2-(3-Chloro­phen­yl)-3,4-di­hydro­benzo[f][1,4]oxazepin-5(2H)-one

Zhong, L.; Shi, J.; Zhong, L.; Wei, X.; Xhang, H.; Cheng, L.; Bai, L.

doi:10.1107/S2414314618005874

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 3| Part 4| April 2018| x180587

https://doi.org/10.1107/S2414314618005874

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2-(3-Chlorophenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

Ling Zhong,^a Jianyou Shi,^a Lei Zhong,^a Xin Wei,^a Hongjia Xhang,^a Liang Cheng ^b ^* and Lan Bai ^a ‡

^aSichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Hospital of the University of Electronic Science and Technology of China, Personalized Drug Therapy Key Laboratory of Sichuan Province, Chengdu, Sichuan Province 610072, People's Republic of China, and ^bDalian Lubricating Oil Research & Development Institute, PetroChina, Dalian 116032, People's Republic of China
^*Correspondence e-mail: chengliang_rhy@petrochina.com.cn

Edited by A. J. Lough, University of Toronto, Canada (Received 14 January 2018; accepted 16 April 2018; online 27 April 2018)

In the title compound, C₁₅H₁₂ClNO₂, the dihedral angle between the two benzene rings is 73.45 (11)°. The central seven-membered ring is in a psuedo-boat conformation. In the crystal, pairs of molecules are linked by N—H⋯O hydrogen bonds, forming inversion dimers.

Keywords: crystal structure; mannich reaction; tankyrase inhibitor; nanomolar activity.

CCDC reference: 1551778

Structure description

The development of benzo[f][1,4]oxazepinone derivatives for medical applications is a research topic of increasing interest because of their easy preparation, good stability and high nanomolar activity (Li et al., 2016 ). It is believed that the derivatives can be modified structurally by using different aldehydes and ketones (Krapcho & Turk, 1966 ). We report here the synthesis and the structure of the title compoun whose molecular structure is shown in Fig. 1. The dihedral angle between the two benzene rings (C2–C7 and C10–C15) is 73.45 (11)°. The central seven-membered ring is in a psuedo-boat conformation with C9 forming the prow and C2/C7 forming the stern. In the crystal, pairs of molecules are linked by N—H⋯O hydrogen bonds, forming inversion dimers (Table 1, Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	1.15 (2)	1.78 (2)	2.849 (2)	153.9 (16)
Symmetry code: (i) -x+1, -y+2, -z.

Figure 1
Molecular structure of the title compound with displacement ellipsoids drawn at 50% probability level.

Figure 2
An inversion dimer of the title compound. Hydrogen bonds are shown as dashed lines

Synthesis and crystallization

A 25 ml round-bottom flask was charged with 3-chlorobenzaldehyde (0.5 mmol), phenylamine (0.75 mmol), I₂ (0.15 mmol) and 1-(2-hydroxyphenyl)ethan-1-one (0.6 mmol) and methanol (10 mL) and stirred at 318 K. After the reaction was complete (as determined by TLC), the solvent was evaporated and 10 mL of saturated Na₂S₂O₃ was added. The solution was extracted with CH₂Cl₂ (three × 10 mL). The organic layers were washed with saturated NaCl solution and then with ice–water. The solution was dried over Na₂SO₄ and concentrated under vacuum to a crude solid. The crude solid (6 mmol) and NaN₃ (500 mg) were added to a round-bottom flask with 9 mL of CH₃COOH and stirred at 273 K. 3 mL of concentrated H₂SO₄ was then added and stirred at 318 K. After the reaction was complete (as determined by TLC), the solvent was neutralized with NaHCO₃. The solution was extracted with ethyl acetate. This was chromatographed on flash silica gel, eluting with 75% cyclohexane and 25% ethyl acetate and concentrated to a solid, giving 1.0 g of product (69% yield), m.p. 352.2–354.3 K. Crystals for X-ray crystallography were grown by slow evaporation of a solution of the title compound in methanol and water.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₅H₁₂ClNO₂
M_r	273.71
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	293
a, b, c (Å)	7.2162 (15), 8.0068 (14), 11.650 (3)
α, β, γ (°)	80.123 (17), 84.570 (18), 88.084 (15)
V (Å³)	660.0 (2)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.29
Crystal size (mm)	0.4 × 0.35 × 0.3

