An efficient and environmentally friendly DABCO catalyzed Henry reaction of isatins

Article abstract of DOI:10.1016/j.tetlet.2011.08.155

An efficient and general method has been described for the synthesis of 3-hydroxy-3-(nitromethyl)indolin- 2-one by the reaction of isatins with nitromethane/nitroethane in the presence of DABCO. The reaction is catalytic, very rapid, yields are very high

Full text of DOI:10.1016/j.tetlet.2011.08.155

Tetrahedron Letters 52 (2011) 5862–5864
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient and environmentally friendly DABCO catalyzed Henry reaction
of isatins
⇑
H.M. Meshram , Palakuri Ramesh, A. Sanjeeva Kumar, A. Swetha
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2011
Revised 25 August 2011
Accepted 27 August 2011
Available online 2 September 2011
An efficient and general method has been described for the synthesis of 3-hydroxy-3-(nitromethyl)indo-
lin-2-one by the reaction of isatins with nitromethane/nitroethane in the presence of DABCO. The reac-
tion is catalytic, very rapid, yields are very high and avoids the use of solvents for reaction. The protocol is
applicable for substituted isatins as well as substituted nitroalkanes.
Ó 2011 Elsevier Ltd. All rights reserved.
3-Hydroxy disubstituted oxindole motifs are considered as
important and useful synthetic building blocks, and are present
in a variety of natural products1 and biologically active molecules.2
Some of the bioactive molecules like convolutamydines,3 diazona-
mide A,4a leptosin D,4b 30-hydroxyglucoisatisin,4c witindolinone
C,4d TMC-95s,5 celogentin K,6 dioxibrassinine7 as well as several
other pharmaceutically active compounds8 have stereogenic cen-
ter alpha to the C-3 position of the 3-hydroxy indoline-2-one ring.
In addition, chiral 3-substituted-3-hydroxyindolin-2-ones are par-
ticularly important molecules in the field of medicinal chemistry as
an antibacterial, anti-inflammatory,9a laxative,9b growth hormone
secretagogue agent,9c as well as they are potential new targets
for chemotherapy.9d Hydroxy indolines are also useful in the syn-
thesis of chiral ligands which are used to obtain high enantioselec-
tivities in numerous catalytic reactions.10 Due to their distinct
biological and chemical properties, their construction has stimu-
lated synthetic chemist,4 and the challenging absolute control of
the quaternary center has been recently achieved.5 Because of
the important medicinal value of 3-hydroxy indolines, an efficient
and general protocol for the synthesis of these molecule is desir-
able. Other reported methods accomplished the synthesis of 3-hy-
droxy-3-(nitromethyl)indolin-2-ones by using base with organic
solvents and electrochemically induced Henry reaction11 which
require special instrumental setup. These methods suffer from
tedious work-up, longer reaction time, unsatisfactory yields, and
narrow scope of substrates. In view of this, there is still need to
develop a general and efficient method for the synthesis of more
functionalized 3-hydroxy-3-(nitromethyl)indolin-2-ones.
CO catalyzed reaction of isatin with nitromethane to give
3-hydroxy-3-(nitromethyl)indolin-2-one. These are obtained effi-
ciently in the presence of 5 mol % of DABCO. The use of nonmetallic
reagents is an area of growing interest because of environmental
regulations. Among the various organic bases, 1,4-diazabicy-
clo[2,2,2]octane (DABCO) has been employed as an organic-hin-
dered base to bring about various organic transformations like
deprotection of peptides,13 as a catalyst for the Baylis–Hillman reac-
tion,14 for isoxazoles preparation,15 o-alkylations of phenols,16
deprotection of benzylic trimethylsilyl ethers,17 and synthesis of
glycidic amidester.18 In continuation of our work in the area of green
chemistry19 and particularly in the development of nonmetallic re-
agents,20 herein we wish to report a simple, efficient, and general
method for the preparation of substituted 3-hydroxy-3-(nitrometh-
yl)indolin-2-one derivatives by the reaction of isatin with nitro-
methane/nitroethane in the presence of DABCO (Scheme 1).21 We
have initiated our study with Henry reaction of isatin with nitro-
methane in the presence of different organic bases such as quinucli-
dine, DABCO, DBU, urotropine, Troger’s base, and DBN (Table 1).
