A new synthetic route to poly[3-hydroxypropionic acid] (P[3-HP]): Ring-opening polymerization of 3-HP macrocyclic esters

Article abstract of DOI:10.1021/ma048092q

A new method for the preparation of high molecular weight of Poly[3-hydroxypropionic acid] P[3-HP] by employing ring opening polymerization (ROP) of macrocyclic esters derived directly from 3-HP was discussed. Good control over the molecular weights of the P[3-HP] polymers was observed both from the pure trimer (n=3) as well as from a mixture of larger cyclics (n= 4 and 5). The ROP of the trimer without solvent at 80 °C was successfully performed. The results show that the partial formation of acrylate groups during the ROP in solution.

Full text of DOI:10.1021/ma048092q

8198
Macromolecules 2004, 37, 8198-8200
Sch em e 1
A New Syn th etic Rou te to
P oly[3-h yd r oxyp r op ion ic a cid ] (P [3-HP ]):
Rin g-Op en in g P olym er iza tion of 3-HP
Ma cr ocyclic Ester s
Don gh u i Zh a n g, Ma r c A. Hillm yer ,* a n d
Willia m B. Tolm a n *
Department of Chemistry, University of Minnesota, 207
Pleasant Street SE, Minneapolis, Minnesota 55455-0431
Received September 15, 2004
In t r od u ct ion . The necessity of environmentally
friendly replacements for commodity plastics has stim-
ulated the development of polymers from biorenew-
able sources.1 A notable example is polylactide, a com-
mercially important material derived from lactic acid.2
Recent efforts in the chemical industry have been
focused on new bioderived starting materials that can
be used for the preparation of new plastics, as well as
other useful products and precursors.3 3-Hydroxypro-
pionic acid (3-HP), a structural isomer of lactic acid, is
such a material,4 which comprises the repeat unit of a
useful polymer, P[3-HP] (Scheme 1). High molecular
weight P[3-HP] has attractive mechanical properties,
such as rigidity, ductility, and exceptional tensile strength
in drawn films (>400 MPa).5 In addition, P[3-HP] has
been shown to be enzymatically and hydrolytically
degradable, thus enhancing its environmental appeal.6
P[3-HP] has been prepared by the condensation of 3-HP
esters7 and the ring-opening polymerization (ROP) of
â-propiolactone (Scheme 1),8 but both methods suffer
from disadvantages. Relative to condensations, ROP
generally provides a greater degree of control over
molecular weight, comonomer incorporation, and end
group definition. Yet while highly strained â-propiolac-
tone can readily be ring opened to yield high molecular
weight P[3-HP], it is carcinogenic9 and its large-scale
synthesis is difficult, especially when starting with the
preferred precursor 3-HP.10 Thus, it would be desirable
to develop an alternative ROP route to P[3-HP] that
avoids the use of â-propiolactone.
We reasoned that less strained macrocyclic esters
could be constructed from 3-HP directly and would be
susceptible to ROP. Such macrocyclic esters of 3-HP
have been generated from â-propiolactone.11 While their
lower degree of strain implies resistance to ROP, various
low-strain macrocylic monomers have nonetheless been
polymerized.12 In a recent example from our group,13
an entropic driving force was identified, and by using a
highly active catalyst,14 high conversions were attained.
Inspired by these precedents, we have developed a new
methodology for the preparation of high molecular
weight P[3-HP] employing macrocyclic monomers11
derived directly from 3-HP.
60%) using a straightforward protocol (Supporting
Information). In principle, the oligomeric fraction could
be recycled and a continuous process for the isolation
of the macrocycles could be devised. The identity of the
macrocycles was confirmed by NMR spectroscopy by
comparison with literature data (Figure S1).11b Ad-
ditional mass spectrometric characterization (Figure S3)
indicated that the macrocyclic mixture contained pre-
dominantly trimer (n ) 3), tetramer, and pentamer, but
cyclics with up to 25 3-HP subunits were observed. By
13C{1H} NMR spectroscopy, we determined the following
weight percentages in the mixture: trimer 31%, tet-
ramer 17%, pentamer 17%, hexamer 12%, and heptamer
8%. For initial polymerization studies, we isolated and
purified the trimer11 by column chromatography and
recrystallization.
