A novel dicationic ionic liquid as a highly effectual and dual-functional catalyst for the synthesis of 3-methyl-4-arylmethylene-isoxazole-5(4H)-ones

Article abstract of DOI:10.1007/s11164-018-3488-8

Abstract: A novel dicationic ionic liquid, N,N,N′,N′-tetramethyl-N,N′-bis(sulfo)ethane-1,2-diaminium mesylate [TMBSED][OMs]₂), has been produced, and identified by analysis of its ¹H NMR, ¹³C NMR, FT-IR, mass and thermal g

Full text of DOI:10.1007/s11164-018-3488-8

Res Chem Intermed
https://doi.org/10.1007/s11164-018-3488-8
A novel dicationic ionic liquid as a highly effectual
and dual-functional catalyst for the synthesis of 3-
methyl-4-arylmethylene-isoxazole-5(4H)-ones
1
1
•
Navid Irannejad-Gheshlaghchaei
1
•
Abdolkarim Zare
1
Seyed Sajad Sajadikhah
•
Alireza Banaei
Received: 5 February 2018 / Accepted: 22 May 2018
Ó Springer Science+Business Media B.V., part of Springer Nature 2018
0
0
0
Abstract A novel dicationic ionic liquid, N,N,N ,N -tetramethyl-N,N -bis(sulfo)ethane-
,2-diaminium mesylate [TMBSED][OMs] ), has been produced, and identified by
1
2
1
13
analysis of its H NMR, C NMR, FT-IR, mass and thermal gravimetric data. There-
after, it has been utilized as a highly effectual, homogeneous and dual-functional catalyst
to promote the multi-component reaction of ethyl acetoacetate, hydroxylamine
hydrochloride and arylaldehydes under solvent-free conditions for the synthesis of
3
-methyl-4-arylmethylene-isoxazole-5(4H)-ones. Due to the dual-functionality of
TMBSED][OMs] (possessing acidic and basic sites), and also having two sites of each,
[
2
it was a highly effective and general catalyst for the synthesis. Moreover, a plausible and
attractive mechanism based on the dual-functionality of the catalyst has been proposed.
&
&
1
Abdolkarim Zare
abdolkarimzare@pnu.ac.ir; abdolkarimzare@yahoo.com
Seyed Sajad Sajadikhah
sssajadi@pnu.ac.ir
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
123

N. Irannejad-Gheshlaghchaei et al.
Graphical Abstract
Cl
Cl
NMe
MeSO
Me N
3
MeSO
3
CH Cl
0 °C
MeSO H
2
2
3
+
2
ClSO
H
+
Me
N
2
NMe2
Me N
NMe2
3
2
2
2
1
r.t.
Neat
SO H SO H r.t.
60 °C
SO H SO H
3
3
3
3
[TMBSED][OMs]2
O
O
[
TMBSED][OMs] (10 mol%)
Ar
2
Ar-CHO
+
NH OH.HCl
N
2
O
Solvent-free, 70 °C
O
O
3
0-50 min
8
7-94%
0
0
0
Keywords N,N,N ,N -Tetramethyl-N,N -bis(sulfo)ethane-1,2-diaminium
mesylate ([TMBSED][OMs] ) Á Dicationic ionic liquid Á Dual-functional
2
catalyst Á 3-Methyl-4-arylmethylene-isoxazole-5(4H)-one Á Multi-component
reaction Á Solvent-free
Introduction
Isoxazole derivatives are a significant group of 5-membered heterocycles which
have a N–O bond in their ring. They have various utilizations in organic and
medicinal chemistry. Many compounds bearing the isoxazole moiety represent
medicinal and biological activities, such as antitumor [1], antifungal [2],
antibacterial [2], analgesic [3], hypoglycemic [4], anti-oxidant [5], anti-HIV
[
6], and COX-2 inhibitor [7]. These compounds are also applied as merocyanine
dyes [8], fluorescent chemosensors for fluoride anions [9], and androgen
antagonists [10]. 3-Methyl-4-arylmethylene-isoxazole-5(4H)-ones, as an important
member of isoxazole derivatives, can be prepared by the multi-component
reaction of ethyl acetoacetate, hydroxylamine hydrochloride and arylaldehydes in
?
the presence of a catalyst, e.g., sodium acetate/hm [11], nanoporous Na -
montmorillonite perchloric acid [12], phthalimide-N-oxyl salts [13], DL-tartaric
acid [14], 2-hydroxy-5-sulfobenzoic acid [15], N-bromosuccinimide [16], sulfated
polyborate [17], Ag/SiO [18], citric acid [19] and montmorillonite nanoclay/
ultrasound [20].
2
In recent times, ionic liquids have been broadly exploited as catalysts to promote
organic transformations. This extensive utilization is because of their unbeat-
able chemical and physical properties, including effectiveness, generality, capability
to catalyze numerous types of organic reactions, ability to use in solvent-free or
solution conditions, capacity to modify their physical and chemical properties by
changing cation and anion structures, negligible vapor pressure, adjustable hy-
drophobics, broad liquid range, unique electrochemical properties, controlled
miscibility, high thermal and chemical stability, good ionic conductivity and non-
flammability [21–28].
1
23

