Synthesis of diverse isatins: Via ring contraction of 3-diazoquinoline-2,4-diones

Article abstract of DOI:10.1039/c6ra13585d

An efficient synthesis of diverse isatin derivatives was accomplished by a copper-mediated reaction of 3-diazoquinoline-2,4-diones via ring contraction through domino Wolff rearrangement, decarboxylation, bromination, substitution, and dehydration. This protocol has several advantages as a one-pot procedure, with functional group tolerance, and high yield.

Full text of DOI:10.1039/c6ra13585d

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Synthesis of diverse isatins via ring contraction of
3-diazoquinoline-2,4-diones†
Cite this: RSC Adv., 2016, 6, 63782
*
Rajeev Shrestha, Gun Joon Lee and Yong Rok Lee
Received 25th May 2016
Accepted 27th June 2016
An efficient synthesis of diverse isatin derivatives was accomplished by a copper-mediated reaction of 3-
diazoquinoline-2,4-diones via ring contraction through domino Wolff rearrangement, decarboxylation,
bromination, substitution, and dehydration. This protocol has several advantages as
procedure, with functional group tolerance, and high yield.
a one-pot
DOI: 10.1039/c6ra13585d
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expensive reagents, multi-step reactions, and limitation of
substrates. To overcome these shortcomings, several effective
approaches for the synthesis of isatin derivatives (Scheme 1)
have recently been reported, which include the copper-catalyzed
intramolecular C–H oxidation/acylation of formyl-N-arylforma-
mides (path a),18 copper-catalyzed or -mediated intramolecular
C–H oxidation of 2-aminoacetophenones (path b),19 palladium-
catalyzed double carbonylation of C–H bonds (path c),20
palladium-catalyzed double hydrolysis to N-benzyl-2-
iodoanilines (path d),21 and I2/TBHP mediated oxidation of
indoles (path e).22 These developed strategies for the construc-
tion of isatins have been accomplished by intra- or intermo-
lecular cyclization through the formation of a C–C bond at the o-
position of aniline with suitable substrates and C–N bond
formation of aniline with o-substituted functional groups. On
the other hand, there is still strong demand for a more conve-
nient synthetic protocol for biologically interesting isatin
derivatives. To the best of the authors' knowledge, synthetic
approaches to isatins through the ring contraction of 3-
diazoquinoline-2,4-diones have not been demonstrated so far.
We have developed simple and facile synthetic methodolo-
gies for the preparation of heterocycles and valuable molecules
by decompositon of diazo compounds.23 In particular, Rh(II)-
catalyzed reaction of diazo compounds for the synthesis of
oxindoles was described.24 As a part of an ongoing study of diazo
compounds, this study examines the copper-mediated reactions
of 3-diazoquinoline-2,4-diones to afford diverse isatin deriva-
tives. This paper describes a one-pot protocol for biologically
interesting isatin derivatives by copper-mediated reactions of 3-
diazoquinoline-2,4-diones in wet benzonitrile (Scheme 2).
Introduction
Isatin is a well-known and important compound found in many
natural products and bioactive materials.1 Molecules bearing an
isatin moiety possess a broad range of biological properties,
such as anticancer,2 antimalarial,3 anticonvulsant,4 antituber-
cular,5 anti-inammatory,6 antifungal,7 antiviral,8 and anti-HIV
activities.9 In addition, they are widely used as building blocks
for the synthesis of bioactive natural products10 and valuable
molecules, such as donaxaridine,11 trikentramides A–D,12 and
ammosamides.13
Owing to their potent biological and pharmacological prop-
erties, many methods have been reported for the construction
of isatins. Among these, Sandmeyer,14 Gassman,15 Martinet,16
17
´
and Stolle reported the classical methods for the preparation
of isatins. These methods suffer from harsh conditions,
Scheme 1 Recently reported approaches for the construction of
isatins.
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic
of Korea. E-mail: yrlee@yu.ac.kr; Fax: +82-53-810-4631; Tel: +82-53-810-2529
† Electronic supplementary information (ESI) available: 1H NMR, 13C NMR, IR
and HRMS. See DOI: 10.1039/c6ra13585d
Scheme 2 Copper-mediated reactions of 3-diazoquinoline-2,4-dio-
nes for the synthesis isatins.
