Synthesis and Characterization of a New Benzofulvene Polymer Showing a Thermoreversible Polymerization Behavior

Article abstract of DOI:10.1021/jo035104h

A new polymer based on a functionalized benzofulvene moiety has been synthesized by spontaneous polymerization of the monomer in the solid state. This polymer shows a very high molar mass, high solubility in the most common organic solvents, and thermorev

Full text of DOI:10.1021/jo035104h

SCHEME 1 a
Syn th esis a n d Ch a r a cter iza tion of a New
Ben zofu lven e P olym er Sh ow in g a
Th er m or ever sible P olym er iza tion Beh a vior
Andrea Cappelli,*,† Gal.la Pericot Mohr,†
Maurizio Anzini,† Salvatore Vomero,†
Alessandro Donati,‡ Mario Casolaro,‡ Raniero Mendichi,§
Gianluca Giorgi,| and Francesco Makovec
Dipartimento Farmaco Chimico Tecnologico, Universita`
degli Studi di Siena, Via A. Moro, 53100 Siena, Italy,
Dipartimento di Scienze Chimiche e dei Biosistemi,
Universita` degli Studi di Siena, Via A. Moro, 53100 Siena,
Italy, Istituto per lo Studio delle Macromolecole (CNR),
Via E. Bassini 15, 20133 Milano, Italy, Centro
Interdipartimentale di Analisi e Determinazioni Strutturali,
Universita` di Siena, Via A. Moro, 53100 Siena, Italy,
and Rotta Research Laboratorium SpA,
via Valosa di Sopra 7, 20052 Monza, Italy
cappelli@unisi.it
Received J uly 29, 2003
a
Reagents: (a) CH3MgBr, C2H5OC2H5; (b) PTSA, CHCl3; (c)
Abstr a ct: A new polymer based on a functionalized ben-
zofulvene moiety has been synthesized by spontaneous
polymerization of the monomer in the solid state. This
polymer shows a very high molar mass, high solubility in
the most common organic solvents, and thermoreversible
polymerization properties. An interesting application in
synthesis is reported.
solvent elimination; (d) solvent, heating; (e) CH2N2, (CH3COO)2Pd,
CHCl3.
This trans-diene represented a very interesting interme-
diate for the preparation of a variety of useful building
blocks to be used in the synthesis of new potentially
bioactive compounds. Thus, we engaged the synthesis of
1 following the procedure outlined in Scheme 1. The key
indenone intermediate 24 was prepared by modifying the
procedure described by Koelsch,5 and its structure was
unambiguously characterized by means of single-crystal
X-ray diffractometry studies (Supporting Information).
The reaction of 2 with methylmagnesium bromide gave
the expected indenol 3 (the structure of this 1,2-addition
product was solved by X-ray diffraction). Dehydration of
3 with p-toluenesulfonic acid (PTSA) in chloroform gave,
as expected, a compound less polar than 3 as shown by
thin-layer chromatography (TLC). However, this com-
pound proved to be of difficult isolation because the
solvent removal led to the isolation of a polymeric
material6-8 containing only trace amounts of the expected
1, as demonstrated by 1H NMR spectroscopy. Conversely,
when the dehydration was performed in CDCl3, allowing
the 1H NMR analysis to be performed without the solvent
In the chemistry of advanced polymers, the properties
of polydibenzofulvenes, polythiophenes, polypyrroles,
polyfulvenes, and self-organized assemblies of poly-
thiophenes are of current interest.1-3
Recently, benzofulvene derivative 1 (BF 1) has been
discovered to form a new macromolecular architecture
that is potentially useful in the chemistry of advanced
polymers. In this paper, we describe the synthesis, the
preliminary characterization, and useful synthetic ap-
plication of the new polymer based on the benzofulvene
moiety.
In a large research program devoted to the discovery
of new drugs, we were interested in the synthesis of 1.
* To whom correspondence should be addressed. Tel: +39 0577
234320. Fax: +39 0577 234333.
† Dipartimento Farmaco Chimico Tecnologico, Universita` degli Studi
di Siena.
1
elimination, a clear H NMR spectrum compatible with
‡ Dipartimento di Scienze Chimiche e dei Biosistemi, Universita`
degli Studi di Siena.
the structure of 1 was obtained.
Thus, dehydration of 3 gave 1 which was stable in
solution and polymerized upon solvent removal to give
§ Istituto per lo Studio delle Macromolecole (CNR).
| Centro Interdipartimentale di Analisi e Determinazioni Strutturali,
Universita` di Siena.
Rotta Research Laboratorium SpA.
(1) Nakano, T.; Takewaki, K.; Yade, T.; Okamoto, Y. J . Am. Chem.
Soc. 2001, 123, 9182-9183.
(4) Babin, P.; Dunogue`s, J . Tetrahedron Lett. 1984, 25, 4389-4392.
(5) Koelsch, C. F. J . Org. Chem. 1960, 25, 2088-2091.
(6) Wadsworth, W. S.; Emmons, W. D. J . Am. Chem. Soc. 1960, 83,
1733-1738.
(2) Pranata, J .; Grubbs, R. H.; Dougherty, D. A. J . Am. Chem. Soc.
1988, 110, 3430-3435.
(3) Reitzel, N.; Greve, D. R.; Kjaer, K.; Howes, P. B.; J ayaraman,
M.; Savoy, S.; McCullough, R. D.; McDevitt, J . T.; Bjornholm, T. J .
Am. Chem. Soc. 2000, 122, 5788-5800.
(7) Fieser, L. F.; J oshel, L. M. J . Am. Chem. Soc. 1940, 62, 957-
958.
(8) Wieland, H.; Probst, O. Liebigs Ann. Chem. 1937, 530, 274-290.
10.1021/jo035104h CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/31/2003
J . Org. Chem. 2003, 68, 9473-9476
9473

