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Acta Crystallogr Sect E Struct Rep Online. 2010 July 1; 66(Pt 7): o1617.
Published online 2010 June 9. doi:  10.1107/S1600536810020969
PMCID: PMC3006937

(RS)-1-(1-Acetyl­indolin-5-yl)-2-chloro­propan-1-one

Abstract

The mol­ecule of the title compound, C13H14ClNO2, is roughly planar [maximum deviation = 0.060 (2) Å] with the disordered Cl/CH3 group asymetrically distributed on both sides of the mean plane. Indeed, the Cl and CH3 located on the stereogenic carbon exchange each other with occupancy factors in the ratio 0.60:0.40. The whole crystal is a racemate. Non-classical C—H(...)O hydrogen bonds and π–π inter­actions [centroid–centroid distance = 3.6959 (9) Å] between symmetry-related phenyl rings stabilize the crystal structure.

Related literature

The title compound was synthesised as an inter­mediate in a search for a new synthetic route for silodosin, an adrenoceptor antagonist, see: Asselin et al. (2000 [triangle]); Bremner et al. (2000 [triangle]); Elworthy et al. (1997 [triangle]); Sorbera et al. (2001 [triangle]). For related structures, see: Moreno et al. (1998 [triangle]); Wang et al. (2007 [triangle]).

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Object name is e-66-o1617-scheme1.jpg

Experimental

Crystal data

  • C13H14ClNO2
  • M r = 251.70
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1617-efi1.jpg
  • a = 8.4748 (5) Å
  • b = 9.0928 (5) Å
  • c = 9.4952 (5) Å
  • α = 112.071 (1)°
  • β = 110.345 (1)°
  • γ = 99.913 (1)°
  • V = 595.92 (6) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.31 mm−1
  • T = 173 K
  • 0.46 × 0.36 × 0.15 mm

Data collection

  • Bruker SMART 1000 CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008a [triangle]) T min = 0.871, T max = 0.955
  • 6682 measured reflections
  • 2594 independent reflections
  • 2242 reflections with I > 2σ(I)
  • R int = 0.018

Refinement

  • R[F 2 > 2σ(F 2)] = 0.043
  • wR(F 2) = 0.111
  • S = 1.18
  • 2594 reflections
  • 178 parameters
  • 3 restraints
  • H-atom parameters constrained
  • Δρmax = 0.27 e Å−3
  • Δρmin = −0.21 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT-Plus (Bruker, 2003 [triangle]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008b [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 [triangle]), ORTEP-3 for Windows (Farrugia, 1997 [triangle]) and PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810020969/dn2565sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810020969/dn2565Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The author thanks Mr Feng for helpful discussions.

supplementary crystallographic information

Comment

In searching for new synthetic route of silodosin, a adrenoceptor antagonist (Sorbera et al. 2001; Elworthy et al. 1997; Asselin et al. 2000; Bremner et al. 2000), we synthesized the racemic intermediate,(R/S)-1-(1-acetylindolin-5-yl)-2-chloropropan-1-one.

The single-crystal structure analysis shows that the Cl and CH3 located on the stereogenic carbon exchange each other with occupancy factor in the ration 60/40. Except for these disordered atoms, the molecule is roughly planar with the largest deviation from the mean plane (all heavy atoms except Cl and C13) being 0.060 (2)Å at C7 (Fig. 1). The two disordered atoms are dissymetrically distributed on both side of the mean plane. The geometry within the 1-acetylindoline fragment compares well with related structures as 1-acetylindoline (Moreno et al., 1998) or 1-(trifluoro)acetylindoline (Wang et al., 2007).

Non-classical C—H···O hydrogen bonds (Table 1, Fig. 2) link the molecules forming layers parallel to the (0 0 1) plane. These layers are further connected throught π-π interactions between symmetry related phenyl rings (Table 2).

