Rapid eco-friendly synthesis and structure of 3-hydroxy-3-nitromethyl-1,3- dihydro-indol-2-one

Article abstract of DOI:10.1007/s10870-009-9662-5

3-Hydroxy-3-nitromethyl-1,3-dihydro-indol-2-one was synthesized from isatin by Henry reaction using an eco-friendly method and characterized by NMR and MS. The crystal structure was determined from single-crystal X-ray diffraction data. It crystallizes in the orthorhombic space group, Pbca, with unit cell dimensions a = 10.515 (2) A, b = 7.3736 (14) A, and c = 23.261 (4) A. The two rings are coplanar and the angle between hydroxyl group and nitromethyl group is 109.07(9)°. In the crystal structure, intermolecular N-H...;O and O-H...;O hydrogen bonds are responsible for the formation of a 3-dimensional network. No intramolecular hydrogen bond exists.

Full text of DOI:10.1007/s10870-009-9662-5

J Chem Crystallogr (2010) 40:369–372
DOI 10.1007/s10870-009-9662-5
ORIGINAL PAPER
Rapid Eco-Friendly Synthesis and Structure of 3-Hydroxy-3-
nitromethyl-1,3-dihydro-indol-2-one
•
Gang Chen Ying Tang Qun-Zheng Zhang
•
•
•
Ya Wu Shun-Zhen Mu
Received: 22 March 2009 / Accepted: 31 October 2009 / Published online: 14 November 2009
Ó Springer Science+Business Media, LLC 2009
Abstract 3-Hydroxy-3-nitromethyl-1,3-dihydro-indol-2-
one was synthesized from isatin by Henry reaction using an
eco-friendly method and characterized by NMR and MS.
The crystal structure was determined from single-crystal
X-ray diffraction data. It crystallizes in the orthorhombic
space group, Pbca, with unit cell dimensions a = 10.515
of 1 as well as its derivatives provides 3-nitromethylene-1,3-
dihydro-indol-2-one, which is used as a dipolarophile in 1,3-
dipolar cycloadditon reactions to synthesis spiro-oxindol
compounds [2, 3]. The reported Henry reactions between
isatin and nitromethane was catalyzed by a strong organic
base catalyst, DBU(1,8-Diazabicyclo[5.4.0]undec-7-ene),
giving moderate yield [1, 3]. Moreover, this costly catalyst
suffers from decomposition in air or under light.
˚
˚
˚
(2) A, b = 7.3736 (14) A, and c = 23.261 (4) A. The two
rings are coplanar and the angle between hydroxyl group
and nitromethyl group is 109.07(9)°. In the crystal struc-
ture, intermolecular N–HÁÁÁO and O–HÁÁÁO hydrogen bonds
are responsible for the formation of a 3-dimensional net-
work. No intramolecular hydrogen bond exists.
Diethylamine, a stable weak base with low price, has
shown great catalysis activity in Aldol reaction between
methyl ketone and isatin [4]. Since Henry reaction is an
aldol-type reaction [5, 6], it is anticipated that great activity
of diethylamine can be displayed in Henry reaction
between isatin and nitromethane. In this article, we
employed diethylamine as catalyst in the synthesis of the
title compound (1) (shown in Scheme 1) and determined its
crystal structure by single-crystal X-ray.
Keywords 3-Hydroxy-3-nitromethyl-1,3-dihydro-indol-
2-one Á X-ray structure Á Henry reaction
Introduction
In recent years, many 3-nitromethylene-1,3-dihydro-indol-
2-one derivatives has been synthesized, due to the interesting
bioactivities of isatin (indole-2,3-dione) derivatives [1–3].
3-Hydroxy-3-nitromethyl-1,3-dihydro-indol-2-one(1), an
important intermediate in the synthesis of 3-nitromethylene-
1,3-dihydro-indol-2-one, has been synthesized by Henry
reaction between isatin and nitromethane [1, 2]. Dehydration
Experimental
All starting materials and solvents (A.R. grade) were com-
mercially available and were used without further purifica-
tion. NMR spectra was recorded in the stated solutions, on a
Bruker Drx-400 spectrometer, operating at 400 MHz for 1H
and 100 MHz for 13C; d values are reported in ppm and J
values in hertz. Mass spectra were recorded on a Micromass
PlatformIIspectrometer, using the direct-inlet system oper-
ating in the electron impact (EI) mode at 75 eV.
