organic compounds
3-Hydroxy-4-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one: cis isomer
aLaboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Mohammed V University, Rabat, Morocco, bUFR-Environnement, UNIV Jean Lorougnon Guédé, BP 150, Daloa, Ivory Coast, and cDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: rida.m.b@hotmail.com
In the title compound, C15H14N2O2, the seven-membered benzodiazepine ring adopts a twist-boat conformation and the two aromatic rings are inclined to one another by 81.06 (15)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming chains propagating along the [10-1] direction. The chains are linked by C—H⋯O hydrogen bonds, forming sheets parallel to the ac plane. Within the sheets, there are N—H⋯π interactions present, and C—H⋯π interactions link the sheets to form a three-dimensional structure.
Keywords: crystal structure; benzodiazepine; cis isomer; hydrogen bonding; N—H⋯π interactions; C—H⋯π interactions.
CCDC reference: 1518908
Structure description
1,5-Benzodiazepine derivatives have been used as therapeutics for viral infections and cardiovascular disorder (Jacob et al., 2011; Maleki et al., 2014). They are active against potassium blockers (Claremon et al., 1996) and are also employed as intermediates for the synthesis of several (Minnih et al., 2014; Ahabchane et al., 1999). As part of our studies in this area, we now describe the synthesis and of the title compound, Fig. 1.
The seven-membered ring (N1/N2/C1/C6–C9) adopts a twist-boat conformation [puckering parameters: Q(2) = 0.571 (3) Å, Q(3) = 0.375 (3) Å, φ(2) = 230.7 (3)° and φ(3) = 326.7 (5)°; total puckering amplitude Q = 0.682 (3) Å]. The dihedral angle between the aromatic rings, C1–C6 and C10–C15, is 81.06 (15)°. There is possibly an intramolecular O1—H1⋯O2 hydrogen bond (Table 1), but the small O—H⋯O angle of 122 (4)° would indicate considerable strain.
In the crystal, molecules are linked by N2—H2A⋯O1i hydrogen bonds, forming chains propagating along [10]; see Table 1 and Fig. 2. The chains are linked by C8—H8⋯O2ii hydrogen bonds, forming sheets parallel to the ac plane (Table 1 and Fig. 2). Within the sheets there are N—H⋯π interactions present, and C—H⋯π interactions link the sheets to form a three-dimensional structure (Table 1 and Fig. 3).
Synthesis and crystallization
A mixture of o-phenylenediamine 1 (0.03 mol) and ethyl glycidate (0.03 mol) was refluxed in 80 ml of xylene for 48 h. The resulting crude mixture was left at room temperature overnight. The trans diastereoisomer which precipitated was filtered. The filtrate was concentrated under reduced pressure and the oil obtained was chromatographed on a silica gel column with a mixture of ether/chloroform (50/50) as and gave the trans and cis isomers, with a predominance of the trans isomers. The cis isomer was recrystallized from ethanol solution to afford the title compound as colourless crystals.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2
|
Structural data
CCDC reference: 1518908
