4-[4-(4-Fluoro-phen-yl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl-pyridinium iodide-4-[3-(4-fluoro-phen-yl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-4-yl]-1-methyl-pyridinium iodide (0.6/0.4).

The crystal structure of the title compound, C(16)H(16)FN(2)O(2) (+)·I(-), was determined as part of a study of the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The X-ray crystal structure of 4-[4-(4-fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl-pyridinium iodide showed the presence of the regioisomer 4-[3-(4-fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-4-yl]-1-methyl-pyridinium iodide. The synthesis of the former compound was achieved by reacting 4-(4-fluoro-phenyl)-3-(4-pyridyl)isoxazol-5(2H)-one after treatment with Et(3)N in dimethyl-formamide, with iodo-methane. The unexpected formation of the regioisomer could be explained by a rearrangement occurring via aziridine of the isoxazolone compound. The regioisomers have site occupancies of 0.632 (4)/0.368 (4). The two six members rings make a dihedral angle of 66.8 (2)°.

Related literature

For general background on the pharmaceutical applications of isoxazolones, see: Laughlin et al. (2005 ▶); Clark et al. (2002 ▶); Wang et al. (1998 ▶); Foster et al. (2000 ▶); Adams et al. (1998 ▶); Laufer & Wagner (2002 ▶); de Laszlo et al. (1998 ▶); Laufer et al. (2005 ▶, 2006 ▶); Revesz et al. (2000 ▶); Ohkawa et al. (2001 ▶). The aziridine rearrangement of isoxazolones was described by Nishiwaki & Saito (1971 ▶) and Sauers (1990 ▶).

Experimental

Crystal data

C15H12FN2O2 +·I−

M = 398.17

Monoclinic,

a = 10.2804 (4) Å

b = 20.5895 (9) Å

c = 7.4907 (3) Å

β = 96.8828 (14)°

V = 1574.12 (11) Å3

Z = 4

Mo Kα radiation

μ = 2.05 mm−1

T = 193 (2) K

0.52 × 0.20 × 0.08 mm

Data collection

Bruker SMART APEXII CCD diffractometer

Absorption correction: multi-scan (APEX2; Bruker, 2006 ▶) T min = 0.415, T max = 0.853

27681 measured reflections

3897 independent reflections

3369 reflections with I > 2σ(I)

R int = 0.126

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.115

S = 1.07

3897 reflections

188 parameters

H-atom parameters constrained

Δρmax = 1.60 e Å−3

Δρmin = −0.51 e Å−3

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: ORTEP (Johnson, 1968 ▶) and PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807055985/bt2577sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807055985/bt2577Isup2.hkl

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

C15H12FN2O2+·I–	F000 = 776
Mr = 398.17	Dx = 1.680 Mg m−3
Monoclinic, P21/c	Mo Kα radiation λ = 0.71069 Å
Hall symbol: -P 2ybc	Cell parameters from 6868 reflections
a = 10.2804 (4) Å	θ = 2.7–28.3º
b = 20.5895 (9) Å	µ = 2.05 mm−1
c = 7.4907 (3) Å	T = 193 (2) K
β = 96.8828 (14)º	Block, brown
V = 1574.12 (11) Å3	0.52 × 0.20 × 0.08 mm
Z = 4

