Oxidative Radical Cyclization of N-methyl-N-arylpropiolamide to Isatins via Cleavage of the Carbon-carbon Triple Bond

Article abstract of DOI:10.1002/adsc.201800592

A radical cyclization of N-methyl-N-arylpropiolamide to isatins via an oxidative cleavage of a carbon-carbon triple bond has been developed. In the presence of oxone and NaNO₂, a variety of N-methyl-N-arylpropiolamides were smoothly transformed into isatins. A nitration reaction proceeded along with the oxidative cyclization; both nitrated and non-nitrated isatins were obtained in a one-pot reaction with moderate to good total yields. This is the first example for the synthesis of isatins via the oxidative radical cleavage of a carbon-carbon triple bond. (Figure presented.).

Full text of DOI:10.1002/adsc.201800592

Title: Oxidative Radical Cyclization of N-methyl-N-arylpropiolamide to
Isatins via Cleavage of the Carbon-carbon Triple Bond
Authors: Yan-Yan Liao, Yong-Chao Gao, Wenxu Zheng, and Ri-Yuan
Tang
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Oxidative Radical Cyclization of N-methyl-N-arylpropiolamide
to Isatins via Cleavage of the Carbon-carbon Triple Bond
Yan-Yan Liao,a Yong-Chao Gao,a Wenxu Zheng*a and Ri-Yuan Tang*ab
a
Department of Applied Chemistry, College of Materials and Energy, South China Agricultural University, Guangzhou
510642, China.
E-mail: rytang@scau.edu.cn, wzheng@scau.edu.cn
Key Laboratory of Natural Pesticide & Chemical Biology, Ministry of Education, South China Agricultural University,
b
Guangzhou 510642, China.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract.
A
radical cyclization of N-methyl-N-
arylpropiolamide to isatins via an oxidative cleavage of a
carbon-carbon triple bond has been developed. In the
presence of oxone and NaNO2, a variety of N-methyl-N-
arylpropiolamides were smoothly transformed into isatins. A
nitration reaction proceeded along with the oxidative
cyclization; both nitrated and non-nitrated isatins were
obtained in a one-pot reaction with moderate to good total
yields. This is the first example for the synthesis of isatins
via the oxidative radical cleavage of a carbon-carbon triple
bond.
Keywords: Radical reaction; Oxidation; Cyclization;
Isatin; Nitration
cyclization that proceeds through an oxidative radical
cleavage of the carbon-carbon triple bond (Scheme
1b). Due to the high chemical bond energy of the
Introduction
The carbon-carbon triple bond is an extremely useful carbon-carbon triple bond and the relatively electron-
synthetic building block for a diverse number of deficient environment resulting from the electron
chemical transformations.[1] Considerable attention withdrawing effect of the carbonyl group, the
has
been
paid
to
the
cyclization,[2a,b] oxidative cleavage of the terminal triple bond in
difunctionalization,[2c,d] and oxidation of alkynes[2e-h] propiolamide remains challenging.
for the construction of a diverse array of molecules. In
recent years, the oxidative cleavage of carbon-carbon
triple bonds has emerged as a powerful tool for a
variety of chemical reactions.[3] Significant effort has
been devoted to the oxidative cleavage of the carbon-
carbon triple bond into the corresponding oxo-
compounds.[3a] For example, the Jiang group[3b]
disclosed an efficient transformation of internal
alkynes to carboxylic esters via a palladium-catalyzed
cleavage of carbon-carbon triple bonds. Xie
developed a facile and convenient Rh(Ⅲ)-catalyzed
acylation of the Csp2−H bond of N-phenoxyacetamide
with a number of alkynes under mild conditions; the
alkynes are employed as a novel acyl source.[3h] In
addition, the transformation of the alkyne group to the
Scheme 1. Synthetic methods for isatins
corresponding nitrile functionality has been achieved
through a C−C bond cleavage.[3d-f] For example, the
Jiao group[3d] reported the first direct conversion of
alkynes into nitriles via a Ag-catalyzed nitrogenation
of alkynes. Inspired by this intriguing alkyne
chemistry, we envisioned that isatins could be
synthesized from N-methyl-N-arylpropiolamide via a
Application of this new chemistry for the preparation
of isatins is of great interest. Isatins are an important
class of indolone derivative which are commonly
found in natural products,[4] pharmaceuticals (such as
1
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
anti-allergenic, antimalarial, and anti-HIV compounds, NaNO2 needed for the reaction was examined (entries
etc.),[5] and dyes.[6] In addition, isatins are important 8-11). Encouragingly, products 2a and 3a could be
skeletons for drug design and functional materials obtained in a total yield of 86% (yields of 32% and
development.[7] Owing to the synthetic utility of 54%, respectively) when 1a was treated with oxone
isatins, the development of efficient methods for the (0.5 eq) and NaNO2 (1.3 equiv) (entry 8).
synthesis of such compounds has become a prominent
Table 1. Screening of optimal conditions [a]
.
area of research. In the past few decades, the
Sandmeyer, Stollé, and Martinet methodologies have
been commonly used for the synthesis of isatins.[8]
However, these traditional methods possess several
disadvantages, such as narrow substrate scope, poor
yields, and the need for strong acids, thus are
insufficient for the preparation of a diverse range of
isatins. In 2010, the Li group[9] reported an intriguing
method for the synthesis of isatins via a Cu-catalyzed
intramolecular C-H oxidative acylation of formyl-N-
arylformamides using O2 as a terminal oxidant
(Scheme 1a, Eqn 1). In 2015, the Ilangovan group[10]
developed an efficient iodine-promoted synthesis of
Yield (%)
Entry Oxidant (eq)
NaNO2 (eq)
NaNO2 (1)
NaNO2 (1)
Solvent
2a
3a
1
2
K2S2O8 (0.5)
(NH4)2S2O8
(0.5)
MeCN
MeCN
13
29
trace trace
3
4
5
6
7
8
9
Oxone (0.5)
DCP (0.5)
BPO (0.5)
DTBP (0.5)
H2O2 (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
NaNO2 (1)
NaNO2 (1)
NaNO2 (1)
NaNO2 (1)
NaNO2 (1)
NaNO2 (1.3) MeCN
NaNO2 (1.7) MeCN
NaNO2 (2)
NaNO2 (3)
－
MeCN
MeCN
MeCN
MeCN
MeCN
22
0
30
0
0
0
0
0
isatins
from
2′-aminophenylacetylenes,
2′-
trace trace
aminostyrenes, and 2′-amino-β-ketoesters through
oxidative processes (Scheme 1a, Eqn 2). Although
progress has been made in the synthesis of isatins
over recent years, efficient synthetic methods for their
preparation remain scarce. In order to enrich the
diversity of the isatins that can be prepared, the
development of efficient synthetic methods with good
functional groups tolerance are desired. Herein we
report the preparation of isatins via a new radical
cyclization of N-methyl-N-arylpropiolamide through
oxidative cleavage of a carbon-carbon triple bond in
the presence of oxone and NaNO2 (Scheme 1b).
