Synthesis of sequence-ordered polymers via sequential addition of monomers in one pot

Article abstract of DOI:10.1039/c3cc42483a

Sequence-ordered polymers can be simply prepared in one pot via sequential monomer addition.

Full text of DOI:10.1039/c3cc42483a

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Synthesis of sequence-ordered polymers via sequential
addition of monomers in one pot†
Jun-Jie Yan,a Di Wang,a De-Cheng Wub and Ye-Zi You*a
Cite this: Chem. Commun., 2013,
49, 6057
Received 6th April 2013,
Accepted 16th May 2013
DOI: 10.1039/c3cc42483a
www.rsc.org/chemcomm
Sequence-ordered polymers can be simply prepared in one pot via built-in sequences.15 Very recently, Zamfir and Lutz used
sequential monomer addition.
kinetically controlled sequential addition of donor and acceptor
monomer feeds to accomplish precise insertion.7 Although these
Nature is an expert at easily controlling properties of bio- methods are very useful for preparing sequence-ordered copolymers,
polymers (DNA, proteins), including tacticity and the monomer they rely on the development of polymerization techniques, catalysts,
sequence, and producing biopolymers with unrivaled properties different comonomer reactivities, and the use of templates. And
and functionalities, which cannot be matched with synthetic most of them involve multi-pot processes. Here, we report a
polymers.1–4 Disorder of units in a biopolymer can result in sequential monomer addition method for preparing sequence-
physical function imbalance, denaturation of the organism’s ordered polymers via quantitative and highly selective reactions
proteins, and even fatal diseases.5 Compared with DNA replica- in a one-pot process.
tion and protein synthesis, the methods for producing synthetic
The Michael addition reaction of an acrylate with an amine
polymers are still primitive. It is very difficult to control the has few side reactions and requires mild reaction conditions.16
monomer sequence in chain-growth or step-growth processes The reaction has been used to synthesize high-molecular-weight
when a polymer is made from more than one different type of poly(amino ester)s in high yields.17 In contrast, methacrylates do not
monomers6–8 although polymer chemists can now design and react with amines without a catalyst, but they react quantitatively
build intriguing compounds such as dendrimers, star-shaped with thiols, even without a catalyst.18 The reaction of a methacrylate
polymers, macromolecular bottle-brushes and macrocycles. with a thiol is therefore highly selective. Using this highly selective
Sequence regulation of synthetic polymers is therefore one of reaction, we prepared ABC-sequenced copolymers simply by sequen-
the goals of polymer chemists,4 and some new methods have tially adding ABC monomers to a polymerization system, as shown
recently been developed for constructing sequence-controlled in Scheme 1. In the experiments, 2-aminoethanethiol (B unit)
copolymers. For example, Liu et al. reported a potential method was first added to a solution of allyl methacrylate (A unit) in
for successfully preparing sequence-defined polymers using methanol at a molar equivalent feed ratio. A thiol quantitatively
DNA-templated polymerization.9 Thomas et al. reported an reacts with methacrylate at room temperature (as shown in
important strategy for controlling monomer sequences using Scheme 1), but it does not react with an alkene without a
ring-opening polymerization of b-lactones.10,11 Sawamoto et al. catalyst, the amino group in 2-aminoethanethiol does not react
described a method for preparing sequence regulated copolymers with methacrylate without a catalyst either. NMR spectroscopy
using tandem catalysis of living-free radical polymerization.12,13 verified that all the methacrylate reacted with thiol via Michael
Kamigaito et al. prepared sequenced copolymers using sequence addition in 1 h at room temperature, because the signals at
living-free radical chain copolymerization of naturally occurring 5.65 (vinyl protons) and 1.92 ppm (methyl protons) shifted
limonene with maleimide.14 Li et al. synthesized periodic vinyl completely to 2.6 and 1.15 ppm, respectively (see Fig. S5, ESI†).
copolymers using acyclic diene metathesis polymerization with The 13C NMR results showed that there was no byproduct from
methacrylate reacting with an amine unit or a thiol reacting
a CAS Key Lab of Soft Matter Chemistry, Department of Polymer Science and
Engineering, University of Science and Technology of China, Hefei, 230026, Anhui,
P. R. China. E-mail: yzyou@ustc.edu.cn; Fax: +86 551 3601592
b Beijing National Laboratory for Molecular Sciences, State Key Laboratory of
Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China
with an alkene unit (Fig. S5, ESI†). Adding 2-aminoethanethiol
to a solution of allyl methacrylate therefore quantitatively yields
an AB sequence containing amine and alkene units (as shown
in Scheme 1). Primary amines are good ring-opening reagents for
aminolysis of thiolactones.19,20 Consequently, when N-acetyl-
homocysteine thiolactone (1 equiv., C unit) was added to the above
reaction mixture, the amine in the AB sequence can ring-open
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3cc42483a
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Scheme 1 (a) Schematic outline of one-pot synthesis of an ABC-sequenced
copolymer via sequential addition of A, B, and C monomers and (b) detailed
