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Unsymmetrical PEG-substituted
tris(triazolyl)amines as bi-functional surfactants
Cite this: New J. Chem., 2022,
46, 6009 for copper-catalyzed aerobic oxidation of
alcohols in water†
Vasut Nakarajouyphon,a Thanthapatra Bunchuay, a Nobuto Yoshinari, b
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Table 1 Copper catalyst systems for aerobic oxidation of benzyl alcohol in water
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Fig. 1 Structures of tris(triazolylmethyl)amine (TTA), tris(triazole)–polyethylene glycol (tris-trz–PEG), and unsymmetrical PEG-functionalized
tris(triazolylmethyl)amine.
immobilized a chiral Cu(II)–alkynylbis(oxazoline) catalyst to the otherwise noted, all solvents were of analytical grade. Anhy-
hydrophobic portion of the poly(ethylene glycol)-b-poly(styrene- drous CH2Cl2 was purified from INERT PureSolv MD5. Water
co-4-vinylbenzyl azide) polymer via copper-catalyzed azide– was purified by Milli-Q and has a resistivity of 18 MO cm1.
alkyne cycloaddition (CuAAC).23 It was found that the resulting
polymeric vesicles containing Cu-bis(oxazoline) catalysts effi- Characterization
ciently catalyzed asymmetric cyclopropanation of styrene deri-
Nuclear magnetic resonance spectra were acquired using a
vatives and ethyl diazoacetate in water. In another example,
400 MHz Bruker Avance spectrometer for 1H (400 MHz) and
Uozumi and co-workers demonstrated that the amphiphilic 13
C{1H} (100 MHz) nuclei. Chemical shifts are reported in d
platinum NCN–pincer complex self-assembled in aqueous sol-
units (parts per million) using residual solvent signals as
vent to produce vesicles capable of catalyzing alkynoic acid
references. Fourier transform infrared spectroscopy (FTIR)
cyclization as well as alkene hydrosilylation in water.24,25
(400–4000 cm1) was performed on a Bruker Alpha instrument
Due to their large copper binding constants,26
(Bruker Optics GmbH, Ettlingen, Germany). Percent substrate
tris(triazolylmethyl)amines (TTA; Fig. 1) have widely been
conversions obtained from catalytic experiments were analyzed
used as ligands in CuAAC27 and copper-catalyzed atom transfer
on a GC6890N Agilent Technology gas chromatograph
radical polymerization.28 The related amphiphilic tris(triazole)–
equipped with a 5973N mass selective detector. High-
polyethylene glycol (tris-trz–PEG) has been shown to stabilize
resolution mass spectra were acquired from a Bruker Data
metal nanoparticles and facilitate various catalytic reactions
Analysis Esquire-LC mass spectrometer (ESI mode). Matrix-
including CuNP-catalyzed azide–alkyne cycloaddition, PdNP-
assisted laser desorption/ionization time-of-flight mass spectra
catalyzed Suzuki–Miyaura cross coupling, and RuNP-catalyzed
were recorded on a Bruker autoflex speed MALDI-TOF (Bruker,
transfer hydrogenation of nitrobenzene.29 Based on these cat-
Germany) using polymer analysis mode. A Shimadzu UV-2600
alytic applications, this work reports the synthesis of unsym-
UV-Vis spectrophotometer was used to record the absorption
metrical amphiphilic tris(triazolyl)amines featuring varying
spectra. Fluorescence emission spectra of pyrene probes were
PEG chain lengths (Fig. 1). Consequently, their efficiency as
collected on a FluoroMax 4+ Horiba spectrofluorometer at 25 1C
bi-functional surfactants containing N-based binding sites for
using an excitation wavelength of 333 nm, with the excitation
copper-catalyzed aerobic oxidation of activated alcohols in
and emission slit width of 1.5 nm. Dynamic light scattering
water was investigated and discussed as a function of PEG
(DLS) was measured at 25 1C using the Zetasizer Nanoseries
chain length.
model S4700 (Malvern Instruments Corporation) laser light
scattering system under the conditions of a He–Ne laser
(l = 632.8 nm). Copper leaching during catalytic alcohol oxida-
Experimental section tion was determined using flame atomic absorption spectro-
Materials metry (FAAS) (PerkinElmer PinAAcle 900T). TEM images of
negatively stained surfactants were recorded on a JEOL JEM-
Air-sensitive experiments were carried out under a dry N2
ARM200F (JEOL Co., Ltd. Tokyo, Japan) operated at 200 kV
atmosphere using standard Schlenk techniques. All chemicals
using phosphotungstic acid as a staining agent.
