[acs symposium series] green polymer chemistry: biocatalysis and materials ii volume 1144 ||...

Chapter 19

Synthesis and NMR Characterizationof Hyperbranched Polyesters fromTrimethylolpropane and Adipic Acid

Tracy Zhang,1,2 Bobby A. Howell,2 Paul K. Martin,1Steven 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, withtrimethylolpropane, TMP, was monitored by 1H and 13C NMRas 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 weredetermined and these reaction products were monitored as afunction of time by both 1H and 13C NMR spectroscopy todetermine the reaction kinetics. The reaction was first order inAA and TMP concentration and the reaction rate was foundto significantly increase with increasing pTSA level up to aconcentration of 2.5 mole% based on acid functionality.

Introduction

Hyperbranched polyesters, HBPE, are attracting much interest becausemany of their monomeric building blocks can be obtained from biobasedsources and are biodegradable, opening many new areas of application.HBPEs have been synthesized from a number of different monomeric buildingblocks, including those from multifunctional aliphatic alcohols and diacids

© 2013 American Chemical Society

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019

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 and2,2-bis(hydroxymethyl)butyric acid (9), aconitic acid and diethylene glycol (10)and several from glycerol and difunctional acids (11–17). Many of the applicationstargeted for these HBPEs from biobased sources include the administration ofpharmaceuticals, pesticides and antimicrobials (18–27). They are synthesizedfrom mutually reactive multifunctional monomers, Ax and By, where x and y arethe functionality of the molecule.

The simplest of these multifunctional monomers is the A2 + B3 reactionsystem, such as adipic acid with trimethylolpropane, which is the system describedin this investigation. This A2 + B3 system forms a hyperbranched polyester by astep-growth polymerization reaction, which if performed in equimolar quantitiesof functional groups, forms an insoluble gel at high conversions. However, byproper choice of monomer stoichiometry, one can produce soluble materials andeven 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 HBPEswill be described in more detail in a future publication. The endgroup compositionfor BMNLP is also determined by the monomer stoichiometry. The endgroupfunctionality is primarily that of the excess component at high conversion asshown in Scheme 1.

Scheme 1

This reaction strategy can lead to either HBPs with B or A endgroups. Theability to easily control endgroup functionality is a valuable attribute for HBsystems since so many polymer properties depend on it including solubility,solution and melt viscosity and thermal properties. The endgroups are capableof further reaction with the addition of the other reactive components. Thisproperty may be exploited to covalently attach active agents or for crosslinkinginto 3D networks. Scheme 2 shows the structure of an HBPE from glyceroland a diprotic acid such as adipic acid with glycerol in excess such that theendgroups are alcohols. The molecular interiors of these polymers contain polarester groups which facilitate host-guest interactions with various active agentsfor encapsulation, which after delivering them to the application site, releasethem by diffusion. Finally, it should also be noted that the versatility and thesimplicity of the BMNLP approach enables the use of biobased polyfunctional

282

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


alcohols and acids for the preparation of HBPEs which possess the ability todegrade to the starting monomers either by hydrolysis or enzymatic degradation,providing a benign process for the HBP carrier to assimilate into the environmentafter delivering the active agent. These HBPEs provide a versatile platform forachieving a variety of material properties.

HBPEs from trimethylolpropane, TMP, and adipic acid, AA, an A2 + B3system was synthesized in this investigation. TMP was used as a model forsynthesis of biobased polyesters since all three alcohol groups are primary andhave equivalent reactivity. The polycondensation reaction was monitored byNMR spectroscopy in order to assist in the assignment of the spectra as well asto understand the rate dependence on catalyst level, side reactions and the timerequired for complete conversion.

Scheme 2

Materials and MethodsTrimethylolpropane, TMP, adipic acid, AA, p-toluenesulfonic acid, p-TSA,

and tetrahydrofuran, THF, were obtained from Sigma Aldrich and used withoutfurther purification.

The polyester was synthesized using p-TSA as catalyst and driven tocompletion by stripping water using a soxhlet extraction apparatus with 4Åmolecular 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 acidfunctionality) or 1.06 g, and 16.34 g of AA were added to 109.6 g of THF (20

283

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


weight% solids). These reactants were added to a 250 ml three neck round bottomflask and brought to reflux conditions, about 66°C, using an oil bath. The reactionwas blanketed with N2. The concentration of reactants and the temperaturecycled as the solvent and water cycled through the soxhlet extractor. The reactionmixture flask was sampled periodically through one of the necks equipped with aseptum. 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 spectrawere used to determine the extent of reaction, as will be discussed later.

1H NMR spectra of neat reaction mixtures (without deuterated solvent) wereobtained using a Varian Inova 500 NMR spectrometer operating at 499.7 MHz for1Hobserve. The pulsewidthwas 8°, the pulse repetition timewas 5 seconds, sweepwidth 8,000 Hz, number of points 65536, 0.1 Hz line broadening, 16 scans. Theanalysis was performed without an internal lock but no significant line broadeningwas observed due to field drift over the 2 minute acquisition time.

