organic compounds
4-(2-Oxopropyl)-1,3-bis(prop-2-yn-1-yl)-2,3,4,5-tetrahydro-1,5-benzodiazepin-2(1H)-one
aLaboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Mohammed V University, Rabat, Morocco, and bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: sebhaoui.jihad@gmail.com
In the title molecule, C18H16N2O2, the seven-membered diazepinone ring adopts a boat conformation. An intramolecular N—H⋯O hydrogen bond encloses an S(6) ring. The two propynyl substituents each point away from the same face of the benzodiazepinone ring system. In the crystal, C—H⋯O hydrogen bonds form double chains of molecules along the c-axis direction.
Keywords: crystal structure; benzodiazepine; alkyne; hydrogen bonds.
CCDC reference: 1486935
Structure description
Benzodiazepine derivatives have been the object of intense investigation in medicinal chemistry because of their remarkable ability to depress activity in the central nervous system and are now one of the most widely prescribed class of psychotropic drugs (Zellou et al., 1998, 1999; Rudolph et al., 1999). The area of biological interest of 1,5-benzodiazepine derivatives has been extended to include antibiotics (Knabe et al., 1995) and the treatment of various diseases such as cancer (Atwal et al., 1987), viral infection (HIV) (Di Braccio et al., 2001) and cardiovascular disorders (Claremon et al., 1998
The conformation of the title molecule is partially determined by an intramolecular N2—H2A⋯O2 hydrogen bond (Table 1 and Fig. 1). The heterocyclic ring adopts a boat conformation with puckering parameters Q(2) = 0.899 (1) Å, φ(2) = 206.26 (8)°, Q(3) = 0.261 (1) Å and φ(3) = 303.1 (3)°. The two propynyl substituents, C14—C15—H15 and C17—C18—H18 each point away from the same face of the benzodiazepinone ring system and one of these is involved in C18—H18⋯O2i hydrogen bonds that form C(10) chains along c. Additional weaker C12—H12A⋯O1ii contacts form inversion dimers, enclosing R22(16) rings, and these link adjacent chains to produce a double chain propagating along c, Fig. 2.
Synthesis and crystallization
To a solution of (4E)-2-oxopropylidene-1,5-benzodiazepin-2-one (0.01 mol, 2.16 g) in N,N-dimethylformamid (60 ml), was added K2CO3 (0.02 mol, 2.76 g), propargyl bromide (0.02 mol, 5,84 g) and tetra n-butylammonium bromide (0.001 mol, 0.321 g). The reaction mixture was stirred at room temperature for 48 h. The solution was filtered and the solvent was removed under reduced pressure. The residue was chromatographed on a silica-gel column using hexane and ethyl acetate (80/20) as eluents. Recrystallization from this solution gave the title compound as a white crystals suitable for X-ray investigation.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1486935