F IGURE 1. Comparison between the 1H NMR spectra (200 MHz) of BF 1 (top) and of p oly-BF 1 (bottom).
p oly-BF 1 showing distinct physicochemical character-
istics. Indeed, the 1H NMR spectrum of this material
showed broad signals in place of the sharp ones typical
of benzofulvene 1. The signals attributable to the vinyl
dCH2 group of 1 (two singlets at 6.35 and 6.55 ppm)
became a broad signal (centered at about 3.2 ppm)
attributable to a -CH2- bridge in p oly-BF 1 (Figure 1).
The transformation of the vinyl dCH2 group of 1 into a
-CH2- bridge strongly support the polymer nature of
p oly-BF 1.
The characterization of the freshly prepared material
by a multiangle laser light scattering on-line to a size-
exclusion chromatography (SEC-MALS) system gave a
molar mass value extraordinarily high (approximately
F IGURE 2. Differential molar mass distribution of p oly-BF 1.
Mw ) 2.5 million g/mol) and a dispersity index a little
broader than 2 (D ) 2.2) (Figure 2). Considering that the
presence of aggregates was not observed in the freshly
synthesized p oly-BF 1, this was a very interesting result.
Both the intrinsic viscosity ([η] ) 1.4 dL/g in THF) and
the gyration radius (Rg ) 58.9 nm) were consistent with
the very high molar mass.
spectrum obtained with dithranol as the matrix (Figure
3) showed the presence of a series of peaks differing by
290 u (the molecular weight of monomer 1) up to a mass-
to-charge ratio of about 8000. Heavier polymeric species
were undetectable under MALDI-TOF conditions.
MALDI-TOF mass spectrometry of p oly-BF 1 con-
In principle, trans-diene 1 can undergo either vinyl
firmed the polymeric nature of this material. The MALDI
(1,2) or diene (1,4) polymerizations, each leading to
9474 J . Org. Chem., Vol. 68, No. 24, 2003