Bruker APEXII CCD diffractometer	3369 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.126
T = 193(2) K	θmax = 28.4º
CCD scan	θmin = 2.0º
Absorption correction: multi-scan(APEX2; Bruker, 2006)	h = −13→13
Tmin = 0.415, Tmax = 0.853	k = −27→27
27681 measured reflections	l = −9→9
3897 independent reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040	H-atom parameters constrained
wR(F2) = 0.115	w = 1/[σ2(Fo2) + (0.0617P)2 + 2.8681P] where P = (Fo2 + 2Fc2)/3
S = 1.07	(Δ/σ)max = 0.001
3897 reflections	Δρmax = 1.60 e Å−3
188 parameters	Δρmin = −0.51 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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)
F1A	1.0107 (3)	0.20467 (16)	1.6192 (4)	0.0292 (4)	0.632 (4)
F1B	0.3217 (5)	0.1835 (3)	0.8219 (7)	0.0292 (4)	0.368 (4)
C1	0.9450 (4)	0.08719 (19)	0.9398 (5)	0.0327 (7)
C2	0.8322 (4)	0.07466 (19)	0.8261 (5)	0.0333 (7)
N3	0.8565 (3)	0.0373 (2)	0.6894 (5)	0.0458 (9)
O4	0.9887 (3)	0.02271 (16)	0.7079 (4)	0.0439 (7)
C5	1.0475 (4)	0.0546 (2)	0.8619 (6)	0.0384 (8)
C6	0.7766 (4)	0.0089 (2)	0.5375 (6)	0.0408 (9)
H6A	0.8320	−0.0168	0.4667	0.061*
H6B	0.7337	0.0435	0.4623	0.061*
H6C	0.7100	−0.0191	0.5806	0.061*
O7	1.1646 (3)	0.04901 (16)	0.8994 (5)	0.0489 (8)
C8	0.9607 (4)	0.12052 (18)	1.1149 (5)	0.0332 (8)
C9	0.8538 (4)	0.1315 (2)	1.2097 (6)	0.0359 (8)
H9	0.7687	0.1187	1.1584	0.043*
C10	0.8700 (4)	0.1609 (2)	1.3781 (6)	0.0399 (9)
H10	0.7969	0.1691	1.4412	0.048*
C11A	0.9937 (5)	0.1776 (2)	1.4501 (6)	0.0462 (9)	0.632 (4)
N11B	0.9937 (5)	0.1776 (2)	1.4501 (6)	0.0462 (9)	0.368 (4)
H11B	1.0046	0.1958	1.5571	0.055*	0.368 (4)
C12	1.1020 (4)	0.1672 (2)	1.3625 (6)	0.0458 (10)
H12	1.1868	0.1795	1.4162	0.055*
C13	1.0846 (4)	0.1386 (2)	1.1952 (6)	0.0413 (9)
H13	1.1586	0.1310	1.1333	0.050*
C15	0.6988 (4)	0.10094 (19)	0.8287 (5)	0.0312 (7)
C16	0.5906 (4)	0.06123 (19)	0.8311 (5)	0.0336 (7)
H16	0.6003	0.0153	0.8348	0.040*
C17	0.4681 (4)	0.0892 (2)	0.8282 (5)	0.0352 (8)
H17	0.3932	0.0623	0.8308	0.042*
N18A	0.4542 (3)	0.15364 (17)	0.8217 (4)	0.0292 (4)	0.632 (4)
H18A	0.3753	0.1705	0.8193	0.035*	0.632 (4)
C18B	0.4542 (3)	0.15364 (17)	0.8217 (4)	0.0292 (4)	0.368 (4)
C19	0.5569 (4)	0.1931 (2)	0.8188 (6)	0.0364 (8)
H19	0.5441	0.2388	0.8156	0.044*
C20	0.6822 (4)	0.16808 (19)	0.8204 (5)	0.0354 (8)
H20	0.7552	0.1961	0.8160	0.042*
I1	0.47781 (2)	0.126317 (12)	0.31747 (3)	0.03385 (11)

