A novel bi-functional surfactant-based paramagnetic deep-eutectic catalyst for improved benzoin condensation and multi-component synthesis of pyrrole derivatives

Article abstract of DOI:10.1016/j.molliq.2019.01.095

A new professional magnetic surfactant-based deep-eutectic (DE) and viscose liquefy catalyst (GS²⁺·2FeCl₄, MGSFe) was synthesized by an optimized reaction of the as-prepared cationic gemini-surfactant (GS) with two moles of FeCl₃·6H₂O. The structure of the GS and MGSFe were characterized by NMR, FT-IR, UV–visible, CHN, pH, surface tension (?), and vibrating sample magnetometry (VSM) analyses. The MGSFe, that is a high viscose brownish liquid at >50 °C, was successfully tested as a highly active paramagnetic catalyst for improved benzoin condensation and three-component synthesis of substituted pyrroles with the highest turnover number (TON) and turnover frequency (TOF) that ever reported for this purpose. The superior activity of MGSFe is due to its amphiphile properties, the synergistic effects between GS²⁺ and 2FeCl₄ ^? as hydrogen-bond-donor and magnetic hydrogen-bond-acceptor components of this novel magneto-responsive DE, and reusability without loss of activity even in four consequence cycles run for synthesis of pyrroles. This magnetic GS-based DE can be used as oil miscible additive, pollutant adsorbent, and carrier of biomaterials to targeted poisons.

Full text of DOI:10.1016/j.molliq.2019.01.095

Accepted Manuscript
A novel bi-functional surfactant-based paramagnetic deep-
eutectic catalyst for improved benzoin condensation and multi-
component synthesis of pyrrole derivatives
Fatemeh Tamaddon, SeydEhsan Tadayonfar
PII:
S0167-7322(18)34940-7
DOI:
Reference:
https://doi.org/10.1016/j.molliq.2019.01.095
MOLLIQ 10326
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
1 October 2018
29 December 2018
17 January 2019
Please cite this article as: F. Tamaddon and S. Tadayonfar, A novel bi-functional
surfactant-based paramagnetic deep-eutectic catalyst for improved benzoin condensation
and multi-component synthesis of pyrrole derivatives, Journal of Molecular Liquids,
https://doi.org/10.1016/j.molliq.2019.01.095
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ACCEPTED MANUSCRIPT
A novel bi-functional surfactant-based paramagnetic deep-eutectic catalyst
for improved benzoin condensation and multi-component synthesis of
pyrrole derivatives
Author 1: Fatemeh Tamaddon, Department of Chemistry, Yazd University, Yazd 89195-741,
Iran, E-mail: ftamaddon@yazd.ac.ir, Tel: +983531232666, Fax: +983538210664
Author 2: SeydEhsan Tadayonfar, Department of Chemistry, Yazd University, Yazd 89195-
741, Iran, E-mail: ehsantadayonfar@stu.yazd.ac.ir
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A novel bi-functional surfactant-based paramagnetic deep-eutectic catalyst
for improved benzoin condensation and multi-component synthesis of
pyrrole derivatives
Fatemeh Tamaddon,* SeydEhsan Tadayonfard
Department of Chemistry, Faculty of Science, Yazd University, Yazd 89195-741, Iran
__________________________________________________
Abstract: A new professional magnetic surfactant-based deep-eutectic (DE) and viscose
liquefy catalyst (GS2+.2FeCl4, MGSFe) was synthesized by an optimized reaction of the as-
prepared cationic gemini-surfactant (GS) with two moles of FeCl3.6H2O. The structure of the
GS and MGSFe were characterized by NMR, FT-IR, UV-visible, CHN, pH, surface tension
(ᵞ), and vibrating sample magnetometry (VSM) analyses. The MGSFe, that is a high viscose
o
brownish liquid at > 50 C, was successfully tested as a highly active paramagnetic catalyst
for improved benzoin condensation and three-component synthesis of substituted pyrroles
with the highest turnover number (TON) and turnover frequency (TOF) that ever reported for
this purpose. The superior activity of MGSFe is due to its amphiphile properties, the
-
synergistic effects between GS2+ and 2FeCl4 as hydrogen-bond-donor and magnetic
hydrogen-bond-acceptor components of this novel magneto-responsive DE, and reusability
without loss of activity even in four consequence cycles run for synthesis of pyrroles. This
magnetic GS-based DE can be used as oil miscible additive, pollutant adsorbent, and carrier
of biomaterials to targeted poisons.
