A ferrocene functionalized Schiff base containing Cu(ii) complex: Synthesis, characterization and parts-per-million level catalysis for azide alkyne cycloaddition

Article abstract of DOI:10.1039/d0dt00915f

Atom economy is one of the major factors in developing catalysis chemistry. Using the minimum amount of catalyst to obtain the maximum product yield is of the utmost priority in catalysis, which drives us to use parts-per-million (ppm) levels of catalyst

Full text of DOI:10.1039/d0dt00915f

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DOI: 10.1039/D0DT00915F
ARTICLE
Ferrocene Functionalized Schiff Base Containing Cu(II) Complex:
Synthesis, Characterization and Parts-per-million Level Catalysis
for azide alkyne cycloaddition
Received 00th January 20xx,
Accepted 00th January 20xx
Firdaus Rahaman Gayen,a,b Abdul Aziz Ali,a Debashree Bora,a,b Saptarshi Roy,a Supriya Saha,b,c
DOI: 10.1039/x0xx00000x
Lakshi Saikia,a,b Rajib Lochan Goswamee,a,b Biswajit Saha*a,b
Atom economy is one of the major factors of growing catalysis chemistry. Minimum use of catalysts and maximum
products is all time priority in the catalysis which drives to use parts-per-million (ppm) levels of catalyst loadings in
syntheses. In this context a new ferrocene functionalized Schiff base and its copper(II) complex has been synthesized and
characterized. This Cu(II) complex is employed as catalyst for the popular ‘Click chemistry’ where 1,2,3-triazoles are the
end product. As low as 5 ppm catalyst loading is enough to produce gram scale product and the highest 140000 Turn Over
Number (TON) and 70000 h-1 Turn Over Frequency (TOF) are achieved. Furthermore this highly efficient protocol has been
successfully applied for the preparation of diverse functionalized materials with pharmaceutical, labeling and
supramolecular properties.
species such as both Cu(II) and Cu(I) salts, preformed Cu(I)
complexes, metallic copper, Cu-nanoparticles and other Cu-
based heterogeneous systems can be used as a precatalyst in
Introduction
1,2,3-triazoles are promising N-heterocyclic compounds in
medicinal chemistry owing to their efficient amide surrogates.1
Based on this important structural motif, several drug
molecules like β-lactum antibiotic tazobactam, broad spectrum
cephalosporin antibiotic cefatrizine, anticonvulsant drug
rufinamide, anticancer drug carboxyamidotriazole are
available in the market.2 However, the chemistry of 1,2,3-
triazoles is not confined in medicinal chemistry and have wide
array of applications in modern science and technology
including materials science, organic chemistry, polymer
chemistry, supramolecular chemistry, biology as well as in
many industries also.3 Although there are several reports for
the synthesis of 1,2,3-triazoles,4 till now famous ‘Click
Chemistry’ approach remains dominant.5 Sharpless and
Meldal are the pioneer of Cu-catalyzed azide alkyne
cycloaddition reaction (CuAAC) for the synthesis of 1,2,3-
triazoles, which afforded spectacular advantages like high
regioselectivity, notable atom economy, mild reaction
conditions and high yield of the products.6
the CuAAC reaction.7 The most convenient catalytic system is
the combination of CuSO4ˑ5H2O and sodium ascorbate in
aqueous media, identified as Sharpless−Fokin catalyst.6
Despite its remarkable catalysis, there is a need to use quite
larger quantities of CuSO4ˑ5H2O and sodium ascorbate to
achieve solely 1,4-regioisomer in short period of time.8 This
creates a serious concern regarding the complete removal of
copper ions, which obstruct its enormous applications in
pharmaceutical industry as well as in biology.9 To address this
problem, recently Uozumi and co-workers reported a reusable,
metalloprotein-inspired polymeric Cu(II) catalyst in parts-per-
million (ppm) level for CuAAC reactions in tBuOH/H2O.10
Similarly, Astruc et al. described the efficient catalytic
behaviour of an amphiphilic recyclable dendrimer nanoreactor
for ppm level of Cu(I) catalyzed click reaction in water.11 In
2016, a new recyclable tris(triazolyl)-poly(ethylene glycol)
based Cu(I) catalyst in ppm level was reported for accelerating
the click reaction in water under inert atmosphere.12
Zimmerman et al. developed copper-containing metal−organic
nanoparticles for ppm level CuAAC reactions.13 Lipshutz and
coworkers devised iron based Cu nanoparticles for efficient
ppm level catalysis of click reaction.14 Although these systems
have received enormous importance due to their low Cu
loading (Scheme 1), there are still some difficulties associated
with them. For instance, complicated and time-consuming
synthetic routes etc, inhibits their practical applications.