https://doi.org/10.1107/S2414314616018794/su4096sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616018794/su4096Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314616018794/su4096Isup3.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2414314616018794/su4096Isup4.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); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C15H14N2O2 | F(000) = 536 |
Mr = 254.28 | Dx = 1.429 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 5.519 (2) Å | Cell parameters from 2522 reflections |
b = 21.594 (8) Å | θ = 2.3–27.3° |
c = 9.917 (4) Å | µ = 0.10 mm−1 |
β = 90.405 (5)° | T = 100 K |
V = 1181.9 (7) Å3 | Plate, colourless |
Z = 4 | 0.41 × 0.17 × 0.09 mm |
Bruker SMART APEX CCD diffractometer | 2955 independent reflections |
Radiation source: fine-focus sealed tube | 2064 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.073 |
Detector resolution: 8.3333 pixels mm-1 | θmax = 28.5°, θmin = 1.9° |
φ and ω scans | h = −7→7 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −28→28 |
Tmin = 0.69, Tmax = 0.99 | l = −13→13 |
10886 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.084 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.211 | All H-atom parameters refined |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0375P)2 + 2.6752P] where P = (Fo2 + 2Fc2)/3 |
2955 reflections | (Δ/σ)max = 0.002 |
228 parameters | Δρmax = 0.51 e Å−3 |
0 restraints | Δρmin = −0.37 e Å−3 |
Experimental. The diffraction data were collected in three sets of 363 frames (0.5° width in ω) at φ = 0, 120 and 240°. A scan time of 40 sec/frame was used. |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.7374 (4) | 0.22601 (11) | 0.6710 (2) | 0.0243 (5) | |
H1 | 0.597 (8) | 0.2125 (19) | 0.656 (4) | 0.037 (11)* | |
O2 | 0.3865 (4) | 0.24635 (11) | 0.5074 (2) | 0.0259 (5) | |
N1 | 1.0082 (5) | 0.36774 (14) | 0.5379 (3) | 0.0231 (6) | |
H1A | 1.152 (8) | 0.385 (2) | 0.567 (4) | 0.043 (12)* | |
N2 | 0.5741 (5) | 0.31730 (13) | 0.3793 (3) | 0.0224 (6) | |
H2A | 0.447 (6) | 0.3124 (15) | 0.326 (3) | 0.016 (8)* | |
C1 | 0.7618 (5) | 0.35486 (15) | 0.3285 (3) | 0.0207 (6) | |
C2 | 0.7369 (6) | 0.37111 (16) | 0.1921 (3) | 0.0231 (7) | |
H2 | 0.605 (7) | 0.3557 (16) | 0.148 (4) | 0.023 (9)* | |
C3 | 0.8982 (6) | 0.40866 (16) | 0.1277 (3) | 0.0257 (7) | |
H3 | 0.872 (7) | 0.4181 (18) | 0.037 (4) | 0.035 (10)* | |
C4 | 1.0966 (6) | 0.43153 (17) | 0.1999 (3) | 0.0263 (7) | |
H4 | 1.206 (7) | 0.4591 (17) | 0.161 (4) | 0.027 (9)* | |
C5 | 1.1238 (5) | 0.41670 (16) | 0.3341 (3) | 0.0238 (7) | |
H5 | 1.271 (7) | 0.4331 (16) | 0.387 (4) | 0.025 (9)* | |
C6 | 0.9597 (5) | 0.37839 (15) | 0.4029 (3) | 0.0205 (6) | |
C7 | 0.8692 (5) | 0.33250 (15) | 0.6340 (3) | 0.0208 (7) | |
H7 | 0.985 (6) | 0.3219 (15) | 0.709 (3) | 0.015 (8)* | |
C8 | 0.7900 (5) | 0.27039 (15) | 0.5704 (3) | 0.0213 (7) | |
H8 | 0.923 (7) | 0.2558 (16) | 0.512 (4) | 0.025 (9)* | |
C9 | 0.5674 (5) | 0.27720 (15) | 0.4819 (3) | 0.0193 (6) | |
C10 | 0.6631 (5) | 0.36864 (15) | 0.6969 (3) | 0.0209 (7) | |