G. Chen (&) Á Y. Tang Á Q.-Z. Zhang Á Y. Wu
College of Chemistry & Chemical Engineering, Xi’an Shiyou
University, Xi’an, Shaanxi 710065, People’s Republic of China
e-mail: gangchen@xsyu.edu.cn
Synthesis of 3-Hydroxy-3-nitromethyl-1,3-dihydro-
indol-2-one
S.-Z. Mu
Key Laboratory of Chemistry for Natural Products of Guizhou
Province and Chinese Academy of Sciences, Guizhou, Guiyang
550002, People’s Republic of China
Isatin (0.294 g, 2 mmol) was dissolved in nitromethane
(15 mL), and a drop of diethylamine was added in. The
123

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J Chem Crystallogr (2010) 40:369–372
H
O
O
HO
O
O
O
N
NO2
O
N
H
N
N
O
HN(C2H5)2
CH3NO2
+
HN(C2H5)2
N
O
N
O
H
H
H
C
A
B
Scheme 1 Synthesis of 3-hydroxy-3-nitromethyl-1,3-dihydro-indol-
2-one
H
O
O
O
N
O
H
N
N
H
HO
mixture was stirred under room temperature for a few
minutes until the solution turned to be colorless from
orange. The solvent was distilled off under reduced pres-
sure to give the target product as a white powder. Colorless
crystals of 1 were obtained in ethanol by recrystallization.
1H-NMR (D6-DMSO, 400 MHz), d: 10.56 (1H, s), 7.39
(1H, d, J = 7.2 Hz), 7.26 (1H, td, J = 7.6, 1.2 Hz), 6.98
(1H, t, J = 7.6 Hz), 6.85 (1H, d, J = 7.6 Hz), 6.75 (1H, s),
4.99 (2H, dd, J = 12.8, 8.0 Hz); 13C-NMR (D6-DMSO,
100 MHz), d: 176.0, 142.6, 130.3, 127.9, 124.7, 121.9,
110.1, 78.5, 72.8; MS (EI) m/z: 208 (M?).
O
NO2
D
N
H
E
O
N
O
H
F
Scheme 2 The mechanism of the Henry reaction between isatin and
nitromethane catalyzed by diethylamine
with isatin (D) proceeding transition state E. In this
bimolecular complex E, the ammonium proton enables
hydrogen bonding between the reaction partners. Several
theoretical studies have highlighted the importance of the
hydrogen bonds in this reaction [7–9]: it ensures the
X-Ray Data Collection and Structure Refinement
All H atoms were positioned geometrically, with C–
˚
H = 0.93–0.98 A, and refined with a riding model, with
Table 1 Experimental data
Empirical formula
Formula weight
Temperature
C9H8N2O4
208.17
U
iso(H) = 1.2Ueq(carrier). Data collection: SMART (Bru-
ker 2002); cell refinement: SAINT (Bruker 2002); data
reduction: SAINT (Bruker 2002); program (s) used to solve
structure: SHELXS97 (Sheldrick 1997); program (s) used
to refine structure: SHELXL97 (Sheldrick 1997); molecu-
lar graphics: Ortep-3 for Windows (Farrugia 1997); soft-
ware used to prepare material for publication: WinGX
(Farrugia 1999).