Experimental

3.3 g aluminium trichloride was added to 20 ml dichloromethane, and stirred for 10 min. Then 2 g chloropropionylchloride was added, controling the temperature below 5¯C. A dichloromethane solution of 1-acetyl-indoline was added dropwise to the reaction solution, and stirred overnight to get 1.3 g crystalline solid (yield 72%). Crystals suitable for X-ray diffraction were obtained by slow evaporation of an ethyl acetate solution. Spectroscopic analysis: 1H NMR (CDCl3,δ, p.p.m.): 1.723–1.760(d, 3H), 2.259–2.269(s, 3H), 3.232–3.289(t, 2H), 4.109–4.166(t, 2H), 5.197–5.263(m, 1H), 7.864(s,1H), 7.864–7.895(d, 1H), 8.245–8.273(d, 1H).

Refinement

All H atoms attached to C atoms and N atom were fixed geometrically and treated as riding with C—H = 0.98 Å (methyl), 0.99 Å (methylene) and 1.0 Å (methine) with Uiso(H) = 1.2Ueq(Cmethine, Cmethylene) or Uiso(H) = 1.5Ueq(Cmethyl).

The Cl and CH3 substituents on the stereogenic carbon are exchanging each other and such disorder induces two configurations. Two sets of positions were defined for the atoms of this group and the site occupation factor of each conformation were refined while restraining their sum to unity and using restraints on C—C and C—Cl distances with the help of SAME and PART instructions within SHELXL97 (Sheldrick, 2008). In the last stage of refinement, the disordered Cl and C atoms were anisotropically refined but the anistropic thermal parameters of the C atoms were restrained to have similar atomic displacement parameters within a tolerance s.u. of 0.01 Å2.

Figures

Fig. 1.
The asymmetric unit of (I) with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii. For clarity, only the major component of the disorder is represented. ...
Fig. 2.
Packing view showing the layers formed by C—H···O interaction. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bondings have been omitted for clarity.

Crystal data

C13H14ClNO2Z = 2
Mr = 251.70F(000) = 264
Triclinic, P1Dx = 1.403 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.4748 (5) ÅCell parameters from 4108 reflections
b = 9.0928 (5) Åθ = 2.6–27.0°
c = 9.4952 (5) ŵ = 0.31 mm1
α = 112.071 (1)°T = 173 K
β = 110.345 (1)°Block, colorless
γ = 99.913 (1)°0.46 × 0.36 × 0.15 mm
V = 595.92 (6) Å3

Data collection

Bruker SMART 1000 CCD diffractometer2594 independent reflections
Radiation source: fine-focus sealed tube2242 reflections with I > 2σ(I)
graphiteRint = 0.018
ω scansθmax = 27.1°, θmin = 2.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a)h = −10→10
Tmin = 0.871, Tmax = 0.955k = −11→11
6682 measured reflectionsl = −12→12

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.111H-atom parameters constrained
S = 1.18w = 1/[σ2(Fo2) + (0.0322P)2 + 0.3925P] where P = (Fo2 + 2Fc2)/3
2594 reflections(Δ/σ)max = 0.001
178 parametersΔρmax = 0.27 e Å3
3 restraintsΔρmin = −0.20 e Å3

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 (Å2)

