4-Methyl-1H-1,5-benzodiazepin-2(3H)-one

Dioukhane, K.; Aouine, Y.; Faraj, H.; Alami, A.; Essassi, E.M.; Zouihri, H.

doi:10.1107/S2414314618017182

organic compounds

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ISSN: 2414-3146

Volume 3| Part 12| December 2018| x181718

https://doi.org/10.1107/S2414314618017182

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4-Methyl-1H-1,5-benzodiazepin-2(3H)-one

Khadim Dioukhane,^a Younas Aouine,^b Hassane Faraj,^b Anouar Alami,^b ^* El Mokhtar Essassi ^c and Hafid Zouihri ^d

^aFormation Doctorale Molécules Bioactives, Santé et Biotechnologies, Centre d'études Doctorales Sciences et Technologies LCO, and Faculté des Sciences Dhar El Marhaz, Fès, Morocco, ^bLaboratoire de Chimie Organique, Faculté des Sciences Dhar el Mahraz, Université Sidi Mohammed Ben Abdellah, Fès, Morocco, ^cLaboratoire de Chimie Organique Hétérocyclique, Faculté des Sciences, Mohammed V University in Rabat, Rabat, Morocco, and ^dLaboratoire de Chimie des Matériaux et Biotechnologie des Produits Naturels, E.Ma.Me.P.S, Université Moulay Ismail, Faculté des Sciences, Meknès, Morocco
^*Correspondence e-mail: anouar.alami@usmba.ac.ma

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 30 November 2018; accepted 3 December 2018; online 14 December 2018)

In the title compound, C₁₀H₁₀N₂O, the seven-membered heterocycle displays a half-chair conformation. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds link the molecules into chains propagating along the a-axis direction.

Keywords: crystal structure; benzodiazepines; hydrogen bonds.

CCDC reference: 1882884

Structure description

Benzodiazepines are a class of drugs that act on the GABA-A receptor as an allosteric modulator and increase the frequency of opening of its chloride channel (Twyman et al. 1989 ). The biological effects of these drugs include hypnotic, anticonvulsant and muscle relaxant properties (De Sarro et al. 1995 ). As part of our studies in this area, we now describe the synthesis and structure of the title compound.

The molecule of the title compound (Fig. 1) is built up from fused six- and seven-membered rings. The seven-membered ring displays a half-chair conformation as indicated by the puckering amplitude Q_T = 0.8734 (16) Å and spherical polar angle φ₂ = 205.48 (11)° and φ₃ = 310.2 (4)°. In the crystal, the molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds (Table 1), generating [100] chains as shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O1ⁱ	0.92 (2)	1.94 (2)	2.8481 (17)	169 (2)
C8—H8A⋯O1ⁱⁱ	0.97	2.57	3.480 (2)	156
Symmetry codes: (i) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]$ ; (ii) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]$ .

Figure 1
Molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.

Figure 2
Structure of the title compound, showing molecules linked through N—H⋯O and C—H⋯O hydrogen bonds (dashed lines).

Synthesis and crystallization

Ethyl acetoacetate (0.011 mmol) was added to a stirred solution of benzene-1,2-diamine (0.01 mmol) in 100 ml of xylene. The mixture was stirred at reflux for 1 h. The resulting precipitate was filtered, washed with ethanol, then dried giving a white powder. Colourless prisms of the title compound were obtained by recrystallization from diethyl ether solution.

Yield = 90% (white solid); m.p. = 176–178°C. ¹H NMR (300.13 MHz; CDCl₃): 2.40 (3H, –CH₃, s); 3.15 (2H, –CH₂–, s); 7.08–7.37 (4H_arom, m); 9.32 (1H, –NH, s). ¹³C NMR (75.47 MHz; CDCl₃): 28.01 (–CH₃); 43.57 (–CH₂–); 121.88–139.62 (6C_arom); 162.89 (CN); 167.36 (CO). MS–EI: [M + 1]⁺ = 175.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₁₀N₂O
M_r	174.20
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	296
a, b, c (Å)	7.5676 (2), 10.7802 (2), 11.4092 (3)
V (Å³)	930.77 (4)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.08
Crystal size (mm)	0.32 × 0.28 × 0.20

