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

The title compound, C₁₅H₁₁Cl₂NO, was synthesized from N-­benzyl­isatin. The compound crystallizes as stacks of mol­ecules running down the c axis. Mol­ecules within each of these stacks inter­act with each other through π–π and C—H...π inter­actions, and inter­act with neighbouring stacks through C—H...O inter­actions.

S1. Comment

Oxindoles occur commonly as subunits of biologically active compounds. For example compound 1 has been found to be a potential inhibitor of the kinase insert domain-containing receptor (KDR), alternatively referred to as VEGFR-2, a receptor for vascular endothelial growth factors (Bouérat et al., 2005). In essence, this compound is believed to function as a key regulator of angiogenesis.

As part of our research programme, we have been interested 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 derivative 2 from N-benzyl isatin 3, where the carbonyl at the 3-position of isatin is replaced by two Cl atoms. The structure of the product, (II), was confirmed by single-crystal X-ray crystallography (Fig. 1).

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 five-membered ring indicates that the N—C1 bond length as well as the C8—N—C1 and N—C1—C2 angles are most affected by the atom type bonded to the N atom (Table 3). Comparing geometric parameters around the rest of the five-membered ring for all three structures leads to differences of less than 0.01 Å and 1° for the bond lengths and angles, respectively.

The title compound is capable of rotation around the C9—N and C9—C10 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 a simultaneous C—H···π and π–π interaction between molecules related by the c-glide plane. The C—H···π interaction occurs between the C9/H9B group and the C10–C15 ring (centroid Cg) of a neighbouring molecule (Table 2 and Fig. 2).

The π–π interaction occurs between the ring defined by N, C1, C2, C3 and C8 (the five-membered ring of the indol-2-one system) and the ring defined by C3–C8 (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 30.2° relative to their ring perpendiculars (the average interplanar distance being 3.484 Å), with the ring centroid to ring centroid distance being 4.0329 (9) Å. Admittedly, the five-membered ring of the indol-2-one system is only partly aromatic, but a significant part of the ring (O, C1 and N) is involved in conjugation with the aromatic six-membered ring as shown by the bond lengths between these atoms (Table 1). The π–π 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 C—H···π and π–π interactions is the creation of stacks of molecules running down the c axis (Fig. 3).

Finally, acting between the stacks of molecules just described are C—H···O and C—H···Cl interactions (Table 2 and Fig. 4).

Related literature

For related literature, see: Allen (2002); Bouérat et al. (2005); Fabbro et al. (2002); Geyer et al. (2005); Koning et al. (2003, 2004); Meketa et al. (2005); Noble et al. (2005); Palazzo (1953); Pathak et al. (2006); Pelly et al. (2005); Zukerman-Schpector, Pinto, da DaC, Silva & Barcellos (1993).

S2. Experimental

The dione (III) (6.40 g, 27.00 mmol) was dissolved in C₆H₆ (70 ml) in a round-bottomed flask 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 purified by column chromatography (5% EtOAc/hexane) to afford (II) as a light-yellow oil. On addition of EtOH, (II) precipitated as a white solid [yield 6.37 g, 81%; m.p. 398–399 K (literature m.p. 399–400 K; Palazzo, 1953)]. ¹H NMR (300 MHz, CDCl₃, Me₄Si): δ_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 × ArH) and 7.64 (1H, d, J = 7.5 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃): δ_C 44.5 (PhCH₂N), 110.1 (ArCCl₂), 124.2 (CH), 124.9 (CH), 127.1 (2 × CH), 128.1 (CH), 129.0 (2 × CH), 129.3 (C), 131.8 (CH), 134.4 (C), 139.8 (C) and 169.2 (C═O) (one CH not observed in spectrum).

S3. Refinement

H atoms were positioned geometrically and allowed to ride on their respective parent atoms, with C—H bond lengths of 0.95 (aromatic CH) or 0.99 Å (CH₂), and isotropic displacement parameters equal to 1.2 times U_eq of the parent atom.

Computing details

Data collection: SMART-NT (Bruker, 1998); cell refinement: SAINT-Plus (Bruker, 1999); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Bruker, 1999); program(s) used to refine structure: SHELXTL; molecular graphics: ORTEP-3 (Farrugia, 1997) and SCHAKAL99 (Keller, 1999); software used to prepare material for publication: PLATON (Spek, 2003) and SHELXTL (Bruker, 1999b).