63782 | RSC Adv., 2016, 6, 63782–63787
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Table 2 Additional reactions for the synthesis of various isatins 3b–3i
bearing substituents on the benzene ring
Results and discussion
This study was initiated by the preparation of diazo compounds
1a–1x by the reported diazo transfer method using mesyl azide
with the respective hydroxyl quinolinone,25 which were ob-
tained from aniline and Meldrum's acid.26 Subsequently, the
reaction of 3-diazoquinoline-2,4-dione (1a) for the synthesis of
isatin (3a) was performed using several catalysts and solvents
(Table 1). When 1a was reuxed in chlorobenzene in the pres-
ence of 1 mol% of Rh2(OPiv)4 for 5 h, oxindole (2a) was
produced in 78% yield without the formation of isatin (3a)
(entry 1). With CuO (20 mol%) and Cu(OAc)2 (20 mol%),
product 2 was isolated in 15 and 13% yields, respectively
whereas product 3 was obtained in trace amount (entry 2 and 3).
Interestingly, product 3a was produced in 19% yield using 20
mol% of CuCl2 in reuxing benzonitrile for 6 h (entry 4).
Increasing the amount of CuCl2 to 1 or 2 equiv. increased the
yield of 3a to 33% and 61%, respectively (entry 5 and 6). Upon
loading 1 or 2 equiv. of various metal salts, such as CuBr2, CuCl
and CuBr, the best yield (84%) was obtained in the presence of 2
equiv. of CuBr in reuxing benzonitrile for 3 h (entries 7–12). In
other polar or nonpolar solvents, such as propionitrile, chlo-
robenzene, and toluene, 3a was produced in 79, 40, and 46%
yields, respectively (entries 13–15). The identity of 3a was
conrmed by an analysis of its spectroscopic data and
a comparison with the reported compound.22 The 1H NMR of 3a
showed NH peak at d ¼ 11.02 ppm as a singlet and four
aromatic protons at d ¼ 7.75, 7.18, 7.05, and 6.90 ppm.
benzene ring (Table 2). Reactions of diazo compounds 1b–1e
bearing electron-donating groups such as 6-methyl, 8-methyl, 6-
isopropyl, or 6-methoxy on the benzene ring for 4–5 h provided
the desired products 3b–3e in 80–86% yields, whereas those of
1f–1i bearing the electron-withdrawing groups, 5-chloro, 6-
chloro, 7-chloro or 6-bromo, for 3–4 h afforded products 3f–3i
(84–88%) in a slightly increased yield.
Further reactions of other N-substituted 3-diazoquinoline-
2,4-diones 1j–1r were successful (Table 3). The treatment of 3-
diazoquinoline-2,4-diones 1j–1n bearing a methyl, ethyl, 3-
methylbut-2-en-1-yl, but-3-en-1-yl, or cinnamyl group on the
nitrogen atom for 3–5 h produced the desired products 3j–3n in
81–91% yields. A reaction of 3-diazoquinoline-2,4-dione 1o
bearing a benzyl group on the nitrogen atom afforded product
3o in 87% yield. Similarly, the diazo compounds 1p–1r bearing
an electron-donating or withdrawing group, such as 3-
Under the optimized reaction conditions, the generality of
this reaction was explored further using various 3-
diazoquinoline-2,4-diones (1b–1i) bearing substituents on the
Table 1 Optimization of the reaction conditions for the synthesis of 3a
Table 3 Additional reactions for the synthesis of various isatins 3j–3r
bearing substituents on the nitrogen atom
Yielda (%)
Entry Catalysts
Solvent
Conditions 2a 3a
1
Rh2(OPiv)4 (0.01 eq.) PhCl
Reux, 5 h 78
0
2
3
4
5
6
7
8
9
10
11
12
13
14
15
CuO (0.2 eq.)
Cu(OAc)2 (0.2 eq.)
CuCl2 (0.2 eq.)
CuCl2 (1 eq.)
CuCl2 (2 eq.)
CuBr2 (1 eq.)
CuBr2 (2 eq.)
CuCl (1 eq.)
CuCl (2 eq.)
CuBr (1 eq.)
CuBr (2 eq.)
CuBr (2 eq.)
CuBr (2 eq.)
CuBr (2 eq.)
PhCl
PhCl
Reux, 8 h 15 Trace
Reux, 8 h 13 Trace
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
Reux, 6 h
Reux, 4 h
Reux, 4 h
Reux, 4 h
Reux, 3 h
Reux, 3 h
Reux, 3 h
Reux, 4 h
Reux, 3 h
0
0
0
0
0
0
0
0
0
0
0
0
19
33
61
26
53
58
64
74
84
79
40
46
CH3CH2CN Reux, 3 h
PhCl
Toluene
Reux, 6 h
Reux, 6 h
a
Isolated yield aer column chromatography.
