Eur. J. Lipid Sci. Technol.

2018, 120, 1700091 1700091 (1 of 20)

Review Article
Macromolecular materials based on the application of the
Diels–Alder reaction to natural polymers and plant oils

Alessandro Gandini1, Antonio J. F. Carvalho1, Eliane Trovatti1, Ricardo K. Kramer1

and Talita M. Lacerda1,2

1
~o Carlos, Universidade de Sa
Escola de Engenharia de Sa ~o Paulo, Sa
~o Carlos, SP, Brazil
2
~o Paulo, Lorena, SP,
Departamento de Biotecnologia, Escola de Engenharia de Lorena, Universidade de Sa
Brazil

The furan-maleimide thermally reversible Diels–Alder reaction applied to the elaboration of novel
macromolecular materials from renewable resources (see image of polymerization and depolymeriza-
tion) is reviewed on the basis of our investigations, which cover predominantly the field to this date.
Different approaches are outlined, depending on the substrate and the results discussed in terms of the
properties and potential applications of the ensuing linear, branched, and crosslinked polymers, with
particular emphasis on their recyclability. These chemical modifications concern triglycerides and
macromonomers derived from them, polysaccharides such as cellulose fibers and nanofibers, starch and
chitosan, as well as natural rubber and gelatin.

Keywords: Cellulose / Chitosan / Diels–Alder reaction / Furan / Maleimide / Natural rubber / Starch / Vegetable oils
Received: May 9, 2017 / Revised: June 27, 2017 / Accepted: June 28, 2017
DOI: 10.1002/ejlt.201700091

1 Introduction maleimide) moieties using a bifunctional maleimide (or furan)

The application of the Diels–Alder (DA) reaction to polymer
synthesis and modification constitutes a rather recent
research topic, which has, however, been developing at a
growing pace. A comprehensive review, dealing with by far
the most widespread furan/maleimide (F/M) diene/dieno-
phile combination [1], discussed the literature covering the
1986–2012 period, already emphasizing the steady increase
in publications within the latter 5 years. Since then, the flow
of contributions, treating different strategies and processes,
has not ceased to increase, highlighting that the area has now
become a well-established scientific and technical macromo-
lecular domain [2]. Two basic approaches characterize this
domain, viz. (i) the synthesis of thermally reversible linear,
branched, and crosslinked polymers based on the polycon-
densation of monomers incorporating complementary furan
and maleimide functions; and (ii) the thermally reversible
crosslinking of linear polymers bearing pendant furan (or
Correspondence: Prof. Alessandro Gandini, Escola de Engenharia de
~o Carlos, Universidade de Sa
Sa ~o Paulo, 13566-590 Sa
~o Carlos, SP,
Brazil
E-mail: agandini@iqsc.usp.br
Fax: þ55 163 3739590
Abbreviations: DA, Diels–Alder; F/M, furan/maleimide; NR, natural
rubber; VO, vegetable oils
crosslinker. The main reason for this success is certainly related
to the fact that the temperature domain affecting the forward
(click) and retro DA (rDA) equilibrium associated with that
particular combination opens the way to original and useful
applications, such as readily accessible polymer deconstruc-
tions and hence the possibility of recycling crosslinked
materials, self-repairing, and other thermally reversible
operations leading to novel macromolecular architectures
with promising applications [1, 2]. Scheme 1 illustrates the DA
equilibrium involving substituted furan (F) and maleimide
(M) reagents with the two corresponding isomeric endo and
exo adducts (AFM). The forward click reaction dominates
up to about 60°C, whereas the rDA return to the reagents is
predominant above about 120°C.
When this DA coupling is applied to monomer or
polymer structures bearing furan and maleimide moieties,
each adduct formation corresponds to a thermally reversible
step in a polymer growth process, or in a macromolecular
modification, as shown in Scheme 2, where the two adduct
stereoisomers are not exhibited because their relevance in
both these approaches is negligible [1]. In polymerization
situations, typical linear step growth reactions are carried
out with difunctional complementary monomers, viz. F-R-
F þ M-R’-M, or with an F-R-M AB-counterpart, whereas
the use of monomers with functionalities higher than two,
leads to branched or crosslinked structures. When polymers

