2,2,2-Trifluoro-N-(isoquinolin-5-ylmeth-yl)acetamide.

The mol-ecular structure of the title compound at 123 K, C(12)H(9)F(3)N(2)O, presents a rotationally disordered CF(3) group. Hydrogen bonds between the amide NH group and the N atom of the isoquinoline form a chain in the b-axis direction. The packed structure forms alternate layers of isoquinoline and amide groups parallel to the ab plane.

Related literature

In the search for biologically active compounds in the area of anti-inflammatory and pain relief drugs, we have found a class of compounds that act as potent antagonists or agonists of the vanilloid VR1 receptor. These have been shown to be useful in the treatment and prevention of inflammatory and other pain conditions in mammals, see: Jetter et al. (2007 ▶, 2008 ▶); Codd et al. (2003 ▶). The title compound was prepared as a precursor for more complex compounds. For analysis of the structures of analogous naphthalenes, see: Weinstein & Leiserowitz (1980 ▶). For a discussion on disorder in crystal structures, see: Müller (2009 ▶).

Experimental

Crystal data

C12H9F3N2O

M = 254.21

Monoclinic,

a = 7.2308 (7) Å

b = 8.3498 (11) Å

c = 18.157 (2) Å

β = 90.583 (9)°

V = 1096.2 (2) Å3

Z = 4

Mo Kα radiation

μ = 0.14 mm−1

T = 123 K

0.45 × 0.12 × 0.02 mm

Data collection

Oxford Diffraction Xcalibur S diffractometer

Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007 ▶) T min = 0.717, T max = 1.000

4377 measured reflections

2071 independent reflections

1346 reflections with I > 2σ(I)

R int = 0.031

Refinement

R[F 2 > 2σ(F 2)] = 0.051

wR(F 2) = 0.133

S = 1.06

2071 reflections

191 parameters

111 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.30 e Å−3

Δρmin = −0.45 e Å−3

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809052994/tk2599sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809052994/tk2599Isup2.hkl

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

C12H9F3N2O	F(000) = 520
Mr = 254.21	Dx = 1.540 Mg m−3
Monoclinic, P21/c	Melting point = 435–438 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 7.2308 (7) Å	Cell parameters from 1879 reflections
b = 8.3498 (11) Å	θ = 2.7–30.1°
c = 18.157 (2) Å	µ = 0.14 mm−1
β = 90.583 (9)°	T = 123 K
V = 1096.2 (2) Å3	Blade, colourless
Z = 4	0.45 × 0.12 × 0.02 mm

Oxford Diffraction Xcalibur S diffractometer	2071 independent reflections
Radiation source: fine-focus sealed tube	1346 reflections with I > 2σ(I)
graphite	Rint = 0.031
Detector resolution: 16.0268 pixels mm-1	θmax = 26.0°, θmin = 2.7°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007)	k = −10→9
Tmin = 0.717, Tmax = 1.000	l = −21→22
4377 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)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.133	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0703P)2 + 0.0571P] where P = (Fo2 + 2Fc2)/3
2071 reflections	(Δ/σ)max < 0.001
191 parameters	Δρmax = 0.30 e Å−3
111 restraints	Δρmin = −0.45 e Å−3

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
F1	−0.3651 (5)	0.3984 (6)	1.0372 (2)	0.0468 (10)	0.50
F2	−0.3741 (5)	0.3253 (6)	0.92452 (18)	0.0266 (10)	0.50
F3	−0.3909 (5)	0.1505 (5)	1.0096 (3)	0.0490 (10)	0.50
F4	−0.3837 (11)	0.2632 (9)	0.9261 (3)	0.042 (2)*	0.30
F5	−0.3858 (10)	0.2219 (12)	1.0445 (4)	0.0590 (19)*	0.30
F6	−0.3263 (9)	0.4512 (6)	1.0002 (4)	0.0530 (17)*	0.30
F7	−0.3639 (12)	0.3146 (15)	1.0568 (3)	0.031 (2)*	0.20
F8	−0.3620 (17)	0.3826 (12)	0.9363 (5)	0.044 (3)*	0.20
F9	−0.3770 (13)	0.1449 (9)	0.9730 (6)	0.043 (2)*	0.20
O1	−0.0083 (3)	0.3065 (3)	1.04575 (11)	0.0574 (7)
N1	−0.0214 (3)	0.2113 (3)	0.92904 (12)	0.0269 (5)
N2	0.2036 (3)	0.5534 (3)	0.69021 (12)	0.0323 (6)
C1	−0.3025 (3)	0.2895 (3)	0.98984 (12)	0.0345 (7)
C2	−0.0925 (4)	0.2699 (3)	0.99042 (14)	0.0323 (7)
C3	0.1779 (3)	0.1840 (3)	0.92121 (13)	0.0291 (6)
H3A	0.2135	0.0859	0.9485	0.035*
H3B	0.2465	0.2752	0.9431	0.035*
C4	0.2312 (3)	0.1660 (3)	0.84124 (13)	0.0248 (6)
C5	0.2834 (3)	0.0198 (3)	0.81357 (14)	0.0285 (6)
H5	0.2895	−0.0697	0.8458	0.034*
C6	0.3287 (3)	−0.0013 (4)	0.73828 (13)	0.0297 (6)
H6	0.3651	−0.1039	0.7211	0.036*
C7	0.3203 (3)	0.1237 (3)	0.69074 (13)	0.0294 (6)
H7	0.3497	0.1090	0.6403	0.035*
C8	0.2672 (3)	0.2763 (3)	0.71693 (13)	0.0249 (6)
C9	0.2235 (3)	0.2993 (3)	0.79266 (13)	0.0230 (6)
C10	0.1718 (3)	0.4552 (3)	0.81438 (13)	0.0264 (6)
H10	0.1419	0.4768	0.8642	0.032*
C11	0.1651 (3)	0.5738 (3)	0.76334 (14)	0.0305 (6)
H11	0.1314	0.6780	0.7794	0.037*
C12	0.2528 (3)	0.4093 (4)	0.66921 (14)	0.0306 (6)
H12	0.2805	0.3935	0.6187	0.037*
H1N	−0.089 (4)	0.189 (4)	0.8928 (16)	0.038 (8)*