xyzUiso*/UeqOcc. (<1)
O10.9779 (2)−0.01243 (19)0.2587 (2)0.0410 (4)
O20.35372 (18)0.39091 (17)0.09272 (18)0.0348 (3)
N10.7298 (2)−0.10127 (19)0.28713 (19)0.0271 (3)
C10.6190 (3)−0.2154 (3)0.3214 (3)0.0394 (5)
H1A0.6802−0.19160.44150.047*
H1B0.5956−0.33540.24630.047*
C20.4441 (3)−0.1788 (2)0.2847 (3)0.0323 (4)
H2A0.3427−0.27650.18240.039*
H2B0.4166−0.15260.38270.039*
C30.4790 (2)−0.0270 (2)0.2553 (2)0.0252 (4)
C40.3712 (2)0.0667 (2)0.2265 (2)0.0253 (4)
H40.25940.04270.23000.030*
C50.4281 (2)0.1977 (2)0.1918 (2)0.0249 (4)
C60.5941 (2)0.2322 (2)0.1900 (2)0.0279 (4)
H60.63190.32080.16610.033*
C70.7055 (2)0.1416 (2)0.2219 (2)0.0292 (4)
H70.81880.16770.22170.035*
C80.6455 (2)0.0109 (2)0.2544 (2)0.0245 (4)
C90.8883 (2)−0.1095 (2)0.2860 (2)0.0296 (4)
C100.9462 (3)−0.2455 (3)0.3189 (3)0.0358 (4)
H10A0.8635−0.35680.22390.054*
H10B0.9452−0.23690.42460.054*
H10C1.0679−0.23130.32980.054*
C110.3175 (2)0.3004 (2)0.1525 (2)0.0264 (4)
C120.1597 (3)0.2956 (2)0.1952 (2)0.0306 (4)
H120.10250.17870.17400.037*
C130.0115 (16)0.3460 (17)0.0833 (16)0.058 (4)0.60
H13A−0.08260.34970.12060.087*0.60
H13B−0.04140.2617−0.03700.087*0.60
H13C0.06780.45760.09750.087*0.60
Cl10.2419 (3)0.4356 (3)0.40972 (18)0.0464 (6)0.60
C13B0.244 (2)0.4216 (19)0.4003 (16)0.072 (6)0.40
H13D0.33290.38510.46310.108*0.40
H13E0.14700.41730.43470.108*0.40
H13F0.30080.53790.42580.108*0.40
Cl1B0.0086 (5)0.3588 (5)0.0840 (4)0.0361 (9)0.40

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0371 (8)0.0425 (8)0.0621 (10)0.0207 (7)0.0328 (7)0.0302 (8)
O20.0361 (8)0.0331 (7)0.0443 (8)0.0126 (6)0.0193 (6)0.0256 (7)
N10.0263 (8)0.0247 (7)0.0326 (8)0.0101 (6)0.0141 (6)0.0145 (6)
C10.0302 (10)0.0397 (11)0.0618 (14)0.0153 (9)0.0227 (10)0.0337 (11)
C20.0300 (10)0.0315 (10)0.0448 (11)0.0132 (8)0.0193 (9)0.0236 (9)
C30.0254 (9)0.0245 (8)0.0262 (9)0.0074 (7)0.0123 (7)0.0123 (7)
C40.0241 (8)0.0263 (9)0.0282 (9)0.0089 (7)0.0139 (7)0.0134 (7)
C50.0261 (9)0.0228 (8)0.0234 (8)0.0082 (7)0.0106 (7)0.0092 (7)
C60.0298 (9)0.0242 (9)0.0324 (9)0.0073 (7)0.0160 (8)0.0150 (8)
C70.0269 (9)0.0290 (9)0.0350 (10)0.0095 (7)0.0174 (8)0.0152 (8)
C80.0247 (9)0.0234 (8)0.0240 (8)0.0091 (7)0.0112 (7)0.0094 (7)
C90.0280 (9)0.0282 (9)0.0300 (9)0.0120 (7)0.0137 (8)0.0097 (8)
C100.0338 (10)0.0345 (10)0.0415 (11)0.0183 (8)0.0179 (9)0.0168 (9)
C110.0277 (9)0.0208 (8)0.0253 (9)0.0056 (7)0.0091 (7)0.0094 (7)
C120.0346 (10)0.0273 (9)0.0390 (10)0.0151 (8)0.0197 (8)0.0195 (8)
C130.058 (7)0.049 (6)0.073 (7)0.007 (4)0.035 (5)0.034 (5)
Cl10.0466 (10)0.0642 (12)0.0263 (6)0.0269 (8)0.0168 (6)0.0158 (6)
C13B0.091 (12)0.052 (7)0.118 (12)0.036 (7)0.066 (9)0.060 (8)
Cl1B0.0366 (17)0.0457 (16)0.0344 (14)0.0273 (14)0.0139 (11)0.0231 (12)