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

1700091 (2 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

incorporating pendant F or M moieties are employed, the

synthesis of thermally reversible networks is carried out
Alessandro Gandini, for the past 57
through the addition of bismaleimides or difuran molecules,
years has conducted research and
respectively [1]. Among other applications, one finds the
taught chronologically in
synthesis of dendritic structures, the decoration of nano-
Switzerland, the United Kingdom,
particles and biomedical constructs [1]. The course of these
Canada, the United States, Cuba,
reactions has been monitored by UV, FTIR, and NMR
Canada, France, Brazil, Portugal,
spectroscopy, including the thermally corresponding decon-
Italy, and now in France and Brazil,
structing processes.
with invited professorships in nu-
The purpose of the present review is to discuss the
merous other countries. Polymer
application of these DA strategies to biomass-based mole-
chemistry, photochemistry, and surface science have
cules and macromolecules, a topic we recently begun to
dominated his professional interests, with a progressively
investigate within our broader research program on polymers
growing involvement in polymers from renewable
from renewable resources [2] and which was progressively
resources, a topic he was one of the first to investigate and
applied to plant-oil monomers, starch, natural rubber,
promote.
cellulose and nanocellulose fibers, chitosan, and gelatin.
To the best of our knowledge, no contributions to this
specific area are available from research groups other than
those reported here, which justifies the apparent lack of
ElianeTrovatti graduated with a
diversity in referencing the relevant publications. Indeed, one
master’s degree in pharmaceutical
of us has very recently refereed a few papers falling within
sciences and biochemistry and a
this realm, showing that interest in it is spreading, but none
Ph.D. degree in biotechnology from
of the studies has yet been published.
S~ao Paulo State University. She held
postdoctoral positions at the Uni-
versity of Aveiro, Portugal, Wallen-
2 Vegetable oils
berg Wood Science Center, Sweden,
and University of S~ao Paulo before
Polymers derived from vegetable oils (VO) have been
gaining a junior professorship in one of Araraquara’s
exploited for millennia, mostly through the aptitude of the
University in S~ao Paulo State. Her research interests
unsaturated triglycerides to undergo a drying process
include materials and composites from renewable
induced by atmospheric oxygen, giving rise to paints,
resources (nanocellulose, chitosan, natural rubber), the
lacquers, inks, linoleum, etc. During the last several decades,
development of biomaterials for biological applications,
however, the interest in preparing more original macromo-
biotechnological processes for the synthesis of biomole-
lecular structures from the pristine oils or from monomers
cules from microorganisms, and the synthesis of peptides
derived from them, has resulted in a remarkably widened
with biological activity.
set of chemical strategies and hence in a promising variety
of materials. This research effort is today in full bloom [3].
To the best of our knowledge, the application of the F/M-
DA reaction to VO-based monomers was first investigated
Talita M. Lacerda received a B.Sc. in
using 10-undecenoic acid [4, 5], a chemical commodity
chemistry in 2008 and a Ph.D. in
derived from castor oil, possessing two terminal reactive sites
chemistry in 2012, both from the S~ao
suitable for the insertion of furan and/or maleimide
Carlos Institute of Chemistry, Uni-
functions. Two similar difuran monomers were synthesized
versity of S~ao Paulo, Brazil. After
following the two alternative routes in which esterification
post-doc positions in Professor
and thiol-ene reactions were employed, as illustrated in
Gandini’s group (2012-2016) on the
Schemes 3 and 4.
synthesis of termoreversible polymers
A third difunctional monomer, but incorporating one
based on renewable resources, and in
furan and one maleimide moiety was also prepared from
Professor Meier’s group (2013–2014) on the synthesis of
10-undecenol, which required the protection of the latter
polymers from itaconic and levulinic acids, she now holds a
function in order to avoid precocious polymerization due to
junior professorship at the Lorena School of Engineering,
the presence of the two complementary DA reactive sites, as
University of S~ao Paulo. Her main research interests
shown in Scheme 5. The protected monomer was isolated
include the synthesis and chemical modification of
and fully characterized before being deprotected by the rDA
polymers and biocomposites based on renewable
illustrated in Scheme 5, cooled and submitted to the DA
resources.
polycondensation.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
The three monomers were polymerized at 65°C in
1,1,2,2-tetrachloroethane (TCE and TCE-d2 for the
1
H NMR studies), the DA reactions being followed by UV
and 1H NMR spectroscopy [4, 5]. The two difuran
monomers were coupled with equimolar amounts of 1,6-
bismaleimidohexane, whereas the FM one self-polymerized.
After the completion of the polycondensations, the tempera-
ture was raised to 110°C and the rDA-induced depolyme-
rizations followed by the same spectroscopic techniques, all
