Olefin metathesis in air using latent ruthenium catalysts: Imidazole substituted amphiphilic hydrogenated ROMP polymers providing nano-sized reaction spaces in water

Article abstract of DOI:10.1039/c8cy01818a

Imidazole substituted hydrogenated amphiphilic ROMP polymers were used as both surfactants and ligand precursors for olefin metathesis reactions in water. Amphiphilic ROMP polymers were synthesized using a two-step procedure. Firstly, dimethyl-5-norbornene-2,3-dicarboxylate was polymerized using ring-opening metathesis polymerization (ROMP)/cross-metathesis (CM) in the presence of allyl-PEG5000 methyl ether and a Grubbs 3rd generation (G3) catalyst. Secondly, a one-pot hydrogenation/aminolysis protocol was used for the post-polymerization modification of PEG end-capped polynorbornene derivatives. Hydrogenation reactions were carried out using residual G3 in the presence of formic acid/sodium formate in THF at 70 °C. The aminolysis reaction was carried out without isolation of the hydrogenated polymer, using triazabicyclodecene (TBD) and 1-(3-aminopropyl)-imidazole, forming imidazole substituted hydrogenated amphiphilic ROMP polymers (mod-Amph1) in an efficient manner. G1-mod-Amph1 formed micelle structures in water with an average particle size of 85.95 (±35) nm as determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. The diffusion of Grubbs 1st generation (G1) catalyst into the micelle structure has led to the formation of nano-sized catalysts which exhibited a latent characteristic. The diffusion of hydrophobic olefinic substrates into the nano-reaction spaces, followed by activation of the catalyst with HCl led to a very efficient catalytic system for ring-closing metathesis reactions. RCM reactions of various hydrophobic dienes can run in non-degassed water under an air atmosphere. The catalyst system exhibits similar performance under an air atmosphere even in tap water, reaching a conversion value of 90% for RCM of diethyl diallylmalonate with a catalytic loading of 1% Ru.

Full text of DOI:10.1039/c8cy01818a

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Qingzhu Zhang et al.
Catalytic mechanism of C–F bond cleavage: insights from QM/MM
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Olefin Metathesis in Air Using Latent Ruthenium Catalysts:
Imidazole Substituted Amphiphilic Hydrogenated ROMP Polymers
Providing Nano-Sized Reaction Spaces in Water
Received 00th January 20xx,
Accepted 00th January 20xx
a,
†
a
a
DOI: 10.1039/x0xx00000x
Bengi Özgün ÖZTÜRK , Burcu DURMUŞ and Solmaz KARABULT ŞEHİTOĞLU
www.rsc.org/
Imidazole substituted hydrogenated amphiphilic ROMP polymers were used as both surfactant and ligand precursor for
olefin metathesis reactions in water. Amphiphilic ROMP polymers were synthesized using a two-step procedure. Firstly,
dimethyl-5-norbornene-2,3-dicarboxylate was polymerized using ring-opening metathesis polymerization(ROMP)/cross-
rd
metathesis (CM) in the presence of allyl-PEG5000 methyl ether and Grubbs 3 generation (G3) catalyst. SEcondly, one-pot
hydrogenation/aminolysis protocol was used for the post-polymerization modification of PEG end-capped polynorbornene
derivatives. Hydrogenation reactions were carried out using residual G3 in the presence of formic acid/sodium formate in
THF at 70 °C. The aminolysis reaction was carried out without isolation of the hydrogenated polymer, using
triazobicyclodecene (TBD) and 1-(3-aminopropyl)-imidazole, forming imidazole substituted hydrogenated amphiphilic
ROMP polymers (mod-Amph1) in an efficient manner. G1-Mod-Amph1 formed micelle structures in water with an average
particle size of 85.95 (±35) nm as determined by transmission electron microscopy (TEM) and dynamic light scattering
st
(
DLS) analysis. The diffusion of Grubbs 1 generation (G1) catalyst into the micelle structure has led to the formation of
nano-sized catalysts which exhibited a latent characteristic. The diffusion of hydrophobic olefinic substrates into the nano-
reaction spaces, followed by activation of the catalyst with HCl led to a very efficient catalytic system for ring-closing
metathesis reactions. RCM reactions of various hydrophobic dienes can run in non-degassed water under air atmosphere.