Therefore, development of a simple and useful strategy for
Any copper source that produces catalytically active Cu(I)
a.Advanced Materials Group, Materials Sciences and Technology Division, CSIR-
North East Institute of Science and Technology, Jorhat, Assam – 785006, India
E-mail: bsaha@neist.res.in, bischem@gmail.com
b.Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus,
Jorhat, Assam – 785006, India
c. Advanced Computation Data Sciences Division, CSIR-North East Institute of
Science and Technology, Jorhat, Assam – 785006, India
† Electronic Supplementary Information (ESI) available: [Synthesis, characterization
studies, and spectra]. See DOI: 10.1039/x0xx00000x
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Scheme 1 Various copper catalysts in ppm level for click reaction.
The unsubstituted ferrocenyl ring showed the characteristic
singlet due to chemically equivalent five protons at 4.00 ppm
while for substituted cyclopentadiene (Cp) ring peaks
appeared at 4.61 and 4.29 ppm, respectively. The singlet at
15.56 ppm attributed to the hydroxyl group. In the 13C NMR
CuAAC reaction with extremely low Cu-loading is of
noteworthy interest. In this prospect, we wish to report herein
the synthesis and characterization of ferrocene functionalized
Schiff base containing Cu(II) complex for the ppm level
catalysis in CuAAC reaction under green condition.
Results and discussion
Synthesis and characterization of ligand and metal complex
The Schiff base (1) was synthesized in 85% (0.659 g) yield by
spectrum of 1, signal at 170.7 ppm showed by azomethine
carbon, and aromatic carbon atoms displayed their signals in
the range of 108.7–142.4 ppm for ligand (Figure S2, ESI†).
Furthermore, the peak observed around 153.2 ppm was
assigned to C-N carbon. Carbon atoms of the substituted
cyclopentadienyl ring appeared in the range of 69.1-69.5 ppm
refluxing 4-ferrocenyl aniline (0.500 g, 1.80 mmol, 1 equiv.)
and 2-hydroxy-1-naphthaldehyde (0.526 g, 3.06 mmol, 1.7
1
while unsubstituted in the 66.3 ppm. Suitable crystal of
1 is
equiv.) for 8 h in ethanol at 80 °C (Scheme 2). In the H NMR
grown in slow evaporation of dichloromethane. Two Cp ring of
ferrocene is staggered to each other (Figure S3, ESI†). The C=N
distance is 1.290(2) Å and OH····N is 1.765 Å.
spectrum of
1 in CDCl3, the azomethine proton showed singlet
at 9.28 ppm while aromatic ring protons provided their signals
in the range of 7.02–8.04 ppm (m, 10H) respectively (Figure S1,
ESI†).
Scheme 2 Synthesis of ferrocene functionalized Schiff base (
2 | J. Name., 2012, 00, 1-3
1
) and its copper(II) complex (
2).
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Figure 1 Molecular structure of
2 with important atoms labeled.
Hydrogen atoms are omitted for clarity. Selected bond lengths
[Å] and angles [°]: Cu1-O1 1.8960(19), Cu1-N1 1.999(2), Fe1-C18
2.035(3), Fe1-C20 2.043(3), Fe1-C23 2.047(3), Fe1-C26 2.040(3).
O1-Cu1-N1 89.41(8), N1-Cu1-N1 180.0, C26-Fe1-C20 109.56(13).
Symmetry code: 0.5-X, 0.5+Y, 0.5-Z.
Figure 2 Cyclic voltammograms of
1 and 2.