It was observed that the reaction preceded efficiently using
DABCO and resulted in high yield of the desired product in a very
short reaction time (1–5 min). However, with other bases the reac-
tion was comparatively slow and gave less yield of the product
even after stretching the reaction time (1 h). In addition to this
we have screened acyclic tertiary amines such as TEA and
N1,N1,N2-triethyl-N2-methylethane-1,2-diamine and found that
the reaction was very sluggish with poor yield (20–30%) even with
extended reaction time (1–2 h). We have attempted different ratios
of DABCO (5, 10, 20, 30 and 40 mol %) and observed that 5 mol %
was suitable for the optimum conversion. The increase in the mole
ratio of DABCO also did not improve the yield. With further optimi-
zation of the reaction conditions, we found that a lower catalyst
loading (1 mol %) did not allow the reaction to proceed. Encour-
aged by our results in the reaction of nitromethane/nitroethane 2
to various isatins 1 proceeded readily employing DABCO as the
base.
As a part of our ongoing research in the development of new
3-hydroxy disubstituted oxindole motif methodologies,12 herein
we wish to report the efficient synthesis of 3-hydroxy-3-(nitrom-
ethyl)indolin-2-one derivatives (Scheme 1). We report herein DAB-
⇑
Corresponding author.
E-mail address: hmmeshram@yahoo.com (H.M. Meshram).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.155

H. M. Meshram et al. / Tetrahedron Letters 52 (2011) 5862–5864
Table 2
5863
R5
R1
R1
HO
3-Hydroxy-3-(nitromethyl)indolin-2-one derivatives formation by using DABCO as
catalyst
O
R2
R2
R3
NO2
DABCO(5 mol%)
solvent free, rt, 1-5 min
NO2
O
+
O
R5
R3
N
N
R5
R4
R1
R4
R1
R
R
HO
O
1
2
R2
R2
3
NO2
O
DABCO(5 mol%)
R5 = H, Me
+
R5
NO2
O
R = H, CH3, Bn
R3
solvent free, rt,1-5 min
R3
N
N
R1 = R2= R3= R4= H, 5-CH3, 5-F, 5-Cl, 5-Br, 5-I , 5-NO2, 5-OCF3,
4-Br, 7-Cl, 7-Br, 4,6-di Bromo, 5,7-di Bromo.
R4
R4
R
R
1
2
3
R5 = H, Me
R = H, CH3, Bn
Scheme 1.
R1 = R2= R3= R4= H, 5-CH3, 5-F, 5-Cl, 5-Br, 5-I , 5-NO2, 5-OCF3,
4-Br, 7-Cl, 7-Br, 4,6-di Bromo, 5,7-di Bromo.
Table 1
Screened bases for the reaction of isatin with nitromethane/nitroethane
Entry Basea
Conversionb Time
(min)
Yield
(%)c
Entry
R
R1
R2
R3
R4
R5
Time (min)
Yields(%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
Br
H
H
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Br
Br
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3
3.5
3
3
2.5
3
3.5
3
1.5
5
4.5
5
5
5
4.5
5
5
3
3.5
4
2
95
90
88
90
82
93
90
89
93
85
86
88
70
75
77
72
Me
Bn
Bn
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
1
60
30
3
55
96
N
N
F
Cl
Br
I
NO2
OCF3
Me
H
H
Br
H
H
H
F
Br
I
2
100
N
N
3
70
50
20
60
60
46
N
N
4
N
N
N
H
70
CH3
CH3
CH3
CH3
CH3
90 (60:40)b
91 (75:25)b
91 (70:30)b
94 (80:20)b
90 (65:35)b
N
H
H
H
H
5
55
55
80
40
30
52
Cl
3
N
a
Reaction conditions: isatin(1 equiv), nitromethane/nitroethane (3 equiv), DAB-
N
CO(5 mol %) at RT, isolated yields.
6
b
Diastereomeric ratio.
N
a
In a typical experiment the isatins (1 equiv) were added to a mixture of the base
However, the reaction of substituted isatins with nitroethane in
identical conditions provided good yields of products with increas-
ing selectivity ((Table 2, entries 19, 20, 21, and 22).