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Table 4 Additional reactions for the synthesis of various isatins 3s–3x
bearing substituents on the benzene ring and nitrogen atom
rearrangement to give ketene 5, which leads to 2a via the
nucleophilic attack of water followed by decarboxylation.24 The
a,a-dibromination of 2a in the presence of CuBr gives the
intermediate 7, which is reacted with water to furnish 8.
Dehydration of 8 gives nal product 3a.27
Conclusions
An efficient and simple method was developed for the
construction of isatin derivatives by ring contraction through
domino reaction from readily available 3-diazoquinoline-2,4-
diones in high yield. This protocol allows the preparation of
diverse and functionalized isatin derivatives, which could be
used widely for the synthesis of bioactive natural products and
pharmaceuticals. This reaction has several advantages, such as
a one-pot procedure, tolerance of various functional groups,
and high yield.
Experimental
General information
All experiments were conducted in a nitrogen atmosphere.
Merck silica gel plates (Art. 5554) precoated with a uorescent
indicator were used for analytical TLC. Flash column chroma-
tography was performed using silica gel 9385 (Merck). The
melting points were determined using micro-cover glasses on
methylbenzyl, 3,5-dimethoxybenzyl, or 4-chlorobenzyl provided
the desired products 3p–3r in 88, 85, or 87% yields respectively.
To further demonstrate the versatility of this protocol, reac-
tions with diazo compounds 1s–1x bearing substituents on the
benzene ring and nitrogen atom were next examined (Table 4).
The reactions of 1s–1u bearing a methyl group on the benzene
ring and but-3-en-1-yl, 3-chloropropyl, or geranyl group on the
nitrogen atom provided the expected products 3s–3u in 80, 78,
and 77% yields, respectively. With 1v and 1w bearing an elec-
tron donating methyl group on the benzene and a 3,5-dime-
thoxy or 4-chlorobenzyl group on the nitrogen atom produced
3v and 3w in 79 and 82% yields, respectively. With 1x bearing an
electron-withdrawing chloro group, the desired product 3x was
produced in 81% yield. These reactions provided a rapid
synthetic route for the synthesis of diverse and various isatin
derivatives.
1
a Fisher-Johns apparatus and were uncorrected. The H NMR
spectra were recorded on a Varian-VNS (300 MHz), DPX (300
MHz) and VNS (600 MHz) spectrometer in DMSO-d6 using the
solvent chemical shi of 2.50 ppm. The 13C NMR spectra were
recorded on a Varian-VNS (75 MHz), DPX (75 MHz) and VNS
(150 MHz) spectrometer in the DMSO-d6 using the solvent
chemical shi, 39.5 ppm. The Fourier transform infrared (FT-
IR) spectra were recorded on PerkinElmer FT-IR spectrometer
Spectrum Two™. The high resolution mass (HRMS) were ob-
tained with a JEOL JMS-700 spectrometer at the Korea Basic
Science Institute.
General procedure for the synthesis of isatin derivatives
(3a–3x)
The formation of 3a can be explained by the reaction
mechanism shown in Scheme 3. In the presence of CuBr, diazo
compound 1a rst forms metal carbenoid 4 by the loss of
To a mixture of 3-diazoquinoline-2,4-diones 1a–1x (0.5 mmol),
benzonitrile (3 mL) and water (0.2 mL), CuBr (143 mg, 1.0
mmol) was added and the reaction mixture was vigorously
nitrogen. The intermediate
4
would undergo Wolff
ꢀ
stirred at 140 C for 3–7 h under N2 atmosphere. The comple-
tion of the reaction was indicated by TLC analysis. The volatiles
were removed in vacuo and the residue was puried by silica gel
column chromatography using hexane/EtOAc (5 : 1) as the
eluent to afford the desired products 3a–3x.
Characterization data of synthesized compounds
Indoline-2,3-dione (3a). Yield 84%; red solid; mp 197–199 ꢀC.
IR (ATR): 3470, 3369, 3176, 3102, 1728, 1675, 1614, 1463, 1362,
1
1326, 1253, 1010, 763, 677, 454, 405 cmꢁ1. H NMR (600 MHz,
DMSO-d6): d 11.02 (1H, s), 7.75 (1H, td, J ¼ 7.2, 1.2 Hz), 7.48 (1H,
d, J ¼ 7.8 Hz), 7.05 (1H, t, J ¼ 7.8 Hz), 6.90 (1H, d, J ¼ 8.4 Hz). 13
C
Scheme 3 Proposed mechanism for the formation of 3a from 1a.
63784 | RSC Adv., 2016, 6, 63782–63787
NMR (150 MHz, DMSO-d6): d 184.4, 159.4, 150.7, 138.5, 124.6,
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122.8, 117.8, 112.2. HRMS m/z (M+): calcd for C8H5NO2: 151.8, 142.3, 126.2, 122.7, 116.7, 112.2. HRMS m/z (M+): calcd
147.0320; found: 147.0322.
for C8H4ClNO2: 180.9931; found: 180.9930.
