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Acta Crystallogr Sect E Struct Rep Online. 2010 January 1; 66(Pt 1): o87–o88.
Published online 2009 December 9. doi:  10.1107/S1600536809052258
PMCID: PMC2980025

2-[2-(4-Methoxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-yl]phenol

Abstract

In the structure of title compound, C22H20O2N2, the 11-membered benzodiazepine ring system adopts a distorted boat conformation. The benzene ring of this system forms dihedral angles of 89.69 (12) and 48.82 (12)° with those of the phenol and methoxy­phenyl substituents, respectively. The dihedral angle between the benzene rings is 49.61 (11)°. An intra­molecular O—H(...)N hydrogen bond generates an S(6) ring.

Related literature

For the biological activity of heterocyclic scaffolds containing nitro­gen atoms, see: MacDonald (2002 [triangle]); Gringauz (1999 [triangle]); Albright et al. (1998 [triangle]); Rahbaek et al. (1999 [triangle]). For related structures, see: Ravichandran et al. (2009a [triangle],b [triangle],c [triangle],d [triangle]). For puckering parameters, see: Cremer & Pople (1975 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]). For the weighting scheme, see: Prince (1982 [triangle]); Watkin (1994 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-00o87-scheme1.jpg

Experimental

Crystal data

  • C22H20N2O2
  • M r = 344.41
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-00o87-efi1.jpg
  • a = 27.5064 (5) Å
  • b = 7.3811 (2) Å
  • c = 19.5038 (4) Å
  • β = 117.699 (2)°
  • V = 3506.02 (15) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 223 K
  • 0.30 × 0.20 × 0.15 mm

Data collection

  • Nonius KappaCCD diffractometer
  • 19187 measured reflections
  • 2507 independent reflections
  • 2836 reflections with I > 3σ(I)
  • R int = 0.06

Refinement

  • R[F 2 > 2σ(F 2)] = 0.055
  • wR(F 2) = 0.065
  • S = 1.04
  • 2507 reflections
  • 235 parameters
  • H-atom parameters constrained
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.25 e Å−3

Data collection: COLLECT (Nonius, 2001 [triangle]); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 [triangle]); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 [triangle]); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: CRYSTALS.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809052258/bq2181sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809052258/bq2181Isup2.hkl

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

Acknowledgments

The authors thank the Spectropôle Service of the Faculty of Sciences and Techniques of Saint Jérôme (France) for the use of the diffractometer.

supplementary crystallographic information

Comment

Heterocyclic scaffolds containing nitrogen atoms have received great attention in organic and medicinal chemistry because of their broad range of beneficial biological properties. These heterocyclic compounds such as benzodiazepines exhibit bioactive profile including anticonvulsant (MacDonald, 2002), hypnotic (Gringauz, 1999) and vasopressin antagonists (Albright et al., 1998) activities. They are also used for treatment of gastrointestinal and central nervous system (CNS) disorder (Rahbaek et al., 1999). As part of continuing work on heterocyclic compounds biologically active, we have synthesized new benzodiazepine derivative in order to explore the effects of substituents on activity and scaffold conformation of this compound class. In this paper, we present molecular structure of the title compound. The molecular structure of title compound is shown in Fig. 1. The benzodiazepine ring system adopts a distorted boat conformation as shown in the recent studies related to benzodiazepine derivatives (Ravichandran et al., 2009a,b,c,d). The puckering parameters (Cremer & Pople, 1975) for this eleven-membered benzodiazepine ring system are: Q2 = 1.087 (3) Å,Q3 = 0.654 (3) Å,[var phi]2 = 320.74 (4)° and [var phi]3 = 26.7 (2)°. The benzene ring of this system forms dihedral angles of 89.69 (12)° and 48.82 (12)° with the phenyl rings of phenol and methoxy-phenyl fragments respectively which make them dihedral angle of 49.61 (11)°. Furthermore, there is in this structure the presence of O—H···N intra-molecular hydrogen bond, which generates an S (6) graph set motif (Bernstein et al., 1995).

Experimental

To a solution of 1-(2-hydroxyphenyl)-3-(p-tolyl) propenone (1.3 g, 5.4 mmol) and 1, 2-diaminobenzene in anhydrous ethanol (20 ml), was added triethylamine (6 ml, 32.4 mmol). The reaction mixture was stirred under shelter from the light for 24 h. The resulting mixture was cooled at room temperature then kept in the freezer all night long. The precipitate was then filtered and purified by chromatography silica gel. Elution solvent: hexane/ethyl acetate (90/10). We obtained yellow single crystals of title compound with a yield of 56% (m.p.: 413–415 K; Rf: 1/2, hexane/ethyl acetate: 80/20).

