organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoIUCrDATA
ISSN: 2414-3146

3-(2,4-Di­fluoro­phen­yl)-1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]triazin-4(3H)-one

aFaculty of Science, Chemistry Department, Islamic University of Gaza Strip, Gaza Strip, Palestinian Territories, bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany, and cHochschule Furtwangen (HFU), Fakultät Medical and Life Sciences, Jakib-Kienzle-Strasse 17, 78054 Villingen-Schwenningen, Germany, and, Fraunhofer IZI, Perlickstrasse 1, 04103 Leipzig, Germany
*Correspondence e-mail: dei@hs-furtwangen.de

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 27 August 2016; accepted 29 August 2016; online 9 September 2016)

In the title compound, C20H11F2N5O, the central 13-membered ring system (r.m.s. deviation = 0.028 Å) makes a dihedral angle of 53.13 (7)° with the di­fluoro­phenyl ring and 79.98 (7)° with the pyridine ring. The crystal packing features aromatic ππ inter­actions between the 13-membered rings [shortest distance between ring centroids = 3.5682 (8) Å].

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Several benzimidazole-based compounds show anti-cancer activity (Thomas et al., 2007[Thomas, H. D., Calabrese, C. R., Batey, M. A., Canan, S., Hostomsky, Z., Kyle, S., Maegley, K. A., Newell, D. R., Skalitzky, D., Wang, L. Z., Webber, S. E. & Curtin, N. J. (2007). Mol. Cancer Ther. 6, 945-956.]) and some of them exhibit cytotoxic effects against a panel of human cancer cell lines (Refaat, 2010[Refaat, H. M. (2010). Eur. J. Med. Chem. 45, 2949-2956.]). For example, benzimidazole-4,7-diones exhibit cytotoxicity against colon, breast and lung cell lines (Gellis et al., 2008[Gellis, A., Kovacic, H., Boufatah, N. & Vanelle, P. (2008). Eur. J. Med. Chem. 43, 1858-1864.]). The good efficacy of imidazole-based compounds as anti-cancer agents prompted this study and the synthesis of a masked benzimidazole in a triazine ring as the new scaffold of a potential anti-cancer candidate. The tile compound is shown in Fig. 1[link]. The central 13-membered ring is almost planar (r.m.s. deviation = 0.028 Å) and makes a dihedral angle of 53.13 (7)° with the di­fluoro­phenyl ring and 79.98 (7)° to the pyridine ring. In the crystal, two mol­ecules related by a centre of inversion show a ππ inter­action: the shortest distance between the ring centroids is 3.5682 (8)°.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Synthesis and crystallization

2.1 mmol of NaH was added slowly to a solution of 2.1 mmol of ethyl-2- benzimidazolcarboxyl­ate in 20 ml dry THF and continued stirring at RT for about 20 minutes. To this flask, 2.0 mmol of N-(2,4-diflurophen­yl)-4-pyridine­carbo­hydra­zon­oyl chloride was added slowly portionwise and in parallel 0.5 ml of Et3N was added dropwise. The reaction was left stirring overnight, and it was monitored by TLC until it had finished. The solution was filtered and concentrated under vacuum. The solid residue was purified by column chromatography (hexa­ne:ethyl acetate; 2:1 then 1:1). Yield: 30%. Colourless plates were obtained from the slow evaporation of a hexa­ne/ ethyl acetate solution.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link].

Table 1
Experimental details

Crystal data
Chemical formula C20H11F2N5O
Mr 375.34
Crystal system, space group Monoclinic, C2/c
Temperature (K) 193
a, b, c (Å) 27.1174 (13), 10.1914 (3), 11.9292 (6)
β (°) 94.075 (4)
V3) 3288.5 (2)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.11
Crystal size (mm) 0.25 × 0.20 × 0.06
 
Data collection
Diffractometer Stoe IPDS 2T
No. of measured, independent and observed [I > 2σ(I)] reflections 8967, 4043, 2985
Rint 0.023
(sin θ/λ)max−1) 0.666
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.098, 1.06
No. of reflections 4043
No. of parameters 253
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.23, −0.22
Computer programs: X-AREA and X-RED32 (Stoe & Cie, 2006[Stoe & Cie (2006). X-AREA and X-RED32. Stoe & Cie, Darmstadt, Germany.]), SIR2004 (Altomare et al., 1995[Altomare, A., Burla, M. C., Cascarano, G., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G. & Polidori, G. (1995). J. Appl. Cryst. 28, 842-846.]) and SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]).