5-Methylindoline-2,3-dione (3b). Yield 86%; red solid; mp
5-Bromoindoline-2,3-dione (3i). Yield 88%; yellow solid; mp
179–181 ꢀC. IR (ATR): 3183, 2922, 2854, 1732, 1613, 1461, 1379, 246–248 ꢀC. IR (ATR): 3196, 2999, 2824, 1746, 1610, 1468, 1290,
1286, 1191, 1122, 1036, 966, 818, 732, 658, 547, 452, 405 cmꢁ1
.
1238, 1166, 1122, 843, 716, 658, 574, 461 cmꢁ1. H NMR (600
1
1H NMR (300 MHz, DMSO-d6): d 10.93 (1H, s), 7.38 (1H, d, J ¼ MHz, DMSO-d6): d 11.02 (1H, s), 7.44 (1H, t, J ¼ 7.8 Hz), 7.21
8.1 Hz), 7.30 (1H, s), 6.79 (1H, d, J ¼ 8.1 Hz), 2.24 (3H, s). 13C (1H, d, J ¼ 7.8 Hz), 6.88 (1H, d, J ¼ 7.8 Hz). 13C NMR (150 MHz,
NMR (150 MHz, DMSO-d6): d 184.6, 159.5, 148.6, 138.8, 132.0, DMSO-d6): d 181.7, 158.6, 152.5, 138.9, 126.7, 119.4, 116.4,
124.8, 117.8, 112.0, 20.1. HRMS m/z (M+): calcd for C9H7NO2: 111.3. HRMS m/z (M+): calcd for C8H4BrNO2: 224.9425; found:
161.0477; found: 161.0479.
224.9424.
1-Methylindoline-2,3-dione (3j). Yield 91%; red solid; mp
7-Methylindoline-2,3-dione (3c). Yield 84%; yellow solid; mp
158–160 ꢀC. IR (ATR): 3458, 3160, 3102, 1730, 1592, 1457, 1381, 125–127 ꢀC. IR (ATR): 3447, 2924, 2857, 1718, 1600, 1464, 1366,
1319, 1250, 1155, 1034, 928, 790, 737, 686, 547, 474, 405 cmꢁ1
.
1323, 1256, 1191, 1161, 1112, 1088, 1028, 953, 861, 808, 699,
1H NMR (300 MHz, DMSO-d6): d 10.99 (1H, s), 7.43 (1H, t, J ¼ 7.8 556, 526, 469 cmꢁ1. 1H NMR (300 MHz, DMSO-d6): d 7.66 (1H, t,
Hz), 6.85 (1H, d, J ¼ 7.5 Hz), 6.70 (1H, d, J ¼ 7.8 Hz), 2.42 (3H, s). J ¼ 7.8 Hz), 7.52 (1H, d, J ¼ 7.5 Hz), 7.14–7.09 (2H, m), 3.13 (3H,
13C NMR (150 MHz, DMSO-d6): d 185.0, 159.2, 150.8, 139.7, s). 13C NMR (75 MHz, DMSO-d6): d 183.5, 158.2, 151.4, 138.2,
137.9, 124.8, 115.9, 109.5, 17.4. HRMS m/z (M+): calcd for 124.2, 123.2, 117.4, 110.6, 26.0. HRMS m/z (M+): calcd for
C9H7NO2: 161.0477; found: 161.0475.
C9H7NO2: 161.0477; found: 161.0474.
5-Isopropylindoline-2,3-dione (3d). Yield 80%; yellow solid;
1-Ethylindoline-2,3-dione (3k). Yield 89%; red solid; mp 87–
ꢀ
mp 137–137 C. IR (ATR): 3304, 2921, 2854, 1739, 1622, 1484, 88 ꢀC. IR (ATR): 3439, 2981, 2873, 1725, 1604, 1461, 1349, 1286,
1381, 1262, 1111, 1024, 830, 726, 657, 594, 498, 473, 427, 404 1195, 1158, 1124, 1090, 1049, 964, 934, 867, 814, 754, 699, 678,
1
cmꢁ1. H NMR (600 MHz, DMSO-d6): d 10.93 (1H, s), 7.48 (1H, 563, 469 cmꢁ1. 1H NMR (600 MHz, DMSO-d6): d 7.65 (1H, td, J ¼
dd, J ¼ 8.4, 1.8 Hz), 7.37 (1H, d, J ¼ 1.8 Hz), 6.83 (1H, d, J ¼ 7.8 8.4, 1.2 Hz), 7.53 (1H, d, J ¼ 7.8 Hz), 7.18 (1H, d, J ¼ 8.4 Hz), 7.11
Hz), 2.88–2.85 (1H, m), 1.17 (6H, d, J ¼ 6.6 Hz); 13C NMR (150 (1H, t, J ¼ 7.8 Hz), 3.71–3.68 (2H, m), 1.18 (3H, t, J ¼ 7.2 Hz). 13
C
MHz, DMSO-d6): d 184.6, 159.5, 148.9, 143.1, 136.5, 122.2, 117.8, NMR (150 MHz, DMSO-d6): d 183.6, 157.7, 150.4, 138.2, 124.6,
112.1, 32.7, 23.7, 23.6. HRMS m/z (M+): calcd for C11H11NO2: 123.0, 117.5, 110.6, 34.3, 12.3. HRMS m/z (M+): calcd for
189.0790; found: 189.0791.