the way to the regeneration of the respective monomers. The
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (3 of 20)
Scheme 1. The thermally reversible DA equi-
librium involving furan (diene) and maleimide
(dienophile) reagents.
Scheme 2. Thermally reversible F/M DA
condensation involved in polymer step growth
or grafting.
Scheme 3. Synthesis of a difuran monomer
from 10-undecenoic acid.
Scheme 4. Synthesis of a second difuran
monomer from 10-undecenoic acid.
solutions were then cooled to 65°C and the DA poly-
condensations resumed following the same pattern as during
their first process, confirming the good reproducibility of the
DA/rDA cycle illustrated in Scheme 6 [4, 5]. The two
polymers prepared with difuran and bismaleimide monomers
had Mw of 7–9 kDa and displayed glass transition temper-
atures of about 30°C in accordance with the molecular
flexibility of both precursors (Scheme 6). The FM-based
polymer had a Mw of 17 kDa and a Tg of 2°C, associated
with a stiffer macromolecular structure.
www.ejlst.com
1700091 (4 of 20) A. Gandini et al.
Scheme 5. Synthesis of a FM-type monomer from 10-undecenol.
This investigation was pursued by studying non-linear
polymers prepared from different trifunctional mono-
mers [6]. A trifuran structure was synthesized following
the steps shown in Scheme 7. A protected F2M monomer was
prepared as illustrated in Scheme 8, and the synthesis of a
protected FM2 monomer is given in Scheme 9.
The trifuran monomer was polymerized with the aliphatic
bismaleimide to produce a thermally reversible highly
branched or crosslinked material, depending on the mono-
mer molar feed (Scheme 10). Similarly, one of the difuran
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
monomers prepared in the initial study was polymerized with
a trismaleimide to give the same types of macromolecular
architectures (Scheme 11). With both systems [6], the use of
a trifunctionl/bifunctional molar ratio of 0.5, the ensuing
branched polymers displayed Mw between 35 and 50 kDa
and Tg values around 0°C. Stoichiometric monomer
conditions produced gels with Tg values of about 15 °C
reflecting the correspondingly higher polymer stiffness.
The DA self-polymerization of the F2M and FM2
monomers, following deprotection, yielded hyperbranched
macromolecules, as shown in Scheme 12 for the latter
monomer, with the former behaving likewise. Their Mw
ranged between 50 and 70 kDa (PDI > 3), with Tg values
around 5°C [6]. All these polymers displayed the expected
thorough rDA deconstruction, hence the ease of recyclabil-
ity, particularly useful in the case of otherwise intractable
network structures.
We then turned to structures derived from plant oils
which were much closer to their pristine triglycerides.
Commercial epoxidized linseed oil bearing an average of
five epoxy groups per triglyceride (Fig. 1) was submitted to a
bulk reaction with an excess of furfuryl amine at 95°C [7],
whereby two concomitant reactions were observed to take
place, namely the transamination of the three ester moieties
and the epoxy ring opening induced by the primary amine, as
shown in Scheme 13. These events were monitored by both
FTIR and 1H NMR spectroscopies (Fig. 2), the former
revealing the progressive ester/amide transformation through
the shift of the respective carbonyl peak from 1740 to
1640 cm1, and the latter the parallel reduction in the
resonance intensity associated with the epoxy protons around
3 ppm.
The net result of this modification was the formation of
a mixture of fatty amides incorporating two or three furan
rings, which constituted potential dienic monomers for
further DA polymerizations with a bismaleimide, here the
Scheme 6. Reversible DA polycondensation
of a difuran monomer with an aliphatic
bismaleimide.
www.ejlst.com
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
aromatic 1,10 -(methylenedi-4,1-phenylene)bismaleimide.
These polycondensations were carried out at 65°C in TCE
and TCE-d2 for the 1H NMR studies [7] and yielded a
mixture of linear and branched polymers with Mw of 35–
40 kDa and Tg of 80–100°C. The mechanism associated
with the reaction, limited to difuran monomers leading to
linear structures, is shown in Scheme 14, together with the
1
H NMR spectrum of a typical precipitated polymer, which
contained both linear and branched macromolecules and
displayed the typical resonances pertaining to the FM
adducts at 6.5, 6.3, 5.3, 3.1, and 3.0 ppm, apart from those
of the aromatic moieties arising from the bismaleimide at
Scheme 8. Synthesis of a difuran monomer bearing a protected maleimide moiety.
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (5 of 20)
Scheme 7. Synthesis of a trifuran monomer
based on 10-undecenoic acid.
7.0–7.5 ppm. These systems did not lead to crosslinking
because of the predominance of difuran monomers over the
trifuran homologues. All the polymers were submitted to
the rDA reaction at 110°C and progressively reversed to the
original reagents, only to repolymerize when the temperature
was decreased to 65°C.
The application of the same strategy to commercial
epoxidized soybean oil resulted in the same overall behavior
and results.
In another approach, commercial tung oil was the starting
triglyceride [8], whose main triglyceride is made up of a-
eleostearic ester moieties containing three conjugated
www.ejlst.com
1700091 (6 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

