The organocatalytic ring-opening polymerization of: N -tosyl aziridines by an N-heterocyclic carbene

Article abstract of DOI:10.1039/c6cc04323b

The ring-opening polymerization of N-tosyl aziridines, in the presence of 1,3-bis(isopropyl)-4,5(dimethyl)imidazol-2-ylidene as an organocatalyst and an N-tosyl secondary amine as initiator mimicking the growing chain, provides the first metal-free route

Full text of DOI:10.1039/c6cc04323b

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ARTICLE
Organocatalytic Ring-Opening Polymerization of N-
Tosyl Aziridines by an N-Heterocyclic Carbene
Camille Bakkali-Hassani,a Elisabeth Rieger,b Joan Vignolle,a Frederik R. Wurm,*b Stéphane Carlotti,*a
and Daniel Taton*a
Received 00th January
20xx,
Accepted 00th January
20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/chemcomm
The ring-opening polymerization of N-tosyl aziridines, in 4,5(dimethyl) imidazolꢀ2ꢀylidene (Me5ꢀIpr). While aziridines and
presence of 1,3-bis(isopropyl)-4,5(dimethyl)imidazol-2-ylidene as oxiranes are isoelectronic, the two types of monomers behave very
organocatalyst and a N-tosyl secondary amine as initiator differently in ROP. For instance, the simplest representative of each
mimicking the growing chain, provides the first metal-free route family, i.e. ethylene oxide and aziridine (or azacyclopropane) are
to well defined poly(aziridine)s (PAz) and related PAz-based polymerized by an anionic and a cationic mechanism, respectively.
block copolymers.
While poly(ethylene oxide) can be prepared by anionic means in a
controlled fashion, the cationic ROP of aziridine is accompanied by
chain transfer reactions to the polymer, forming hyperbranched
poly(ethylene imine) (PEI) with a broad dispersity (Ð). Interestingly,
Toste, Bergman et al. have reported in 2005 that 2ꢀnꢀalkylꢀNꢀ
sulfonylaziridines can be subjected to a controlled anionic ROP
through monomer activation by Nꢀtosylation.10 Typically, the ROP
of the Nꢀsulfonylaziridine is performed at 50 °C in DMF, in presence
of 1:1 molar of Nꢀalkylꢀmethanesulfonamide: KHMDS as initiating
system, which affords substituted polyaziridines (PAz) of narrow
molar mass distribution. Corresponding linear 2ꢀnꢀalkyl substituted
PEI derivatives can next be obtained upon deprotection of the Nꢀ
sulfonyl moieties, under mild conditions.10,11 Ensuing reports by
Wurm et al. have resorted to the living anionic ROP pathway to
achieve “inꢀchain” functional PAz incorporating vinyl or acetal
moieties, from purposely designed functional Nꢀsulfonyl aziridines.12
Owing to their near unlimited structural diversity allowing their
steric and electronic properties to be finely tuned, Nꢀheterocyclic
carbenes (NHCs) have revolutionized organometallic chemistry as
ligands for transition metals in the last two decades.1 NHCs have
also gained an increasing popularity as true organic catalysts in
molecular chemistry.1,2 Polymer synthesis has also greatly benefited
from the potential of NHCs, providing a straightforward and metalꢀ
free synthetic strategy to a wide range of polymers.3 Cyclic esters
(e.g. D,Lꢀlactide and lactones) have been by far the most
investigated monomers for the NHCꢀorganocatalyzed ringꢀopening
polymerization (OROP).3,4 The range of monomers amenable to
polymerization by a NHC catalysis has also been expanded, not only
to the ROP of other heterocycles5 (e.g. oxiranes, cyclic carbonates,
carbosiloxanes), but also to the group transfer polymerization of
alkyl (meth)acrylates,6 and to some stepꢀgrowth polymerizations.7
Besides their role as catalysts, a few NHCs can also serve as direct
As mentioned, this Nꢀsulfonylaziridine ROP method employs
nucleophilic initiators, for chainꢀgrowth polymerization reactions, stoichiometric amount of KHMDS rel. to the Nꢀactivated amine.
