An efficient synthesis of spiro[indoline-3,9-xanthene]trione derivatives catalyzed by magnesium perchlorate

Article abstract of DOI:10.3390/molecules22081295

A simple and efficient method for the synthesis of spiro[indoline-3,9-xanthene]trione derivatives by means of condensation between isatins and 1,3-cyclohexanedione in the presence of a catalytic amount of magnesium perchlorate at 80^?C in 50% aqueous ethanol medium has been described. Notably, the present method offers desirable advantages of good yields, simplicity of workup procedure, easy purification, and reduced reaction times.

Full text of DOI:10.3390/molecules22081295

molecules
Article
An Efficient Synthesis of Spiro[indoline-3,90-
xanthene]trione Derivatives Catalyzed by
Magnesium Perchlorate
Chunfeng Chen 1,2, Chunlei Lv 2, Jianfeng Liang 2, Jianqing Jin 2, Lijun Wang 1, Chunlei Wu 1,
*
and Runpu Shen 1,
*
1
Department of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing 312000, Zhejiang,
China; ljwang@usx.edu.cn
Zhejiang Medicine Co., Ltd., Shaoxing 312000, Zhejiang, China; chenchunfeng@zmc-china.com (C.C.);
lcl@zmc-china.com (C.L.); ljf@zmc-china.com (J.L.); jjq@zmc-china.com (J.J.)
Correspondence: wuchunlei2006@usx.edu.cn (C.W.); srunpu@usx.edu.cn (R.S.);
Tel.: +86-575-8834-8939 (C.W.)
2
*
Received: 19 July 2017; Accepted: 1 August 2017; Published: 4 August 2017
Abstract: A simple and efficient method for the synthesis of spiro[indoline-3,90-xanthene]trione
derivatives by means of condensation between isatins and 1,3-cyclohexanedione in the presence of
a catalytic amount of magnesium perchlorate at 80 ◦C in 50% aqueous ethanol medium has been
described. Notably, the present method offers desirable advantages of good yields, simplicity of
workup procedure, easy purification, and reduced reaction times.
Keywords: aqueous; isatin; spiro[indoline-3,90-xanthene]trione; magnesium perchlorate
1. Introduction
Heterocyclic compounds play important roles in the drug discovery process. The indole
moiety is probably the most well-known heterocycle, which occurs in many important natural
products, pharmaceuticals, and other synthetic materials exhibiting a variety of biological activities
and other properties [
substances characterized by highly pronounced biological properties [
is the core structure of many pharmacological agents and natural alkaloids [4–6
1,
2
]. Spiro compounds represent an important class of naturally occurring
]. The spirooxindole system
]. The key structural
3
characteristic of these compounds is the spiro ring fused at the 3-carbon position of the oxindole core with
varied heterocyclic motifs. These spirooxindoles seem to be promising candidates for drug discovery,
since they incorporate both oxindoles and other heterocyclic moieties simultaneously. For example,
MI-219, a spiroindoline-3,30-pyrrolidine, was described by Wang et al. as a potent MDM2 inhibitor [
7].
Xanthenes have been reported to possess pharmacological activities such as antiviral, antibacterial, and
anti-inflammatory properties, and are also known as sensitizers in photodynamic therapy (PDT) for
abolishing tumor cells [8–
11].Spiro[indoline-3,90-xanthene]trione, as a member of spiro compounds,
has attracted researchers’ attentions for its unique structure and biological effects since the first
report by Lorenc in 1959 [12], and various catalysts for its synthesis have been developed such as
p-tert-Butylcalix[8]arene [13], p-TSA [14,15], ZnO [16], ZnFe2O4 [17], B(HSO4)3 [18], HBF4 supported
on silica nanoparticles [19], and SnCl4 [20]. Although these reported protocols have their eligibilities,
they also suffer from one or more drawbacks. So, the development of novel, efficient methods is still
a valid goal.