A novel dicationic ionic liquid as a highly effectual and…
Production of compounds by multi-component techniques has been broadly used
in organic and pharmaceutical chemistry. In this technique, at least three reactants
are condensed in one-pot to produce a complex product in which there are the main
elements of all the reactants. Accordingly, it is associated with many benefits with
respect to classical multi-step reactions, including enhancement of yield, decrement
of reaction time, minimizing application of volatile organic solvents, decreasing
generation of side-products/waste, saving energy and time, and adoption with green
chemistry [29–31].
Another important practical technique in synthetic organic chemistry is carrying
out reactions in solvent-free conditions. This technique has many advantages
compared with solution conditions, which consist of compliance with green
chemistry, higher yields, shorter reaction times, simplicity of reaction procedure,
workup and purification, increment of selectivity, need for milder conditions, high
effectiveness and minimization of by-product/waste synthesis [32–35].
Considering the above issues, it can be said that the production of 3-methyl-4-
arylmethylene-isoxazole-5(4H)-ones by a multi-component reaction using a novel
ionic liquid-catalyst under solvent-free conditions, is an ideal process. We report
this ideal process in this research with the production of a novel ionic liquid, i.e.,
0
0
0
N,N,N ,N -tetramethyl-N,N -bis(sulfo)ethane-1,2-diaminium mesylate ([TMBSED]
13
1
[OMs] ), and its characterization by analysis of H NMR, C NMR, FT-IR, mass
2
and TGA data. Thereafter, we have introduced [TMBSED][OMs] as a highly
2
effective, homogeneous and dual-functional catalyst for the synthesis of 3-methyl-4-
arylmethylene-isoxazole-5(4H)-ones via the multi-component reaction of ethyl
acetoacetate, hydroxylamine hydrochloride and arylaldehydes under solvent-free
conditions.
Experimental
Materials and methods
The reactants and solvents were purchased from Merck, Fluka or Acros.
Identification of the known compounds was accomplished by comparing their
melting points and spectroscopic data with the reported ones. Monitoring progress
of the reactions was achieved by thin layer chromatography (TLC). Recording the
melting points was performed using a B u¨ chi B-545 device in open capillary tubes.
1
Spectra were recorded on the following devices: H NMR (400 or 500 MHz) and
1
3
C NMR (100 or 125 MHz) on Bruker Advance DPX, FT-NMR spectrometers; TG
on Linseis STAPT 1000; IR on Shimadzu IR-60; and mass spectra on a
spectrometer 5975C VL MSD model Tripe-Axis Detector.
Preparation of [TMBSED][OMs]2
0
0
A solution of N,N,N ,N - tetramethylethane-1,2-diamine (5 mmol, 0.581 g) in dry
CH Cl (20 mL) was added dropwise to a stirring solution of chlorosulfonic acid
2
2
(
10 mmol, 1.165 g) in dry CH Cl (200 mL) over a period of 10 min at 10 °C. After
2
2
123