Keywords: Gemini-surfactant; Magnetic deep-eutectic; Molecular liquid; MGSFe; Benzoin
condensation; Substituted pyrroles.
________________________________________________
*Corresponding author: Tel.: 00983531232666; fax: 00983538210644; e-mail:
ftamaddon@yazd.ac.ir
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1. Introduction
Recently, deep eutectic solvents (DESs) have been extensively used in various fields of
science as low-cost and low toxic alternatives for organic solvents and even traditional ionic
liquids (Ils) [1-7]. DESs are mainly composed of two or more solid hydrogen-bond-donor
(HBD) and hydrogen-bond-acceptor (HBA) components that fused to each other to create a
o
very large (> 150 C) depression of freezing/melting points in contrast with the individual
components [8-10]. Despite the advancements in HBD/HBA of DESs, high melting point
hydrated metal halides and quaternary ammonium salts (QAS) are of the extreme HBD/HBA
components used in the second type of DESs defined by Abbott [10], even though anhydrous
metal salts and cationic phosphonium/ammonium salts creates the forth class of DESs [11].
However, the easily prepared second category of DESs are more economic than the forth
type ones, due to the lower cost of hydrated metal halides and choline chloride (ChCl) as the
most abundant QASs in the structure of DESs used in organic synthesis [12-15]. Even more
the advantages, reusability issues restricted application of DESs, hence immobilization on
supports [16] and magnetization [17-21] are two reasonable accounts to these issues. At ever
time, magnetization of DESs has been achieved by immobilization of DESs on magnetic
particles [20, 21] or dissolving of anhydrous FeCl3 in ChCl-based DESs [19], however a DES
catalyst with both of magnetic and surfactant properties is highly anticipated.
Pyrrole derivatives are valued structural units and building blocks of natural products [22-
24], conductive luminescent materials [25], and important pharmaceuticals, which as in
classic Hantzsch, Knorr, Pall-Knorr, and Barton-Zard methods [24] have been prepared by
evolutional multi-component reactions (MCRs) [25-32]. In addition to various eco-
environmental advantages of MCRs, incorporation of various groups in pyrrole moiety is
readily accessed via the change of reaction components. In this context, we have recently
designed a three-component strategy for synthesis of substituted pyrroles by condensation of
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benzoins with ammonium acetate and 1,3-dicarbonyls in the presence of solid acid catalysts
[28, 29], aqueous ethanolic solution [30], and micelle medium of betaines [31]. Due to the
reusability issues and recovery drawbacks of acid catalysts and aqueous mediums, replacing
a magnetically-separable surfactant prepared by incorporation of the magnetic complex anion
of [FeCl4]- in surfactant-based DESs is highly proficient. This efficacy can be improved by
hosting of more strategic surface-active gemini-surfactants (GSs) instead of simple
surfactants due to their lower critical micelle concentration, higher polarity, and more self-
assembly [33-38]. However, the object of this work is preparation and characterization of a
new bi-functional magnetically-separable and GS-based DES-catalyst with formula of
GS2+.2[FeCl4]- from the synthetic cationic GS as HBD and low-cost salt of FeCl3.6H2O as
HBA. This magnetic DES-catalyst has been used in our successful tactic for pyrrole synthesis
and benzoin condensation. In this new protocol which is faster than previously reported
methods, water was added in the end of the reactions, the magnetic aqueous solution of DES
was isolated by an external magnet, and the precipitated product was filtered and washed
with water (Scheme 1).
Scheme 1. Preparation and application of GS and MGSFe in synthesis of pyrroles.
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2. Experimental
2.1. General
All chemicals were purchased from Merck (Darmstadt, Germany) and used without further
purification, except for N,N-dimethyldodecylamine (97%) and epichlorohydrin which were
prepared from Sigma-Aldrich. The NMR spectra of GS and pyrroles were recorded by a
Bruker 500 MHz spectrophotometer in DMSO-d6 and D2O. The FT-IR spectra of GS,
MGSFe, and products as KBr discs were recorded on a Bruker spectrophotometer. Melting
points were determined by a Buchi B-540 apparatus. The absorbance UV-Vis spectra of GS
and MGSFe were run in acetonitrile by Bruker spectrophotometer. Comparative surface
tensions of GS and MGSFe were determined by a pendant drop method on a dataphysics
OCA 20 apparatus. The pH of samples was recorded at room temperature by inolab pH 7110.