The catalyst system exhibits similar performance under air atmosphere even in tap water, reaching a conversion value of
9
0
%
for
RCM
of
diethyl
diallyl
malonate
with
a
catalytic
loading
of
1
%
Ru.
tested in ring closing metathesis reactions of dienes using non-
degassed solvents and turn-over numbers (TON) up to 7000
5
was observed. In the continuous search for more sustainable
Introduction
and environmentally friendly catalyst systems, the design and
synthesis of water compatible ruthenium metathesis catalysts
Olefin metathesis is an efficient method for the formation of
new carbon-carbon bonds to build complex molecular
6
are of great importance . In 2007, Raines et al. reported the
1
structures. Transition metal complexes are used as catalysts
2
for olefin metathesis reactions. Although Mo and W based
olefin metathesis activity of conventional Grubbs type
complexes (G1, G2, HG1 and HG2) in binary organic/water
mixtures. HG2 catalyst performed better among the tested
catalysts in dimethoxyethane/water and acetone/water
catalysts are highly active in metathesis of various olefins, the
main drawbacks of these complexes are their high sensitivity
3
towards air and moisture. The invention of air and moisture
mixtures. The integration of ribonuclease
A to above
stable Grubbs type ruthenium metathesis catalysts has opened
a new era in olefin metathesis chemistry. When compared to
Schrock type Mo, W complexes, Grubbs type catalysts are
tolerant to variety of functional groups and tolerates air and
mentioned catalytic systems improves the conversion of RCM
of N-tosyldiallyamine in aqueous media, thus eliminating the
7
need for water-soluble ruthenium metathesis catalyst. Grela
4
et al. used commercially available catalysts; G1 and G2
catalysts, in olefin metathesis reactions including RCM, cross-
metathesis (CM) and enyne metathesis (EM), in aqueous
media under sonification conditions in the absence of any
surfactants
moisture to an extent. Recently, the air compatibility of
commercially available ruthenium metathesis catalysts; such
nd
nd
as Grubbs 2 generation (G2), Hoveyda-Grubbs 2 generation
HG2) and ruthenium indenylidene derivatives (Figure 1) were
(
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Figure 1. Ruthenium based olefin metathesis catalysts
Figure 2. Water compatible ruthenium metathesis catalysts
.
Although promising results were observed in these catalytic
systems, high catalytic loadings and harsh reaction conditions
8
are the main drawbacks of the reported system. The active 14
electron species must be protected from water in order to
obtain high turnover numbers and high yields in olefin
metathesis transformations of challenging olefinic substrates.
Ionic group tagged phosphine ligands are used to design water
9
soluble analogs of the G1 catalyst. Later on, Schanze et al.
prepared benzylidene functionalized Grubbs type catalyst for Figure 3. Amphiphilic polymer supported ruthenium catalysts
1
ROMP reactions in aqueous media. Although both of the
0
catalyst (Figure 2, Ru-1 and Ru-2) was found to be compatible Nanoreactor systems that are based on amphiphilic polymeric
with water-soluble ROMP monomers, the catalyst exhibited materials offer a greener, sustainable and environmentally
poor performance in RCM reactions of various dienes in pure friendly approach for the selective synthesis of organic
nd
17-19
aqueous media. Grubbs 2 generation analogs bearing materials.
Amphiphilic
polymers
bearing
1,3,5-
quaternary ammonium group substituted phosphine ligands tricarboxamide side chains as the self-assembly agent provide
were used in RCM reactions under biphasic solvent condition; nano-reaction spaces in water for ruthenium catalyzed
1
O. In addition to ionic transfer hydrogenation reactions.
1
20-21
CH
2
Cl
2
/H
2
O and CH
2
Cl
2
/aqueous H
2
In addition to
tagged ligands, polyethyleneglycol substituted pyridine ligands amphiphilic synthetic polymers, proteins and enzyme-like
rd
were used to mimic Grubbs 3 generation catalysts to conduct molecules are used to provide nano-reaction spaces for olefin
2
2-23
olefin metathesis reactions in aqueous media (Figure 2, Ru-3 metathesis transformation reactions.
and Ru-4). This catalyst was used in ROMP of water-soluble Latent ruthenium catalysts are of great importance owing to
1
2
24
norbornene derivatives.
carbene ligands were used to develop water compatible The stimuli responses such as heat, UV irradiation, acid
PEG-substituted N-heterocyclic their unique control ability over olefin metathesis reactions.