C
10H9NO2: 175.0633; found: 175.0635.
5-Methoxyindoline-2,3-dione (3e). Yield 83%; red solid; mp
1-(3-Methylbut-2-en-1-yl)indoline-2,3-dione (3l). Yield 86%;
194–196 ꢀC. IR (ATR): 3435, 3094, 2842, 1732, 1484, 1630, 1304, red solid; mp 85–87 ꢀC. IR (ATR): 3462, 2997, 2915, 1727, 1605,
1237, 1195, 1152, 1031, 977, 901, 821, 732, 695, 597, 454, 405 1463, 1348, 1174, 1092, 1030, 937, 757, 611, 553, 466 cmꢁ1. H
1
1
cmꢁ1. H NMR (600 MHz, DMSO-d6): d 11.02 (1H, s), 7.17 (1H, NMR (600 MHz, DMSO-d6): d 7.65 (1H, td, J ¼ 7.8, 1.2 Hz), 7.54
dd, J ¼ 7.8, 3.0 Hz), 7.06 (1H, d, J ¼ 2.4 Hz), 6.84 (1H, d, J ¼ 9.0 (1H, d, J ¼ 6.6 Hz), 7.12 (1H, t, J ¼ 7.2 Hz), 7.01 (1H, d, J ¼ 7.8
Hz), 3.74 (3H, s). 13C NMR (150 MHz, DMSO-d6): d 184.6, 159.5, Hz), 5.20–5.17 (1H, m), 4.26 (2H, d, J ¼ 7.2 Hz), 1.78 (3H, s), 1.69
155.3, 144.6, 124.9, 118.1, 113.2, 108.8, 55.8. HRMS m/z (M+): (3H, s). 13C NMR (150 MHz, DMSO-d6): d 183.5, 157.6, 150.5,
calcd for C9H7NO3: 177.0426; found: 177.0424.
138.16, 136.8, 124.4, 123.2, 117.8, 117.5, 110.9, 37.5, 25.3, 18.0.
4-Chloroindoline-2,3-dione (3f). Yield 84%; yellow solid; mp HRMS m/z (M+): calcd for C13H13NO2: 215.0946; found:
253–255 ꢀC. IR (ATR): 3451, 3181, 2989, 1735, 1606, 1471, 1437, 215.0948.
1312, 1273, 1242, 1195, 1154, 912, 782, 660, 546, 452, 405 cmꢁ1
.
1-(But-3-en-1-yl)indoline-2,3-dione (3m). Yield 83%; red
1H NMR (600 MHz, DMSO-d6): d 11.20 (1H, s), 7.54 (1H, t, J ¼ 8.4 solid; mp 72–73 ꢀC. IR (ATR): 3456, 3084, 2933, 2856, 1729,
Hz), 7.06 (1H, d, J ¼ 8.4 Hz), 6.84 (1H, t, J ¼ 7.8 Hz). 13C NMR 1598, 1466, 1353, 1292, 1179, 1127, 1089, 1042, 999, 921, 869,
(150 MHz, DMSO-d6): d 181.2, 158.6, 152.1, 139.0, 131.0, 123.6, 705, 637, 589, 552, 471 cmꢁ1 1H NMR (600 MHz, DMSO-d6):
.
114.8, 111.0. HRMS m/z (M+): calcd for C8H4ClNO2: 180.9931; d 7.66 (1H, t, 7.8), 7.53 (1H, d, J ¼ 6.6 Hz), 7.21 (1H, d, J ¼ 7.8
found: 180.9928.
