1-Benzyl-3,3-dichloro-1H-indol-2(3H)-one

Article abstract of DOI:10.1107/S0108270107002028

The title compound, C15H11Cl2NO, was synthesized from N - benzyl-isatin. The compound crystallizes as stacks of mol-ecules running down the c axis. Mol-ecules within each of these stacks inter-act with each other through π-π and C - H...π inter-actions, a

Full text of DOI:10.1107/S0108270107002028

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
As part of our research programme, we have been inter-
ested in the synthesis of substituted heterocycles, such as
carbazoles (de Koning et al., 2003; Pelly et al., 2005; Pathak et
al., 2006) and fused indole systems (de Koning et al., 2004).
During the course of our work on the synthesis of potential
kinase inhibitors (Fabbro et al., 2002; Geyer et al., 2005; Noble
et al., 2005), we had reason to synthesize the simple oxindole
ISSN 0108-2701
1-Benzyl-3,3-dichloro-1H-indol-
2(3H)-one
A. N. C. Lotter, M. A. Fernandes, W. A. L. van Otterlo and
È
C. B. de Koning*
School of Chemistry, Molecular Sciences Institute, University of the Witwatersrand,
PO Wits 2050, Johannesburg, South Africa
Correspondence e-mail: dekoning@chem.wits.ac.za
Received 14 November 2006
Accepted 15 January 2007
Online 10 February 2007
The title compound, C15H11Cl2NO, was synthesized from
N-benzylisatin. The compound crystallizes as stacks of mol-
ecules running down the c axis. Molecules within each of these
stacks interact with each other through ꢀ±ꢀ and CÐHÁ Á Áꢀ
interactions, and interact with neighbouring stacks through
CÐHÁ Á ÁO interactions.
Figure 1
A view of the title molecule, showing the atom-numbering scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown with an arbitrary radius.
Comment
Oxindoles occur commonly as subunits of biologically active
compounds. For example, compound (I) (see scheme) has
been found to be a potential inhibitor of the kinase insert
Figure 2
Weak interactions between molecules related by the c-glide plane
producing a stack of molecules running down the c axis. Indicated with a
star (?) on the diagram are the ꢀ±ꢀ interactions between the N/C1±C3/C8
and C3±C8 rings. Indicated with a hash (#) are the CÐHÁ Á Áꢀ interactions
between the C9ÐH9B group and the C10±C15 ring. Molecules (i), (ii)
and (iii) are at the symmetry positions (x, y, z), (x, 12 y, 21 + z) and (x, y,
1 + z), respectively.
domain-containing receptor (KDR), alternatively referred to
as VEGFR-2, a receptor for vascular endothelial growth
Â
factors (Bouerat et al., 2005). In essence, this compound is
believed to function as a key regulator of angiogenesis.
Acta Cryst. (2007). C63, o157±o159
DOI: 10.1107/S0108270107002028
# 2007 International Union of Crystallography o157

