Crystal and geometry-optimized structure, and Hirshfeld surface analysis of 1-(2-bromo-eth-yl)indoline-2,3-dione.

In the title compound, C10H8BrNO2, the isatin (1H-indole-2,3-dione) moiety is nearly planar (r.m.s. deviation = 0.026 Å). In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming layers parallel to the ab plane, and enclosing R44(24) loops. There are a low percentage (19.3%) of inter-molecular H⋯H contacts in the structure, as estimated by the analysis of Hirshfeld surfaces. This could be due to the presence of the Br atom, present in the bromo-ethyl-ene group, which makes ca 18.7% Br⋯H contacts.

Chemical context

Isatin (<span class="Chemical">1H-indole-2,3-dione) is an endogenous compound that has been identified in humans and possesses a wide range of biological activities, such as anxiogenic and sedative activities. It serves as a synthetically useful substrate which can be used to prepare a broad range of heterocyclic compounds, including mol­ecules of pharmacological significance (Bekircan & Bektas, 2008 ▸). A variety of biological activities are associated with isatin, including central nervous system (CNS) activities (Raj, 2012 ▸). As part of our inter­est in the identification of bioactive compounds, we report herein on the synthesis, the crystal structure, and the geometry optimization and Hirshfeld surface analysis of the title isatin derivative, (I).

Structural commentary

The mol­ecular structure of the title isatin derivative, (I), is illustrated in Fig. 1 ▸. It crystallized in the ortho­rhom­bic space group P212121 with an absolute structure parameter of 0.015 (8). The bond lengths and angles of the <span class="Chemical">isatin moiety are comparable with those reported for similar N-substituted isatin derivatives (Qachchachi et al., 2016a ▸,b ▸).

Figure 1

The mol­ecular structure of compound (I), showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

In compound (I), the isatin ring system is almost planar, with an r.m.s. deviation of the fitted atoms C1–C8/N1/O1/O2 of 0.026 Å. The sum of the bond angles around atom N1 is ca 360°, indicating little evidence for the presence of an sp 3 lone pair.

Supra­molecular features

In the crystal of (I), mol­ecules are linked by C—H⋯O hydrogen bonds, viz C2—H2⋯O1 and <span class="Gene">C10—H10A⋯O2 (Table 1 ▸), which individually form C(6) and C(7) chains, respectively. Together they form layers parallel to the ab plane and enclose (24) loops (Table 1 ▸ and Fig. 2 ▸). An analysis of the crystal packing of (I) indicated that no further significant inter­molecular inter­actions were present (PLATON; Spek, 2009 ▸).

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O1i	0.93	2.41	3.286 (6)	156
C10—H10A⋯O2ii	0.97	2.42	3.309 (6)	151

Symmetry codes: (i) ; (ii) .

Figure 2

A view along the c axis of the crystal packing of compound (I). The hydrogen bonds are shown as dashed lines (see Table 1 ▸) and, for clarity, only H atoms H2 and H10A have been included.

Database survey

A search of the Cambridge Structural Database (Version 5.37, update May 2016; Groom et al., 2016 ▸) for N-substituted isatin derivatives yielded 58 hits. These include five reports of the structure of <span class="Chemical">isatin itself and four reports of the structure of N-methyl­isatin. 13 of the structures involve an alkyl chain of two or more C atoms. The compound most similar to the title compound is 1-(3-bromo­prop­yl)-1H-indole-2,3-dione (AKO­BIN), whose structure was published very recently (Qachchachi et al., 2016a ▸). A view of the structural overlap of this compound with that of compound (I) is shown in Fig. 3 ▸.

Figure 3

The structural fit of compound (I) and 1-(3-bromo­prop­yl)-1H-indole-2,3-dione (AKOBIN; Qachchachi et al., 2016a ▸); mol­ecules are shown in blue and red, respectively.