were used as received from commercial sources. Benzyl azide
was prepared according to the previously reported method,30
while the synthesis of the azido-poly(ethylene) glycol substrates UV-Vis spectrophotometric titration
(i.e., PEG200-N3, mPEG550-N3, and mPEG2000-N3),31 (1-benzyl- The 2.0 mL aqueous solution of NBBT550 (1.0 104 M) in a
1H-1,2,3-triazol-4-yl)methanol (1),32 1-benzyl-1H-1,2,3-triazole- 1 cm quartz cell was directly titrated by successive additions of
4-carbaldehyde (2),33 and N,N-bis((1-benzyl-1H-1,2,3-triazol-4- aqueous solutions of CuBr2 (1.0 102 M) mixed with
yl)methyl)prop-2-yn-1-amine (3)34 followed the literature NBBT550 (1.0 104 M). The UV-Vis spectra were recorded at
methods with slight modifications (see ESI† for details). Unless 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2.0, 3.0, 4.0, 5.0,
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6.0, 7.0, 8.0, 9.0, and 10.0 equivalents of Cu ions. Based on the and NMI (3.98 mL, 0.050 mmol, 10 mol%) in 0.5 mL water was
absorption data at the wavelength 300 nm, binding constants subsequently added and the reaction mixture was vigorously
were determined using the BindFit program.35–37 stirred. After a given time, 0.050 mmol anisole was added as an
internal standard and the product was extracted using ca. 2 mL
General procedure for the synthesis of NBBT200-OH, NBBT550, of EtOAc. Then, the filtrate was filtered through a 0.45 mm
and NBBT2000 nylon membrane syringe filter and was subjected to GC-MS
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compounds NBBT200-OH, NBBT550, and NBBT2000 were Table 3 Control study for aerobic alcohol oxidationa
investigated as bi-functional surfactants and ligands for
copper-catalyzed alcohol oxidation in water. 4-Methoxybenzyl
alcohol was used as a model substrate catalyzed by 5 mol%
CuBr, 5 mol% of surfactants, 5 mol% of TEMPO, and 10 mol%
of NMI in 0.5 mL water at room temperature. The catalyst
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systems containing the surfactants NBBT550 and NBBT2000 Entry Additive Time (h) Conversionb (%)
showed comparable oxidation activities with 37% and 39% 1 — 2 60
conversions to 4-methoxybenzaldehyde, respectively, at 0.5 h. 2 TBTA 2 59
3 bpy 2 90
On the other hand, the ligand NBBT200-OH, afforded a lower 4 bpy/mPEG-550 2 88
conversion of 28% under the same conditions (Fig. 3). After 2 h, 5 NBBT-550 2 94
catalyst systems with NBBT550 gave the highest alcohol con- 6 bpy/TPGS-750-Mc 4 10020
version of 94% followed by NBBT2000 (88%) and NBBT200-OH a
Reaction conditions: 4-methoxybenzyl alcohol (0.5 mmol), CuBr
(84%). Quantitative conversions to 4-methoxybenzaldehyde (0.025 mmol), additive(s) (0.025 mmol), TEMPO (0.025 mmol), NMI
(0.05 mmol) in water (0.5 mL), room temperature with 0.05 mmol
with 100% selectivity were obtained at 3 h for all surfactants. anisole as internal standard. b Calculated from GC results, average of
In a control study, without a surfactant and ligand/additive, two runs (entries 1–5). c 2 wt% TPGS-750-M.
only 60% of 4-methoxybenzyl alcohol was converted to the
oxidized product after 2 h (entry 1, Table 3). The structurally
remaining aqueous solution to initiate the second catalytic
related ligand tris(benzyltriazolylmethyl)amine (TBTA) did not
run. It was found that only the catalyst system featuring the
improve the catalytic activity of copper ions (entry 2) and
bi-functional surfactant NBBT550 provided high conversions
precipitation of the copper complexes as a green solid, probably
(86–100%) for at least six catalytic runs with an addition of
the CuII–TBTA complex, was also observed.40 On the other
5 mol% CuBr to the fourth run (Fig. 4). On the contrary, catalyst
hand, the catalyst systems CuBr/bpy (bpy = 2,2-bipyridine)
systems containing bpy and bpy/mPEG-550 showed an appar-
and CuBr/bpy/mPEG550 afforded high alcohol conversions of
ent decrease in oxidation activity, giving ca. 60–70% conver-
90% and 88%, respectively, comparable to that of CuBr/
sions in the third catalytic cycle. The reduced conversions are
NBBT550 (entries 3–5). Notably, under similar conditions, the
attributed to a loss of Cu species and bpy ligands during the
catalyst system CuBr/TEMPO/NMI with 2 wt% of the surfactant
product extraction step. Thus, the reusability study underlines
TPGS-750-M oxidized 4-methoxybenzyl alcohol to the corres-
the importance of the bi-functional surfactant, which allows
ponding aldehyde in a quantitative yield at 4 h (entry 6).20
the catalytic reactions to take place in the hydrophobic areas of
Based on their high activities (entries 3–5, Table 3), three
vesicles while impeding a catalyst loss during the work-up
catalyst systems CuBr/TEMPO/NMI with the following addi-