The vibration sample-magnetometry (VSM) of Teflon sealed MGSFe was monitored by a
Lake Shore Cryotronics 7404 at 298 K.
2.2. Synthesis and characterization of 1,3-bis(dodecyldimethylammonio)-2-hydroxypropane
dichloride (GS)
The GS was prepared according to the previously reported methods [34-37] by reaction of (5
mmol) epichlorohydrin and N,N-dimethyldodecylamine (10 mmol) in n-butanol at reflux
conditions for 8 h [37]. After the completion of the reaction, the solvent was evaporated to
give a 39% white solid powder of GS. The structure of GS was assigned by FT-IR, 1H NMR,
melting point, and CHN analysis, although the given results were in accordance with some of
the previously reported literature data for GS [36].
2.3. Preparation and characterization of magnetic DES of MGSFe from GS and FeCl3.6H2O
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A mixture of GS (5 mmol) and FeCl3.6H2O (10 mmol) in a 150 mL round bottomed flask
o
was stirred for 2 h at 80 C. Then the mixture was kept under vacuum for 12 h for removing
of the volatile materials. The given MGSFe was a brownish soft solid that melted to a viscose
o
oil at 65-68 C and characterized by pendant drop tensiometry, UV-Vis spectroscopy, pH,
VSM, and magnetic responsivity analysis that were done for its aqueous solution by both
phase-inversion over hexane and drop-movement over the dichloromethane organic phase.
2.4. Catalytic evaluation of MGSFe
The catalytic potential of MGSFe was checked in both of benzoin condensation and synthesis
of substituted pyrroles.
2.4.1. Typical procedure for the MGSFe-catalyzed benzoin condensation
Benzaldehyde (5 mmol) and sodium cyanide (20 mol%) were added to a stirred solution of
o
H2O/EtOH and MGSFe (10 mol%) and the mixture was stirred for the given time at 80 C.
Then the aqueous phase of MGSFe was isolated by magnet and the magnetic catalyst MGSFe
was recovered in quantitative yield by evaporation of the added water with a vacuum pump,
while the precipitated benzoin was filtered, washed, dried, and isolated in 97% yield. The
purity of benzoin product was so that the spectroscopic data was further confirmed its
structure.
2-Hydroxy-1,2-bis(4-methylphenyl)ethanone (benzoin): white powder; mp = 80–81 °C. FT-
IR (KBr): 3445 (OH stretching), 2922, 1609 (C=O), 1574, 1511, 1419, 1285, 1183, 1117,
1083, 971, 806, 754, 724, 667 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 2.21 (s, 3 H, CH3),
2.30 (s, 3 H, CH3), 5.80 (d, 1 H, OH), 6.10 (s, 1 H, CH), 7.01 (d, J = 7.2 Hz, 2 HAr ), 7.25 (d,
13
J = 10.8 Hz, 4 HAr), 7.85 (d, J = 6.8 Hz, 2 HAr). C NMR (100 MHz, DMSO-d6): δ = 21.3,
21.7, 75.8, 124.8, 127.4, 128.1, 129.9, 135.96, 136.0, 141.5, and 197.0 ppm.
2.4.2. General procedure for the MGSFe-catalyzed synthesis of pyrroles
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For improved synthesis of pyrroles, MGSFe (10 mol%) was added to a mixture of the
corresponding 1,3-dicarbonyl (5 mmol), ammonium acetate (6 mmol), and benzoin
o
derivatives (5 mmol) and the mixture was stirred under the solvent-free conditions at 80 C.
After the completion of this step (detected by TLC monitoring), the catalyst and product were
isolated by two different procedures. In the first work-up, cold water (5 mL) was added,
aqueous phase of surfactant-based MGSFe was kept by magnet, the precipitated pyrrole
product was isolated, and the MGSFe catalyst was recovered in 99.9% yield after the vacuum
evaporation of water from the aqueous phase and reused. In the second alternative work-up,
ethyl acetate (50 mL) was added to dissolve the pyrrole product, the viscous catalyst was
isolated by magnet, and the product was obtained in pure form by evaporation of the EtOAc
from the organic phase.