N. Irannejad-Gheshlaghchaei et al.
that, the reaction mixture was allowed to heat to room temperature (accompanied by
stirring), and stirred for another 4 h. The solvent was evaporated under reduced
pressure, and the liquid residue was triturated with dry petroleum ether (3 9 2 mL),
and dried under powerful vacuum at 90 °C to give [TMBSED][Cl] [24]. Then,
2
methanesulfonic acid (10 mmol, 0.96 g) was added dropwise to [TMBSED][Cl]
(5 mmol, 1.74 g) over a period of 3 min at room temperature under pressure of
nitrogen gas (to remove the HCl produced during the reaction). The resulting
2
mixture was stirred for 12 h at room temperature, and 2 h at 60 °C under a
continuous flow of nitrogen gas to give [TMBSED][OMs] as a viscous light-brown
liquid in quantity yield.
2
Spectroscopic data of [TMBSED][OMs]2
-
1
1
IR (KBr) m, cm : 874, 1045, 1173, 2000–3600. H NMR (400 MHz, DMSO-d ) d
6
1
ppm): 2.47 (6H, s) 2.86 (12H, s), 3.51 (4H, s), 9.94 (2H, br.). C NMR (100 MHz,
3
(
?
?
DMSO-d ) d (ppm): 39.9, 43.2, 50.9. Mass, m/z: 468 [M ], 469 [M ? 1].
6
General procedure for the production of 3-methyl-4-arylmethylene-
isoxazole-5(4H)-ones
A mixture of ethyl acetoacetate (1 mmol, 0.130 g), hydroxylamine hydrochloride
(
1.2 mmol, 0.083 g) and [TMBSED][OMs] (0.1 mmol, 0.047 g) was stirred at
2
7
0 °C for 1 min. Then, aldehyde (1 mmol) was added to it, and the resulting
mixture was stirred at the same temperature. After the reaction was completed (as
monitored by TLC), the mixture was cooled to room temperature, and the resulting
precipitate was washed by water (2 9 2 mL), dried under vacuum, and recrystal-
lized from methanol to give the p ure product.
Selected spectroscopic data of the products
1
H
3
-Methyl-4-phenylmethylene-isoxazole-5(4H)-one (A)
NMR (400 MHz,
DMSO-d ) d (ppm): 2.32 (3H, s, CH ), 7.61 (2H, t, J = 7.6 Hz, H ), 7.68 (1H, t,
6
3
Ar
1
J = 7.2 Hz, H ), 8.00 (1H, s, = CH), 8.43 (2H, d, J = 7.2 Hz, H ). C NMR
3
Ar
Ar
(
100 MHz, DMSO-d ) d (ppm): 11.8, 119.3, 129.4, 132.9, 134.0, 134.4, 152.2,
6
?
62.7, 168.3. Mass, m/z: 187 [M ].
1
1
3
-Methyl-4-(2,4-dimethylphenyl)methylene-isoxazole-5(4H)-one (B)
H
NMR
(
Ph), 2.46 (3H, s, CH -Ph), 7.15 (1H, d, J = 7.9 Hz, H ), 7.20 (1H, s, H ), 8.01
400 MHz, DMSO-d ) d (ppm): 2.30 (3H, s, CH -heterocycle), 2.35 (3H, s, CH -
6
3
3
3
Ar
Ar
1
3
(
1H, s, =CH), 8.33 (1H, d, J = 8.1 Hz, HAr). C NMR (100 MHz, DMSO-d ) d
6
(
ppm): 11.2, 19.5, 21.3, 126.3, 126.5, 127.9, 130.8, 131.1, 131.4, 141.1, 144.3,
?
49.3, 162.1. Mass, m/z: 215 [M ].
1
1
3
-Methyl-4-(4-methoxyphenyl)methylene-isoxazole-5(4H)-one
(C)
H
NMR
(
d, J = 8.8 Hz, H ), 7.89 (1H, s, =CH), 8.55 (2H, d, J = 8.8 Hz, H ). C NMR
400 MHz, DMSO-d ) d (ppm): 2.28 (3H, s, CH ), 3.91 (3H, s, OCH ), 7.18 (2H,
6
3
3
13
Ar
Ar
1
23