Geometric parameters (Å, °)

O1—C91.225 (2)C7—C81.393 (3)
O2—C111.216 (2)C7—H70.9500
N1—C91.362 (2)C9—C101.504 (3)
N1—C81.408 (2)C10—H10A0.9800
N1—C11.482 (2)C10—H10B0.9800
C1—C21.525 (3)C10—H10C0.9800
C1—H1A0.9900C11—C121.525 (3)
C1—H1B0.9900C12—C131.598 (10)
C2—C31.509 (2)C12—C13B1.641 (13)
C2—H2A0.9900C12—Cl1B1.689 (3)
C2—H2B0.9900C12—Cl11.736 (3)
C3—C41.380 (2)C12—H120.9997
C3—C81.398 (2)C13—H13A0.9800
C4—C51.402 (2)C13—H13B0.9800
C4—H40.9500C13—H13C0.9800
C5—C61.395 (3)C13B—H13D0.9800
C5—C111.487 (2)C13B—H13E0.9800
C6—C71.385 (3)C13B—H13F0.9800
C6—H60.9500
C9—N1—C8126.44 (15)N1—C9—C10116.09 (17)
C9—N1—C1123.37 (15)C9—C10—H10A109.5
C8—N1—C1110.18 (14)C9—C10—H10B109.5
N1—C1—C2105.33 (15)H10A—C10—H10B109.5
N1—C1—H1A110.7C9—C10—H10C109.5
C2—C1—H1A110.7H10A—C10—H10C109.5
N1—C1—H1B110.7H10B—C10—H10C109.5
C2—C1—H1B110.7O2—C11—C5121.51 (17)
H1A—C1—H1B108.8O2—C11—C12119.99 (16)
C3—C2—C1104.15 (15)C5—C11—C12118.47 (15)
C3—C2—H2A110.9C11—C12—C13112.2 (5)
C1—C2—H2A110.9C11—C12—C13B106.7 (7)
C3—C2—H2B110.9C13—C12—C13B112.7 (8)
C1—C2—H2B110.9C11—C12—Cl1B112.0 (2)
H2A—C2—H2B108.9C13—C12—Cl1B2.8 (6)
C4—C3—C8120.43 (16)C13B—C12—Cl1B110.3 (6)
C4—C3—C2129.55 (16)C11—C12—Cl1108.14 (15)
C8—C3—C2109.99 (15)C13—C12—Cl1109.6 (5)
C3—C4—C5119.36 (16)C13B—C12—Cl13.1 (7)
C3—C4—H4120.3Cl1B—C12—Cl1107.28 (18)
C5—C4—H4120.3C11—C12—H12109.1
C6—C5—C4119.17 (16)C13—C12—H12108.7
C6—C5—C11117.85 (16)C13B—C12—H12107.3
C4—C5—C11122.97 (16)Cl1B—C12—H12111.2
C7—C6—C5122.22 (16)Cl1—C12—H12109.0
C7—C6—H6118.9C12—C13—H13A109.5
C5—C6—H6118.9C12—C13—H13B109.5
C6—C7—C8117.69 (17)C12—C13—H13C109.5
C6—C7—H7121.2C12—C13B—H13D109.5
C8—C7—H7121.2C12—C13B—H13E109.5
C7—C8—C3121.11 (16)H13D—C13B—H13E109.5
C7—C8—N1129.13 (16)C12—C13B—H13F109.5
C3—C8—N1109.75 (15)H13D—C13B—H13F109.5
O1—C9—N1121.97 (17)H13E—C13B—H13F109.5
O1—C9—C10121.94 (17)
C9—N1—C1—C2−172.04 (17)C9—N1—C8—C3175.76 (17)
C8—N1—C1—C27.0 (2)C1—N1—C8—C3−3.2 (2)
N1—C1—C2—C3−7.7 (2)C8—N1—C9—O11.8 (3)
C1—C2—C3—C4−175.90 (19)C1—N1—C9—O1−179.33 (19)
C1—C2—C3—C86.2 (2)C8—N1—C9—C10−177.82 (17)
C8—C3—C4—C51.6 (3)C1—N1—C9—C101.1 (3)
C2—C3—C4—C5−176.09 (18)C6—C5—C11—O212.3 (3)
C3—C4—C5—C6−1.0 (3)C4—C5—C11—O2−166.21 (17)
C3—C4—C5—C11177.50 (16)C6—C5—C11—C12−165.37 (16)
C4—C5—C6—C7−0.2 (3)C4—C5—C11—C1216.1 (3)
C11—C5—C6—C7−178.82 (17)O2—C11—C12—C1325.4 (6)
C5—C6—C7—C80.8 (3)C5—C11—C12—C13−156.9 (5)
C6—C7—C8—C3−0.2 (3)O2—C11—C12—C13B−98.5 (6)
C6—C7—C8—N1178.75 (17)C5—C11—C12—C13B79.3 (6)
C4—C3—C8—C7−1.0 (3)O2—C11—C12—Cl1B22.4 (3)
C2—C3—C8—C7177.12 (17)C5—C11—C12—Cl1B−159.9 (2)
C4—C3—C8—N1179.83 (16)O2—C11—C12—Cl1−95.6 (2)
C2—C3—C8—N1−2.0 (2)C5—C11—C12—Cl182.12 (19)
C9—N1—C8—C7−3.3 (3)C5—C11—C12—Cl182.12 (19)
C1—N1—C8—C7177.69 (19)C5—C11—C12—Cl1B−159.9 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C1—H1B···O2i0.992.443.252 (3)139
C4—H4···O1ii0.952.483.430 (2)177
C12—H12···O1ii1.002.413.318 (2)151