Refinement

The H atoms were all located in a difference of Fourier map. They were all initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.95–0.97 Å, O—H = 0.87 Å, N—H = 0.88 Å and Uiso(H)in the range 1.2–1.7 times Ueq of the parent atom), after which their positions were refined with riding constraints.

Figures

Fig. 1.
The molecular structure of the title compound and the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.

Crystal data

C22H20N2O2F(000) = 1456
Mr = 344.41Dx = 1.305 Mg m3
Monoclinic, C2/cMelting point = 413–415 K
Hall symbol: -C 2ycMo Kα radiation, λ = 0.71073 Å
a = 27.5064 (5) ÅCell parameters from 19187 reflections
b = 7.3811 (2) Åθ = 0–0°
c = 19.5038 (4) ŵ = 0.08 mm1
β = 117.699 (2)°T = 223 K
V = 3506.02 (15) Å3Block, yellow
Z = 80.30 × 0.20 × 0.15 mm

Data collection

Nonius KappaCCD diffractometerRint = 0.06
graphiteθmax = 29.1°, θmin = 1.7°
[var phi] and ω scansh = −37→32
19187 measured reflectionsk = −10→10
2507 independent reflectionsl = −25→25
2836 reflections with I > 3σ(I)

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.055H-atom parameters constrained
wR(F2) = 0.065 Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)2]2 Ai are: 76.3 80.0 28.8 -10.0 -11.5
S = 1.04(Δ/σ)max = 0.0004
2507 reflectionsΔρmax = 0.25 e Å3
235 parametersΔρmin = −0.25 e Å3
0 restraints

