5′-Chloro­spiro­[1,3-dioxolane-2,3′-indolin]-2′-one: a potential anti­convulsant

The title compound, C₁₀H₈ClNO₃, is a significant anti­convulsant agent. The indolinone system is essentially planar, the dihedral angle between the rings being 2.24 (8)°. The dioxolane ring adopts an envelope conformation; the dihedral angle between the plane through its four coplanar atoms and the indolinone system is 89.8 (1)°. The crystal structure is stabilized by a three-dimensional network of inter­molecular N—H...O hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.050
• wR factor = 0.190
• Data-to-parameter ratio = 14.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT128_ALERT_4_C Non-standard setting of Space-group C2/c    ....      I2/c
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C10

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Anti-epileptic drugs have diverse chemical structures and complex physiological and pharmacological actions. The search for potential drugs and their mechanism of action has been difficult because of their complexity. A series of spiro(1,3-dioxane-2,3'-indolin)-2'-one and structural analogues active against electrically and chemically induced seizures have been studied. These compounds contain both an oxoindole and a dioxolane moiety which have independently been seen in other anticonvulsants (Popp, 1977, 1984). The basic model compound, mentioned above, was used to study the effects of various electron-donating, electron withdrawing and hydrophobic groups on the activity of the molecule. A bulky hydrophobic substituent at the 1'-position (oxoindole) generally tends to decrease the activity. The present compound, a chloro analogue was found to be most potent in the MES test. Since no common target site has yet been established, X-ray analysis was undertaken to search structural information which may help in the understanding of the mechanism of action at the molecular level.

The conformation of the title compound along with the atom-numbering scheme is shown in Fig 1. The carbonyl C atom to tetrahedral C atom distance is typical of a single bond. The C(2) - C(3) bond distance is slightly shorter but closely similar to the values found in other indoline nuclie (Itai et al., 1978; Chakraborty & Talapatra, 1985; Chakraborty et al., 1985; De & Kitagawa, 1991a,b; De, 1992). The lone pair of electrons on N(1) is involved in conjugation with the carbonyl group. This is also indicated by the slight lengthening of the C=O double bond [1.220 (4) Å] and the concomitant shortening of the two N - C(sp²) single bonds [1.341 (4) Å and 1.412 (4) Å] (Codding et al., 1984). The least-squares planes through the five- and six-membered rings are inclined to one another at 2.24 (8)° and each of them are almost planar. The plane containing the atoms C(2), O(2), O(3), C(9) and C(10) is inclined to the overall plane through the indolinone group by 89.8 (1)°. The C—NH—CO—C grouping resembles a cis peptide bond. Six atoms of this group [C(8), N(1), H1,C(1),O(1),C(2)] are almost planar. The OC—N bond distance [1.341 (4) Å] is not as short as the normal peptide bond(1.325 Å) (Dickerson & Geis,1969). The packing of the molecule is shown in Fig. 2. The amide nitrogen, N(1), forms a hydrogen bond with the carbonyl oxygen O(1) [N(1) - H1] = 0.82 (3), N(1)···O(1) = 2.885 (4), H1···O(1) = 2.11 (3) Å, N(1) –H1···O(1) = 157.4 (3) °]. The molecules are thus held together by a three-dimensional network of hydrogen bonds.

Related literature

For related literature, see: Codding et al. (1984); De (1990, 1992); De & Kitagawa (1991a,b); De & Kusunoki (1991); Dickerson & Geis (1969); Itai et al. (1978); James & Williams (1972); Popp (1977, 1984); Rajopadhye & Popp (1988); Chakraborty & Talapatra (1985); Chakraborty et al. (1985).

S2. Experimental

The synthesis of the compound has been described earlier (Rajopadhye & Popp, 1988). Diffraction quality crystals were obtained by slow evaporation of an ethanol solution at room temperature.

S3. Refinement

All the hydrogen atoms in the structure were located in a difference map except the two H-atoms on C10. They were placed at geometrically idealized positions. Geometric calculations were performed using SHELXL-97, PARST (Nardelli, 1983) programs.

Computing details

Data collection: AFC-4 Diffractometer Control Software (Rigaku, 1997); cell refinement: AFC-4 Diffractometer Control Software (Rigaku, 1997); data reduction: AFC-4 Diffractometer Control Software (Rigaku, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP (Johnson, 1965); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PARST (Nardelli, 1983).

Figures

	Fig. 1. ORTEP (Johnson, 1965) diagram of the Molecular structure with atom labels showing displacement ellipsoids at 50% probablity.
	Fig. 2. Packing of the molecule viewed down the b axis.