Scheme 9. Synthesis of a monofuran monomer bearing two protected maleimide moieties.

unsaturations (Fig. 3), exploited for millennia in coatings and
lacquers because of their very pronounced air siccativity.
They also behave as “dienes” in the DA reaction, as first
recognized by Metzger and coworkers [9] who studied the
bulk reaction of the methyl ester of a-eleostearic with maleic
anhydride as dienophile at 150°C. Before tackling polymeri-
zation systems, we showed that methylmaleimide behaved
likewise, even at 65°C, i.e., a temperature sufficiently low to
avoid side free radical reactions [8]. The adduct formed in
these DA couplings is thermally stable and cannot therefore
be exploited for the reversibility strategy discussed above for
the FM counterpart.
We combined this specific feature to study the DA
crosslinking of tung oil at 65°C with three bismaleimides

Scheme 10. Non-linear thermally reversible DA polycondensation using a trifuran and a bismaleimide monomer.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091 Diels–Alder on natural polymers 1700091 (7 of 20)

Scheme 11. Non-linear thermally reversible DA polycondensation of a difuran with a trismaleimide monomer.

Scheme 12. Deprotection and thermally reversible DA self-polymerization of the F2M monomer.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

1700091 (8 of 20) A. Gandini et al.
Figure 1. The structure of the commercial epoxidized linseed oil.
with variable molecular flexibility, as shown in
Scheme 15 [8]. The ensuing gels had Tg values ranging
from 10 to 75°C depending on the bismaleimide and a
thermal stability exceeding 350°C, confirming the lack of
reversibility of the corresponding DA adducts. The
application of this bulk reaction to coating different surfaces
at 80°C for 24 h in an inert atmosphere, produced a regular-
structure, thermally stable crosslinked film uniquely gener-
ated by the DA reaction, i.e., a better controlled and
catalyst-less process alternative to the conventional atmo-
spheric drying of tung oil.
A second approach to the exploitation of tung oil
called upon the same transamination reaction described
above for epoxidized plant oils, followed by the linear
polycondensation of the ensuing furan/triene difunc-
tional DA dienes with the same three bismaleimides [8],
as pictured in Scheme 16 for the stiff aromatic
homologue.
Scheme 13. Transamidation and epoxy coupling of epoxidized linseed oil induced by furfuryl amine.
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
Interestingly, here the ensuing polymers incorporated in
each monomer unit one thermally labile FM adduct and a
thermally stable one formed by a maleimide function with the
a-eleostearic triene moiety, so that the application of the rDA
at about 110°C to them resulted in a depolymerization
process only involving the FM adducts, leading to dimers
bearing two terminal furan rings and incorporating the stable
adduct, as indeed verified experimentally [8]. The polymers
had Tg values ranging from 30 to 105°C, i.e., 30–50°C
higher than the corresponding gels discussed above because
of the stiffening contribution of intermolecular amide-based
hydrogen bonds, and Mw of 20–40 kDa.
3 Natural rubber
After a period of decline with respect to synthetic
elastomers, the world production of natural rubber (NR),
www.ejlst.com
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091 Diels–Alder on natural polymers 1700091 (9 of 20)

Figure 2. The kinetics of the reactions shown in Scheme 13, monitored by FTIR (transamidation) and 1H NMR (epoxy ring opening)
spectroscopy.

concentrated in Asia (Thailand, Indonesia, Malaysia,
China, and India) and Australia, is now following a similar
growth, as shown in Fig. 4, with a 45% contribution to the
total output. The latex from a variety of species, but
dominated industrially by Hevea brasiliensis (Figs. 5 and 6) is
an aqueous emulsion of 30–40 wt% cis-1,4-poly(isoprene)
and some 5 wt% of proteins, resins, and sugars. The major
use of NR is destined to tires and conveyor belts, followed
by gloves, automotive parts, footwear, adhesives, and
medical appliances.
The vast majority of applications of NR require a
crosslinking process induced by sulfur, called vulcanization,
invented by Goodyear in the mid-XIX century and developed
industrially at the end of the same century, before being
extended to synthetic elastomers like poly(butadiene) and its
copolymers and poly(isobutene-co-isoprene) known as “butyl
rubber.” The basic features of this operation are the same today
and arguably the most striking of its aspects is the chemical
stability of these loose networks (typically formed through the
reaction of only 3–5 mole% of the monomer units) in terms of

Scheme 14. The thermally reversible DA linear polycondensation and the 1H NMR spectrum of a typical polymer.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

1700091 (10 of 20) A. Gandini et al.
Figure 3. 1H NMR spectrum of commercial tung oil.
recalcitrance to deconstruction, quite apart from the proneness
to material degradation due to atmospheric oxidation of the
unsaturated chains. Although a number of approaches have
been tested [10], in fact no viable industrial process has found
the way to recycle tires. The net result is visible throughout the
planet, with mounds of discarded tires, amounting to more
than one billion objects every year. The existing measures to
alleviate this huge environmental problem, which of course also
Scheme 15. The DA crosslinking reaction of tung oil with bismaleimides.
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
applies to tires made from synthetic elastomers like poly-
(butadiene) and butyl rubber, such as their use in road flooring
or combustion for energy recovery, are far too modest to reduce
their accumulation in any significant way [10]. New methods of
recycling vulcanized elastomers are therefore urgently needed.
The mechanism of the FM DA/rDA reaction, with its
specific temperature range affecting the equilibrium between
reagents and adducts, appeared as a suitable approach to the
www.ejlst.com
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091 Diels–Alder on natural polymers 1700091 (11 of 20)

