4-{3-[(4-Fluoro­benzyl­idene)­amino]-2-oxo-1,3-oxazolidin-5-yl­methyl}morpholine

A series of derivatives of 3-amino-2-oxazolidinone have been prepared. The 5-morpholino­methyl-3-(4-chloro­benzyl­idene­amino)-2-ox­azol­idin­one derivative is a potential psychotropic drug. Preliminary clinical data showed that the compound exhibits antidepressive activity in humans. The molecular geometry of the title compound, C₁₅H₁₈FN₃O₃, is similar to 5-morpholino­methyl-3-(4-chloro­benzyl­idene­amino)-2-ox­azol­idin­one. Two atoms of the title compound are disordered so that two different conformations of the ox­azol­idin­one ring were found; one is a twist and the other is an envelope con­formation. The crystal structure of title compound is formed by weak intermolecular C—H...O hydrogen bonds resulting in a two-dimensional infinite hydrogen-bond network.

Key indicators

• Single-crystal X-ray study
• T = 291 K
• Mean [sigma](C-C) = 0.004 Å
• Disorder in main residue
• R factor = 0.075
• wR factor = 0.177
• Data-to-parameter ratio = 12.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



PLAT_301  Alert C Main Residue Disorder ........................       8.00 Perc.


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

---

S1. Comment

In the Pharmaceutical Research Institute in Warsaw, a series of derivatives of 3-amino-2-oxazolidinone have been prepared (Chilmonczyk et al., 1997). It has been found that the oxazolidinone derivative 5-morpholinomethyl-3-(4-chlorobenzylideneamino)-2-oxazolidinone, (II), is a potential psychotropic drug (Chilmonczyk, 1995). Preliminary clinical data show that the compound exhibits antidepressive activity in humans (Rybakowski & Araszkiewicz, 1999). It can be supposed that other derivatives of this class can also exhibit biological activity. It is generally accepted that a specific,energetically preferred conformation of a compound (so-called bioactive conformation) decides about the nature of interactions with its molecular target or pharmacological receptor. Therefore, it is of basic importance to get an insight into such molecular parameters as charge distribution, the most preferred conformation or distances between specified points within a molecule (Krzywda et al., 2000).

A perspective view of the title compound, (I), together with the atom-numbering scheme are shown in Fig. 1. A l l interatomic distances are normal. The molecular geometry of (I) is similar to the chloride monohydrate of (II) (Bartczak et al., 2001). The weighted r.m.s. deviation for all atoms of (I) and the inverted molecule of (II) is 0.218 (2) Å. A fit of (I) and (II) is depicted in Fig. 2. Bartczak et al. (2001) found that the primary place of molecular interaction with an acid residue within a putative receptor site is on N1. Thus, we can suppose that for (I) proton transfer also occurs from the acid residue, and (I) will be interacting by the same N1 atom. The oxazolidinone ring exists in a twist and an envelope conformation shown by the asymmetry parameters; ΔC₂ = 2.77 (5) and ΔC_s = 4.62 (5), and ΔC₂ = 13.66 (8) and ΔC_s = 2.90 (6), respectively (Duax & Norton, 1975). According to asymmetry parameters, the morpholine ring exists in an almost ideal chair conformation. The structure of (I) is assembled by intermolecular weak C—H···O hydrogen bonds into a two-dimensional infinite hydrogen bond network (Fig. 3 and Table 2). The absence of an intermolecular hydrogen bond linking C1 and O2 in (I), which creates a fused three-membered ring system in (II), could be one of the reasons for the disorder observed in (I).

The decreased number of hydrogen bonds and its weakening in (I) does not change the molecular geometry, what suggests that inserting hydrochloric acid into the structure, even if it increases the number of hydrogen bonds, does not change its geometry and can eliminate disorder.

S2. Experimental

The title compound was prepared according to the method of Chilmonczyk et al. (1997).

Computing details

Data collection: CrysAlis CCD (UNIL IC & Kuma, 2000); cell refinement: CrysAlis RED (UNIL IC & Kuma, 2000); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990a); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC (Sheldrick, 1990b) ORTEP-3 (Farrugia 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level. The disordered part is indicated by dashed lines.
	Fig. 2. Fit of inverted (I) and (II). The structure of (II) is indicated by dashed lines. The disordered atoms have been omitted for clarity.
	Fig. 3. Packing diagram of (I) showing intermolecular hydrogen bonds creating a two-dimensional net structure. Hydrogen bonds are indicated by dashed lines.