2.4.3. Spectroscopic data for selected pyrrole products
2.4.3.1. 1-(2-Methyl-4,5-diphenyl-1H-pyrrol-3-yl)ethanone (Entry 1): Pale yellow solid, mp =
1
170–172 °C. FT-IR (KBr): 3177 (NH stretching), 1635 (C=O), 1455, 767, and 698 cm−1. H
NMR (DMSO-d6, 400 MHz) δ = 1.72 (s, 3H, CH3), 2.46 (s, 3H, CH3), 7.10–7.36 (m, 10H,
13
HAr), and 11.61 (br s, 1H, NH) ppm. C NMR (DMSO, 100 MHz): δ = 14.3, 30.9, 122.5,
122.6, 126.5, 127.0, 127.3, 128.6, 128.7, 131.2, 132.6, 135.7, 137.67, and 194.9 ppm.
2.4.3.2. Methyl 2-Methyl-4,5-diphenyl-1H-pyrrole-3-carboxylate (Entry 2): Pale yellow
needles; mp = 177–179 °C. IR (KBr): 3340, 1681, 1598, 1522, 756, 696 cm–1. 1H NMR (400
MHz, DMSO-d6): δ = 2.47 (s, 3 H, CH3), 3.45 (s, 3 H, OCH3), 7.07-7.24 (m, 10 HAr), 11.58
(s, 1 H, NH) ppm. 13C NMR (100 MHz, DMSO-d6): δ = 13.8, 50.5, 111.6, 123.0, 126.6,
127.3, 127.6, 127.9, 128.6, 130.1, 131.0, 132.7, 136.3, 136.9, 165.5 ppm.
2.4.3.3. Ethyl 2-Methyl-4,5-diphenyl-1H-pyrrole-3-carboxylate (Entry 3): Yellow solid; mp =
207–209 °C. FT-IR (KBr): 3306 (NH stretching), 1673 (C=O), 1598, 1442, 1480, 1181,
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1
1098, 758, 693 cm–1. H NMR (400 MHz, DMSO-d6): δ = 0.98 (s, 3 H, CH3), 3.34 (s, 3 H,
CH3), 3.91 (q, 2 H, CH2), 7.11–7.24 (m, 10 HAr), 11.56 (br s, 1 H, NH). 13C NMR (100 MHz,
DMSO-d6): δ = 13.7, 14.3, 50.8, 111.9, 123.0, 126.5, 127.2, 127.3, 127.9, 128.6, 131.1,
132.7, 136.3, 137.1, and 165.1 ppm.
2.4.3.4. 1-(4,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrole-3-yl)ethanone (Entry 4): White
crystals, mp = 234-235 °C. FT-IR (KBr): 3195, 1631, 1576, 1523, 1445, 829, and 798 cm−1.
1H NMR (400 MHz, DMSO-d6): δ = 1.82 (s, 3H, CH3), 3.33 (s, 3H, CH3), 7.08-7.40 (m, 8H,
13
HAr), and 11.73 (s, 1H, NH) ppm. C NMR (100 MHz, DMSO-d6): δ = 14.4, 31.1, 121.6,
122.5, 126.2, 128.8, 128.8, 131.1, 131.4, 132.1, 132.9, 136.0, 136.2, and 194.5 ppm.
2.4.3.5. Methyl 4,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrole-3-carboxylate (Entry 5): White
1
crystals; mp = 212-214 °C. IR (KBr): 3330, 1685, 1524, 1499 cm–1. H NMR (400 MHz,
DMSO-d6): δ = 3.33 (s, 3 H, CH3), 3.49 (s, 3 H, OCH3), 7.07-7.31 (m, 8 HAr), 11.80 (s, 1 H,
NH) ppm. 13C NMR (100 MHz, DMSO-d6): δ = 13.8, 50.6, 111.5, 122.0, 126.6, 128.1, 128.8,
129.0, 131.1, 131.5, 131.9, 132.8, 135.4, 136.8, and 165.3 ppm.
2.4.3.6. Ethyl 4,5-bis(4-chlorophenyl)-2-methyl-1H-pyrrole-3-carboxylate (Entry 6): Pale
yellow crystals, mp = 155–156 ◦ C. FT-IR (KBr): 3286, 1672, 1498, 1481, 831, and 732
1
cm−1. H NMR (400 MHz, CDCl3): δ = 1.09 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.58 (s, 3H,
CH3), 4.09 (q, J = 7.2 Hz, 2H, OCH2CH3), 6.99-7.26 (m, 8 HAr), and 8.66 (s, 1H, NH) ppm.
13C NMR (100 MHz, CDCl3): δ = 13.9, 14.0, 59.4, 112.4, 122.5, 126.5, 127.9, 128.1, 128.7,
130.4, 132.1, 132.5, 134.3, 136.1, and 165.5 ppm.