Data collection
Diffractometer	Agilent Xcalibur, Eos
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2014 )
T_min, T_max	0.896, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4864, 2678, 2002
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.118, 1.03
No. of reflections	2678
No. of parameters	176
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.32
Computer programs: CrysAlis PRO (Agilent, 2014), SHELXS97 (Sheldrick, 2008 ), SHELXL2014 (Sheldrick, 2015 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1551778

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314618005874/lh5867sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618005874/lh5867Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314618005874/lh5867Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314618005874/lh5867Isup4.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314618005874/lh5867Isup5.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

2-(3-Chlorophenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one top

Crystal data top

C₁₅H₁₂ClNO₂	Z = 2
M_r = 273.71	F(000) = 284
Triclinic, P1	D_x = 1.377 Mg m⁻³
a = 7.2162 (15) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.0068 (14) Å	Cell parameters from 1590 reflections
c = 11.650 (3) Å	θ = 3.5–27.6°
α = 80.123 (17)°	µ = 0.29 mm⁻¹
β = 84.570 (18)°	T = 293 K
γ = 88.084 (15)°	, colorless
V = 660.0 (2) Å³	0.4 × 0.35 × 0.3 mm

Data collection top

Agilent Xcalibur, Eos diffractometer	2678 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2002 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.016
Detector resolution: 16.0874 pixels mm^-1	θ_max = 26.4°, θ_min = 3.2°
ω scans	h = −9→8
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −7→9
T_min = 0.896, T_max = 1.000	l = −14→14
4864 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.118	w = 1/[σ²(F_o²) + (0.0452P)² + 0.2184P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
2678 reflections	Δρ_max = 0.29 e Å⁻³
176 parameters	Δρ_min = −0.32 e Å⁻³
0 restraints