32
27
26
17
0
54
50
48
25
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23[b]
24[c]
25[d]
26[e]
MeCN
MeCN
MeCN
－
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) Toluene trace
NaNO2 (1.3) dioxane trace
NaNO2 (1.3) Acetone
NaNO2 (1.3) H2O
NaNO2 (1.3) HFIP
NaNO2 (1.3) DMF
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
NaNO2 (1.3) MeCN
0
0
Oxone (0.1)
Oxone (0.2)
Oxone (1)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
Oxone (0.5)
trace trace
10
19
28
35
0
0
0
0
0
0
trace trace
0
0
trace 14
Results and Discussion
27
32
11
15
32
50
15
47
Our study began with the reaction of N-methyl-N-
arylpropiolamide (1a) with radical oxidants. The
inexpensive NaNO2 is an oxidative radical initiator.[11]
It was assumed that a combination of peroxide and
NaNO2 is expected to be a radical system for the
cleavage of carbon-carbon triple bonds. Thus,
combinations of NaNO2 with different peroxides,
including K2S2O8, (NH4)2S2O8, oxone, DCP (Dicumyl
peroxide), BPO (Benzoyl peroxide), DTBP (Di-tert-
butyl peroxide), and H2O2 were examined (entries 1-
7). The results show that a nitration reaction occurs
along with the oxidative cyclization of 1a, leading to
the formation of non-nitrated and nitrated products 2a
27[f]
[a]
Reaction conditions: 1a (0.1 mmol), solvent (1 mL), at
110 C for 12 h. [b] at 70 C. [c] at 90 C. [d] at 130 C. [e]
o
o
o
o
under N2. [f] under O2.
Unexpectedly, the reaction yield began to decrease
when more than 1.3 equivalents of NaNO2 were used
(entries 9-11); the high concentration of NaNO2 led to
the formation of unknown by-products. In addition to
NaNO2, the reaction yield is also dependent on the
amount of oxone. In the absence of oxone, no product
was obtained (entry 13). Compared with conducting
the reaction with 0.5 equiv of oxone, increasing or
decreasing the amount of oxone led to a decrease in
yield (entries 14-16). Next, different solvents,
including toluene, 1,4-dioxane, acetone, H2O, HFIP
and DMF, were investigated (entries 17-22).
Compound 1a was almost completely recovered when
the reaction was carried out in acetone, H2O, or HFIP.
The starting material was consumed when the
reaction was conducted in toluene, 1,4-dioxane, and
DMF, but the reaction was messy and none of the
target product was isolated. The results show that the
reaction temperature is also crucial for this
and 3a, respectively. NaNO2 adopts the role of a
16a]
radical initiator and a nitro source.[12e,
The
treatment of 1a with NaNO2 (1 equiv) and K2S2O8
(0.5 equiv) gave products 2a and 3a in yields of 13%
and 29%, respectively (entry 1). (NH4)2S2O8 is
ineffective in this reaction (entry 2). Compared with
K2S2O8, oxone is more effective for the reaction, and
the yield of product 2a could be improved to 22%.
Next, other organic peroxides, such as DCP, BPO,
DTBP, and H2O2, were also evaluated. However,
these oxidants were all ineffective, and the starting
material was mostly recovered. In order to improve
the reaction efficiency and selectivity, the quantity of
2
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
Table 2. Substrates scope [a]
.
transformation (entries 23-25). Reaction at 70 oC only
gave product 3a in 14% yield with none of product 2a
being observed. This result indicates that the
formation of 2a by hydrogen elimination requires
more energy than nitration (entry 23). Reactivity was
greatly surpressed when the reaction was carried out
under a nitrogen atmosphere, resulting in a low yield
of the desired product (entry 26). An oxygen
atmosphere was favorable to the formation of product
3a, but the total yield of products 2a and 3a was
lower (entry 27).
With the optimal reaction conditions in hand, the
reaction scope was investigated (Table 2). The results
show that substrates bearing electron-withdrawing
groups, including nitro, cyano, trifluoromethyl, acetyl,
ester, fluoro, chloro, bromo, and iodo substituents, are
all tolerated well with the corresponding products
being obtained in moderate to good total yields
(Table 2, substrates 1a-j, 1m). All of these functional
groups are synthetically useful in medicinal chemistry.
Substrates bearing a strong electron-withdrawing
group lead to the formation of the corresponding non-
nitrated product 2 because the electron-deficient
aromatic rings disfavor the nitration reaction. For
example, nitro substituted compound 1b only gave its
corresponding product 2b in 55% yield. A substrate
bearing a trifluoromethyl group afforded product 2d
in 59% yield, with 3d being obtained in 12% yield.
The structure of product 3d was confirmed by single
crystal X-ray diffraction (see ESI).[13] Interestingly, a
substrate bearing a bromo group gave the dinitrated
product 4i rather than the mono-nitrated product 3i.
Iodo-substrate 1j was amenable to the reaction
conditions giving product 2j in 40% yield. However,
product 3j underwent deiodination during column
chromatography purification, affording 3a in 32%
yield. When a chloro group was present at the meta-
position of substrate 1m, the 4-nitro substituted
product 3m was obtained in 20% yield. NOE NMR
experiments were conducted on products 3f and 3m in
order to confirm the selectivity of the nitration (See
ESI). The ortho methyl substituted substrate
underwent reaction smoothly to give products 2n and
3n in 19% and 39% yields, respectively. For the
reaction of substrate 1o bearing both a methyl and a
bromo group, in addition to the formation of products
2o and 3o, a dinitrated product 4o was also isolated.
Susbtrates in which the methyl substituent at the
nitrogen atom was replaced with an ethyl, isopropyl,
prop-2-ynyl, cyanopropyl or phenyl group, also
performed well to give their corresponding products
in moderate total yields (Products 1p-t). Finally, N-
methyl-N,3-diphenylpropiolamide was subjected to
our reaction conditions; however, cyclization of the
interal alkyne was unsuccessful. Instead, nitrosation
occurred at the para-position of the acylamino group,
affording product 5 in 72% yield.
[a]
Reaction conditions: reaction conditions: 1a (0.2 mmol),
Oxone (0.1 mmol, 0.5 equiv), NaNO2 (0.26 mmol, 1.3
equiv), at 110 oC in MeCN for 12 h.
Next, a gram-scale reaction was conducted with
substrate 1a (7 mmol and 15 mmol, respectively). The
reactions proceeded well to give products 2a and 3a
in moderate total yields (Scheme 2, eqn 1). It is
important to note that isatins bearing a nitro group are
important compounds because the nitro group can be
reduced to an amino group, a process that is useful for
further derivatization.[12] In the presence of iron
powder (3.0 equiv) and HCl (37%, conc.), the nitro
functionality was reduced to an amino group in a
mixed solvent system of H2O/MeOH, providing
product 6 in 84% yield (Scheme 2, Eqn 2).
3
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
of N-(4-chlorophenyl)-N-methylformamide 11 was
observed by GC-MS analysis (Scheme 3, Eqn 7)
Scheme 2. Gram-scale reaction and the reduction of nitro
group.
To better understand the reaction mechanism, control
experiments were conducted. Initially, radical
scavengers such as 2,6-di-tertbutyl-4-methylphenol
(BHT)
and
2,2,6,6-Tetramethylpiperidinooxy
(TEMPO) were added to the reaction. In the presence
of BHT or TEMPO, the reaction was completely
inhibited and the starting material was recovered in
93% and 91% yields, respectively (Scheme 3, Eqn 1).