13C NMR spectra of neat reaction mixtures were obtained using the sameinstrument at 125.7 MHz. A 90° pulse width was used, the pulse repetitiontime 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 linebroadening 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 carbonresonances of TMP, were expected to have very similar NOEs and relaxationtimes such that quantitative data could be obtained from the ratio of their areas. Infact, the conversion values calculated from the 1H NMR spectra and the carbonylcarbons of adipic acid or the quaternary carbon of TMP gave very consistentconversion values.

Results

NMR Assignments

The esterification of TMP with AA was expected to provide a simple modelfor hyperbranched polyesterification reactions since each TMP hydroxyl is anequivalent primary hydroxyl unit, having equal reactivity towards esterification.The expected reactions are given in Scheme 3, which incorporates somesimplifying assumptions, namely that the reactivity of one acid group of adipicacid is not affected by whether the other is acid or ester. This reaction is ignoredin Scheme 3. The substitution of one hydroxyl unit of TMP might also affect thereactivity of the other hydroxyl units on the TMP molecule. Therefore, k1, k2and k3 might each be different. The model used to fit the reaction profile, whichis described later in this work, assumes that k1 = k2 = k3. This model fits theobserved 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 theprogress of the esterification reactions.

284

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


Scheme 3

Figure 1 gives the 1HNMR spectrum of a reaction mixture of TMP and adipicacid of stoichiometry 2.1:1, [OH]:[COOH]. The assignments are given on thespectrum. 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 themultiplicity 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 and2.28 ppm. Resonances from residual THF are also noted in the spectrum. Theresonances from 3.3 to about 4.0 ppm are those of the -OCH2 protons of TMP aswell 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 withStoichiometry of 2.1:1, [OH]:[COOH], with Assignments.

285

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


The -OCH2 proton resonances of TMP, labeled 4 on the figure are separatedinto 2 distinct regions, one group located between 3.3 and 3.7 ppm and a secondgroup 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, andthe downfield group are those of the -OCH2s of TMP which are esters. Thesegroups are further split due to substituent effects. Unreacted TMP is observed at3.55 ppm and water at 3.60 ppm. Within the alcohol group of resonances, themonoester, labeled 4m, is located at 3.45 ppm and the diester, 4d, is observed at3.35 ppm. The -OCH2 proton resonances of the TMP esters are observed between3.9 and 4.5 ppm. The resonance of the triester, 4′t, is located at about 4.02 ppm andthat of the diester, 4′d, is located with the monoester, 4′m, at about 3.92 ppm. Theassignments were determined from the kinetic sequence of the reaction, knowingthat the TMP substitution would proceed from mono ester to di and tri. Theseassignments are also consistent with the 13C NMR spectra, which are much easierto assign.

Figure 2 gives the 13C NMR spectrum of a TMP, AA reaction product inCDCl3 as solvent, with assignments. An expansion of the quaternary carbon regionof the spectrum, between 40 and 44 ppm, is given in Figure 3. The assignments ofthe quaternary carbons of TMP as a function of substitution were determined fromkinetic runs like the one given in Figure 3 and are consistent with those describedelsewhere1. At early reaction times only TMP and the monoester are observed. Asthe reaction proceeds, these resonances diminish and the di and triester resonancesgrow in. The same trends can be followed with the carbonyl resonances of adipicacid. These 13C NMR assignments, which are straightforward, were used to assistin assigning the 1H NMR spectra such that all the spectra were self-consistent.

Figure 2. The 13C NMR Spectrum of the Hyperbranched Copolymer of TMPand AA in CDCl3 with assignments.

286

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


Figure 3. The 13C NMR Spectra of the Quaternary Carbon Resonances of TMPfor 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 ofTMP and that the carboxylic acid functionality of adipic acid has equal reactivityregardless 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 whichis usually not the case because acid catalyzed esterifications are equilibriumreactions. However, since water is being removed throughout the reaction to drivethe equilibrium to the right, this expression represents a good approximation ofthe process. The rate equation for this reaction is the following:

287

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


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 ofslope k [R]0 with an intercept of 1.0. Figure 4 shows a typical plot of 1/(1-P) as afunction of time for the 1:1, [OH]:[COOH] stoichiometry TMP, AA reaction with2.5 mole% p-TSA as catalyst. The plot behaves as one would expect, a straightline behavior with an intercept of 1.0. (Time zero on these plots is shifted 10 to20 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 NMRspectra of the reaction as a function of time as well as the quaternary carbon andthe carbonyl carbon from the 13C NMR spectra, validating the assumption thatcarbons 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 kineticdata consistent with the quantitative 1H NMR spectra. The rate constant valuesfrom the three sets of data, 4.2, 4.4 and 3.5 x 10-3 l/mol-min are equivalent withinthe precision of the experiment (10% relative). Therefore, the assumption that k1= k2 = k3 and that each carboxylic acid functional group of adipic acid has equalreactivity 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 catalystconcentrations are given in Table 1. The rates showed a significant increase in rateas the catalyst level is increased, leveling off above 2.5 mole%.