	U11	U22	U33	U12	U13	U23
F1	0.0389 (18)	0.068 (3)	0.0337 (18)	0.0250 (19)	0.0054 (15)	−0.022 (2)
F2	0.0278 (17)	0.020 (2)	0.0314 (19)	0.0033 (19)	0.0001 (12)	0.0036 (17)
F3	0.0405 (18)	0.048 (2)	0.058 (2)	−0.0050 (16)	0.0009 (18)	0.038 (2)
O1	0.0464 (13)	0.094 (2)	0.0313 (11)	0.0251 (12)	−0.0109 (9)	−0.0248 (12)
N1	0.0266 (11)	0.0317 (14)	0.0223 (11)	0.0007 (10)	0.0021 (9)	−0.0017 (11)
N2	0.0275 (11)	0.0318 (16)	0.0376 (13)	−0.0004 (10)	0.0000 (9)	0.0053 (12)
C1	0.0418 (16)	0.0372 (19)	0.0247 (14)	0.0078 (14)	0.0052 (11)	0.0029 (13)
C2	0.0382 (15)	0.0337 (18)	0.0250 (14)	0.0089 (13)	0.0028 (11)	0.0004 (13)
C3	0.0300 (13)	0.0301 (17)	0.0271 (13)	0.0042 (12)	0.0006 (10)	0.0016 (12)
C4	0.0197 (12)	0.0290 (17)	0.0258 (13)	0.0025 (11)	−0.0001 (9)	−0.0002 (12)
C5	0.0279 (13)	0.0236 (16)	0.0340 (14)	0.0044 (11)	0.0000 (10)	0.0032 (13)
C6	0.0286 (14)	0.0272 (16)	0.0335 (14)	0.0035 (11)	0.0035 (10)	−0.0048 (13)
C7	0.0263 (13)	0.0356 (18)	0.0263 (13)	0.0000 (12)	0.0042 (10)	−0.0055 (13)
C8	0.0203 (12)	0.0283 (15)	0.0262 (13)	−0.0023 (11)	0.0014 (9)	0.0011 (12)
C9	0.0182 (11)	0.0253 (15)	0.0255 (13)	−0.0007 (10)	−0.0007 (9)	−0.0004 (12)
C10	0.0235 (13)	0.0270 (16)	0.0286 (13)	0.0004 (11)	−0.0003 (10)	−0.0024 (12)
C11	0.0246 (13)	0.0273 (17)	0.0396 (15)	0.0002 (11)	0.0001 (10)	−0.0013 (13)
C12	0.0264 (13)	0.0371 (18)	0.0284 (13)	−0.0021 (12)	0.0013 (10)	0.0029 (13)