C11 | 0.5912 (6) | 0.42582 (16) | 0.6492 (3) | 0.0241 (7) | |
H11 | 0.668 (6) | 0.4453 (15) | 0.572 (3) | 0.019 (8)* | |
C12 | 0.4053 (6) | 0.45873 (17) | 0.7111 (3) | 0.0257 (7) | |
H12 | 0.354 (6) | 0.4998 (16) | 0.676 (4) | 0.021 (9)* | |
C13 | 0.2881 (6) | 0.43370 (17) | 0.8217 (3) | 0.0257 (7) | |
H13 | 0.159 (7) | 0.4587 (17) | 0.864 (4) | 0.031 (10)* | |
C14 | 0.3598 (6) | 0.37627 (17) | 0.8703 (3) | 0.0270 (7) | |
H14 | 0.286 (8) | 0.3569 (19) | 0.943 (4) | 0.041 (11)* | |
C15 | 0.5472 (6) | 0.34412 (17) | 0.8103 (3) | 0.0253 (7) | |
H15 | 0.589 (7) | 0.3010 (19) | 0.842 (4) | 0.032 (10)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0168 (11) | 0.0391 (14) | 0.0168 (11) | −0.0029 (10) | −0.0052 (9) | 0.0048 (9) |
O2 | 0.0156 (10) | 0.0420 (14) | 0.0200 (11) | −0.0051 (9) | −0.0028 (8) | 0.0034 (10) |
N1 | 0.0114 (11) | 0.0413 (17) | 0.0167 (13) | −0.0052 (11) | 0.0007 (9) | −0.0008 (11) |
N2 | 0.0141 (12) | 0.0399 (17) | 0.0133 (12) | −0.0030 (11) | −0.0017 (9) | 0.0015 (11) |
C1 | 0.0126 (13) | 0.0320 (17) | 0.0176 (14) | 0.0016 (12) | 0.0017 (11) | −0.0017 (12) |
C2 | 0.0187 (15) | 0.0354 (18) | 0.0152 (14) | 0.0005 (13) | −0.0026 (11) | −0.0017 (12) |
C3 | 0.0230 (16) | 0.0355 (19) | 0.0185 (16) | 0.0031 (13) | 0.0024 (12) | 0.0001 (13) |
C4 | 0.0196 (15) | 0.0359 (19) | 0.0235 (17) | −0.0016 (14) | 0.0066 (12) | 0.0009 (14) |
C5 | 0.0126 (13) | 0.0367 (19) | 0.0221 (16) | 0.0002 (12) | 0.0021 (11) | −0.0022 (13) |
C6 | 0.0133 (13) | 0.0322 (17) | 0.0159 (14) | 0.0024 (12) | 0.0022 (10) | −0.0023 (12) |
C7 | 0.0126 (13) | 0.0355 (18) | 0.0143 (14) | −0.0015 (12) | −0.0006 (11) | 0.0006 (12) |
C8 | 0.0147 (14) | 0.0342 (18) | 0.0150 (14) | −0.0014 (12) | 0.0011 (11) | 0.0018 (12) |
C9 | 0.0120 (13) | 0.0321 (17) | 0.0136 (14) | 0.0000 (11) | −0.0010 (10) | −0.0010 (11) |
C10 | 0.0149 (14) | 0.0347 (18) | 0.0130 (13) | −0.0015 (12) | −0.0014 (10) | −0.0025 (12) |
C11 | 0.0227 (15) | 0.0329 (18) | 0.0169 (15) | −0.0036 (13) | 0.0018 (12) | −0.0001 (13) |
C12 | 0.0229 (16) | 0.0340 (19) | 0.0203 (16) | −0.0002 (13) | 0.0022 (12) | −0.0002 (13) |
C13 | 0.0176 (15) | 0.039 (2) | 0.0207 (16) | 0.0010 (13) | 0.0008 (12) | −0.0034 (14) |
C14 | 0.0243 (16) | 0.038 (2) | 0.0191 (16) | 0.0009 (14) | 0.0032 (12) | 0.0017 (14) |
C15 | 0.0205 (15) | 0.038 (2) | 0.0177 (15) | 0.0005 (14) | −0.0002 (12) | 0.0022 (13) |
O1—C8 | 1.415 (4) | C5—H5 | 1.03 (4) |
O1—H1 | 0.84 (4) | C7—C10 | 1.517 (4) |
O2—C9 | 1.228 (4) | C7—C8 | 1.544 (5) |
N1—C6 | 1.383 (4) | C7—H7 | 1.00 (3) |
N1—C7 | 1.444 (4) | C8—C9 | 1.512 (4) |
N1—H1A | 0.93 (5) | C8—H8 | 0.99 (4) |
N2—C9 | 1.337 (4) | C10—C11 | 1.380 (5) |
N2—C1 | 1.412 (4) | C10—C15 | 1.402 (4) |
N2—H2A | 0.88 (4) | C11—C12 | 1.394 (5) |
C1—C2 | 1.403 (4) | C11—H11 | 0.98 (3) |
C1—C6 | 1.409 (4) | C12—C13 | 1.387 (5) |
C2—C3 | 1.366 (5) | C12—H12 | 0.99 (4) |
C2—H2 | 0.91 (4) | C13—C14 | 1.387 (5) |
C3—C4 | 1.394 (5) | C13—H13 | 0.99 (4) |
C3—H3 | 0.94 (4) | C14—C15 | 1.384 (5) |
C4—C5 | 1.376 (5) | C14—H14 | 0.93 (4) |
C4—H4 | 0.93 (4) | C15—H15 | 1.01 (4) |
