Synthesis and enantiomeric analysis of cyclotriphosphazene derivatives with one centre of chirality Bünyemin Ços ßut, Hanife _ Ibis ßog ˘lu, Adem Kılıç, Serkan Yes ßilot * Department of Chemistry, Gebze Institute of Technology, Gebze, Turkey article info Article history: Received 24 April 2009 Received in revised form 13 July 2009 Accepted 22 July 2009 Available online 27 July 2009 Keywords: Cyclotriphosphazene derivatives Chirality NMR CSA (chiral solvating agent) Chiral HPLC abstract A series of chiral cyclotriphosphazene compounds 2–9 in which the spiro 3-amino-1-propanoxy moiety provides the one centre of chirality have been synthesised and characterised by elemental analysis, MS, 1 H and 31 P NMR spectroscopies. The enantiomers of newly synthesised compounds have been analysised by the changes in the 31 P NMR spectra on addition of a Chiral Solvating Agent (CSA), (S)-(+)-2,2,2-tri- fluoro-1-(9 0 -anthryl)ethanol. HPLC methods have been developed for the enantiomeric separations of chiral cyclotriphosphazenes containing one centre of chirality. It is found that chiral HPLC gave a good resolution of enantiomers of the racemic compounds 2–9 with resolution factors between 2.49 and 7.50 making them good candidates for enantiomeric separations and determination of absolute configuration. Ó 2009 Elsevier B.V. All rights reserved. 1. Introduction Chiral phosphorus compounds (P-chiral) have been attracting great interest [1] because of their importance as chiral solvating agents [2], chiral ligands in solution [3] and enzyme inhibitors [4]. Cyclophosphazenes are an important class of organophospho- rus chemistry and their derivatives have been of considerable interest because, for example, it is possible to design materials with special properties such as thermal stability, catalytic proper- ties, electrical conductivity, liquid crystal and biomedical activity [5]. Tetracoordinated phosphorus atoms in cyclophosphazenes are pentavalent and potential stereocentres. There has been consider- able interest recently in the determination of the stereogenic properties of chiral cyclotriphosphazene derivatives as an aid in studying reaction mechanisms [6]. There are two reports of the separation of enantiomers by chiral HPLC [7]. Other studies on the stereogenic properties of cyclotriphosphazene derivatives pro- vide examples in which an optically-active acyclic precursor was cyclised [2] and those in which the substituent group was stere- ogenic [8,9]. In the main, the investigations of reaction mecha- nisms have utilised cyclotriphosphazenes containing two equivalent centres of chirality giving either meso or racemic products [6]. Similarly, the stereogenic properties of symmetri- cally-substituted bridged-cyclotriphosphazenes usually contain two centres of chirality and have been characterised as diasteroi- somers existing as meso and racemic forms [6]. In these investi- gations the stereogenic properties of chiral cyclotriphosphazene derivatives have been determined by X-ray crystallography and/ or 31 P NMR spectroscopy on addition of a chiral solvating agent (CSA), (S)-(+)-2,2,2-trifluoro-1-(9 0 -anthryl)ethanol [6,10]. There are a number of problems with these methodologies and a more routine method is required to investigate the stereogenic proper- ties of cyclotriphosphazenes. Firstly, it is not always possible to get crystals that are suitable for X-ray crystallography and it is not always possible using the 31 P NMR/CSA method to show that the molecules are chiral, even on addition of CSA up to a very large molar ratio [11]. Secondly, it has been shown for bridged- cyclophosphazenes with symmetrically-substituted centres of chirality that the 31 P NMR/CSA method gives peak separations for both the meso and racemic forms and cannot be used to char- acterise the diasteroisomers unequivocally [12]. Therefore, chiral HPLC has been used recently for the characterisation of stereo- genic properties of chiral cyclotriphosphazenes containing two equivalent centres of chirality [11,13]. On the other hand, chiral HPLC methods have also been developed for the enantio-separa- tion of racemic cyclotriphosphazene derivatives that allowing their characterizations by circular dichroism (CD) spectroscopy [7a] or X-ray crystallography [7b]. For these enantiomeric cyclo- triphosphazene derivatives have containing two equivalent cen- tres of chirality [7]. One reason might be that enantio- separations of chiral cyclotriphosphazenes containing two equiv- alent centres of chirality are much better than for analogous mol- ecules with one centre of chirality [11]. It is necessary to develop the chiral HPLC methods for the enantiomeric separations of chi- ral cyclotriphosphazenes containing one centre of chirality. 0020-1693/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2009.07.022 * Corresponding author. Tel.: +90 262 6053137; fax: +90 262 6053101. E-mail address: yesil@gyte.edu.tr (S. Yes ßilot). Inorganica Chimica Acta 362 (2009) 4931–4936 Contents lists available at ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica