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

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ISSN: 2056-9890

2,6-Di­fluoro-N-(prop-2-yn­yl)benzamide

aH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan, and bDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jaddhah, Saudi Arabia
*Correspondence e-mail: dr.sammer.yousuf@gmail.com

(Received 21 July 2013; accepted 29 July 2013; online 17 August 2013)

In the mol­ecule of the title di­fluoro­benzamide derivative, C10H7F2NO, the angle formed by the least-squares mean line through the prop-2-ynyl group [maximum deviation = 0.011 (3) Å] and the normal to the benzene ring is 59.03 (7)°. In the crystal, mol­ecules are linked via N—H⋯O and C—H⋯F hydrogen bonds into layers parallel to the ac plane.

Related literature

For the biological activity of di­fluoro­benzamide derivatives, see: Chang et al. (2002[Chang, Y. Y., Chung, Y. H., Lee, C. W., Lee, H. D., Lee, J. S., Park, W. J. & Yang, W. Y. (2002). Patent AU2002345403.]); Kees et al. (1989[Kees, K. L., Cheeseman, R. S., Prozialeck, D. H. & Steiner, K. E. (1989). J. Med. Chem., 32, 11-13.]); Ragavan et al. (2010[Ragavan, R. V., Vijayakumar, V. & Kumari, S. N. (2010). Eur. J. Med. Chem. 43, 1173-1180.]); Carmellino et al. (1994[Carmellino, M. L., Pagani, G., Pregnolato, M., Terreni, M. & Pastoni, F. (1994). Eur. J. Med. Chem. 29, 743-751.]); Rauko et al. (2001[Rauko, P., Novotny, L., Dovinova, I., Hunakova, L., Szekeres, T. & Jayaram, H. N. (2001). Eur. J. Pharm. Sci. 12, 387-394.]). For the crystal structure of a related compound, see: Fun et al. (2010[Fun, H.-K., Goh, J. H., Gowda, J., Khader, A. M. & Kalluraya, B. (2010). Acta Cryst. E66, o3192.]).

[Scheme 1]

Experimental

Crystal data
  • C10H7F2NO

  • Mr = 195.17

  • Monoclinic, P 21 /c

  • a = 5.0479 (8) Å

  • b = 19.738 (3) Å

  • c = 9.2428 (15) Å

  • β = 91.432 (4)°

  • V = 920.6 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.12 mm−1

  • T = 273 K

  • 0.38 × 0.17 × 0.10 mm

Data collection
  • Bruker SMART APEX CCD diffractometer

  • 5388 measured reflections

  • 1669 independent reflections

  • 1283 reflections with I > 2σ(I)

  • Rint = 0.022

Refinement
  • R[F2 > 2σ(F2)] = 0.040

  • wR(F2) = 0.099

  • S = 1.03

  • 1669 reflections

  • 135 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.13 e Å−3

  • Δρmin = −0.15 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O1i 0.83 (2) 2.10 (2) 2.8387 (19) 147.4 (17)
C2—H2A⋯F2ii 0.93 2.49 3.394 (2) 164
Symmetry codes: (i) x-1, y, z; (ii) [x-1, -y+{\script{3\over 2}}, z+{\script{1\over 2}}].

Data collection: SMART (Bruker, 2000[Bruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2000[Bruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Some difluorobenzamide derivatives are known to have excellent antiviral and antiproliferation activities (Chang et al., 2002). They are also well known for their anti-diabetic (Kees et al., 1989), anti-fungal (Carmellino et al., 1994), anti-bacterial (Ragavan et al., 2010) and anti-cancer (Rauko et al., 2001) properties.

The structure of the title fluorinated benzamide derivative (Fig. 1) is distinctly similar to that of the previously reported compound N-(4-cyanophenyl)-2,6-difluorobenzamide (Fun et al., 2010), with the difference that the N-(4-cyanophenyl) moiety is replaced by a prop-2-ynyl chain (C8–C10). The observed distance for the C9—C10 acetylene bond is 1.162 (3) Å. The angle between the least-squares mean line through the prop-2-ynyl group (maximum deviation 0.011 (3) Å for atom C9) and the normal to the benzene ring is 59.03 (7)°. The molecule has no prominent intramolecular non-covalent interactions. In the crystal, molecules are linked via C—H···F (Fig. 2) and N—H···O hydrogen bonds (Table 1) to form layers parallel to the ac plane. No π···π stacking interactions are observed.

Related literature top

For the biological activity of difluorobenzamide derivatives, see: Chang et al. (2002); Kees et al. (1989); Ragavan et al. (2010); Carmellino et al. (1994); Rauko et al. (2001). For the crystal structure of a related compound, see: Fun et al. (2010).

Experimental top

Prop-2-yn-1-amine (36.3 mmol, 1.0 eq) was dissolved in dichloromethane (20 mL) in a round bottom flask and kept at 0 °C. Diisopropylethylamine (DIPEA) (145 mmol, 4.0 eq) and 2,6-diflurobenzoyl chloride (54.4 mmol, 1.5 eq) were then added and the mixture stirred for 1.5 h. Progress of the reaction was monitored by thin layer chromatography. On completion of the reaction the mixture was dissolved in water and extracted with diethyl ether (2 × 25 mL). The organic layer was dried with anhydrous Na2SO4 and concentrated to obtain a crude gummy product. The crude product was finally purified by flash column chromatography by using EtOAc/hexane (3:7 v/v) as eluent to afford the title compound in 77% yield. Crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution.