nd
analogs of Grubbs 2 generation and Hoveyda-Grubbs 2
nd
addition
can
be used
to
tune
the
generation catalyst. and found to catalyze RCM reactions of initiation/propagation rate and in some cases, M values for
reaction
1
3
n
2
5
water-soluble dienes in excellent yields (Figure 2, Ru-5). The ROMP polymers can be controlled. The diffusion of catalyst
performance of water-soluble ruthenium catalysts is found to or reactants into the micelle center is important in emulsion
be poor in olefin metathesis reactions of hydrophobic based reactions. In traditional approaches using commercial
substrates. For this challenge, amphiphilic polymers that act Grubbs type catalysts such as G1, G2 or HG1-2, dissolving the
both as surfactant and ligand precursors were developed to catalyst in the olefinic substrate before dispersing into the
carry out olefin metathesis transformation of hydrophobic emulsion is not possible due to the fast initiation of the
1
4
substrates in aqueous media.
catalyst; the reaction starts as the catalyst dissolves in the
Different amphiphilic block polymers bearing non-ionic substrate. Therefore, latent ruthenium catalysts offer a great
PEG) and cationic groups as hydrophilic parts were used in the solution for the current challenge in aqueous emulsion
(
2
6-27
design of the support materials to achieve water solubility and reactions.
hydrophobic parts are used to ensure the micelle formation in amphiphilic polymer supports will ease the dispersion of
Integration of latent catalyst systems with
1
5
water (Figure 3, Ru-6). Amphiphilic polymer supported reactant in micelle structures. The high control over reaction
ruthenium catalysts, Ru-6, Ru-7 performed very well with will ease the formation of uniform nano-sized micelles bearing
hydrophobic dienes in RCM reaction in water, reaching a max both catalyst and reactant in the hydrophobic center without
conversion value of 91 % for RCM of diethyl diallylmalonate any reaction. In this study, a latent ruthenium-based nano-
even run in non-degassed water under air atmosphere and can reactor system was designed and used in olefin metathesis
easily recycle by extraction with organic solvents. Carboxylic reactions under air in aqueous media. To the best of our
acid functionalized poly(2-oxazoline) block copolymers bearing knowledge, no study has been reported up to date regarding
chelating isopropoxy styrene ligands were used to support the integration of latent ruthenium catalysts in nano-reactor
nd
16
Grubbs 2 generation catalyst (Figure 3, Ru-7).
systems.
Experimental
Otherwise noted all chemicals are purchased from Sigma-
Aldrich and used as received.CH Cl was dried over P O and
2
2
2 5
distilled under a nitrogen atmosphere. Toluene was dried over
Na wire/benzophenone and distilled under nitrogen
a
atmosphere. Number average molar masses (M ) were
n
determined by a size exclusion chromatography (SEC) system
2
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LC-20A from Shimadzu equipped with a SIL-20A auto-sampler, remained in the reactor was dissolved in dry THF ( 10 ml) and
RID-10A and a refractive index detector. The analysis was sodium formate(0.143 mmol, 0.0096 g) and formic acid (0.06
performed on the following column system operating on THF mol, 2.76 g) was added to the reactor and stirred at 70 °C for 8
(
flow rate 1 mL/min) at 40°C: main-column PSS SDV analytical h. After that aminolysis reaction was initiated by adding 1-(3-
5 μm, 300 mm × 8.0 mm, 10,000 Å) and a PSS SDV analytical aminopropyl)imidazole (0.021 mol, 2.63 g) and 1,5,7-
(
pre-column (5 μm, 50 mm × 8.0 mm). The calibration was triazabicyclodecene (1.43 mmol, 0.20 g) to the reactor. The
created using narrow linear poly(methylmethacrylate) reaction mixture was stirred for 24 h at 70 °C. The resulting
standards (Polymer Standards Service PPS, Germany) ranging polymer was isolated by pouring the reaction mixture to cold
1
13
from 1100 to 981,000 Da. H and C NMR spectra were diethyl ether. Yellowish sticky solid was washed with toluene
recorded at 25 °C with a Bruker GmbH 400-MHz high and diethyl ether several times.