The X-Ray Photoelectron Spectroscopy (XPS) spectra for Fe and
Cu metal of the metal complex were shown in Figure 3. The Fe
The Schiff base ligand was crystallized in a monoclinic crystal 2p3/2 peak was observed at 707.98 eV, which is consistent to
system with P21/c space group. that of ferrocene (707.84 eV) and besides, the core level
Copper complex was synthesized by refluxing spectrum of Fe 2p1/2 demonstrates the peaks with binding
anhydrous copper(II) acetate (0.181 g, 1 mmol, 1 equiv.) and
energy at 720.80 eV.16 The peaks at 934.84 eV and 954.72 eV
(2)
1
(0.862 g, 2 mmol, 2 equiv.) in ethanol for 6 h at 80 °C under are attributed to the binding energies of 2p3/2 and 2p1/2 of Cu
nitrogen atmosphere in 95% (0.876 g) yield (Scheme 2). The respectively. In addition, satellite peak observed at around 943
NMR spectra of
paramagnetic nature. The molecular structure of
2
could not be obtained due to its eV confirmed the +2 oxidation state of copper in 2 17
reveals that
.
2
two ligands coordinate to copper via oxygen and nitrogen
centre forming square planar geometry (Figure 1). The ligands
are trans to each other having ˂O-Cu-O and ˂ N-Cu-N 180˚ in
both of them.
The cyclic voltammetric response of
1 and 2 were recorded
in dichloromethane solution containing 0.1 M Bu4NPF6 (100 m
Vs-1 scan rate) at 30 °C is shown in Figure 2 and the
corresponding electrochemical parameters are summarized in
Figure 3 XPS spectra of 2.
Table S1, ESI†. The observed anodic E1/2 values of
1 and 2 are
close to typical value of for pure ferrocene redox couple (0.45
± 0.02 V on GC electrode in dichloromethane) suggesting the Catalytic studies
oxidations are due to FeII/FeIII couple of the ferrocene moiety
Initially the catalytic activity of
is click reaction. mmol benzyl azide and 1.2 mmol
with Cu2+ ion and the overall phenylacetylene were reacted in presence of 2 mol% reducing
process remains one electron reversible for the complex 2 15
agent, sodium ascorbate and 1 mol% of in the aqueous
2 was tested in the model
present in them. The higher positive reduction potential of
due to the complexation of
2
1
1
.
2
We have examined the origin of redox behaviour by density media at 30 °C and 80% of 1,4 substituted triazole i.e 1-benzyl-
functional theory (DFT) calculation. From the Frontier 4-phenyl-1H-1,2,3-triazole was isolated after 2 h of the
Molecular Orbitals (FMO) of
the electron pair in the Highest Occupied Molecular Orbital for this CuAAC cycloaddition reaction with 1 mol%
(HOMO) of more localized on * orbitals of ferrocene (Figure mol% sodium ascorbate for 2 h. Using various organic solvents
S4, ESI†) whereas in Singly Occupied Molecular Orbital (SOMO) like THF, DMSO, DMF, acetonitrile and chloroform led to low
of there is an extensive mixing of the * orbitals of ferrocene yield of the desired 1,2,3-triazole (entries 2-6). Furthermore,
with the * orbitals of the substituted Schiff base ligand this (3+2) cycloaddition reaction in toluene furnished the
(Figure 4). Due to this extensive delocalization, the SOMO of triazole product in 55% yield (entry 7). On the other hand,
is stabilized from the HOMO of free ligand by 10 kJ mol-1. protic solvents like methanol, ethanol were also investigated in
Interestingly in cyclic voltammetry, the anodic couple of have this transformation leading to 60 and 65% yield respectively
1
and
2
, it is also very clear that reaction (Table 1, entry 1). Different solvents were screened
2
and 2
1

2


2
2
been shifted from that of
supporting the fact.
