Facile synthesis of spiro thiazolidinone via cyclic ketones, amines and thioglycolic acid by MCM-41-Schiff base-CuSO4·5H2O

Article abstract of DOI:10.1007/s11164-020-04283-9

Mesoporous MCM-41-supported Schiff base and CuSO₄?5H₂O (MCM-41@Schiff base-CuSO₄?5H₂O) catalyzed one-pot three-component condensation of cyclic ketones, amines and thioglycolic acid in toluene. And a series of corresponding spiro thiazolidinone derivatives were obtained in high yields (up to 97%). The synthesized catalyst was characterized via FT-IR, XRD, SEM, TEM and EDS and can be easily recovered by centrifugation and reused at 10 times without any change in catalytic activity. Moreover, the scale-up experiment also demonstrated the practicability of the catalytic system on the condensation. The possible mechanisms pave the way to investigation on the reactions of other cyclic ketones with thioglycolic acid.

Full text of DOI:10.1007/s11164-020-04283-9

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04283-9
Facile synthesis of spiro thiazolidinone via cyclic
ketones, amines and thioglycolic acid by MCM‑41‑Schif
base‑CuSO4·5H2O
Yonghai Hui1 · Yongfei Zhang1 · Yongyue Luo2 · Jianpeng Li1 · Yun Wang1 ·
Tianming Gao1 · Jialiang Xia1 · Sheng Wang1 · Shiqi Zhang1
Received: 21 June 2020 / Accepted: 26 September 2020
© Springer Nature B.V. 2020
Abstract
Mesoporous MCM-41-supported Schif base and CuSO4·5H2O (MCM-41@Schif
base-CuSO4·5H2O) catalyzed one-pot three-component condensation of cyclic
ketones, amines and thioglycolic acid in toluene. And a series of corresponding spiro
thiazolidinone derivatives were obtained in high yields (up to 97%). The synthesized
catalyst was characterized via FT-IR, XRD, SEM, TEM and EDS and can be easily
recovered by centrifugation and reused at 10 times without any change in catalytic
activity. Moreover, the scale-up experiment also demonstrated the practicability of
the catalytic system on the condensation. The possible mechanisms pave the way to
investigation on the reactions of other cyclic ketones with thioglycolic acid.
Keywords Heterogeneous · MCM-41 · Schif base · Thiazole · Condensation
Introduction
Thiazole is key structural subunits in heterocyclic chemistry and is present in many
natural products, pharmaceuticals, polymers and agrochemicals [1]. Because of the
signifcant medicinal value and physiological activity, such as anti-infammatory [2],
antitumoral [3], antiviral [4] and antibacterial activity [5], thiazole-containing deriv-
atives have attracted many chemical and medical researchers’ interest. And recently,
thiazole derivatives have also a wide range of applications in functional materials
[6–8]. Many diferent catalytic methods are available to synthesize thiazolidinone
*
Shiqi Zhang
qiqiqi249@163.com; hyhai97@126.com
1
College of Chemistry and Chemical Engineering, Key Laboratory of Clean Energy
Materials Chemistry of Guangdong Higher Education Institute, Lingnan Normal University,
Zhanjiang 524048, China
2
Agriculture Products Processing Research Institute, Chinese Academy of Tropical Agriculture
Science, Zhanjiang 524001, China
Vol.:(0123456789)
1 3

