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

Hussain, Z.; Hussain, E.; Siddiqui, H.; Choudhary, M.I.; Yousuf, S.

doi:10.1107/S1600536813021120

organic compounds

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Volume 69| Part 9| September 2013| Page o1440

doi:10.1107/S1600536813021120

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

Zahid Hussain,^a Ejaz Hussain,^a Hina Siddiqui,^a M. Iqbal Choudhary ^a,^b and Sammer Yousuf ^a ^*

^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 ); 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

Crystal data

C₁₀H₇F₂NO
M_r = 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)
R_int = 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
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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 ); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536813021120/rz5082sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813021120/rz5082Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813021120/rz5082Isup3.cml

checkCIF report

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.

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

	Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids at the 50% probability level.
	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

C₁₀H₇F₂NO	F(000) = 400
M_r = 195.17	D_x = 1.408 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1280 reflections
a = 5.0479 (8) Å	θ = 2.4–22.9°
b = 19.738 (3) Å	µ = 0.12 mm⁻¹
c = 9.2428 (15) Å	T = 273 K
β = 91.432 (4)°	Block, colourless
V = 920.6 (3) Å³	0.38 × 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 tube	R_int = 0.022
Graphite monochromator	θ_max = 25.5°, θ_min = 2.1°
phi and ω scans	h = −6→6
5388 measured reflections	k = −23→22
1669 independent reflections	l = −10→11

Refinement top

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)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.099	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.0397P)² + 0.172P] where P = (F_o² + 2F_c²)/3
1669 reflections	(Δ/σ)_max < 0.001
135 parameters	Δρ_max = 0.13 e Å⁻³
0 restraints	Δρ_min = −0.15 e Å⁻³

Crystal data top

C₁₀H₇F₂NO	V = 920.6 (3) Å³
M_r = 195.17	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 5.0479 (8) Å	µ = 0.12 mm⁻¹
b = 19.738 (3) Å	T = 273 K
c = 9.2428 (15) Å	0.38 × 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 reflections	R_int = 0.022
1669 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.099	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	Δρ_max = 0.13 e Å⁻³
1669 reflections	Δρ_min = −0.15 e Å⁻³
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

	x	y	z	U_iso*/U_eq
F1	0.4706 (2)	0.66642 (6)	0.01184 (13)	0.0784 (4)
F2	1.1590 (2)	0.68247 (6)	−0.31627 (13)	0.0808 (4)
O1	1.0617 (2)	0.56728 (6)	−0.15774 (16)	0.0689 (4)
N1	0.6219 (3)	0.55850 (7)	−0.17077 (17)	0.0520 (4)
C1	0.6337 (3)	0.70378 (9)	−0.06950 (19)	0.0533 (5)
C2	0.6133 (4)	0.77291 (10)	−0.0635 (2)	0.0670 (6)
H2A	0.4884	0.7934	−0.0055	0.080*
C3	0.7807 (4)	0.81150 (10)	−0.1445 (2)	0.0690 (6)
H3A	0.7685	0.8585	−0.1419	0.083*
C4	0.9655 (4)	0.78117 (10)	−0.2290 (2)	0.0664 (5)
H4A	1.0802	0.8071	−0.2835	0.080*
C5	0.9778 (3)	0.71209 (9)	−0.2314 (2)	0.0546 (5)
C6	0.8147 (3)	0.66992 (8)	−0.15372 (17)	0.0453 (4)
C7	0.8430 (3)	0.59431 (9)	−0.16021 (17)	0.0475 (4)
C8	0.6276 (4)	0.48497 (9)	−0.1809 (2)	0.0607 (5)
H8A	0.4535	0.4673	−0.1599	0.073*
H8B	0.7519	0.4674	−0.1085	0.073*
C9	0.7041 (4)	0.46128 (9)	−0.3233 (2)	0.0621 (5)
C10	0.7642 (5)	0.44382 (12)	−0.4380 (3)	0.0880 (7)
H1	0.475 (4)	0.5775 (9)	−0.1715 (19)	0.061 (6)*
H2	0.817 (5)	0.4327 (13)	−0.524 (3)	0.120 (10)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0691 (7)	0.0792 (8)	0.0889 (9)	−0.0091 (6)	0.0395 (6)	−0.0161 (6)
F2	0.0727 (7)	0.0810 (8)	0.0907 (9)	−0.0041 (6)	0.0418 (7)	−0.0052 (6)
O1	0.0315 (6)	0.0655 (8)	0.1096 (11)	0.0057 (5)	0.0013 (6)	−0.0028 (7)
N1	0.0316 (7)	0.0521 (9)	0.0726 (11)	0.0022 (6)	0.0071 (7)	−0.0047 (7)
C1	0.0412 (9)	0.0628 (11)	0.0559 (11)	−0.0019 (8)	0.0054 (8)	−0.0104 (9)
C2	0.0543 (10)	0.0674 (13)	0.0794 (14)	0.0088 (9)	0.0033 (10)	−0.0230 (10)
C3	0.0648 (12)	0.0532 (11)	0.0885 (16)	0.0037 (9)	−0.0073 (11)	−0.0048 (10)
C4	0.0604 (11)	0.0634 (12)	0.0753 (14)	−0.0065 (9)	0.0039 (10)	0.0069 (10)
C5	0.0432 (9)	0.0629 (11)	0.0579 (11)	−0.0003 (8)	0.0070 (8)	−0.0048 (9)
C6	0.0320 (8)	0.0553 (10)	0.0484 (10)	0.0000 (7)	−0.0021 (7)	−0.0053 (8)
C7	0.0328 (8)	0.0571 (10)	0.0527 (10)	0.0014 (7)	0.0052 (7)	−0.0023 (8)
C8	0.0503 (10)	0.0529 (11)	0.0794 (14)	−0.0025 (8)	0.0094 (9)	0.0042 (9)
C9	0.0579 (11)	0.0451 (10)	0.0835 (16)	0.0055 (8)	0.0048 (11)	−0.0031 (10)
C10	0.1032 (19)	0.0689 (15)	0.092 (2)	0.0121 (12)	0.0132 (16)	−0.0128 (14)