Refinement top

The amide and acetylenic H atoms were located in a difference Fourier map and refined freely. All other H atoms were placed at calculated positions and refined as riding, with C—H = 0.93–0.97 Å and with Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids at the 50% probability level.
[Figure 2] Fig. 2. Packing diagram of the title compound showing intermolecular hydrogen bonding as dashed lines.
2,6-Difluoro-N-(prop-2-ynyl)benzamide top
Crystal data top
C10H7F2NOF(000) = 400
Mr = 195.17Dx = 1.408 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 1280 reflections
a = 5.0479 (8) Åθ = 2.4–22.9°
b = 19.738 (3) ŵ = 0.12 mm1
c = 9.2428 (15) ÅT = 273 K
β = 91.432 (4)°Block, colourless
V = 920.6 (3) Å30.38 × 0.17 × 0.10 mm
Z = 4
Data collection top
Bruker SMART APEX CCD
diffractometer
1283 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.022
Graphite monochromatorθmax = 25.5°, θmin = 2.1°
phi and ω scansh = 66
5388 measured reflectionsk = 2322
1669 independent reflectionsl = 1011
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.099H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0397P)2 + 0.172P]
where P = (Fo2 + 2Fc2)/3
1669 reflections(Δ/σ)max < 0.001
135 parametersΔρmax = 0.13 e Å3
0 restraintsΔρmin = 0.15 e Å3
Crystal data top
C10H7F2NOV = 920.6 (3) Å3
Mr = 195.17Z = 4
Monoclinic, P21/cMo Kα radiation
a = 5.0479 (8) ŵ = 0.12 mm1
b = 19.738 (3) ÅT = 273 K
c = 9.2428 (15) Å0.38 × 0.17 × 0.10 mm
β = 91.432 (4)°
Data collection top
Bruker SMART APEX CCD
diffractometer
1283 reflections with I > 2σ(I)
5388 measured reflectionsRint = 0.022
1669 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0400 restraints
wR(F2) = 0.099H atoms treated by a mixture of independent and constrained refinement
S = 1.03Δρmax = 0.13 e Å3
1669 reflectionsΔρmin = 0.15 e Å3
135 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.4706 (2)0.66642 (6)0.01184 (13)0.0784 (4)
F21.1590 (2)0.68247 (6)0.31627 (13)0.0808 (4)
O11.0617 (2)0.56728 (6)0.15774 (16)0.0689 (4)
N10.6219 (3)0.55850 (7)0.17077 (17)0.0520 (4)
C10.6337 (3)0.70378 (9)0.06950 (19)0.0533 (5)
C20.6133 (4)0.77291 (10)0.0635 (2)0.0670 (6)
H2A0.48840.79340.00550.080*
C30.7807 (4)0.81150 (10)0.1445 (2)0.0690 (6)
H3A0.76850.85850.14190.083*
C40.9655 (4)0.78117 (10)0.2290 (2)0.0664 (5)
H4A1.08020.80710.28350.080*
C50.9778 (3)0.71209 (9)0.2314 (2)0.0546 (5)
C60.8147 (3)0.66992 (8)0.15372 (17)0.0453 (4)
C70.8430 (3)0.59431 (9)0.16021 (17)0.0475 (4)
C80.6276 (4)0.48497 (9)0.1809 (2)0.0607 (5)
H8A0.45350.46730.15990.073*
H8B0.75190.46740.10850.073*
C90.7041 (4)0.46128 (9)0.3233 (2)0.0621 (5)
C100.7642 (5)0.44382 (12)0.4380 (3)0.0880 (7)
H10.475 (4)0.5775 (9)0.1715 (19)0.061 (6)*
H20.817 (5)0.4327 (13)0.524 (3)0.120 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0691 (7)0.0792 (8)0.0889 (9)0.0091 (6)0.0395 (6)0.0161 (6)
F20.0727 (7)0.0810 (8)0.0907 (9)0.0041 (6)0.0418 (7)0.0052 (6)
O10.0315 (6)0.0655 (8)0.1096 (11)0.0057 (5)0.0013 (6)0.0028 (7)
N10.0316 (7)0.0521 (9)0.0726 (11)0.0022 (6)0.0071 (7)0.0047 (7)
C10.0412 (9)0.0628 (11)0.0559 (11)0.0019 (8)0.0054 (8)0.0104 (9)
C20.0543 (10)0.0674 (13)0.0794 (14)0.0088 (9)0.0033 (10)0.0230 (10)
C30.0648 (12)0.0532 (11)0.0885 (16)0.0037 (9)0.0073 (11)0.0048 (10)