Geometry optimization

The geometry optimization of compound (I) was performed using the density functional theory (DFT) method with a 6-311++G** basis set. The crystal structure in the solid state was used as the starting structure for the calculations. The DFT calculations are performed with the GAUSSIAN09 program package (Frisch et al., 2013 ▸). The resulting geometrical parameters are compared with those obtained from an X-ray crystallography study. A superimposed analysis of (I) with its optimized structure gives an r.m.s. deviation of 0.068 Å (Fig. 4 ▸). This indicates a twist leading to further separation between the isatin moiety and the <span class="Chemical">benzene ring. Also, this suggests that the crystal packing could be influenced by the collective effect of the inter­molecular inter­actions. To probe further, structure-based theoretical parameters, viz. HOMO and LUMO energy levels, total energy and dipole moment, were calculated and found to be −6.860 eV, −3.091 eV, −86134.81 eV and 7.2176 Debye, respectively. As a further structure-based test, semi-empirical mol­ecular orbital calculations are carried out using the PM7 method in MOPAC2012 (Stewart, 2012 ▸; Maia et al., 2012 ▸). The PM7 method gave the HOMO and LUMO energy levels, total energy and dipole moment as −9.276 eV, −1.271 eV, −2334.96 eV and 5.8952 Debye, respectively. Also, the superimposed analysis of the X-ray structure with the isolated mol­ecule in the gas phase by the PM7 method gave an r.m.s. deviation of 0.211 Å. Further, the N1—C8 and N1—C1 (X-ray: 1.367 Å; DFT: 1.392 Å; PM7: 1.424 Å) bond lengths increased, while the bond angles O2—C7—C6 (X-ray: 131.3°; DFT: 130.8°; PM7: 131.2°) and O1—C8—N1 (X-ray: 127.4°; DFT: 126.8°; PM7: 123.8°) decreased. These confirm the influence of the packing inter­actions in the solid state of the mol­ecule. The relative conformation about the bond joining the isatin and bromo­ethyl­ene moieties of (I) is defined by the N1—C9—C10—Br1 torsion angle of 62.0 (5)°. This indicates that the conformation of the mol­ecule is (+)-synclinal.

Figure 4

Superimposed fit of the mol­ecule of compound (I) in the crystalline state (red) and after energy minimization (blue).

Hirshfeld surface analysis

A detailed Hirshfeld surface analysis is useful for identifing the various inter­molecular inter­actions and inter­molecular contacts present in crystal structures, with the aid of decomposed two-dimensional fingerprint plots. The Hirshfeld surface (HS) and the two-dimensional fingerprint plots were generated based on the d i and d e distances using Crystal Explorer (Wolff et al., 2012 ▸); d i is the distance from the nearest atom inside the surface, while d e is the distance from the HS to the nearest atom outside the surface. This analysis identified the various inter­molecular contacts (O—H, H—H, C—H, C—C and H—Br) and their relative contributions in the crystal structure. The bond lengths (C—H = 1.083 Å, N—H = 1.009 Å and O—H = 0.983 Å) were adjusted to typical neutron diffraction values before the HS calculation (Venkatesan et al., 2015 ▸, 2016a ▸,b ▸). In Hirshfeld surface diagrams, the contacts with distances shorter than the sum of the van der Waals radii are indicated as red and the contacts with distances longer than the van der Waals radii are represented as blue, whereas the contacts with distances equal to the sum of the van der Waals radii are indicated as white. The HS area of compound (I) is shown in Fig. 5 ▸, and the respective points of inter­molecular inter­actions are labelled.

Figure 5

Views of the Hirshfeld surfaces mapped with d norm in two different orientations for compound (I). The represented inter­actions are labelled (see Table 1 ▸).

Two-dimensional fingerprint plots are used to qu­antify and visualize the inter­molecular inter­actions present in the crystal structure and the same for the title compound is shown in Fig. 6 ▸. The result suggests that the share of inter­molecular H⋯H contacts in (I) is about 19.3%. The low percentage could be attributed to the presence of the Br atom in the bromo­ethyl­ene group, which makes ca 18.7% contacts with H atoms (Br⋯H). The next significant inter­molecular contacts observed in the structure, i.e. O⋯H, C⋯H and C⋯C, have relative contributions of 30.6, 18.8 and 3.1%, respectively.