1
by 0.06 V towards higher potential (entries 8 and 9). Interestingly, significant improvement of
yield was observed when the reaction was carried out in
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ethylene glycol (EG) (entry 10). Mixed solvents were also with TON and TOF of the catalyst 18400 and 9200 h−1
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DOI: 10.1039/D0DT00915F
evaluated and we found that the best yield 95% obtained in respectively (Table 2, entry 3). However, decreasing the
EG/H2O (entry 15) whereas in DMSO/H2O, DMF/H2O, catalyst level up to 20 ppm resulted in moderate yield of 75%
MeOH/H2O, EtOH/H2O systems, only 35, 40, 65, 68% products product (entry 4). The highest 140000 TON and 70000 h-1 TOF
were isolated (entries 11-14). After ascertaining EG/H2O were achieved with 5 ppm loading of
2 and 70% desired
mixture as the best solvent for this reaction, the catalyst was triazole was isolated (entry 5). Rest of the click reactions were
evaluated for its effective lowest level. It was worthwhile to carried out with 50 ppm catalyst loading of
mention that lowering the catalyst loading to 0.5 mol% (5000 sodium ascorbate in EG/H2O (1:1) at 30 °C.
ppm) and 0.1 mol% (1000 ppm) resulted in same yield of 95%
2 and 1 mol%
of the corresponding triazole (entries 16 and 17). Furthermore,
the effective level of sodium ascorbate was determined and
found that 1 mol% was sufficient for this transformation (entry
Table
2. Click reaction between benzyl azide and
phenylacetylene using ppm loading of 2a
.
Entry
[2]
(ppm)
1000
Time Yield (%)
(h)
TON
TOF(h-1)
18). The reaction does not proceed in absence of
2 or sodium
ascorbate (entries 19 and 20). Under same reaction conditions
1 mol% Cu(OAc)2∙xH2O afforded 78% triazole product.18
95
94
92
75
70
950
9400
475
1
2
2
2
2
2
2
100
50
20
5
4700
Table 1. Solvent and Catalyst Optimization Studiesa
18400
37500
140000
9200
3
18750
70000
4
5b
aAll the reactions were carried out with 1 mmol of benzyl azide, 1.2
mmol of phenylacetylene, said amount of , 1 mol% sodium
ascorbate in 1 mL EG/H2O (1:1) at 30 °C. 10 mmol of benzyl azide,
12 mmol of phenylacetylene, 5 ppm of were used in 10 mL
EG/H2O (1:1) and rest of the conditions were maintained same
Entry
2
Sodium
Solvent
Yieldb
(%)
2
b
(mol%) Ascorbate
(mol%)
2
.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19d
20
21c
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
H2O
THF
DMSO
DMF
CH3CN
CHCl3
Toluene
MeOH
EtOH
EG
DMSO/H2O
DMF/H2O
MeOH/H2O
EtOH/H2O
EG/H2O
EG /H2O
EG/H2O
EG/H2O
EG/H2O
EG/H2O
EG/H2O
80
25
10
30
20
20
55
60
65
75
35
40
65
68
95
95
95
95
0
Phenylacetylene and benzyl azide were reacted in presence
of excess amount of mercury metal where other standard
condition was followed. After 2 h 92% desired triazole product
was isolated which confirmed the homogeneous path is
maintained during the reaction.19 The high catalytic activity of
2
is probably attributed to the presence of extended π-
conjugation in the Schiff base ligand and the attachment of
robust redox active ferrocene moiety enhances it further.20 In
the catalyst, the Schiff base fully covered the Cu(I) centre
which was generated by the reduction of
2 with sodium
ascorbate, leaving lack of free binding sites on the Cu(I) centre
for possible destabilizing interactions.21 Generally Schiff base
ligands are able to stabilize various oxidation states of
transition metal ions22 and in CuAAC reaction it was necessary
to control the stereoelectronic properties of the active Cu(I)
0.5
0.1
0.1
-
1.0
1.0
species in the reaction medium. Besides, the precatalyst
2 also
1.0
1.0
-
eliminated the need of handling the air sensitive Cu(I)
compounds along with excess ligand/additives.7 The formation
0
78
of Cu(I) by reduction of
2 with sodium ascorbate was
2.0
aReagents and reaction conditions: Benzyl azide (1 mmol),
monitored by UV-Vis spectroscopy (Figure S5, ESI†). For
Cu(OAc)2ˑxH2O, an absorption band in the range 700-800 nm
was assigned to the characteristic metal d-d electronic
transition.12 The appearance of a intense band in the range
phenylacetylene (1.2 mmol), mentioned amount of
ascorbate in the given solvent were stirred at 30 °C in open air;
bIsolated yield; CCu(OAc)2ˑxH2O was used instead of
2 and sodium
2
;
dThe
reaction was carried in a new glassware using new
magnetic stir bar each time in triplicate without using
between 300-400 nm of
2 was assigned to a metal to ligand
2
.
charge transfer (MLCT) transition indicating Cu(I) in the
complex. The phantom reactivity of magnetic stir bars due to
metal contamination in catalysis is one of the major
The efficiency of the protocol was checked with ppm level
of catalyst loading using the same standard reaction of
phenylacetylene and benzyl azide in EG/H2O mixture (Table 2).