Hz), 7.12 (1H, t, J ¼ 7.2 Hz), 5.85–5.78 (1H, m), 5.06 (1H, dd, J ¼
5-Chloroindoline-2,3-dione (3g). Yield 86%; orange solid; mp 16.8, 1.2 Hz), 5.00 (1H, d, J ¼ 9.6 Hz), 3.73 (2H, t, J ¼ 6.6 Hz), 2.38
247–249 ꢀC. IR (ATR): 3066, 2846, 1742, 1697, 1613, 1450, 1307, (2H, dd, J ¼ 13.8, 6.6 Hz). 13C NMR (150 MHz, DMSO-d6):
1264, 1209, 1165, 1116, 1042, 843, 742, 650, 578, 456, 405 cmꢁ1
.
d 183.6, 158.1, 150.7, 138.4, 135.1, 124.6, 123.3, 117.4, 117.3,
1H NMR (600 MHz, DMSO-d6): d 11.13 (1H, s), 7.59 (1H, d, J ¼ 111.0, 39.0, 31.2. HRMS m/z (M+): calcd for C12H11NO2:
9.0 Hz), 7.52 (1H, s), 6.91 (1H, d, J ¼ 7.8 Hz). 13C NMR (150 MHz, 201.0790; found: 201.0787.
DMSO-d6): d 183.3, 159.1, 149.2, 137.3, 126.8, 124.1, 119.1,
1-Cinnamylindoline-2,3-dione (3n). Yield 81%; red solid; mp
113.9. HRMS m/z (M+): calcd for C8H4ClNO2: 180.9931; found: 88–90 C. IR (ATR): 3451, 2920, 2852, 1735, 1603, 1465, 1371,
180.9927.
1319, 1142, 1069, 1039, 964, 896, 783, 745, 694, 540, 517 cmꢁ1
ꢀ
.
6-Chloroindoline-2,3-dione (3h). Yield 85%; red solid; mp 1H NMR (600 MHz, DMSO-d6): d 7.63 (1H, t, J ¼ 7.8 Hz), 7.57
255–257 ꢀC. IR (ATR): 3482, 3164, 3063, 1741, 1475, 1442, 1324, (1H, d, J ¼ 7.8 Hz), 7.41 (2H, d, J ¼ 8.4 Hz), 7.31 (2H, t, J ¼ 8.4
1278, 1245, 1097, 1063, 917, 892, 830, 788, 702, 664, 596, 664, Hz), 7.23 (1H, t, J ¼ 7.8 Hz), 7.15–7.11 (2H, m), 6.74 (1H, d, J ¼
596, 518, 470 cmꢁ1. 1H NMR (600 MHz, DMSO-d6): d 11.15 (1H, 16.2 Hz), 6.30 (1H, dt, J ¼ 16.2, 6.0 Hz), 4.47 (2H, d, J ¼ 6.0 Hz).
s), 7.52 (1H, d, J ¼ 8.4 Hz), 7.11 (1H, dd, J ¼ 7.8, 1.2 Hz), 6.93 13C NMR (150 MHz, DMSO-d6): d 183.3, 158.0, 150.5, 138.0,
(1H, d, J ¼ 1.2). 13C NMR (150 MHz, DMSO-d6): d 183.0, 159.4, 136.1, 132.0, 128.6, 127.7, 126.3, 124.5, 122.8, 119.1, 117.7,
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111.1, 41.3. HRMS m/z (M+): calcd for C17H13NO2: 263.0946;
found: 263.0948.
(E)-5-Methyl-1-(3,6,7-trimethylocta-2,6-dien-1-yl)indoline-
2,3-dione (3u). Yield 77%; red solid; mp 55–57 ꢀC; IR (ATR):
3447, 2964, 2916, 1734, 1621, 1489, 1438, 1374, 1334, 1261,
1-Benzylindoline-2,3-dione (3o). Yield 87%; red solid; mp
126–127 ꢀC. IR (ATR): 3447, 3032, 2970, 1728, 1605, 1463, 1344,
1172, 1021, 888, 822, 764, 657, 580, 467 cmꢁ1 1H NMR (300
.
1300, 1174, 1079, 1001, 816, 754, 690, 624, 551, 504, 465 cmꢁ1
.
MHz, DMSO-d6): d 7.42 (1H, d, J ¼ 8.1 Hz), 7.31 (1H, s), 6.86 (1H,
d, J ¼ 8.1 Hz), 5.14 (1H, t, J ¼ 6.0 Hz), 4.97 (1H, m), 4.22 (2H, d, J
¼ 6.3 Hz), 2.24 (3H, s), 2.02–1.97 (4H, m), 1.76 (3H, s), 1.54 (3H,
s), 1.49 (3H, s). 13C NMR (75 MHz, DMSO-d6): d 183.7, 157.6,
148.3, 140.1, 138.4, 132.6, 131.0, 124.6, 123.7, 117.8, 117.4,
110.7, 38.7, 37.5, 25.7, 25.4, 20.0, 17.5, 16.2. HRMS m/z (M+):
calcd for C19H23NO2: 297.1729; found: 297.1731.
