrogen ring systems. However, hybrid cyclotriphosphazenes with pendant arm(s) have been quite less explored. In the present study, the unsymmetrical bulky 4-methoxybenzyldiamines, CHOPhCHNH(CH)NHR (n = 0, R=CH2; n = 0, R = CH3 and n = 1, R = CH4), were obtained after the reduction of the corresponding Schiff bases formed as a result of condensation reactions of aliphatic diamines with 4-methoxybenzaldehyde. Reactions of the diamines (2–4) with HCCP (1) gave the new monospiro-(5–7), cis-dispiro (8–10) and trans-dispiro (11–13) cyclotriphosphazenes with 4-methoxybenzyl (p-anisyl) pendant arm(s). The fully substituted monospiro derivatives; 5a–7a, 5b–7b and 5c–7c, were prepared from the reactions of 5, 6 and 7 with pyrrolidine, tetra-1,4-dioxa-8-azaspiro[4.5]decane and piperidine, respectively. FTIR, ESI–MS and H, C, P NMR spectral data of all cyclotriphosphazenes were presented. The cis-dispiro (8–10) and trans-dispiro (11–13) cyclotriphosphazenes have two-equal stereogenic P-centers, and they can form cis (meso; RS/SR) and trans (racemic; RR/SS) optical isomers. The molecular and crystal structures of 7 and 11 were revealed by X-ray crystallography. The space group of compound 11 was found to be P − 1, and the absolute configurations of the centers P1 and P2 were determined as S and S, respectively. In addition, the antibacterial and antifungal activities of fourteen cyclotriphosphazenes against G(−) and G(+) bacteria and fungi were determined. The interactions of cyclotriphosphazenes with plasmid DNA were investigated using agarose gel electrophoresis. Graphic abstract: [Figure not available: see fulltext.]