Y. Hui et al.
derivatives, among which the main catalysts to the synthesis are metal complexes[9],
ionic liquids [10–13], DCC [14, 15], organic acids [16–18] and enzymes [19, 20]
and magnetic materials [21]. However, most of these catalysts are homogeneous cat-
alysts that are difcult to separate and reuse, environmentally unfriendly and waste
control. Recently, the development of heterogeneous catalysts [10, 22] for the recy-
cling and catalytic life has become an important research feld for economic and
environmental [23]. And, to further address the idea of high activity, recyclability
and reusability, organic functional groups have emerged as the ordered mesoporous
siliceous material support because of their high active site to catalysis. Thus, design-
ing and searching for a highly efective and recyclable catalytic system is still
strongly interesting and desirable. Up to now, only two catalytic examples of cycli-
zation reaction with cycloketimines and mercaptoacetic acid have been reported.
One is HClO4–SiO2 system reported by Chakraborti’s group [24], and the other is
MCM-41@Schif base-metal complex system reported by our group [25]. And to
the best of our knowledge, all of the examples focus on aromatic aldehydes. Herein,
we reported our eforts on the development of the catalytic cyclization reaction of
spiro thiazolidinone with cycloketone, aromatic amines and mercaptoacetic acid by
MCM-41@Schif base-CuSO4·5H2O (Scheme 1).
Results and discussion
The amine-functionalized MCM-41 and Schif base-supported MCM-41 were pre-
pared according to the procedure shown in Scheme 1. Amine-functionalized MCM-
41 was achieved by MCM-41 and 3-(triethoxysilyl)propan-1-amine in ethanol [26].
Then, salicylaldehyde was added to suspension of MCM-41@NH2 in ethanol. The
mixture was fltered, and the residue was washed by dichloromethane and ether.
MCM-41@Schif base was dried under vacuum. The catalysts were characterized by
SEM, TEM and FT-IR.
The FT-IR spectra of MCM-41, MCM-41@NH2 (L1), MCM-41@Schif base
(L2) and L2-CuSO4·5H2O are shown in Fig. 1. The observation of prominent peaks
at 1085 cm−1 and 799 cm−1 in FT-IR spectrum of these catalysts was related to the
Si–O–Si band. In the FT-IR spectrum of MCM-41@NH2 (L1), new absorption
peaks appeared at around 1500 cm−1 and 1250 cm−1 that were corresponding to
Scheme 1 Synthesis of thiazolidinone and the ligands
1 3

Facile synthesis of spiro thiazolidinone via cyclic ketones,…
Fig. 1 IR patterns of MCM-41, amine-functionalized MCM-41 L1, MCM-41@Schif base L2 and L2-
CuSO4·5H2O
NH2 symmetric bending vibration and N–H bending vibration [27]. The character-
istic peaks at 2924 cm−1 and 2855 cm−1 were corresponding to vibration of C-H
stretching vibration peaks. The free ligand, MCM-41@Schif base (L2), exhibits a
C=N asymmetric bending vibration at 1646 cm−1 [28, 29]. Besides, compared with
the spectrum of L2, the absorption shift of C=N band in L2-CuSO4·5H2O struc-
ture moves to lower frequency, which considers that the C=N bond was successfully
coordinated with copper ion.
The low-angle XRD patterns and wide-angle XRD patterns of MCM-41, MCM-
41@NH2 (L1), MCM-41@Schif base (L2) and L2-CuSO4·5H2O are outlined
in Fig. 2, respectively. In the low-angle XRD patterns, the MCM-41 shows three
Fig. 2 Low-angle XRD patterns of ligands (a) and wide-angle XRD patterns of ligands (b)
1 3