either through ringꢀopening of heterocyclic monomers,8 such as Consequently, it also introduces metallic residues in the final PAz
lactide, Nꢀcarboxyanhydrides or lactams, or through 1,4ꢀconjugate compounds. Here, the Me5ꢀIpr NHC is used in true catalytic amount
addition of some (meth)acrylics.9
(10% mol. rel. to the amine initiator). We thus provide a facile
OROP synthesis to wellꢀdefined metalꢀfree PAz via a novel NHC
catalytic pathway, as depicted in Scheme 1. We also report first
examples of all PAzꢀbased block copolymer by sequential Me5ꢀIprꢀ
mediated OROP of two different Nꢀsulfonylaziridines.
In this communication we demonstrate the first OROP of Nꢀ
activated aziridines using
a NHC, namely, 1,3ꢀbis(isopropyl)ꢀ
a.Laboratoire de Chimie des Polymères Organiques (LCPO), Université de Bordeaux,
IPB-ENSCBP, 16 av. Pey Berland, 33607 PESSAC cedex, France. E-mails:
carlotti@enscbp.fr; taton@enscbp.fr ; Fax: +33 (0)5 40 00 84 87; Tel: +33 (0)5 40
00 84 86.
b.Max-Planck-Institut für Polymerforschung (MPI-P), Ackermannweg 10, D-55128
Mainz, Germany E-mail: wurm@mpip-mainz.mpg.de (F.R.W.).
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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signals due to aliphatic protons and to the pendant methyl group in
the backbone precluded an accurate determination of molar masses
of these compounds (Fig S7 in ESI).
N
N
Ts
C6H13
R
N
O
N
O
S
C6H13
N
H
10% mol rel. to 3
N
H
O
S
O
n
+
The presence of the Nꢀhexylꢀpꢀtoluenesulfonylamino group
from 3 in αꢀposition could yet be evidenced by MALDIꢀToF MS
analysis of a low molar mass PAz(1) (entry 1, Table1). A single
population, corresponding to a cationized PAz(1), with a peakꢀtoꢀ
peak mass increment of 211.3 g.molꢀ1 corresponding to the molar
mass of one monomer unit derived from 1, was indeed
unambiguously observed, as shown in Fig. 1b) and c).
Ts
R
1/ THF, 50°C
2/ MeOH
PAz(1) R=Me
PAz(2) R=Ph
1. R=Me
2. R=Ph
3
Scheme 1. OROP of Nꢀtosylaziridines induced by Me5-Ipr
Both 2ꢀmethylꢀNꢀpꢀtoluenesulfonyl aziridine (1) and 2ꢀphenylꢀ
Nꢀpꢀtoluenesulfonyl aziridine (2) were investigated as monomer
substrates for the Me5ꢀIprꢀOROP. The polymerization of (1) was first
carried out at 50 °C in THF ꢀinstead of DMF used in previous
work10,12ꢀ in presence of Nꢀhexylꢀpꢀtoluenesulfonylamine (3) as
initiator and Me5ꢀIpr as catalyst (Scheme 1). Under those conditions,
wellꢀdefined PAz(1) with excellent control over molar masses (up to
20,000 g.molꢀ1) and low dispersities (Ð < 1.10) were obtained
(entries 1ꢀ4, Table 1 and Fig. S1). While 100 eq. of 1 could be
quantitatively converted within 24h, 5 days were needed to reach
completion of the OROP of 2, witnessing the effect of steric
hindrance of the 2ꢀsubstituent on the aziridine ring on monomer
reactivity. Yet, PAz(2) exhibiting molar masses increasing with the
initial [2]0/[3]0 molar ratio (entries 5–7, Table 1) were also achieved
in this case. In contrast to PAz(1), however, a small shoulder
progressively appeared in the high molar mass region of SEC traces
of PAz(2) (Fig. S2 in ESI), as the initial [2]0/[3]0 was increased, i.e.
for higher molar masses targeted.