273(2)
Wavelength (Mo Ka)
Crystal system
0.71073
Orthorhombic
Pbca
Space group
Unit cell dimensions
10.515(2)
7.3736(14)
23.261(4)
1,803.6(6)
8
Volume
Z
Results and Discussion
Density (calculated)
Absorption coefficient
F (000)
1.533 mg/m3
0.123
The reported method for the synthesis of 3-nitromethylene-
1,3-dihydro-indol-2-one derivatives was catalyzed by DBU
in EtOH, and the yield was relatively low [1–3]. Based on
the comparability of Aldol reaction and Henry reaction and
the catalysis activity of diethylamine in Aldol reaction,
diethylamine was introduced into the solvent-free reaction
between isatin and nitromethane. Fortunately, the result
proved to be effective. The reaction processed quickly,
only few minutes was needed, and the yield was as high as
near to 100%. Besides, it was so neat that it could be used
to synthesize 3-nitromethylene-1,3-dihydro-indol-2-one
directly avoiding a separation course.
864
0.21 9 0.18 9 0.15 mm3
Crystal size
Theta range for data
collection (°)
Index ranges
1.8–34.3
-12 B h B 12; -9 B k B 11; -
28 B l B 36
Reflections collected
Independent reflections
Reflections theta (°)
Absorption correction
transmission
3,007
2,098
1.75–34.30
0.9407–0.9608
Refinement method
Full-matrix least-squares on F2
3,007/0/136
Based on the mechanism of diethylamine catalyzed
Aldol reaction, the mechanism of the reaction between
isatin and nitromethane catalyzed by diethylamine was
proposed and shown in Scheme 2. Initially, nitromethane
(A) isomerizes to B, and then combines with diethylamine
to form a hexahydroxy cycle intermediate C, which reacts
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2s(I)]
R indices (all data)
1.034
R1 = 0.0683; wR2 = 0.1347
R1 = 0.0452; wR2 = 0.1204
-0.209–0.308
Refine different density
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J Chem Crystallogr (2010) 40:369–372
371
Table 2 Atomic coordinates (9104) and equivalent isotropic dis-
Table 3 Selected bond lengths (A) and angles (°)
˚
2
placement parameters (A 9 10 )
3
˚
Bond
Dist.
Bond
Dist.
Atom
x
y
z
Ueq
N1 C1
C7 C6
C8 C3
C2 O2
C2 C1
C3 C4
C6 C5
N2 O3
1.3500(16)
1.3822(17)
1.3823(17)
1.4180(13)
1.5563(16)
1.3940(19)
1.391(2)
N1 C7
C7 C8
C8 C2
C2 C9
O1 C1
C9 N2
N2 O4
C5 C4
1.4130(16)
1.3893(17)
1.5042(15)
1.5340(16)
1.2237(14)
1.4819(17)
1.2155(18)
1.383(2)
N1
7,379.3(10)
8,121
2,253.6(14)
2,684
5,957.5(4)
5,882
345(2)
41
H1A
C7
6,887 (11)
5,674.4(11)
5,321.1(11)
6,714 (9)
5,008.7(12)
4,196
2,032 (15)
1,289.8(14)
1,026.2(14)
1,657.4(14)
8,802(17)
6,966
6,518.3(5)
6,488.7(5)
5,867.7(5)
5,034.6(4)
6,984.4(5)
386
313(3)
294(2)
287(2)
452(3)
374(3)
45
C8
C2
O1
C3
1.2130(19)
H3A
C9
Angle
(°)
Angle
(°)
4,122.1(12)
4,059
2,058 (16)
2,048
5,682.8(5)
5,267
354(3)
43
C1 N1 C7
C6 C7 N1
C3 C8 C7
C7 C8 C2
O2 C2 C9
O2 C2 C1
C9 C2 C1
N2 C9 C2
O4 N2 O3
O3 N2 C9
C5 C4 C3
O1 C1 C2
111.51(10)
128.55(11)
120.63(11)
108.98(10)
109.07(9)
108.19(9)
112.70(9)
111.13(9)
124.39(14)
117.33(13)
120.30(12)
125.24(10)
C6 C7 C8
C8 C7 N1
C3 C8 C2
O2 C2 C8
C8 C2 C9
C8 C2 C1
C8 C3 C4
C7 C6 C5
O4 N2 C9
C4 C5 C6
O1 C1 N1
N1 C1 C2
121.81(11)
109.63(10)
130.37(11)
110.71(9)
114.09(9)
101.81(9)
118.27(12)
117.02(12)
118.28(14)
121.94(12)
126.62(11)
108.05(10)
H9A
H9B
C6
3,377
1,453
5,837
43
7,460.9(13)
8,264