These results suggest that the reaction proceeds
through a radical process. Classically, alkynes can be
transformed into ketones or a compound with one less
carbon atom by the cleavage of a carbon-carbon triple
bond under oxidative conditions.[14] We speculated
that the compound 7 may be the reaction intermediate
that is obtained from the oxidation of the terminal
alkyne. However, compound 7 was not detected by
GC-MS analysis. Additionally, the reaction of
compound 7 under standard conditions only gave
product 2a in 70% yield; the nitrated product 3a was
not observed (Scheme 3, Eqn 2). This result suggests
that compound 7 may not be the reaction intermediate.
Based on previous reports,[15] the generation of
compound 8 from 1a is possible. However, none of
the desired product was formed for the reaction of
compound 8 under the reaction conditions, with only
compound 7 being obtained in 15% yield (Scheme 3,
Eqn 3). To better understand the chemical
transformation of the terminal alkyne, compound 9
was prepared and subjected to the reaction conditions;
no oxidized product was formed (Scheme 3, Eqn 4).
In order to gain a better understanding of the nitration
step, product 2a was subjected to the reaction
conditions, but no nitration occurred (Scheme 3, Eqn
5). The results suggest that the oxidative cyclization
and nitration may be a collaborative pathway. Next,
the source of the oxygen atoms in the carbonyl and
nitro groups was studied by adding H2O18 to the
reaction mixture (Scheme 3, Eqn 6). The O18-labelled
product 2a was obtained as the major product. A
mixture of product 3a, possessing one or two O18-
labelled atoms, was observed in a 1:1 ratio,
suggesting that the oxygen atoms in the carbonyl and
nitro groups originate from the H2O. We envisaged
that the cleavage of the carbon-carbon triple bond
may produce an active carbonyl species which can be
trapped by an amine. Thus, 4-chloro-N-methylaniline
was added to the reaction mixture in order to trap the
active carbonyl species. Fortunately, a small amount
Scheme 3. Control experiments.
According to the present results and previous
reports,[16] a possible reaction mechanism has been
proposed (Scheme 4). Initially, NaNO2 is quickly
converted to an NO radical via the assistance of
oxone at high temperature. The NO radical may be
further oxidized to an NO2 radical for the nitration
reaction. The NO2 radical can be trapped by the C−C
triple bond to afford intermediate A, which can
undergo isomerization to give intermediate B that also
has a resonance structure C.[17] Subsequently, a rapid
cyclization occurs to give intermediate D. Hydrogen
radical elimination of D leads to intermediate E,
which undergoes a decarbonylation reaction to
produce intermediate F. Alternatively, intermediate D
could be trapped by the NO2 radical to give
intermediate G. A subsequent decarbonylation of G
gives intermediate H. Finally, both intermediates F
and H undergo hydrolysis to afford 2a and 3a,
respectively. Intermediates E, F, G, and H may all be
unstable under the reaction conditions or
electrospraying environment - these compounds were
not observed by LC-MS analysis. A more detailed
reaction mechanism remains to be uncovered.
4
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
chromatography (hexane/ethyl acetate) to afford the desired
products 2a and 3a.
1-methylindoline-2,3-dione (2a)[9]. Yield: 10.3 mg (32%),
o
o
Crimson solid, m.p. 124.1–125.0 C (lit. 121.7–124.5 C).
1H NMR (600 MHz, CDCl3) δ=7.65–7.58 (m, 2H), 7.14 (t,
J = 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 3.26 (s, 3H). 13C
NMR (151 MHz, CDCl3) δ = 183.3, 158.2, 151.5, 138.4,
125.2, 123.8, 117.5, 109.9, 26.2. IR (KBr) δ= 1742, 1727,
1609, 1471, 1327cm-1. LRMS (EI, 70 eV) m/z (%): 161
(83), 133 (32), 105 (59), 104 (100), 78 (35).
1-methyl-6-nitroindoline-2,3-dione (3a). Yield: 22.2 mg
(54%), Crimson solid, m.p. 117.9–118.3 oC (CAS No.
108726-52-9). 1H NMR (600 MHz, CDCl3) δ = 8.03 (dd, J
= 8.0, 1.6 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 1.4
Hz, 1H), 3.38 (s, 3H). 13C NMR (151 MHz, CDCl3) δ =
182.0, 157.2, 153.7, 152.0, 126.1, 120.9, 119.2, 105.2, 26.8.
IR (KBr) δ = 1748, 1724, 1603, 1468, 1324 cm-1. LRMS
(EI, 70 eV) m/z (%): 206 (100), 178 (56), 150 (79), 104
(74), 77 (44), 63 (47).
Scheme 4. A possible mechanism.
1-methyl-5-nitroindoline-2,3-dione (2b)[12a]. Yield: 22.7
mg (55%), Yellow solid, m.p. 201.1–202.3 oC (lit. 201–202
oC). LRMS (EI, 70 eV) m/z (%): 206 (100), 178 (73), 150
Conclusion
1
In summary, a novel method for the oxidative radical
cyclization of N-methyl-N-arylpropiolamide into
isatins, in the presence of NaNO2 and oxone, has been
developed. This represents the first example for the
synthesis of isatins through a sequential radical
oxidative cleavage and cyclization of a terminal
carbon-carbon triple bond. Although perfect
selectivity for the formation of isatins or nitrated
isatins has not been achieved, the preparation of two
(66), 149 (43), 120 (23), 104 (58), 77 (45), 63(35). H
NMR (600 MHz, CDCl3) δ = 8.58 (dd, J = 8.7, 2.4 Hz, 1H),
8.49 (d, J = 2.3 Hz, 1H), 7.08 (d, J = 8.7 Hz, 1H), 3.38 (s,
3H).13C NMR (151 MHz, CDCl3) δ = 179.9, 156.7, 154.3,
143.1, 132.5, 119.8, 115.9, 109.0, 25.7.
1-methyl-2,3-dioxoindoline-5-carbonitrile (2c)[18a]. Yield:
o
13.8 mg (37%), Crimson solid, m.p. 191.8–192.6 C (lit.
1
157.6–160oC). H NMR (600 MHz, Acetone) δ = 8.07 (dd,
J = 8.3, 1.7 Hz, 1H), 7.93 (d, J = 1.4 Hz, 1H), 7.35 (d, J =
8.3 Hz, 1H), 3.29 (s, 3H). 13C NMR (151 MHz, Acetone)
different isatins in a one-pot reaction is of interest to δ=181.8, 157.9, 154.7, 141.8, 127.6, 118.0, 117.6, 111.3,
106.5, 25.8. IR (KBr) δ = 1763, 1742, 1739, 1624, 1592,
the synthetic community. It is noteworthy that isatins
1489, 1468, 1339 cm-1. LRMS (EI, 70 eV) m/z (%):
bearing a nitro group cannot be easily prepared using
186(69), 158(35), 130(73), 129(100), 103(38).
other methodologies. Moreover, the nitro group can
be readily transformed into an amino group allowing
for further diversification. This study provides an
alternative protocol for the preparation of isatins,
particularly for the synthesis of nitro and amino
derivatives.
1-methyl-6-nitro-2,3-dioxoindoline-5-carbonitrile (3c).
Yield: 7.8 mg (17%), Crimson solid, m.p. 196.0–197.0 oC.
1H NMR (600 MHz, Acetone) δ 8.22 (s, 1H), 8.08 (s, 1H),
3.42 (s, 3H). 13C NMR (151 MHz, Acetone) δ 180.6, 157.5,
155.4, 130.2, 128.7, 120.5, 114.3, 107.6, 101.5, 26.3. IR
(KBr) δ = 1765, 1746, 1735, 1621, 1598, 1487, 1465 cm-1.