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

xyzUiso*/Ueq
O10.93812 (7)0.1834 (2)0.28604 (9)0.0613
O20.74005 (6)0.9744 (2)0.19252 (11)0.0715
N10.92187 (7)0.2773 (2)0.15267 (10)0.0441
N20.82826 (7)0.4219 (3)0.02002 (10)0.0518
C10.90766 (9)0.2197 (3)0.07668 (13)0.0465
C20.86133 (9)0.2877 (3)0.01157 (13)0.0481
C30.84587 (10)0.2063 (4)−0.06017 (14)0.0600
C40.87638 (12)0.0637 (4)−0.06710 (17)0.0694
C50.92265 (12)0.0009 (4)−0.00312 (18)0.0690
C60.93752 (10)0.0773 (3)0.06788 (16)0.0572
C70.92184 (7)0.4477 (3)0.16870 (12)0.0385
C80.91134 (8)0.5878 (3)0.10725 (12)0.0404
C90.85020 (8)0.6032 (3)0.04950 (12)0.0435
C100.81802 (8)0.6940 (3)0.08532 (11)0.0405
C110.82500 (9)0.8789 (3)0.10081 (14)0.0547
C120.79940 (9)0.9683 (3)0.13693 (15)0.0584
C130.76448 (8)0.8738 (3)0.15756 (14)0.0526
C140.75569 (9)0.6925 (3)0.14123 (13)0.0509
C150.78302 (8)0.6032 (3)0.10597 (12)0.0475
C160.93285 (8)0.4968 (3)0.24729 (12)0.0384
C170.93531 (8)0.6780 (3)0.27066 (12)0.0442
C180.94419 (8)0.7245 (3)0.34386 (13)0.0506
C190.95159 (9)0.5901 (3)0.39714 (13)0.0532
C200.95014 (9)0.4115 (3)0.37696 (13)0.0532
C210.94043 (8)0.3622 (3)0.30257 (13)0.0455
C220.69528 (10)0.8907 (4)0.19955 (17)0.0766
H820.93090.54950.07750.0489*
H810.92440.70790.13090.0491*
H1910.95680.62220.44950.0668*
H910.84710.68090.00550.0540*
H1110.84890.94420.08490.0673*
H1410.73080.62580.15470.0624*
H1510.77630.47300.09420.0604*
H2010.95650.31670.41330.0656*
H510.9445−0.0943−0.00830.0953*
H1710.93050.77350.23340.0558*
H1810.94600.85070.35830.0644*
H210.79270.4133−0.00980.0665*
H410.86600.0108−0.11670.0911*
H1210.80621.09510.14970.0723*
H310.81350.2496−0.10430.0789*
H610.96930.03250.11340.0794*
H2220.68050.98580.22100.1264*
H2230.66830.85140.14730.1269*
H2210.70940.78490.23500.1273*
H110.93220.17250.23850.0949*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0752 (11)0.0399 (10)0.0615 (10)0.0001 (8)0.0257 (9)0.0135 (8)
O20.0518 (10)0.0654 (12)0.1058 (14)−0.0043 (9)0.0437 (10)−0.0231 (10)
N10.0415 (10)0.0383 (10)0.0543 (11)−0.0021 (8)0.0238 (9)0.0006 (8)
N20.0363 (9)0.0547 (12)0.0585 (12)−0.0069 (9)0.0171 (9)−0.0094 (10)
C10.0465 (12)0.0374 (12)0.0636 (15)−0.0115 (10)0.0324 (12)−0.0060 (11)
C20.0481 (13)0.0476 (13)0.0560 (14)−0.0169 (11)0.0305 (11)−0.0092 (11)
C30.0607 (15)0.0623 (16)0.0641 (16)−0.0240 (13)0.0348 (13)−0.0153 (13)
C40.0840 (19)0.0658 (18)0.0814 (19)−0.0386 (16)0.0579 (17)−0.0348 (16)
C50.0725 (18)0.0542 (16)0.100 (2)−0.0212 (14)0.0570 (18)−0.0257 (16)
C60.0564 (13)0.0436 (13)0.0811 (17)−0.0112 (12)0.0401 (13)−0.0116 (13)
C70.0296 (10)0.0354 (11)0.0507 (12)−0.0019 (8)0.0187 (9)0.0036 (9)
C80.0369 (10)0.0366 (11)0.0494 (12)−0.0043 (9)0.0216 (9)0.0028 (10)
C90.0388 (11)0.0449 (13)0.0442 (12)−0.0031 (10)0.0171 (9)0.0070 (10)
C100.0321 (10)0.0391 (12)0.0441 (12)−0.0001 (9)0.0123 (9)0.0076 (9)
C110.0426 (12)0.0419 (14)0.0816 (17)−0.0022 (10)0.0307 (12)0.0095 (12)
C120.0417 (12)0.0384 (13)0.0939 (19)−0.0027 (10)0.0305 (13)−0.0044 (13)
C130.0370 (12)0.0511 (14)0.0664 (15)0.0017 (11)0.0211 (11)−0.0061 (12)
C140.0436 (12)0.0480 (14)0.0668 (15)−0.0064 (11)0.0304 (11)−0.0008 (12)
C150.0457 (12)0.0391 (12)0.0596 (14)−0.0059 (10)0.0262 (11)0.0006 (11)
C160.0296 (10)0.0379 (11)0.0459 (12)0.0015 (8)0.0161 (9)0.0061 (9)
C170.0392 (11)0.0400 (13)0.0526 (13)0.0036 (9)0.0206 (10)0.0063 (10)
C180.0472 (13)0.0501 (13)0.0550 (14)0.0061 (11)0.0242 (11)−0.0012 (11)
C190.0447 (12)0.0661 (16)0.0488 (13)0.0071 (12)0.0217 (11)0.0046 (12)
C200.0476 (13)0.0612 (15)0.0501 (13)0.0048 (12)0.0221 (11)0.0162 (12)
C210.0369 (11)0.0418 (12)0.0544 (13)0.0019 (10)0.0182 (10)0.0107 (11)
C220.0595 (15)0.087 (2)0.097 (2)−0.0058 (16)0.0485 (16)−0.0176 (18)

Geometric parameters (Å, °)