C40.0604 (11)0.0634 (12)0.0753 (14)0.0065 (9)0.0039 (10)0.0069 (10)
C50.0432 (9)0.0629 (11)0.0579 (11)0.0003 (8)0.0070 (8)0.0048 (9)
C60.0320 (8)0.0553 (10)0.0484 (10)0.0000 (7)0.0021 (7)0.0053 (8)
C70.0328 (8)0.0571 (10)0.0527 (10)0.0014 (7)0.0052 (7)0.0023 (8)
C80.0503 (10)0.0529 (11)0.0794 (14)0.0025 (8)0.0094 (9)0.0042 (9)
C90.0579 (11)0.0451 (10)0.0835 (16)0.0055 (8)0.0048 (11)0.0031 (10)
C100.1032 (19)0.0689 (15)0.092 (2)0.0121 (12)0.0132 (16)0.0128 (14)
Geometric parameters (Å, º) top
F1—C11.3482 (19)C3—H3A0.9300
F2—C51.3530 (18)C4—C51.365 (3)
O1—C71.2256 (17)C4—H4A0.9300
N1—C71.323 (2)C5—C61.384 (2)
N1—C81.455 (2)C6—C71.501 (2)
N1—H10.830 (19)C8—C91.458 (3)
C1—C21.370 (3)C8—H8A0.9700
C1—C61.387 (2)C8—H8B0.9700
C2—C31.374 (3)C9—C101.162 (3)
C2—H2A0.9300C10—H20.87 (3)
C3—C41.369 (3)
C7—N1—C8121.31 (15)F2—C5—C6117.42 (16)
C7—N1—H1120.7 (13)C4—C5—C6124.38 (16)
C8—N1—H1118.0 (13)C5—C6—C1114.22 (16)
F1—C1—C2118.34 (15)C5—C6—C7121.27 (14)
F1—C1—C6118.01 (16)C1—C6—C7124.49 (15)
C2—C1—C6123.65 (17)O1—C7—N1121.78 (16)
C1—C2—C3118.85 (17)O1—C7—C6121.24 (14)
C1—C2—H2A120.6N1—C7—C6116.97 (13)
C3—C2—H2A120.6N1—C8—C9112.60 (15)
C4—C3—C2120.37 (18)N1—C8—H8A109.1
C4—C3—H3A119.8C9—C8—H8A109.1
C2—C3—H3A119.8N1—C8—H8B109.1
C5—C4—C3118.53 (18)C9—C8—H8B109.1
C5—C4—H4A120.7H8A—C8—H8B107.8
C3—C4—H4A120.7C10—C9—C8178.5 (2)
F2—C5—C4118.19 (16)C9—C10—H2176.4 (19)
F1—C1—C2—C3179.19 (17)C2—C1—C6—C50.6 (3)
C6—C1—C2—C30.2 (3)F1—C1—C6—C70.3 (2)
C1—C2—C3—C40.4 (3)C2—C1—C6—C7179.05 (18)
C2—C3—C4—C50.4 (3)C8—N1—C7—O10.4 (3)
C3—C4—C5—F2179.33 (17)C8—N1—C7—C6178.68 (15)
C3—C4—C5—C60.1 (3)C5—C6—C7—O141.8 (2)
F2—C5—C6—C1179.83 (15)C1—C6—C7—O1136.53 (18)
C4—C5—C6—C10.6 (3)C5—C6—C7—N1137.26 (17)
F2—C5—C6—C71.7 (2)C1—C6—C7—N144.4 (2)
C4—C5—C6—C7179.07 (18)C7—N1—C8—C975.0 (2)
F1—C1—C6—C5178.74 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.83 (2)2.10 (2)2.8387 (19)147.4 (17)
C2—H2A···F2ii0.932.493.394 (2)164
Symmetry codes: (i) x1, y, z; (ii) x1, y+3/2, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.83 (2)2.10 (2)2.8387 (19)147.4 (17)
C2—H2A···F2ii0.932.493.394 (2)164.3
Symmetry codes: (i) x1, y, z; (ii) x1, y+3/2, z+1/2.
 

References

First citationBruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationCarmellino, M. L., Pagani, G., Pregnolato, M., Terreni, M. & Pastoni, F. (1994). Eur. J. Med. Chem. 29, 743–751.  CrossRef CAS Web of Science
First citationChang, Y. Y., Chung, Y. H., Lee, C. W., Lee, H. D., Lee, J. S., Park, W. J. & Yang, W. Y. (2002). Patent AU2002345403.
First citationFun, H.-K., Goh, J. H., Gowda, J., Khader, A. M. & Kalluraya, B. (2010). Acta Cryst. E66, o3192.  Web of Science CSD CrossRef IUCr Journals
First citationKees, K. L., Cheeseman, R. S., Prozialeck, D. H. & Steiner, K. E. (1989). J. Med. Chem., 32, 11–13.  CrossRef CAS PubMed Web of Science
First citationRagavan, R. V., Vijayakumar, V. & Kumari, S. N. (2010). Eur. J. Med. Chem. 43, 1173–1180.  Web of Science CrossRef
First citationRauko, P., Novotny, L., Dovinova, I., Hunakova, L., Szekeres, T. & Jayaram, H. N. (2001). Eur. J. Pharm. Sci. 12, 387–394.  Web of Science CrossRef PubMed CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals

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