Aromatic polyanhydrides

Aromatic Polyanhydrides. Aromatic homopolyanhydrides are insoluble in common organic solvents and melt at temperatures above 200°C (29). These properties limit the use of purely aromatic polyanhydrides, since they cannot be fabricated into films or microspheres using solvent or melt techniques. Fully aromatic polymers that are soluble in chlorinated hydrocarbons and melted at temperatures below 100°C were obtained by copolymerization of aromatic diacids such as isophthalic acid (IPA), terephthalic acid (TA), l,3-bis(carboxyphenoxy)propane (CPP), or l,3-bis(carboxyphenoxy)hexane (CPH). 

A considerable number of non-cross-linked aromatic and heterocyclic polymers has been produced. These include polyaromatic ketones, aromatic and heterocyclic polyanhydrides, polythiazoles, polypyrazoles, polytriazoles, poly-quinoxalines, polyketoquinolines, polybenzimidazoles, polyhydantoins, and polyimides. Of these the last two have achieved some technical significance, and have already been considered in Chapters 21 and 18 respectively. The most important polyimides are obtained by reacting pyromellitic dianhydride with an aromatic diamine to give a product of general structure (Figure 29.17). 

Several new series of polyanhydrides with advantageous properties for a variety of applications were also synthesized (8). The first ai e aliphatic-aromatic homopolyanhydrides of the structure... 

The stability of polyanhydrides composed of the diacids sebacic acid (SA), bis( -carboxyphenoxy)methane (CPM), l,3-bis(g-carboxyphe-noxy)propane (CPP), l,6-bis( -carboxyphenoxy)hexane (CPH), and phenylenedipropionic acid (PDP), in solid state and in organic solutions, was studied over a 1-year period. Aromatic polyanhydrides such as poly(CPM) and poly(CPH) maintained their original molecular weight for at least a year in both solid state and solution (20). 

Synthesis of polyanhydrides from the aromatic dicarboxylic acids (isophthalic and terephthalic acids) by melt polycondensation was first... 

Fatty acids have also been converted to difunctional monomers for polyanhydride synthesis by dimerizing the unsaturated erucic or oleic acid to form branched monomers. These monomers are collectively referred to as fatty acid dimers and the polymers are referred to as poly(fatty acid dimer) (PFAD). PFAD (erucic acid dimer) was synthesized by Domb and Maniar (1993) via melt polycondensation and was a liquid at room temperature. Desiring to increase the hydrophobicity of aliphatic polyanhydrides such as PSA without adding aromaticity to the monomers (and thereby increasing the melting point), Teomim and Domb (1999) and Krasko et al. (2002) have synthesized fatty acid terminated PSA. Octanoic, lauric, myristic, stearic, ricinoleic, oleic, linoleic, and lithocholic acid acetate anhydrides were added to the melt polycondensation reactions to obtain the desired terminations. As desired, a dramatic reduction in the erosion rate was obtained (Krasko et al., 2002 Teomim and Domb, 1999). 

Sanders et al. (1999) attempted to lower the melting points of aromatic polyanhydrides by substituting branched alkyl groups in place of the linear alkyls of P(CPP-SA). They synthesized poly[l,2-bis(/ -carboxyphenoxy)-propane-co-sebacic acid] (P(1,2-CPP-SA)), poly[l,3-bis(/ -carboxyphenoxy)-2-methyl propane-co-sebacic anhydride] (P(CPMP-SA)), and poly[l,3-bis (/ -carboxyphenoxy)-2,2-dimethyl propane-co-sebacic anhydride] (P(CPDP SA)), all of which had melting points below 165°C. 