3
performance digital FT-NMR spectrometer using CDCl as the Representative ring closing metathesis reaction procedure
solvent. Dynamic light scattering (DLS) analysis was carried out
using a Malvern Seta-Sizer. GC–MS analyses were performed
with a Shimadzu GC–MS 2010Plus using a Restek Rxi-5Sil
column (30m × 0.25 mm x0.25 μm) and temperature range of
A 50 ml beaker was equipped with a magnetic stirring bar. 10
ml of 10 mg/ml solution of Mod-Amph1 (4.45 mmol
imidazole/g polymer) in water was added to the beaker and
stirred at 1000 rpm for 5 minutes. Following the dissolution of
50–320 °C with a helium flow rate of 1 ml/min. MALDI ToF
2 2
mod-Amph1, G1 (0.01 g, 0.012 mmol) in 100 µL CH Cl was
mass spectra were recorded by a Voyager-DE Pro MALDI-TOF
mass spectrometer (Applied Biosystems, USA). Sample
desorption and ionization were carried out using the 337 nm
output from a pulsed nitrogen laser (Spectra-Physics, USA) at
added and stirred for 5 minutes. Diethyldiallyl malonate (1.2
mmol, 290 µL) was added and stirred for 5 minutes to ensure
the formation of homogenous emulsion. The acid solution was
−7
added in one portion (500 µL) to initiate the reaction.
ca. 2.0×10 torr vacuum and an acceleration voltage of 25 kV.
Trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-
propenylidene]malononitrile (DCTB) was used as the matrix (
Results and discussion
20 mg/mL in THF). Silver (I) trifluoroacetate (AgTFA) was used
as ionization agent (10 mg/mL in THF). The polymer sample Amphiphilic polymers are of great importance owing to their
was dissolved in THF (10 mg/mL) and three solutions were unique ability to form nano-sized micelle structures in water,
mixed in a ratio of 10/1/1 (matrix: sample: ionization agent). thus providing hydrophobic reaction centers for catalytic
2
8
Emulsions were characterized by means of DLS using a reactions to take place. In these catalytic systems amphiphilic
Malvern Zeta sizer Nano-ZS90 with a fixed scattering angle of polymer act as both surfactant and ligand precursor. In this
9
0°. ICP-MS analysis was performed on a Perkin Elmer DRC II study, we used the advantages of ROMP/CM reactions to build
model ICP-MS. High contrast TEM images were recorded using amphiphilic ROMP polymers using allyl PEG as the chain
a FEI Tecnai G2 Spirit Bio(TWIN) TEM at 120 kV using carbon transfer agent (or cross-metathesis partner) and dimethyl-5-
filmed coated copper grids.
norbornene-2,3-dicarboxylate as the ROMP monomer,
followed by post-polymerization modification by aminolysis
reactions using 1-(3-aminopropyl)imidazole. Imidazole
functionalized amphiphilic ROMP polymers are used as ligand
pre-cursors for nano-reactor systems. Amphiphilic ROMP
polymer; Amph1, was synthesized using ROMP/CM reactions
in the presence of allyl polyethylene glycol methyl ether (Allyl-
Synthesis of amphiphilic ROMP polymers (Amph1)
A Schlenk reactor was charged with dimethyl-5-norbornene-
2,3-dicarboxylate (1.0 g, 4.76 mmol) and 5 ml of dry
CH Cl /toluene (v/v: 1/1) mixture was added to the reactor.
2
2
rd
Grubbs 3 generation catalyst (0.0476 mmol, 0.042 g) was
added under nitrogen atmosphere and stirred at room
temperature for 30 minutes. Allyl poly(ethylene glycol) methyl
n
PEG5000, M : 5000 Da) as the chain-transfer agent (CTA) and
rd
Grubbs 3 generation catalyst as the initiator (Figure 4). For
this purpose, dimethyl-5-norbornene-2,3-dicarboxylate (M1)
n
ether (M : 5000 Da, 0.238 mmol, 1.19 g) was added in one
was polymerized with a M1/CTA/G3 (mol/mol/mol) ratio of
1
/toluene (v/v: 1/1). H NMR
portion and reaction mixture was stirred at 40 °C for 12 h.