Y. Hui et al.
difraction peaks at 2θ 2.2°, 3.8° and 4.4°, attributed to 100, 110 and 200 refec-
tion planes, respectively. The X-ray difraction pattern of the L1, L2 and L2-
CuSO4·5H2O reveals 2D hexagonally structured pores at low angles, and the dif-
fraction pattern is not observed at high angle because of the amorphous nature of
the hole wall [30]. In the wide-angle XRD patterns, there is a wide and intense peak
(2θ=23°) of amorphous silica. These results demonstrated that hexagonally ordered
mesostructures of L1, L2 and L2-CuSO4·5H2O remained unchanged after modify-
ing, compared with MCM-41. And, there is no difraction peak of metal phase in
XRD pattern of L2-CuSO4·5H2O. Combined with the FT-IR spectra analysis, we
think that the loaded copper salt is highly dispersed and its structure size is lower
than the size limit of detection [31].
The diferent catalysts were characterized by SEM as illustrated in Fig. 3a, b.
It was observed that the porous spherical structure exhibited no signifcant altera-
tions after the immobilization. The elemental composition of L2-CuSO4·5H2O was
illustrated by the energy-dispersive X-ray spectroscopy (EDS), and confrmed the
presence of C, O, Si and Cu elements (Fig. 3c). The TEM images of the MCM-41
and L2-CuSO4·5H2O catalyst show that the immobilized catalyst L2-CuSO4·5H2O
maintained hexagonally ordered mesostructures (Fig. 3e).
The activity of the catalysts as described above was tested in the model reaction
of cyclohexanone, aniline and thioglycolic acid in toluene at 110 °C. The results are
shown in Table 1. The reaction occurred smoothly in the presence of 0.005 g MCM-
41, MCM-41@NH2 (L1) and MCM-41@Schif base (L2), afording the correspond-
ing products in 38%, 45% and 60% (Table 1, entries 1, 3 and 4). At the same time, a
comparative experiment was performed. When the model reaction was catalyzed by
SiO2 leading to low yield, 4-phenyl-1-thia-4-azaspiro[4.5]decan-3-one (4a) has been
reported (Table 1, entry 2). Compared with MCM-41, the reaction would greatly be
facilitated by the pores [32]. And then, the metal salts were added in the reaction
system, because Schif base-metal salt shows high catalytic activity in the catalysis
feld. The copper salt-supported MCM-41@Schif base was found that the efciency
superior to other metal salts in the catalytic experiments. And the co-catalytic efect
of CuSO4·5H2O and L2 was better than that of other copper salts (Table 1, entries
Fig. 3 SEM images of MCM-41 (a) and L2-CuSO4·5H2O (b), EDS image of L2-CuSO4·5H2O (c), TEM
images of MCM-41 (d) and L2-CuSO4·5H2O (e)
1 3

Facile synthesis of spiro thiazolidinone via cyclic ketones,…
Table 1 Optimization of the
Entry Catalyst
Solvent
Time (h)
Yield (%) a
reaction conditions
1
2
3
4
5
6
7
8
MCM-41
SiO2
L1
Toluene
Toluene
Toluene
Toluene
10
10
10
10
10
10
10
10
10
10
10
10
10
38
11
45
60
79
93
77
70
84
50
10
85
Trace
Trace
Trace
Trace
76/83
78/85
79/93
79
L2
L2-Cu(NO3)2·3H2O Toluene
L2-CuSO4·5H2O
Toluene
L2-Cu(AcO)2·H2O Toluene
L2-CuCl2·2H2O
L2-CuCl
CuSO4·5H2O
Toluene
Toluene
Toluene
H2O
EtOH
CH3CN
CH3COCH3 10
CH2Cl2
THF
Toluene
Toluene
Toluene
–
9
10
11
12
13
14
15
16
17b
18c
19d
20
21
22e
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
L2-CuSO4·5H2O
10
10
10
10
10
10
Toluene
Toluene
8/12 80/94
10 94
Reaction conditions (unless noted otherwise): cyclohexanone
(0.1 mmol), aniline (0.1 mmol), thioglycolic acid (0.12 mmol), L
(0.005 g) and metal salt (5 mol%) in toluene (0.5 mL) at 110 °C 10 h
aIsolated yield
bUse 3 mol%/10 mol% CuSO4·5H2O
cUse 0.0025/0.0100 g L2
d0.3 mL/1.0 mL toluene
eThe complex of L2-CuSO4·5H2O was pre-prepared
5–9). After solvent screening, toluene proved to be the best choice for the reaction
(Table 1, entry 6). The reaction was also monitored with diferent ratios of L2 and
CuSO4·5H2O, and the results showed that 0.0050 g L2/5 mol% CuSO4·5H2O of cat-
alyst was the best ratio for the catalytic reaction (Table 1, entries 17 and 18). In the
subsequent investigation of the solvent consumption of the system, the yield of the
reaction decreased with the decrease in the amount of solvent, even in the solvent-
free condition (Table 1, entries 19 and 20). Moreover, shortening the reaction time
resulted in a lower yield, and prolonging reaction time could not improve the yield
(94% yield), either. Finally, compared with the catalyst prepared in situ, the same
result was obtained with the pre-prepared complex of L2-CuSO4·5H2O (Table 1,
entry 22).
1 3