In recent years, magnesium perchlorate has received considerable attention as an inexpensive,
nontoxic, readily available catalyst for various transformations under mild and convenient conditions,
affording the corresponding products in excellent yields with high selectivity [21–25]. Our previous
Molecules 2017, 22, 1295; doi:10.3390/molecules22081295
www.mdpi.com/journal/molecules

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work on the catalytic synthesis of spiro[4H-pyran-oxindole] derivatives was carried out smoothly in
the presence of magnesium perchlorate [26]. The handling, storage, and precautionary information of
the oxidative Mg(ClO4)2 can be found in the literature, and it is relatively safe when used as a Lewis
acid catalyst [27,28].
In continuance of our research on the synthesis of spiro compounds and the application of
perchlorate, we herein investigated the synthesis of a series of spiro[indoline-3,90-xanthene]trione via
the condensation of isatin and 1,3-cyclohexanedione in the presence of green catalyst magnesium
perchlorate in aqueous ethanol medium (Scheme 1).
R2
R2
O
O
O
O
R2
R2
Mg(ClO4)2, 10mol%
EtOH/H2O
2
O
+
O
R1
, 12h
(v/ v = 1:1)
N
R2
H
R1
R2
O
O
N
2
1
H
3
R2=H;CH3
R1 = H; 5-CH3; 5-Cl; 5-NO2; 5-F;
5-Br; 6-F; 7-CH3; 7-Cl
0
Scheme 1. Synthesis of spiro[indoline-3,9 -xanthene]trione.
2. Results and Discussion
In our initial study, the reaction of isatin 1a and dimedone 2 was used as a simple model substrate
in different solvents in the presence of magnesium perchlorate to achieve suitable conditions for
the synthesis of spiro[indoline-3,90-xanthene]trione. After screening, we found that the reaction can
proceed smoothly in good yield in aqueous ethanol solution (50%, v/v). The reaction mixture was
presented as a suspension state throughout all the process. The color of the reaction mixture changed
from pale red to pale yellow along with the reaction proceeding. The results are summarized in Table 1.
Table 1. Solvent effects on the reaction of isatin and dimedone, in the presence of 10 mol % magnesium
perchlorate a.
◦
Yield b (%)
Entry
Solvent/T ( C)
Time (h)
1
2
3
4
5
6
7
8
PhCH3(reflux)
CH2Cl2(reflux)
CH3OH(reflux)
C2H5OH(reflux)
C2H5OH/H2O(1/1)(80)
H2O(80)
24
24
12
12
10
12
12
12
Trace
Trace
64
71
83
77
60
58
CH3CN(reflux)
THF(reflux)
a
b
Isatin (2 mmol), dimedone (4 mmol); solvent (5 mL), Mg(ClO4)2 (10%mol). Isolated yield.
As shown in Table 2, it was found that this procedure works with a wide variety of substrates.
Nine types of substituted isatins as well as 1,3-cyclohexanedione were used in this reaction (Scheme 1).
After the reaction was over monitored by the thin layer chromatography (TLC), the resulting solid
was filtered and washed with aqueous ethanol solution to yield a crude product, which was then
0
recrystallized from ethanol to afford pure substituted spiro[indoline-3,9 -xanthene]trione 3a
–
3m. All of
the products were crystalline and characterized based on their melting points, elemental analysis, and
spectral data (IR, 1H-NMR, 13C-NMR).

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0
Table 2. Synthesis of spiro[indoline-3,9 -xanthene]trione 3.
Product
R1
R2
Time (h)
Yield a (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
5-Me
5-Cl
5-NO2
7-Me
7-Cl
H
5-Me
5-Cl
5-F
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
CH3
H
CH3
CH3
10
12
10
10
12
10
10
12
10
10
10
10
10
83
75
79
81
71
78
80
69
82
83
71
78
85
3j
3k
3l
5-Br
5-Br
6-F
3m
a
Isolated yield.