Figures

	Fig. 1. A view of the title molecule showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown with an arbitrary radius.
	Fig. 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 π–π interactions between the N/C1–C3/C8 and C3–C8 rings. Indicated with a hash (#) are the C—H···π interactions between the C9/H9B group and the C10–C15 ring. Molecules (i), (ii) and (iii) are in the symmetry positions (x, y, z), (x, 1/2 - y, 1/2 + z) and (x, y, 1 + z), respectively.
	Fig. 3. The crystal packing in (II) showing the stacks of molecules running down the c axis.
	Fig. 4. C—H···O 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 in the symmetry positions (x, y, z), (2 - x, 1/2 + y, 1/2 - z), (x, 1 + y, z) and (2 - x, 3/2 + y, 1/2 - z), respectively.

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

Crystal data

C15H11Cl2NO	F(000) = 600
Mr = 292.15	Dx = 1.453 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 918 reflections
a = 10.4847 (13) Å	θ = 2.5–28.1°
b = 14.4641 (18) Å	µ = 0.48 mm^−1
c = 9.2203 (11) Å	T = 173 K
β = 107.244 (2)°	Irregular, colourless
V = 1335.4 (3) Å^3	0.48 × 0.30 × 0.26 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometer	2603 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
Graphite monochromator	θmax = 28.0°, θmin = 2.0°
ϕ and ω scans	h = −13→11
8835 measured reflections	k = −19→17
3213 independent reflections	l = −11→12

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.032	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.088	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0453P)^2 + 0.2606P] where P = (Fo^2 + 2Fc^2)/3
3213 reflections	(Δ/σ)max = 0.001
172 parameters	Δρmax = 0.33 e Å^−3
0 restraints	Δρmin = −0.35 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.81611 (13)	0.08784 (10)	0.34296 (15)	0.0290 (3)
C2	0.70179 (13)	0.07206 (9)	0.41592 (15)	0.0277 (3)
C3	0.65767 (13)	0.16757 (9)	0.44019 (15)	0.0255 (3)
C4	0.55791 (14)	0.19881 (10)	0.49812 (16)	0.0317 (3)
H4	0.5008	0.1566	0.5278	0.038*
C5	0.54361 (15)	0.29423 (11)	0.51175 (17)	0.0353 (3)
H5	0.4755	0.3175	0.5505	0.042*
C6	0.62796 (14)	0.35510 (10)	0.46923 (16)	0.0332 (3)
H6	0.6171	0.4196	0.4806	0.040*
C7	0.72862 (14)	0.32418 (9)	0.41007 (15)	0.0287 (3)
H7	0.7857	0.3663	0.3804	0.034*