1-methyl-5-(trifluoromethyl)indoline-2,3-dione (2d)[9].
o
Yield: 27.0 mg (59%), Yellow solid, m.p. 124.9–125.5 C
Experimental Section
(lit. 126.7–128.2oC). 1H NMR (600 MHz, CDCl3) δ 7.89 (d,
J = 8.3 Hz, 1H), 7.85 (s, 1H), 7.05 (d, J = 8.3 Hz, 1H), 3.32
(s, 3H). 13C NMR (151 MHz, CDCl3) δ = 181.98, 157.81,
153.70, 135.3 (q, J = 3.6 Hz, 1C), 126.4 (q, J = 33.9 Hz,
1C), 123.4 (q, J = 272.1 Hz, 1C), 122.4 (q, J = 3.6 Hz, 1C),
117.2, 110.2, 26.52. IR (KBr) δ = 1742, 1624, 1598, 1324,
1283, 1162cm-1. LRMS (EI, 70 eV) m/z (%): 229 (53), 201
(25), 173 (50), 172 (100), 146 (24), 145 (24).
General remarks
1H and 13C NMR spectra were measured on a Bruker
1
Avance-Ⅲ 500 instrument (600MHz for H, 151 MHz for
13C NMR spectroscopy) using CDCl3 as the solvent.
Chemical shifts for 1H and 13C NMR were referred to
internal Me4Si (0 ppm) as the standard. The following
abbreviations (or combinations thereof) were used to
explain multiplicities: s = singlet, d = doublet, t = triplet, q
= quartet, m = multiplet. Mass spectra were measured on
an Agilent GC-MS-5975C Plus spectrometer (EI). HRMS
(ESI) analysis was measured on a Thermo Scientific LTQ
Orbitrap XL.
1-methyl-6-nitro-5-(trifluoromethyl)indoline-2,3-dione
(3d). Yield: 6.6 mg (12%), Yellow solid, m.p. 163.1–163.7
1
oC. H NMR (600 MHz, CDCl3) δ 8.04 (s, 1H), 7.32 (s,
1H), 3.38 (s, 3H). 13C NMR (151 MHz, CDCl3) δ = 180.1,
156.8, 154.7, 154.1, 125.0(q, J = 5.1 Hz, 1C), 121.4(q, J =
273.8 Hz, 1C) 118.7(q, J = 35.6 Hz, 1C), 118.1, 106.5, 27.0.
IR (KBr) δ = 1757, 1742, 1633, 1598, 1551, 1365, 1292cm-
1. LRMS (EI, 70 eV) m/z (%): 274 (45), 246 (30), 229 (26),
218(31), 201 (22), 173 (34), 172 (100), 152 (22), 145 (52).
+
HRMS (ESI) m/z calcd for C10H6F3N2O4 (M+H)+
Typical Experimental Procedure To a flame-dried
Schlenk tube with a magnetic stirring bar was charged 1a
(0.2 mmol), oxone (0.1 mmol), NaNO2 (0.26 mmol) and
MeCN (2 mL) under an air atmosphere. The reaction
mixture was stirred at 110 °C for 12 hours. After reaction
completion, the mixture was poured into ethyl acetate and
washed with saturated Na2CO3.The aqueous layer was
extracted with ethyl acetate and the combined organic
layers were dried over anhydrous Na2SO4 and evaporated
under vacuum. The residue was purified by flash column
275.02742, found 275.02661.
5-acetyl-1-methylindoline-2,3-dione (2e)[9]. Yield: 14.2
o
mg (35%), Yellow solid, m.p. 140.2–140.7 C (lit. 145.3–
o
1
148.4 C). H NMR (600 MHz, Acetone) δ = 8.32 (dd, J =
8.3, 1.8 Hz, 1H), 8.10 (d, J = 1.8 Hz, 1H), 7.26 (d, J = 8.3
Hz, 1H), 3.29 (s, 3H), 2.60 (s, 3H). 13C NMR (151 MHz,
Acetone) δ = 195.1, 182.9, 158.4, 155.0, 138.3, 132.7,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800592
Advanced Synthesis & Catalysis
124.0, 117.4, 110.2, 25.7, 25.6. IR (KBr) δ = 1756, 1683, (33), 102 (46), 99 (39), 88 (29), 74 (25), 62 (22). HRMS
1622, 1371, 1321, 1265 cm-1. LRMS (EI, 70 eV) m/z (%): (ESI) m/z calcd for C9H5ClN2O4Na+ (M+Na)+ 262.98301,
203 (58), 160 (100), 132 (54).
found 262.98331.
5-acetyl-1-methyl-6-nitroindoline-2,3-dione (3e). Yield: 5-bromo-1-methylindoline-2,3-dione (2i)[18b]. Yield: 14.9
o
1
o
15.9 mg (32%), Yellow solid, m.p. 218.1–219.2 C. H mg (31%), Crimson solid, m.p. 161.8–162.3 C (lit. 163–
o
1
NMR (600 MHz, DMSO) δ = 8.20 (s, 1H), 7.78 (s, 1H), 164 C). H NMR (600 MHz, CDCl3) δ = 7.76-7.70 (m,
3.18 (s, 3H), 2.62 (s, 3H). 13C NMR (151 MHz, DMSO) δ 2H), 6.83 (d, J = 8.3 Hz, 1H), 3.26 (s, 3H). 13C NMR (151
196.4, 181.4, 159.0, 154.9, 153.8, 126.2, 126.0, 119.5, MHz, CDCl3) δ 182.1, 157.5, 150.1, 140.6, 128.1, 118.6,
106.7, 28.8, 27.1. IR (KBr) δ = 1758, 1734, 1685, 1629, 116.6, 111.6, 26.3. IR (KBr) δ = 1751, 1733, 1722, 1607,
1376, 1325, 1261 cm-1. LRMS (EI, 70 eV) m/z (%): 248 1474, 1442, 1327 cm-1. LRMS (EI, 70 eV) m/z (%): 241
(47), 233 (45), 205 (100), 175 (21), 131 (35), 103 (22).
(74), 239 (75), 213 (64), 211 (61), 186 (67), 185 (97), 183
(75), 182 (100), 159 (22), 156 (26), 77 (38), 76 (20), 75
(31), 74 (27), 63 (38).
Ethyl 1-methyl-2,3-dioxoindoline-5-carboxylate (2f).
o
Yield: 21.4 mg (46%), Yellow solid, m.p. 136.6–136.8 C.
1H NMR (600 MHz, CDCl3) δ = 8.35 (dd, J = 8.3, 1.5 Hz, 5-bromo-1-methyl-6-nitroindoline-2,3-dione (4i). Yield:
o
1
1H), 8.28 (d, J = 1.2 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 4.39 16.0 mg (28%), Yellow solid, m.p. 212.6–213.5 C. H
(q, J = 7.1 Hz, 2H), 3.32 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). NMR (600 MHz, CDCl3) δ = 7.94 (s, 1H), 3.33 (s, 3H). 13C
13C NMR (151 MHz, CDCl3) δ 182.4, 164.9, 158.3, 154.4, NMR (151 MHz, CDCl3) δ 180.7, 156.5, 155.2, 150.5,
134.0, 126.5, 126.4, 117.1, 109.7, 61.5, 26.5, 14.3. IR 131.3, 119.5, 108.4, 106.9, 26.8. IR (KBr) δ = 1748, 1621,
(KBr) δ = 1754, 1739, 1709, 1612, 1592, 1321, 1268, 1238 1542, 1409, 1345, 1306 cm-1. LRMS (EI, 70 eV) m/z (%):
cm-1. LRMS (EI, 70 eV) m/z (%): 233(97), 205 (48), 188 331(4), 329 (6), 286 (56), 284 (50), 258 (46), 256 (70), 254
(27), 176 (34), 160 (100), 149 (36), 148 (35), 132 (89), 104 (41), 230 (46), 228 (28), 199 (27), 197 (70), 184 (39), 182
(30), 77 (27), 63 (21).