reactions for preparing an ABC-sequenced copolymer.
Scheme 2 (a) Schematic outline of one-pot synthesis of a CBABCD-sequenced
copolymer via sequential addition of A, B, C, and D monomers and (b) detailed
reactions for preparing a CBABCD-sequenced copolymer.
the thiolactone, generating an ABC-sequence containing thiol
and alkene units from the AB sequence. We monitored the ring-
opening reaction using NMR spectroscopy, and the results
showed that it took 3 h to complete the ring-opening of thiolactone
at room temperature. After complete ring-opening of the thiol- the quantitative reaction of 2-dimethacrylate with 2-amino-
actone, the signal (methene protons) at 2.1 ppm shifted completely ethanethiol, as the vinyl carbon signals (1 and 2) at 126 and
to 1.85 ppm (see Fig. S6, ESI†). Amine ring-opening of the 137 ppm completely shifted to 40 and 34 ppm, respectively
thiolactone was further verified by transformation of the lactone (as shown in Fig. S9, ESI†). N-acetylhomocysteine thiolactone
unit (10, chemical shift at 207 ppm) to amide (100, chemical shift at (C unit) was added to the mixture, and the amines in the BAB
173 ppm) as shown by the 13C NMR spectrum (see Fig. S6, ESI†) sequence can quantitatively ring-open thiolactones, giving the
after complete ring-opening of the thiolactone. A thiol–ene click CBABC sequence with a thiol at each end (as shown in Scheme 2).
reaction (as shown in Scheme 1 and Fig. S7, ESI†) then occurred This was verified by NMR, because the signal at 2.1 ppm (methene
when the mixture was subjected to UV irradiation, and a polymer protons of thiolactone) shifted completely to 1.85 ppm (see
with the ABC sequence, a Mn of 5160 and a PDI of 1.57 was Fig. S10, ESI†), and the lactone unit (8, 207 ppm) was completely
obtained after UV irradiation for 30 min. The NMR results show transformed to an amide (80, 173 ppm) (see Fig. S10, ESI†), after
that only trace (o1%) signals of a double bond, between 5.5 and complete ring-opening. Finally, 2,3-dibromomaleimide (D unit)
6.5 ppm, were detected (see Fig. S7, ESI†). The ABC sequenced was added to the reaction mixture. The reaction solution imme-
copolymer can therefore be simply prepared via ABC sequential diately changed from colorless to bright yellow. The coupling of
monomer additions in a one-pot process.
2,3-dibromomaleimide with the thiol was almost complete in only
Recently, Baker and Haddleton et al. reported that bromo- 5 min, and the viscosity of the polymerization mixture increased
maleimides can react rapidly (o10 min) and selectively with noticeably. 2,3-Dibromomaleimide underwent rapid and highly
thiols to form thiomaleimides. The reaction between the thiol efficient conjugation with a thiol via a thiol substitution reaction,
and the maleimide proceeded via a thiol substitution reaction, yielding a CBABCD-sequenced copolymer with a Mn of 8460 and a
and was highly efficient and quantitative.21–25 Polymers can be PDI of 1.17 only in a one-pot process.
easily linked with proteins via this reaction. We used this
Bromomaleimide can not only react with a thiol via a thiol
quantitative thiol substitution reaction in the preparation of substitution reaction, but can also react with a thiol or an amine
sequence-ordered copolymers. Using sequential Michael addition, via nucleophilic addition. Compared with the thiol substitution
amine ring-opening of thiolactone, and thiol substitution reac- reaction, the nucleophilic addition reaction of thiomaleimide
tions (as shown in Scheme 2), a CBABCD-sequenced copolymer with a thiol or an amine is very slow, so it can only occur after
was easily obtained in one pot via ABCD sequential monomer complete substitution of the bromide in bromomaleimides.21–25
addition as follows. First, 2-aminoethanethiol (B unit) was Inspired by this, we prepared a DCBABCDE-sequenced copolymer
added to a solution of ethylene dimethacrylate (A unit), yielding via ABCDE sequential monomer addition as follows. A BAB
a BAB sequence with an amine at each end via Michael addition sequence with an amine at each end was formed via quantitative
of the thiol and the methacrylate (amine did not react with the Michael addition of a thiol with a methacrylate (the amine did not
methacrylate because no catalyst was added). After 1 h, signals react with the methacrylate in the absence of a catalyst) when
at 5.5–6.1 ppm, assigned to vinyl protons, shifted to 2.6 ppm, 2-aminoethanethiol (B unit) was added to a solution of ethylene
and the signal at 1.85 ppm, assigned to methyl protons (next to dimethacrylate (A unit) (as shown Scheme 3). The signals
the vinyl unit), shifted to 1.2 ppm in the 1H NMR spectrum at 5.5–6.1 ppm, assigned to vinyl protons, shifted to 2.6 ppm,
(as shown in Fig. S9, ESI†). The 13C NMR results also verified and the signal at 1.85 ppm, assigned to methyl protons
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6058 Chem. Commun., 2013, 49, 6057--6059
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one-pot reactions. Via this method, ABC-, CBABCD-, and
DCBABCDE-sequenced copolymers were easily obtained by
sequentially adding ABC monomers, ABCD monomers, and
ABCDE monomers.
Financial support from National Natural Science Foundation
of China (51033005, 20974103, 21074121 and 21090354) and
the Program for New Century Excellent Talents in Universities
(NCET-11-0882) is gratefully acknowledged.
Notes and references
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Chem. Commun., 2013, 49, 6057--6059 6059