Decreasing the catalyst loading to 50 ppm, the click reaction
proceeds smoothly affording the desired product in 92% yield
consequences in catalysis.23 So to ensure the reactivity of
2, a
test experiment of the standard click reaction of
phenylacetylene and benzyl azide under optimized condition
was carried out using a new 25 mL round-bottomed flask
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equipped with a new magnetic stirring bar and to our delight
same result (92% yield) was obtained.
With this encouraging result in hand, the scope of this low
ppm level protocol was further explored for variety of azide
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To know the extent of π-conjugation, DFT calculations at and alkynes (Table 3). As expected, all the reactions proceeded
the B3LYP level of theory were carried out. The optimized smoothly leading to the desired 1,4-disubstituted 1,2,3-
structures have similar bond distances and angles with the triazoles in good to excellent yields. Benzyl azide readily reacts
molecular structure which is determined by single crystal with electron donating groups (4-Me, 4-OMe, 3-Me, 2-Me-3-
(Table S3, ESI†). Presence of extended π-conjugation is OMe) of substituted terminal aromatic alkynes giving rise to
confirmed in the SOMO of optimized structure of
delocalized throughout the copper complex (Figure 4).
2
which is the corresponding triazoles in yields of 90−92% (entries 3b-3e).
The reaction of electron-poor (2-CF3, 4-F) phenylacetylenes
with benzyl azide proceeded easily to give the corresponding
1,2,3-triazoles in 90-95% isolated yield (entries 3f and 3g).
Similarly, nitro substituted benzyl azide reacted readily with
phenylacetylene affording the desired product in excellent
yield. Interestingly, the reaction of 1,4-diethynylbenzene with
benzyl azide affording alkynyl-containing 1,2,3-triazole
eliminates the need of protecting group manipulation strategy
which can be applied in peptide ligation (entry 3i).24 On the
other hand, aromatic azides also undergo efficient conversion
with various aromatic alkynes to form the target products in
good to excellent yields (entries 3j-3p). In case of aliphatic
alkyne, 1-hexyne smoothly underwent the reaction with
phenyl azide forming the cyclized products in yields of 75%
(entry 3q). Moreover, heterocyclic alkyne such as 2-
ethynylfuran was also tested in this (3+2) cycloaddition which
led to the expected triazole product in excellent yield (entry
3r).
Figure 4. Contour surfaces of the SOMO of 2.
Table 3. Substrates scope of azide-alkyne cycloaddition reaction by 2a
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aConditions: Azide (1 mmol), alkyne (1.2 mmol), 50 ppm of
stated; Yield of the products are given; Gram scale synthesis using 5 ppm loading of
2 and sodium ascorbate (1 mol%) in EG/H2O (1:1) at 30 °C for 2 h in open air otherwise
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b
2
; creaction time was 4 h.
DOI: 10.1039/D0DT00915F
Especially, functional groups like hydroxyl, ester were also ethynylpyridine under 50 ppm catalyst loading gave 2-pyridyl-
tolerated under this condition and could easily participate in 1,2,3-triazole in 88% yield after 4 h (Table 4, entry 4a).
this click reaction affording good to excellent yield of the Similarly, 1-ethynylcyclohexanol, an active metabolite of the
corresponding triazoles (Table 3, entries 3s and 3t). central nervous system depressant drug ethinamate,12 readily
Gratifyingly, gram scale reaction of benzyl azide (1.33 g, 10 reacts with phenyl azide affording the targeted product in
mmol, 1 equiv.) and phenylacetylene (1.22 g, 12 mmol, 1.2 good yield (84%, entry 4b). 17α-ethynylestradiol a synthetic
equiv.) furnish the 1-benzyl-4-phenyl-1H-1,2,3-triazole in good orally bioactive estrogen which is a derivative of the natural
yields (1.64 g, 70%) using only 5 ppm of this highly active hormone, estradiol and used for the treatment of menopausal
catalyst. Similarly, 1,4-diphenyl-1H-1,2,3-triazole (3j) was symptoms.10 In this case, the reaction of 17α-ethynylestradiol
synthesized in 72% isolated yield (1.59 g) from the reaction of with phenyl azide provided the desired triazole in 50% isolated
phenyl azide (1.19 g, 10 mmol, 1 equiv.) and phenylacetylene yield (entry 4c). Coumarin and its derivatives have found broad
(1.22 g, 12 mmol, 1.2 equiv.) using this efficient protocol.