(5 mol %) and the nitromethane/nitroethane (3 equiv) stirred at RT.
b
Conversion of oxindols evaluated by 1H NMR.
c
Isolated yields.
In conclusion, we have demonstrated an efficient and mild
method for the synthesis of functionalized 3-hydroxy-3-(nitrom-
ethyl)indolin-2-one derivatives using DABCO as catalyst. This
method is applicable for a variety of isatins and nitroalkanes. This
method offers several advantages including mild reaction condi-
tions, highly catalytic (5 mol%) process, no formations of by-prod-
ucts, high yields were obtained.
Generally, excellent yields of 3-hydroxy-3-(nitromethyl)indo-
lin-2-one were obtained with 3 equiv of nitromethane 2 and
5 mol % of DABCO at rt. The scope and limitations of this protocol
were studied with respect to isatins and results are summarized
in the Table 2. The addition of nitromethane 2 to various isatins
1 proceeded readily and resulted into expected product. Though
the reaction proceeds with 1:1 ratio of the reactants, the best re-
sults were obtained by 3 equiv ratio of nitromethane. Further we
extended this protocol to different substituted isatins. For example,
5-halo isatins reacted with nitromethane in the optimized condi-
tion and resulted into high yields (Table 2, entries 6, 7, 8 and 9).
Other 5-substituted isatins also afforded comparative good yields
of products (Table 2, entries 10, 11 and 12). In addition to this N-
substituted isatins (Table 2, entries 2, 3, 4, and 5) were subjected
to Henry reaction in the identical reaction condition to give high
yields. Similarly, 4-substitued, 7-substitued, and also disubstituted
isatins (Table 2, entries 13, 14, 15, 16, and 17) participated in the
reaction, but gave comparatively less yields. Then we extended this
protocol for nitroethane which gave good yields with less selectiv-
ity. For example, simple isatin reacted with nitroethane and gave
high yields with 60:40 diastereo selectivity (Table 2, entry 18).
Acknowledgments
The authors P.R., A.S.K. and A.S. thank CSIR-UGC for the award of
a fellowship and Dr. J. S. Yadav, Director IICT, for his support and
encouragement.
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iodo-3-(nitromethyl)-1,3-dihydro-2H-indol-2-one (Table 2, entry 9): White solid;
mp 274–276 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d 4.91–4.81 (m, 2H),
6.66 (s, 1H), 6.70 (d, 1H, J = 8.30 Hz), 7.53 (dd, 1H, J = 1.70, 8.30 Hz), 7.64 (d, 1H,
J = 1.51 Hz), 10.46 (s, 1H); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 72.6, 78.1,
4. (a) Nicolaou, K. C.; Rao, P. B.; Hao, J. L.; Reddy, M. V.; Rassias, G.; Huang, X. H.;
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84.2, 112.6, 130.5, 133.1, 138.6, 142.4, 175.2; IR (KBr)
m = 3388, 3271, 2924,
1726, 1612, 1555, 1471, 1182, 822 cmÀ1; MS (ESI): m/z 357(M+Na). 3-hydroxy-
5. (a) Lin, S.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2002, 41, 512; (b) Lin, S.;
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3 (nitromethyl)-5-(trifluoromethoxy)indolin-2-one (Table 2, entry 11): Pale
yellow solid; mp 115–117 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d 4.88 (s,
2H), 6.76 (s, 1H), 6.90 (d, 1H, J = 8.49 Hz), 7.10 (d, 1H, J = 8.49 Hz), 7.30 (s, 1H),
10.55 (s, 1H); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 84.6, 91.4, 111.5, 113.4,
6. Suzuki, H.; Morita, H.; Shiro, M.; Kobayashi, J. Tetrahedron 2004, 60, 2489.
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113.9, 121.7, 128.9, 134.7, 156.5, 179.6; IR (KBr) m = 3258, 3171, 2944, 1722,
1632, 1545, 1374, 1102, 748 cmÀ1; MS (ESI): m/z 315 (M+Na). 3-Hydroxy-4,6-
Dibromo-3-(nitromethyl)-1,3-dihydro-2H-indol-2-one (Table 2, entry 14): White
solid; mp 195–197 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d 4.95 (d, 1H,
J = 13.40 Hz), 5.30 (d, 1H, J = 13.40 Hz), 6.75 (s, 1H), 6.98 (s, 1H), 7.23 (s, 1H),
10.75 (s, 1H); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 83.4, 87.7, 113.5, 122.0,
9. (a) Pajouhesh, H.; Parsons, R.; Popp, F. D. J. Pharm. Sci. 1983, 72, 318; (b)
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2010, 40, 39; (b) Meshram, H. M.; Ramesh, P.; Reddy, B. C.; Sridhar, B.; Yadav, J.