A novel dicationic ionic liquid as a highly effectual and…
(
100 MHz, DMSO-d ) d (ppm): 11.8, 56.3, 115.2, 115.7, 126.3, 137.4, 151.8, 162.8,
6
?
64.7, 169.1. Mass, m/z: 217 [M ].
1
3
-Methyl-4-(3,4-dimethoxyphenyl)methylene-isoxazole-5(4H)-one (D) IR (KBr) m,
cm : 776, 1247, 1276, 1376, 1459, 1508, 1558, 1589, 1608, 1730, 2939, 3096. H
-
1
1
NMR (500 MHz, DMSO-d ) d (ppm): 2.26 (3H, s, CH ), 3.83 (3H, s, OCH ), 3.90
6
3
3
(
3H, s, OCH ), 7.20 (1H, d, J = 8.6 Hz, H ), 7.85 (1H, s, =CH), 8.01 (1H, d,
3 Ar
1
3
J = 8.6 Hz, H ), 8.49 (1H, d, J = 2.0 Hz, H ). C NMR (125 MHz, DMSO-d ) d
Ar
Ar
6
(
ppm): 11.7, 55.9, 56.4, 112.1, 115.5, 116.0, 126.5, 131.5, 148.8, 152.2, 154.8,
?
62.7, 169.3. Mass, m/z: 247 [M ].
1
Cl
Cl
NMe
2
CH Cl
0 °C
MeSO H
2
2
3
Me N
NMe2
+
2
ClSO
3
H
Me
2
N
2
1
r.t.
Neat
SO H SO H r.t.
60 °C
3
3
[
TMBSED][Cl]2
MeSO3
MeSO3
NMe2
Me N
2
SO H SO H
3
3
[TMBSED][OMs]2
Scheme 1 Preparation of [TMBSED][OMs]
2
1
Fig. 1 H NMR spectrum of [TMBSED][OMs]
2
123

N. Irannejad-Gheshlaghchaei et al.
1
Table 1 Analysis of the H
H C
CH3
NMR data of
[TMBSED][OMs]
3
N
N
[CH SO ]
2
CH3
3 3 2
H C
3
SO H SO H
3
3
Chemical shift (ppm)
2.47
2.86
3.51
9.94
Integral
5.99
12.13
Singlet
4.11
1.97
Splitting pattern
Hydrogen kind
Hydrogen number
Singlet
Singlet
Broad
CH
6
3
–SO
3
CH –N
3
CH
2
3
SO H
12
4
2
1
Fig. 2 C NMR spectrum of the [TMBSED][OMs]
3
2
1
3
-Methyl-4-(2-methoxyphenyl)methylene-isoxazole-5(4H)-one
(E)
H
NMR
(
d, J = 8.4 Hz, H ), 7.52 (1H, t, J = 8.0 Hz, H ), 7.94 (1H, d, J = 7.6 Hz, H ),
400 MHz, DMSO-d ) d (ppm): 2.31 (3H, s, CH ), 3.85 (3H, s, OCH ), 7.27 (1H,
6
3
3
Ar
Ar
Ar
1
3
7
1
.97 (1H, s, =CH), 8.21 (1H, s, HAr). C NMR (100 MHz, DMSO-d ) d (ppm):
6
1.8, 55.8, 118.0, 119.5, 120.8, 127.1, 130.4, 134.2, 152.1, 159.6, 162.7, 168.3.
?
Mass, m/z: 217 [M ].
1
3
-Methyl-4-(4-hydroxyphenyl)methylene-isoxazole-5(4H)-one
(F)
H
NMR
(
400 MHz, DMSO-d ) d (ppm): 2.27 (3H, s, CH ), 6.97 (2H, d, J = 8.8 Hz, H ),
.83 (1H, s, = CH), 8.48 (2H, d, J = 8.8 Hz, H ), 11.06 (1H, s, OH). C NMR
Ar
6
3
Ar
1
3
7
1
23