4-{3-[(4-Fluorobenzylidene)amino]-2-oxo-1,3-oxazolidin-5-ylmethyl}morpholine

Crystal data

C15H18FN3O3	F(000) = 324
Mr = 307.32	Dx = 1.371 Mg m^−3
Triclinic, P1	Melting point: 432.6-433.5 K K
a = 6.4808 (7) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.9636 (9) Å	Cell parameters from 1319 reflections
c = 12.2753 (11) Å	θ = 5–22°
α = 91.600 (9)°	µ = 0.11 mm^−1
β = 101.048 (10)°	T = 291 K
γ = 106.114 (12)°	Plate, colourless
V = 744.62 (12) Å^3	0.30 × 0.11 × 0.08 mm
Z = 2

Data collection

Kuma KM4-CCD diffractometer	2638 independent reflections
Radiation source: fine-focus sealed tube	2090 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.000
ω scans	θmax = 25.1°, θmin = 3.4°
Absorption correction: numerical (X-RED; Stoe & Cie, 1999)	h = −7→7
Tmin = 0.969, Tmax = 0.992	k = −11→11
2638 measured reflections	l = 0→14

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.075	H-atom parameters constrained
wR(F^2) = 0.177	w = 1/[σ^2(Fo^2) + (0.0691P)^2 + 0.2292P] where P = (Fo^2 + 2Fc^2)/3
S = 1.20	(Δ/σ)max < 0.001
2638 reflections	Δρmax = 0.20 e Å^−3
219 parameters	Δρmin = −0.17 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.020 (5)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	−0.1389 (5)	0.2692 (3)	0.8864 (3)	0.0623 (8)
H1A	−0.0254	0.3475	0.9298	0.075*
H1B	−0.0816	0.2375	0.8263	0.075*
C2	−0.2009 (6)	0.1533 (4)	0.9585 (3)	0.0730 (10)
H2A	−0.3082	0.0735	0.9136	0.088*
H2B	−0.0722	0.1244	0.9895	0.088*
O1	−0.2894 (5)	0.1940 (3)	1.04620 (19)	0.0946 (9)
C3	−0.4751 (6)	0.2383 (5)	1.0036 (3)	0.0888 (12)
H3A	−0.5300	0.2694	1.0649	0.107*
H3B	−0.5898	0.1597	0.9613	0.107*
C4	−0.4230 (6)	0.3549 (4)	0.9303 (3)	0.0799 (11)
H4A	−0.5557	0.3792	0.8991	0.096*
H4B	−0.3193	0.4370	0.9741	0.096*
N1	−0.3302 (4)	0.3137 (3)	0.8410 (2)	0.0657 (8)
C5A	−0.2649 (9)	0.4568 (6)	0.7954 (5)	0.0528 (19)	0.571 (9)
H5A1	−0.3910	0.4928	0.7786	0.063*	0.571 (9)
H5A2	−0.1519	0.5225	0.8505	0.063*	0.571 (9)
C6A	−0.1805 (9)	0.4409 (8)	0.6916 (6)	0.0491 (16)	0.571 (9)
H6A	−0.2449	0.3476	0.6515	0.059*	0.571 (9)
C5B	−0.3304 (10)	0.3687 (8)	0.7263 (6)	0.045 (2)	0.429 (9)
H5B1	−0.2970	0.3029	0.6775	0.054*	0.429 (9)
H5B2	−0.4752	0.3763	0.6944	0.054*	0.429 (9)
C6B	−0.1636 (12)	0.5100 (11)	0.7339 (7)	0.046 (2)	0.429 (9)
H6B	−0.1574	0.5756	0.7962	0.055*	0.429 (9)
C8	−0.2067 (4)	0.5637 (4)	0.6167 (3)	0.0633 (9)
H8A	−0.3040	0.5281	0.5452	0.076*
H8B	−0.2615	0.6300	0.6535	0.076*
N2	0.0155 (4)	0.6262 (3)	0.6047 (2)	0.0643 (8)
C7	0.1620 (4)	0.5715 (3)	0.6681 (3)	0.0596 (8)