10.1107/S2414314616010130/sj4049sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2414314616010130/sj4049Isup2.hkl
Supporting information file. DOI: 10.1107/S2414314616010130/sj4049Isup4.cdx
Supporting information file. DOI: 10.1107/S2414314616010130/sj4049Isup4.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C18H16N2O2 | Z = 2 |
Mr = 292.33 | F(000) = 308 |
Triclinic, P1 | Dx = 1.290 Mg m−3 |
a = 8.6905 (2) Å | Cu Kα radiation, λ = 1.54178 Å |
b = 9.0249 (3) Å | Cell parameters from 5019 reflections |
c = 10.8240 (3) Å | θ = 5.4–72.4° |
α = 68.803 (1)° | µ = 0.69 mm−1 |
β = 78.520 (1)° | T = 150 K |
γ = 72.980 (1)° | Block, colourless |
V = 752.69 (4) Å3 | 0.17 × 0.13 × 0.13 mm |
Bruker D8 VENTURE PHOTON 100 CMOS diffractometer | 2802 independent reflections |
Radiation source: INCOATEC IµS micro–focus source | 2554 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.026 |
Detector resolution: 10.4167 pixels mm-1 | θmax = 72.4°, θmin = 5.4° |
ω scans | h = −10→10 |
Absorption correction: multi-scan (SADABS, Bruker, 2016) | k = −11→11 |
Tmin = 0.82, Tmax = 0.92 | l = −12→13 |
5877 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.038 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.107 | w = 1/[σ2(Fo2) + (0.0623P)2 + 0.166P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max < 0.001 |
2802 reflections | Δρmax = 0.20 e Å−3 |
205 parameters | Δρmin = −0.22 e Å−3 |
0 restraints | Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0185 (19) |
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. 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 > 2sigma(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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å) and included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.29131 (10) | −0.00462 (10) | 0.35510 (9) | 0.0299 (2) | |
O2 | 0.08148 (11) | 0.34999 (11) | 0.72733 (8) | 0.0283 (2) | |
H2A | 0.225 (2) | 0.395 (2) | 0.5665 (18) | 0.041 (4)* | |
N1 | 0.44188 (11) | 0.17555 (12) | 0.32357 (10) | 0.0235 (2) | |
N2 | 0.24209 (12) | 0.37133 (12) | 0.48668 (10) | 0.0222 (2) | |
C1 | 0.36309 (13) | 0.42678 (14) | 0.38710 (12) | 0.0220 (3) | |
C2 | 0.39430 (14) | 0.57554 (15) | 0.37361 (13) | 0.0265 (3) | |
H2 | 0.3329 | 0.6365 | 0.4301 | 0.032* | |
C3 | 0.51333 (16) | 0.63519 (16) | 0.27926 (14) | 0.0313 (3) | |
H3 | 0.5339 | 0.7361 | 0.2716 | 0.038* | |
C4 | 0.60277 (16) | 0.54749 (17) | 0.19572 (14) | 0.0345 (3) | |
H4 | 0.6834 | 0.5892 | 0.1298 | 0.041* | |
C5 | 0.57435 (15) | 0.39900 (17) | 0.20856 (14) | 0.0305 (3) | |
H5 | 0.6356 | 0.3396 | 0.1509 | 0.037* | |
C6 | 0.45668 (14) | 0.33579 (14) | 0.30532 (12) | 0.0232 (3) | |
C7 | 0.29822 (14) | 0.13457 (14) | 0.33893 (11) | 0.0221 (3) | |
