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

The N 3 P 3 ring of hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 ( 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, CH 3 OPhCH 2 NH(CH 2 ) n NHR ( n = 0, R=CH 3 2 ; n = 0, R = C 2 H 5 3 and n = 1, R = CH 3 4 ), 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 1 H, 13 C, 31 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