0
The mechanism for the synthesis of spiro[indoline-3,9 -xanthene]trione was via the intermediate 4,
followed by the removal of a molecule of water (Figure 1), which can be proved by the following
process. 6-Fuloro-isatine and dimedone were stirred for 24 h at room temperature and then catalyzed
by magnesium perchlorate in the aqueous ethanol. Then the precipitate was filtered, washed and
dried. The 1H-NMR spectra data of the obtained solid showed that there was a strong peak in the
shift of 11.68, which was assigned to the hydroxyl hydrogen of the compound 4. Finally, the solid was
stirred at 80 ◦C for another 10 h to afford the product 3m. This proposed mechanism is in consistent
with that reported in References [15,29,30].
R2
R2
OH
OH
O
O
O
R2
R2
O
2
Product 3
+
O
R1
-H2O
N
R2
R1
H
R2
O
O
N
2
1
H
4
0
Figure 1. Proposed mechanism for the synthesis of spiro[indoline-3,9 -xanthene]trione.
3. Experimental Section
All chemicals used were obtained from commercial suppliers and used without further
purifications. IR spectra were recorded on a Nicolet-6700 spectrometer (Thermo Scientific, MMAS,
1
Waltham, MA, USA). H-NMR spectra were determined on a Bruker AVANCE DMX III 400 M
spectrometer (Bruker, Fallanden, Switzerland) and 13C-NMR spectra were obtained on the same
instrument. Samples were dissolved in deuterated DMSO, which provided the deuterium lock
for the spectrometers. Elemental microanalysis was carried out on a Euro vector EA 3000 CHN
analyzer (Milan, Italy). Melting points were measured using a BUCHI M-560 melting point apparatus
(Buchi labortechnik AG, Flawil, Switzerland). HRMS measurements were performed on a Waters
Micromass GCT Premier (Waters, MMAS, New York, NY, USA). Reactions were monitored by
thin-layer chromatography (TLC), carried out on 0.25 mm silica gel plates and visualized with UV light.
General Procedure for the Synthesis of Spiro[indoline-3,90-xanthene]trione (3)
Mg(ClO4)2 (0.1 g) was added to a mixture of isatin (2 mmol), and dimedone (4 mmol) in
aqueous ethanol solution (50%, v/v, 5 mL), and the resulting mixture was stirred at 80 ◦C for 10–12 h.

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Upon completion of the reaction (TLC, Ethyl acetate/Petroleum ether = 1:4), the mixture was allowed
to cool to room temperature. The resulting solid was filtered and washed successively with water
(
2 × 30 mL) and cold aqueous ethanol (2 × 1 mL) to afford a crude product, which was recrystallized
from EtOH to afford the pure product . Some insolubility could be observed in the refluxing ethanol
3
during the recrystallization process, which should be filtered when hot.
30,30,60,60-Tetramethyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3a). White
powder; m.p.: 306–307 ◦C (305 ◦C) [15]; IR (KBr) cm−1: 3431, 2957, 1733, 1666, 1616, 1469, 1345, 1222,
1
1168. H-NMR (400 MHz, CDCl3): δH (ppm) 1.04 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.11 and 2.25 (4H,
AB system, J = 16 Hz, 2CH2), 2.44 and 2.56 (4H, J = 17.6Hz, 2CH2), 6.83–6.90 (3H, m, H-Ar), 7.13–7.17
(1H, m, H-Ar), 7.62 (1H, s, NH); 13C-NMR (100 MHz, CDCl3): δC (ppm) 27.2, 29.0, 32.0, 41.2, 45.7, 50.9,
109.4, 113.6, 121.9, 122.3, 128.5, 133.6, 142.3, 163.5, 178.8, 195.3; Anal. Calcd. for C24H25NO4: C, 73.64;
H, 6.44; N, 3.58%. Found: C, 73.67; H, 6.36; N, 3.52%.
5,30,30,60,60-Pentamethyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione
(3b).