tives: NBBT550; bpy; and bpy/mPEG-550 were investigated in
the reusability study. In particular, after 4 h of the first catalytic
reaction, the product was extracted by EtOAc, after which the
alcohol substrate, TEMPO, and NMI were added to the
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Table 4 Substrate scope studya addition of 5 mol% CuBr was required to achieve quantitative
conversions in subsequent runs. Consistent with these results,
FAAS reveals 35 ppm of Cu species leached into the EtOAc
extracts on average for each catalytic reaction from the first
three catalytic runs (Table S1, ESI†). In comparison, a similar
loss in activity was also observed with the catalyst system CuBr/
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Entry Aldehyde Time (h) Conversionb (%) bpy/TEMPO/NMI with 2 wt% TPGS-750-M as 5 mol% of CuBr
must be added to the third catalytic run to maintain efficient
alcohol oxidation.20
1 4 100 Other alcohol substrates were also explored using the
catalyst system CuBr/TEMPO/NMI/NBBT550 in water
(Table 4). It appears that our catalyst system was able to
2 4 100 efficiently catalyze aerobic oxidation of benzyl alcohol deriva-
tives containing both electron-donating (i.e., OMe) and
electron-withdrawing groups (i.e., NO2, Cl, Br), which are often
more difficult to oxidize, as well as cinnamyl and furfuryl
3 4 100 alcohols in water affording high conversions at 4 h. Steric
hindrance at the ortho-position of the phenyl ring (i.e., 2-
methoxy- and 2-nitrobenzyl alcohols) also did not negatively
impact the catalytic activities. The 4-hydroxybenzyl alcohol
4 4 94 substrate, however, resulted in only 50% conversion, possibly
due to a reaction between Cu and phenol or the property of
phenolic compounds as antioxidants.41 Furthermore, the unac-
tivated 11 and 21 aliphatic alcohol substrates including 1-
5 4 95 hexanol, 2-methyl-1-pentanol, and cyclohexanol did not yield
the oxidized products under these catalytic conditions based on
GC-MS. Overall, CuBr/TEMPO/NMI in the presence of the
triazole-based surfactant NBBT550 exhibits higher catalytic
6 4 84 oxidation activities toward activated alcohols in water under
mild conditions with good reusability, compared with those of
previously reported copper catalyst systems (Table 1).
7 4 100
Conclusions
8 4 50
We have demonstrated a new synthetic protocol for unsymme-
trical, amphiphilic PEG-substituted triazole-based compounds
a
Reaction conditions: alcohol substrate (0.5 mmol), CuBr (0.025 mmol), NBBT200-OH, NBBT550, and NBBT2000, which are bifunc-
NBBT550 (0.025 mmol), TEMPO (0.025 mmol), NMI (0.05 mmol) in
water (0.5 mL), room temperature with 0.05 mmol anisole as internal tional, potentially serving both as chelate ligands for Cu ions
standard. b % Conversion calculated from GC results. and as surfactants to facilitate copper-catalyzed aerobic alcohol
oxidation in water without the need for additional ligands. Only
the NBBT550 and NBBT2000 surfactants with longer
procedure. To confirm strong binding between Cu ions and the poly(ethylene glycol) chains and HLB values 4 10 are soluble
triazole-based surfactant in water, UV-Vis spectrophotometric in water and form vesicles with average diameters of ca. 480
titrations between the water-soluble CuBr2 and NBBT550 were and 270 nm, respectively, based on DLS and negatively stained
performed in aqueous solutions. Absorption data collected at TEM. Among all three surfactants, CuBr/TEMPO/NMI in the
300 nm were analyzed using the BindFit program,35–37 which presence of NBBT550 was the most active catalyst system
suggests a 2 : 1 stoichiometric ratio of NBBT550:CuBr2 with toward aerobic oxidation of 4-methoxybenzyl alcohol in water.
strong interactions in water, as evidenced by the relatively large Although UV-Vis spectrophotometric titrations between CuBr2
binding constants of K11 = 2.5 104 M1 and K21 = 6.3 and NBBT550 reveal strong Cu2+–surfactant binding, dissocia-
103 M1 (Fig. S2, S3 and Table S2, ESI†). It should be noted that tion of Cu ions from the catalyst system was still evident,
the binding constant of 5.1 107 M1 was previously reported according to FAAS. As a result, addition of 5 mol% CuBr to
for TBTA–Cu2+ in CH3CN.26 the reaction mixture before the fourth catalytic cycle was
However, even in the presence of NBBT550, the loss of Cu needed to achieve high conversions for at least six runs. To
species still affected the catalytic performance of CuBr/TEMPO/ improve the efficiency and reusability for this type of catalyst–
NMI/NBBT550 after three catalytic cycles, at which point an surfactant system, ligand structure modification to enhance
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