A novel dicationic ionic liquid as a highly effectual and…
1
3
Table 2 Analysis of the C NMR data of [TMBSED][OMs]
2
H C
CH3
3
N
N
[
CH SO
]
3 2
CH3
3
H C
3
SO H SO H
3
3
Chemical shift (ppm)
Carbon kind
38.4–39.71
39.9
43.2
CH
50.9
CH
DMSO-d
6
(solvent)
CH
3
–SO
3
3
–N
2
Fig. 3 IR spectrum of [TMBSED][OMs]
2
(
100 MHz, DMSO-d ) d (ppm): 11.8, 114.4, 116.6, 125.1, 138.0, 152.1, 162.8,
6
?
64.3, 169.3. Mass, m/z: 203 [M ].
1
1
3
-Methyl-4-(2-hydroxyphenyl)methylene-isoxazole-5(4H)-one
(G)
H
NMR
(
400 MHz, DMSO-d ) d (ppm): 2.25 (3H, s, CH ), 6.93 (1H, t, J = 7.5 Hz, H ),
6
3
Ar
7
.0 (1H, d, J = 8.4 Hz, H ), 7.49 (1H, t, J = 7.7 Hz, H ), 8.08 (1H, s, =CH), 8.73
Ar Ar
1
3
(
1H, d, J = 8.1 Hz, H ), 11.04 (1H, s, OH). C NMR (100 MHz, DMSO-d ) d
Ar
6
(ppm): 11.2, 116.0, 116.5, 119.1, 119.5, 132.3, 136.7, 136.8, 145.1, 159.6, 162.2.
?
Mass, m/z: 203 [M ].
1
3
-Methyl-4-(4-dimethylaminophenyl)methylene-isoxazole-5(4H)-one
(H)
H
NMR (400 MHz, DMSO-d ) d (ppm): 2.23 (3H, s, CH ), 3.16 (6H, s, N(CH ) ),
6
3
3 2
1
3
6
.89 (2H, d, J = 8.8 Hz, H ), 7.65 (1H, s, =CH), 8.49 (2H, d, J = 8.8 Hz, H ).
C
Ar
Ar
NMR (100 MHz, DMSO-d ) d (ppm): 11.8, 40.4, 109.5, 112.1, 121.5, 138.1, 151.0,
6
?
54.9, 162.6, 170.3. Mass, m/z: 230 [M ].
1
123

N. Irannejad-Gheshlaghchaei et al.
Related bond or functional group
Table 3 FT-IR data of
TMBSED][OMs]
-1
Peak (cm
)
[
2
8
1
1
2
74
Symmetric N–S stretching vibration
Bending of S–OH
045
173
Stretching of S=O in mesylate
000–3600
3
OH groups of the two SO H
Fig. 4 Mass spectrum of the catalyst
3
-Methyl-4-(5-bromo-2-hydroxyphenyl)methylene-isoxazole-5(4H)-one
1
(I) IR
-
(
KBr) m, cm : 582, 825, 1105, 1259, 1368, 1477, 1578, 1602, 1735, 2918, 3076,
1
3
d, J = 8.8 Hz, H ), 7.63 (1H, d, J = 8.8 Hz, H ), 7.96 (1H, s, =CH), 8.92 (1H, d,
000–3350. H NMR (500 MHz, DMSO-d ) d (ppm): 2.26 (3H, s, CH ), 6.97 (1H,
6
3
Ar
Ar
1
3
J = 2.5 Hz, H ), 11.33 (1H, br., OH). C NMR (125 MHz, DMSO-d ) d (ppm):
Ar
6
11.6, 110.5, 118.4, 118.8, 121.6, 134.3, 138.9, 143.7, 159.1, 162.5, 168.6. Mass, m/
?
z: 282 [M ].
1
3
-Methyl-4-(4-chlorophenyl)methylene-isoxazole-5(4H)-one
(J)
H
NMR
(
400 MHz, DMSO-d ) d (ppm): 2.31 (3H, s, CH ), 7.70 (2H, d, J = 8.4 Hz, H ),
.00 (1H, s, =CH), 8.45 (2H, d, J = 8.4 Hz, HAr). C NMR (100 MHz, DMSO-d6)
6
3
1
Ar
3
8
d (ppm): 11.8, 119.9, 129.6, 131.7, 135.5, 139.1, 150.5, 162.7, 168.3. Mass, m/z: 221
?
M ].
[
3
cm : 769, 1118, 1236, 1381, 1482, 1568, 1606, 1618, 1735, 3112. H NMR
-Methyl-4-(2-fluorophenyl)methylene-isoxazole-5(4H)-one (K) IR (KBr) m,
-
1
1
(
500 MHz, DMSO-d ) d (ppm): 2.30 (3H, s, CH ), 7.37–7.43 (2H, m, H ), 7.70
6
3
Ar
13
1H, m, H ), 7.96 (1H, s, =CH), 8.55 (1H, t, J = 7.8 Hz, H ). C NMR
(
Ar
Ar
1
23