White powder; m.p.: 294–295 ◦C (310 ◦C) [16]; IR (KBr) cm−1: 3314, 2959, 1745, 1670, 1618, 1349, 1315,
1
1168. H-NMR (CDCl3): δH (ppm) 1.04 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.13 and 2.24 (4H, AB system,
J = 16.4 Hz, 2CH2), 2.21 (3H, s, CH3), 2.45 and 2.55 (4H, AB system, J = 17.6 Hz, 2CH2), 6.66 (1H, s,
H-Ar), 6.73 (1H, d, J = 8.0 Hz, H-Ar), 6.95 (1H, d, J = 7.6 Hz, H-Ar), 7.46 (1H, s, NH). 13C-NMR (CDCl3):
δC (ppm) 21.2, 27.4, 28.9, 31.9, 41.2, 45.7, 50.9, 108.9, 113.7, 123.2, 128.9, 132.2, 133.7, 139.8, 163.4, 178.7,
195.3. Anal. Calcd. for C25H27NO4: C, 74.05; H, 6.71; N, 3.45%. Found: C, 73.58; H, 6.41; N, 3.48%.
0
0
0
0
0
0
0
0
0
0
0
0
0
5-Chloro-3 ,3 ,6 ,6 -tetramethyl-3 ,4 ,6 ,7 -tetrahydrospiro[indoline-3,9 -xanthene]-1 ,2,8 (2 H,5 H)-trione (3c).
White powder; m.p.: 309–310 ◦C; IR (KBr) cm−1: 3457, 2958, 1739, 1665, 1616, 1509, 1349, 1224, 1120.
1H-NMR (CDCl3): δH (ppm) 1.06 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.16 and 2.26 (4H, AB system,
J = 16.4 Hz, 2CH2), 2.48 and 2.56 (4H, J = 17.6 Hz, 2CH2), 6.76 (1H, d, J = 8.4 Hz, H-Ar), 6.83 (1H, d,
J = 1.6 Hz, H-Ar), 7.12 (1H, dd, J = 1.6 Hz, J = 8.4 Hz, H-Ar), 7.89 (1H, s, NH). 13C-NMR (CDCl3): δC
(ppm) 27.5, 28.7, 31.9, 41.2, 45.8, 50.9, 110.3, 113.2, 122.6, 126.9, 128.3, 135.2, 141.2, 163.8, 178.3, 195.4.
Anal. Calcd. for C24H24ClNO4: C, 67.68; H, 5.68; N, 3.29%. Found: C, 67.59; H, 5.62; N, 3.37%. HRMS
(ESI): m/z [M + H]+ calcd. for C24H24ClNO4: 425.9047; found: 425.9041.
5-Nitro-30,30,60,60-tetramethyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3d).
Pale yellow powder; m.p.: 276–277 ◦C (278 ◦C) [15]; IR (KBr) cm−1: 3452, 2958, 1745, 1667, 1629, 1346,
1
1225, 1169. H-NMR (CDCl3): δH (ppm) 1.00 (6H, s, 2CH3), 1.11 (6H, s, 2CH3), 2.17 and 2.26 (4H, AB
system, J = 16 Hz, 2CH2), 2.53 and 2.59 (4H, AB system, J = 18 Hz, 2CH2), 6.89 (1H, d, J = 8.8 Hz, H-Ar),
7.80 (1H, d, J = 2.0 Hz, H-Ar), 8.14 (1H, dd, J = 2.0 Hz, J = 8.8 Hz, H-Ar), 8.37 (1H, s, NH). 13C-NMR
(CDCl3): δC (ppm) 27.7, 28.5, 32.1, 41.1, 45.5, 50.8, 108.9, 112.8, 118.1, 125.9, 134.5, 143.0, 148.6, 164.5, 178.6,
195.8. Anal. Calcd. for C24H24N2O6: C, 66.04; H, 5.54; N, 6.42%. Found: C, 65.91; H, 5.47; N, 6.29%.
7,30,30,60,60-Pentamethyl-30,40,60,7◦0-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione
(3e).
White powder; m.p.: 287–289 C; IR (KBr) cm−1: 3336, 2955, 1731, 1671, 1618, 1348, 1224, 1168.