Structural data


Computing details top

Data collection: X-AREA (Stoe & Cie, 2006); cell refinement: X-AREA (Stoe & Cie, 2006); data reduction: X-RED32 (Stoe & Cie, 2006); program(s) used to solve structure: SIR2004 (Altomare et al., 1995); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015).

3-(2,4-Difluorophenyl)-1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]triazin-4(3H)-one top
Crystal data top
C20H11F2N5OF(000) = 1536
Mr = 375.34Dx = 1.516 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
a = 27.1174 (13) ÅCell parameters from 8710 reflections
b = 10.1914 (3) Åθ = 2.1–28.3°
c = 11.9292 (6) ŵ = 0.11 mm1
β = 94.075 (4)°T = 193 K
V = 3288.5 (2) Å3Plate, colourless
Z = 80.25 × 0.20 × 0.06 mm
Data collection top
Stoe IPDS 2T
diffractometer
2985 reflections with I > 2σ(I)
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focusRint = 0.023
Detector resolution: 6.67 pixels mm-1θmax = 28.3°, θmin = 2.7°
rotation method scansh = 3636
8967 measured reflectionsk = 1312
4043 independent reflectionsl = 1315
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.098 w = 1/[σ2(Fo2) + (0.0433P)2 + 1.3818P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
4043 reflectionsΔρmax = 0.23 e Å3
253 parametersΔρmin = 0.22 e Å3
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
xyzUiso*/Ueq
N10.66970 (4)0.29698 (11)0.47943 (9)0.0261 (2)
C10.63343 (4)0.25857 (13)0.39840 (11)0.0264 (3)
N20.60540 (4)0.15937 (11)0.41154 (9)0.0285 (2)
N30.61157 (4)0.08983 (11)0.51134 (9)0.0284 (2)
C40.64512 (5)0.11782 (13)0.60141 (11)0.0284 (3)
C50.67531 (4)0.23382 (13)0.58282 (11)0.0277 (3)
N60.70939 (4)0.28491 (12)0.65223 (10)0.0321 (3)
C70.72797 (5)0.38863 (14)0.59241 (12)0.0307 (3)
C80.76485 (5)0.47860 (15)0.62792 (13)0.0372 (3)
H80.78130.47330.70080.045*
C90.77631 (5)0.57509 (15)0.55318 (15)0.0410 (4)
H90.80100.63770.57540.049*
C100.75252 (5)0.58334 (15)0.44541 (14)0.0391 (3)
H100.76160.65140.39650.047*
C110.71615 (5)0.49545 (14)0.40798 (12)0.0336 (3)
H110.70020.50060.33450.040*
C120.70418 (5)0.39889 (13)0.48411 (11)0.0282 (3)
C130.62513 (5)0.33508 (13)0.29263 (11)0.0273 (3)
C140.64386 (5)0.29223 (15)0.19487 (12)0.0350 (3)
H140.66230.21310.19340.042*
C150.63516 (6)0.36720 (16)0.09878 (12)0.0383 (3)
H150.64890.33790.03210.046*
N160.60912 (5)0.47670 (14)0.09364 (11)0.0403 (3)
C170.59074 (7)0.51542 (19)0.18872 (15)0.0525 (4)
H170.57150.59340.18690.063*
C180.59783 (7)0.44954 (17)0.28996 (13)0.0474 (4)
H180.58430.48210.35580.057*
C190.58143 (5)0.02544 (13)0.51111 (11)0.0291 (3)
C200.58144 (5)0.11194 (15)0.42175 (12)0.0354 (3)
H200.60290.09730.36340.042*
C210.55029 (6)0.21993 (16)0.41718 (14)0.0439 (4)
H210.54980.27950.35580.053*
C220.52009 (6)0.23884 (16)0.50342 (15)0.0446 (4)
C230.51848 (5)0.15508 (17)0.59252 (14)0.0424 (4)
H230.49700.17040.65070.051*