Scheme 16. Linear DA polycondensation of a-eleostearic furfurylamide with an aromatic bismaleimide.

solution of the problem of “recycling tires” [11]. The idea limited to about 4% of its monomer units. The modified
was to append furan heterocycles on the elastomer chains and PBD was then treated with a stoichiometric amount of 1,10 -
then crosslink them using a bismaleimide. The thiol-ene click (methylenedi-4,1-phenylene)bismaleimide in DCE at
reaction seemed appropriate for the first task, based on the 60°C and the solution gelled within several hours, as
coupling of furfuryl thiol to the unsaturations of the polymer. indicated by the absence of flow. Upon heating to 110°C,
We first studied this possibility with a 1,2-rich poly- the medium viscosity decreased progressively and within
(butadiene) commercial sample (PBD), typically employed hours the network was completely decrosslinked, as revealed
for tire manufacture, because the side vinyl moieties would
display a good reactivity in the thiol-ene coupling, as
illustrated in Scheme 17.
In order to simulate the degree of crosslinking typically
associated with the vulcanization process, viz. 3–5% of
monomer units reacting with sulfur, the thiol-ene random
coupling of furfuryl thiol to the side vinyl group of PBD was

Figure 4. Annual production of natural and synthetic rubber with

projection to 2020. Figure 5. Tapping the latex from Hevea Brasiliensis trees.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

1700091 (12 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

Figure 6. Furan-modified natural rubber before (a) and after (b) the DA reaction with the aromatic bismaleimide (note the separation of the
solvent below the formed gel), and after the DA decrosslinking at 110°C (c).

by 1H NMR spectroscopy. The DA/rDA cycle was repeated
to confirm the absence of side reactions and to validate the
working hypothesis about the possibility of recycling cross-
linked elastomers [11].
We subsequently applied the same concepts to natural
rubber [12] and synthesized a 2% furan derivative, as shown
in Scheme 18, before successfully crosslinking it with the
same bismaleimide. Again, the decrosslinking of this DA
network at 110°C produced a full return to the reagents
within hours, and again the DA/rDA cycle was shown to be
reproducible over a few sequences. Figure 7 shows one such
cycle visually. As expected, the crosslinking enhanced the
mechanical properties of the natural rubber (Fig. 8), as in the
case of the conventional sulfur vulcanization.
This strategy, based on the application of the thermally
reversible FM DA reaction applied to unsaturated polyolefin
elastomers, provided strong evidence that it could represent a
viable and sustainable solution to the recycling of otherwise
chemically intractable conventional sulfur-based network
materials, such as tires.
4 Cellulose fibers and nanofibers
The surface modification of cellulose fibers and nanofibers
has attracted considerable attention in recent years, particu-
larly within the booming area of materials based on
nanocelluloses [13]. These modifications include both
chemical and physical treatments of the fiber surface and
are aimed at a variety of potential applications, including,
among others, the improvement of the mechanical properties
of composite materials through better interface compatibi-
lization, where the fibers play the role of reinforcing elements,
novel materials based on nanocellulose, and biomedical gels
and devices. It is within the former topic that we looked into
the possibility of establishing continuous covalent linkages

Scheme 17. The thiol-ene addition of furan heterocycles to PBD and the thermally reversible DA crosslinking of the ensuing polymer with
an aromatic bismaleimide [11].