Table 1. Polymerization of 2ꢀalkylꢀNꢀpꢀtoluenesulfonyl aziridines 1 and 2
in THF at 50 °C (see Scheme 1).
Ðc
b
c
ꢀꢀꢀꢀꢀ
ꢁꢂcalcd
ꢀꢀꢀꢀꢀ
ꢁꢂexp
Run
R
[M]/[3]/[Me5-Ipr ]
Time
(h)
Conv
(%)a
(g/mol)
(g/mol)
1
2
3
4
5
6
7
Me
Me
Me
Me
Ph
Ph
Ph
10/1/0.1
20/1/0.1
50/1/0.1
100/1/0.1
20/1/0.1
50/1/0.1
100/1/0.1
24
24
100
100
100
100
97
2100
4200
1880
2500
6000
11700
2600
6250
10800
1.07
1.06
1.06
1.04
1.06
1.12
1.15
24
10600
21100
5300
24
120
120
120
98
13400
99
27000
ꢀꢀꢀꢀ
a Determined by 1H NMR; b Theoretical molar masses: Mncalcd = ([M]/[3]) x MAz
x
c
conv. (MAz
=
molar mass of one monomer unit); Determined by size exclusion
chromatography in THF (PS calibration)
The discrepancy noted between experimental and theoretical
molar masses (Table 1) was attributed to the calibration of SEC with
1
PS standards. Molar masses of PAz(2), as determined by H NMR
spectroscopy (5,200 and 27,000 g.molꢀ1, entries 5 and 7, Table 1,
respectively) indeed closely matched theoretical values. Fig. 1a)
shows a typical 1H NMR of a purified PAz(2) (entry 5), with the
presence, in particular, of the characteristic signals of the hexyl
group from the amine initiator at 0.7ꢀ1.3 ppm. Relative integration of
these signals with those corresponding to the main chain protons (d)
of PAz(2) allowed estimation of PAz(2) molar mass (Table 1). The
agreement between experimental and theoretical molar masses
attested to the complete initiation of polymer chains by the
secondary amine 3. In the case of PAz(1), overlapping of both
Fig. 1.a) 1H NMR spectrum of PAz(2) (entry 5, Table 1). Experimental b)
and computed c) MALDI ToF MS of PAz(1) (entry 1, Table 1)
In combination, characterizations by SEC, NMR and MALDIꢀ
ToF MS are consistent with a controlled OROP of Nꢀtosyl aziridines.
This was also supported by the perfectly linear evolution of
ln([M]0/[M]) vs. time, when monitoring the Me5ꢀIprꢀOROP of 2 by
realꢀtime 1H NMR spectroscopy a (Fig. S9 and S10).
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Based on background literature regarding other examples of NHCꢀ 1.06; Scheme 2) after 1 day, followed by addition of 20 eq. of the
mediated OROP,3ꢀ5 either a nucleophilic or a basic mechanism, i.e. less reactive aziridine (2). Block copolymerization proved effective,
through the aziridine or the amine activation by the Me5ꢀIpr NHC, as illustrated by the SEC trace of the compound collected after 5
respectively (vide infra) could be operative (see Scheme S1 in ESI). days of reaction at 50 °C in THF, showing a clear shift to the higher
The former mechanism would involve ring opening of the aziridine molar masses (Mn = 4,500 g.molꢀ1; Ð = 1.06) compared with the
by direct attack by Me5ꢀIpr, forming an imidazolium amide SEC trace of the PAz(1) macroinitiator (Fig. 3a), Scheme 2), thus
zwitterionic intermediate that would be further displaced by the attesting to an effective crossover reaction. Interestingly, the PAz(1)ꢀ
secondary amine (3). However, given the high basicity of Me5ꢀIpr bꢀPAz(2) block copolymer (9b) could also be obtained by reversing
(pKa = 24 in DMSO13), in particular compared to that of the the order of addition of the two monomers (2 then 1; see Scheme 2).
sulfonylamine group (pKa ≈16 in DMSO14), a basic mechansim A shoulder in the high molar mass region was observed though,
where the amine initiator/chain end would be deprotonated by Me5ꢀ presumably to some coupling reactions at high monomer
Ipr cannot be ruled out. Data are lacking at this stage to state on the conversions, as shown in Fig. 3b).
correct mechanism, and both experimental and theoretical
investigations on these NHCꢀmediated OROP’s of
sulfonylaziridines are in progress.