Symmetry codes: (i) x, y−1, z; (ii) x−1, y, z.

Table 2 π-π stacking between symmetry-related phenyl rings. [Symmetry code: (iii) 1-x, -y, -z]

Centroid–Centroid (Å)Centroid-to-plane (Å)Slippage (Å)
Cg1···Cg1iii3.6959 (9)3.4713 (6)1.269

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DN2565).

References

  • Asselin, A. A., Humber, L. G., Crocilla, D., Oshiro, G., Wojdan, A., Grimes, D., Heaslip, R. J., Rimele, T. J. & Shaw, C. C. (2000). J. Med. Chem.29, 1009–1015. [PubMed]
  • Bremner, J. B., Coban, B., Griffith, G., Groenewoud, K. M. & Yates, B. F. (2000). Bioorg. Med. Chem.8, 201–214. [PubMed]
  • Bruker (2001). SMART Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bruker (2003). SAINT-Plus Bruker AXS Inc., Madison, Wisconsin, USA.
  • Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.
  • Elworthy, T. R., Ford, A. P., Bantle, G. W. & Morgans, D. J. (1997). J. Med. Chem.40, 2674–2687. [PubMed]
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Moreno, M. M. T., Santos, R. H. A., Gambardella, M. T. P., Camargo, A. J., da Silva, A. B. F. & Trsic, M. (1998). Struct. Chem.9, 365–373.
  • Sheldrick, G. M. (2008a). SADABS. University of Göttingen, Germany.
  • Sheldrick, G. M. (2008b). Acta Cryst. A64, 112–122. [PubMed]
  • Sorbera, L. A., Caster, J. & Silvestre, J. S. (2001). Drugs Future, 26, 553–555.
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Wang, Z., Wan, W., Jiang, H. & Hao, J. (2007). J. Org. Chem.72, 9364–9367. [PubMed]

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