application in flavourings, perfumery, pesticides, fluorescent
In order to explore the applicability of this ppm level dyes as well as in medicinal chemistry.12 In our study, the click
efficient protocol, different functionalized material was reaction of 7-(prop-2-yn-1-yloxy)-2H-chromen-2-one with
successfully synthesized (Table 4). Bulk scale synthesis of benzyl azide offered the expected triazole product in 60%
pyridyl-1,2,3-triazole ligands is a lucrative proposition as it is isolated yield (entry 4d).
an alternative to the bipyridine and terpyridine ligands which
have wide applications in the synthesis of functional metal
complexes.25 The reaction of phenyl azide and 2-
Table 4. Application of 2 for synthesis of different functional materials
Conclusion
disubstituted 1,2,3-triazoles were synthesized in good to
excellent yields. Furthermore, gram scale synthesis, biomedical
and material science application of this efficient catalytic
system undoubtedly opens an exciting avenue to the scientific
community.
In summary, we have synthesized an air and moisture
stable ferrocene functionalized Schiff base containing Cu(II)
complex and characterised by single crystal XRD and
spectroscopic techniques. Only ppm level of copper catalyst is
enough for the well-known Cu-AAC reaction fulfilling the
principles of click reaction and green chemistry. With this
convenient and easily accessible protocol, a wide range of 1,4-
Experimental
Unless otherwise stated, all the reactions were performed in
oven dried glassware under air. Chemicals were purchased
6 | J. Name., 2012, 00, 1-3
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from commercial suppliers (TCI, Alfa Aesar and Sigma-Aldrich) Preparation of stock solution of 2
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and used without further purification. Purifications of products In a 25 mL screw cap vial containing aDmOIa:g10n.e10ti3c9/sDt0irDrTe0r0b91a5rF,
were carried out by column chromatography using silica gel complex (9.24 mg) was dissolved in 10 mL THF and stirred for
2
(200-300 mesh). Analytical thin-layer chromatography was 10 min at 30 °C. A dark orange stock solution of
performed using silica gel 60F254 plates and visualization was obtained for subsequent ppm level click reaction.
2 was
1
carried out with UV light. H NMR (500 MHz), 13C NMR (125
MHz) were recorded on
spectrometer using TMS as an internal standard. Chemical
shifts are reported in parts-per-million (ppm, d) downfield In a 25 mL round-bottomed flask equipped with a magnetic
from residual solvents peaks and coupling constants are stirring bar, 46 µL (50 ppm) of stock solution of was added
a Brucker Avance 500 MHz General procedure for azide alkyne cycloaddition reaction by
2
2
reported as Hertz (Hz). Splitting patterns are designated as: s = and the THF was removed in vacuo. To this, 1 mmol of organic
singlet, d = doublet, t = triplet, q = quartet, m = multiplet etc. azide, 1.2 mmol of alkyne, 1.9 mg (1 mol%) of sodium
UV-visible spectra were recorded on UV-visible Spectrometer ascorbate and 1 mL of EG/H2O (1:1) were added. The reaction
(Specord – 200, Analytik Jena) in the range of 200-800 nm. XPS mixture was stirred for 2 h at 30 °C under air. After 2 h, the
spectra were recorded by X-ray photo electron Spectrometer mixture was extracted using EtOAc (3x10 mL). The organic
(ESCALAB Xi+, Thermo Fisher Scientific Pvt. Ltd., UK). The layer was dried over Na2SO4 and the solvent was removed in
voltammetric analysis was carried out using conventional three vacuo. The crude product was purified via silica gel column
electrode system by using GAMRY Interface 1000E chromatography using a gradient mixture of n-hexanes and
Potentiostat. FT-IR spectra were recorded on a Perkin Elmer ethyl acetate to obtain the corresponding 1,2,3-triazoles.