O1—C211.353 (2)C9—H911.002
O1—H110.867C10—C111.392 (3)
O2—C131.376 (3)C10—C151.378 (3)
O2—C221.440 (3)C11—C121.374 (3)
N1—C11.411 (3)C11—H1110.975
N1—C71.297 (3)C12—C131.389 (3)
N2—C21.405 (3)C12—H1210.964
N2—C91.470 (3)C13—C141.371 (3)
N2—H210.877C14—C151.397 (3)
C1—C21.409 (3)C14—H1410.972
C1—C61.393 (3)C15—H1510.986
C2—C31.395 (3)C16—C171.405 (3)
C3—C41.391 (3)C16—C211.409 (3)
C3—H310.960C17—C181.375 (3)
C4—C51.384 (4)C17—H1710.976
C4—H410.956C18—C191.381 (3)
C5—C61.370 (3)C18—H1810.968
C5—H510.960C19—C201.371 (3)
C6—H610.970C19—H1910.993
C7—C81.505 (3)C20—C211.396 (3)
C7—C161.463 (3)C20—H2010.953
C8—C91.533 (3)C22—H2220.997
C8—H820.999C22—H2230.985
C8—H810.987C22—H2210.995
C9—C101.515 (3)
C21—O1—H11108.1C11—C10—C15117.3 (2)
C13—O2—C22116.84 (19)C10—C11—C12122.0 (2)
C1—N1—C7120.97 (18)C10—C11—H111117.5
C2—N2—C9121.12 (16)C12—C11—H111120.5
C2—N2—H21117.0C11—C12—C13119.7 (2)
C9—N2—H21117.0C11—C12—H121120.9
N1—C1—C2122.16 (19)C13—C12—H121119.3
N1—C1—C6117.7 (2)C12—C13—O2115.8 (2)
C2—C1—C6119.7 (2)C12—C13—C14119.6 (2)
C1—C2—N2120.6 (2)O2—C13—C14124.6 (2)
C1—C2—C3118.5 (2)C13—C14—C15119.8 (2)
N2—C2—C3120.6 (2)C13—C14—H141120.1
C2—C3—C4120.4 (3)C15—C14—H141120.1
C2—C3—H31118.6C14—C15—C10121.6 (2)
C4—C3—H31120.9C14—C15—H151119.3
C3—C4—C5120.6 (2)C10—C15—H151119.2
C3—C4—H41119.9C7—C16—C17122.07 (19)
C5—C4—H41119.5C7—C16—C21120.80 (19)
C4—C5—C6119.4 (3)C17—C16—C21117.1 (2)
C4—C5—H51120.6C16—C17—C18122.2 (2)
C6—C5—H51120.0C16—C17—H171118.5
C1—C6—C5121.3 (3)C18—C17—H171119.4
C1—C6—H61118.5C17—C18—C19119.7 (2)
C5—C6—H61120.2C17—C18—H181120.2
N1—C7—C8119.71 (19)C19—C18—H181120.2
N1—C7—C16118.03 (19)C18—C19—C20120.0 (2)
C8—C7—C16122.26 (18)C18—C19—H191120.2
C7—C8—C9112.03 (16)C20—C19—H191119.7
C7—C8—H82108.3C19—C20—C21121.0 (2)
C9—C8—H82107.3C19—C20—H201121.4
C7—C8—H81110.6C21—C20—H201117.5
C9—C8—H81108.3C16—C21—C20120.0 (2)
H82—C8—H81110.3C16—C21—O1122.1 (2)
C8—C9—N2109.30 (17)C20—C21—O1117.9 (2)
C8—C9—C10111.76 (17)O2—C22—H222105.8
N2—C9—C10111.18 (16)O2—C22—H223107.2
C8—C9—H91107.4H222—C22—H223112.5
N2—C9—H91109.2O2—C22—H221109.1
C10—C9—H91107.8H222—C22—H221111.4
C9—C10—C11118.86 (19)H223—C22—H221110.6
C9—C10—C15123.85 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O1—H11···N10.871.742.523 (3)148

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BQ2181).

References

  • Albright, J. D., Feich, M. F., Santos, E. G. D., Dusza, J. P., Sum, F.-W., Venkatesan, A. M., Coupet, J., Chan, P. S., Ru, X., Mazandarani, H. & Bailey, T. (1998). J. Med. Chem.41, 2442–2444. [PubMed]
  • Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst.27, 435.
  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst.36, 1487.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Gringauz, A. (1999). Introduction to Medicinal Chemistry, pp. 578–580. New York: Wiley-VCH.
  • MacDonald, R. L. (2002). Benzodiazepines - Mechanisms of Action In Antiepileptic Drugs, 5th ed., edited by R. H. Levy, R. H. Mattson, B. S. Meldrum & E. Perucca, pp. 179–186. Philadelphia: Lippincott Williams and Wilkins.
  • Nonius (2001). COLLECT Nonius BV, Delft, The Netherlands.
  • Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  • Prince, E. (1982). Mathematical Techniques in Crystallography and Materials Science New York: Springer-Verlag.
  • Rahbaek, L., Breinholt, J., Frisvad, J. C. & Christophersen, C. (1999). J. Org. Chem.64, 1689–1692. [PubMed]
  • Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Ramesh, P. & Ponnuswamy, M. N. (2009a). Acta Cryst. E65, o2361. [PMC free article] [PubMed]
  • Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Ramesh, P. & Ponnuswamy, M. N. (2009b). Acta Cryst. E65, o2362. [PMC free article] [PubMed]
  • Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Shalini, M. & Ponnuswamy, M. N. (2009c). Acta Cryst. E65, o2551–o2552. [PMC free article] [PubMed]
  • Ravichandran, K., Sathiyaraj, K., Ilango, S. S., Ponnuswamy, S. & Ponnuswamy, M. N. (2009d). Acta Cryst. E65, o2363–o2364. [PMC free article] [PubMed]
  • Watkin, D. (1994). Acta Cryst. A50, 411–437.

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