S. Tetrahedron 2011, 67, 3150; (c) Meshram, H. M.; Ramesh, P.; Reddy, B. C.;
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14. (a) De Souza, R. O. M. A.; Vas Concellos, M. L. A. A. Catal. Commun. 2003, 5, 21;
(b) Krishna, P. R.; Sekhar, E. R.; Kannan, V. Tetrahedron Lett. 2003, 44, 4973; (c)
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259, 121.
124.5, 126.6, 129.4, 144.2, 179.6; IR (KBr) m = 3356, 3178, 1714, 1610, 1556,
1373, 1064, 846 cmÀ1; MS (ESI): m/z 387 (M+H). 3-Hydroxy-5,7-Dibromo-3-
(nitromethyl)-1,3-dihydro-2H-indol-2-one (Table 2, entry 15): White solid; mp
163–165 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d 4.90 (s, 2H), 6.83 (s, 1H),
7.47 (d, 1H, J = 1.51 Hz), 7.53 (d, 1H, J = 1.51 Hz), 10.75 (s, 1H); 13C NMR
(75 MHz, CDCl3+DMSO-d6): d 84.4, 89.7, 105.5, 118.4, 127.5, 132.3, 133.4,
140.0, 179.6; IR (KBr)
m
= 3346, 3148, 1718, 1625, 1566, 1014, 856 cmÀ1; MS
(ESI): 387 m/z (M+H) and (M+2). 3-Hydroxy-7-Bromo-3-(nitromethyl)-1,3-
dihydro-2H-indol-2-one (Table 2, entry 16): White solid; mp 136–138 °C; 1H
NMR (300 MHz, CDCl3+DMSO-d6): d 4.90 (d, 2H, J = 6.23 Hz), 6.76 (s, 1H), 6.90
(t, 1H, J = 7.74 Hz), 7.34 (d, 1H, J = 11.33 Hz), 7.38 (d, 1H, J = 11.89 Hz), 10.64 (s,
1H); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 73.3, 78.4, 102.4, 123.0, 123.1,
129.2, 132.7, 141.7, 175.4; IR (KBr) m .
= 3196, 1717, 1612, 1550, 1443, 777 cmÀ1
MS (ESI): m/z 308 (M+Na). 3-hydroxy-3-(1-nitroethyl)indolin-2-one (Table 2,
entry 18): Pale yellow solid; mp 110–112 °C; diastereomeric ratio 60:40; 1H
NMR (300 MHz, CDCl3+DMSO-d6): d 1.35(d, 3H, J = 6.79 Hz), 4.0 (s, 1H), 4.95 (q,
1H), 6.80–7.10 (m, 3H), 7.18 (dd, 1H, J = 2.45, 5.85 Hz), 10.46 (s, 1H) (major);
1.74 (d, 3H, J = 6.79 Hz), 3.9 (s, 1H), 5.43 (q, 1H), 6.90–7.05 (m, 3H), 7.30–7.40
(m, 1H), 10.36 (s, 1H) (minor); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 7.2, 88.6,