2.4.3.7. 1-[4,5-Bis-(4-fluoro-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid methyl ester
(Entry 8): Yellow solid, mp = 211-213 °C. 1H NMR (400 MHz, DMSO-d6 ): δ = 2.49 (s, 3H,
CH3), 3.50 (s, 3H, OCH3), 7.08-7.15 (m, 8 H, HAr), 11.64 (s, 1H, NH). 13C NMR (100 MHz,
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DMSO-d 6 ): δ = 13.3, 50.0, 114.2, 115.0, 115.2, 115.4, 115.5, 127.4, 127.3, 128.8, 128.9,
132.2 (1J C-F = 120.0 Hz), 132.4, 135.8, and 164. 9 ppm.
2.4.3.8. 2-Methyl-4,5-di-p-tolyl-1H-pyrrole-3-yl)-ethanone (Entry 10):: White solid, mp =
237-238 °C. 1H NMR (400 MHz, DMSO-d 6 ): δ = 1.74 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.34
(s, 3H, CH3), 2.46 (s, 3H, CH3), 6.99-7.05 (m, 4H, HAr), 7.09 (d, 2H, J = 7.6 Hz, HAr), 7.17
13
(d, 2H, J = 8.0 Hz, HAr), 11.52 (s, 1H, NH). C NMR (100 MHz, DMSO-d 6 ): δ = 13.8,
20.6, 20.8, 30.5, 121.5, 122.0, 126.4, 126.5, 128.7, 128.9, 129.4, 130.6, 134.0, 134.8, 135.3,
135.7, and 194.5 ppm.
3. Results and discussion
3.1. Synthesis and characterization of GS as HBD component of magnetic DES
To access to a GS-based magnetic DES with dual advantages of GSs and magnetic catalysts,
initially we designed a GS-based HBD component with two hydrophobic tails and two
quaternary nitrogen atoms plus one hydroxyl group attached to three carbon atoms in
hydrophilic head of its QAS part (Scheme 1). This GS has been previously synthesized for
o
other purposes [34-38], so we prepared it as a white solid with mp = 227-229 C following
the synthetic procedure [35] and assigned its structure by CHN, NMR, and FT-IR analyses.
The experimental CHN analysis of GS showed 66.90% C, 12.38% H, and 5.08% N in
excellent accordance with the calculated amounts of 66.95%, 12.36%, and 5.06%, for C, H,
and N, respectively.
1
In the H NMR (500 MHz) spectrum of GS in DMSO-d6 and D2O, the 68 hydrogens at
chemical shifts of 0.74, 1.23, 3.38, 3.45, 4.69 and 7.1 ppm are observable, so the protons
observed at chemical shifts δ = 3.45 ppm and δ = 4.6 ppm are related to the four methyl
groups attached to two positively charged nitrogen atoms in QAS parts of GS and CH-
methine group of this designed GS-based HBD (Fig. 1).
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Fig. 1. 1H NMR and 13C NMR spectra of GS as HBD component of magnetic DES.
The 13C NMR (125 MHz, DMSO-d6/D2O) spectrum of GS shows also all characteristic
aliphatic carbons at expected chemical shifts from < 20 ppm to < 70 ppm (Fig. 1). However,
the NMR data are in accordance with the structure of the as-prepared GS. The KBr-disk FT-
IR spectrum of GS (Fig. 2a) shows characteristic absorption bands for O-H stretching,
aliphatic C-H stretching, CH2-bending, and overlapped C-N/C-O stretching at 3100-3400 cm-
1, < 3000 cm-1, ~ 1480 cm-1, 1399 cm-1, and 1135-1015 cm-1, respectively.
3.2. Preparation of GS2+.2[FeCl4]-as a magnetic DES (MGSFe)
-
To access to magnetic DES, the incorporation of the magnetic chlorometallate anion FeCl4
into DES-structure was considered. So, the commercially available iron trichloride
hexahydrate was mixed with the as-prepared GS in controlled stoichiometric ratios of
components to give the iron-based magnetic responsive MGSFe. However, the vacuumed 1:1
o
mixture of GS and FeCl3.6H2O was a solid with mp = 105-109 C and no magnetic
responsively, while a highly viscose magnetic DES was obtained by vacuuming of the mixed
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GS and FeCl3.6H2O in mole ratio of 1:2. Therefore, the following structural formula has been
-
proposed for the MGSFe deep eutectic as GS2+.2FeCl4 (Scheme 2).