C240.54937 (5)0.04707 (15)0.59455 (12)0.0335 (3)
F250.48935 (4)0.34381 (11)0.49899 (11)0.0706 (4)
F260.54621 (3)0.04138 (10)0.67697 (7)0.0446 (2)
O270.64870 (3)0.05067 (10)0.68590 (8)0.0350 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0272 (5)0.0265 (5)0.0244 (5)0.0003 (4)0.0002 (4)0.0006 (4)
C10.0274 (6)0.0285 (6)0.0231 (6)0.0014 (5)0.0006 (4)0.0004 (5)
N20.0322 (5)0.0295 (6)0.0232 (5)0.0017 (4)0.0024 (4)0.0043 (4)
N30.0305 (5)0.0294 (6)0.0246 (5)0.0027 (4)0.0020 (4)0.0049 (4)
C40.0273 (6)0.0316 (7)0.0260 (6)0.0030 (5)0.0002 (5)0.0022 (5)
C50.0281 (6)0.0309 (7)0.0239 (6)0.0023 (5)0.0007 (5)0.0018 (5)
N60.0304 (5)0.0342 (6)0.0309 (6)0.0010 (5)0.0033 (4)0.0011 (5)
C70.0276 (6)0.0312 (7)0.0331 (7)0.0012 (5)0.0005 (5)0.0035 (6)
C80.0305 (7)0.0382 (8)0.0423 (8)0.0027 (6)0.0022 (6)0.0080 (6)
C90.0317 (7)0.0364 (8)0.0551 (10)0.0067 (6)0.0042 (6)0.0104 (7)
C100.0384 (7)0.0322 (7)0.0479 (9)0.0058 (6)0.0117 (6)0.0025 (6)
C110.0353 (7)0.0318 (7)0.0340 (7)0.0011 (5)0.0064 (5)0.0005 (6)
C120.0262 (6)0.0274 (6)0.0312 (7)0.0002 (5)0.0032 (5)0.0045 (5)
C130.0299 (6)0.0276 (6)0.0241 (6)0.0033 (5)0.0003 (5)0.0018 (5)
C140.0399 (7)0.0339 (7)0.0319 (7)0.0021 (6)0.0064 (6)0.0027 (6)
C150.0462 (8)0.0424 (8)0.0269 (7)0.0042 (6)0.0073 (6)0.0008 (6)
N160.0474 (7)0.0429 (7)0.0304 (6)0.0012 (6)0.0008 (5)0.0090 (6)
C170.0697 (11)0.0496 (10)0.0390 (9)0.0248 (9)0.0088 (8)0.0120 (8)
C180.0680 (11)0.0455 (9)0.0298 (8)0.0211 (8)0.0111 (7)0.0063 (7)
C190.0280 (6)0.0296 (6)0.0288 (7)0.0022 (5)0.0041 (5)0.0046 (5)
C200.0370 (7)0.0356 (7)0.0329 (7)0.0001 (6)0.0020 (5)0.0016 (6)
C210.0504 (9)0.0349 (8)0.0447 (9)0.0032 (7)0.0087 (7)0.0038 (7)
C220.0416 (8)0.0368 (8)0.0535 (10)0.0137 (6)0.0116 (7)0.0114 (7)
C230.0339 (7)0.0515 (9)0.0410 (8)0.0109 (7)0.0033 (6)0.0141 (7)
C240.0308 (6)0.0395 (8)0.0294 (7)0.0007 (6)0.0030 (5)0.0034 (6)
F250.0691 (7)0.0532 (7)0.0871 (9)0.0348 (6)0.0104 (6)0.0085 (6)
F260.0385 (4)0.0609 (6)0.0350 (5)0.0032 (4)0.0062 (3)0.0062 (4)
O270.0350 (5)0.0400 (6)0.0292 (5)0.0021 (4)0.0036 (4)0.0097 (4)
Geometric parameters (Å, º) top
N1—C11.3857 (16)C13—C141.3759 (19)
N1—C51.3900 (17)C13—C181.381 (2)
N1—C121.3958 (16)C14—C151.384 (2)
C1—N21.2810 (17)C14—H140.9500
C1—C131.4867 (18)C15—N161.320 (2)
N2—N31.3854 (15)C15—H150.9500
N3—C41.3874 (16)N16—C171.331 (2)
N3—C191.4310 (17)C17—C181.383 (2)
C4—O271.2165 (16)C17—H170.9500
C4—C51.4637 (19)C18—H180.9500
C5—N61.3047 (16)C19—C201.383 (2)
N6—C71.3898 (19)C19—C241.385 (2)
C7—C81.4000 (19)C20—C211.386 (2)
C7—C121.4064 (19)C20—H200.9500
C8—C91.378 (2)C21—C221.373 (3)
C8—H80.9500C21—H210.9500
C9—C101.399 (2)C22—F251.3550 (17)
C9—H90.9500C22—C231.366 (3)
C10—C111.383 (2)C23—C241.383 (2)
C10—H100.9500C23—H230.9500
C11—C121.393 (2)C24—F261.3412 (17)
C11—H110.9500
C1—N1—C5121.03 (11)C14—C13—C18118.57 (13)
C1—N1—C12132.71 (11)C14—C13—C1120.68 (12)