5'-Chlorospiro[1,3-dioxolane-2,3'-indolin]-2'-one

Crystal data

C10H8ClNO3	F(000) = 928
Mr = 225.62	Dx = 1.506 Mg m^−3 Dm = 1.498 Mg m^−3 Dm measured by flotation
Monoclinic, I2/c	Melting point: 460 K
Hall symbol: -I 2yc	Mo Kα radiation, λ = 0.71073 Å
a = 18.266 (2) Å	Cell parameters from 25 reflections
b = 7.360 (1) Å	θ = 2.2–27.5°
c = 14.821 (1) Å	µ = 0.37 mm^−1
β = 92.855 (7)°	T = 298 K
V = 1990.0 (4) Å^3	Needle, colourless
Z = 8	0.50 × 0.30 × 0.30 mm

Data collection

Rigaku AFC-4 diffractometer	Rint = 0.042
Radiation source: fine-focus sealed tube	θmax = 27.5°, θmin = 2.2°
Graphite monochromator	h = −23→23
ω scans	k = 0→9
2479 measured reflections	l = 0→19
2297 independent reflections	3 standard reflections every 100 reflections
1591 reflections with I > 2σ(I)	intensity decay: 0.2%

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.189	H atoms treated by a mixture of independent and constrained refinement
S = 0.83	w = 1/[σ^2(Fo^2) + (0.1365P)^2 + 2.6179P] where P = (Fo^2 + 2Fc^2)/3
2297 reflections	(Δ/σ)max = 0.006
160 parameters	Δρmax = 0.34 e Å^−3
0 restraints	Δρmin = −0.52 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 on F² for ALL reflections except for 0 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating _R_factor_obs 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
Cl1	0.40898 (6)	−0.00775 (11)	0.43060 (5)	0.0825 (4)
O1	0.3184 (2)	0.5049 (4)	0.0001 (2)	0.0931 (9)
O2	0.37608 (10)	0.5934 (2)	0.18885 (12)	0.0534 (5)
O3	0.45532 (9)	0.4244 (2)	0.11210 (12)	0.0494 (4)
N1	0.28723 (12)	0.2542 (4)	0.0815 (2)	0.0612 (6)
C1	0.3263 (2)	0.4038 (4)	0.0651 (2)	0.0596 (7)
C2	0.38452 (12)	0.4261 (3)	0.1450 (2)	0.0442 (5)
C3	0.36853 (11)	0.2671 (3)	0.20354 (15)	0.0418 (5)
C4	0.40017 (12)	0.2147 (3)	0.2858 (2)	0.0446 (5)
C5	0.3712 (2)	0.0628 (3)	0.3264 (2)	0.0516 (6)
C6	0.3125 (2)	−0.0317 (4)	0.2873 (2)	0.0634 (8)
C7	0.2809 (2)	0.0217 (4)	0.2041 (2)	0.0606 (7)
C8	0.31030 (12)	0.1704 (3)	0.1639 (2)	0.0484 (5)
C9	0.4219 (2)	0.7216 (4)	0.1450 (2)	0.0678 (8)
C10	0.4787 (2)	0.6085 (4)	0.1035 (3)	0.0759 (9)
H4	0.4389 (16)	0.275 (4)	0.3142 (18)	0.051 (7)*
H6	0.2955 (19)	−0.126 (5)	0.316 (2)	0.069 (9)*
H7	0.234 (2)	−0.037 (5)	0.181 (2)	0.077 (10)*
H1	0.2565 (18)	0.206 (5)	0.047 (2)	0.062 (9)*
H91	0.393 (2)	0.792 (6)	0.102 (3)	0.110 (14)*
H92	0.441 (2)	0.808 (7)	0.189 (3)	0.086 (11)*
H101	0.5260	0.6263	0.1351	0.08*
H102	0.4822	0.6401	0.0403	0.08*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.1293 (9)	0.0619 (5)	0.0567 (5)	0.0119 (4)	0.0092 (5)	0.0165 (3)
O1	0.099 (2)	0.100 (2)	0.077 (2)	0.0173 (14)	−0.0313 (13)	0.0273 (14)
O2	0.0595 (10)	0.0389 (9)	0.0630 (10)	0.0018 (7)	0.0167 (8)	−0.0016 (7)
O3	0.0459 (8)	0.0434 (9)	0.0594 (10)	0.0071 (7)	0.0089 (7)	0.0065 (7)
N1	0.0475 (11)	0.0723 (15)	0.0617 (13)	0.0053 (11)	−0.0181 (10)	−0.0182 (12)
C1	0.0552 (13)	0.065 (2)	0.0573 (14)	0.0149 (12)	−0.0140 (11)	0.0000 (12)
C2	0.0427 (10)	0.0426 (11)	0.0467 (11)	0.0043 (8)	−0.0024 (8)	0.0014 (9)
C3	0.0367 (9)	0.0384 (10)	0.0500 (11)	0.0013 (8)	−0.0004 (8)	−0.0026 (9)
C4	0.0426 (11)	0.0400 (11)	0.0509 (12)	−0.0019 (9)	−0.0016 (9)	−0.0015 (9)
C5	0.0677 (14)	0.0371 (11)	0.0514 (12)	0.0043 (10)	0.0157 (11)	0.0016 (9)
C6	0.077 (2)	0.0349 (11)	0.081 (2)	−0.0119 (12)	0.031 (2)	−0.0082 (12)
C7	0.0508 (13)	0.0505 (14)	0.081 (2)	−0.0119 (11)	0.0094 (12)	−0.0206 (13)
C8	0.0393 (10)	0.0447 (11)	0.0608 (13)	0.0020 (9)	0.0001 (9)	−0.0156 (10)
C9	0.083 (2)	0.0459 (14)	0.076 (2)	−0.0025 (13)	0.022 (2)	0.0066 (14)
C10	0.086 (2)	0.051 (2)	0.095 (2)	−0.0020 (15)	0.041 (2)	0.005 (2)