Figure 6

Decomposed two-dimensional fingerprint plots for compound (I). Various close contacts and their relative contributions are indicated.

Synthesis and crystallization

To a solution of 1-{2-[(2-bromo­eth­yl)amino]­phen­yl}ethanone (1 equivalent) in DMSO were added <span class="Chemical">I2 (0.1 equivalents) and TBHP (1 equivalent, 70% in H2O) at ambient temperature, and the mixture was heated to 353 K. The progress of the reaction was monitored by thin-layer chromatography. Upon completion, the reaction mixture was allowed to cool to ambient temperature and was quenched with aqueous sodium thio­sulfate and ethyl acetate. The organic phase was separated, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica-gel column chromatography using hexa­ne–ethyl acetate (9:1 v/v) as eluent. The title compound was obtained as a red solid (yield: 71%, 74.5 mg; m.p. 404–406 K). It was dissolved in a mixture of hexa­ne–ethyl acetate (9:1 v/v) and left to slowly evaporate at room temperature, yielding brown block-like crystals after a period of 3 d.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. C-bound H atoms were included in calculated positions and treated as riding, with C—H = 0.93–0.97 Å and U iso(H) = 1.2U eq(C).

Table 2

Experimental details

Crystal data
Chemical formula	C10H8BrNO2
M r	254.08
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	293
a, b, c (Å)	4.6834 (2), 12.9567 (7), 16.1130 (8)
V (Å3)	977.76 (8)
Z	4
Radiation type	Mo Kα
μ (mm−1)	4.18
Crystal size (mm)	0.25 × 0.20 × 0.20
Data collection
Diffractometer	Bruker Kappa APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2004 ▸)
T min, T max	0.419, 0.498
No. of measured, independent and observed [I > 2σ(I)] reflections	8226, 3150, 1663
R int	0.037
(sin θ/λ)max (Å−1)	0.762
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.055, 0.084, 1.02
No. of reflections	3150
No. of parameters	127
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.70, −0.59
Absolute structure	Flack x determined using 503 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)
Absolute structure parameter	0.015 (8)

Computer programs: APEX2, SAINT and XPREP (Bruker, 2004 ▸), SHELXS97 (Sheldrick, 2008 ▸), SHELXL2014 (Sheldrick, 2015 ▸), QMOL (Gans & Shalloway, 2001 ▸), Mercury (Macrae et al., 2008 ▸), WinGX (Farrugia, 2012 ▸) and PLATON (Spek, 2009 ▸).

Crystal structure: contains datablock(s) I, Global. DOI: 10.1107/S2056989016015760/su5327sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016015760/su5327Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016015760/su5327Isup3.cml

CCDC reference: 1508554

Additional supporting information: crystallographic information; 3D view; checkCIF report

C10H8BrNO2	Dx = 1.726 Mg m−3
Mr = 254.08	Melting point: 406 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
a = 4.6834 (2) Å	Cell parameters from 2844 reflections
b = 12.9567 (7) Å	θ = 2.5–26.7°
c = 16.1130 (8) Å	µ = 4.18 mm−1
V = 977.76 (8) Å3	T = 293 K
Z = 4	Block, brown
F(000) = 504	0.25 × 0.20 × 0.20 mm

Bruker Kappa APEXII CCD diffractometer	1663 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.037
ω and φ scan	θmax = 32.8°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −7→6
Tmin = 0.419, Tmax = 0.498	k = −19→17
8226 measured reflections	l = −22→18
3150 independent reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.055	H-atom parameters constrained
wR(F2) = 0.084	w = 1/[σ2(Fo2) + (0.0167P)2 + 0.3638P] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max < 0.001
3150 reflections	Δρmax = 0.70 e Å−3
127 parameters	Δρmin = −0.59 e Å−3
0 restraints	Absolute structure: Flack x determined using 503 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.015 (8)