1H NMR (600 MHz, DMSO-d6): d 7.58–7.56 (2H, m), 7.42 (2H, d, J
¼ 7.8 Hz), 7.34 (2H, t, J ¼ 7.2 Hz), 7.27 (1H, t, J ¼ 7.8 Hz), 7.11
(1H, t, J ¼ 7.8 Hz), 6.96 (1H, d, J ¼ 8.4 Hz), 4.90 (2H, s). 13C NMR
(150 MHz, DMSO-d6): d 183.1, 158.3, 150.3, 137.9, 135.5, 128.7,
127.5, 127.4, 124.5, 123.3, 117.7, 111.1, 43.0. HRMS m/z (M+):
calcd for C15H11NO2: 237.0790; found: 237.0791.
1-(3-Methylbenzyl)indoline-2,3-dione (3p). Yield 88%; red
solid; mp 130–132 C. IR (ATR): 3460, 2920, 2853, 1732, 1606,
1-(3,5-Dimethoxybenzyl)-7-methylindoline-2,3-dione
(3v).
ꢀ
Yield 79%: red solid; mp 138–139 ꢀC. IR (ATR): 3001, 2834, 1781,
1730, 1601, 1463, 1369, 1234, 1152, 1027, 927, 779, 734, 684,
593, 514, 427 cmꢁ1. 1H NMR (600 MHz, DMSO-d6): d 7.43 (1H, t,
J ¼ 8.4 Hz), 6.91 (1H, d, J ¼ 7.2 Hz), 6.77 (1H, d, J ¼ 7.8 Hz), 6.55
(2H, s), 6.39 (1H, s), 4.79 (2H, s), 3.70 (6H, s), 2.47 (3H, s). 13C
NMR (150 MHz, DMSO-d6) 184.0, 161.2, 158.6, 150.9, 139.8,
138.4, 137.7, 125.9, 116.1, 109.0, 105.8, 99.5, 55.6, 43.4, 17.9.
HRMS m/z (M+): calcd for C18H17NO4: 311.1158; found:
311.1157.
1466, 1338, 1148, 1092, 1007, 935, 876, 775, 691, 633, 509, 556,
466, 429 cmꢁ1. 1H NMR (600 MHz, DMSO-d6): d 7.56 (2H, t, J ¼
8.4 Hz), 7.24–7.21 (3H, m), 7.12–7.08 (2H, m), 6.95 (1H, d, J ¼ 7.8
Hz), 4.86 (2H, s), 2.26 (3H, s). 13C NMR (150 MHz, DMSO-d6):
d 183.1, 158.3, 150.4, 138.0, 137.9, 135.4, 128.5, 128.2, 127.8,
124.5, 124.4, 123.3, 117.7, 111.1, 42.9, 21.0. HRMS m/z (M+):
calcd for C16H13NO2: 251.0946; found: 251.0943.
1-(3,5-Dimethoxybenzyl)indoline-2,3-dione (3q). Yield 85%;
red solid; mp 183–185 ꢀC. IR (ATR): 2966, 2834, 1734, 1603,
1463, 1347, 1294, 1199, 1156, 1040, 938, 865, 837, 762, 681, 599,
1-(4-Chlorobenzyl)-5-methylindoline-2,3-dione (3w). Yield
82%; red solid; mp 167–169 ꢀC. IR (ATR): 3439, 2921, 2854,
1744, 1721, 1614, 1486, 1334, 1263, 1224, 1176, 1092, 1017, 950,
1
469, 542, 469 cmꢁ1. H NMR (600 MHz, DMSO-d6): d 7.58–7.55
705, 659, 598, 462, 425 cmꢁ1 1H NMR (600 MHz, DMSO-d6):
.