Data collection
Diffractometer	Bruker X8 APEXII CCD area-detector
No. of measured, independent and observed [I > 2σ(I)] reflections	25369, 1825, 1747
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.028, 0.086, 1.03
No. of reflections	1825
No. of parameters	123
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.14, −0.15
Absolute structure	Flack x determined using 705 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.3 (2)
Computer programs: APEX2 aand SAINT (Bruker, 2009 ), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), PLATON (Spek, 2009 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1882884

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314618017182/hb4272sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618017182/hb4272Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314618017182/hb4272Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

4-Methyl-1H-1,5-benzodiazepin-2(3H)-one top

Crystal data top

C₁₀H₁₀N₂O	D_x = 1.243 Mg m⁻³
M_r = 174.20	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 245 reflections
a = 7.5676 (2) Å	θ = 0.5–32°
b = 10.7802 (2) Å	µ = 0.08 mm⁻¹
c = 11.4092 (3) Å	T = 296 K
V = 930.77 (4) Å³	Prism, colourless
Z = 4	0.32 × 0.28 × 0.20 mm
F(000) = 368

Data collection top

Bruker X8 APEXII CCD area-detector diffractometer	1747 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.018
Graphite monochromator	θ_max = 26.0°, θ_min = 3.6°
ω and φ scans	h = −9→9
25369 measured reflections	k = −13→13
1825 independent reflections	l = −13→14

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.028	w = 1/[σ²(F_o²) + (0.0631P)² + 0.0577P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.086	(Δ/σ)_max < 0.001
S = 1.03	Δρ_max = 0.14 e Å⁻³
1825 reflections	Δρ_min = −0.15 e Å⁻³
123 parameters	Absolute structure: Flack x determined using 705 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: −0.3 (2)
Primary atom site location: dual

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.

Refinement. The H atoms were located in a difference map and treated as riding with C—H = 0.93–0.97 Å and N—H = 0.86 Å, and with U_iso(H) = 1.2–1.5Ueq(C, N).

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

	x	y	z	U_iso*/U_eq
C1	0.0092 (2)	0.51751 (13)	0.91727 (13)	0.0373 (3)
C9	0.2131 (2)	0.35141 (15)	0.97843 (13)	0.0379 (3)
C6	0.1120 (2)	0.58213 (14)	0.83489 (13)	0.0410 (4)
C8	0.3621 (2)	0.44253 (15)	0.96221 (14)	0.0402 (3)
H8A	0.4723	0.4076	0.9906	0.048*
H8B	0.3383	0.5185	1.0049	0.048*
C2	−0.1472 (2)	0.56990 (16)	0.95911 (15)	0.0466 (4)
H2	−0.2167	0.5258	1.0119	0.056*
C5	0.0527 (3)	0.69915 (16)	0.79881 (16)	0.0550 (5)
H5	0.1177	0.7428	0.7433	0.066*
C7	0.3736 (2)	0.46818 (16)	0.83226 (14)	0.0439 (4)
C3	−0.2001 (3)	0.68650 (18)	0.92309 (17)	0.0601 (5)
H3	−0.3034	0.7213	0.9524	0.072*
C4	−0.0983 (3)	0.75106 (17)	0.84313 (19)	0.0641 (6)
H4	−0.1325	0.8300	0.8193	0.077*
C10	0.5213 (3)	0.4081 (3)	0.76664 (19)	0.0667 (6)
H10A	0.5044	0.4201	0.6840	0.100*
H10B	0.5230	0.3209	0.7837	0.100*
H10C	0.6316	0.4445	0.7900	0.100*
N1	0.05078 (16)	0.39599 (12)	0.95461 (12)	0.0394 (3)
N2	0.26065 (19)	0.53402 (13)	0.77731 (12)	0.0459 (3)
O1	0.23581 (16)	0.24292 (11)	1.00743 (13)	0.0519 (3)
H1N	−0.042 (3)	0.3435 (19)	0.9707 (19)	0.057 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0376 (7)	0.0352 (7)	0.0392 (7)	0.0012 (6)	−0.0087 (6)	0.0009 (6)
C9	0.0332 (7)	0.0387 (8)	0.0419 (7)	0.0000 (6)	−0.0015 (6)	0.0047 (6)
C6	0.0467 (8)	0.0381 (7)	0.0382 (7)	−0.0027 (7)	−0.0076 (6)	0.0028 (6)
C8	0.0325 (7)	0.0438 (8)	0.0443 (8)	−0.0043 (6)	−0.0057 (6)	0.0036 (6)
C2	0.0424 (8)	0.0501 (9)	0.0473 (8)	0.0056 (7)	−0.0035 (7)	0.0015 (7)
C5	0.0670 (12)	0.0448 (9)	0.0531 (10)	−0.0003 (9)	−0.0084 (9)	0.0125 (8)
C7	0.0378 (8)	0.0483 (8)	0.0454 (8)	−0.0078 (7)	0.0004 (6)	0.0011 (7)
C3	0.0616 (11)	0.0585 (11)	0.0601 (10)	0.0239 (9)	−0.0067 (9)	−0.0046 (9)
C4	0.0828 (14)	0.0448 (9)	0.0648 (12)	0.0172 (10)	−0.0152 (11)	0.0076 (9)
C10	0.0471 (10)	0.0954 (16)	0.0576 (11)	0.0069 (11)	0.0063 (8)	−0.0033 (11)
N1	0.0317 (6)	0.0351 (6)	0.0514 (7)	−0.0029 (5)	−0.0022 (5)	0.0078 (5)
N2	0.0466 (7)	0.0498 (8)	0.0413 (6)	−0.0051 (7)	−0.0003 (6)	0.0054 (6)
O1	0.0383 (6)	0.0411 (6)	0.0764 (8)	0.0023 (5)	−0.0022 (6)	0.0167 (5)