Polymer mixture was isolated by pouring the reaction mixture
to cold diethyl ether. White solid was washed several times
with toluene and methanol, filtrated and dried under high
vacuum. The white polymer was characterized by means of
1
00/5/1 at 40 °C in CH
2
Cl
2
1
spectrum of Amph1 is given in Figure 5. (For H NMR spectrum
of allyl PEG methyl ether please see supporting information, SI,
Figure S1). Olefinic –CH=CH- group signal was observed at 5.55
1
ppm. –O-CH - group signal of PEG overlapped with methoxy
2
SEC, FTIR, MALDI-ToF MS and H NMR analysis. The polymer
ester group signal of norbornene moiety (-OCH
Small peaks appearing at 3.81, 3.49 and 3.38 ppm was related
with the PEG-norbornene bridging groups –OCH CH O-CH-
denoted as H , H and H in Figure 1)
3
) at 3.65 ppm.
was denoted as Amph1.
Post-polymerization modification of Amph1 via transfer
hydrogenation/aminolysis reactions
2
2
(
4
5
6
For the one pot post-polymerization process, ROMP/CM
procedure was repeated but this time polymer was not
isolated since residual ruthenium catalyst will be used in
transfer hydrogenation step. Instead of isolation, all volatiles
were removed by high vacuum. Sticky white solid that was
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Figure 4. ROMP/CM reactions using a ratio of M1/CTA/G3; 100/5/1
Figure 6. MALDI-ToF MS spectrum of Amph1 polymer (For full spectrum see SI,
Figure S3-S4)
The intense peaks of Amph1 (for example 7925.84 Da) have
two small neighboring peaks (7969.90 Da and 7891.80 Da)
differing from each other by PEG repeating units (44 Da). On
the other hand, the other peak series appearing at the
spectrum with relatively lower intensity confirms the presence
of unfunctionalized polyNBE.At this stage, the removal of non-
functionalized
–poly(dimethyl-5-norbornene-2,3-
dicarboxylate) is not possible due to the limited solubility of
Amph1 in water. The separation process was carried out after
the post-polymerization modification of Amph1. ROMP/CM
reactions were repeated using NBE/PEG ratios of 150/2 and
1
00/2 and results are given in Table 1. These results showed
that allyl PEG methyl ether act as chain transfer agent in
ROMP/CM reactions thus reducing the molar mass of the
polymer as PEG/NBE ratio increases. Considering the NBE/PEG
ratio, 100/5 NBE/PEG ratio was chosen as the optimal ratio for
ROMP/CM synthesis reactions.
1
Figure 5. H NMR spectrum of Amph1 in CDCl
3
.
Cyclopentane ring signals were observed at 3.08, 2.86 and
.90 ppm. The ratio of norbornene(n) to PEG (m) moiety was
1
On the next trial, post-polymerization modifications were
carried out using aminolysis reactions. Recently, our research
group reported the post-polymerization modification of
calculated using the following formula:
ꢀ
ꢄꢅꢀꢆꢇꢈꢉꢊꢆꢋꢌꢀꢄ5.50ꢍ ꢎ 2ꢍ
ꢄꢅꢀꢆꢇꢈꢉꢊꢆꢋꢌꢀꢄ3.60ꢍ ꢏ ꢅꢀꢆꢇꢈꢉꢊꢆꢋꢌꢀꢄ5.50ꢍꢐ3
4
30
ꢂ ꢃ
ꢑ
polynorbornene derivatives by aminolysis reactions. It has
ꢁ
been reported that ruthenium metathesis catalysts can also
perform transfer hydrogenation reactions of both ketones,
3
1
NBE/PEG ratio (n/m) was found to be 0.193 using the
corresponding formula for the ROMP polymer obtained from
alkenes and alkynes in an efficient manner. More recently,
Grela and his research group have reported a tandem olefin
metathesis/transfer hydrogenation reaction protocol utilizing
formic acid as the hydrogen source using Grubbs type
1
00/5/1; M1/CTA/ G3 ratio. FTIR analysis of Amph1 confirmed
the presence of norbornene moiety (Supporting information
-1
3
2
(
SI), Figure S2). The peak appearing at 1728 cm showed the
presence of ester group (-COOCH ). –CH stretching peaks were
observed at 2874.88 and 2952.8 cm for PEG (–OCH
for NBE (-CH) moieties. The olefinic –CH=CH- peaks were
catalysts. A slightly modified literature procedure was used
to combine transfer hydrogenation/aminolysis reactions in a
one-step synthesis protocol (Figure 7).