(45), 143 (34), 141 (41), 115 (34),103 (100), 88 (55), 83
(40).
Ethyl 1-methyl-6-nitro-2,3-dioxoindoline-5-carboxylate
(3f). Yield: 13.9 mg (25%), Yellow solid, m.p. 159.8–160.0 5-iodo-1-methylindoline-2,3-dione (2j)[18d]. Yield: 26.6
1
o
oC. H NMR (600 MHz, CDCl3) δ = 8.13 (s, 1H), 7.18 (s, mg (40%), Crimson solid, m.p. 166.4–167.0 C (lit. 150–
1H), 4.37 (q, J = 7.1 Hz, 2H), 3.36 (s, 3H), 1.36 (t, J = 7.1 152 oC). 1H NMR (600 MHz, CDCl3) δ = 7.92 (dd, J = 8.2,
Hz, 3H).13C NMR (151 MHz, CDCl3) δ = 180.7, 162.5, 1.5 Hz, 1H), 7.88 (d, J = 1.4 Hz, 1H), 6.72 (d, J = 8.2 Hz,
157.2, 155.6, 154.3, 127.8, 120.7, 118.1, 105.4, 62.9, 26.2, 1H), 3.25 (s, 3H). 13C NMR (151 MHz, CDCl3) δ = 181.9,
13.8. IR (KBr) δ = 1754, 1724, 1627, 1551, 1359, 1315, 157.2, 150.7, 146.4, 133.7, 119.0, 112.1, 86.0, 26.3. IR
1283 cm-1. LRMS (EI, 70 eV) m/z (%): 278 (100), 250 (61), (KBr) δ= 1751, 1724, 1601, 1483, 1456, 11427, 1324 cm-1.
248 (37), 233 (41), 222 (54), 205 (94), 194 (24), 177 (65), LRMS (EI, 70 eV) m/z (%): 287 (100), 259 (56), 231 (59),
176 (60), 174 (45), 148 (38), 131 (30), 104 (24), 103 (25), 230 (65), 104 (20), 77 (24), 63 (23).
+
81 (29), 62 (25). HRMS (ESI) m/z: calcd for C12H11N2O6
(M+H)+ 279.06116, found 279.06137.
1,5-dimethylindoline-2,3-dione (2k)[9]. Yield: 8.7 mg
(25%), Crimson solid, m.p.147.5–149.3 oC (lit. 150.5–
5-fluoro-1-methylindoline-2,3-dione (2g)[9]. Yield: 7.2 151.2 oC). 1H NMR (600 MHz, CDCl3) δ = 7.42 (d, J = 7.6
o
mg (10 %), Deep crimson solid, m.p. 142.5–143.5 C (lit. Hz, 2H), 6.80 (d, J = 8.5 Hz, 1H), 3.24 (s, 3H), 2.35 (s, 3H).
150.7-152.5 C). H NMR (600 MHz, CDCl3) δ = 7.37 – 13C NMR (151 MHz, CDCl3) δ 183.6, 158.4, 149.3, 138.7,
7.29 (m, 2H), 6.87 (dd, J = 8.2, 3.5 Hz, 1H), 3.26 (s, 3H). 133.7, 125.7, 117.5, 109.7, 26.2, 20.7. LRMS (EI, 70 eV)
13C NMR (151 MHz, CDCl3) δ 182.8, 159.4 (d, J = 246.1 m/z (%):175 (67), 147 (32), 119 (52), 118 (100), 91 (29).
Hz, 1C), 158.0, 147.5, 124.7(d, J = 24.2 Hz, 1C), 118.0,
o
1
117.8, 112.4 (d, J = 24.2 Hz, 1C), 111.1(d, J = 3.2 Hz, 1C),
1,5-dimethyl-6-nitroindoline-2,3-dione (3k). Yield: 13.6
mg (31%), Crimson solid, m.p. 180.4–181.5oC. H NMR
(600 MHz, DMSO) δ 7.68 (d, J = 15.1 Hz, 2H), 3.16 (s,
3H), 2.39 (s, 3H). 13C NMR (151 MHz, DMSO) δ 182.8,
1
26.4. LRMS (EI, 70 eV) m/z (%): 179 (63), 151 (27), 123
(46), 122 (100), 96 (30).
5-fluoro-1-methyl-6-nitroindoline-2,3-dione (3g). Yield: 158.4, 154.5, 150.0, 128.3, 126.9, 120.7, 106.2, 26.9, 18.4.
o
18.9 mg (42 %), Deep crimson solid, m.p. 147.4–148.2 C. LRMS (EI, 70 eV) m/z (%): 220 (100), 207 (26), 190 (25),
1H NMR (600 MHz, CDCl3) δ = 7.56 (d, J = 8.1 Hz, 1H), 175 (39), 147 (85), 119 (38), 118 (24), 117 (42), 92 (42),
7.50 (d, J = 5.1 Hz, 1H), 3.34 (s, 3H). 13C NMR (151 MHz, 91 (54), 77 (53), 65 (28), 65 (28).
CDCl3) δ = 181.2, 156.7, 152.3(d, J = 265 Hz, 1C), 146.7,
142.68, 142.6, 120.7, 115.6 (d, J = 24.0, 1C), 106.9, 26.8.
1,5-dimethyl-4,6-dinitroindoline-2,3-dione (4k). Yield:
o
1
IR (KBr) δ = 1769, 1748, 1639, 1606, 1536, 1462, 1442,
1345cm-1. LRMS (EI, 70 eV) m/z (%): 224 (98), 196 (47),
194 (44), 168 (77), 167 (31), 138 (33), 137 (44), 123 (23),
122 (89), 95 (48), 81(100).
6.4 mg (12%), Crimson solid, m.p. 214.5–215.5 C. H
NMR (600 MHz, Acetone) δ = 7.93 (s, 1H), 3.39 (s, 3H),
2.33 (s, 3H). 13C NMR (151 MHz, Acetone) δ = 183.0,
161.9, 161.2, 156.0, 150.4, 122.7, 115.3, 113.3, 31.6, 16.9.