Scheme 2. The structural formula of the MGSFe.
3.3. Characterization of the MGSFe by FT-IR
The comparative FT-IR spectra of GS and the given Fe-based magnetic DES (Fig. 2)
supports contribution of the GS in the structural formula of MGSFe. So the FT-IR spectrum
of MGSFe shows characteristic broad absorption bands for O-H stretching at 3100-3300
centered at 3235, asymmetrical and symmetrical stretchings of C-H at 2988 cm-1, CH2
bending at 1461 cm-1, CH3 bending at 1399 cm-1, and overlapped C-O/C-N stretchings at
1165-1011 cm-1. All these mode of vibrations confirmed the structure of the as-prepared
MGSFe (Fig. 2)
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Fig. 2. The overlaid FT-IR spectra of GS and MGSFe.
3.4. Characterization of MGSFe by melting point analysis
While the synthesized GS and FeCl3.6H2O were solids with respective melting points of 222-
224 oC and 37 oC, a 1:2 mixture of them represented a deep reduction of melting point to 65-
68 oC. The reasonable response to this phenomenon is formation of a new polar and viscous
magnetic DE in borderline of the second and fourth types of DESs according to the Abbott’s
definition [10], where the head hydroxyl of GS is HBD and the two tetrachlorometallate
-
anions of FeCl4 are HBA components of DES.
3.5. Comparative UV-Vis spectra of MGSFe and GS
The comparative overlaid UV-Vis spectra of GS and MGSFe in acetonitrile show dissimilar
absorption wavelengths due to the diverse types of metal/ligand charge-transfer complexes.
As a result, a hypochromic shift for absorption peak at λmax = 295 nm together with
appearance of two new absorbance peaks at 320 nm and 375 nm maximum wavelengths in
-
MGSFe spectrum cnfirms the presence of the tetrachlorometallate anion of FeCl4 in the
complex structure of MGSFe (Fig. 3). No characteristic d-d-transition bands at 500-800 nm
was also found for MGSFe complex, presumably due to the half-fullness of 3d orbital in 3d5
electronic configuration Fe3+.
MGSFe
GS
1
0
225 250 275 300 325 350 375 400
-1
-2
λ
Fig. 3. Comparative UV-Vis spectra of MGSFe and GS.
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3.6. The pH measurements for MGSFe
The determined pH for the 0.01 M aqueous solutions of GS and FeCl3.6H2O were 6.45 and
-
1.20, respectively, while the acidity level of the aqueous solution of GS2+.2FeCl4 in the same
concentration was 2.28. This more than 4 units decrease in pH from 6.45 to 2.28 is attributed
to the incorporation of FeCl3 in the structure of MGSFe and the tolerant Lewis acidity of
-
hydrated Fe3+ in two tetrachlorometallate anions of FeCl4 .
3.7. Experiments for magnetic responsivity of MGSFe
-
The magnetic properties of the MGSFe bearing two tetrahedral anionic complexes of FeCl4
prepared from GS and FeCl3.6H2O was evaluated by three different experiments including,
VSM curve analysis depicted at room temperature and field range of -2 to 2 T, magnetic field
drop-deviation test, and magnetically phase-inversion experiment. As the VSM curve shows,
MGSFe is a very good magnetic-responsive material with effective magnetic parameters;
magnetic moment (Ms) = 0.1379 emu/g; Hci = 69.836 G, and Initial slop = 10.66 E-6
emu/g.G-1. Because of no response of GS to magnet, the magnetic activity of MGSFe is
-
related to the tetrachlorometallate anion FeCl4 and spin alignment of unpaired electrons in 3d
orbital of Fe3+ that bring about paramagneticity for MGSFe a material with moderately
effective magnetic moment (Fig. 4).
MGSFe
200
100
0
-20000 -10000
0
10000 20000
-100
-200
Moment/mass (memu/g)
Fig. 4. VSM curve of MGSFe.
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The second experiment to confirm the potent magnetic response of the as-prepared MGSFe is
the movement of the 20 wt% aqueous magnetic drop of MGSFe over the surface of the
dichloromethane organic phase by nearing of a neodymium-based magnet (NdFeB) with
magnetic power of 3.2 T that showed in a video (https://youtu.be/EvRavAmrCyo). An
alternative conjugated magnetic-responsivity and surface activity test was also performed to
show the deviation of pendant drops of MMGSs using an external magnetic field (Fig. 5).