F IGURE 3. MALDI-TOF spectrum of p oly-BF 1.
different polymer backbones. The nature of the vinyl
polymer of p oly-BF 1 was suggested by the presence of
two unusually shielded aromatic protons at about 6 ppm,
consistent with the presence of strong interactions among
the aromatic moieties (π-stacking). Indeed, preliminary
molecular modeling studies indicated a higher degree of
stacking in the assumed vinyl polymer with respect to
the 1,4-enchained one. Moreover, 1,2-polymerization
would preserve conjugation in the polymer between the
donor aryl group and the acceptor ester group. However,
1,4-polymerization cannot be ruled out, and further
studies are in progress in order to define the molecular
structure of p oly-BF 1 unambiguously.
F IGURE 4. Thermal-induced depolymerization of p oly-BF 1,
followed by H NMR (600 MHz). Peak intensity of the spectra
1
Benzofulvene derivative 1 was stable in solution at
reflux in the presence of a catalytic amount of dibenzoyl
peroxide. Moreover, p oly-BF 1 was obtained also in the
case of the solvent elimination in the presence of a radical
inhibitor such as 2,6-di-tert-butyl-p-cresol. These results
suggest that free radical species are not involved in the
polymerization mechanism, which would be ionic in
nature. Again, the polymerization of 1 was active also in
the absence of PTSA, suggesting cationic catalysis to be
unnecessary. Probably, the solvent removal induces the
strongly polarized9 exocyclic double bonds of two mol-
ecules of 1 to interact with each other with the formation
of a dimer featuring a zwitterionic tetramethylene moi-
ety.10 This zwitterionic intermediate would show a nega-
tive charge stabilized as an aromatic indenyl anion and
collected at 1.5 and 6.0 h were reduced by 25% and 50%,
respectively. Arrows indicate the solvent (nitrobenzene) peaks.
The asterisk indicates the water peak.
by NMR spectroscopy at high temperature. Owing to the
relatively low speed of the process at low temperatures,
we chose to perform the experiments at different times
in nitrobenzene at 140 °C. Figure 4 shows that the broad
lines typical of the polymer progressively disappeared as
a consequence of the exposure to high temperature to be
replaced by the sharp signals of the fulvene monomer 1.
Thus, the restoring of the solvated conditions led the
polymer to release the monomer at a temperature-
dependent rate.
Finally, a significant change in the solubility of p oly-
BF 1 was observed after its prolonged storage as a solid.
This suggests the possible formation of macromolecular
aggregates or the increasing of the molecular weight by
specific combination of the individual chains of p oly-BF 1
in the solid state.
On the basis of these interesting properties, i.e., the
high solubility in the most common organic solvents, and
the susceptibility to molecular manipulation of p oly-BF 1,
intriguing potential applications in synthesis can be
envisioned, as well as in drug-controlled release, in the
development of photoconducting and luminescent materi-
als, in solid phase synthesis, and in catalysis, all of which
will be suitably explored. As far as the application we
have tested is concerned, we found that the polymer can
be used as a stock form of benzofulvene derivative 1. In
+
an unstabilized CH2 which could initiate the cationic
polymerization process leading to p oly-BF 1. If this
mechanism is operating, the presence of terminal charges
can be assumed along with the reversibility of the
polymerization process.
Heating the solutions of the polymer to reflux in aprotic
solvents showing different boiling points (e.g., ethyl
acetate, toluene, and xylene) led to both the depolymer-
ization of p oly-BF 1 and the regeneration of the fulvene
monomer 1. The fragmentation of the polymer was faster
in xylene than in ethyl acetate. On the basis on these
observations, the depolymerization process was followed
(9) Bergmann, E. D. Chem. Rev. 1968, 68, 41-84.
(10) Hall, H. K. J R.; Padias, A. B. Acc. Chem. Res. 1997, 30, 322-
329.
J . Org. Chem, Vol. 68, No. 24, 2003 9475

fact, compound 1 generated from the polymer was used
for the synthesis of spirocyclopropane derivative 4 by
means of a palladium-catalyzed cyclopropanation11 with
diazomethane (Scheme 1).
cial support. Prof. Stefania D’Agata D’Ottavi’s careful
reading of the manuscript is also acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for the synthesis and the characterization of compounds
1-4 and p oly-BF 1 (chemistry, NMR, MS, X-ray crystal-
lography, SEC analysis). This material is available free of
charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. Thanks are due to Rotta Re-
search Laboratorium SpA and Italian MIUR for finan-
(11) Suda, M. Synthesis 1981, 714.
J O035104H
9476 J . Org. Chem., Vol. 68, No. 24, 2003