A novel dicationic ionic liquid as a highly effectual and…
Fig. 5 TG, DTG and DTA diagrams of [TMBSED][OMs]
2
(
125 MHz, DMSO-d ) d (ppm): 11.6, 116.3, 120.4, 121.4, 125.0, 132.8, 136.5,
6
?
42.2, 162.3, 162.8, 167.6. Mass, m/z: 205 [M ].
1
Results and discussion
Production and characterization of [TMBSED][OMs]2
0
0
0
At the outset, the dicationic ionic liquid N,N,N ,N -tetramethyl-N,N -bis(-
sulfo)ethane-1,2-diaminium mesylate ([TMBSED][OMs] ) was produced by the
2
0
0
reaction of N,N,N ,N - tetramethylethane-1,2-diamine (1 eq.) with chlorosulfonic
acid (2 eq.), and then with methanesulfonic acid (2 eq.) (Scheme 1).
1 13
TMBSED][OMs] was characterized by analyzing its H NMR, C NMR, FT-
[
IR, mass and thermal gravimetric analysis (TGA) data.
2
1
The H NMR spectrum of [TMBSED][OMs] is shown in Fig. 1. There are four
2
kinds of hydrogen in this compound; interpretation of the spectrum is summarized
in Table 1.
1
3
In the C NMR spectrum (Fig. 2), three peaks can be seen. The carbons related
to each peak are displayed in Table 2.
123

N. Irannejad-Gheshlaghchaei et al.
Fig. 6 TG diagram of the ionic liquid
O
O
[
TMBSED][OMs]2
Solvent-free
CHO
+
NH OH.HCl
+
N
2
O
O
O
Scheme 2 Reaction of ethyl acetoacetate with hydroxylamine hydrochloride and benzaldehyde
The FT-IR spectrum (Fig. 3) verified the presence of the expected functional
groups and bonds in [TMBSED][OMs] . The main IR data are summarized in
Table 3.
2
In the mass spectrum of [TMBSED][OMs] (Fig. 4), the peaks observed at m/z
2
?
68 and 469 corresponding to the molecular mass (M ) and (M ? 1).
?
4
Thermogravimetric analysis of [TMBSED][OMs]2 was also studied. The
corresponding diagrams are illustrated in Figs. 5 and 6. The thermogravimetry
TG), differential thermogravimetry (DTG) and differential thermal analysis (DTA)
(
show the main weight loss in one step (about at 285 °C).
Catalytic performance of [TMBSED][OMs] for the synthesis of 3-methyl-4-
2
arylmethylene-isoxazole-5(4H)-ones
The catalytic performance of the ionic liquid was examined for the synthesis of
3
-methyl-4-arylmethylene-isoxazole-5(4H)-ones. For the selection of the best
1
23

A novel dicationic ionic liquid as a highly effectual and…
Table 4 Production of 3-methyl-4-arylmethylene-isoxazole-5(4H)-ones using [TMBSED][OMs]
2
O
O
[
TMBSED][OMs]2 (10 mol%)
Ar
Ar-CHO
+
NH OH.HCl
+
N
2
O
Solvent-free, 70 °C
O
O
a
Yield (%)
Product
Ar
Time (min)
M.p. (°C) [Ref.]
A
B
C
D
E
F
G
H
I
C
6
H
5
40
40
30
40
50
50
30
30
40
30
40
93
91
90
92
89
92
91
91
87
93
94
141–143 (141–143) [20]
192–194 (193–195) [18]
178–179 (175–177) [16]
134–136 (135) [11]
157–159 (159–160) [19]
213–215 (214–215) [20]
199–201 (198–200) [16]
226–227) 224–226 ([20]
199–201
2,4-(Me)
4-MeOC
3,4-(MeO)
2-MeOC
2
C
6
H
3
6 4
H
2
C
6
H
3
6 4
H
4-HOC
6
H
H
4
4
2-HOC
6
4-(Me
5-Br-2-HOC
4-ClC
2-FC
2
N)C
6
H
4
6
H
3
J
6
H
4
128–130 (128–130) [14]
155–157
K
6 4
H
a
Isolated yield
Fig. 7 Acidic and basic sites of
TMBSED][OMs]
O
[
2
Me S O
O
Basic site
Acidic site
O
S
H
O
Me N
2
O
O
S O
Me N
2
O
H
Acidic site
Basic site
O
Me S O
O
reaction conditions (the catalyst mol% and temperature), the reaction of ethyl
acetoacetate (1 mmol) with hydroxylamine hydrochloride (1 mmol) and benzalde-
hyde (1 mmol) was studied in the presence of 5, 10 and 15 mol% of
[
The best results were obtained when 10 mol% of the catalyst was employed at
TMBSED][OMs] in the range of 60–80 °C in solvent-free conditions (Scheme 2).
2
7
0 °C (time: 40 min; yield: 93%).
After choosing the best mol% of [TMBSED][OMs] and temperature, these
conditions were utilized for the condensation of ethyl acetoacetate with
2
123