Fig. 5. The pendant drop-deviation of GS and MGSFe under the NdFeB magnetic field.
As Fig. 5 shows, nearing of the NdFeB magnet caused the pulling of the magneto-responsive
pendant aqueous drops of MGSFe toward the magnet and their deviation from the normal
direction.
The third experiment to support the magnetic activity of this DES was evaluation of the
phase-inversion in the biphasic aqueous solution of 20 wt% MGSFe and n-hexane by
movement of the magnet on the surface of organic phase. For this purpose, the magnet was
vertically moved up and down to pull the aqueous phase of MGSFe by overcoming of its
magnetic power to both of the water-hexane interfacial tension (∼50 mN•m1) and gravity
(Fig. 6).
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Fig. 6. Phase-inversion in biphasic aqueous solution of MGSFe in hexane by rising of
NdFeB.
According to the results, response of the MFeGS to external magnet led to the phase-
inversion of magnetic DES by pulling of the MGSFe from the lower aqueous phase to upper
organic phase. This phase-inversion ability is very excellent for delivery of such magnetic
solutions from emulsional mixtures to targeted positions and also catalysis and make MGSFe
as a candidate for delivery of biomaterials to targeted positions.
3.8. The catalytic efficiency of MGSFe in synthesis of benzoin and substituted pyrroles
To efficient synthesis of benzoin, condensation of two moles of benzaldehyde in the presence
of NaCN was compared with similar reactions using 5-12 mol% MGSFe. Based on the
results, the pure benzoin was obtained in maximum 97% yield from the reaction run with 5
mol% MGSFe in mixture of EtOH/H2O for 20 min. The catalytic role of MGSFe as an acidic
catalyst is activation of aldehyde group together with help to controlling of pH by
bufferization of the CN- anion with the in situ produced HCN (Scheme 3).
Scheme 3. MGSFe-catalyzed benzoin condensation
Next, the three-component condensation of benzoin (A), ethyl acetoacetate (B), and
ammonium acetate (C) was selected as the model reaction and screened under various
conditions to access to optimized synthesis of 2-methyl-4,5-diphenyl-1H-pyrrole-3-
carboxylic acid ethyl ester (D) (Table 1).
Table 1
Opimization of conditions for model reactiona.
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Entry
Catalyst
Time
(min)
300
40
Isolated yield
TONb
TOFc
(mol %)
(%)
25
71
74
89
91
96
95
93
94
94
96
96
98
1
-
-
-
2
FeCl3.6H2O (10)
GS (10)
710
740
1780
1300
960
791
930
940
940
756
960
-
17.75
29.6
56
3
25
4
MGSFe (5)
MGSFe (7)
MGSFe (10)
MGSFe (12)
MGSFe (10)/EtOH
30
5
23
56.52
64
6
15
7
15
52.73
23.25
31.33
31.33
21.6
38.4
-
8
40
9
MGSFe (10)/EtOH:H2O 30
10
11
12
13
MGSFe (10)/H2O
SSA (0.02)d [28]
MSA(5) [29]
30
35
25
-/H2O:EtOH [30]
240
a 10 mmol of A, 10 mmol of B, 12 mmol of NH4OAc, catalyst, 80 oC.
b The mmol of product per mmol of catalyst
c The TON divided by reaction time.
d 0.02 g SSA is equal to 0.125 mmol of H+ [28].
As results show, the highest TON/TOF and catalytic activity is due to the MGSFe, when used
under solvent-free conditions (entry 6) that provides maximum contact between starting
materials and magnetic DES catalyst compared to reactions run in solvents (entries 7-9) or
nonmagnetic catalysts (entries 11 and 12). The main reasons for the high catalytic activity of
the MGSFe are molecular level size of catalyst, hydrophobic tails on QAS part of GS that
helps to dissolving of organic materials, polarity due to the existence of ionic sites on
-
surfactant head and anionic complex FeCl4 , tolerance Lewis acidity, and high diffusion
power of this liquefy magnetic DES resulted from synergistic effects between magnetic HBD
and gemini-surfactant-based HBA part (Scheme 3).
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The scope of the MGSFe-catalyzed synthesis of substituted pyrroles was then investigated by
the reactions of substituted benzoins and 1,3-dicarbonyls with NH4OAc (Table 2).
Table 2
Synthesis of substituted pyrroles using MGSFe.