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

	x	y	z	Uiso*/Ueq
Br1	0.83217 (12)	0.83821 (4)	0.06227 (4)	0.0609 (2)
O1	0.4527 (9)	0.7005 (3)	0.2349 (3)	0.0719 (13)
O2	0.8447 (9)	0.6409 (2)	0.3684 (2)	0.0688 (10)
N1	0.6516 (8)	0.8607 (2)	0.2584 (2)	0.0378 (8)
C1	0.8490 (10)	0.9005 (3)	0.3156 (3)	0.0326 (9)
C2	0.9288 (9)	1.0020 (3)	0.3268 (3)	0.0429 (12)
H2	0.8520	1.0548	0.2947	0.051*
C3	1.1289 (12)	1.0218 (4)	0.3883 (3)	0.0538 (14)
H3	1.1896	1.0894	0.3966	0.065*
C4	1.2414 (10)	0.9446 (4)	0.4377 (4)	0.0572 (14)
H4	1.3755	0.9606	0.4783	0.069*
C5	1.1551 (10)	0.8445 (4)	0.4267 (3)	0.0503 (11)
H5	1.2276	0.7920	0.4599	0.060*
C6	0.9592 (9)	0.8233 (4)	0.3656 (3)	0.0362 (11)
C7	0.8222 (12)	0.7276 (3)	0.3414 (3)	0.0447 (12)
C8	0.6167 (11)	0.7569 (4)	0.2703 (3)	0.0458 (13)
C9	0.4985 (10)	0.9198 (4)	0.1964 (3)	0.0464 (12)
H9A	0.4179	0.9805	0.2227	0.056*
H9B	0.3412	0.8784	0.1757	0.056*
C10	0.6765 (12)	0.9533 (3)	0.1248 (3)	0.0499 (12)
H10A	0.8325	0.9956	0.1451	0.060*
H10B	0.5612	0.9955	0.0881	0.060*

	U11	U22	U33	U12	U13	U23
Br1	0.0714 (3)	0.0570 (3)	0.0543 (3)	−0.0008 (3)	0.0059 (3)	−0.0069 (3)
O1	0.090 (3)	0.055 (2)	0.071 (3)	−0.036 (2)	−0.003 (2)	−0.012 (2)
O2	0.102 (3)	0.0323 (18)	0.072 (3)	0.005 (2)	0.013 (3)	0.0138 (17)
N1	0.042 (2)	0.035 (2)	0.036 (2)	−0.0055 (19)	−0.001 (2)	0.0022 (16)
C1	0.038 (2)	0.032 (2)	0.028 (2)	−0.001 (2)	0.007 (2)	−0.0028 (18)
C2	0.057 (3)	0.029 (2)	0.043 (3)	−0.001 (2)	0.006 (2)	0.000 (2)
C3	0.069 (4)	0.045 (3)	0.047 (3)	−0.016 (3)	0.011 (3)	−0.015 (3)
C4	0.060 (3)	0.078 (4)	0.034 (3)	−0.011 (2)	0.003 (3)	−0.007 (3)
C5	0.053 (2)	0.063 (3)	0.036 (3)	0.006 (3)	0.004 (3)	0.008 (3)
C6	0.045 (2)	0.038 (3)	0.026 (3)	0.002 (2)	0.006 (2)	−0.001 (2)
C7	0.060 (3)	0.032 (2)	0.043 (3)	0.003 (3)	0.017 (3)	0.002 (2)
C8	0.058 (3)	0.038 (3)	0.041 (3)	−0.011 (3)	0.010 (3)	−0.005 (2)
C9	0.041 (3)	0.053 (3)	0.045 (3)	0.004 (2)	−0.004 (3)	0.000 (3)
C10	0.061 (3)	0.040 (2)	0.048 (3)	0.005 (3)	−0.005 (3)	0.005 (2)