C8 | 0.14850 (13) | 0.27376 (14) | 0.34124 (12) | 0.0210 (3) | |
H8 | 0.1702 | 0.3757 | 0.2708 | 0.025* | |
C9 | 0.13465 (13) | 0.29586 (13) | 0.47525 (12) | 0.0205 (3) | |
C10 | 0.02525 (13) | 0.23893 (14) | 0.57948 (12) | 0.0224 (3) | |
H10 | −0.0429 | 0.1812 | 0.5672 | 0.027* | |
C11 | 0.00868 (14) | 0.26233 (14) | 0.70643 (12) | 0.0235 (3) | |
C12 | −0.10022 (16) | 0.17527 (17) | 0.81733 (13) | 0.0311 (3) | |
H12A | −0.1656 | 0.1320 | 0.7809 | 0.047* | |
H12B | −0.1717 | 0.2522 | 0.8611 | 0.047* | |
H12C | −0.0345 | 0.0848 | 0.8824 | 0.047* | |
C13 | 0.59039 (15) | 0.04794 (15) | 0.31350 (14) | 0.0289 (3) | |
H13A | 0.6825 | 0.0767 | 0.3329 | 0.035* | |
H13B | 0.5781 | −0.0576 | 0.3814 | 0.035* | |
C14 | 0.62650 (15) | 0.02832 (15) | 0.18111 (14) | 0.0305 (3) | |
C15 | 0.65303 (19) | 0.00942 (19) | 0.07573 (16) | 0.0421 (4) | |
H15 | 0.6744 | −0.0058 | −0.0090 | 0.050* | |
C16 | −0.00053 (14) | 0.24122 (15) | 0.31059 (12) | 0.0249 (3) | |
H16A | −0.0093 | 0.1284 | 0.3643 | 0.030* | |
H16B | −0.0994 | 0.3185 | 0.3341 | 0.030* | |
C17 | 0.01388 (14) | 0.26199 (15) | 0.16813 (13) | 0.0271 (3) | |
C18 | 0.03206 (17) | 0.28788 (17) | 0.05105 (14) | 0.0336 (3) | |
H18 | 0.0466 | 0.3086 | −0.0425 | 0.040* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0299 (5) | 0.0217 (4) | 0.0404 (5) | −0.0055 (3) | −0.0037 (4) | −0.0135 (4) |
O2 | 0.0341 (5) | 0.0294 (5) | 0.0250 (5) | −0.0108 (4) | −0.0018 (4) | −0.0113 (4) |
N1 | 0.0198 (5) | 0.0203 (5) | 0.0298 (5) | −0.0021 (4) | −0.0012 (4) | −0.0104 (4) |
N2 | 0.0231 (5) | 0.0224 (5) | 0.0234 (5) | −0.0063 (4) | −0.0021 (4) | −0.0095 (4) |
C1 | 0.0194 (5) | 0.0221 (6) | 0.0241 (6) | −0.0043 (4) | −0.0048 (4) | −0.0062 (5) |
C2 | 0.0255 (6) | 0.0227 (6) | 0.0329 (7) | −0.0040 (5) | −0.0076 (5) | −0.0100 (5) |
C3 | 0.0299 (6) | 0.0262 (6) | 0.0407 (7) | −0.0117 (5) | −0.0080 (5) | −0.0080 (6) |
C4 | 0.0281 (6) | 0.0361 (7) | 0.0388 (7) | −0.0152 (5) | 0.0008 (5) | −0.0079 (6) |
C5 | 0.0241 (6) | 0.0327 (7) | 0.0350 (7) | −0.0081 (5) | 0.0022 (5) | −0.0131 (6) |
C6 | 0.0201 (5) | 0.0215 (6) | 0.0280 (6) | −0.0042 (4) | −0.0044 (4) | −0.0079 (5) |
C7 | 0.0236 (6) | 0.0217 (6) | 0.0216 (6) | −0.0042 (4) | −0.0017 (4) | −0.0091 (5) |
C8 | 0.0199 (5) | 0.0207 (6) | 0.0231 (6) | −0.0039 (4) | −0.0027 (4) | −0.0085 (5) |
C9 | 0.0194 (5) | 0.0166 (5) | 0.0250 (6) | −0.0001 (4) | −0.0053 (4) | −0.0080 (5) |
C10 | 0.0218 (5) | 0.0209 (5) | 0.0251 (6) | −0.0047 (4) | −0.0029 (4) | −0.0082 (5) |
C11 | 0.0229 (5) | 0.0207 (6) | 0.0246 (6) | −0.0019 (4) | −0.0048 (4) | −0.0062 (5) |
C12 | 0.0325 (7) | 0.0364 (7) | 0.0243 (6) | −0.0128 (5) | −0.0015 (5) | −0.0067 (6) |
C13 | 0.0220 (6) | 0.0245 (6) | 0.0373 (7) | 0.0006 (5) | −0.0034 (5) | −0.0114 (5) |