F1—C1	1.334 (3)	C3—H3A	0.9900
F2—C1	1.324 (4)	C3—H3B	0.9900
F3—C1	1.374 (4)	C4—C5	1.374 (4)
F4—C1	1.311 (5)	C4—C9	1.421 (4)
F5—C1	1.295 (5)	C5—C6	1.420 (3)
F6—C1	1.375 (5)	C5—H5	0.9500
F7—C1	1.316 (5)	C6—C7	1.356 (4)
F8—C1	1.314 (5)	C6—H6	0.9500
F9—C1	1.356 (5)	C7—C8	1.414 (4)
O1—C2	1.209 (3)	C7—H7	0.9500
N1—C2	1.326 (3)	C8—C12	1.412 (4)
N1—C3	1.467 (3)	C8—C9	1.427 (3)
N1—H1N	0.84 (3)	C9—C10	1.411 (4)
N2—C12	1.312 (3)	C10—C11	1.357 (4)
N2—C11	1.370 (3)	C10—H10	0.9500
C1—C2	1.527 (4)	C11—H11	0.9500
C3—C4	1.514 (3)	C12—H12	0.9500
C2—N1—C3	121.9 (2)	C4—C3—H3B	109.3
C2—N1—H1N	121 (2)	H3A—C3—H3B	108.0
C3—N1—H1N	117.2 (19)	C5—C4—C9	118.5 (2)
C12—N2—C11	117.0 (2)	C5—C4—C3	120.8 (2)
F5—C1—F4	113.3 (6)	C9—C4—C3	120.6 (2)
F8—C1—F7	118.6 (8)	C4—C5—C6	122.0 (2)
F2—C1—F1	106.9 (3)	C4—C5—H5	119.0
F8—C1—F9	103.5 (7)	C6—C5—H5	119.0
F7—C1—F9	102.3 (7)	C7—C6—C5	120.5 (3)
F2—C1—F3	104.2 (3)	C7—C6—H6	119.7
F1—C1—F3	104.2 (3)	C5—C6—H6	119.7
F5—C1—F6	105.3 (5)	C6—C7—C8	119.4 (2)
F4—C1—F6	103.3 (5)	C6—C7—H7	120.3
F5—C1—C2	114.7 (4)	C8—C7—H7	120.3
F4—C1—C2	115.1 (4)	C12—C8—C7	121.4 (2)
F8—C1—C2	112.7 (6)	C12—C8—C9	118.0 (2)
F7—C1—C2	110.8 (4)	C7—C8—C9	120.6 (2)
F2—C1—C2	114.2 (2)	C10—C9—C4	123.9 (2)
F1—C1—C2	114.4 (2)	C10—C9—C8	117.1 (2)
F9—C1—C2	107.4 (5)	C4—C9—C8	119.0 (2)
F3—C1—C2	111.9 (3)	C11—C10—C9	119.3 (2)
F6—C1—C2	103.3 (3)	C11—C10—H10	120.3
O1—C2—N1	126.5 (3)	C9—C10—H10	120.3
O1—C2—C1	118.1 (2)	C10—C11—N2	124.4 (3)
N1—C2—C1	115.3 (2)	C10—C11—H11	117.8
N1—C3—C4	111.6 (2)	N2—C11—H11	117.8
N1—C3—H3A	109.3	N2—C12—C8	124.2 (2)
C4—C3—H3A	109.3	N2—C12—H12	117.9
N1—C3—H3B	109.3	C8—C12—H12	117.9
C3—N1—C2—O1	−0.3 (5)	N1—C3—C4—C9	69.5 (3)
C3—N1—C2—C1	−179.4 (2)	C9—C4—C5—C6	−0.3 (4)
F5—C1—C2—O1	−52.4 (6)	C3—C4—C5—C6	178.1 (2)
F4—C1—C2—O1	173.4 (5)	C4—C5—C6—C7	−0.4 (4)
F8—C1—C2—O1	122.9 (6)	C5—C6—C7—C8	0.5 (4)
F7—C1—C2—O1	−12.8 (7)	C6—C7—C8—C12	−178.7 (2)
F2—C1—C2—O1	148.2 (4)	C6—C7—C8—C9	0.3 (3)
F1—C1—C2—O1	24.5 (5)	C5—C4—C9—C10	179.9 (2)
F9—C1—C2—O1	−123.8 (5)	C3—C4—C9—C10	1.5 (4)
F3—C1—C2—O1	−93.7 (4)	C5—C4—C9—C8	1.0 (3)
F6—C1—C2—O1	61.6 (4)	C3—C4—C9—C8	−177.4 (2)
F5—C1—C2—N1	126.8 (6)	C12—C8—C9—C10	−1.0 (3)
F4—C1—C2—N1	−7.4 (5)	C7—C8—C9—C10	−180.0 (2)
F8—C1—C2—N1	−57.9 (7)	C12—C8—C9—C4	178.0 (2)
F7—C1—C2—N1	166.4 (6)	C7—C8—C9—C4	−1.0 (3)
F2—C1—C2—N1	−32.7 (4)	C4—C9—C10—C11	−178.6 (2)
F1—C1—C2—N1	−156.3 (4)	C8—C9—C10—C11	0.3 (3)
F9—C1—C2—N1	55.4 (5)	C9—C10—C11—N2	0.8 (4)
F3—C1—C2—N1	85.5 (4)	C12—N2—C11—C10	−1.1 (3)
F6—C1—C2—N1	−119.2 (4)	C11—N2—C12—C8	0.3 (4)
C2—N1—C3—C4	−162.6 (2)	C7—C8—C12—N2	179.7 (2)
N1—C3—C4—C5	−108.9 (3)	C9—C8—C12—N2	0.8 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···N2i	0.84 (3)	2.05 (3)	2.847 (3)	158 (3)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯N2i	0.84 (3)	2.05 (3)	2.847 (3)	158 (3)

Symmetry code: (i) .