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	1.11743 (9)	0.53184 (10)	0.26327 (7)	0.0761 (3)
O1	0.52072 (19)	0.63356 (16)	0.32657 (12)	0.0408 (4)
O2	0.3115 (2)	1.0113 (2)	0.10901 (13)	0.0595 (5)
N1	0.5962 (3)	0.8897 (2)	0.13595 (14)	0.0419 (4)
H1	0.668 (3)	0.905 (2)	0.0428 (18)	0.045 (6)*
C1	0.4288 (3)	0.9404 (3)	0.17520 (17)	0.0425 (5)
C2	0.3808 (3)	0.9133 (3)	0.30392 (17)	0.0390 (5)
C3	0.2785 (3)	1.0356 (3)	0.3555 (2)	0.0492 (5)
H3	0.2416	1.1353	0.3091	0.059*
C4	0.2312 (3)	1.0108 (3)	0.4745 (2)	0.0507 (6)
H4	0.1646	1.0942	0.5083	0.061*
C5	0.2823 (3)	0.8631 (3)	0.54278 (19)	0.0509 (6)
H5	0.2488	0.8460	0.6229	0.061*
C6	0.3830 (3)	0.7394 (3)	0.49404 (18)	0.0450 (5)
H6	0.4171	0.6392	0.5410	0.054*
C7	0.4330 (3)	0.7651 (2)	0.37516 (17)	0.0354 (4)
C8	0.7130 (3)	0.6560 (2)	0.28206 (16)	0.0362 (4)
H8	0.7901	0.6389	0.3481	0.043*
C9	0.7429 (3)	0.8348 (2)	0.21354 (17)	0.0406 (5)
H9A	0.7467	0.9132	0.2681	0.049*
H9B	0.8622	0.8383	0.1673	0.049*
C10	0.7614 (3)	0.5194 (2)	0.20902 (16)	0.0342 (4)
C11	0.9417 (3)	0.4563 (3)	0.19450 (18)	0.0426 (5)
C12	0.9891 (3)	0.3338 (3)	0.1260 (2)	0.0522 (6)
H12	1.1112	0.2935	0.1179	0.063*
C13	0.8542 (4)	0.2723 (3)	0.0700 (2)	0.0554 (6)
H13	0.8845	0.1900	0.0236	0.066*
C14	0.6739 (4)	0.3327 (3)	0.0825 (2)	0.0551 (6)
H14	0.5826	0.2910	0.0443	0.066*
C15	0.6279 (3)	0.4545 (3)	0.15140 (19)	0.0445 (5)
H15	0.5054	0.4939	0.1593	0.053*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0405 (4)	0.0984 (6)	0.0982 (6)	0.0052 (3)	−0.0205 (3)	−0.0348 (4)
O1	0.0441 (8)	0.0336 (7)	0.0422 (8)	0.0024 (6)	0.0056 (6)	−0.0054 (6)
O2	0.0676 (11)	0.0680 (11)	0.0408 (9)	0.0247 (9)	−0.0110 (8)	−0.0048 (8)
N1	0.0568 (11)	0.0367 (9)	0.0304 (9)	0.0036 (8)	−0.0024 (8)	−0.0020 (7)
C1	0.0573 (14)	0.0360 (11)	0.0341 (10)	0.0076 (10)	−0.0080 (10)	−0.0054 (9)
C2	0.0426 (11)	0.0397 (11)	0.0352 (10)	0.0050 (9)	−0.0057 (9)	−0.0074 (8)
C3	0.0537 (14)	0.0438 (12)	0.0508 (13)	0.0123 (10)	−0.0111 (11)	−0.0091 (10)
C4	0.0486 (13)	0.0533 (14)	0.0530 (13)	0.0093 (11)	−0.0001 (11)	−0.0210 (11)
C5	0.0540 (14)	0.0579 (14)	0.0405 (12)	−0.0033 (11)	0.0080 (11)	−0.0133 (11)
C6	0.0493 (13)	0.0441 (12)	0.0389 (11)	0.0008 (10)	0.0018 (10)	−0.0032 (9)
C7	0.0359 (10)	0.0341 (10)	0.0361 (10)	0.0024 (8)	−0.0018 (8)	−0.0073 (8)
C8	0.0395 (11)	0.0366 (11)	0.0325 (10)	0.0033 (8)	−0.0059 (8)	−0.0053 (8)
C9	0.0456 (12)	0.0367 (11)	0.0392 (11)	−0.0014 (9)	−0.0009 (9)	−0.0074 (9)
C10	0.0373 (10)	0.0315 (10)	0.0314 (9)	0.0024 (8)	−0.0015 (8)	0.0001 (8)
C11	0.0398 (11)	0.0429 (12)	0.0432 (11)	0.0030 (9)	−0.0029 (9)	−0.0034 (9)
C12	0.0510 (14)	0.0461 (13)	0.0550 (14)	0.0153 (11)	0.0076 (11)	−0.0053 (11)
C13	0.0765 (18)	0.0374 (12)	0.0513 (13)	0.0048 (12)	0.0069 (13)	−0.0130 (10)
C14	0.0655 (16)	0.0495 (14)	0.0549 (14)	−0.0079 (12)	−0.0089 (12)	−0.0188 (11)
C15	0.0414 (12)	0.0434 (12)	0.0506 (12)	0.0031 (9)	−0.0073 (10)	−0.0118 (10)

Geometric parameters (Å, º) top

Cl1—C11	1.739 (2)	C6—C7	1.380 (3)
O1—C7	1.386 (2)	C8—H8	0.9800
O1—C8	1.441 (2)	C8—C9	1.527 (3)
O2—C1	1.255 (3)	C8—C10	1.510 (3)
N1—H1	1.14 (2)	C9—H9A	0.9700
N1—C1	1.326 (3)	C9—H9B	0.9700
N1—C9	1.464 (3)	C10—C11	1.386 (3)
C1—C2	1.487 (3)	C10—C15	1.387 (3)
C2—C3	1.391 (3)	C11—C12	1.383 (3)
C2—C7	1.389 (3)	C12—H12	0.9300
C3—H3	0.9300	C12—C13	1.370 (3)
C3—C4	1.378 (3)	C13—H13	0.9300
C4—H4	0.9300	C13—C14	1.376 (3)
C4—C5	1.368 (3)	C14—H14	0.9300
C5—H5	0.9300	C14—C15	1.380 (3)
C5—C6	1.378 (3)	C15—H15	0.9300
C6—H6	0.9300