(2H, m), 7.11 (1H, t, J ¼ 7.8 Hz), 6.94 (1H, d, J ¼ 7.8 Hz), 6.58 (2H,
s), 6.40 (1H, s), 4.81 (2H, s), 3.70 (6H, s). 13C NMR (150 MHz,
DMSO-d6): d 183.1, 160.7, 158.4, 150.4, 137.9, 137.8, 124.4,
123.3, 117.8, 111.1, 105.4, 99.1, 55.2, 43.0. HRMS m/z (M+): calcd
for C17H15NO4: 297.1001; found: 297.1001.
d 7.44 (2H, t, J ¼ 8.4 Hz), 7.39 (4H, d, J ¼ 8.4 Hz), 6.85 (1H, t, J ¼
9.0 Hz), 4.88 (2H, s), 2.25 (3H, s). 13C NMR (150 MHz, DMSO-d6):
d 183.1, 158.4, 148.0, 138.2, 134.6, 132.8, 132.1, 129.3, 128.5,
124.7, 117.7, 110.8, 42.2, 20.0. HRMS m/z (M+): calcd for
1-(4-Chlorobenzyl)indoline-2,3-dione (3r). Yield 87%; red
solid; mp 167–169 C. IR (ATR): 3443, 2922, 2853, 1731, 1607,
C
16H12ClNO2: 285.0557; found: 285.0558.
5-Chloro-1-(3,5-dimethoxybenzyl)indoline-2,3-dione
ꢀ
(3x).
Yield 81%; red solid; mp 172–174 ꢀC. IR (ATR) 3458, 2934, 2842,
1464, 1343, 1164, 1088, 1010, 928, 846, 796, 755, 599, 546, 464,
1
419 cmꢁ1. H NMR (600 MHz, DMSO-d6): d 7.57 (2H, t, J ¼ 7.2
1734, 1595, 1465, 1433, 1322, 1259, 1211, 1155, 1055, 1021, 933,
851, 810, 733, 666, 595, 526, 459 cmꢁ1 1H NMR (600 MHz,
.
Hz), 7.46 (2H, d, J ¼ 8.4 Hz), 7.39 (2H, d, J ¼ 7.8 Hz), 7.11 (1H, t, J
¼ 7.8 Hz), 6.95 (1H, d, J ¼ 7.8 Hz), 4.90 (2H, s). 13C NMR (150
MHz, DMSO-d6): d 183.1, 158.5, 150.2, 138.1, 134.7, 132.3, 129.4,
128.7, 124.7, 124.5, 123.5, 117.9, 111.1, 111.0, 42.4. HRMS m/z
(M+): calcd for C15H10ClNO2: 271.0400; found: 271.0403.
1-(But-3-en-1-yl)-5-methylindoline-2,3-dione (3s). Yield 80%;
red solid; mp 73–75 ꢀC. IR (ATR): 3460, 2964, 2922, 2852, 1733,
DMSO-d6) d 7.62–7.61 (2H, m), 6.92 (1H, d, J ¼ 9.6 Hz), 6.59 (2H,
s), 6.40 (1H, s), 4.8 (2H, s), 3.70 (6H, s). 13C NMR (150 MHz,
DMSO-d6): d 182.0, 160.7, 158.2, 148.8, 137.6, 136.7, 127.5,
123.9, 119.3, 112.7, 105.4, 99.1, 55.2, 43.1. HRMS m/z (M+) calcd
for C17H14ClNO4: 331.0611; found: 331.0614.
1617, 1594, 1452, 1345, 1296, 1122, 997, 822, 660, 588, 472 cmꢁ1
.
1H NMR (600 MHz, DMSO-d6): d 7.45 (1H, d, J ¼ 7.2 Hz), 7.32
(1H, s), 7.08 (1H, d, J ¼ 7.8 Hz), 5.82–5.77 (1H, m), 5.04 (1H, d, J
¼ 17.4 Hz), 4.9 (1H, d, J ¼ 9.6 Hz), 3.69 (2H, t, J ¼ 7.2 Hz), 2.35
(2H, dd, J ¼ 14.4, 7.2 Hz), 2.25 (3H, s). 13C NMR (150 MHz,
DMSO-d6): d 183.6, 157.9, 148.4, 138.6, 135.0, 132.5, 124.7,
117.2, 117.1, 110.7, 38.9, 31.2, 19.9. HRMS m/z (M+): calcd for
Acknowledgements
This study was supported by the National Research Foundation
of Korea (NRF) grant funded by the Korea government (MSIP)
(NRF-2014R1A2A1A11052391) and the Nano Material Tech-
nology Development Program (2012M3A7B4049675).
C
13H13NO2: 215.0946; found: 215.0949.
1-(3-Chloropropyl)-5-methylindoline-2,3-dione (3t). Yield
78%; red solid; mp 98–100 ꢀC. IR (ATR): 3466, 2935, 2861, 1728,
Notes and references
1619, 1488, 1451, 1346, 1290, 1201, 1165, 1126, 832, 639, 754,
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716, 469 cmꢁ1. H NMR (600 MHz, DMSO-d6): 7.46 (1H, d, J ¼
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63786 | RSC Adv., 2016, 6, 63782–63787
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