Polyanhydrides chlorides

Cortisone acetate has been incorporated into several polyanhydrides (15). The rates of release of cortisone acetate from microcapsules of poly(terephthaUc acid), poly(terephthaUc acid-sebacic acid) 50 50, and poly(carboxyphenoxypropane-sebacic acid) 50 50 are shown in Fig. 8. These microcapsules were produced by an interfacial condensation of a diacyl chloride in methylene chloride with the appropriate dicarboxylic acid in water, with or without the crosslinking agent trimesoyl chloride. This process produces irregular microcapsules with a rough surface. The release rates of cortisone acetate from these microcapsules varied correspondingly with the rate of degradation of the respective polyanhydrides. It can be expected that the duration of release of cortisone acetate from solid microspheres, such as those produced by the hot-melt process, would be considerably longer. 

The Schotten-Bauman condensation produces polyanhydrides with moderate molecular weights by a dehydrochlorination reaction between a diacid chloride and a dicarboxylic acid. The polymerization takes place by reacting the monomers for 1 hr at room temperature, and it can be conducted via solution or interfacial methods. Solvents that are used in solution polymerization include dichloromethane, chloroform, benzene, and ethyl ether. The degree of polymerization obtained with this method is approximately 20-30. Lower molecular weight products are obtained for less reactive monomers such as isophthaloyl chloride. 

Polyanhydrides have been synthesized by the following methods a) bulk melt condensation of activated diadds, b) ring opening polymerization, c) reaction between dibasic acid and diacid chlorides, and d) interfacial polymerization. A detailed study of these polymerization methods and various polymerization conditions for a range of diadds were previously described [25-27],... 

Polyanhydrides can be synthesized by melt condensation of trimethylsilyl dicarboxylates and diacid chlorides to yield polymers with intrinsic viscosities up to 0.43 dl/g [31, 32] ... 

The solution polymerization is carried out by Schotten-Baumann technique. In this method, the solution of diacid chloride is added dropwise into an ice-cooled solution of a dicarboxylic acid. The reaction is facilitated by using an acid acceptor such as triethylamine. Polymerization takes place instantly on contact of the monomers and is essentially complete within 1 h. The solvents employed can be a single solvent or a mixture of solvents like dichlorometh-ane, chloroform, benzene, and ethyl ether. It was found that the order of addition is very important in obtaining relatively high-molecular-weight polyanhydrides. Addition of... 

Low molecular weight polyanhydrides (4) were obtained by Yoda and Miyakefrom the reaction of terephthalic acid in pyridine with adlpyl and sebacyl chloride in ether or benzene at 25-30 C for four hours. In similar studies poorer yields were obtained when employing aliphatic dlaclds and terephthaloyl chloride. 

Polyanhydrides can be synthesised by melt condensation of trimethylsilyl dicarbox-ylates and diacid chlorides (Kricheldorf and Lubbers, 1990) as shown in Scheme 5.2. Polymerisation is carried out at 100 °C under vacuum in the presence of benzyltriethy-lammonium chloride. This method possesses several disadvantages over the acetic anhydride melt condensation method it requires pure chloride and trimethylsilyl... 

Scheme 5.2 Synthesis of polyanhydrides by melt condensation of trimethylsilyl dicarboxylates and diacid chlorides.

Scheme 5.5 Synthesis of polyanhydrides from diacid chloride and dicarboxylic acid.

Kricheldorf, H.R., Lubbers, D., 1990. New polymer syntheses, 38. Synthesis of polyanhydrides from trimethylsilyl dicarboxylates and dicarbonyl chlorides. Die Makromolekulare Chemie, Rapid Communications 11, 83—88. 

Polyanhydrides can be synthesized by melt condensation of trimethylsilyl dicar-boxylates and diacid chlorides to yield polymers with an intrinsic viscosity 0.43 dl/g (Gupta 1988). Direct polycondensation of sebacic acid and adipic acid at a high temperature under vacuum resulted in low molecular weight oligomers (Knobloch et al, 1975). The preparation of adipic acid polyanhydride from cyclic adipic anhydride (oxepane-2,7-dione) was investigated (Albertsson et al., 1990). 

General methods for the synthesis of poly(amide-anhydrides) and poly(amide-esters) based on naturally occurring amino acids were described (Domb et at, 1990). The polymers were synthesized from dicarboxylic acids prepared by amidation of the amino group of an amino acid with a cyclic anhydride, or by the amide coupling of two amino acids with a diacid chloride. Low molecular weight polymers from methylene bis(p-carboxybenzamide) were symthesized by melt condensation (Hartmann et al, 1989). A series of amido containing polyanhydrides based on p-aminobenzoic acid were sy nthesized by melt condensation. The polymers melted at 58 to 177°C and had a molecular weight of 2500 to 12400. 

Because melt polycondensation often requires a high temperature, it is not suitable for making heat sensitive polymers. A variety of solution pol5mierizations at ambient temperature have been reported (18,22). Polyanhydride formation can be effected at room temperature by a dehydrochlorination between a diacid chloride and a dicarboxylic acid (eq. 3). 

Low molecular weight polyanhydrides were prepared from the reaction of diacid with dehydrating agents such as AT,Ar-bis[2-oxo-3-oxazolidinyllphosphoramidoyl chloride and phenyl-A(-phenylphosphonamidoyl chloride (18) or by direct condensation at elevated temperature imder vacuum and acid catalysis (eq. 5). 

On the other hand, if the initial cyclopolymer is heated in presence of pyridine, isomerization of the syndiotactic form into the isotactic one is observed, probably by enolization of the position in a, whose hydrolysis gives rise to isotactic poly(acrylic acid) the latter can easily be transformed into polyanhydride by thionyl chloride ... 

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