Br1—C10	1.942 (5)	C4—C5	1.370 (7)
O1—C8	1.204 (6)	C4—H4	0.9300
O2—C7	1.210 (5)	C5—C6	1.373 (6)
N1—C8	1.367 (5)	C5—H5	0.9300
N1—C1	1.404 (6)	C6—C7	1.449 (6)
N1—C9	1.449 (6)	C7—C8	1.544 (7)
C1—C2	1.380 (6)	C9—C10	1.488 (7)
C1—C6	1.384 (6)	C9—H9A	0.9700
C2—C3	1.388 (7)	C9—H9B	0.9700
C2—H2	0.9300	C10—H10A	0.9700
C3—C4	1.382 (7)	C10—H10B	0.9700
C3—H3	0.9300
C8—N1—C1	110.4 (4)	C1—C6—C7	107.2 (4)
C8—N1—C9	123.9 (4)	O2—C7—C6	131.3 (5)
C1—N1—C9	125.7 (4)	O2—C7—C8	123.3 (5)
C2—C1—C6	120.7 (4)	C6—C7—C8	105.4 (4)
C2—C1—N1	128.0 (4)	O1—C8—N1	127.4 (5)
C6—C1—N1	111.2 (4)	O1—C8—C7	126.9 (5)
C1—C2—C3	116.9 (4)	N1—C8—C7	105.7 (4)
C1—C2—H2	121.5	N1—C9—C10	114.3 (4)
C3—C2—H2	121.5	N1—C9—H9A	108.7
C4—C3—C2	122.3 (5)	C10—C9—H9A	108.7
C4—C3—H3	118.8	N1—C9—H9B	108.7
C2—C3—H3	118.8	C10—C9—H9B	108.7
C5—C4—C3	119.9 (5)	H9A—C9—H9B	107.6
C5—C4—H4	120.1	C9—C10—Br1	112.9 (3)
C3—C4—H4	120.1	C9—C10—H10A	109.0
C4—C5—C6	118.6 (5)	Br1—C10—H10A	109.0
C4—C5—H5	120.7	C9—C10—H10B	109.0
C6—C5—H5	120.7	Br1—C10—H10B	109.0
C5—C6—C1	121.5 (4)	H10A—C10—H10B	107.8
C5—C6—C7	131.3 (5)
C8—N1—C1—C2	−175.9 (5)	C5—C6—C7—O2	−0.3 (9)
C9—N1—C1—C2	2.7 (7)	C1—C6—C7—O2	−178.2 (6)
C8—N1—C1—C6	2.1 (5)	C5—C6—C7—C8	178.1 (5)
C9—N1—C1—C6	−179.4 (4)	C1—C6—C7—C8	0.2 (5)
C6—C1—C2—C3	1.9 (7)	C1—N1—C8—O1	175.8 (5)
N1—C1—C2—C3	179.7 (4)	C9—N1—C8—O1	−2.8 (8)
C1—C2—C3—C4	−1.2 (7)	C1—N1—C8—C7	−1.8 (5)
C2—C3—C4—C5	−0.1 (8)	C9—N1—C8—C7	179.6 (4)
C3—C4—C5—C6	0.7 (8)	O2—C7—C8—O1	2.0 (8)
C4—C5—C6—C1	0.0 (7)	C6—C7—C8—O1	−176.6 (5)
C4—C5—C6—C7	−177.6 (5)	O2—C7—C8—N1	179.6 (5)
C2—C1—C6—C5	−1.4 (7)	C6—C7—C8—N1	1.0 (5)
N1—C1—C6—C5	−179.5 (4)	C8—N1—C9—C10	−107.9 (5)
C2—C1—C6—C7	176.8 (4)	C1—N1—C9—C10	73.7 (6)
N1—C1—C6—C7	−1.3 (5)	N1—C9—C10—Br1	62.0 (5)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O1i	0.93	2.41	3.286 (6)	156
C10—H10A···O2ii	0.97	2.42	3.309 (6)	151