Geometric parameters (Å, º)

Cl1—C5	1.740 (3)	C4—C5	1.386 (3)
O1—C1	1.220 (4)	C4—H4	0.92 (3)
O2—C2	1.404 (3)	C5—C6	1.381 (4)
O2—C9	1.438 (3)	C6—C7	1.392 (5)
O3—C2	1.405 (3)	C6—H6	0.88 (4)
O3—C10	1.429 (4)	C7—C8	1.369 (4)
N1—C1	1.341 (4)	C7—H7	1.01 (4)
N1—C8	1.412 (4)	C9—C10	1.487 (4)
N1—H1	0.82 (3)	C9—H91	0.96 (4)
C1—C2	1.560 (3)	C9—H92	0.96 (4)
C2—C3	1.494 (3)	C10—H101	0.97
C3—C4	1.378 (3)	C10—H102	0.97
C3—C8	1.386 (3)
C2—O2—C9	106.6 (2)	C4—C5—Cl1	118.8 (2)
C2—O3—C10	107.9 (2)	C5—C6—C7	120.6 (2)
C1—N1—C8	112.1 (2)	C5—C6—H6	119 (2)
C1—N1—H1	127 (2)	C7—C6—H6	121 (2)
C8—N1—H1	121 (2)	C8—C7—C6	117.2 (2)
O1—C1—N1	127.0 (3)	C8—C7—H7	123 (2)
O1—C1—C2	125.8 (3)	C6—C7—H7	119 (2)
N1—C1—C2	107.3 (2)	C7—C8—C3	122.4 (2)
O3—C2—O2	107.0 (2)	C7—C8—N1	128.2 (2)
O3—C2—C3	113.9 (2)	C3—C8—N1	109.4 (2)
O2—C2—C3	112.9 (2)	O2—C9—C10	104.7 (2)
O3—C2—C1	109.8 (2)	O2—C9—H91	110 (3)
O2—C2—C1	110.9 (2)	C10—C9—H91	114 (3)
C3—C2—C1	102.3 (2)	O2—C9—H92	109 (2)
C4—C3—C8	120.7 (2)	C10—C9—H92	115 (2)
C4—C3—C2	130.3 (2)	H91—C9—H92	105 (4)
C8—C3—C2	108.9 (2)	O3—C10—C9	106.0 (2)
C3—C4—C5	117.2 (2)	O3—C10—H101	110.3
C3—C4—H4	123.2 (17)	C9—C10—H101	111.0
C5—C4—H4	119.6 (17)	O3—C10—H102	110.3
C6—C5—C4	122.0 (3)	C9—C10—H102	110.3
C6—C5—Cl1	119.2 (2)	H101—C10—H102	110.0
C9—O2—C2—O3	28.9 (2)	O2—C2—C3—C8	118.8 (2)
C9—O2—C2—C1	−90.9 (2)	O3—C2—C3—C4	63.6 (3)
C9—O2—C2—C3	155.0 (2)	O3—C2—C3—C8	−118.9 (2)
C2—O2—C9—C10	−23.5 (3)	C1—C2—C3—C4	−177.9 (2)
C10—O3—C2—O2	−22.6 (3)	C1—C2—C3—C8	−0.4 (2)
C10—O3—C2—C1	97.9 (2)	C2—C3—C4—C5	177.2 (2)
C10—O3—C2—C3	−148.1 (2)	C2—C3—C8—N1	0.9 (3)
C2—O3—C10—C9	7.5 (3)	C2—C3—C8—C7	−176.9 (2)
C8—N1—C1—O1	−179.1 (3)	C4—C3—C8—N1	178.7 (2)
C8—N1—C1—C2	0.8 (3)	C4—C3—C8—C7	0.9 (4)
C1—N1—C8—C3	−1.1 (3)	C3—C4—C5—Cl1	−179.6 (2)
C1—N1—C8—C7	176.6 (3)	C3—C4—C5—C6	−0.9 (4)
O1—C1—C2—O2	59.0 (4)	Cl1—C5—C6—C7	179.8 (2)
O1—C1—C2—O3	−59.1 (4)	C4—C5—C6—C7	1.0 (4)
O1—C1—C2—C3	179.7 (3)	C5—C6—C7—C8	−0.2 (4)
N1—C1—C2—O2	−120.9 (2)	C6—C7—C8—N1	−178.1 (3)
N1—C1—C2—O3	121.0 (2)	C6—C7—C8—C3	−0.7 (4)
N1—C1—C2—C3	−0.2 (3)	O2—C9—C10—O3	9.7 (3)
O2—C2—C3—C4	−58.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.82 (3)	2.11 (3)	2.885 (4)	157.4 (3)

Symmetry code: (i) −x+1/2, y−1/2, −z.