C7—O1—C8	117.07 (14)	C9—C8—H8	108.8
C1—N1—H1	130.6 (11)	C10—C8—H8	108.8
C1—N1—C9	122.40 (17)	C10—C8—C9	113.14 (15)
C9—N1—H1	105.8 (11)	N1—C9—C8	112.49 (16)
O2—C1—N1	123.09 (19)	N1—C9—H9A	109.1
O2—C1—C2	119.0 (2)	N1—C9—H9B	109.1
N1—C1—C2	117.87 (19)	C8—C9—H9A	109.1
C3—C2—C1	120.30 (19)	C8—C9—H9B	109.1
C7—C2—C1	121.27 (18)	H9A—C9—H9B	107.8
C7—C2—C3	118.42 (19)	C11—C10—C8	121.44 (18)
C2—C3—H3	119.6	C11—C10—C15	117.21 (18)
C4—C3—C2	120.8 (2)	C15—C10—C8	121.34 (18)
C4—C3—H3	119.6	C10—C11—Cl1	120.02 (16)
C3—C4—H4	120.1	C12—C11—Cl1	117.79 (18)
C5—C4—C3	119.8 (2)	C12—C11—C10	122.2 (2)
C5—C4—H4	120.1	C11—C12—H12	120.4
C4—C5—H5	119.7	C13—C12—C11	119.3 (2)
C4—C5—C6	120.7 (2)	C13—C12—H12	120.4
C6—C5—H5	119.7	C12—C13—H13	120.0
C5—C6—H6	120.2	C12—C13—C14	119.9 (2)
C5—C6—C7	119.6 (2)	C14—C13—H13	120.0
C7—C6—H6	120.2	C13—C14—H14	119.8
O1—C7—C2	120.41 (17)	C13—C14—C15	120.4 (2)
C6—C7—O1	118.60 (18)	C15—C14—H14	119.8
C6—C7—C2	120.71 (19)	C10—C15—H15	119.5
O1—C8—H8	108.8	C14—C15—C10	121.0 (2)
O1—C8—C9	110.50 (16)	C14—C15—H15	119.5
O1—C8—C10	106.64 (15)

Cl1—C11—C12—C13	−179.61 (17)	C7—O1—C8—C10	−166.47 (15)
O1—C8—C9—N1	−43.5 (2)	C7—C2—C3—C4	0.4 (3)
O1—C8—C10—C11	−152.15 (17)	C8—O1—C7—C2	74.4 (2)
O1—C8—C10—C15	29.4 (2)	C8—O1—C7—C6	−111.7 (2)
O2—C1—C2—C3	−38.0 (3)	C8—C10—C11—Cl1	1.2 (3)
O2—C1—C2—C7	140.7 (2)	C8—C10—C11—C12	−178.64 (19)
N1—C1—C2—C3	141.2 (2)	C8—C10—C15—C14	178.42 (19)
N1—C1—C2—C7	−40.1 (3)	C9—N1—C1—O2	168.99 (19)
C1—N1—C9—C8	76.9 (2)	C9—N1—C1—C2	−10.1 (3)
C1—C2—C3—C4	179.2 (2)	C9—C8—C10—C11	86.2 (2)
C1—C2—C7—O1	−4.4 (3)	C9—C8—C10—C15	−92.3 (2)
C1—C2—C7—C6	−178.2 (2)	C10—C8—C9—N1	76.0 (2)
C2—C3—C4—C5	−1.1 (4)	C10—C11—C12—C13	0.2 (3)
C3—C2—C7—O1	174.33 (18)	C11—C10—C15—C14	−0.1 (3)
C3—C2—C7—C6	0.6 (3)	C11—C12—C13—C14	−0.1 (3)
C3—C4—C5—C6	0.8 (4)	C12—C13—C14—C15	−0.2 (4)
C4—C5—C6—C7	0.1 (3)	C13—C14—C15—C10	0.2 (3)
C5—C6—C7—O1	−174.72 (19)	C15—C10—C11—Cl1	179.69 (15)
C5—C6—C7—C2	−0.8 (3)	C15—C10—C11—C12	−0.1 (3)
C7—O1—C8—C9	−43.1 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	1.15 (2)	1.78 (2)	2.849 (2)	153.9 (16)

Symmetry code: (i) −x+1, −y+2, −z.

Footnotes

‡Additional correspondance author: e-mail:blci@163.com. Lan Bai, Ling Zhong and Jianyou Shi contributed equally to this paper.

Funding information

Funding for this research was provided by: Construction of key specialty of national clinical pharmacy (award No. 30305030698); New type of antitumor drug molecular design and research based Triptolide as lead compound targeted TFIIH protein subunit XPB (award No. 2016QN08).

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