98.4, 110.2, 123.6, 124.4, 126.8, 131.2, 141.0, 176.0 (major); 6.9, 89.2, 97.3,
17. Sharafi, T.; Heravi, M. M. Phosphorus, Sulfur Silicon 2004, 179, 2437.
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109.0, 122.4, 123.8, 125.6, 131.0, 140.8, 176.4 (minor); IR (KBr) m = 3250, 2906,
1717, 1630, 1552, 1480, 1313, 1088 cmÀ1; MS (ESI): m/z 245(M+Na). 5-Fluoro-
3-hydroxy-3-(1-nitroethyl)indolin-2-one (Table 2, entry 19): White solid; mp
128–130 °C; diastereomeric ratio 75:25; 1H NMR (300 MHz, CDCl3+DMSO-d6): d
1.35 (d, 3H, J = 6.79 Hz), 4.95 (q, 1H, J = 6.79 Hz), 6.78 (s, 1H), 6.82 (dd, 1H,
J = 4.15, 4.53 Hz), 6.95–7.00 (m, 1H), 7.17 (dd, 1H, J = 2.45, 5.85 Hz), 10.48 (s,
1H) (major); 1.74 (d, 3H, J = 6.79 Hz), 4.95 (q, 1H, J = 6.79 Hz), 6.71 (s, 1H),
7.30–7.35 (m, 3H), 10.38 (s, 1H) (minor);13C NMR(75 MHz, CDCl3+DMSO-d6): d
13.4, 86.5, 110.9, 112.9, 116.4,116.7, 128.7, 138.6, 159.4, 175.5 (major); 12.3,
85.4, 111.0, 112.6, 116.3, 116.6, 128.9, 138.7, 159.4, 176.2 (minor); IR (KBr)
m
= 3361, 3277, 2927, 1731, 1617, 1558, 1377, 1192, 749 cm-1; MS (ESI): m/z
21. General procedure: To a solution of isatin 1 (1 mmol), nitromethane/nitroethane
(3 mmol) was added DABCO (5 mol %). The mixture was stirred at rt this
temperature for 1–5 min. The reaction was monitered by TLC. After completion
of the reaction, the mixture was extracted with ethyl acetate (3 Â 5 mL). The
combined organic layers were washed with brine solution, dried over Na2SO4,
and concentrated under reduced pressure (rotary evaporator). The crude
products were purified by silica gel column chromatography (ethyl acetate/
hexanes: 30:70). All novel compounds were characterized by M.P., NMR, Mass
and IR spectral data.
263(M+Na). 5-Bromo-3-hydroxy-3-(1-nitroethyl)indolin-2-one (Table 2, entry
20): White solid; mp 167–169 °C; diastereomeric ratio 70:30; 1H NMR
(300 MHz, CDCl3+DMSO-d6): d 1.40(d, 3H, J = 6.92 Hz), 5.0 (q, 1H), 6.73 (s,
1H), 6.77–6.81 (m, 1H), 7.34–7.40 (m, 1H), 7.51 (s, 1H), 10.50 (s, 1H) (major);
1.77 (d, 3H, J = 6.92 Hz), 4.98 (q, 1H), 6.68 (s, 1H), 6.83–6.87 (m, 1H), 7.20–7.30
(m, 1H), 7.34 (s, 1H), 10.43 (s, 1H) (minor); 13C NMR (75 MHz, CDCl3+DMSO-
d6): d 6.8, 89.6, 96.9, 118.8, 123.8, 129.4, 133.0, 133.2, 139.6, 179.2 (major); 6.4,
88.9, 96.2, 118.2, 124.0, 128.8, 129.6, 133.4, 139.2, 178.8 (minor); IR (KBr)
m
= 3356, 1729, 1628, 1572, 1558, 1487, 1371, 1161, 847 cmÀ1; MS (ESI): m/z
Spectral data for new compounds:
323(M+Na). 5-Iodo-3-hydroxy-3-(1-nitroethyl)indolin-2-one (Table 2 entry 21):
White solid; mp 278–280 °C; diastereomeric ratio 80:20; 1H NMR (300 MHz,
CDCl3+DMSO-d6): d 1.40(d, 3H, J = 6.98 Hz), 4.50 (s, 1H) 4.96 (q, 1H), 6.70 (d,