LRMS (EI, 70 eV) m/z (%): 265 (30), 235 (52), 160 (33),
5-chloro-1-methylindoline-2,3-dione (2h)[9]. Yield: 13.4 145 (22), 133 (23), 117 (27), 93 (70).
mg (35%), Crimson solid, m.p. 171.9–172.6 C (lit. 165.1–
o
o
1
5-methoxy-1-methylindoline-2,3-dione (2l)[9]. Yield: 9.2
mg (24%), Deep red solid, m.p. 163.9–164.6 oC (lit. 171.2–
172.5 oC). 1H NMR (600 MHz, CDCl3) δ 7.17 (dd, J = 8.0,
2.1 Hz, 2H), 6.83 (dd, J = 7.4, 1.6 Hz, 1H), 3.82 (s, 3H),
3.24 (s, 3H). 13C NMR (151 MHz, CDCl3) δ = 183.7, 158.3,
156.6, 145.4, 124.6, 117.9, 110.8, 109.6, 56.0, 26.2. IR
(KBr) δ = 1742, 1724, 1627, 1486, 1292 cm-1. LRMS (EI,
70 eV) m/z (%): 191 (100), 148 (48), 135 (57), 134 (70),
166.8 C). H NMR (600 MHz, CDCl3) δ=7.61–7.56 (m,
2H), 6.88 (d, J = 8.0 Hz, 1H), 3.27 (s, 3H). 13C NMR (151
MHz, CDCl3) δ 182.3, 157.7, 149.7, 137.7, 129.7, 125.2,
118.3, 111.2, 26.4. IR (KBr) δ = 1748, 1733, 1725, 1610,
1483, 1468, 1445, 1327 cm-1. LRMS (EI, 70 eV) m/z (%):
197 (23), 195 (76), 169 (13), 167 (39), 141 (23), 140 (39),
139 (72), 138 (100), 114 (10), 112 (30).
5-chloro-1-methyl-6-nitroindoline-2,3-dione (3h). Yield: 120 (85), 92 (22).
o
1
19.4 mg (40%), Yellow solid, m.p. 205.1–205.7 C. H
NMR (600 MHz, CDCl3) δ = 7.78 (s, 1H), 7.29 (s, 1H),
3.33 (s, 3H). 13C NMR (151 MHz, CDCl3) δ = 180.8, 156.6,
149.8, 128.3, 122.1, 119.3, 106.8, 100.0, 26.8. IR (KBr)
δ=1762, 1754, 1736, 1616, 1554, 1412, 1350 cm-1. LRMS
(EI, 70 eV) m/z (%): 242 (34), 240 (100), 214 (21), 212
(70), 186 (31), 184 (100), 140 (26), 138 (79), 111 (30), 103
5-methoxy-1-methyl-6-nitroindoline-2,3-dione
(3l).
Yield: 23.1 mg (49%), Crimson solid, m.p.193.4–194.6 oC.
1H NMR (600 MHz, CDCl3) δ = 7.41 (s, 1H), 7.26 (s, 1H),
3.98 (s, 3H), 3.29 (s, 3H). 13C NMR (151 MHz, CDCl3) δ =
182.3, 157.1, 149.6, 144.1, 119.7, 111.1, 106.8, 99.8, 57.4,
26.6. LRMS (EI, 70 eV) m/z (%): 236 (100), 208 (61), 180
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800592
Advanced Synthesis & Catalysis
(33), 106 (23), 91 (20), 77 (28). HRMS (ESI) m/z calcd for 1-ethylindoline-2,3-dione (2p)[18b]. Yield: 5.0 mg (14%),
o
o
1
C10H9N2O5+ (M+H)+ 237.05060, found 237.05031.
Crimson solid, m.p. 93.0–93.9 C(lit. 92–94 C). H NMR
(600 MHz, CDCl3) δ = 7.60 (dd, J = 12.3, 4.4 Hz, 2H),
7.12 (t, J = 7.5 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H), 3.80 (q, J
= 7.3 Hz, 2H), 1.32 (t, J = 7.3 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ = 183.7, 157.9, 150.7, 138.3, 125.5, 123.6,
117.7, 110.0, 35.0, 12.5. IR (KBr) δ = 1739, 1727, 1613,
1471, 1374, 1350cm-1. LRMS (EI, 70 eV) m/z (%): 175
(100), 132 (42), 119 (63), 118 (78), 104 (61), 90 (28), 77
(34).
6-chloro-1-methylindoline-2,3-dione (2m)[18b]
.
Yield:
o
21.4 mg (55%), Crimson solid, m.p. 171.6–172.4 C (lit.
177-178 oC). 1H NMR (600 MHz, CDCl3) δ 7.55 (d, J = 8.0
Hz, 1H), 7.12 (dd, J = 7.9, 0.9 Hz, 1H), 6.92 (s, 1H), 3.26
(s, 3H). 13C NMR (151 MHz, CDCl3) δ 181.8, 158.2, 152.4,
144.9, 126.3, 124.0, 115.8, 110.8, 26.4. LRMS (EI, 70 eV)
m/z (%): 197 (31), 195 (90), 167 (38), 141 (24), 140 (36),
139 (73), 138 (100), 126 (23), 112 (30), 75 (25).
1-ethyl-6-nitroindoline-2,3-dione (3p) Yield: 18.5 mg
o
1
(42%), Crimson solid, m.p. 159.6–159.8 C. H NMR (600
MHz, CDCl3) δ = 8.01 (dd, J = 8.1, 1.8 Hz, 1H), 7.80 (d, J
= 8.1 Hz, 1H), 7.74 (d, J = 1.7 Hz, 1H), 3.90 (q, J = 7.3 Hz,
2H), 1.39 (t, J = 7.3 Hz, 3H). 13C NMR (151 MHz, CDCl3)
δ 182.3, 156.8, 153.7,151.3, 126.2, 121.1, 118.9, 105.1,
35.6, 12.3. IR (KBr) δ = 1756, 1736, 1624, 1603, 1542,
1439, 1342cm-1. LRMS (EI, 70 eV) m/z (%): 220 (100),
175 (40), 147 (27), 145 (23), 119 (31), 118 (21), 117 (38),
6-chloro-1-methyl-4-nitroindoline-2,3-dione (3m). Yield:
o
1
9.7 mg (20%), Crimson solid, m.p. 163.1–163.7 C. H
NMR (600 MHz, CDCl3) δ = 7.95 (d, J = 1.7 Hz, 1H), 7.63
(d, J = 1.6 Hz, 1H), 3.38 (s, 3H). 13C NMR (151 MHz,
CDCl3) δ 179.0, 156.4, 153.3, 153.0, 134.8, 120.7, 117.6,
103.3, 26.9. LRMS (EI, 70 eV) m/z (%): 242 (34), 240
(100), 214 (19), 212 (64), 186 (24), 184 (76), 140 (24), 138
(71), 111 (30), 103 (45), 102 (42), 99 (24), 97 (36), 88 (38),
75 (23), 74 (26), 62 (20). HRMS (ESI) m/z calcd for
C9H5ClN2O4Na+ (M+Na)+ 262.98301, found 262.98367.
+
92 (45), 77 (33). HRMS (ESI) m/z calcd for C10H9N2O4
(M+H)+ 221.05568, found 221.05603.
1-isopropylindoline-2,3-dione (2q)[18a]. Yield: 8.0 mg
(21%), Crimson solid, m.p. 113.9–114.5 oC(lit. 124.4–
1,7-dimethylindoline-2,3-dione (2n)[9]. Yield: 6.7 mg
o
(19%), Deep red solid, m.p. 157.8–158.3 C (lit. 162.3–
o
1
o
1
125.7 C). H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 7.4
Hz, 1H), 7.57 (td, J = 8.0, 1.3 Hz, 1H), 7.10 (t, J = 7.5 Hz,
1H), 7.04 (d, J = 8.0 Hz, 1H), 4.55 (dt, J = 14.0, 7.0 Hz,
1H), 1.53 (d, J = 7.0 Hz, 6H). 13C NMR (151 MHz, CDCl3)
δ = 183.8, 157.8, 150.5, 138.0, 125.6, 123.2, 118.0, 111.3,
44.8, 19.4. IR (KBr) δ = 1739, 1719, 1607, 1598, 1465,
1351cm-1. LRMS (EI, 70 eV) m/z (%): 189 (66), 146 (100),
132 (64), 92 (20), 90 (27).