O2	0.0568 (3)	0.4768 (2)	0.72964 (19)	0.0747 (7)
O3	0.3540 (3)	0.5969 (3)	0.6704 (2)	0.0831 (8)
N3	0.0861 (4)	0.7241 (2)	0.53426 (19)	0.0532 (6)
C9	−0.0568 (4)	0.7691 (3)	0.4718 (2)	0.0491 (7)
H9	−0.2045	0.7331	0.4739	0.059*
C10	0.0094 (4)	0.8765 (3)	0.3973 (2)	0.0445 (6)
C11	0.2295 (4)	0.9442 (3)	0.4010 (2)	0.0531 (7)
H11	0.3366	0.9191	0.4512	0.064*
C12	0.2925 (5)	1.0474 (3)	0.3320 (2)	0.0591 (8)
H12	0.4401	1.0926	0.3351	0.071*
C13	0.1316 (5)	1.0815 (3)	0.2588 (2)	0.0589 (8)
C14	−0.0859 (5)	1.0196 (3)	0.2522 (2)	0.0593 (8)
H14	−0.1910	1.0461	0.2017	0.071*
C15	−0.1475 (5)	0.9160 (3)	0.3225 (2)	0.0548 (7)
H15	−0.2956	0.8726	0.3194	0.066*
F1	0.1919 (3)	1.1824 (2)	0.18925 (16)	0.0858 (7)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0587 (18)	0.0667 (19)	0.071 (2)	0.0278 (15)	0.0198 (15)	0.0281 (16)
C2	0.096 (2)	0.079 (2)	0.061 (2)	0.0444 (19)	0.0280 (18)	0.0310 (18)
O1	0.112 (2)	0.139 (2)	0.0575 (14)	0.0628 (18)	0.0329 (14)	0.0357 (15)
C3	0.093 (3)	0.120 (3)	0.073 (2)	0.042 (2)	0.045 (2)	0.028 (2)
C4	0.065 (2)	0.071 (2)	0.118 (3)	0.0304 (18)	0.036 (2)	0.016 (2)
N1	0.0506 (14)	0.0818 (18)	0.0805 (18)	0.0293 (13)	0.0302 (13)	0.0502 (15)
C5A	0.054 (3)	0.058 (4)	0.054 (4)	0.023 (3)	0.017 (3)	0.018 (3)
C6A	0.040 (3)	0.057 (4)	0.056 (4)	0.020 (3)	0.015 (3)	0.015 (3)
C5B	0.034 (3)	0.048 (4)	0.050 (4)	0.005 (3)	0.009 (3)	0.019 (4)
C6B	0.039 (4)	0.057 (6)	0.049 (5)	0.016 (4)	0.023 (3)	0.018 (4)
C8	0.0394 (15)	0.093 (2)	0.0670 (19)	0.0227 (15)	0.0223 (13)	0.0443 (17)
N2	0.0390 (12)	0.0868 (18)	0.0774 (17)	0.0229 (12)	0.0237 (12)	0.0490 (15)
C7	0.0424 (16)	0.070 (2)	0.074 (2)	0.0199 (14)	0.0203 (14)	0.0348 (16)
O2	0.0434 (11)	0.0971 (17)	0.0905 (16)	0.0219 (11)	0.0206 (11)	0.0588 (14)
O3	0.0381 (11)	0.1048 (18)	0.118 (2)	0.0279 (11)	0.0257 (12)	0.0564 (16)
N3	0.0481 (13)	0.0596 (14)	0.0585 (14)	0.0158 (11)	0.0231 (11)	0.0270 (12)
C9	0.0430 (14)	0.0587 (17)	0.0496 (15)	0.0152 (12)	0.0167 (12)	0.0150 (13)
C10	0.0484 (14)	0.0470 (15)	0.0390 (14)	0.0126 (12)	0.0125 (11)	0.0090 (12)
C11	0.0499 (16)	0.0579 (17)	0.0482 (16)	0.0103 (13)	0.0089 (12)	0.0128 (13)
C12	0.0543 (17)	0.0582 (18)	0.0594 (18)	0.0041 (14)	0.0151 (14)	0.0151 (15)
C13	0.076 (2)	0.0518 (17)	0.0488 (16)	0.0112 (15)	0.0219 (15)	0.0180 (14)
C14	0.0657 (18)	0.0637 (19)	0.0520 (17)	0.0229 (15)	0.0119 (14)	0.0211 (15)
C15	0.0496 (16)	0.0610 (18)	0.0560 (17)	0.0171 (13)	0.0130 (13)	0.0157 (14)
F1	0.1029 (15)	0.0773 (13)	0.0717 (12)	0.0103 (11)	0.0236 (11)	0.0387 (11)