3
-1
2
2
CH -) and
-1 29
observed at 980.70 (trans) and 747.84 (cis) cm . In addition
1
to H NMR analysis, Amph1 was also characterized by means
Table 1. ROMP/CM reactions using different NBE/PEG ratio
s
of MALDI-ToF MS analysis (Figure 6). The mass spectrum of
Amph1 showed the presence of two different polymers; non-
functionalized poly(dimethyl-5-norbornene-2,3-dicarboxylate)
and mono functionalized Amph1. The repeating units for
Amph1 were found to be 210 Da and 44 Da indicating the
presence of both norbornene and PEG moiety.
a: Determined by SEC against linear poly(methylmethacrylate) standards in THF
Figure 7. One pot transfer hydrogenation/aminolysis reactions
4
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In order to obtain a hydrogenated ROMP polymer, we
envisioned to use residual ruthenium that was remained
within ROMP/CM polymer. For this purpose, ROMP/CM
reaction was carried out in a Schlenk reactor using pre-
determined reaction conditions and the reaction volatiles were
removed by vacuum. THF was added to the Schlenk reactor to
dissolve the polymer and then formic acid/sodium formate
was added to the reaction media in order to initiate the
transfer hydrogenation reactions. After 8 h of reaction time at
70 °C, % 30 TBD and 1-(3-aminopropyl)imidazole were added
to the reaction media to initiate aminolysis reaction. After 24
h, the reaction mixture was cooled to room temperature,
filtrated and poured into diethyl ether to isolate the modified
polymer (denoted as mod-Amph1).
1
H NMR spectrum of mod-Amph1 in CDCl showed that double
3
Figure 10. SEC chromatogram of Amph1 and mod-Amph1
bonds are successfully hydrogenated (Figure 8). The olefinic
proton signal appearing at 5.53 ppm was completely
disappeared after the transfer hydrogenation reaction.
Imidazole ring signals appeared at 7.50, 7.,06 and 6.94 ppm. –
13
C NMR in D
ester groups to amide groups. Only amide carbon peak (-NH-
C=O-, labeled as ) appeared at 173.87 ppm. Imidazole ring
carbons were observed at 137.80, 128.52 and 119.47,
respectively. –OCH - signals appeared between 65.78-69.83
2
O confirmed the complete conversion of
a
OCH signals were observed at 3.60-3.70 ppm. The peak group
2
appearing between 3.29-3-48 ppm was associated with
norbornene ring protons (labeled as 12 and 13 in Figure 8).
2
ppm. (Figure 9). Imidazole content of the mod-Amph1 was
found to be 4.45 mmol imidazole/g polymer as determined by
elemental analysis. SEC analysis showed the effect of both
Other norbornene ring signals were observed between 1.92-
1
0.85 ppm.
H NMR spectrum of mod-Amph1 was also
recorded in D O (SI, Figure S4).
2
hydrogenation
and
aminolysis
post-polymerization
modification reactions on the hydrodynamic volume of the
polymer (Figure 10).
Following the post-polymerization modification reactions,
nano-reactor experiments were carried out in water. For this
n
purpose, mod-Amph1 polymer (M : 7800 Da) was dissolved in
pure water (10 mg/ml). mod-Amph1 was readily dissolved in
water at room temperature. DLS analysis showed the
formation of a micelle structure with a number average
particle size of 33.64 (± 11) nm (Figure 11). G1 (0.005g, 0.006
2 2
mmol) was dissolved in minimum amount of CH Cl (200 µL)
and resulting solution was added dropwise to the water (10
ml) with intense magnetic stirring at 1000 rpm. The colour of
the solution turned to light green after 5 minutes of intense
stirring and reaction mixture was analyzed by means of DLS
and high contrast TEM. A small increase in average particle
size (85.95 ±35 nm) was observed in DLS analysis due to the
coordination of functional imidazole groups in mod-Amph1 to
the ruthenium center (Figure 13). As previously demonstrated
by several studies, Grubbs type complexes can bind two
imidazole groups
1
Figure 8. H NMR spectrum of mod-Amph1 in CDCl
3
(400 MHz)
1
3
2
Figure 9. C NMR spectrum of mod-Amph1 in D O
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1
Figure 14. H NMR spectrum of G1-mod-amph1
Figure 11. DLS results of mod-Amph1 in pure water
Figure 15. High contrast TEM images of G1-mod-amph1
Figure 12. Synthesis of G1-mod-amph1
On the next trial, the performance of nano-reactors was tested
on ring closing metathesis reactions of diethyl diallyl malonate
under air atmosphere. For this purpose, a glass reactor was
charged with an aqueous mod-amph1 solution (10 mg/ml) and
stirred at 1000 rpm for five minutes. After that G1 solution was
added dropwise to the emulsion solution.
to form a metathesis inactive 18 electron complex. The
complex was isolated by pouring the solution to diethyl ether.