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
Scheme 18. The thiol-ene reaction of natural rubber with furfuryl
thiol.
between natural rubber and nanofibrillated cellulose (NFC)
fibers by crosslinking them through the FM DA
reaction [12].
For this purpose, the furan-modified natural rubber
described above was mixed with maleimide-grafted NFC. In
order to append the maleimide moieties to the nanofibers,
these were first oxidized using the TEMPO process that
Figure 7. Dynamic mechanical properties of furan-modified natural
rubber before (FNR) and after its DA crosslinking with the aromatic
bismaleimide (FNR-BM).
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (13 of 20)
generates carboxylic groups from the nanocellulose surface
primary alcohol functions (ToNFC). A protected maleimide
molecule bearing primary amino groups was synthesized and
made to condense with those COOH functions to induce the
grafting, after which the maleimide moiety was regenerated
by rDA deprotection [12], as shown in Scheme 19.
When the furan-modified natural rubber was mixed
with the maleimide-modified cellulose nanofibers in THF,
gel formation occurred within minutes (Scheme 20) and
the only technique we could use to follow this rapid
crosslinking was DMA, as depicted in Fig. 8, which shows
the dramatic increase in modulus within 2 min, in contrast
with the lack of modulus variation when the mixing
involved unmodified ToNFC. This rapid FM DA cross-
linking thus produced a natural rubber composite in which
the nanocellulose fibers became covalently linked to the
elastomeric matrix.
It is worth pointing out that the furan-modified natural
rubber played two key roles in the course of these studies
based on the application of the FM DA reaction to renewable
resources, as pictured in Fig. 9.
In a different vein, refined, “never dried” industrial
cellulose pulp fibers were submitted to surface TEMPO
oxidation and the ensuing carboxylic groups converted into
furfuryl amide moieties by an aqueous-medium reaction with
furfuryl amine [14], as sketched in Scheme 21. A water-
soluble bismaleimide was then synthesized following the
steps shown in Scheme 22. The furan-modified fibers were
then treated with this bismaleimide in an aqueous medium in
order to induce their crosslinking through the FM DA
reaction at 65°C, which was confirmed by the progressive
increase of the medium viscosity and the formation of a
Figure 8. The variation in elastic modulus as a function of time
following the mixing of furan-modified natural rubber with oxidized
cellulose nanofibers compared with using maleimide-modified
counterparts.
www.ejlst.com
1700091 (14 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

Scheme 19. Grafting maleimide functions at the surface of oxidized NFC.

hydrogel made up of the water-swollen fiber chemical 5 Starch

network. This product was heated to 95°C and within an
hour it started flowing, with the individual fibers swirling
within the stirred medium, owing to the occurrence of the
rDA reaction. Finally, the system was brought back to
65°C and the gelling process took place for the second time,
as illustrated in Fig. 10.
The interest of generating chemically crosslinked pulp
fibers resides, among other potential applications, in the
preparation of strong papers for special domains in which
moreover this additional mechanical strength can be
reversibly erased upon a simple thermal treatment.
Starch-based materials occupy an important place in
renewable polymers and a considerable research and
development work effort is being devoted to optimize their
performances [2, 15]. This includes the development of
thermoplastic starch (TPS), copolymers, blends, and
chemical modifications, the latter involving in particular
the use of reactive extrusion. One of the main drawbacks of
TPS, a cheap, biodegradable, and readily manufactured
material, is its sensitivity to moisture which engenders loss of
mechanical properties and dimensional stability. Efforts to

Scheme 20. DA crosslinking between furan-modified natural rubber and maleimide grafted nanocellulose fibers.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
Figure 9. The two strategies applied to exploit the furan-modified natural rubber.
minimize this problem have provided some improvements,
but the real solution is still at large [2, 15]. Our latest
contribution to this context was to combine reactive
extrusion and FM DA crosslinking/decrosslinking, as well
as to enhance the mechanical properties of the ensuing
starch-based materials [16].
The basic tenants of the present study consisted again in
appending furan rings to the starch macromolecules and
inducing their crosslinking with a bismaleimide. The major
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (15 of 20)
difference here was the fact that during the reactive extrusion
process, only the furan grafting occurred, despite the later
injection of the bismaleimide along the extruder screw,
because the temperature at this point was well above the
adduct formation, i.e., the rDA reaction prevailed. The
actual crosslinking therefore only occurred during the cooling
of the extruded material [16]. The overall chemical process is
shown in Scheme 23. The furan-isocyanate reagent was
prepared by the condensation of furfuryl alcohol with MDI
Scheme 21. Grafting furan heterocycles onto
surface-oxidized cellulose fibers.
www.ejlst.com
1700091 (16 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

Scheme 22. Synthesis of a water-soluble bismaleimide.

and it was mixed with starch at the feeding end of the
extruder, the grafting reaction taking place during the
advancing of the molten mixture in the heated screw
chamber. The 1,10 -(methylenedi-4,1-phenylene)bismalei-
mide was introduced further downfield, but, as pointed
out, the FM DA reaction did not occur because of the
high temperature of the material in the extruder.
When the cooling extruded mixture reached about
60°C, the grafted furan rings reacted with the maleimide
functions through DA coupling and produced the cross-
linked starch. Heating this material above 100°C resulted
in its recovering a thermoplastic consistency with a typical
viscous flow. Figure 11 compares the dynamic mechanical
properties of a standard TPS with those of the FM DA
crosslinked material, emphasizing the large gain in
modulus, but also its drop at high temperature, associated
with the rDA decrosslinking [16]. Figure 12 highlights the
remarkable improvement in water resistance resulting
from the network formation by comparing again conven-
tional TPS with the crosslinked counterpart. As a
consequence, the effect of atmospheric moisture was
reduced very drastically. Figure 13 shows the extruded
material after cooling and a plate prepared by hot pressing
it, as a proof of the possibility of processing the network

Figure 10. The DA/rDA cycle applied to furan-bearing cellulose fibers reacting with a water-soluble bismaleimide. Initial suspension (a),
hydrogel after the FM DA crosslinking reaction (b), Return to the individual fiber suspension after the rDA reaction (c), and hydrogel formed
after the second DA coupling (d).