Y. Hui et al.
Table 2 Substrate scope for the
Entry
R
Product
Yield (%)a
Yield (%)b
condensation reaction
1
2
3
4
5
6
7
8
C6H5
p-FC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
93
82
85
93
95
93
95
92
97
–
63 [24]
70 [33]
71 [34]
72 [35]
68 [36]
77 [37]
–
[38]
–
–
–
–
–
p-ClC6H4
p-BrC6H4
p-CH3C6H4
p-CH3OC6H4
m-FC6H4
m-ClC6H4
m-BrC6H4
m-CH3OC6H4
m-CH3C6H4
o-CH3OC6H4
C6H5CH2
9
10
11
12
13
4j
4k
4l
–
90
96
4m
Reaction conditions (unless noted otherwise): cyclohexanone
(0.1 mmol), aniline (0.1 mmol), thioglycolic acid (0.12 mmol), L2
(0.005 g) and CuSO4·5H2O (5 mol%) in toluene (0.5 mL) at 110 °C
10 h
aIsolated yield
bYield of reference
Scheme 2 The cyclization of cyclohexanone, aniline and thioglycolic
Under the optimized conditions, an investigation of the substrate scope of this
reaction of the scope of cyclohexanone, amines and thioglycolic acid was examined
(Table 2). Compound 4a with no substituents in the phenyl ring of amine was high
active, 93% yield. The best compounds were obtained when withdrawing substitu-
ents (F, Cl and Br) and donating substituents (CH3 and OCH3) were introduced in
para position of the amines (4b–f). Halogen substituents in meta position are well
tolerated, and>90% yields were obtained (4 g–i). However, in comparison with
entries 7–9, none of the desired product was obtained when meta-methoxy and
meta-methyl aniline were used in this reaction. We thought the electronic efect is
the main reason, because only at the meta position lower the ortho and para elec-
tron-donating groups on the increasing electron density. Benzylamine can also be
used as a substrate with the current catalytic system, the corresponding product 4 m
was obtained in 96% yield (Table 2, entry 13) (Scheme 2).
We then examined the synthetic utility of the catalyst system, a scaled-up reaction
of cyclohexanone, aniline and thioglycolic acid by using the L2-CuSO4·5H2O was
1 3

Facile synthesis of spiro thiazolidinone via cyclic ketones,…
performed. As shown in Scheme 3, by treatment of the starting materials (20 mmol),
a good yield (90%) was still aforded (Scheme 3, Eq. 1). Subsequently, under the
optimized conditions, the three-component reaction of cyclopentanone (and cyclo-
heptanone), aniline and thioglycolic acid was investigated. Disappointingly, the spiro
thiazolidinone derivatives could not be detected with the cyclopentanone and cyclo-
heptanone, and the ring opening of 2-mercapto-N-phenylacetamide 4n was pro-
duced (Scheme 3, Eqs. 2 and 3). And then, the experiment of cyclohexanone and 4n
was performed (Scheme 3, Eq. 4). What is more, Chakraborti et al. [24] introduced
the main amide product 4n formed by condensation of open-chain ketone (such as
acetophenone) is obtained. We think that the steric distortion of cyclopentanone and
cycloheptanone may be responsible for the increase in steric resistance. Unfortu-
nately, the target product 4a was not observed. According to our previous works
[25], plausible reaction mechanisms are explained in Scheme 4. In the frst step, the
thioglycolic acid is activated by the Lewis acid catalyst L2-CuSO4·5H2O to start the
addition reaction of N-cyclohexylideneaniline that is synthesized by cyclohexanone
and aniline. An intramolecular cyclocondensation is then promoted by the Cu thio-
glycolic acid and aniline of the intermediate. Finally, the L2-Cu-spiro thiazolidinone
is converted to the product by the loss of H2O (Route A). Additionally, L2 has some
catalytic activity to this reaction. The cyclization reaction may proceed via phenolic
hydroxyl group of L2 to enhance nucleophilicity of mercapto group of thioglycolic
acid, which causes thioglycolic acid facile addition on the imino. Subsequently, the
cyclocondensation product of 4-thiazolidinone is formed in successive steps (Route
B) [20].
Under optimized conditions, as a heterogeneous catalyst, the recyclability of
MCM-41@Schif base-CuSO4·5H2O was examined in the cyclization reaction
Scheme 3 Scaled-up version and condensation of other cyclic ketones
1 3