Use of the ubiquitous15 catalyst Sn(octanoate)2 in the
presence of benzyl alcohol for the polymerization of the
trimer was not successful; no polymerization occurred
either in solution state at room temperature (RT) or in
the melt (70 °C) after 48 h at high catalyst loadings
(Supporting Information). With a more active Zn-
alkoxide reagent,14 however, ROP of the trimer pro-
ceeded rapidly at RT in CH2Cl2 (Scheme 1). In less than
30 min, 90% of the trimer was converted into P[3-HP]
([trimer]0 ) 1.2 M, [trimer]0:[Zn]0 ) 50:1), which was
isolated by precipitation from THF/hexane (1:1). The
product was characterized by SEC (Table 1) and NMR
(1H and 13C{1H}) spectroscopy (Figure S2). Further
analysis of a similarly prepared low molecular weight
P[3-HP] sample (Mn ) 2.4 kg‚mol-1, PDI ) 1.7) by
matrix assisted laser desorption/ionization (MALDI) MS
revealed three envelopes of peaks (Figure S4). Of these,
two were assigned to P[3-HP], with the third indicative
of cyclic oligomers (see below). The P[3-HP] fractions
contain ethoxy ester and hydroxyl end groups or ethoxy
ester and acrylate end groups. These assignments were
1
confirmed by H NMR spectroscopy, which indicated a
ratio of 1:3 for the two types of polymers (Figure S2).
The formation of ethoxy ester end groups confirms that
the ROP occurs through the cleavage of the acyl-C-O
bond and insertion of an ethoxy group from the catalyst.
By monitoring the reaction in situ, we established that
the acrylate end group was formed during the course of
the reaction, but mechanistic details are still under
investigation.
Resu lts a n d Discu ssion . Commercially available
aqueous solutions of 3-HP (20 wt %) were converted via
acid-catalyzed (1-10 mol %) self-condensation with
concomitant removal of water to a mixture of macro-
cycles and linear oligomers. After limited optimization,
the macrocycles were isolated in good yield (as high as
To assess the control of polymer molecular weight,
1
reaction aliquots were analyzed by H{1H} NMR spec-
* To whom correspondence should be addressed. Fax: (612)
6247029. E-mail: (M.A.H.) hillmyer@chem.umn.edu; (W.B.T.)
tolman@chem.umn.edu.
troscopy and SEC (Figure S5). At early reaction times,
the Mn increased linearly with conversion, followed by
10.1021/ma048092q CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/07/2004

Macromolecules, Vol. 37, No. 22, 2004
Communications to the Editor 8199
Ta ble 1. Da ta for ROP Rea ction s of Tr im er in Solu tion
Sta tea n d in Melta
RT in 60 min ([tetramer + pentamer]0 ) 1.1 M,
[tetramer + pentamer]0:[Zn]0 ) 572:1). These results
imply that the ability to polymerize the macrocycles
derived from 3-HP is not limited by ring strain, and that
it may ultimately be practical to use the macrocyclic
ester mixtures in large scale polymerizations.
In conclusion, we have implemented a new synthetic
route for preparing P[3-HP] through ROPs of macro-
cyclic esters prepared directly from commercial aque-
ous solutions of 3-HP, an inexpensive and renewable
starting material. Good control over the molecular
weights of the P[3-HP] polymers was observed and
high molecular weight samples were accessed, both from
pure trimer (n ) 3) as well as from a mixture of larger
cyclics (n ) 4 and 5). Moreover, we successfully per-
formed the ROP of the trimer without solvent at
80 °C. End group analysis indicated the partial forma-
tion of acrylate groups during the ROP in solution,
which may enable further elaboration of P[3-HP] into
more complex macromolecular architectures (e.g., graft
polymers).