1H-NMR (CDCl3): δH (ppm) 1.04 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.15 and 2.25 (4H, AB system,
J = 17.2 Hz, 2CH2), 2.27 (3H, s, CH3), 2.45 and 2.56 (4H, AB system, J = 17.6 Hz, 2CH2), 6.70 (1H, d,
J = 7.2 Hz, H-Ar), 6.80 (1H, J = 7.2 Hz, J = 7.6 Hz, H-Ar), 6.97 (1H, d, J = 7.6 Hz, H-Ar), 7.48 (1H, s, NH).
13C-NMR (CDCl3): δC (ppm) 16.3, 27.1, 29.0, 33.6, 41.2, 54.8, 111.9, 113.7, 118.0, 120.0, 121.9, 140.8, 163.4,
168.7, 179.0, 181.6, 195.4, 202.3. Anal. Calcd. for C25H27NO4: C, 74.05; H, 6.71; N, 3.45%. Found: C,
73.53; H, 6.53; N, 3.37%. HRMS (ESI): m/z [M + H]+ calcd for C25H27NO4: 405.4862; found: 405.4857.
0
0
0
0
0
0
0
0
0
0
0
0
0
7-Chloro-3 ,3 ,6 ,6 -tetramethyl-3 ,4 ,6 ,7 -tetrahydrospiro[indoline-3,9 -xanthene]-1 ,2,8 (2 H,5 H)-trione (3f).
White powder; m.p.: 270–271 C; IR (KBr) cm−1: 3451, 2959, 1738, 1666, 1623, 1348, 1224, 1131. H-NMR
(CDCl3): δH (ppm) 1.02 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.14 and 2.26 (4H, AB system, J = 16.0 Hz,
2CH2), 2.45 and 2.56 (4H, AB system, J = 17.6 Hz, 2CH2), 6.75 (1H, d, J = 7.2 Hz, H-Ar), 6.80 (1H,
J = 7.2 Hz, J = 8.0 Hz, H-Ar), 7.14 (1H, d, J = 8.0 Hz, H-Ar), 7.48 (1H, s, NH). 13C-NMR (CDCl3): δC
(ppm) 27.2, 28.9, 32.0, 46.7, 50.8, 113.3, 114.7, 120.5, 122.7, 128.4, 134.7, 140.1, 163.7, 177.9, 195.3. Anal.
◦
1

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Calcd forC24H24ClNO4: C, 67.68; H, 5.68; N, 3.29%. Found: C, 67.53; H, 5.61; N, 3.18%. HRMS (ESI):
m/z [M + H]+ calcd. for C24H24ClNO4: 425.1394; found: 425.1391.
30,40,60,70-Tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3g). White powder; m.p.:
336–337 ◦C (m.p. 336 ◦C) [31]; 1H-NMR (CDCl3): δH(ppm) 1.60–2.09 (4H, m, CH2), 2.25–2.62 (4H, m,
CH2), 2.64 (4H, t, J = 6.4 Hz, CH2), 6.83–6.89 (3H, m, H-Ar), 7.13–7.18 (1H, m, H-Ar), 7.59 (1H, s, NH).
13C-NMR (CDCl3): δC (ppm) 20.0, 27.6, 37.2, 45.8, 109.1, 114.8, 121.9, 122.7, 128.5, 133.8, 142.2, 164.9,
178.9, 195.4. Anal. Calcd. for C20H17NO4: C, 71.63; H, 5.11; N, 4.18%. Found: C, 71.52; H, 5.03; N, 4.35%.
5-Methyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3h). White powder;
1
m.p.: 287–288 ◦C; IR (KBr) cm−1: 3312, 2957, 1743, 1668, 1618, 1350, 1314, 1167. H-NMR (CDCl3):
δH (ppm) 1.83–2.10 (4H, m, CH2), 2.23 (3H, s, CH3), 2.26–2.66 (4H, m, CH2), 2.64 (4H, t, J = 6.8 Hz,
CH2), 6.67 (1H, s, H-Ar), 6.72 (1H, d, J = 8.0 Hz, H-Ar), 6.95 (1H, d, J = 7.6 Hz, H-Ar), 7.59 (1H, s, NH).