	U11	U22	U33	U12	U13	U23
F1A	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
F1B	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C1	0.0289 (17)	0.0352 (19)	0.0353 (18)	0.0032 (14)	0.0087 (14)	0.0040 (14)
C2	0.0329 (18)	0.0339 (19)	0.0339 (18)	0.0020 (14)	0.0065 (14)	0.0026 (14)
N3	0.0312 (17)	0.061 (2)	0.045 (2)	0.0125 (16)	0.0037 (15)	−0.0117 (17)
O4	0.0336 (14)	0.0525 (18)	0.0474 (17)	0.0086 (13)	0.0122 (12)	−0.0064 (14)
C5	0.0325 (19)	0.038 (2)	0.045 (2)	0.0013 (16)	0.0092 (16)	0.0042 (16)
C6	0.040 (2)	0.042 (2)	0.042 (2)	0.0019 (17)	0.0108 (17)	−0.0077 (17)
O7	0.0292 (14)	0.0528 (18)	0.067 (2)	0.0032 (12)	0.0151 (14)	0.0009 (16)
C8	0.0303 (18)	0.0346 (19)	0.0349 (19)	−0.0006 (14)	0.0047 (15)	0.0048 (14)
C9	0.0286 (17)	0.046 (2)	0.0336 (19)	0.0007 (15)	0.0036 (15)	0.0009 (15)
C10	0.037 (2)	0.048 (2)	0.035 (2)	0.0035 (17)	0.0049 (16)	−0.0002 (17)
C11A	0.055 (2)	0.043 (2)	0.039 (2)	−0.0025 (18)	−0.0002 (18)	0.0000 (17)
N11B	0.055 (2)	0.043 (2)	0.039 (2)	−0.0025 (18)	−0.0002 (18)	0.0000 (17)
C12	0.037 (2)	0.050 (3)	0.048 (2)	−0.0095 (18)	−0.0029 (18)	0.0029 (19)
C13	0.0297 (19)	0.048 (2)	0.047 (2)	−0.0043 (16)	0.0057 (17)	0.0058 (18)
C15	0.0331 (17)	0.0352 (18)	0.0257 (16)	0.0025 (14)	0.0045 (13)	−0.0009 (14)
C16	0.0372 (19)	0.0332 (18)	0.0313 (17)	−0.0009 (15)	0.0079 (15)	−0.0007 (14)
C17	0.0360 (19)	0.038 (2)	0.0323 (18)	−0.0024 (15)	0.0063 (15)	−0.0016 (14)
N18A	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C18B	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C19	0.0344 (18)	0.0363 (19)	0.0381 (19)	0.0028 (15)	0.0025 (15)	0.0013 (15)
C20	0.0318 (18)	0.0329 (19)	0.041 (2)	−0.0005 (14)	0.0037 (15)	−0.0014 (15)
I1	0.03172 (15)	0.03684 (16)	0.03268 (16)	−0.00256 (9)	0.00260 (10)	−0.00114 (9)