1
The isolated green solid was analysed by H NMR. Ruthenium
alkylidene proton signal was shifted to 20.41 ppm indicating
the complete conversion of G1 to corresponding bis-imidazole
ruthenium complex (Figure 14). The peak appearing at 5.38
ppm was related to the imidazole back-bone proton signals
that were shifted to upfield due to the coordination of
nitrogen atoms to the ruthenium center. Aromatic phenyl
signals were overlapped with imidazole ring signals at 6-8 ppm
The colour of the solution immediately turned to light green,
indicating the coordination of imidazole groups to the
ruthenium center. Diethyl diallylmalonate was added dropwise
to the stirring solution and stirred at 1000 rpm for five minutes
in order to ensure the diffusion of diethyl diallylmalonate
inside the micelle structures. the homogeneity of the emulsion
was confirmed by DLS analysis (Figure 16a). The average
particle size containing only nano-reactors and diethyl
diallylmalonate before the reaction was found to be 94.40 nm
3
region. PCy signals appeared between 1.25-2.07 ppm. G1-
mod-amph1 complex formed micelle structure in aqueous
media as proved by DLS analysis. Micelle particles with an
average particle size of 85.95 (±35) nm were formed in the
water medium. TEM analysis of G1-mod-amph1 showed the
formation of spherical nano-reactors in water with an average
particle size of 89.69 (±34) nm which is close to the DLS
particle size value (Figure 15).
(±41.35). At this stage catalyst was inactive and diethyldiallyl
malonate remains unreacted as confirmed by GC-MS analysis.
HCl (2 M) was added to initiate the reaction. The colour of the
solution slowly turned from green to yellow-brown as the HCl
diffuses inside the micelle core, initiating the reaction. After
complete conversion of diethyl diallyl malonate, the particle
size was increased to 120.70 (±18.20) nm. These results
showed that nano-reactors are very stable even after the
reaction and no significant emulsion particle size extension
was observed (Figure 16b). G2 catalyst was not supported to
mod-Amph1 since It has been reported that the coordination
reaction between imidazole and G2 complex is relatively
3
3
slow. Considering the “in-situ” nature of the overall catalytic
process, our attempts to coordinate imidazole groups to G2
complex was failed, resulting in heterogeneous non-uniform
mixtures.
Figure 13. DLS analysis of G1-mod-amph1 (left) and photos of mod-amph1 and
G1-mod-amph1 solutions in water.
In order to optimize reaction conditions, different acids
and different acid/Ru ratios were used in RCM reactions of
diethyl diallyl malonate in non-degassed pure water under an
air atmosphere (Table 2). No conversion to desired RCM
product was observed in the absence of HCl even in higher
temperatures (80 °C). Addition of 2 M HCl (HCl/Ru: 80/1) at 80
°
C resulted in a conversion value of 73 % after 24 h. A
conversion value of 96 % was reached by repeating the
reactions under the same conditions at 25 °C. Among the
3 4 3 2 4 3
tested acids (H PO , HNO , HCl, H SO and CH COOH), HCl was
found to be the most effective acid for the activation of nano-
reactors, thus protonating nitrogen atoms of imidazole groups
and forming a metathesis active 14 electron ruthenium
6
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species. It is noteworthy that increased HCl/Ru ratio
decreased the conversion rate due to the fast initiation
followed by fast decomposition of active species.