288

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


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 CatalystConcentration

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 ahyperbranched polyester were characterized by NMR spectroscopy. The reactionkinetics are approximations only, due to the process by which water was removedfrom the reaction with a soxhlet extraction. This process caused the concentrationof the reactants to cycle as well as the reaction temperature, due to the factthat the temperature was controlled by reflux conditions. Even so, the analysisis instructive since it provided assurance that the NMR assignments of thesecopolymers are correct. It also documented that the rate of the reaction increasesas the level of p-TSA is increased from 0.5 mole% to 5 mole%. Most synthesesof this type in the literature use very low levels of p-TSA catalyst. This studyindicates that higher levels of p-TSA promote faster esterification rates.

289

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


References

1. Kulshrestha, A. S.; Gao, W.; Fu, H.; Gross, R. A. Biomacromolecules 2007, 8,1794–1801.

2. Kricheldorf, H. R.; Behnken, G. Macromolecules 2008, 41, 5651–5657.3. Kricheldorf, H. R.; Behnken, G. J. Polym. Sci., Part A: Polym. Chem. 2009,

47, 231–238.4. Malmstrom, E.; Johansson, M.; Hult, A. Macromolecules 1995, 28,

1698–1703.5. Bruggeman, J. P.; Bettinger, C. J.; Nijst, C. L. E.; Kohane, D. S.; Langer, R.

Adv. Mater. 2008, 20, 1922–927.6. Barret, D. G.; Luo, W.; Yousaf, M. N. Polym. Chem. 2010, 1, 296–302.7. Kricheldorf, H. R.; Behnken, G. Macromolecules 2008, 41, 5651–5657.8. Magnusson, H.; Malmstrom, E.; Hult, A. Macromolecules 2000, 33,

3099–3104.9. Fischer, A. M.; Frey, H. Macromolecules 2010, 43, 8539–85448.10. Cao, H.; Zheng, Y.; Zhou, J.; Wang, W.; Pandit, A. Polym. Int. 2011, 60,

630–634.11. Yang, Y.; Lu, W.; Cai, J.; Hou, Y.; Ouyang, S.; Xie, W.; Gross, R. A.

Macromolecules 2011, 44, 1977–1985.12. Kulshrestha, A. S.; Gao, W.; Gross, R. A. Macromolecules 2005, 38,

3193–3204.13. Carnahan, M. A.; Grinstaff, M. W. Macromolecules 2001, 34, 7648–7655.14. Stumbe, J.-F.; Bruchmann, B.Macromol. Rapid Commun. 2004, 25, 921–924.15. Wyatt, V. T.; Strahan, G. D. Polymers 2012, 4, 396–407.16. Carnahan,M.A.; Grinstaff,M.W. J. Amer. Chem. Soc. 2001, 123, 2905–2906.17. Brioude, M. d. M.; Guimaraes, D. H.; Fiuza, R. d. P.; Prado, L. A. S. d. A.;

Boaventura, J. S.; Jose, N. M. Mat. Res. 2007, 10, 335–339.18. Coneski, P. N.; Rao, K. S.; Schoenfisch, M. H. Biomacromolecules 2010, 11,

3208–3215.19. Cao, W.; Zhou, Z.; Wang, Y.; Zhu, L. Biomacromolecules 2010, 11,

3680–3687.20. Ifran, M.; Seiler, M. Ind. Eng. Chem. Res. 2010, 49, 1169–1196.21. Lin, C.; Gitsov, I. Macromolecules 2010, 43, 10017–10030.22. Shi, X.; Wang, S. H.; Lee, I.; Shen, M.; Baker, J. R., Jr. Biopolymers 2009, 91,

936–942.23. Ye, L.; Letchford, K.; Heller, M.; Liggins, R.; Guan, D.; Kizhakkedathu, J.

N.; Brooks, D. E.; Jackson, J. K.; Burt, H. M. Biomacromolecules 2011, 12,145–155.

24. Chaterjee, S.; Ramakrishnan, S. Macromolecules 2011, 44, 4658–4664.25. Gao, C.; Yan, D. Prog. Polym. Sci. 2004, 29, 183–275.26. Mishra, M. K.; Kobayashi, S. Star and Hyperbranched Polymers; Mercel

Dekker, Inc.: New York, 1999; p 53.27. Coullerez, G.; Lundmark, S.; Malmstrom, E.; Hult, A.; Mathieu, H. J. Surf.

Interface Anal. 2003, 35, 693–708.28. Dvornic, P. U.S. Patent 6,812,298, 2004.

290

Dow

nloa

ded

by U

NIV

OF

RO

CH

EST

ER

on

Nov

embe

r 6,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate

(Web

): N

ovem

ber

22, 2

013

| doi

: 10.

1021

/bk-

2013

-114

4.ch

019


[acs symposium series] green polymer chemistry: biocatalysis and materials ii volume 1144 ||...

Documents