13C-NMR (CDCl3): δC (ppm) 20.0, 21.2, 27.6, 37.2, 45.9, 108.8, 114.9, 123.7, 128.9, 131.2, 133.7, 139.7,
167.9, 178.9, 195.5. Anal. Calcd. for C21H19NO4: C, 72.19; H, 5.48; N, 4.01%. Found: C, 71.67; H, 5.33;
N, 4.15%. HRMS (ESI): m/z [M + H]+ calcd. for C21H19NO4: 349.1314; found: 349.1310.
0
0
0
0
0
0
0
0
0
5-Chloro-3 ,4 ,6 ,7 -tetrahydrospiro[indoline-3,9 -xanthene]-1 ,2,8 (2 H,5 H)-trione (3i). White powder; m.p.:
364–365 C; IR (KBr) cm−1: 3455, 2959, 1747, 1670, 1637, 1349, 1228, 1175. H-NMR (CDCl3): δH (ppm)
1.97–2.10 (4H, m, CH2), 2.23 (3H, s, CH3), 2.29–2.37 (4H, m, CH2), 2.65 (4H, t, J = 6.4Hz, CH2), 6.77 (1H,
d, J = 8.0 Hz, H-Ar), 6.84 (1H, d, J = 2.0 Hz, H-Ar), 7.13 (1H, dd, J = 2.0 Hz, J = 8.0 Hz, H-Ar), 7.60 (1H,
s, NH). 13C-NMR (CDCl3): δC (ppm) 19.9, 27.5, 37.1, 46.0, 110.0, 114.4, 123.2, 127.0, 128.3, 135.3, 140.9,
165.3, 178.4, 195.4. Anal. Calcd for C20H16ClNO4: C, 64.96; H, 4.36; N, 3.79%. Found: C, 64.87; H, 4.28;
N, 3.61%. HRMS (ESI): m/z [M + H]+ calcd. for C20H16ClNO4: 369.0768; found: 369.0764.
◦
1
5-Fuloro-30,30,60,60-tetramethyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,0H)-trione (3j).
White powder; m.p.: 302–303 ◦C; IR (KBr) cm−1: 3457, 2958, 1732, 1667, 1618, 1492, 1349, 1222, 1167.
1H-NMR (CDCl3): δH (ppm) 1.04 (6H, s, 2CH3), 1.12 (6H, s, 2CH3), 2.15 and 2.27 (4H, AB system,
J = 16.0 Hz, 2CH2), 2.45 and 2.57 (4H, AB system, J = 17.6 Hz, 2CH2), 6.60 (1H, dd, J = 2.0 Hz, J = 7.6 Hz
,
H-Ar), 6.72 (1H, J = 4.4 Hz, J = 8.4 Hz, H-Ar), 6.80–6.85 (1H, m, H-Ar), 8.16 (1H, s, NH). 13C-NMR
(CDCl3): δC (ppm) 27.3, 28.9, 32.0, 41.2, 46.2, 50.9, 110.1, 113.3, 114.6, 134.9, 138.6, 157.7, 160.1, 163.8,
178.7, 195.4. Anal. Calcd. for C24H24FNO4: C, 70.40; H, 5.91; N, 3.42%. Found: C, 69.93; H, 5.86; N,
3.35%. HRMS (ESI): m/z [M + H]+ calcd. for C24H24FNO4: 409.1689; found: 409.1685.
0
0
0
0
0
0
0
0
0
5-Bromo-3 ,4 ,6 ,7 -tetrahydrospiro[indoline-3,9 -xanthene]-1 ,2,8 (2 H,5 H)-trione (3k). White powder; m.p.:
288–289 ◦C; IR (KBr) cm−1: 3447, 2959, 1733, 1668, 1619, 1495, 1349, 1224, 1169. H-NMR (CDCl3): δH
1
(ppm) 1.98–2.10 (4H, m, 2CH2), 2.29–2.37 (4H, m, 2CH2), 2.65 (4H, t, J = 6.4 Hz, 2CH2), 6.72 (1H, d,
J = 8.4 Hz, H-Ar), 6.97 (1H, d, J = 1.6 Hz, H-Ar), 7.25–7.28 (1H, m, H-Ar), 7.71 (1H, s, NH). 13C-NMR
(CDCl3): δC (ppm) 19.9, 27.5, 37.1, 45.9, 110.5, 114.3, 114.4, 125.9, 131.2, 135.7, 141.4, 165.3, 178.3, 195.4.