O
R2
Ar
O
OH
Ar
MGSFe (10 mol%)
2 H2O
NH4OAc
°
Solvent-free/
R1
80 C
Ar
Ar
N
H
O
O
R1
Entry Ar
R2
R1
R2
Time
(min)
15
Yield
(%)
96
1
2
3
4
5
Ph
Ph
Ph
Me Me
Me OMe 30
96
Me OEt
Me Me
25
25
93
4-ClC6H4
4-ClC6H4
94
Me OMe 15
96
6
4-ClC6H4
4-ClC6H4
4-FC6H4
Me OEt
Me CF3
15
35
93
88
95
94
91
87
7
8
Me OMe 15
9
4-FC6H4
Me OEt
Me Me
Me Me
15
40
60
10
11
4-MeC6H4
4-MeOC6H4
As shown in Table 2, the catalyst is applicable to a broad substrate scope on 1,3-dicarbonyls
and benzoin derivatives. The purity of the isolated products were high for showing the
spectral data in accordance with the literature [28-31], although in some cases product was
recrystallized from H2O/EtOH.
To set up the mechanism for the GS2+.2[FeCl4]--catalyzed synthesis of pyrroles, the 3-amino-
but-2-enoic acid ethyl ester (E) was reacted with benzoin (A) in the presence of 5 mol%
MGSFe under solvent-free conditions and the desired pyrrole product (D) was quantitatively
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isolated after 10 min. So the following mechanism is proposed for the MGSFe-catalyzed
synthesis of substiuted pyrroles (Scheme 4).
-
Scheme 4. Proposed mechanism for GS2+.2FeCl4 -catalyzed synthesis of pyrroles.
3.9. Sheldon,s leaching [39] and reusability tests for MGSFe-catalyst
In our previous communications for synthesis of pyrroles, reusability of catalysts or reaction
medium was problematic [28-31], thus we evaluated the Sheldon,s leaching [39] and
reusability tests for molecular catalyst of MGSFe. The leaching test was run for a 50%
progressed model reaction to synthesis of pyrrole D and in the half time of the reaction, the
MGSFe was attracted by an external magnet and reaction was monitored by TLC. No
progress of reaction in the absence of catalyst demonstrated no leaching of HBD or HBA
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components from the magnetic DES catalyst of MGSFe into the reaction mixture. Next, we
investigated the reusability and recycling of MGSFe for the large-scale model reaction. So,
after the completion of the reaction, the MGSFe catalyst was recovered in quantitative yield
by a magnet following the second work-up method in experimental part. The recovered
catalyst was used in the four consequent cycles of the model reaction for synthesis of pyrrole
D without significant loss of the weight and catalytic activity of MGSFe (Fig. 6).
96
96
95
94
100
80
60
40
20
0
1
2
3
4
Reusability time
Fig. 6. Reusability of the MGSFe catalyst from the model reaction.
4. Conclusion
In conclusion, a novel magnetic gemini-surfactant-based deep eutectic (MGSFe) was
prepared from a synthetic gemini-surfactant (GS) and FeCl3.6H2O as HBA and HBD
components. The MGSFe was characterized by various methods, so the results of the
magnetic tests support the paramagnetic properties plus drop-deviation and phase-inversion
abilities of the aqueous phase of the as-prepared MGSFe. This magnetic DES represented an
excellent catalytic activity in developed high yielding benzoin condensation and synthesis of
substituted pyrroles without leaching or loss of mass of catalyst. The performance of the as-
prepared MGSFe DES-catalyst is due to its amphiphilicity, high polarity, structural duality,
molecular size, action as a homogeneous DES catalyst together with its magnetic separation
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as a heterogeneous catalyst, and easily reusing in addition to the high efficiency for
production of pyrrole products in a shorter reaction time than that ever reported.
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A novel bi-functional surfactant-based paramagnetic deep-eutectic catalyst
for improved benzoin condensation and multi-component synthesis of
pyrrole derivatives
Fatemeh Tamaddon,* SeydEhsan Tadayonfard
Graphical Abstract
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Highlights
 A novel gemini-surfactant-based magnetic deep eutectic liquid is MGSFe.
 The magnetic response of MGSFe is due to the counter anion [FeCl4.6H2O]-.
 MGSFe is a simply recovered and reusable magnetic molecular liquid.
 MGSFe efficiently catalyzes synthesis of benzoin and substituted pyrroles.
24