Poly dichloro phosphazene

An overview of the synthesis and characterization of a unique class of polymers with a phosphorus-nitrogen backbone Is presented, with a focus on poly(dichloro-phosphazene) as a common Intermediate for a wide variety of poly(organophosphazenes). Melt and solution polymerization techniques are Illustrated, Including the role of catalysts. The elucidation of chain structure and molecular weight by various dilute solution techniques Is considered. Factors which determine the properties of polymers derived from poly(dichlorophos-phazene) are discussed, with an emphasis on the role that the organic substituent can play In determining the final properties. 

Cationic polymerization of phosphoranimines initiated by small amounts of PCI5 in dichloromethane at ambient temperature offers a new route for the preparation of polyphosphazenes. Initiation of Me3SiNPCl3 gives poly(dichloro-phosphazene) with a narrow molecular weight distribution. The polymerization can be characterized as a living cationic polymerization. ... 

It is the high reactivity of the phosphorus-chlorine bonds in 3 that allows the chlorine atoms to be replaced by reactions with reagents such as alkoxides, aryloxides, amines, or other nucleophiles. Because the average chain length in 3 corresponds to approximately 15,000 repeating units, this means that roughly 30,000 halogen atoms per molecule are replaced in these reactions. Thus, in many ways, poly(dichloro-phosphazene) is the ultimate functional polymer. 

The poorly reproducible polymerization is presumably initiated by traces of cationic impurities. The poly(phosphonitrile chlorides) or poly(dichloro-phosphazenes), II, mostly have PCI3 end groups. They depolymerize at higher temperatures to hexachlorocyclotriphosphazene, I, and octachlorocyclo-tetraphosphazene and hydrolyze even in moist air. The products obtained at high yield are cross-linked and exhibit all the properties of inorganic elastomers. Consequently, they are also called inorganic rubbers. 

Heating N3P3CU at 250 °C in vacuum and by allowing the conversion to proceed only up to 70%, linear poly(dichloro-phosphazene) could be isolated (see Eq. 3.30). This polymer was soluble in a number of organic solvents such as benzene, toluene, tetrahydrofuran etc., to form clear viscous solutions. 

One, complete replacement of chlorine atoms from poly(dichloro-phosphazene) is not possible with all nucleophiles. Thus, with sterically hindered nucleophiles such as diethylamine, only partial replacement of chlorines occurs. The remaining chlorines have to be replaced with other less hindered substituents (see Eq. 3.54) [21]. 

The R group can be an alkoxy, aryloxy, amino, alkyl, heterocyclic ring or an inorganic or organometallic unit. Allcock and co-workers were the first who did study extensively the synthesis of poly[(organo)phosphazene] derivatives. Most polyphosphazene derivatives are prepared starting from a precursor polymer, poly[(dichloro)phosphazene]. A variety of polymers with variable properties can be prepared by nucleophilic displacement reactions (Allcock, 1972, 1979, 1986) (Figure 2). 

Several methods are described for the preparation of poly [ (dichloro)phosphazene]. 

It was later noticed that the hexachlorocyclotriphosphazene can be polymerized by heating in the melt to yield an uncrosslinked linear high polymer, poly[(dichloro)-phosphazene] (Allcock et al, 1965-1966 Rose, 1968). Further heating results in the formation of an insoluble crosslinked material. This leads in both cases to a transparent, rubbery elastomer which hydrolyzes slowly, when exposed to moisture, forming phosphate, ammonia and hydrochloric acid. At temperatures above 350°C, the polymer depolymerizes to cyclic oligomers. The uncrosslinked species serve as highly reactive polymeric precursor. 

Another polymerization method was mentioned by Hornbaker and Li (1978). This method describes the direct formation of poly[(dichloro)phosphazene] starting from the basic compounds PCI3, CI2 and NH4CI and without intermediate isolation of a precursor compound (Figure 6). 

Poly [ (amino) phosphazenes] have been synthetised by the replacement of chlorine atoms in poly[(dichloro)phosphazene] by amines (Allcock et al, 1966). Drug molecules bearing an amino-group are substituted in the same way, such as the anesthetic molecules procaine, benzocaine, chloroprocaine, butyl-p-aminobenzoyl and 2-amino-4-picoline (Allcock et al, 1982). The poly [(diamino) phosphazene] is not water soluble but this can be achieved by cosubstitution with methylamine, procaine or 2-amino-4-picolino. 

A large variety of drugs and other bioactive molecules have been covalently linked to the polyphosphazene chain. Steroids were covalently linked by reaction of the sodium salt of steroidal alcohol functional groups with poly [ (dichloro) phosphazene ] (Allcock et al, 1980). Remaining chlorine side groups were replaced with methyl-amine, a side group which promotes the water solubility of the resulting polymer. 

Ganapathianppan, S., Dhathathreyan K.S. and Krishnamurthy S.S. (1987) New initiators for the ring-opening thermal polymerization ofhexachlorocyclotriphosphazene . synthesis of linear poly(dichloro-phosphazene) in high yields. Mai rom.olecuks, 20(7), 1501-1505. 

Figure 1.3 Stabilisation of poly(dichloro)phosphazene in diglyme. THF tetrahydrofuran. Reproduced with permission from A.K. Andrianov, J. Chen and M.P. LeGolvan, MacromoleculeSy 2004, 37, 2, 414. 2004, American Chemical Society [2]...

Figure 1.4 Most common routes for the macromolecular substitution of poly(dichloro)phosphazene...

The traditional and most widely used route to prepare high molecular weight poly(dichloro)phosphazene is the thermally induced ring-opening polymerisation (ROP) of hexachlorophosphazene [9]. This is most commonly carried out in the molten state under... 

Furthermore, despite still being the route able to prepare the highest Mjy, ROP inherently produces polymers with broad polydispersities (Mjy/M >2) due to its initiation mechanism, in which the formation of new chains can occur throughout. Although such polydispersity is perfectly tolerable for many medical applications, for example, as inert biomaterials, the method is less suitable for some biomedical applications, in which precise molecular size is often an essential property. Furthermore, advanced polymer architectures and macromolecular constructs cannot be readily attained via this method, due to the absence of end-group control, and hence the development of poly(dichloro)phosphazene with controlled... 

Figure 1.13 Examples of the three most common routes to hetero poly(dichloro)phosphazene block copolymers with organic or inorganic polymers...

The most hydrolysis-susceptible side-substituent is chlorine and hence if preparing polymers from a poly(dichloro)phosphazene precursor, knowledge of the residual chlorines is required [27, 30]. Not only is the P-Cl moiety itself extremely labile, its hydrolysis leads directly to the degradation intermediate hydroxyphosphazene [31] and also produces HCl as a by-product, which is known to further catalyse hydrolysis (see Section 1.1). Although through the partial substitution of poly(dichloro)phosphazene it is thus possible to prepare degradable materials, in practice however, full substitution is usually strived for, not least for the sake of reproducibility. 

Figure 3.23 Covalent linkage of the water-insoluble photosensitiser hypericin to poly(dichloro)phosphazene is followed by Jeffamine oligomers. The resulting water-soluble conjugate can be easily administered and is readily taken up by cells for PDT. DIEA N,N-diisopropylethylamine, O/N overnight, RT room temperature and THF tetrahydrofuran. Reproduced with permission from D. Feinweber, T. Verwanger, O. Briiggemann, I. Teasdale and B. Krammer, Photochemical Photobiological Sciences, Royal Society of Chemistry, Cambridge, UK, 2014, DOI 10.1039/ C4PP00251B. 2014, Royal Society of Chemistry [145]...

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