C8	0.74163 (12)	0.22953 (9)	0.39654 (14)	0.0242 (3)
C9	0.93948 (14)	0.22510 (11)	0.29027 (16)	0.0307 (3)
H9A	0.8999	0.2752	0.2176	0.037*
H9B	0.9785	0.1789	0.2365	0.037*
C10	1.04906 (13)	0.26494 (9)	0.42161 (15)	0.0258 (3)
C11	1.08127 (15)	0.35817 (10)	0.42543 (18)	0.0348 (3)
H11	1.0333	0.3979	0.3458	0.042*
C12	1.18380 (16)	0.39374 (11)	0.5457 (2)	0.0432 (4)
H12	1.2049	0.4577	0.5485	0.052*
C13	1.25468 (15)	0.33616 (12)	0.66092 (19)	0.0413 (4)
H13	1.3248	0.3605	0.7425	0.050*
C14	1.22367 (14)	0.24302 (12)	0.65765 (17)	0.0379 (4)
H14	1.2728	0.2034	0.7366	0.046*
C15	1.12072 (14)	0.20756 (10)	0.53890 (16)	0.0305 (3)
H15	1.0990	0.1437	0.5376	0.037*
N	0.83419 (11)	0.18114 (8)	0.34084 (13)	0.0264 (2)
O	0.87652 (11)	0.02811 (8)	0.29883 (14)	0.0436 (3)
Cl1	0.77076 (4)	0.01204 (3)	0.59136 (4)	0.03919 (12)
Cl2	0.57445 (4)	0.00267 (2)	0.29337 (4)	0.03877 (12)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0271 (7)	0.0296 (7)	0.0291 (7)	−0.0042 (5)	0.0066 (6)	−0.0071 (6)
C2	0.0272 (6)	0.0251 (7)	0.0283 (7)	−0.0046 (5)	0.0044 (5)	−0.0006 (5)
C3	0.0236 (6)	0.0261 (6)	0.0243 (6)	−0.0017 (5)	0.0032 (5)	0.0003 (5)
C4	0.0261 (7)	0.0374 (8)	0.0320 (7)	−0.0016 (6)	0.0092 (6)	0.0021 (6)
C5	0.0300 (7)	0.0419 (9)	0.0344 (8)	0.0082 (6)	0.0100 (6)	−0.0003 (6)
C6	0.0357 (8)	0.0290 (7)	0.0304 (7)	0.0088 (6)	0.0031 (6)	0.0011 (6)
C7	0.0323 (7)	0.0251 (7)	0.0269 (7)	−0.0017 (5)	0.0059 (6)	0.0025 (5)
C8	0.0231 (6)	0.0272 (7)	0.0205 (6)	−0.0011 (5)	0.0036 (5)	−0.0009 (5)
C9	0.0304 (7)	0.0376 (8)	0.0260 (7)	−0.0071 (6)	0.0115 (6)	−0.0027 (6)
C10	0.0244 (6)	0.0302 (7)	0.0262 (6)	−0.0035 (5)	0.0129 (5)	−0.0033 (5)
C11	0.0340 (8)	0.0300 (7)	0.0414 (8)	−0.0037 (6)	0.0129 (6)	0.0027 (6)
C12	0.0397 (9)	0.0343 (8)	0.0588 (11)	−0.0140 (7)	0.0197 (8)	−0.0142 (7)
C13	0.0266 (7)	0.0573 (10)	0.0403 (9)	−0.0072 (7)	0.0104 (6)	−0.0191 (8)
C14	0.0271 (7)	0.0534 (10)	0.0333 (8)	0.0047 (7)	0.0089 (6)	−0.0007 (7)
C15	0.0303 (7)	0.0283 (7)	0.0354 (7)	0.0005 (5)	0.0138 (6)	−0.0014 (6)
N	0.0251 (6)	0.0272 (6)	0.0278 (6)	−0.0052 (4)	0.0089 (5)	−0.0048 (5)
O	0.0453 (6)	0.0340 (6)	0.0566 (7)	−0.0010 (5)	0.0231 (6)	−0.0132 (5)
Cl1	0.0488 (2)	0.0328 (2)	0.0331 (2)	0.00729 (15)	0.00766 (16)	0.00495 (14)
Cl2	0.0370 (2)	0.0331 (2)	0.0417 (2)	−0.01408 (14)	0.00464 (16)	−0.00475 (15)