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
Scheme 23. Grafting furan heterocycles onto starch and FM DA/rDA reaction with a bismaleimide.
thanks to the rDA decrosslinking occurring at the press
temperature [16].
In conclusion, the outcome of this approach turned out to
be interesting as a potential technological solution for the
improvement of the properties of starch-based materials in
terms of their durability and mechanical performances.
6 Gelatin-based hydrogels
Hydrogels play a key role in numerous domains, principally
in biomedical applications. The preparation of one such
material was synthesized in an aqueous medium by the FM
DA crosslinking process using furan-modified gelatin and an
oligomeric water-soluble bismaleimide [17]. The grafting of
Figure 11. Dynamic mechanical properties of the FM DA cross-
linked starch (a) compared with those of TPS prepared in the same
conditions (b).
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (17 of 20)
furan heterocycles onto gelatin macromolecules was carried
out by the coupling of its primary amine groups with furfuryl
glycidyl ether, as shown in Scheme 24 and the water-soluble
bismaleimide was synthesized from an oligoether Jeffamine
following the reaction sequence given in Scheme 25. Three
hydrogels were then prepared in water at 65°C for 6 h using
the FM DA coupling, varying the molar F/M ratio, i.e., by
changing the crosslink density of the ensuing materials. The
reactions were followed by UV spectroscopy by monitoring
the decrease in optical density at 300 nm reflecting the loss of
conjugation between the maleimide carbonyl groups and its
C –– C unsaturation associated with the FM DA adduct. The
rDA reaction was also investigated by raising the medium
temperature to 90°C, which produced the progressive
dissolution of the hydrogels and the corresponding increase
in the 300 nm peak absorption [17].
The rheological properties and swelling aptitude of the
hydrogels at different pH values and ionic strengths indicated
that they should comply adequately with biomedical
applications, given the similarity of their behavior compared
with hydrogels currently employed in those areas.
7 Chitosan-based hydrogels
Another interesting source of hydrogels was studied within
the strategy of FM DA mechanism of crosslinking, namely
furan-grafted chitosan reacting with water-soluble bismalei-
mide [18]. Furan rings were appended to chitosan macro-
molecules by condensing furfural onto the primary amino
groups of the substrate to give a Schiff base, which was then
reduced to avoid hydrolysis. The crosslinking bismaleimide
was the same as that shown in Scheme 22 and the FM DA
coupling (Scheme 26) was carried out after mixing the
reagents in an acidic aqueous medium at room temperature
and then dripping this solution into an excess of vegetable oil
www.ejlst.com
1700091 (18 of 20) A. Gandini et al. Eur. J. Lipid Sci. Technol. 2018, 120, 1700091

Figure 12. Comparison of solvent resistance of conventional TPS and FM DA crosslinked starch.

in order to generate microdrops, before heating to 65°C to

Figure 13. FM DA crosslinked starch after extrusion and cooling
(left) and a plated prepared by hot pressing and decrosslinking
(right).
induce the FM DA coupling (Scheme 26) and thus generate
hydrogel microdroplets.
The characterization of the microdroplets included
rheological, porosity, swelling, morphological (spherical
particles with diameters of several hundred mm), and
mechanical tests and some of these properties were found
to depend on the F/M reaction stoichiometry, i.e., the degree
of crosslinking, but always with good viscoelastic fea-
tures [18]. Environmental scanning electron microscopy
images of a typical droplet are given in Fig. 14 with a
sequence going from 5% humidity (A) progressively to 100%

Scheme 24. The condensation of furfuryl glycidyl ether with the primary amino groups of gelatin.

Scheme 25. Synthesis of the oligoether bismaleimide.

ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
Scheme 26. Preparation of the furan-grafted chitosan and its FM DA crosslinking reaction with the water soluble bismaleimide.
(B and C9 and then back to 5% (D). The swelling/deswelling
cycle associated with this experiment confirmed the high
viscoelastic aptitude of the droplets and their tendency to
develop pores (arrows in C) for the water outlet and inlet,
which could be exploited as delivery vehicles.
Since the purpose of this study was to apply the hydrogel
microdroplets as drug-release agents, this feature was
simulated by using methylene blue and following its release
by visible spectroscopy, which followed a second-order
behavior for up to 10 h at room temperature.
8 Conclusions
The recent extension of the by-now frequent macromolecu-
lar application of the furan-maleimide Diels–Alder reaction
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Diels–Alder on natural polymers 1700091 (19 of 20)
Figure 14. Images of a microdroplet submitted
to variations in humidity: see text.
to the realm of polymers from renewable resources has
proven successful in providing promising new materials and
this review should be seen as a prelude to further progress.
We acknowledge FAPESP and CNPq for financial support (PVE
401656/2013-6).
The authors have declared no conflict of interest.
References
[1] Gandini, A., The furan/maleimide Diels–Alder reaction: A
versatile click–unclick tool in macromolecular synthesis.
Progr. Polym. Sci. 2013, 38, 1–29.
[2] Gandini, A., Lacerda, T. M., Carvalho, A. J. F., Trovatti, E.,
Progress of polymers from renewable resources: Furans,
www.ejlst.com
1700091 (20 of 20) A. Gandini et al.
vegetable oils, and polysaccharides. Chem. Rev. 2016, 116,
1637–1669.
[3] Gandini, A., Lacerda, T. M., Polymers From Plant Oils,
Smithers Rapra, Shawbury 2015.
[4] Vilela, C., Cruciani, L., Silvestre, A. J. D., Gandini, A.,
A double click strategy applied to the reversible polymeriza-
tion of furan/vegetable oil monomers. Macromol. Rapid
Commun. 2011, 32, 1319–1323.
[5] Vilela, C., Cruciani, L., Silvestre, A. J. D., Gandini, A.,
Reversible polymerization of novel monomers bearing furan
and plant oil moieties. A double click exploitation of
renewable resources. RSC Adv. 2012, 2, 2966–2974.
[6] Vilela, C., Silvestre, A. J. D., Gandini, A., Thermoreversible
nonlinear Diels–Alder polymerization of furan/plant oil
monomers. J. Polym. Sci. Polym. Chem. 2013, 51, 2260–2270.
[7] Gandini, A, Lacerda, T. M., Carvalho, A. J. F.,
A straightforward double coupling of furan moieties onto
epoxidized triglycerides: Synthesis of monomers based on
two renewable resources. Green Chem. 2013, 15, 1514–1519.
[8] Lacerda, T. M., Carvalho, A. J. F., Gandini, A., Two
alternative approaches to the DA polymerization of tung oil.
RSC Adv. 2014, 4, 26829–26837.
[9] Biermann, U., Butte, W., Eren, T., Haase, D., Metzger,
J. O., Regio- and stereo-selective Diels–Alder additions of
maleic anhydride to conjugated triene fatty acid methyl
esters. Eur. J. Org. Chem. 2007, 23, 3859–3862.
[10] Imbernon, L., Norvez, S., From landfilling to vitrimer chemistry
in rubber life cycle. Eur. Polym. J. 2016, 82, 347–376.
ß 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Lipid Sci. Technol. 2018, 120, 1700091
[11] Trovatti, E., Lacerda, T. M., Carvalho, A. J. F., Gandini, A.,
Recycling tires? Reversible crosslinking of poly(butadiene).
Adv. Mater. 2015, 27, 2242–2245.
[12] Trovatti, E., Cunha, A. G, Carvalho, A. J. F., Gandini, A.,
Furan-modified natural rubber: A substrate for its reversible
crosslinking and for clicking it onto nanocellulose. Int. J.
Biol. Macromol. 2017, 95, 762–769.
[13] Gandini, A., Belagacem, M. N., The surface and in-depth
modification of cellulose fibers. Adv. Polym. Sci. 2016, 271,
169–206.
[14] Kramer, R. K., Gandini, A., Carvalho, A. J. F., Belgacem,
M.N., Doctoral research of R. K. Kramer, unpublished
results.
[15] Carvalho, A. J. F., in: Kalia, S., Avérous, L. (Eds.),
Biopolymers: Biomedical and Environmental Applications, 1st
ed., John Wiley & Sons, Hoboken, NJ 2011, pp. 81–98.
[16] Nossa, T. S., Belgacem, N. M., Gandini, A., Carvalho,
A. J. F., Thermoreversible crosslinked thermoplastic starch.
Polym. Intern. 2015, 64, 1366–1372.
[17] Garcıa-Astrain, C., Gandini, A., Pe~
na, C., Algar, I., et al.,
Diels–Alder “click” chemistry for the cross-linking of
furfuryl-gelatin-polyetheramine hydrogels. RSC Adv. 2014,
4, 35578–35587.
[18] Montiel-Herrera, M., Gandini, A., Goycoolea, F. M.,
Jacobsen, N. E., et al., N-(furfural) chitosan hydrogels
based on Diels–Alder cycloadditionsand application as
microspheres for controlled drug release. Carbohydr. Polym.
2015, 128, 220–227.
www.ejlst.com