164.8 C). H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 7.3
Hz, 1H), 7.37–7.31 (m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 3.53
(s, 3H), 2.57 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 183.7,
159.2, 149.0, 142.2, 123.9, 123.4, 121.9, 118.5, 29.7, 18.8.
IR (KBr) δ = 1736, 1598, 1453, 1436, 1362, 1315cm-1.
LRMS (EI, 70 eV) m/z (%): 175 (87), 147 (27), 119 (67),
118 (100), 91 (41).
1,7-dimethyl-6-nitroindoline-2,3-dione (3n). Yield: 17.2
mg (39%), Crimson solid, m.p. 154.0–154.8 oC. LRMS (EI,
70 eV) m/z (%): 220 (100), 203 (24), 175 (36), 147 (45),
1-isopropyl-6-nitroindoline-2,3-dione (3q). Yield: 18.9
o
1
mg (40%), Yellow solid, m.p. 161.9–162.7 C. H NMR
(600 MHz, CDCl3) δ = 7.98 (dd, J = 8.1, 1.8 Hz, 1H), 7.85
(d, J = 1.8 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 4.58 (dt, J =
14.0, 7.0 Hz, 1H), 1.59 (d, J = 7.0 Hz, 6H). 13C NMR (151
MHz, CDCl3) δ = 182.5, 156.8, 153.5, 151.1, 126.2, 121.3,
118.6, 106.2, 45.8, 19.2. IR (KBr) δ = 1754, 1736, 1267,
1601, 1536, 1439, 1345 cm-1. LRMS (EI, 70 eV) m/z (%):
234 (95), 191 (100), 177 (23), 161 (48), 145 (70), 133 (22).
1
119 (24), 118 (25), 117 (48), 91 (35), 77 (34). H NMR
(600 MHz, CDCl3) δ = 7.61 (d, J = 7.9 Hz, 1H), 7.37 (d, J
= 7.9 Hz, 1H), 3.62 (s, 3H), 2.57 (s, 3H). 13C NMR (151
MHz, CDCl3) δ=182.2, 158.5, 158.3, 150.9, 123.8, 119.7,
119.0, 116.0, 30.7, 13.7. IR (KBr) δ = 1756, 1733, 1598,
1530, 1448, 1357, 1303cm-1. HRMS (ESI) m/z calcd for
+
C10H9N2O4 (M+H)+ 221.05568, found 221.05505.
+
HRMS (ESI) m/z calcd for C11H11N2O4 (M+H)+
235.07133, found 235.07153.
7-bromo-1,5-dimethylindoline-2,3-dione (2o). Yield: 7.7
o
mg (15%), Crimson solid, m.p. 150.7–151.6 C (CAS No.
1-(prop-2-ynyl)indoline-2,3-dione (2r)[18e]. Yield: 4.1 mg
1
906660-35-3). H NMR (600 MHz, CDCl3) δ = 7.54 (s,
o
1H), 7.39 (s, 1H), 3.63 (s, 3H), 2.32 (s, 3H). 13C NMR (151
MHz, CDCl3) δ = 182.8, 158.7, 146.0, 143.7, 135.4,
125.1,120.4, 103.9, 29.6, 20.1. IR (KBr) δ = 1742, 1621,
1569, 1474, 1438cm-1. LRMS (EI, 70 eV) m/z (%): 255
(63), 253 (59), 227 (23), 225 (24), 199 (45), 198 (37), 197
(44), 196 (38), 118 (100), 117 (22), 103 (21), 91 (29), 89
(32), 63 (20).
(11%), Crimson solid, m.p. 142.3–144.9 C (lit. 144–146
1
oC). H NMR (600 MHz, CDCl3) δ = 7.71–7.62 (m, 2H),
7.19 (m, 2H), 4.56 (d, J = 2.5 Hz, 2H), 2.32 (s, 1H). 13
C
NMR (151 MHz, CDCl3) δ = 182.5, 157.2, 149.6, 138.4,
125.5, 124.2, 117.7, 111.1, 75.7, 73.3, 29.7. IR (KBr) δ =
3261, 2917, 2843, 2124, 1745, 1616, 1465, 1348 cm-1.
LRMS (EI, 70 eV) m/z (%): 185 (45), 156 (30), 146 (22),
129 (100), 102 (56), 90 (45).
7-bromo-1,5-dimethyl-6-nitroindoline-2,3-dione
(3o).
Yield: 12.5 mg (21%), Crimson solid, m.p. 161.5–162.3 oC.
1H NMR (600 MHz, CDCl3) δ = 7.47 (s, 1H), 3.61 (s, 3H),
2.24 (s, 3H).13C NMR (151 MHz, CDCl3) δ = 181.3, 158.0,
157.8, 147.7, 127.2, 126.8, 119.5, 95.9, 29.9, 16.9. IR
(KBr) δ = 1751, 1624, 1548, 1542, 1460cm-1. LRMS (EI,
70 eV) m/z (%): 300 (99), 298 (100), 254 (26), 253 (30),
227 (33), 225 (67), 207 (31), 191 (26), 146 (26), 145 (41),
116 (26), 118 (32), 117 (58), 76 (55), 75 (45).
6-nitro-1-(prop-2-ynyl)indoline-2,3-dione (3r). Yield:
o
1
14.7 mg (32%), Crimson solid, m.p. 186.5–187.1 C. H
NMR (600 MHz, CDCl3) δ 8.12 – 8.05 (m, 2H), 7.91 (d, J
= 8.1 Hz, 1H), 4.78 (d, J = 2.5 Hz, 2H), 2.98 (t, J = 2.5 Hz,
1H). 13C NMR (151 MHz, Acetone) δ 181.8, 156.6, 153.4,
150.5, 125.4, 122.0, 118.9, 106.0, 76.0, 73.9. IR (KBr) δ =
3264, 2975, 2922, 2124, 1745, 1624, 1601, 1536, 1445,
1345 cm-1. LRMS (EI, 70 eV) m/z (%): 230 (100), 174 (60),
156 (28), 145 (47), 128 (62), 117 (33), 101 (46), 89 (32),
+
75 (31). HRMS (ESI) m/z calcd for C11H7N2O4 (M+H)+
7-bromo-1,5-dimethyl-4,6-dintroindoline-2,3-dione (4o)
231.04003, found 231.04012.
o
Yield: 8.3 mg (12%), Crimson solid, m.p. 202.1–203.1 C.
1H NMR (600 MHz, Acetone) δ = 3.72 (s, 3H), 2.23 (s,
3H). 13C NMR (151 MHz, Acetone) δ = 176.9, 158.0, 157.4,
149.3, 144.3, 117.3, 110.7, 97.6, 29.6, 11.0. IR (KBr) δ =
1745, 1630, 1542, 1451, 1380, 1365, 1289 cm-1. LRMS (EI,
70 eV) m/z (%): 345 (40), 343 (34), 315 (54), 313 (57), 241
(29), 239 (30),181 (34),174 (23), 173 (41), 172 (25), 171
(31), 160 (65), 144 (100), 132 (43), 131 (32), 130 (33), 129
(46), 117 (32), 116 (51), 104 (42), 101 (36), 92 (46).