Geometric parameters (Å, º)

C1—O	1.2107 (17)	C8—N	1.4109 (17)
C1—N	1.3637 (18)	C9—N	1.4647 (17)
C1—C2	1.5555 (19)	C9—C10	1.5145 (18)
C2—C3	1.4945 (19)	C9—H9A	0.9900
C2—Cl2	1.7811 (13)	C9—H9B	0.9900
C2—Cl1	1.7888 (14)	C10—C11	1.388 (2)
C3—C4	1.3837 (19)	C10—C15	1.393 (2)
C3—C8	1.3966 (18)	C11—C12	1.394 (2)
C4—C5	1.398 (2)	C11—H11	0.9500
C4—H4	0.9500	C12—C13	1.380 (2)
C5—C6	1.384 (2)	C12—H12	0.9500
C5—H5	0.9500	C13—C14	1.384 (2)
C6—C7	1.397 (2)	C13—H13	0.9500
C6—H6	0.9500	C14—C15	1.388 (2)
C7—C8	1.3851 (19)	C14—H14	0.9500
C7—H7	0.9500	C15—H15	0.9500
O—C1—N	127.78 (13)	N—C9—C10	112.05 (11)
O—C1—C2	125.98 (13)	N—C9—H9A	109.2
N—C1—C2	106.23 (11)	C10—C9—H9A	109.2
C3—C2—C1	103.98 (11)	N—C9—H9B	109.2
C3—C2—Cl2	114.13 (10)	C10—C9—H9B	109.2
C1—C2—Cl2	109.70 (9)	H9A—C9—H9B	107.9
C3—C2—Cl1	111.92 (9)	C11—C10—C15	119.20 (13)
C1—C2—Cl1	107.79 (9)	C11—C10—C9	120.74 (13)
Cl2—C2—Cl1	109.04 (7)	C15—C10—C9	120.05 (13)
C4—C3—C8	120.99 (13)	C10—C11—C12	120.20 (15)
C4—C3—C2	131.50 (13)	C10—C11—H11	119.9
C8—C3—C2	107.49 (11)	C12—C11—H11	119.9
C3—C4—C5	118.07 (13)	C13—C12—C11	120.12 (15)
C3—C4—H4	121.0	C13—C12—H12	119.9
C5—C4—H4	121.0	C11—C12—H12	119.9
C6—C5—C4	120.52 (14)	C12—C13—C14	120.07 (14)
C6—C5—H5	119.7	C12—C13—H13	120.0
C4—C5—H5	119.7	C14—C13—H13	120.0
C5—C6—C7	121.79 (14)	C13—C14—C15	119.97 (15)
C5—C6—H6	119.1	C13—C14—H14	120.0
C7—C6—H6	119.1	C15—C14—H14	120.0
C8—C7—C6	117.22 (13)	C14—C15—C10	120.44 (14)
C8—C7—H7	121.4	C14—C15—H15	119.8
C6—C7—H7	121.4	C10—C15—H15	119.8
C7—C8—C3	121.40 (12)	C1—N—C8	111.85 (11)
C7—C8—N	128.30 (12)	C1—N—C9	123.72 (12)
C3—C8—N	110.30 (11)	C8—N—C9	124.41 (11)
O—C1—C2—C3	−176.71 (14)	C2—C3—C8—N	1.99 (14)
N—C1—C2—C3	3.88 (14)	N—C9—C10—C11	−122.02 (14)
O—C1—C2—Cl2	−54.26 (18)	N—C9—C10—C15	59.29 (17)
N—C1—C2—Cl2	126.33 (10)	C15—C10—C11—C12	−0.3 (2)
O—C1—C2—Cl1	64.35 (17)	C9—C10—C11—C12	−178.97 (13)
N—C1—C2—Cl1	−115.06 (11)	C10—C11—C12—C13	0.7 (2)
C1—C2—C3—C4	178.48 (14)	C11—C12—C13—C14	−0.3 (2)
Cl2—C2—C3—C4	59.00 (18)	C12—C13—C14—C15	−0.4 (2)
Cl1—C2—C3—C4	−65.44 (17)	C13—C14—C15—C10	0.8 (2)
C1—C2—C3—C8	−3.51 (14)	C11—C10—C15—C14	−0.4 (2)
Cl2—C2—C3—C8	−122.99 (10)	C9—C10—C15—C14	178.28 (12)
Cl1—C2—C3—C8	112.57 (11)	O—C1—N—C8	177.71 (14)
C8—C3—C4—C5	0.0 (2)	C2—C1—N—C8	−2.90 (15)
C2—C3—C4—C5	177.77 (14)	O—C1—N—C9	−3.7 (2)
C3—C4—C5—C6	−0.5 (2)	C2—C1—N—C9	175.65 (11)
C4—C5—C6—C7	0.7 (2)	C7—C8—N—C1	−179.33 (13)
C5—C6—C7—C8	−0.5 (2)	C3—C8—N—C1	0.67 (15)
C6—C7—C8—C3	0.00 (19)	C7—C8—N—C9	2.1 (2)
C6—C7—C8—N	180.00 (12)	C3—C8—N—C9	−177.86 (12)
C4—C3—C8—C7	0.3 (2)	C10—C9—N—C1	−107.55 (15)
C2—C3—C8—C7	−178.01 (12)	C10—C9—N—C8	70.82 (17)
C4—C3—C8—N	−179.75 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11···O^i	0.95	2.64	3.325 (2)	129
C9—H9B···Cg^ii	0.99	2.93	3.660 (2)	132
C6—H6···Cl2^iii	0.95	2.98	3.4461 (15)	112
C13—H13···Cl1^iv	0.95	3.01	3.4815 (18)	112

Symmetry codes: (i) −x+2, y+1/2, −z+1/2; (ii) x, −y−1/2, z−3/2; (iii) −x+1, y+1/2, −z+1/2; (iv) −x+2, y+1/2, −z+3/2.