2,426.8(17)
2,951
7,038 (5)
7,055
39.6(3)
48
H6A
N2
4,152.4(12)
6,783.2(15)
7,145
3,958.6(15)
2,004.9(18)
2,253
5,889.4(5)
7,533.6(6)
7,890
47 (3)
45 (3)
54
C5
H5A
C4
5,587.2(14)
5,167
1,227(2)
934
7,512.3(5)
7,852
44.8(3)
54
H4A
O3
5,050.8(14)
3,288.1(14)
6,539.4(11)
5,162.1(8)
4,586
4,884.3(17)
4,482.7(19)
1,704.4(15)
-841.4(11)
-966
5,745 (9)
6,194.1(6)
5,554.5(5)
5,741.4(4)
5,507
90.4(5)
77.6(4)
31.7(3)
39.1(2)
59
O4
C1
O2
H2A
˚
Table 4 Hydrogen bond geometry (A, and °)
incoming of isatin; it lowers the activation barrier of the
reaction by charge stabilization along the C–C bond for-
mation. During the transition state E, by a series of elec-
trons transfer, a proton transfers from the ammonium to the
oxygen anion, the desired adduct (3-nitromethylene-1,3-
dihydro-indol-2-one, F) is formed, and diethylamine is
released into another catalysis cycle.
D–HÁÁÁA
D–H
HÁÁÁA
DÁÁÁA
D–HÁÁÁA
N(1)–H(1A)ÁÁÁO(2)
O(2)–H(2A)ÁÁÁO(1)
O(5)–H(5B)ÁÁÁO(3)
0.86
0.82
0.97
2.13
1.92
2.42
2.9833(17)
2.7396(16)
2.383(2)
171
171
170
Symmetry codes: -x ? 1/2, -y, z ? 1/2; -x, y ? 1/2, -z ? 1/2;
x ? 1/2, -y ? 1/2, -z
In order to provide the structural information of com-
pound 1, we studied its crystal structure by single crystal
X-ray diffraction in the following research. The main data
is displayed from Tables 1, 2, 3 and 4. The molecular
structure is shown in Fig. 1, the intermolecular hydrogen
bonds and a packing diagram are depicted in and Figs. 2
and 3, respectively. The X-ray structural determination of 1
confirmed the assignment of its structure from NMR and
MS spectra data.
structure, which are primarily responsible for the formation
of the framework (Fig. 2). The N and O of nitro group are
not involved in any hydrogen bond. There is no intramo-
lecular hydrogen bond. In the crystal, the non-polar parts,
phenyls, pack together by p–p stacking, while the polar
parts are fixed one another by intermolecular hydrogen
bonds. The molecules are oriented layer by layer by the
interactions as shown in Fig. 3.
Geometric parameters of the title compound (1) are in
the usual ranges. It crystallizes in the orthorhombic space
˚
group, Pbca, with unit cell dimensions a = 10.515 (2) A,
˚
˚
b = 7.3736 (14) A, and c = 23.261 (4) A. The two rings
are coplanar, and the angle between hydroxyl group and
the nitromethyl group is 109.07(9)°. In the crystal structure,
intermolecular N–HÁÁÁO and O–HÁÁÁO hydrogen bonds
(Table 4) seem to be effective in the stabilization of the
Supplementary Material
Crystallographic data for the structure reported in this paper
have been deposited at the Cambridge Crystallographic
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J Chem Crystallogr (2010) 40:369–372
Fig. 3 A packing diagram of the title molecular
Acknowledgments This work was financially supported by the
grants from Scientific Research Plan Projects of Natural Science
Research Plan Projects of Shaanxi Science and Technology Depart-
ment (SJ08B20), Scientific Research Plan Projects of Shaanxi Edu-
cation Department (08JK413, 09JK702) and Scientific Research
Foundation for PhD of Xi’an Shiyou University (Z08008).
Fig. 1 The molecular structure of the title molecule
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