Y. Hui et al.
Scheme 4 Proposed catalytic mechanism
(Fig. 4). Following the completion of reaction, the catalyst was recovered by cen-
trifugation and dried, and then the amount of substrates was determined accord-
ing to the amount of recovered catalyst for the next cycle. It was found that the
catalyst was able to perform the reaction for ten runs without signifcant efect
on the yield. The spiro thiazolidinone 4a was still obtained with 90% yield after
the tenth recycle. In addition, the recovered catalyst was characterized by FT-IR,
which was consistent with the spectrum of the original catalyst. In the “hot fltra-
tion” test, the separated organic phase was used as catalyst for the reactions, but
no product was observed.
Fig. 4 Catalyst recycling studies
1 3

Facile synthesis of spiro thiazolidinone via cyclic ketones,…
Experimental
All chemicals and mesoporous materials were purchased from Adamas-Beta and
used without further purifcation. The purity of compounds was checked by thin-
layer chromatography (TLC) using ethyl acetate/petroleum ether(v/v) as an elu-
ent, and FT-IR spectrum was recorded on Bruker Equinox 55 FT-IR spectropho-
1
tometer as KBr discs. The H NMR and 13C NMR spectra were recorded on an
1
INOVA-400 spectrometer operating at 400 MHz for H and 100 MHz for 13C in
DCl3 using TMS as an internal standard. The prepared ligands were characterized
by FT-IR, XRD, SEM and TEM.
Typical procedure for synthesis of thiazolidinone derivatives
A mixture of L2 (0.005 g) and CuSO4·5H2O (5 mol%) in toluene (0.5 mL)
was stirred at room temperature for 0.5 h. Then, cyclohexanone (0.0098 g,
0.10 mmol), aromatic amine (0.0093 g, 0.10 mmol) and thioglycolic acid
(0.014 g, 0.12 mmol) were added and stirred at refux for 10 h. The process was
monitored by TLC. The reaction mixture was purifed by column chromatography
on silica gel using petroleum ether/ethyl acetate to give the product 4a.
Physical and spectroscopic data for 4a–4m
4‑Phenyl‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4a
1
Yellow solid, 90% yield, m.p: 169 °C. H NMR (400 MHz, CDCl3) δ 7.50–7.39
(m, 3H), 7.20–7.12 (m, 2H), 3.69 (s, 2H), 2.03–1.96 (m, 2H), 1.77–1.54 (m, 8H).
4‑(4‑Fluorophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4b
White solid, 82% yield, m.p: 170–171 °C. 1H NMR (400 MHz, CDCl3) δ 7.15 (d,
J = 1.5 Hz, 2H), 7.13 (s, 2H), 3.67 (s, 2H), 1.97 (d, J = 8.2 Hz, 2H), 1.79–1.54 (m,
8H).
4‑(4‑Chlorophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4c
1
White solid, 85% yield, m.p: 180 °C. H NMR (400 MHz, CDCl3) δ 7.45–7.41
(m, 2H), 7.12–7.08 (m, 2H), 3.67 (s, 2H), 1.97 (d, J = 8.3 Hz, 2H), 1.83–1.57 (m,
8H).
1 3