organic compounds
derivative (II) from N-benzylisatin, (III), where the carbonyl
group at the 3-position of isatin is replaced by two Cl atoms.
The structure of the product, (II), was con®rmed by single-
crystal X-ray crystallography (Fig. 1).
membered ring for all three structures leads to differences of
ꢀ
Ê
less than 0.01 A and 1 for the bond lengths and angles,
respectively.
The title compound is capable of rotation around the C9Ð
N1 and C9ÐC10 bonds (Fig. 1). The conformation adopted by
the molecule is one in which the indol-2-one system is rotated
such that it is almost perpendicular [82.03 (3)ꢀ] to the phenyl
ring (Fig. 2). This conformation allows for simultaneous CÐ
HÁ Á Áꢀ and ꢀ±ꢀ interactions between molecules related by the
c-glide plane. The CÐHÁ Á Áꢀ interaction occurs between the
C9ÐH9B group and the C10±C15 ring of a neighbouring
molecule (Table 2 and Fig. 2).
The ꢀ±ꢀ interaction occurs between the N1/C1±C3/C8 ring
(the ®ve-membered ring of the indol-2-one system) and the
C3±C8 ring (the six-membered ring of the indol-2-one system)
of a neighbouring molecule (Fig. 2). In this interaction, the two
rings are slipped by 30.2ꢀ relative to their ring perpendiculars
The bond lengths and angles for (II) were found to be
typical for compounds of this type. Bond lengths and angles
for the nitrogen-containing ring of the indol-2-one system are
given in Table 1. A search of the Cambridge Structural
Database (CSD; Version 5.27; Allen, 2002) for indol-2-one
compounds with dichloro substitution on C2 (or IUPAC
position 3; Fig. 1) yielded only two structures, viz. 3,3-dichloro-
1H-indol-2(3H)-one, (IV) (CSD refcode KUNMUB;
Zukerman-Schpector et al., 1993), and 1,3,3,5-tetrachloro-1,3-
dihydroindol-2-one, (V) (QASXEO; Meketa et al., 2005).
Comparison of the bond angles around the N-containing ®ve-
membered ring indicates that the N1ÐC1 bond length, as well
as the C8ÐN1ÐC1 and N1ÐC1ÐC2 angles, are most
affected by the atom type bonded to the N atom (Table 3).
Comparing geometric parameters around the rest of the ®ve-
Ê
(the average interplanar distance is 3.484 A), the ring-
Ê
centroid-to-ring-centroid distance being 4.0329 (9) A.
Admittedly, the ®ve-membered ring of the indol-2-one system
is only partly aromatic, but a signi®cant part of the ring (O1,
C1 and N1) is involved in conjugation with the aromatic six-
membered ring, as shown by the bond lengths between these
atoms (Table 1). The ꢀ±ꢀ interaction is therefore really
between these atoms and those of the neighbouring ring, and
if this were taken into account the centroid-to-centroid
distance would be even shorter. A consequence of the CÐ
HÁ Á Áꢀ and ꢀ±ꢀ interactions is the creation of stacks of mol-
ecules running down the c axis (Fig. 3).
Finally, acting between the stacks of molecules just
described are CÐHÁ Á ÁO and CÐHÁ Á ÁCl interactions (Table 2
and Fig. 4).
Experimental
Figure 3
The crystal packing in (II), showing the stacks of molecules running down
the c axis.
The dione (III) (6.40 g, 27.00 mmol) was dissolved in C6H6 (70 ml) in
a round-bottomed ¯ask and cooled to 273 K. PCl5 (12.80 g,
62.10 mmol, 2.3 equivalents) was added and the solution was warmed
to 298 K for 24 h. The solvent was removed in vacuo to obtain a
yellow±brown residue, which was further puri®ed by column chro-
matography (5% EtOAc/hexane) to afford (II) as a light-yellow oil.
On addition of EtOH, (II) precipitated as a colourless solid [yield
6.37 g, 81%; m.p. 398±399 K (literature m.p. 399±400 K; Palazzo &
1
Rosnati, 1953)]. H NMR (300 MHz, CDCl3, Me4Si): ꢁH 4.94 (2H, s,
PhCH2N), 6.72 (1H, d, J = 7.9 Hz, ArH), 7.14 (1H, t, J = 7.6 Hz, ArH),
7.22±7.39 (6H, m, 6 Â ArH) and 7.64 (1H, d, J = 7.5 Hz, ArH). 13C
NMR (75 MHz, CDCl3): ꢁC 44.5 (PhCH2N), 110.1 (ArCCl2), 124.2
(CH), 124.9 (CH), 127.1 (2 Â CH), 128.1 (CH), 129.0 (2 Â CH), 129.3
(C), 131.8 (CH), 134.4 (C), 139.8 (C) and 169.2 (C O) (one CH not
observed in spectrum).
Crystal data
C15H11Cl2NO
Mr = 292.15
Monoclinic, P21=c
Z = 4
Dx = 1.453 Mg m
Mo Kꢃ radiation
ꢄ = 0.48 mm
T = 173 (2) K
Irregular, colourless
0.48 Â 0.30 Â 0.26 mm
3
1
Figure 4
Ê
a = 10.4847 (13) A
Ê
b = 14.4641 (18) A
CÐHÁ Á ÁO interactions between molecules related by the screw symmetry
running down the b axis. These interactions act between the stacks shown
in Fig. 2. Molecules (i), (ii), (iii) and (iv) are at the symmetry positions (x,
y, z), (2 x, 12 + y, 21 z), (x, 1 + y, z) and (2 x, 23 + y, 12 z), respectively.
Ê
c = 9.2203 (11) A
ꢂ = 107.244 (2)ꢀ
3
Ê
V = 1335.4 (3) A
ꢁ
o158 Lotter et al. C15H11Cl2NO
Acta Cryst. (2007). C63, o157±o159
È