[M]0/[Zn]0
convn (%)
Mn(theor)
Mn(SEC)
PDI(SEC)
10b
50b
94
94
95
95
88
2.0
10.2
20.5
41.0
76.4
157
10.8
20.1
38.1
67.6
69.9
2.4
11.6
19.5
32.0
53.0
66.5
12.3
15.3
27.6
43.6
52.7
1.7
1.5
1.6
1.6
1.6
1.5
1.5
1.6
1.9
1.8
1.7
100b
200b
400b
800b
50c
91
∼100
100c
200c
400c
800c
93
88
78
40
a
Mn values are in units of kg‚mol-1; [M]0 ) initial concentration
of the trimer of 3-HP; [Zn]0 ) initial concentration of the catalyst
(Scheme 1); Mn(theor) is based on the conversion from1H{1H} NMR
b
spectra. Reactions quenched at different times between 2 and
60 min. Conditions: room temperature, CH2Cl2, [M]0 ) 1.54 M.
c Reactions were quenched after 80 min. Conditions: 80 °C, no
solvent.
a modest decrease in molecular weight at high conver-
sions. This behavior is consistent with intramolecular
transesterification and concomitant extrusion of cyclic
oligomers. The proposed formation of cyclic oligomers
was supported by the 1H and 13C{1H} NMR spectra and
MALDI-MS data (third set of peaks, Figure S4). Impor-
tantly, by controlling the reaction time and catalyst
loading, we were able to obtain P[3-HP] with molecular
weights (Mn) between 2.4 and 67 kg‚mol-1 (Table 1). The
Mn values we determined by SEC using polystyrene
standards were in reasonable agreement with the Mn
values calculated considering the initial monomer-to-
catalyst ratios and trimer conversion for the first five
entries in Table 1.
Ack n ow led gm en t. We thank the University of
Minnesota Initiative for Renewable Energy and the
Environment (IREE), Cargill Corporation, and NSF
(CHE-0236662) for financial support of this research
and Cargill Corporation for donation of the aqueous
solution of 3-HP.
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental details, figures plotting NMR spectroscopic, MALDI
MS, and DSC data and showing plots of the dependence of
Mn on reaction time and conversion, and tables showing
the depenence of yield on reaction conditions and DSC data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
All P[3-HP] samples generated by polymerization of
the trimer were semicrystalline by differential scan-
ning calorimetry (DSC, 18-47% depending on Mn).
Both glass transition temperatures (Tg) and melting
temperatures (Tm) generally increased with increasing
Mn between 2.4 and 30.7 kg‚mol-1 and remained
constant at higher molecular weight (Figure S7). The
Tg (≈ -22 °C) and Tm (≈76 °C) of the high molecular
weight P[3-HP] generated from the polymerization of
the trimer agreed with those reported in the litera-
Refer en ces a n d Notes
(1) (a) Mecking, S. Angew. Chem., Int. Ed. 2004, 43, 1078. (b)
Wedin, R. Chemistry 2004, Spring, 30.
(2) Drumright, R. W.; Gruber, P. R.; Henton, D. E. Adv. Mater.
2000, 12, 1841.
(3) Ritter, S. K. Chem. Eng. News 2004, 82 (22), 31.
(4) McCoy, M. Chem. Eng. News 2003, 81 (50), 17.
(5) Yamashita, M.; Hattori, N.; Nishida, H. Polym. Prepr., J pn.
1994, 43, 3980.
(6) (a) Nishida, H.; Suzuki, S.; Tokiwa, Y. J . Environ. Polym.
Degrad. 1998, 6, 43. (b) Kasuya, K.; Inoue, Y.; Doi, Y. Int.
J . Bio. Macromol. 1996, 19, 35. (c) Mathisen, T.; Lewis, M.;
Albertsson, A. J . Appl. Polym. Sci. 1991, 42, 2365. (d)
Mathisen, T.; Albertsson, A. J . Appl. Polym. Sci. 1990, 39,
591.
ture (Tg ) -21 °C, Tm ) 79 °C;16a Tg ) -23 °C, Tm
)
73 °C16b).
With the successful controlled ROP of the trimer in
CH2Cl2 solution at RT demonstrating that 3-HP may
be converted to P[3-HP] via the macrocyclic approach,
we assessed variations with the aim of further enhanc-
ing practical utility. For example, melt polymerizations
are desirable since they avoid the use of solvent. Given
the low melting point of the trimer (56 °C)11a and the
high-temperature stability of the Zn catalyst,17 we
explored the polymerization of the neat trimer at 80 °C
(Table 1). While the molecular weight control was not
quite at the level demonstrated for the solution poly-
merizations, we were able to generate high molecular
weight P[3-HP] using as little as 0.13 mol % catalyst in
80 min.