Spectrum 100 spectrometer with KBr pellet in the frequency
range of 4000-400 cm-1. HRMS were recorded on a Q-TOF 1-benzyl-4-phenyl-1H-1,2,3-triazole
spectrometer (Xevo XS QTof mass spectrometer) in bottom flask containing a magnetic stirring bar was charged
electrospray ionization mode. Elemental analyses were with 46 µL of stock solution (5 ppm) of was added and the
(3a): A 25 mL round
2
conducted on a CHN analyzer PE-2400 (Perkin Elmer, USA).
THF was removed in vacuo. To this, benzyl azide (1.33 g, 10
mmol, 1 equiv.), phenylacetylene (1.22 g, 12 mmol, 1.2 equiv.),
1.9 mg (0.01 mmol) of sodium ascorbate and 10 mL of EG/H2O
(1:1) were added. The reaction mixture was stirred for 2 h at
30 °C under air and after completion, the mixture was
extracted using EtOAc (3x30 mL). The organic layer was dried
over Na2SO4 and the solvent was removed in vacuo. The
residue was purified on silica gel (hexanes/ethyl acetate) to
furnish the 1-benzyl-4-phenyl-1H-1,2,3-triazole in 70% yield
(1.64 g).
Synthesis of ferrocene-based Schiff base (1)
The Schiff base
1 was synthesized by refluxing 4-ferrocenyl
aniline (0.500 g, 1.80 mmol, 1 equiv.) and 2-hydroxy-1-
naphthaldehyde (0.526 g, 3.06 mmol, 1.7 equiv.) for 8 h in
absolute ethanol at 80 °C. After completion of reaction, the
orange yellow precipitate was filtered, washed several times
with ethanol, dried under vacuo and recrystallized from
dichloromethane. Yield 0.659 g (85%), M.p. 210-215 °C; FT-IR
1
(KBr pellet, cm-1): 3480, 1620; H NMR (500 MHz, CDCl3) δ:
1,4-diphenyl-1H-1,2,3-triazole
(3j): The triazole 3j was
15.56 (s, 1H), 9.28 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.73 (d, J =
9.1 Hz, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.47 (t, J = 9.0 Hz, 3H), 7.25
(t, J = 8.5 Hz, 3H), 7.02 (d, J = 9.1 Hz, 1H), 4.61 (s, 2H), 4.29 (s,
2H), 4.00 (s, 5H); 13C NMR (126 MHz, CDCl3) δ: 170.7, 153.2,
142.4, 138.1, 136.5, 133.1, 129.2, 127.9, 127.0, 123.3, 122.4,
120.1, 118.7, 108.7, 84.2, 69.5, 69.1, 66.3. HRMS (ESI-TOF-Q)
calcd for C27H21FeNO: 431.0973, found: 431.0992 [M]+; Anal.
Calcd for Chemical Formula: C27H21FeNO: C, 75.19; H, 4.91; N,
3.25. Found: C, 75.17; H, 4.89; N, 3.23.
synthesized in 72% isolated yield (1.59 g) utilizing phenyl azide
(1.19 g, 10 mmol, 1 equiv.), phenylacetylene (1.22 g, 12 mmol,
1.2 equiv.), 1.9 mg (0.01 mmol) of sodium ascorbate, 5 ppm of
2
and 10 mL of EG/H2O (1:1) according to the procedure
described for the gram scale synthesis of 3a
.