Geometric parameters (Å, º) top

C1—C2	1.395 (2)	C2—H2	0.9300
C1—C6	1.405 (2)	C5—C4	1.370 (3)
C1—N1	1.4131 (19)	C5—H5	0.9300
C9—O1	1.2275 (19)	C7—N2	1.276 (2)
C9—N1	1.347 (2)	C7—C10	1.493 (3)
C9—C8	1.507 (2)	C3—C4	1.382 (3)
C6—C5	1.401 (2)	C3—H3	0.9300
C6—N2	1.402 (2)	C4—H4	0.9300
C8—C7	1.511 (2)	C10—H10A	0.9600
C8—H8A	0.9700	C10—H10B	0.9600
C8—H8B	0.9700	C10—H10C	0.9600
C2—C3	1.382 (2)	N1—H1N	0.918 (18)

C2—C1—C6	119.86 (14)	C6—C5—H5	119.1
C2—C1—N1	117.45 (14)	N2—C7—C10	119.78 (16)
C6—C1—N1	122.54 (14)	N2—C7—C8	123.06 (15)
O1—C9—N1	121.47 (14)	C10—C7—C8	117.11 (16)
O1—C9—C8	123.32 (14)	C4—C3—C2	119.55 (18)
N1—C9—C8	115.16 (13)	C4—C3—H3	120.2
C5—C6—N2	116.89 (15)	C2—C3—H3	120.2
C5—C6—C1	117.76 (16)	C5—C4—C3	120.20 (17)
N2—C6—C1	125.06 (14)	C5—C4—H4	119.9
C9—C8—C7	106.43 (13)	C3—C4—H4	119.9
C9—C8—H8A	110.4	C7—C10—H10A	109.5
C7—C8—H8A	110.4	C7—C10—H10B	109.5
C9—C8—H8B	110.4	H10A—C10—H10B	109.5
C7—C8—H8B	110.4	C7—C10—H10C	109.5
H8A—C8—H8B	108.6	H10A—C10—H10C	109.5
C3—C2—C1	120.80 (17)	H10B—C10—H10C	109.5
C3—C2—H2	119.6	C9—N1—C1	126.51 (13)
C1—C2—H2	119.6	C9—N1—H1N	115.8 (14)
C4—C5—C6	121.79 (18)	C1—N1—H1N	117.5 (14)
C4—C5—H5	119.1	C7—N2—C6	120.87 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1ⁱ	0.92 (2)	1.94 (2)	2.8481 (17)	169 (2)
C8—H8A···O1ⁱⁱ	0.97	2.57	3.480 (2)	156

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

References

Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
De Sarro, G., Chimirri, A., De Sarro, A., Gitto, R., Grasso, S. & Zappalà, M. (1995). Eur. J. Med. Chem. 30, 925–929. CrossRef Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Twyman, R. E., Rogers, C. J. & Macdonald, R. L. (1989). Ann. Neurol. 25, 213–220. CrossRef Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

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IUCrDATA

ISSN: 2414-3146

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4-Methyl-1H-1,5-benzodiazepin-2(3H)-one

Structure description

Synthesis and crystallization

Refinement

Structural data

References

organic compounds