C14 | 0.0236 (6) | 0.0235 (6) | 0.0408 (8) | −0.0042 (5) | 0.0050 (5) | −0.0118 (6) |
C15 | 0.0430 (8) | 0.0423 (8) | 0.0427 (9) | −0.0178 (7) | 0.0148 (6) | −0.0200 (7) |
C16 | 0.0224 (6) | 0.0278 (6) | 0.0270 (6) | −0.0053 (5) | −0.0038 (4) | −0.0119 (5) |
C17 | 0.0246 (6) | 0.0283 (6) | 0.0319 (7) | −0.0050 (5) | −0.0058 (5) | −0.0134 (5) |
C18 | 0.0370 (7) | 0.0386 (7) | 0.0302 (7) | −0.0101 (6) | −0.0055 (5) | −0.0151 (6) |
O1—C7 | 1.2219 (14) | C8—C16 | 1.5290 (15) |
O2—C11 | 1.2478 (15) | C8—H8 | 1.0000 |
N1—C7 | 1.3662 (15) | C9—C10 | 1.3713 (17) |
N1—C6 | 1.4280 (15) | C10—C11 | 1.4376 (16) |
N1—C13 | 1.4726 (15) | C10—H10 | 0.9500 |
N2—C9 | 1.3529 (14) | C11—C12 | 1.5017 (17) |
N2—C1 | 1.4088 (15) | C12—H12A | 0.9800 |
N2—H2A | 0.939 (18) | C12—H12B | 0.9800 |
C1—C2 | 1.3975 (16) | C12—H12C | 0.9800 |
C1—C6 | 1.4027 (17) | C13—C14 | 1.4681 (18) |
C2—C3 | 1.3823 (18) | C13—H13A | 0.9900 |
C2—H2 | 0.9500 | C13—H13B | 0.9900 |
C3—C4 | 1.388 (2) | C14—C15 | 1.182 (2) |
C3—H3 | 0.9500 | C15—H15 | 0.9500 |
C4—C5 | 1.3862 (19) | C16—C17 | 1.4685 (17) |
C4—H4 | 0.9500 | C16—H16A | 0.9900 |
C5—C6 | 1.3969 (17) | C16—H16B | 0.9900 |
C5—H5 | 0.9500 | C17—C18 | 1.1888 (19) |
C7—C8 | 1.5247 (15) | C18—H18 | 0.9500 |
C8—C9 | 1.5113 (15) | ||
C7—N1—C6 | 124.46 (9) | C16—C8—H8 | 108.0 |
C7—N1—C13 | 116.81 (10) | N2—C9—C10 | 122.14 (10) |
C6—N1—C13 | 118.50 (9) | N2—C9—C8 | 115.06 (10) |
C9—N2—C1 | 125.92 (10) | C10—C9—C8 | 122.76 (10) |
C9—N2—H2A | 114.6 (11) | C9—C10—C11 | 123.22 (10) |
C1—N2—H2A | 119.3 (11) | C9—C10—H10 | 118.4 |
C2—C1—C6 | 119.19 (11) | C11—C10—H10 | 118.4 |
C2—C1—N2 | 118.15 (10) | O2—C11—C10 | 122.72 (11) |
C6—C1—N2 | 122.61 (10) | O2—C11—C12 | 119.61 (11) |
C3—C2—C1 | 120.91 (11) | C10—C11—C12 | 117.67 (10) |
C3—C2—H2 | 119.5 | C11—C12—H12A | 109.5 |
C1—C2—H2 | 119.5 | C11—C12—H12B | 109.5 |
C2—C3—C4 | 119.91 (12) | H12A—C12—H12B | 109.5 |
C2—C3—H3 | 120.0 | C11—C12—H12C | 109.5 |
C4—C3—H3 | 120.0 | H12A—C12—H12C | 109.5 |
C5—C4—C3 | 119.92 (12) | H12B—C12—H12C | 109.5 |
C5—C4—H4 | 120.0 | C14—C13—N1 | 112.32 (10) |
C3—C4—H4 | 120.0 | C14—C13—H13A | 109.1 |
C4—C5—C6 | 120.72 (12) | N1—C13—H13A | 109.1 |
C4—C5—H5 | 119.6 | C14—C13—H13B | 109.1 |
C6—C5—H5 | 119.6 | N1—C13—H13B | 109.1 |
C5—C6—C1 | 119.31 (11) | H13A—C13—H13B | 107.9 |
C5—C6—N1 | 118.84 (11) | C15—C14—C13 | 178.17 (14) |
C1—C6—N1 | 121.74 (10) | C14—C15—H15 | 180.0 |
O1—C7—N1 | 122.21 (11) | C17—C16—C8 | 109.32 (10) |
O1—C7—C8 | 123.08 (10) | C17—C16—H16A | 109.8 |
N1—C7—C8 | 114.65 (10) | C8—C16—H16A | 109.8 |
C9—C8—C7 | 105.29 (9) | C17—C16—H16B | 109.8 |
C9—C8—C16 | 115.45 (9) | C8—C16—H16B | 109.8 |
C7—C8—C16 | 111.90 (9) | H16A—C16—H16B | 108.3 |
C9—C8—H8 | 108.0 | C18—C17—C16 | 174.84 (13) |