C5—C6 | 1.407 (4) | ||
C8—O1—H1 | 108 (3) | C10—C7—H7 | 106.8 (19) |
C6—N1—C7 | 128.8 (3) | C8—C7—H7 | 106.3 (18) |
C6—N1—H1A | 113 (3) | O1—C8—C9 | 107.8 (2) |
C7—N1—H1A | 118 (3) | O1—C8—C7 | 111.1 (2) |
C9—N2—C1 | 131.9 (3) | C9—C8—C7 | 112.3 (3) |
C9—N2—H2A | 111 (2) | O1—C8—H8 | 111 (2) |
C1—N2—H2A | 116 (2) | C9—C8—H8 | 107 (2) |
C2—C1—C6 | 119.0 (3) | C7—C8—H8 | 108 (2) |
C2—C1—N2 | 114.9 (3) | O2—C9—N2 | 122.3 (3) |
C6—C1—N2 | 126.1 (3) | O2—C9—C8 | 119.1 (3) |
C3—C2—C1 | 122.6 (3) | N2—C9—C8 | 118.6 (3) |
C3—C2—H2 | 121 (2) | C11—C10—C15 | 118.8 (3) |
C1—C2—H2 | 117 (2) | C11—C10—C7 | 122.3 (3) |
C2—C3—C4 | 118.8 (3) | C15—C10—C7 | 118.9 (3) |
C2—C3—H3 | 119 (2) | C10—C11—C12 | 121.1 (3) |
C4—C3—H3 | 122 (3) | C10—C11—H11 | 122 (2) |
C5—C4—C3 | 119.6 (3) | C12—C11—H11 | 117 (2) |
C5—C4—H4 | 119 (2) | C13—C12—C11 | 119.9 (3) |
C3—C4—H4 | 122 (2) | C13—C12—H12 | 119 (2) |
C4—C5—C6 | 122.7 (3) | C11—C12—H12 | 121 (2) |
C4—C5—H5 | 120 (2) | C12—C13—C14 | 119.3 (3) |
C6—C5—H5 | 118 (2) | C12—C13—H13 | 118 (2) |
N1—C6—C5 | 116.5 (3) | C14—C13—H13 | 123 (2) |
N1—C6—C1 | 126.3 (3) | C15—C14—C13 | 120.7 (3) |
C5—C6—C1 | 117.2 (3) | C15—C14—H14 | 116 (3) |
N1—C7—C10 | 113.8 (3) | C13—C14—H14 | 123 (3) |
N1—C7—C8 | 109.8 (2) | C14—C15—C10 | 120.2 (3) |
C10—C7—C8 | 113.8 (2) | C14—C15—H15 | 120 (2) |
N1—C7—H7 | 105.7 (19) | C10—C15—H15 | 120 (2) |
C9—N2—C1—C2 | 155.0 (3) | C10—C7—C8—C9 | 47.4 (3) |
C9—N2—C1—C6 | −27.6 (5) | C1—N2—C9—O2 | −176.8 (3) |
C6—C1—C2—C3 | 0.5 (5) | C1—N2—C9—C8 | 4.0 (5) |
N2—C1—C2—C3 | 178.1 (3) | O1—C8—C9—O2 | 0.4 (4) |
C1—C2—C3—C4 | 0.4 (5) | C7—C8—C9—O2 | −122.2 (3) |
C2—C3—C4—C5 | −0.9 (5) | O1—C8—C9—N2 | 179.6 (3) |
C3—C4—C5—C6 | 0.7 (5) | C7—C8—C9—N2 | 57.0 (4) |
C7—N1—C6—C5 | 177.8 (3) | N1—C7—C10—C11 | 10.6 (4) |
C7—N1—C6—C1 | −1.9 (5) | C8—C7—C10—C11 | −116.2 (3) |
C4—C5—C6—N1 | −179.5 (3) | N1—C7—C10—C15 | −167.2 (3) |
C4—C5—C6—C1 | 0.2 (5) | C8—C7—C10—C15 | 66.0 (4) |
C2—C1—C6—N1 | 178.9 (3) | C15—C10—C11—C12 | −0.6 (5) |
N2—C1—C6—N1 | 1.6 (5) | C7—C10—C11—C12 | −178.3 (3) |
C2—C1—C6—C5 | −0.7 (4) | C10—C11—C12—C13 | −0.7 (5) |
N2—C1—C6—C5 | −178.1 (3) | C11—C12—C13—C14 | 0.7 (5) |
C6—N1—C7—C10 | −83.5 (4) | C12—C13—C14—C15 | 0.4 (5) |
C6—N1—C7—C8 | 45.3 (4) | C13—C14—C15—C10 | −1.7 (5) |
N1—C7—C8—O1 | 157.8 (2) | C11—C10—C15—C14 | 1.7 (5) |
C10—C7—C8—O1 | −73.4 (3) | C7—C10—C15—C14 | 179.5 (3) |
N1—C7—C8—C9 | −81.4 (3) |
Cg1 and Cg2 are the centroids of the C1–C6 and C10–C15 rings, respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O2 | 0.84 (4) | 2.01 (4) | 2.556 (3) | 122 (4) |
N2—H2A···O1i | 0.88 (4) | 2.09 (4) | 2.922 (3) | 157 (3) |
C8—H8···O2ii | 0.99 (4) | 2.57 (4) | 3.395 (4) | 141 (3) |
C12—H12···Cg1iii | 0.99 (4) | 2.85 (3) | 3.696 (4) | 144 (3) |
N1—H1A···Cg2ii | 0.99 (5) | 2.63 (3) | 3.457 (3) | 149 (3) |
Symmetry codes: (i) x−1/2, −y+1/2, z−1/2; (ii) x+1, y, z; (iii) −x+1, −y+1, −z+1. |
Acknowledgements
JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.
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