Geometric parameters (Å, º) top

F1—C1	1.3482 (19)	C3—H3A	0.9300
F2—C5	1.3530 (18)	C4—C5	1.365 (3)
O1—C7	1.2256 (17)	C4—H4A	0.9300
N1—C7	1.323 (2)	C5—C6	1.384 (2)
N1—C8	1.455 (2)	C6—C7	1.501 (2)
N1—H1	0.830 (19)	C8—C9	1.458 (3)
C1—C2	1.370 (3)	C8—H8A	0.9700
C1—C6	1.387 (2)	C8—H8B	0.9700
C2—C3	1.374 (3)	C9—C10	1.162 (3)
C2—H2A	0.9300	C10—H2	0.87 (3)
C3—C4	1.369 (3)

C7—N1—C8	121.31 (15)	F2—C5—C6	117.42 (16)
C7—N1—H1	120.7 (13)	C4—C5—C6	124.38 (16)
C8—N1—H1	118.0 (13)	C5—C6—C1	114.22 (16)
F1—C1—C2	118.34 (15)	C5—C6—C7	121.27 (14)
F1—C1—C6	118.01 (16)	C1—C6—C7	124.49 (15)
C2—C1—C6	123.65 (17)	O1—C7—N1	121.78 (16)
C1—C2—C3	118.85 (17)	O1—C7—C6	121.24 (14)
C1—C2—H2A	120.6	N1—C7—C6	116.97 (13)
C3—C2—H2A	120.6	N1—C8—C9	112.60 (15)
C4—C3—C2	120.37 (18)	N1—C8—H8A	109.1
C4—C3—H3A	119.8	C9—C8—H8A	109.1
C2—C3—H3A	119.8	N1—C8—H8B	109.1
C5—C4—C3	118.53 (18)	C9—C8—H8B	109.1
C5—C4—H4A	120.7	H8A—C8—H8B	107.8
C3—C4—H4A	120.7	C10—C9—C8	178.5 (2)
F2—C5—C4	118.19 (16)	C9—C10—H2	176.4 (19)

F1—C1—C2—C3	179.19 (17)	C2—C1—C6—C5	0.6 (3)
C6—C1—C2—C3	−0.2 (3)	F1—C1—C6—C7	−0.3 (2)
C1—C2—C3—C4	−0.4 (3)	C2—C1—C6—C7	179.05 (18)
C2—C3—C4—C5	0.4 (3)	C8—N1—C7—O1	−0.4 (3)
C3—C4—C5—F2	179.33 (17)	C8—N1—C7—C6	178.68 (15)
C3—C4—C5—C6	0.1 (3)	C5—C6—C7—O1	41.8 (2)
F2—C5—C6—C1	−179.83 (15)	C1—C6—C7—O1	−136.53 (18)
C4—C5—C6—C1	−0.6 (3)	C5—C6—C7—N1	−137.26 (17)
F2—C5—C6—C7	1.7 (2)	C1—C6—C7—N1	44.4 (2)
C4—C5—C6—C7	−179.07 (18)	C7—N1—C8—C9	−75.0 (2)
F1—C1—C6—C5	−178.74 (15)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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+3/2, z+1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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)	164.3

Symmetry codes: (i) x−1, y, z; (ii) x−1, −y+3/2, z+1/2.

References

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CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 69| Part 9| September 2013| Page o1440

doi:10.1107/S1600536813021120

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