C7—C8—H8 | 108.0 | C17—C18—H18 | 180.0 |
C9—N2—C1—C2 | 141.12 (11) | C13—N1—C7—C8 | −176.84 (10) |
C9—N2—C1—C6 | −41.41 (16) | O1—C7—C8—C9 | 103.58 (12) |
C6—C1—C2—C3 | 1.36 (17) | N1—C7—C8—C9 | −73.45 (12) |
N2—C1—C2—C3 | 178.93 (11) | O1—C7—C8—C16 | −22.58 (16) |
C1—C2—C3—C4 | 0.50 (19) | N1—C7—C8—C16 | 160.39 (10) |
C2—C3—C4—C5 | −1.1 (2) | C1—N2—C9—C10 | 176.94 (10) |
C3—C4—C5—C6 | −0.2 (2) | C1—N2—C9—C8 | −0.93 (15) |
C4—C5—C6—C1 | 2.10 (19) | C7—C8—C9—N2 | 74.96 (11) |
C4—C5—C6—N1 | −174.11 (11) | C16—C8—C9—N2 | −161.10 (10) |
C2—C1—C6—C5 | −2.63 (17) | C7—C8—C9—C10 | −102.89 (12) |
N2—C1—C6—C5 | 179.92 (11) | C16—C8—C9—C10 | 21.05 (15) |
C2—C1—C6—N1 | 173.46 (10) | N2—C9—C10—C11 | 3.68 (17) |
N2—C1—C6—N1 | −3.99 (17) | C8—C9—C10—C11 | −178.62 (10) |
C7—N1—C6—C5 | −136.02 (12) | C9—C10—C11—O2 | 7.22 (18) |
C13—N1—C6—C5 | 38.24 (16) | C9—C10—C11—C12 | −172.22 (11) |
C7—N1—C6—C1 | 47.87 (16) | C7—N1—C13—C14 | 77.54 (14) |
C13—N1—C6—C1 | −137.87 (12) | C6—N1—C13—C14 | −97.15 (13) |
C6—N1—C7—O1 | −179.55 (11) | C9—C8—C16—C17 | 166.39 (10) |
C13—N1—C7—O1 | 6.11 (17) | C7—C8—C16—C17 | −73.20 (12) |
C6—N1—C7—C8 | −2.49 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2A···O2 | 0.939 (18) | 1.918 (18) | 2.6678 (13) | 135.2 (14) |
C18—H18···O2i | 0.95 | 2.35 | 3.3012 (16) | 178 |
C12—H12A···O1ii | 0.98 | 2.70 | 3.664 (2) | 168 |
Symmetry codes: (i) x, y, z−1; (ii) −x, −y, −z+1. |
Acknowledgements
The support of NSF–MRI Grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.
References
Atwal, K. S., Bergey, J. L., Hedberg, A. & Moreland, S. (1987). J. Med. Chem. 30, 635–640. CrossRef CAS PubMed Web of Science Google Scholar
Brandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2016). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Claremon, D. A., Liverton, N., Smith, G. R. & Selnick, H. G. (1998). US Patent 5 725 171. Google Scholar
Di Braccio, M., Grossi, G., Roma, G., Vargiu, L., Mura, M. & Marongiu, M. E. (2001). Eur. J. Med. Chem. 36, 935–949. Web of Science CrossRef PubMed CAS Google Scholar
Knabe, J., Büch, H. P. & Bender, S. (1995). Arch. Pharm. Pharm. Med. Chem. 328, 59–66. CrossRef CAS Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Rudolph, U., Crestani, F., Benke, D., Brünig, I., Benson, J. A., Fritschy, J.-M., Martin, J. R., Bluethmann, H. & Möhler, H. (1999). Nature, 401, 796–800. CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. 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
Zellou, A., Cherrah, Y., Hassar, M. & Essassi, E. M. (1998). Ann. Pharm. Fr. 56, 169–174. CAS PubMed Google Scholar
Zellou, A., Keita, A., Cherrah, Y., Essassi, E. M. & Hassar, M. (1999). Therapie, 54, 645–649. PubMed CAS Google Scholar
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