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Chapter 19

Downloaded by UNIV OF ROCHESTER on November 6, 2014 | http://pubs.acs.org Publication Date (Web): November 22, 2013 | doi: 10.1021/bk-2013-1144.ch019

Synthesis and NMR Characterization of Hyperbranched Polyesters from Trimethylolpropane and Adipic Acid Tracy Zhang,1,2 Bobby A. Howell,2 Paul K. Martin,1 Steven J. Martin,1 and Patrick B. Smith*,1 1Michigan

Molecular Institute, 1910 West St., Andrews Road, Midland, Michigan 48640 2Central Michigan University, Department of Chemistry, Dow Science Complex 263, Mount Pleasant, Michigan 48859 *E-mail: [email protected]

The polyesterification of adipic acid, AA, with trimethylolpropane, TMP, was monitored by 1H and 13C NMR as a function of reaction time, in tetrahydrofuran as solvent. The reaction was catalyzed by p-toluenesulfonic acid, pTSA. NMR assignments of the mono, di and triester of TMP were determined and these reaction products were monitored as a function of time by both 1H and 13C NMR spectroscopy to determine the reaction kinetics. The reaction was first order in AA and TMP concentration and the reaction rate was found to significantly increase with increasing pTSA level up to a concentration of 2.5 mole% based on acid functionality.

Introduction Hyperbranched polyesters, HBPE, are attracting much interest because many of their monomeric building blocks can be obtained from biobased sources and are biodegradable, opening many new areas of application. HBPEs have been synthesized from a number of different monomeric building blocks, including those from multifunctional aliphatic alcohols and diacids © 2013 American Chemical Society In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


(1–7), from 2,2-bis(hydroxymethyl)propionic acid (8), from glycolide and 2,2-bis(hydroxymethyl)butyric acid (9), aconitic acid and diethylene glycol (10) and several from glycerol and difunctional acids (11–17). Many of the applications targeted for these HBPEs from biobased sources include the administration of pharmaceuticals, pesticides and antimicrobials (18–27). They are synthesized from mutually reactive multifunctional monomers, Ax and By, where x and y are the functionality of the molecule. The simplest of these multifunctional monomers is the A2 + B3 reaction system, such as adipic acid with trimethylolpropane, which is the system described in this investigation. This A2 + B3 system forms a hyperbranched polyester by a step-growth polymerization reaction, which if performed in equimolar quantities of functional groups, forms an insoluble gel at high conversions. However, by proper choice of monomer stoichiometry, one can produce soluble materials and even have some control over the molecular weight of the resulting HBPE (28). This is the basis of bimolecular nonlinear polymerization (BMNLP) methodology (see Scheme 1). The use of BMNLP to control the molecular weight of HBPEs will be described in more detail in a future publication. The endgroup composition for BMNLP is also determined by the monomer stoichiometry. The endgroup functionality is primarily that of the excess component at high conversion as shown in Scheme 1.

Scheme 1 This reaction strategy can lead to either HBPs with B or A endgroups. The ability to easily control endgroup functionality is a valuable attribute for HB systems since so many polymer properties depend on it including solubility, solution and melt viscosity and thermal properties. The endgroups are capable of further reaction with the addition of the other reactive components. This property may be exploited to covalently attach active agents or for crosslinking into 3D networks. Scheme 2 shows the structure of an HBPE from glycerol and a diprotic acid such as adipic acid with glycerol in excess such that the endgroups are alcohols. The molecular interiors of these polymers contain polar ester groups which facilitate host-guest interactions with various active agents for encapsulation, which after delivering them to the application site, release them by diffusion. Finally, it should also be noted that the versatility and the simplicity of the BMNLP approach enables the use of biobased polyfunctional 282 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


alcohols and acids for the preparation of HBPEs which possess the ability to degrade to the starting monomers either by hydrolysis or enzymatic degradation, providing a benign process for the HBP carrier to assimilate into the environment after delivering the active agent. These HBPEs provide a versatile platform for achieving a variety of material properties. HBPEs from trimethylolpropane, TMP, and adipic acid, AA, an A2 + B3 system was synthesized in this investigation. TMP was used as a model for synthesis of biobased polyesters since all three alcohol groups are primary and have equivalent reactivity. The polycondensation reaction was monitored by NMR spectroscopy in order to assist in the assignment of the spectra as well as to understand the rate dependence on catalyst level, side reactions and the time required for complete conversion.

