An answer to the spiro versus ansa dilemma in cyclophosphazenes

Formation of novel spiro, spiroansa and dispiroansa derivatives of cyclotetraphosphazene from the reactions of polyfunctional amines with octachlorocyclotetraphosphazatetraene

“…14 The reactions of hexachlorocyclotriphosphazatriene, N 3 P 3 Cl 6 , with di-, tri-and tetra-functional amines have been extensively studied [15][16][17][18] and especially large difunctional diamines were reported for a potential value in cancer chemotherapy as selective carriers for delivering anticancer drugs to malignant target cells. 19,20 Although, a large number of octachlorocyclotetraphosphazatetraene (1), N 4 P 4 Cl 8 , with monofunctional amines were prepared and studied, 21-31 discussion on a substitution with polyfunctional amines is relatively limited in the literature. [32][33][34][35][36][37] We report here, the synthesis and structural characterization of six new cyclotetraphosphazene derivatives (scheme 1) and, to the best of our knowledge, there is no report so far of any derivative in this series that has been structurally characterized by any spectral data or x-ray crystallography.…”

Synthesis and characterization of per-substituted spermine-bridged cyclophosphazene derivatives: the first example of syn/anti conformational polymorphism in a bridged cyclophosphazene

“…For example, the diastereoisomeric properties of spermine-bridged cyclotriphosphazene derivatives that are geminally di-substituted in each cyclophosphazene ring have been compared with the analogous di-gem tetrasubstituted analogues which are achiral [9]. In those cases, where crystal structures are available [2,4,5,7,9,10], two broad ranges of conformers are observed as a result of rotation of the cyclophosphazene rings about the bridge; the conformations may be described as syn or anti. For example, it was found by Labarre and co-workers [5] that the spermine-bridged cyclophosphazene compound, [N 3 P 3 X 4 (NHCH 2 CH 2 CH 2 N)CH 2 CH 2 ] 2 , (1a) (X = Cl), exists with an anti conformation of the two cyclophosphazene rings about the single bridge.…”

“…Bridged compounds such as 1a-1h may exist as syn or anti conformers in the solid state and the first example of syn and anti conformational polymorphism is reported for a bridged cyclophosphazene, viz. for compound 1a.Although numerous fully and partially substituted derivatives of cyclotriphosphazene and cyclotetraphosphazene are known [1], the literature on singly and doubly bridged derivatives is sparse [2][3][4][5], until relatively recently [6-10]. Most bridged cyclophosphazene compounds are based on linking two cyclophosphazene derivatives with linear primary di-amines [2,3,6], polyamines, such as spermidine [4] or spermine [5,9] and with secondary diamines [7,8].…”

“…Most bridged cyclophosphazene compounds are based on linking two cyclophosphazene derivatives with linear primary di-amines [2,3,6], polyamines, such as spermidine [4] or spermine [5,9] and with secondary diamines [7,8]. A focus of recent work on bridged cyclophosphazenes has been to investigate their stereogenic properties [7][8][9] by X-ray crystallography and NMR spectroscopy.…”

“…Although numerous fully and partially substituted derivatives of cyclotriphosphazene and cyclotetraphosphazene are known [1], the literature on singly and doubly bridged derivatives is sparse [2][3][4][5], until relatively recently [6][7][8][9][10]. Most bridged cyclophosphazene compounds are based on linking two cyclophosphazene derivatives with linear primary di-amines [2,3,6], polyamines, such as spermidine [4] or spermine [5,9] and with secondary diamines [7,8].…”