C5—N1—C12106.17 (10)C18—C13—C1120.74 (12)
N2—C1—N1122.38 (12)C13—C14—C15118.39 (14)
N2—C1—C13117.54 (11)C13—C14—H14120.8
N1—C1—C13120.06 (11)C15—C14—H14120.8
C1—N2—N3118.19 (10)N16—C15—C14124.37 (14)
N2—N3—C4126.36 (11)N16—C15—H15117.8
N2—N3—C19112.60 (10)C14—C15—H15117.8
C4—N3—C19120.89 (11)C15—N16—C17116.28 (13)
O27—C4—N3122.36 (12)N16—C17—C18124.27 (16)
O27—C4—C5124.57 (12)N16—C17—H17117.9
N3—C4—C5113.06 (11)C18—C17—H17117.9
N6—C5—N1113.96 (12)C13—C18—C17118.11 (15)
N6—C5—C4127.21 (12)C13—C18—H18120.9
N1—C5—C4118.78 (11)C17—C18—H18120.9
C5—N6—C7104.12 (11)C20—C19—C24119.14 (13)
N6—C7—C8128.32 (13)C20—C19—N3119.56 (12)
N6—C7—C12111.64 (11)C24—C19—N3121.12 (13)
C8—C7—C12120.03 (13)C19—C20—C21120.19 (14)
C9—C8—C7117.44 (14)C19—C20—H20119.9
C9—C8—H8121.3C21—C20—H20119.9
C7—C8—H8121.3C22—C21—C20118.43 (15)
C8—C9—C10121.79 (14)C22—C21—H21120.8
C8—C9—H9119.1C20—C21—H21120.8
C10—C9—H9119.1F25—C22—C23118.03 (16)
C11—C10—C9121.98 (14)F25—C22—C21118.65 (16)
C11—C10—H10119.0C23—C22—C21123.29 (14)
C9—C10—H10119.0C22—C23—C24117.26 (15)
C10—C11—C12116.17 (14)C22—C23—H23121.4
C10—C11—H11121.9C24—C23—H23121.4
C12—C11—H11121.9F26—C24—C23118.53 (13)
C11—C12—N1133.32 (12)F26—C24—C19119.74 (13)
C11—C12—C7122.58 (12)C23—C24—C19121.65 (14)
N1—C12—C7104.10 (11)
C5—N1—C1—N24.15 (19)C5—N1—C12—C70.28 (13)
C12—N1—C1—N2179.67 (13)N6—C7—C12—C11179.80 (12)
C5—N1—C1—C13174.45 (12)C8—C7—C12—C110.8 (2)
C12—N1—C1—C131.7 (2)N6—C7—C12—N10.27 (15)
N1—C1—N2—N30.81 (19)C8—C7—C12—N1178.71 (12)
C13—C1—N2—N3177.82 (11)N2—C1—C13—C1480.58 (16)
C1—N2—N3—C41.05 (19)N1—C1—C13—C14100.75 (15)
C1—N2—N3—C19174.38 (12)N2—C1—C13—C1898.39 (17)
N2—N3—C4—O27179.03 (13)N1—C1—C13—C1880.27 (17)
C19—N3—C4—O273.9 (2)C18—C13—C14—C151.1 (2)
N2—N3—C4—C50.36 (18)C1—C13—C14—C15179.89 (13)
C19—N3—C4—C5175.44 (12)C13—C14—C15—N161.4 (2)
C1—N1—C5—N6176.87 (12)C14—C15—N16—C170.4 (2)
C12—N1—C5—N60.21 (15)C15—N16—C17—C180.8 (3)
C1—N1—C5—C45.47 (18)C14—C13—C18—C170.0 (2)
C12—N1—C5—C4177.45 (11)C1—C13—C18—C17179.04 (16)
O27—C4—C5—N61.5 (2)N16—C17—C18—C131.0 (3)
N3—C4—C5—N6179.17 (13)N2—N3—C19—C2049.73 (16)
O27—C4—C5—N1175.86 (13)C4—N3—C19—C20125.98 (14)
N3—C4—C5—N13.51 (17)N2—N3—C19—C24125.31 (13)
N1—C5—N6—C70.04 (15)C4—N3—C19—C2458.98 (17)
C4—C5—N6—C7177.38 (13)C24—C19—C20—C211.1 (2)
C5—N6—C7—C8178.73 (14)N3—C19—C20—C21176.22 (13)
C5—N6—C7—C120.15 (15)C19—C20—C21—C220.5 (2)
N6—C7—C8—C9178.81 (14)C20—C21—C22—F25179.60 (14)
C12—C7—C8—C90.0 (2)C20—C21—C22—C231.4 (2)
C7—C8—C9—C100.4 (2)F25—C22—C23—C24178.73 (13)
C8—C9—C10—C110.1 (2)C21—C22—C23—C240.5 (2)
C9—C10—C11—C120.6 (2)C22—C23—C24—F26175.62 (13)
C10—C11—C12—N1178.28 (14)C22—C23—C24—C191.2 (2)
C10—C11—C12—C71.1 (2)C20—C19—C24—F26174.80 (12)
C1—N1—C12—C113.1 (2)N3—C19—C24—F260.26 (19)
C5—N1—C12—C11179.73 (14)C20—C19—C24—C232.0 (2)
C1—N1—C12—C7176.32 (13)N3—C19—C24—C23177.06 (13)
 