It would also be desirable to be able to polymerize the
larger ring macrocycles present in the macrocyclic
fraction obtained from the self-condensation of aqueous
3-HP. Indeed, we isolated a fraction containing only
tetramer and pentamer (85:15) and found that it was
rapidly converted (83%) into high molecular weight
P[3-HP] (Mn ) 74.3 kg‚mol-1, PDI ) 1.6) in CH2Cl2 at
(7) Nanba, T.; Ito, H.; Kobayashi, H.; Hayashi, T. J P 06329774,
1994.
(8) (a) Gresham, T. L.; J ansen, J . E.; Shaver, F. W. J . Am.
Chem. Soc. 1948, 70, 998. (b) Asahara, T.; Katayama, S.
Kogyo Kagaku Zasshi 1966, 69, 725. (c) Fukui, K.; Yuasa,
S.; Kagitani, T.; Shimizu, T.; Sano, T. J P 38026596, 1963.
(d) Marans, N. S. US 3111469, 1963. (e) Matsumura, S.;
Beppu, H.; Toshima, K. Enzymes in Polymer Synthesis; ACS
Symposium Series 684; American Chemical Society: Wash-
ington, DC, 1998; p 74. (f) Noltes, J . G.; Verbeek, F.;
Overmars, H. G. J .; Boersma, J . J . Organomet. Chem. 1970,
24, 257. (g) Ouhadi, T.; Heuschen, J . M. J . Macromol. Sci.,
Chem. 1975, A9, 1183. (h) Yamashita, M.; Takemoto, Y.;
Ihara, E.; Yasuda, H. Macromolecules 1996, 29, 1798. (i)
J edlinski, Z.; Kurcok, P.; Kowalczuk, M. Polym. Int. 1995,
37, 187.
(9 ) h t t p ://w w w .os h a .gov/d t s /ch e m ica ls a m p lin g/d a t a /
CH_264200.html.
(10) (a) Simanda, T. L.; Vladea, R. V.; Siclovan, T. M.; Rusnac,
L. M.; Simandan, C.; Petcu, M. RO 102187, 1992. (b)
Miyazawa, T.; Endo, T. J . Org. Chem. 1985, 50, 3930. (c)
Drent, E.; Kragtwijk, E. EP 577206, 1994. (d) Hattori, N.;

8200 Communications to the Editor
Macromolecules, Vol. 37, No. 22, 2004
Nishida, H. J P 09169753, 1997. (f) Khusnutdinov, R. I.;
Shchadneva, N. A.; Baiguzina, A. R.; Lavrentieva, Y. Y.;
Dzhemilev, U. M. Russ. Chem. Bull. 2002, 51, 2074. (g)
Kung, F. E. US 2356459, 1944.
(14) Williams, C. K.; Breyfogle, L. E.; Choi, S. K.; Nam, W. W.;
Young, V. G.; Hillmyer, M. A.; Tolman, W. B. J . Am. Chem.
Soc. 2003, 125, 11350.
(15) (a) Gruber, P. R.; Hall, E. S.; Kolstad, J . J .; Iwen, M. L.;
Benson, R. D.; Borchardt, R. L. US 5247059, 1993. (b)
Sterzel, H.-J .; Ruetter, H.; Dauns, H.; Matthies, H. G.;
Minges, R. GB 2277324, 1994.
(11) (a) Shanzer, A.; Libman, J .; Frolow, F. J . Am. Chem. Soc.
1981, 103, 7339. (b) Roelens, S. J . Chem. Soc., Chem.
Commun. 1990, 58.
(12) (a) Brunelle, D. J .; Shannon, T. G. Macromolecules 1991,
24, 3035. (b) Hodge, P.; Hall, A. J . React. Funct. Polym.
2001, 48, 15.
(13) Zhang, D.; Xu, J .; Alcazar-Roman, L.; Greenman, L.; Cram-
er, C. J .; Hillmyer, M. A.; Tolman, W. B. Macromolecules
2004, 37, 5274.
(16) (a) He, Y.; Asakawa, N.; Inoue, Y. Polym. Int. 2000, 49, 609.
(b) Cao, A.; Asakawa, N.; Yoshie, N.; Inoue, Y. Polym. J .
1998, 30, 743.
(17) Schreck, K. M.; Hillmyer, M. A. Tetrahedron 2004, 60, 7177.
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