Scheme 2

Materials and Methods Trimethylolpropane, TMP, adipic acid, AA, p-toluenesulfonic acid, p-TSA, and tetrahydrofuran, THF, were obtained from Sigma Aldrich and used without further purification. The polyester was synthesized using p-TSA as catalyst and driven to completion by stripping water using a soxhlet extraction apparatus with 4Å molecular sieves. A typical reaction used a stoichiometry of [OH] / [COOH] equal to 1.0. In one example, 10.0 g of TMP, 2.5 mole% p-TSA (based on acid functionality) or 1.06 g, and 16.34 g of AA were added to 109.6 g of THF (20 283 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


weight% solids). These reactants were added to a 250 ml three neck round bottom flask and brought to reflux conditions, about 66°C, using an oil bath. The reaction was blanketed with N2. The concentration of reactants and the temperature cycled as the solvent and water cycled through the soxhlet extractor. The reaction mixture flask was sampled periodically through one of the necks equipped with a septum. Roughly 1 ml samples were taken with a syringe throughout the reaction. The samples were cooled in a freezer to quench the reaction for analysis by NMR. The samples were always taken directly after the siphon dumped. NMR spectra were used to determine the extent of reaction, as will be discussed later. 1H NMR spectra of neat reaction mixtures (without deuterated solvent) were obtained using a Varian Inova 500 NMR spectrometer operating at 499.7 MHz for 1H observe. The pulse width was 8°, the pulse repetition time was 5 seconds, sweep width 8,000 Hz, number of points 65536, 0.1 Hz line broadening, 16 scans. The analysis was performed without an internal lock but no significant line broadening was observed due to field drift over the 2 minute acquisition time. 13C NMR spectra of neat reaction mixtures were obtained using the same instrument at 125.7 MHz. A 90° pulse width was used, the pulse repetition time was 5 seconds with complete decoupling, the sweep width was 31 KHz, number of points 131,072, 3.0 Hz line broadening, 256 scans. No significant line broadening due to field drift was observed over the 21 minute acquisition time. These conditions were not strictly quantitative but carbons of the same type, e.g., the carbonyl carbon resonances of adipic acid and the quaternary carbon resonances of TMP, were expected to have very similar NOEs and relaxation times such that quantitative data could be obtained from the ratio of their areas. In fact, the conversion values calculated from the 1H NMR spectra and the carbonyl carbons of adipic acid or the quaternary carbon of TMP gave very consistent conversion values.

Results NMR Assignments The esterification of TMP with AA was expected to provide a simple model for hyperbranched polyesterification reactions since each TMP hydroxyl is an equivalent primary hydroxyl unit, having equal reactivity towards esterification. The expected reactions are given in Scheme 3, which incorporates some simplifying assumptions, namely that the reactivity of one acid group of adipic acid is not affected by whether the other is acid or ester. This reaction is ignored in Scheme 3. The substitution of one hydroxyl unit of TMP might also affect the reactivity of the other hydroxyl units on the TMP molecule. Therefore, k1, k2 and k3 might each be different. The model used to fit the reaction profile, which is described later in this work, assumes that k1 = k2 = k3. This model fits the observed kinetics quite well. Each of the structures given in Scheme 3 possesses distinct NMR signatures, both in their 1H and 13C NMR spectra. Therefore, NMR was able to monitor the progress of the esterification reactions. 284 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Scheme 3 Figure 1 gives the 1H NMR spectrum of a reaction mixture of TMP and adipic acid of stoichiometry 2.1:1, [OH]:[COOH]. The assignments are given on the spectrum. The methyl resonance of TMP is a multiplet located at about 0.8 ppm, the methylene resonances are located between 1.0 and 1.5 ppm, the origin of the multiplicity is very complex, being due to both coupling and substituent effects, as will be discussed later. The adipic acid methylenes are located at 1.58 and 2.28 ppm. Resonances from residual THF are also noted in the spectrum. The resonances from 3.3 to about 4.0 ppm are those of the -OCH2 protons of TMP as well as a resonance from THF and water which are labeled on the spectrum.

Figure 1. The 1H NMR Spectrum of a Copolymer of TMP and AA with Stoichiometry of 2.1:1, [OH]:[COOH], with Assignments. 285 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