X-ray data collection and refinement
Single-crystal X-ray studies were performed on a CCD Bruker
SMART APEX diffractometer equipped with an Oxford
Instruments low-temperature attachment. All the data were
collected at 100(2) K using graphite-monochromated MoKα
radiation (λα=0.71073 Å). The frames were indexed,
integrated, and scaled by using the SMART and SAINT software
packages26 and the data were corrected for absorption by
using the SADABS program.27 The structures were solved and
refined with the SHELX suite of programs.28 All hydrogen
atoms were included in the final stages of the refinement and
were refined with a typical riding model. Structure solution
Synthesis of 2
Copper(II) complex bearing ferrocenyl Schiff base was
synthesized by refluxing anhydrous copper(II) acetate (0.181 g,
1 mmol, 1 equiv.) and
1 (0.862 g, 2 mmol, 2 equiv.) in ethanol
for 6 h at 80 °C under nitrogen atmosphere. After cooling the
reaction mixture to 30 °C, the brown colour precipitates were
separated out from mother liquor, washed with ethanol and
dried well in high vacuo. Crystals suitable for X-ray structure
analysis were obtained by recrystallization from
dichloromethane. Yield 0.876 g (95%), M.p. 310-315 °C. FT-IR
(KBr pellet, cm-1): 3393, 3053, 1599, 510, 415; Anal. Calcd for
C54H40CuFe2N2O2: C, 70.18; H, 4.36; N, 3.03. Found: C, 70.16; H,
4.34; N, 3.01.
and refinement details for compounds
1 and 2 are provided in
the Supporting Information. Anisotropic treatment of these
three atoms resulted nonpositive definite displacement
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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ARTICLE
Journal Name
2
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(a) A. Lauria, R. Delisi, F. Mingoia, A. Terenzi, A. Martorana,
tensors and were therefore subjected to isotropic refinement.
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G. Barone and A.M. Almerico, Eur. J. ODrgO.I:C1h0e.1m03.,9/2D001D4T,030298159F;
(b) D. Dheer, V. Singh, and R. Shankar, Bioorg. Chem., 2017,
71, 30.
Pertinent crystallographic data for compounds
1 and 2 are
summarized in Table S2 in the Supporting Information. The
crystallographic figures used in this manuscript have been
generated using Diamond 3.1e software.29 CCDC-1967275
For selected reviews, see: (a) J. E. Moses and A. D.
Moorhouse, Chem. Soc. Rev., 2007, 36
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,
,
http://www.ccdc.cam.ac.uk/cgi-bin/catreq.cgi
http://www.ccdc.cam.ac.uk/cgi-bin/catreq.cgi (
supplementary crystallographic data for this paper. These data
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Computational Study
Calculations were performed using density functional theory
(DFT) with Becke’s three-parameter hybrid exchange
functional30 and the Lee-Yang-Parr correlation functional
(B3LYP).31 Geometry-optimized structures were characterized
fully via analytical frequency calculations as minima on the
potential energy surface. The double-ζ basis set of Hay and
Wadt (LanL2DZ) with effective core potential (ECP)32 was used
for Fe and Cu. The 6-31G(d,p) basis sets were used to describe
H, N, C, and O ligand atoms. All optimization calculations were
performed with the Gaussian 16 (G16)33 suite of programs.
Optimization of copper complex has been performed in gas
phase.
4
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Conflicts of interest
There are no conflicts to declare.
S. Saha, M. Kaur, and J. K. Bera, Organometallics, 2015, 34
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Acknowledgements
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The authors are thankful for the financial support by DST-SERB
(ECRA and EEQ Project) and CSIR (FBR Project) New Delhi,
India. FRG and DB thank SERB for fellowship
(ECR/2016/000849; GPP-0315) and (EEQ/2017/000156; GPP-
0333) respectively and AAA, SR acknowledge CSIR-FBR project
(MLP-1010) for scholarship. We are also grateful to Director,
CSIR-NEIST for permission to carry out the work. Dr Sarat Ch.
Patra and Sanjay Biswas are duly acknowledged for fruitful
discussion about the electrochemistry. We thank to Prof.
Dibyendu Mallick, Presidency University, Kolkata for his input
in DFT study.
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DOI: 10.1039/D0DT00915F
Graphical Abstract
Ferrocene Functionalized Schiff Base Containing Cu(II) Complex:
Synthesis, Characterization and Parts-per-million Level Catalysis
for azide alkyne cycloaddition
Highly efficient ferrocene functionalized Schiff base containing copper(II) complex enables
diverse 1,2,3-triazoles under green condition with parts-per-million catalyst level.
e
F
N
O
Cu
O
N
e
F
N
R
N
N
R'
N3
R
+
ppm loading
R'
Ease synthesis of catalyst
High TON and TOF
Gram scale
Green Solvent
Supramolecular
applicaion
Biomedical
application