organic compounds
Ê
Data collection
(aromatic CH) or 0.99 A (CH2) and isotropic displacement para-
meters equal to 1.2 times Ueq of the parent atom.
Bruker SMART CCD area-detector
diffractometer
' and ! scans
8835 measured re¯ections
3213 independent re¯ections
2603 re¯ections with I > 2ꢅ(I)
Rint = 0.028
Data collection: SMART-NT (Bruker, 1998); cell re®nement:
SAINT-Plus (Bruker, 1999); data reduction: SAINT-Plus; program(s)
used to solve structure: SHELXTL (Bruker, 1999); program(s) used
to re®ne structure: SHELXTL; molecular graphics: ORTEP-3
(Farrugia, 1997) and SCHAKAL99 (Keller, 1999); software used to
prepare material for publication: PLATON (Spek, 2003) and
SHELXTL.
ꢆmax = 28.0ꢀ
Re®nement
Re®nement on F2
R[F2 > 2ꢅ(F2)] = 0.032
wR(F2) = 0.088
S = 1.05
3213 re¯ections
w = 1/[ꢅ2(F2o) + (0.0453P)2
+ 0.2606P]
where P = (F2o + 2Fc2)/3
(Á/ꢅ)max = 0.001
3
Ê
Áꢇmax = 0.33 e A
3
Ê
0.35 e A
172 parameters
H-atom parameters constrained
Áꢇmin
=
This work was supported by the National Research Foun-
dation (NRF, GUN 2053652), Pretoria, and the University of
the Witwatersrand [University (Sellschop award) and Science
Faculty Research Councils].
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
C1ÐO
C1ÐN
C1ÐC2
1.2107 (17)
1.3637 (18)
1.5555 (19)
C2ÐC3
C3ÐC8
C8ÐN
1.4945 (19)
1.3966 (18)
1.4109 (17)
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: DN3029). Services for accessing these data are
described at the back of the journal.
NÐC1ÐC2
C3ÐC2ÐC1
C8ÐC3ÐC2
106.23 (11)
103.98 (11)
107.49 (11)
C3ÐC8ÐN
C1ÐNÐC8
110.30 (11)
111.85 (11)
References
Allen, F. H. (2002). Acta Cryst. B58, 380±388.
Â
Bolvig, S. & Andersson, C. (2005). J. Med. Chem. 48, 5412±5414.
Bruker (1998). SMART-NT. Version 5.050 Bruker AXS Inc., Madison,
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Table 2
Hydrogen-bond geometry (A, ).
Bouerat, L., Fensholdt, J., Liang, X., Havez, S., Nielsen, S. F., Hansen, J. R.,
ꢀ
Ê
Cg is the centroid of the C10±C15 ring.
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DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
C11ÐH11Á Á ÁOi
C9ÐH9BÁ Á ÁCgii
C6ÐH6Á Á ÁCl2iii
C13ÐH13Á Á ÁCl1iv
Symmetry codes: (i) x ‡ 2; y ‡ 12; z ‡ 21; (ii) x;
z ‡ 12; (iv) x ‡ 2; y ‡ 21; z ‡ 32.
0.95
0.99
0.95
0.95
2.64
2.93
2.98
3.01
3.325 (2)
3.660 (2)
3.4461 (15)
3.4815 (18)
129
132
112
112
y
12; z 32; (iii) x ‡ 1, y ‡ 12,
Table 3
Comparison of selected bond lengths and angles (A, ꢀ) for compound
(II), KUNMUB and QASXEO.
Ê
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4749±4751.
Structure/CSD refcode
NÐC1
C8ÐNÐC1
NÐC1ÐC2
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& Zawaira, A. (2005). Biochim. Biophys. Acta, 1754, 58±64.
Palazzo, G. & Rosnati, V. (1953). Gazz. Chim. Ital. 83, 211±223.
Pathak, R., Nhlapo, J. M., Govender, S., Michael, J. P., van Otterlo, W. A. L. &
de Koning, C. B. (2006). Tetrahedron, 62, 2820±2830.
Pelly, S. C., Parkinson, C. J., van Otterlo, W. A. L. & de Koning, C. B. (2005).
J. Org. Chem. 70, 10474±10481.
(II)
KUNMUBa
QASXEOb
1.364 (2)
1.339 (5)
1.37
111.8 (1)
112.8 (3)
114
106.2 (1)
106.1 (3)
105
Notes: (a) Zukerman-Schpector et al. (1993); (b) Meketa et al. (2005).
Spek, A. L. (2003). J. Appl. Cryst. 36, 7±13.
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H atoms were positioned geometrically and allowed to ride on
their respective parent atoms, with CÐH bond lengths of 0.95
ꢁ
Acta Cryst. (2007). C63, o157±o159
Lotter et al. C15H11Cl2NO o159
È