Anal. Calcd. for C20H16BrNO4: C, 57.99; H, 3.89; N, 3.38%. Found: C, 57.71; H, 3.81; N, 3.42%. HRMS
(ESI): m/z [M + H]+ calcd. for C20H16BrNO4: 413.0263; found: 413.0259.
5-Bromo-30,30,60,60-tetramethyl-30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3l).
◦
◦
White powder; m.p.: 290 C (290 C) [15]; IR (KBr) cm−1: 3449, 2958, 1731, 1665, 1617, 1347, 1223,
1
1165. H-NMR (CDCl3): δH (ppm) 1.05 (6H, s, 2CH3), 1.11 (6H, s, 2CH3), 2.15 and 2.25 (4H, AB system,
J = 16.4 Hz, 2CH2), 2.47 and 2.56 (4H, AB system, J = 17.6 Hz, 2CH2), 6.72 (1H, d, J = 8.4 Hz, H-Ar),
6.95 (1H, d, J = 2.0 Hz, H-Ar), 7.26(1H, m, H-Ar), 7.98 (1H, s, NH). 13C-NMR (CDCl3): δC (ppm) 27.5,
28.7, 32.0, 41.2, 45.8, 50.9, 110.9, 113.2, 114.3, 125.5, 131.3, 135.6, 141.5, 164.0, 178.4, 195.6. Anal. Calcd.
for C24H24BrNO4: C, 61.28; H, 5.14%; N, 2.98%. Found: C, 61.03; H, 5.17; N, 2.92%.
6-Fuloro-30,30,60,60-tetramethyl-◦30,40,60,70-tetrahydrospiro[indoline-3,90-xanthene]-10,2,80(20H,50H)-trione (3m).
1
White powder; m.p.: 281–283 C; IR (KBr) cm−1: 3453, 2959, 1739, 1664, 1619, 1347, 1223, 1130. H-NMR
(CDCl3): δH (ppm) 1.04 (6H, s, 2CH3), 1.13 (6H, s, 2CH3), 2.15 and 2.28 (4H, AB system, J = 16.4 Hz,
2CH2), 2.46 and 2.58 (4H, AB system, J = 17.6 Hz, 2CH2), 6.74 (1H, d, J = 6.8 Hz, H-Ar), 6.70–7.03 (1H,

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m, H-Ar), 8.03 (1H, s, NH). 13C-NMR (CDCl3): δC (ppm) 27.2, 28.9, 32.0, 41.2, 45.4, 50.9, 112.9, 113.2,
121.9, 123.4, 124.8, 132.6, 143.6, 163.8, 178.6, 195.5. Anal. Calcd. for C24H24FNO4: C, 70.40; H, 5.91; N,
3.42%. Found: C, 69.99; H, 5.85; N, 3.47%. HRMS (ESI): m/z [M + H]+ calcd for C24H24FNO4: 409.1689;
found: 409.1685.
4. Conclusions
The present report describes the synthesis of spiro[indoline-3,90-xanthene]trione derivatives in
◦
good yields, catalyzed by Mg(ClO4)2 at 80 C in aqueous ethanol media. This protocol is efficient, simple,
mild, eco-friendly, and also advantageous in terms of short reaction time and easy workup procedure.
Supplementary Materials: Supplementary materials are available online.
Acknowledgments: We gratefully acknowledge the financial support from Public Projects of Zhejiang Province of
China (No. 2016C31032, NO. 2015C31147) and the National Natural Science Foundation of China (No. 51402195).
Author Contributions: R.S. and C.W. conceived and designed the experiments; C.C., C.L., J.L. and J.J. performed
the experiments; L.W. analyzed the data; C.W. wrote the paper
Conflicts of Interest: The authors declare no conflict of interest.
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