Y. Hui et al.
4‑(4‑Bromophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4d
White solid, 93% yield, m.p: 184–185 °C. 1H NMR (400 MHz, CDCl3) δ
7.63–7.54 (m, 2H), 7.06–7.01 (m, 2H), 3.67 (s, 2H), 1.97 (d, J = 8.3 Hz, 2H),
1.82–1.49 (m, 8H).
4‑p‑Tolyl‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4e
1
Yellow solid, 95% yield, m.p: 189 °C. H NMR (400 MHz, CDCl3) δ 7.24 (d,
J=0.6 Hz, 2H), 7.05–7.01 (m, 2H), 3.67 (s, 2H), 2.38 (s, 3H), 1.97 (d, J=10.3 Hz,
2H), 1.75–1.53 (m, 8H).
4‑(4‑Methoxyphenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4f
Yellow solid, 93% yield, m.p: 144–145 °C. 1H NMR (400 MHz, CDCl3) δ 7.09–7.05
(m, 2H), 6.96 (d, J=9.0 Hz, 2H), 3.83 (s, 3H), 3.67 (s, 2H), 1.96 (d, J=10.6 Hz,
2H), 1.80–1.57 (m, 8H).
4‑(3‑Fluorophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4g
White solid, 95% yield, m.p: 156–157 °C. 1H NMR (400 MHz, CDCl3) δ 7.53–7.47
(m, 1H), 7.28 (dd, J=8.2, 1.8 Hz, 1H), 7.18–7.14 (m, 1H), 6.84 (tdd, J=8.3,
2.5, 0.9 Hz, 1H), 3.52 (s, 2H), 2.20–2.05 (m, 5H), 1.70–1.57 (m, 5H). 13C NMR
(100 MHz, CDCl3) δ 172.5, 162.3, 144.4, 130.7, 123.6, 116.3, 109.8, 74.1, 43.4,
39.1, 25.6, 24.9. Analysis calc. for C14H16FNOS (265.09): C, 63.37; H, 6.08; N,
5.28. Found: C, 63.21; H, 6.03; N, 5.43.
4‑(3‑Chlorophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4h
1
White solid, 92% yield, m.p: 180 °C. H NMR (400 MHz, CDCl3) δ 7.64 (t,
J=2.0 Hz, 1H), 7.39–7.37 (m, 1H), 7.28 (s, 1H), 7.13–7.10(m, 1H), 3.52 (s, 2H),
2.19–2.06 (m, 5H), 1.74–1.56 (m, 5H). 13C NMR (100 MHz, CDCl3) δ 172.7,
149.8, 135.3, 130.7, 128.7, 126.9, 120.8, 68.4, 43.4, 39.8, 25.3, 24.9. Analysis calc.
for C14H16FNOS (265.09): C, 59.67; H, 5.72; N, 4.97. Found: C, 59.60; H, 5.91; N,
4.85.
4‑(3‑Bromophenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4i
White solid, 97% yield, m.p: 182–183 °C. 1H NMR (400 MHz, CDCl3) δ 7.58–7.54
(m, 1H), 7.36–7.31 (m, 2H), 7.12–7.09 (m, 1H), 3.67 (s, 2H), 2.01–1.95 (m, 2H),
1.84–1.58 (m, 8H). 13C NMR (100 MHz, CDCl3) δ 171.9, 143.9, 130.1, 127.5,
126.9, 123.5, 121.1, 69.2, 43.5, 39.8, 26.0, 24.2. Analysis calc. for C14H16BrNOS
(325.01): C, 51.54; H, 4.94; N, 4.29. Found: C, 51.41; H, 4.87; N, 4.55.
4‑(2‑Methoxyphenyl)‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4l Yellow solid, 90%
1
yield, m.p: 169–170 °C. H NMR (400 MHz, CDCl3) δ 8.35 (dd, J = 8.0, 1.6 Hz,
1 3