F1A—C11A	1.376 (5)	C10—C11A	1.365 (6)
C1—C2	1.378 (5)	C10—H10	0.9500
C1—C5	1.431 (5)	C11A—C12	1.375 (7)
C1—C8	1.472 (5)	C12—C13	1.378 (7)
C2—N3	1.328 (5)	C12—H12	0.9500
C2—C15	1.477 (5)	C13—H13	0.9500
N3—O4	1.383 (4)	C15—C16	1.383 (5)
N3—C6	1.444 (6)	C15—C20	1.393 (6)
O4—C5	1.400 (5)	C16—C17	1.382 (5)
C5—O7	1.208 (5)	C16—H16	0.9500
C6—H6A	0.9800	C17—N18A	1.336 (6)
C6—H6B	0.9800	C17—H17	0.9500
C6—H6C	0.9800	N18A—C19	1.334 (5)
C8—C13	1.392 (6)	N18A—H18A	0.8800
C8—C9	1.397 (6)	C19—C20	1.386 (5)
C9—C10	1.390 (6)	C19—H19	0.9500
C9—H9	0.9500	C20—H20	0.9500
C2—C1—C5	105.4 (3)	C10—C11A—C12	122.8 (4)
C2—C1—C8	129.2 (3)	C10—C11A—F1A	118.4 (4)
C5—C1—C8	125.1 (4)	C12—C11A—F1A	118.8 (4)
N3—C2—C1	111.3 (3)	C11A—C12—C13	118.5 (4)
N3—C2—C15	118.9 (3)	C11A—C12—H12	120.8
C1—C2—C15	129.6 (4)	C13—C12—H12	120.8
C2—N3—O4	108.8 (3)	C12—C13—C8	121.3 (4)
C2—N3—C6	134.4 (4)	C12—C13—H13	119.4
O4—N3—C6	116.8 (3)	C8—C13—H13	119.4
N3—O4—C5	107.6 (3)	C16—C15—C20	119.5 (3)
O7—C5—O4	117.8 (4)	C16—C15—C2	122.2 (4)
O7—C5—C1	135.3 (4)	C20—C15—C2	118.1 (3)
O4—C5—C1	106.9 (3)	C17—C16—C15	119.1 (4)
N3—C6—H6A	109.5	C17—C16—H16	120.4
N3—C6—H6B	109.5	C15—C16—H16	120.4
H6A—C6—H6B	109.5	N18A—C17—C16	120.5 (4)
N3—C6—H6C	109.5	N18A—C17—H17	119.7
H6A—C6—H6C	109.5	C16—C17—H17	119.7
H6B—C6—H6C	109.5	C19—N18A—C17	121.6 (3)
C13—C8—C9	118.2 (4)	C19—N18A—H18A	119.2
C13—C8—C1	120.4 (4)	C17—N18A—H18A	119.2
C9—C8—C1	121.3 (4)	N18A—C19—C20	120.7 (4)
C10—C9—C8	121.1 (4)	N18A—C19—H19	119.6
C10—C9—H9	119.5	C20—C19—H19	119.6
C8—C9—H9	119.5	C19—C20—C15	118.5 (4)
C11A—C10—C9	118.2 (4)	C19—C20—H20	120.7
C11A—C10—H10	120.9	C15—C20—H20	120.7
C9—C10—H10	120.9
C5—C1—C2—N3	0.7 (5)	C1—C8—C9—C10	177.6 (4)
C8—C1—C2—N3	−173.3 (4)	C8—C9—C10—C11A	−1.2 (6)
C5—C1—C2—C15	−173.3 (4)	C9—C10—C11A—C12	0.7 (7)
C8—C1—C2—C15	12.7 (7)	C9—C10—C11A—F1A	−177.8 (4)
C1—C2—N3—O4	0.6 (5)	C10—C11A—C12—C13	−0.1 (7)
C15—C2—N3—O4	175.3 (3)	F1A—C11A—C12—C13	178.4 (4)
C1—C2—N3—C6	178.3 (5)	C11A—C12—C13—C8	0.2 (7)
C15—C2—N3—C6	−7.0 (8)	C9—C8—C13—C12	−0.7 (6)
C2—N3—O4—C5	−1.7 (5)	C1—C8—C13—C12	−177.1 (4)
C6—N3—O4—C5	−179.9 (4)	N3—C2—C15—C16	60.6 (5)
N3—O4—C5—O7	−178.4 (4)	C1—C2—C15—C16	−125.8 (5)
N3—O4—C5—C1	2.1 (4)	N3—C2—C15—C20	−116.6 (4)
C2—C1—C5—O7	178.9 (5)	C1—C2—C15—C20	57.0 (6)
C8—C1—C5—O7	−6.8 (8)	C20—C15—C16—C17	−1.0 (5)
C2—C1—C5—O4	−1.7 (4)	C2—C15—C16—C17	−178.1 (3)
C8—C1—C5—O4	172.6 (3)	C15—C16—C17—N18A	0.5 (5)
C2—C1—C8—C13	−168.6 (4)	C16—C17—N18A—C19	−0.4 (5)
C5—C1—C8—C13	18.5 (6)	C17—N18A—C19—C20	0.7 (6)
C2—C1—C8—C9	15.1 (6)	N18A—C19—C20—C15	−1.2 (6)
C5—C1—C8—C9	−157.8 (4)	C16—C15—C20—C19	1.4 (6)
C13—C8—C9—C10	1.3 (6)	C2—C15—C20—C19	178.6 (4)