Acknowledgements

BAT thanks the Palestinian research council (Ramallah) for funding.

References

First citationAltomare, A., Burla, M. C., Cascarano, G., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G. & Polidori, G. (1995). J. Appl. Cryst. 28, 842–846.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationGellis, A., Kovacic, H., Boufatah, N. & Vanelle, P. (2008). Eur. J. Med. Chem. 43, 1858–1864.  Web of Science CrossRef PubMed CAS Google Scholar
First citationRefaat, H. M. (2010). Eur. J. Med. Chem. 45, 2949–2956.  Web of Science CrossRef CAS PubMed Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationStoe & Cie (2006). X-AREA and X-RED32. Stoe & Cie, Darmstadt, Germany.  Google Scholar
First citationThomas, H. D., Calabrese, C. R., Batey, M. A., Canan, S., Hostomsky, Z., Kyle, S., Maegley, K. A., Newell, D. R., Skalitzky, D., Wang, L. Z., Webber, S. E. & Curtin, N. J. (2007). Mol. Cancer Ther. 6, 945–956.  Web of Science CrossRef PubMed CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoIUCrDATA
ISSN: 2414-3146
Follow IUCr Journals
Sign up for e-alerts
Follow IUCr on Twitter
Follow us on facebook
Sign up for RSS feeds