The -OCH2 proton resonances of TMP, labeled 4 on the figure are separated into 2 distinct regions, one group located between 3.3 and 3.7 ppm and a second group at 3.9 to 4.1 ppm. The upfield group of resonances, from 3.3 to 3.7 ppm, are those of the TMP methylene with alcohol functional groups, –CH2-OH, and the downfield group are those of the -OCH2s of TMP which are esters. These groups are further split due to substituent effects. Unreacted TMP is observed at 3.55 ppm and water at 3.60 ppm. Within the alcohol group of resonances, the monoester, labeled 4m, is located at 3.45 ppm and the diester, 4d, is observed at 3.35 ppm. The -OCH2 proton resonances of the TMP esters are observed between 3.9 and 4.5 ppm. The resonance of the triester, 4′t, is located at about 4.02 ppm and that of the diester, 4′d, is located with the monoester, 4′m, at about 3.92 ppm. The assignments were determined from the kinetic sequence of the reaction, knowing that the TMP substitution would proceed from mono ester to di and tri. These assignments are also consistent with the 13C NMR spectra, which are much easier to assign. Figure 2 gives the 13C NMR spectrum of a TMP, AA reaction product in CDCl3 as solvent, with assignments. An expansion of the quaternary carbon region of the spectrum, between 40 and 44 ppm, is given in Figure 3. The assignments of the quaternary carbons of TMP as a function of substitution were determined from kinetic runs like the one given in Figure 3 and are consistent with those described elsewhere1. At early reaction times only TMP and the monoester are observed. As the reaction proceeds, these resonances diminish and the di and triester resonances grow in. The same trends can be followed with the carbonyl resonances of adipic acid. These 13C NMR assignments, which are straightforward, were used to assist in assigning the 1H NMR spectra such that all the spectra were self-consistent.

Figure 2. The 13C NMR Spectrum of the Hyperbranched Copolymer of TMP and AA in CDCl3 with assignments. 286 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Figure 3. The 13C NMR Spectra of the Quaternary Carbon Resonances of TMP for a Reaction Mixture of TMP and AA of Stoichiometry [OH]:[COOH] Equal to 1:1.

Kinetic Analysis The esterification reaction between trimethylolpropane, TMP, and adipic acid, AA, was modeled as:

This expression assumes equal reactivity of the three hydroxyl groups of TMP and that the carboxylic acid functionality of adipic acid has equal reactivity regardless of whether the other carboxylate group in the molecule is acid or ester. A second assumption is that the esterification only proceeds to the right which is usually not the case because acid catalyzed esterifications are equilibrium reactions. However, since water is being removed throughout the reaction to drive the equilibrium to the right, this expression represents a good approximation of the process. The rate equation for this reaction is the following:

287 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.

If the reaction is run at 1:1 [OH]:[COOH] stoichiometry such that:


Integrating:

The extent of reaction, P, is defined as:

If one plots 1/(1-P) as a function of time, one should get a straight line of slope k [R]0 with an intercept of 1.0. Figure 4 shows a typical plot of 1/(1-P) as a function of time for the 1:1, [OH]:[COOH] stoichiometry TMP, AA reaction with 2.5 mole% p-TSA as catalyst. The plot behaves as one would expect, a straight line behavior with an intercept of 1.0. (Time zero on these plots is shifted 10 to 20 minutes because there is a finite time for the reactor to come to temperature.) The three overlayed plots on the graph of Figure 4 were taken from the 1H NMR spectra of the reaction as a function of time as well as the quaternary carbon and the carbonyl carbon from the 13C NMR spectra, validating the assumption that carbons of the same type (e.g., the quaternary carbon of TMP and that of the mono, di and triester) have very similar NOE and T1 values and therefore, give kinetic data consistent with the quantitative 1H NMR spectra. The rate constant values from the three sets of data, 4.2, 4.4 and 3.5 x 10-3 l/mol-min are equivalent within the precision of the experiment (10% relative). Therefore, the assumption that k1 = k2 = k3 and that each carboxylic acid functional group of adipic acid has equal reactivity is valid within the precision of the measurement. The reaction was run as a function of catalyst level, varying from 0.5 mole% to 5 mole% based on TMP hydroxyl functionality. The rates for these catalyst concentrations are given in Table 1. The rates showed a significant increase in rate as the catalyst level is increased, leveling off above 2.5 mole%. 288 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Figure 4. The Reaction Profile for TMP, AA 1:1, [OH]:[COOH] Stoichiometry, 2.5 mole% p-TSA.

Table 1. The Dependence of the Reaction Rate Constant, k, on Catalyst Concentration Catalyst Level (Mole%)

Reaction Rate [l/mol-min]

0.0

0.08 x 10-3

0.5

1.6 x 10-3

1.0

1.7 x 10-3

2.5

4.2 x 10-3

5.0

4.7 x 10-3

Conclusions The kinetics of the esterification reaction of TMP and AA yielding a hyperbranched polyester were characterized by NMR spectroscopy. The reaction kinetics are approximations only, due to the process by which water was removed from the reaction with a soxhlet extraction. This process caused the concentration of the reactants to cycle as well as the reaction temperature, due to the fact that the temperature was controlled by reflux conditions. Even so, the analysis is instructive since it provided assurance that the NMR assignments of these copolymers are correct. It also documented that the rate of the reaction increases as the level of p-TSA is increased from 0.5 mole% to 5 mole%. Most syntheses of this type in the literature use very low levels of p-TSA catalyst. This study indicates that higher levels of p-TSA promote faster esterification rates. 289 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.

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290 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.

Synthesis and NMR Characterization of ... - ACS Publications

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