Nꢀ
In order to verify that a majority of Me5ꢀIprꢀOROPꢀderived PAz
chains could be reactivated, chain extension experiments were
performed as follows (see also Fig. S3). Polymerization in THF
at 50 °C of 20 eq. of
PAz(1) precursor (Mn = 2,500 g.molꢀ1; Ð = 1.06). Addition of 30 eq.
of
increased the molar mass to Mn = 6,000 g.molꢀ1 while
1
, using 10%mol. of Me5ꢀIpr, afforded a
1
maintaining a low dispersity (Ð = 1.06) after 24h of reaction at 50
°C (Fig. S3), confirming quantitative reinitiation of the OROP
from the PAz(
investigate the synthesis of PAzꢀbased block copolymers, via
sequential NHCꢀOROP of and . As displayed in Scheme 2,
both monomers were added either in this order ( then ) or in
the other ( then ).
1) precursor. These results prompted us to further
a
1
2
1
2
2
1
N
C6H13
H
N
N
+
Ts
Fig. 2. SEC traces (refractometric detection) of a) PAz(
1)ꢀbꢀPAz(2) and
0.1eq
1eq
b) PAz( )ꢀ ꢀPAz( ) block copolymers (see Scheme 2.).
2
b
1
1 (20eq)
THF, 50°C, 24h
2 (20eq)
THF, 50°C,5 days
In summary, we describe for the first time the “controlled/living”
organocatalyzed ringꢀopening polymerization (OROP) of Nꢀ
activated aziridines by a Nꢀheterocyclic carbene (NHC), namely,
1,3ꢀbis(isopropyl)ꢀ4,5(dimethyl)imidazolꢀ2ꢀylidene. Reactions can
be conducted in THF at 50 °C in presence of a Nꢀactivated
secondary amine as initiator to mimic the growing chains. This
provides a straightforward access to structurally wellꢀdefined and
metalꢀfree polyaziridines (PAz) that can serve as precursors of linear
2ꢀnꢀalkylꢀsubstituted poly(ethylene imine)s after removal of the Nꢀ
tosyl groups. This method can also be applied to achieve wellꢀ
defined all PAzꢀbased block copolymers by sequential OROP
utilizing a carbene catalysis. Overall, this work further expands the
monomer substrate diversity in NHCꢀmediated polymerization
reactions.
Ts
Ts
C6H13
N
C6H13
N
N
H
n
N
H
n
Ts Ph
Ts Me
8a. Mn=2500 g.mol-1
Ð= 1.07
9a. Mn=2400 g.mol-1
Ð= 1.08
2
1
(50eq)
(20eq)
THF, 50°C, 5 days
THF, 50°C, 24h
Ts Ph
Ts Me
C6H13
N
H
C6H13
N
H
N
N
N
N
m
m
n
n
Ts Me
Ts
Ts Ph
9b. Mn=9000 g.mol-1
Ts
8b. Mn=4500 g.mol-1
Ð= 1.06
Ð= 1.12
Scheme 2. Synthesis of PAz(1)ꢀbꢀPAz(2) and PAz(2)ꢀbꢀPAz(1) block
copolymers by sequential OROP catalyzed by Me5ꢀIpr
Acknowledgments
The authors are grateful to the French Ministry of Education and Research
for financial support of CBH and to the European Commission through
project SUSPOLꢀEJD 642671.
Synthesis of a wellꢀdefined PAz(1)ꢀbꢀPAz(2) block copolymer
(8b) was first achieved, i.e. using the more reactive aziridine (1) first
(20 eq.), giving a PAz(1) precursor (8a, Mn = 2,500 g.molꢀ1; Ð =
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