1H, J = 8.12 Hz), 7.55–7.60 (m, 1H), 7.68 (s, 1H), 10.451 (s, 1H) (major); 1.77 (d,
3H, J = 6.98 Hz), 4.52 (s, 1H), 5.02 (q, 1H), 6.75 (d, 1H, J = 8.12 Hz), 7.57–7.62
(m, 2H), 10.38 (s, 1H) (minor); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 6.78,
89.6, 97.4, 110.7, 113.0, 115.4, 132.4, 136.5, 158.6, 179.4 (major); 6.74, 89.4,
1-Benzyl-5-bromo-3-hydroxy-3-(nitromethyl)indolin-2-one (Table 2, entry 4):
Pale yellow solid; mp 121–123 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d
4.85(d, 1H, J = 15.8 Hz), 4.95(d, 1H, J = 15.8 Hz), 5.05(s, 2H), 6.66 (d, 1H,
J = 8.3 Hz), 6.95 (s, 1H), 7.41–7.19(m, 6H), 7.62 (s, 1H); 13C NMR (70 MHz,
CDCl3+DMSO-d6): d 48.7, 77.7, 83.0, 101.0, 116.6, 120.0, 132.4, 132.7, 134.7,
135, 138.1, 140.4, 147.6, 179.2; IR (KBr)
m = 3331, 2921, 1711, 1621, 1561,
1391, 1097, 757 cmÀ1. MS (ESI): m/z 399(M+Na). 3-Hydroxy-3-(nitromethyl)-1-
phenylindolin-2-one (Table 2, entry 5): White solid; mp 99–101 °C; 1H NMR
(300 MHz, CDCl3+DMSO-d6): d 4.92–5.11 (m, 2H), 6.75 (d, 1H, J = 7.7 Hz), 6.91
(s, 1H), 7.08 (t, 1H, J = 7.4 Hz), 7.29 (t, 1H, J = 7.5 Hz), 7.40–7.55 (m, 6H); 13C
NMR (75 MHz, CDCl3+DMSO-d6): d 72.7, 78.4, 109.1, 122.3, 125.4, 126.4, 128.1,
97.3, 110.2, 113.4, 115.0, 132.0, 136.7, 158.2, 179.4 (minor); IR (KBr)
m = 3381,
3248, 2934, 1733, 1614, 1552, 1472, 1188, 816 cmÀ1
;
MS (ESI): m/z
371(M+Na). 5-Chloro-3-hydroxy-3-(1-nitroethyl)indolin-2-one (Table 2, entry
22): White solid; mp 166–168 °C; diastereomeric ratio 65:35; 1H NMR (300 z,
CDCl3+DMSO-d6): d 1.37(d, 3H, J = 6.98 Hz), 4.98 (q, 1H), 6.77 (s, 1H), 6.84 (d,
1H, J = 3.21 Hz), 7.23–7.26 (m, 1H), 7.38 (d, 1H, J = 2.45 Hz), 10.56 (s, 1H)
(major); 1.76 (d, 3H, J = 6.98 Hz), 5.0 (q, 1H), 6.71 (s, 1H), 6.81 (d, 1H, J = 3.21),
7.18–7.30 (m, 1H), 7.39 (d, 1H, J = 2.45 Hz), 10.49 (s, 1H) (minor); 13C NMR
(75 MHz, CDCl3+DMSO-d6): d 6.8, 89.3, 96.4, 111.7, 113.0, 115.8, 133.4, 136.5,
157.6, 176.4 (major); 6.7, 88.8, 96.7, 111.2, 113.4, 116.0, 132.9, 136.9, 156.8,
128.4, 129.7, 133.8, 143.7, 174.1; IR (KBr)
m = 3328, 2933, 1709, 1617, 1559,
1467, 1389, 761 cmÀ1
;
MS (ESI): m/z 307(M+Na). 5-Fluoro-3-hydroxy-3-
(nitromethyl)-1,3-dihydro-2H-indol-2-one (Table 2, entry 6): White solid; mp
161–163 °C; 1H NMR (300 MHz, CDCl3+DMSO-d6): d 4.90–4.82 (m, 2H), 6.69 (s,
1H), 6.84–6.80 (m, 1H), 6.946 (dt, 1H, J = 2.26, 9.06 Hz), 7.14 (d, 1H, J = 7.74 Hz),
10.39 (s, 1H); 13C NMR (75 MHz, CDCl3+DMSO-d6): d 72.9, 78.0, 110.8, 112.7,
176.9 (minor); IR (KBr)
m = 3351, 3248, 2976, 1727, 1620, 1562, 1482, 1088,
116.6, 129.7, 138.7, 159.4, 175.8; IR (KBr)
m = 3358, 3271, 2924, 1726, 1612,
516 cmÀ1; MS (ESI): m/z 279 (M+Na).