3-(2,3-dioxoindolin-1-yl)propanenitrile (2s)[18f]
. Yield:
o
6.0 mg (15%), Crimson solid, m.p. 127.1–127.9 C (lit.
1
101.1 oC). H NMR (600 MHz, Acetone) δ = 7.73 (td, J =
7.9, 1.2 Hz, 1H), 7.60 (dd, J = 7.4, 0.5 Hz, 1H), 7.37 (d, J =
8.0 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 4.16 (t, J = 6.8 Hz,
2H), 2.98 (t, J = 6.8 Hz, 2H). 13C NMR (151 MHz,
Acetone) δ = 182.9, 158.1, 150.4, 138.3, 124.6, 123.6,
117.9,117.5,110.7, 36.0, 15.7. IR (KBr) δ = 1736, 1615,
1465, 1359, 1321cm-1. LRMS (EI, 70 eV) m/z (%): 200
(27), 132 (100), 77 (19).
7
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
3-(6-nitro-2,3-dioxoindolin-1-yl)propanenitrile
(3s). Crisom oil. 1H NMR (600 MHz, DMSO) δ = 7.23 (d, J =
o
Yield: 14.2 mg (29%), Yellow solid, m.p. 178.6–179.5 C. 8.4 Hz, 1H), 7.15 (s, 2H), 6.17 (dd, J = 8.4, 1.7 Hz, 1H),
1H NMR (600 MHz, Acetone) δ = 8.20 (d, J = 1.9 Hz, 1H), 6.11 (d, J = 1.6 Hz, 1H), 3.04 (s, 3H). 13C NMR (151 MHz,
8.06 (dd, J = 8.1, 1.9 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), DMSO) δ 177.6, 161.7, 159.4, 154.7, 127.9, 108.0, 106.0,
4.33 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 6.8 Hz, 2H). 13C NMR 94.3, 26.0. LRMS (EI, 70 eV) m/z (%): 176 (100), 148 (49),
(151 MHz, Acetone) δ = 182.0, 157.6, 153.6, 151.1, 125.4, 147 (26), 120 (50), 119 (62), 93 (23). HRMS (ESI) m/z
121.9, 118.7, 117.6, 105.8, 36.4, 15.7. IR (KBr) δ= 1756, calcd for C9H9N2O2+ (M+H)+ 177.06585, found 177.06538.
1742, 1627, 1616, 1536, 1439, 1351cm-1. LRMS (EI, 70
eV) m/z (%): 245 (28), 177 (100), 147 (32), 131 (48), 119
(24).
N-mesityl-N-methylpropiolamide (9)
o
1
While solid, m.p. 108.3–108.9 C. H NMR (600 MHz,
CDCl3) δ 6.92 (s, 2H), 3.15 (s, 3H), 2.64 (s, 1H), 2.29 (s,
3H), 2.19 (s, 6H). 13C NMR (151 MHz, CDCl3) δ 153.8,
138.4, 137.6, 136.0, 129.3, 79.4, 76.1, 34.0, 21.0, 17.5.
LRMS (EI, 70 eV) m/z (%): 201 (93), 186 (40), 184 (32),
148 (39), 91 (31), 66 (100). HRMS (ESI) m/z calcd for
C13H6NO+ (M+H)+ 202.12264, found 202.12282.
1-phenylindoline-2,3-dione (2t)[18c]. Yield: 7.6 mg (17%),
o
o
1
Crimson solid, m.p. 135.3–136.1 C (lit.137–139 C). H
NMR (600 MHz, CDCl3) δ = 7.71 (m, 1H), 7.61–7.52 (m,
3H), 7.50-7.40 (m, 3H), 7.19 (td, J = 7.5, 0.8 Hz, 1H), 6.91
(d, J = 8.0 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 182.9,
157.3, 151.7, 138.3, 132.9, 130.0, 128.8, 126.0, 125.6,
124.3, 117.5, 111.3. IR (KBr) δ = 1739, 1613, 1468, 1365,
1294cm-1. LRMS (EI, 70 eV) m/z (%): 223 (17), 195 (100),
167 (31).
Acknowledgements
6-nitro-1-phenylindoline-2,3-dione (3t). Yield: 10.2 mg
(19%), Crimson solid, m.p. 177.9–178.3 oC (CAS No.
We gratefully thank the South China Agricultural University,
Science Technology Program Project of Guangdong Province
(No. 2016B020204005) and Guangzhou Science Technology
Program Project (No. 201607010142) for their financial support.
1
681467-58-3). H NMR (600 MHz, CDCl3) δ = 8.06 (dd, J
= 8.1, 1.7 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 1.5
Hz, 1H), 7.65 (t, J = 7.8 Hz, 2H), 7.56 (t, J = 7.5 Hz, 1H),
7.44 (d, J = 7.5 Hz, 2H). 13C NMR (151 MHz, CDCl3)
δ=181.7, 156.2, 153.6, 152.3, 132.0, 130.5, 129.7, 126.5,
125.9, 120.8, 119.5, 106.4. IR (KBr) δ= 1751, 1622, 1607, References
1530, 1347, 1262 cm-1. LRMS (EI, 70 eV) m/z (%): 268
(24), 240 (100), 194 (33), 166 (58), 139 (23), 77 (31).
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N-methyl-N-(4-nitrosophenyl)-3-phenylpropiolamide
(5). Yield: 38.0 mg (72%), Yellow solid, m.p. 163.2–164.2
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Hz, 1H), 7.38 (t, J = 7.8 Hz, 2H), 7.31-7.27 (m, 2H), 6.64
(d, J = 10.2 Hz, 2H), 6.57 (d, J = 10.2 Hz, 2H), 2.92 (s, 3H).
13C NMR (151 MHz, CDCl3) δ= 183.0, 160.0, 150.0, 142.1,
134.4, 131.6, 129.4, 127.5, 127.4, 126.6, 65.5, 26.4. IR
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LRMS (EI, 70 eV) m/z (%): 264 (67), 233(87), 197 (21),
186 (30), 164 (23), 79 (27), 66 (100), 53 (46). HRMS (ESI)
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m/z calcd for C16H13N2O2 (M+H)+ 265.09715, found
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Colorless oil. 1H NMR (600 MHz, CDCl3) δ = 8.09 (d, J =
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6.9 Hz, 2H), 3.35 (s, 3H), 2.86 (s, 1H), 1.40 (t, J = 7.0 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 165.7, 152.6, 146.4,
130.6, 130.0, 126.9, 79.9, 76.1, 61.3, 36.3, 14.3. LRMS (EI,
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o
1
While solid, m.p. 105.2–106.2 C. H NMR (600 MHz,
CDCl3) δ 7.45 – 7.39 (m, 3H), 7.23 – 7.14 (m, 2H), 5.06 –
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eV) m/z (%): 187 (100), 172 (82), 145 (33), 144 (55), 120
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8
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
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9
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10.1002/adsc.201800592
Advanced Synthesis & Catalysis
Oxidative Radical Cyclization of N-methyl-N-
arylpropiolamide to Isatins via Cleavage of
Carbon-carbon Triple Bond
Adv. Synth. Catal. Year, Volume, Page – Page
Yan-Yan Liao,a Yong-Chao Gao,a Wen-Xu
Zheng,*a Ri-Yuan Tang*ab
10
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