Facile synthesis of spiro thiazolidinone via cyclic ketones,…
1H), 7.08–7.06 (m, 1H), 6.99–6.94 (m, 1H), 6.89 (dd, J = 8.1, 1.3 Hz, 1H), 3.89 (s,
3H), 3.53 (s, 2H), 2.21–2.16 (m, 2H), 2.12–1.75 (m, 3H), 1.75–1.50 (m, 5H). 13
C
NMR (100 MHz, CDCl3) δ 172.0, 163.4, 129.1, 128.8, 122.5, 116.1, 112.9, 68.1,
56.4, 39.2, 25.8, 24.5. Analysis calc. for C15H19NO2S (277.11): C, 64.95; H, 6.90;
N, 5.05. Found: C, 64.87; H, 6.92; N, 5.15.
4‑Benzyl‑1‑thia‑4‑azaspiro[4.5]decan‑3‑one 4m White solid, 96% yield, m.p:
1
249–250 °C. H NMR (400 MHz, CDCl3) δ 7.34–7.27 (m, 4H), 7.25–7.21 (m,
1H), 4.58 (s, 2H), 3.63 (s, 2H), 1.81–1.52 (m, 10H). 13C NMR (100 MHz, CDCl3)
δ 171.8, 137.5, 129.2, 128.9, 127.2, 64.0, 47.4, 36.1, 35.9, 33.1, 25.6, 24.6. Analy-
sis calc. for C15H19NOS (261.12): C, 68.93; H, 7.33; N, 5.36. Found: C, 68.72; H,
7.50; N, 5.33.
2‑Mercapto‑N‑phenylacetamide 4n White solid, m.p: 159–160 °C. 1H NMR
(400 MHz, CDCl3) δ 8.41 (s, 1H), 7.61 (d, J = 7.6 Hz, 2H), 7.35 (t, J = 8.0 Hz,
2H), 7.16 (d, J = 7.4 Hz, 1H), 3.66 (d, J = 9.0 Hz, 2H), 2.30 (s, 1H).
Conclusion
In summary, MCM-41-Schif base-CuSO4·5H2O has been synthesized and was
characterized using various spectroscopic techniques. Its catalytic activity as
heterogeneous catalyst for the cyclocondensation of spiro thiazolidinone deriva-
tives through a three-component one-pot synthesis has been described. The corre-
sponding products were obtained in good yields (up to 97%). The reaction could
be amplifed to gram scales under the optimized conditions without loss of yield.
What is more, the catalyst showed a good level of recyclability (90% yield was
aforded after ten cycles of reaction). Finally, comparative investigations of thio-
glycolic acid and other cyclic ketones and the proposed reaction of by-product
and cyclohexanone confrm the mechanism might be operating in the intermedi-
ate of imine. In our group, further applications of the ordered mesoporous sili-
ceous material to other reactions are ongoing.
Acknowledgements The authors are grateful to the Special Fund for Outstanding Talented Young and
Middle-aged Persons of Lingnan Normal University (No. ZL1908), Guangdong Natural Science Foun-
dation (Grant Nos. 2018A030307022 and 2020A1515010252) and Adamas-beta Chemical Co. for all
chemical reagents.
References
1. B. Eftekhari-Sis, M. Zirak, A. Akbari, Chem. Rev. 113, 2958 (2013)
2. Z.Q. Li, X.Z. Li, M.B. Su, L.X. Gao, Y.B. Zhou, B.C. Yuan, X.L. Lyu, Z.Q. Yan, C.J. Hu, H.
Zhang, C. Luo, Z. Chen, J. Li, Y.J. Zhao, J. Med. Chem. 63, 4388 (2020)
1 3