The analysis of 1H NMR spectra of aliphatic and aromatic polyanhydrides has been reported by Ron et al. (1991), and McCann et al. (1999) and Shen et al. (2002), and 13C NMR has been reported by Heatley et al. (1998). In 1H NMR, the aliphatic protons have chemical shifts between 1 and 2 ppm, unless they are adjacent to electron withdrawing groups. Aliphatic protons appear at about 2.45 ppm when a to an anhydride bond and can be shifted even further when adjacent to ether oxygens. Aromatic protons typically appear with chemical shifts between 6.5 and 8.5 ppm and are also shifted up by association with anhydride bonds. The sequence distribution of copolymers can be assessed, for example in P(CPH-SA), by discerning the difference between protons adjacent to CPH-CPH bonds, CPH SA bonds, and SA-SA bonds (Shen et al., 2002). FTIR and 111 NMR spectra for many of the polymers mentioned in Section II can be found in their respective references. 

The branched aromatic polyanhydrides synthesized by Sanders et al. (1999 Mathiowitz et al., 1990b) demonstrated lower Tgs than the corresponding P(PCPP-SA) copolymers. The para-xylyl polymers synthesized by Anastasiou and Uhrich (2000a) (Pp-o-CPX and Pp-m-CPX) had systematically higher Tgs than the ortho-isomers (Po-o-CPX, Pm-o-CPX, P/uo-CPX). 

Domb, A., and Langer, R. Poly(anhydrides) III. (Polyanhydrides) based on aliphatic-aromatic diacids. Macromolecules 22 3200—3204, 1989. 

With the discovery of benzyne formation by pyrolysis of phthalic anhydride, a new field was opened for the investigation of aryne reactions at high temperatures. A first concern was to determine the generality of aryne formation from aromatic acid anhydrides. Such syntheses could be of considerable significance because of the enormous quantities of aromatic mono- and polyanhydrides available from petroleum aromatics by oxidation. 

Several combinations of monomers used to prepare polyanhydrides are classified as aliphatic, aromatic, aliphatic-aromatic, amine-based, and fatty acid-based polyanhydrides. The structures of these monomers determine... 

Polyanhydrides Polyanhydrides have a hydrophobic backbone with a hydrolytically labile anhydride linkage. These polymers widely vary in chemical composition and include aliphatic, aromatic, and fatty acid-based polyanhydrides. The rate of degradation depends on the chemical composition of the polymer. In general, aliphatic polyanhydrides degrade more rapidly than the aromatic polymer. Hence, copolymer blends with varying ratios of aliphatic-to-aromatic polyanhydrides can be synthesized to suit specific applications. 

Biocompatible ortho aromatic polyanhydrides, (IV), prepared by Uhrich [5] were used in drug delivery systems and as scaffolding implants for tissue reconstruction. 

Typically, homopolymers are not studied because they possess unfavorable characteristics rendering their handling and manufacture difficult. Poly(SA), poly(CPP), and poly (FA) are semicrystalline and thus suffer from either being brittle or having high Tn,. Conversely, poly(FAD) is a liquid. Therefore, polyanhydrides are often prepared as copolymers of aliphatic and/or aromatic monomers. The most common copolymers under investigation in drug delivery applications include poly(FAD-SA) and poly(CPP-SA). 

There are three major classes of polyanhydrides aliphatic, unsaturated, and aromatic. The chemical structures are shown in Table 1. 

The first aromatic polyanhydrides synthesized were poly(isophthalic acid) (IPA) and poly(terephthalic acid) (TA). A few common aromatic polyanhydrides are shown in Table 1. Homopolymers of aromatic diacids... 

Aromatic polyanhydrides meta isophthalic anhydride (IPA) para terephthalic anhydride (TA)... 

The polyanhydrides synthesized by melt condensation have fiber-forming properties in the molten state. They hydrolyze when exposed to air and this degradation is mainly controlled by the composition of the polymer. Homopolymers of aromatic monomers, such as CPH, degrade at a rate that is several orders of magnitude lower than that of homopolymers of aliphatic monomers. 

Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy have also been used to authenticate polyanhydride structures. Aliphatic polymers absorb at 1740 and 1810 cm while aromatic polymers absorb at 1720 and 1780 cm All the polyanhydrides show methylene bands because of deformation, stretching, rocking, and twisting. Aside from being used to ascertain polyanhydride structures, these techniques can be used to determine degradation progress, by monitoring the area of carboxylic acid peak (1770-1675 cm ) with respect to the characteristic anhydride peaks over time. 

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