N. Irannejad-Gheshlaghchaei et al.
MeSO3
O
Me N
NMe2
Me
2
S
O
O
HO S O S O
3
O
H
H
NHOH
O
O
HO
EtO C
NHOH
[
TMBSED][OMs]2
[TMBSED][OMs]2
EtO C
2
EtO C
2
2
(
I)
MeSO3
Me
HO
MeSO3
Me N
NMe2
O
N
2
NMe
2
2
O
O S O
O
HO S O S O
S
3
3
O
S
O
H
O
Me
O S Me
O
H
H
O
HO
OEt
NOH
N
[TMBSED][OMs]
2
H
_
OH
_
H O
2
EtOH
O
CO Et
CO
(
2
Et
N
2
II)
MeSO3
Me Me
N
NMe
2
2
O
S
HO S O S O
O
H
3
O
O
H
HO
H
O
O
O
Ar
O
[
TMBSED][OMs]2
[TMBSED][OMs]
_
Ar
2
O
O
O
H O
N
N
N
(IV)
2
(
III)
Ar
N
O
O
The Isoxazole
Scheme 3 Proposed mechanism for the synthesis of 3-methyl-4-arylmethylene-isoxazole-5(4H)-ones
hydroxylamine hydrochloride and different arylaldehydes; the results are illustrated
in Table 4. According to these results, [TMBSED][OMs] was highly effective and
2
a general catalyst for the synthesis, because all the aldehydes, including
benzaldehyde and arylaldehydes bearing various substituents on the ortho, meta
and para positions, afforded the relevant 3-methyl-4-arylmethylene-isoxazole-
5
(4H)-ones with high yields in relatively short times.
Our novel ionic liquid is a dual-functional catalyst, because it has both acidic and
basic sites (the SO H group is acidic and the mesylate is basic); moreover, there are
3
two acidic sites, and two basic sites in the catalyst (Fig. 7). Consequently,
[
TMBSED][OMs] can in particular act as a highly effective and general catalyst for
2
1
23

A novel dicationic ionic liquid as a highly effectual and…
reactions which need to be both acidic and basic catalysts simultaneously; e.g., the
production of 3-methyl-4-arylmethylene-isoxazole-5(4H)-ones. This issue has been
shown in the reaction mechanism (Scheme 3). Two acidic and two basic sites of the
ionic liquid can simultaneously catalyze the reaction.
Conclusions
0
0
0
We have introduced N,N,N ,N -tetramethyl-N,N -bis(sulfo)ethane-1,2-diaminium
mesylate as a novel and homogeneous catalyst for the production of 3-methyl-4-
arylmethylene-isoxazole-5(4H)-ones. The merits of the presented protocol consist
of effectiveness, generality, relatively short reaction times, high yields, purifying the
products by a non-chromatography method (crystallization only), broad range of
substrate applicability, clean reaction profile, simple experimental procedure, low
cost, simple synthesis of the catalyst from available reactants, and dual-functionality
of the catalyst.
Acknowledgement We thank the Research Council of Payame Noor University for providing the
necessary research facilities and the financial support of this work.
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