Table 2. RCM of diethyl diallyl malonate using different acids
Figure 16. a) Average particle size before RCM reaction b) Average particle size
after RCM reaction
Table 4.RCM reactions under various conditions
a: A 50 ml beaker was equipped with a magnetic stirring bar. 10 ml of 10 mg/ml
solution of Mod-Amph1 (4.45 mmol imidazole/g polymer) in water was added to the
beaker and stirred at 1000 rpm for 5 minutes. Following the dissolution of mod-Amph1,
After optimizing reaction conditions, different olefinic
2 2
G1 (0.01 g, 0.012 mmol) in 100 µL CH Cl
was added and stirred for 5 minutes. hydrophobic substrates were used under optimum conditions
Diethyldiallyl malonate (1.2 mmol, 290 µL) was added and stirred for 5 minutes to and results are given in Table 3. Sterically hindered RCM
ensure the formation of homogenous emulsion. The acid solution was added in one
substrate, diethyl-2-allyl-2-(-2-methyl allyl)malonate (Table 3,
portion (500 µL) to initiate the reaction. b: Determined by GC-MS using n-tetradecane
entry 6) was converted to the desired RCM product in 60 %
as an internal standard
conversion value. After optimizing reaction conditions,
different olefinic hydrophobic substrates were used under
Table 3. Olefin metathesis reactions of various substrates using the nano-reactor
system
optimum conditions. N, N-diallyl-trifluoroacetamide was found
to be highly reactive under pre-determined reaction conditions
reaching a conversion value of 95 % even in low catalytic
loading ( 0.5 % Ru). 1-octene was used as a hydrophobic self-
metathesis partner, reaching a conversion 86 % after 12 h
giving corresponding internal olefin, 7-tetradecene with the
cis/trans ratio of 36/64. In order to investigate the
performance of the catalyst under harsh reaction conditions
RCM reactions were repeated under nitrogen and air
atmospheres using degassed, non-degassed pure water and
tap water. The results are given in Table 4. These results
showed that nano-reactor system perfectly protects active
species from decomposition and the RCM reaction can even
run in harsh conditions eliminating the need for distilled
degassed solvents and inert atmosphere.
On the next trial, the activity of the nano-reactor system
was compared with homogeneous bisimidazole substituted
Schanz catalyst in RCM reactions of diethyldiallyl malonate
using pre-determined reaction conditions (Figure 17). For this
a: Representative reaction procedure as follows: A 50 ml beaker was equipped with a purpose, a beaker was charged with 10 ml of water and a
3
4
magnetic stirring bar. 10 ml of 10 mg/ml solution of Mod-Amph1 (4.45 mmol magnetic stirrer. In a 1 ml glass vial, Schanz catalyst (5 % mol,
imidazole/g polymer) in water was added to the beaker and stirred at 1000 rpm for 5
0
2 2
.012 mmol), diethyldiallyl malonate (0.24 mmol) and CH Cl (
minutes. Following the dissolution of mod-Amph1, G1 (0.01 g, 0.012 mmol) in 100 µL
CH Cl was added and stirred for 5 minutes. Diethyldiallyl malonate (1.2 mmol, 290 µL)
was added and stirred for 5 minutes to ensure the formation of homogenous emulsion.
5
0 µL) were added and mixed for five minutes. The resulting
2
2
green solution in the vial was added to the water in a beaker
2
M HCl solution was added in one portion (500 µL) to initiate the reaction (HCl/Ru under a constant
ratio: 80/1). b: Determined by GC-MS.
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Acknowledgments
The Scientific and Technological Research Council of TURKEY
TUBITAK) is acknowledged for the financial support with the
(
project number 116Z734 (TUBITAK-KBAG). We would like to
thank Prof. Dr. Bekir Salih and Dr. Mehmet Atakay from
Hacettepe University-Chemistry Department for their help
with MALDI ToF MS analysis. Semra Akgönüllü and Prof. Dr.
Adil Denizli are highly acknowledged for their help on DLS
measurements.
Notes and references
Figure 17. Schanz catalyst vs. nano-reactor system in RCM reactions
‡ Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
§
stirring rate of 1000 rpm. After 5 minutes of intense stirring,
RCM reaction was initiated by addition of 2M HCl ( HCl/Ru
ratio; 80/1). The performance of both nano-reactor and Schanz
catalyst was compared in terms of RCM performance. As it can
be seen in Figure 17, Schanz catalyst initiated faster than the
nano-reactor system. However, Schanz catalyst decomposed
faster than the nano-reactor system and the reaction was
stopped at 80 % conversion of diethyldiallyl malonate. As
confirmed by DLS analysis, the reaction proceeds inside of
micro-sized droplets that are heterogeneously dispersed in
water. On the other hand, the nano-reactor system performed
better than Schanz catalyst in water, reaching a conversion
value of 99 % under emulsion conditions.
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