Y. Hui et al.
3. S.D. Shen, M. Hadley, K. Ustinova, J. Pavlicek, T. Knox, S. Noonepalle, M.T. Tavares, C.A.
Zimprich, G.P. Zhang, M.B. Robers, C. Bařinka, A.P. Kozikowski, A. Villagra, J. Med. Chem.
62, 8557 (2019)
4. S. Sinha, S.L. Manju, M. Doble, ACS Med. Chem. Lett. 10, 1415 (2019)
5. E.S.H. El-Tamany, S.Z. Sowellim, A.A. Hamed, A.S. Radwan, Res. Chem. Intermed. 41, 2675
(2015)
6. L. Zhang, W.Y. Deng, B.Q. Wu, L. Ye, X.F. Sun, Z.F. Wang, K. Gao, H.B. Wu, C.H. Duan, F.
Huang, Y. Cao, ACS Appl. Mater. Int. 12, 753 (2020)
7. K. Dölling, H. Zaschke, H. Schubert, J. Prakt. Chem. 321, 643 (1979)
8. L.L. Zhang, X.J. Liu, S.S. Lu, J. Liu, S.L. Zhong, Y.B. Wei, T. Bing, N. Zhang, D.H. Shangguan,
ACS Appl. Bio. Mater. 3, 2643 (2020)
9. A. Ahlawat, P. Khatkar, V. Singh, S. Asija, Res. Chem. Intermed. 44, 4415 (2018)
10. N. Azgomi, M. Mokhtary, J. Mol. Catal. A Chem. 398, 58 (2015)
11. A. Daghlavi, E. Kowsari, M. Abdouss, M.H. Ghasemi, E. Asadi, Res. Chem. Intermed. 46, 3593
(2020)
12. A.K. Yadav, M. Kumar, T. Yadav, R. Jain, Tetrahedron Lett. 50, 5031 (2009)
13. L.D. Khillare, M.R. Bhosle, A.R. Deshmukh, R.A. Mane, Res. Chem. Intermed. 41, 8955 (2015)
14. T. Srivastava, W. Haq, S.B. Katti, Tetrahedra 58, 7619 (2002)
15. Z. Turgut, C. Yolacan, F. Aydogan, E. Bagdatli, N. Ocal, Molecules 12, 2151 (2007)
16. M. Singh, M. Saquib, S.B. Singh, S. Singh, P. Ankit, S. Fatma, J. Singh, Tetrahedron Lett. 55, 6175
(2014)
17. M.A. Chaudhari, J.B. Gujar, D.S. Kawade, P.V. Shinde, M.S. Shingare, Res. Chem. Intermed. 41,
10027 (2015)
18. H. Mohammadi, H.R. Shaterian, Res. Chem. Intermed. 46, 1109 (2020)
19. H. Zheng, Y.J. Mei, K. Du, Q.Y. Shi, P.F. Zhang, Catal. Lett. 143, 298 (2013)
20. U.R. Pratap, D.V. Jawale, M.R. Bhosle, R.A. Mane, Tetrahedron Lett. 52, 1689 (2011)
21. L. Shiri, A. Ghorbani-Choghamarani, M. Kazemi, Res. Chem. Intermed. 43, 2707 (2017)
22. N. Foroughifar, S. Ebrahimi, Chin. Chem. Lett. 24, 389 (2013)
23. J.S.M. Lee, A.I. Cooper, Chem. Rev. 120, 2171 (2020)
24. D. Kumar, M. Sonawane, B. Pujala, V.K. Jain, S. Bhagat, A.K. Chakraborti, Green Chem. 15, 2872
(2013)
25. H.X. Pang, Y.H. Hui, K. Fan, X.J. Xing, Y. Wu, J.H. Yang, W. Shi, Z.F. Xie, Chin. Chem. Lett. 27,
335 (2016)
26. C.C. Wang, S.L. Xie, Z.F. Xie, Y.H. Hui, Chin. J. Org. Chem. 33, 2391 (2013)
27. E.M. Flefel, W.A. Ei-Sayed, A.M. Mohamed, W.I. Ei-Sofany, H.M. Awad, Molecules 22, 170
(2017)
28. N. Amirmahami, N.O. Mahmovdi, M. Malakootian, A. Pardakhty, N. Seyedi, Res. Chem. Intermed.
46, 4595 (2020)
29. M. Nikoorazm, A. Ghorbani-Choghamarani, H. Mahdavi, S.M. Esmaeili, Micropor. Mesopor. Mat.
211, 174 (2015)
30. M. Nikoorazm, A. Ghorbani-choghamarani, N. Noori, Res. Chem. Intermed. 42, 4621 (2016)
31. S. Karthikeyan, M.P. Pachamuthu, M.A. Isaacs, S. Kumar, A.F. Lee, G. Sekaran, Appl. Catal. B
Environ. 199, 323 (2016)
32. K. Fan, Y.H. Hui, X.M. Hu, W. Shi, H.X. Pang, Z.F. Xie, New J. Chem. 39, 5916 (2015)
33. Y.H. Wu, Y.P. Jin, J.L. Cao, P. Yilihan, Y.J. Wen, J.X. Zhou, J. Ind. Eng. Chem. 20, 2792 (2014)
34. D. Kaminskyy, D. Khyluk, O. Vasylenko, R. Lesyk, Tetrahedron Lett. 53, 557 (2012)
35. E.M. Flefel, H.H. Sayed, A.I. Hashem, E.A. Shalaby, W. Ei-Sofany, F.M.E. Abdel-Megeid, Med.
Chem. Res. 23, 2515 (2014)
36. D.V. Kaminśkyi, Farmatsevtichnii Zhurnal (Kiev, Ukraine) 6, 36 (2010)
37. A.K. Chakraborti, Indian Pat. Appl., 2011DE03148
38. K.J. Mehta, J. Inst. Chem. (India) 50, 81 (1978)
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional afliations.
1 3