Geometric parameters (Å, º)

C1—N1	1.448 (3)	C6B—C8	1.551 (8)
C1—C2	1.488 (4)	C6B—O2	1.563 (8)
C1—H1A	0.9700	C6B—H6B	0.9800
C1—H1B	0.9700	C8—N2	1.440 (3)
C2—O1	1.412 (4)	C8—H8A	0.9700
C2—H2A	0.9700	C8—H8B	0.9700
C2—H2B	0.9700	N2—C7	1.353 (3)
O1—C3	1.409 (4)	N2—N3	1.363 (3)
C3—C4	1.493 (5)	C7—O3	1.193 (3)
C3—H3A	0.9700	C7—O2	1.344 (3)
C3—H3B	0.9700	N3—C9	1.275 (3)
C4—N1	1.448 (4)	C9—C10	1.455 (3)
C4—H4A	0.9700	C9—H9	0.9300
C4—H4B	0.9700	C10—C15	1.384 (4)
N1—C5B	1.525 (6)	C10—C11	1.390 (4)
N1—C5A	1.525 (6)	C11—C12	1.374 (4)
C5A—C6A	1.501 (10)	C11—H11	0.9300
C5A—H5A1	0.9700	C12—C13	1.366 (4)
C5A—H5A2	0.9700	C12—H12	0.9300
C6A—O2	1.457 (6)	C13—C14	1.358 (4)
C6A—C8	1.578 (6)	C13—F1	1.360 (3)
C6A—H6A	0.9800	C14—C15	1.387 (4)
C5B—C6B	1.506 (13)	C14—H14	0.9300
C5B—H5B1	0.9700	C15—H15	0.9300
C5B—H5B2	0.9700
N1—C1—C2	109.4 (2)	H5B1—C5B—H5B2	108.0
N1—C1—H1A	109.8	C5B—C6B—C8	105.5 (7)
C2—C1—H1A	109.8	C5B—C6B—O2	104.8 (7)
N1—C1—H1B	109.8	C8—C6B—O2	98.6 (4)
C2—C1—H1B	109.8	C5B—C6B—H6B	115.3
H1A—C1—H1B	108.2	C8—C6B—H6B	115.3
O1—C2—C1	111.8 (3)	O2—C6B—H6B	115.3
O1—C2—H2A	109.3	N2—C8—C6B	100.2 (3)
C1—C2—H2A	109.3	N2—C8—C6A	101.8 (3)
O1—C2—H2B	109.3	C6B—C8—C6A	30.3 (3)
C1—C2—H2B	109.3	N2—C8—H8A	111.4
H2A—C2—H2B	107.9	C6B—C8—H8A	136.6
C3—O1—C2	110.5 (3)	C6A—C8—H8A	111.4
O1—C3—C4	111.7 (3)	N2—C8—H8B	111.4
O1—C3—H3A	109.3	C6B—C8—H8B	84.4
C4—C3—H3A	109.3	C6A—C8—H8B	111.4
O1—C3—H3B	109.3	H8A—C8—H8B	109.3
C4—C3—H3B	109.3	C7—N2—N3	119.3 (2)
H3A—C3—H3B	107.9	C7—N2—C8	113.1 (2)
N1—C4—C3	110.5 (3)	N3—N2—C8	127.5 (2)
N1—C4—H4A	109.6	O3—C7—O2	122.9 (3)
C3—C4—H4A	109.6	O3—C7—N2	127.9 (3)
N1—C4—H4B	109.6	O2—C7—N2	109.2 (2)
C3—C4—H4B	109.6	C7—O2—C6A	111.5 (3)
H4A—C4—H4B	108.1	C7—O2—C6B	106.5 (3)
C1—N1—C4	110.1 (3)	C6A—O2—C6B	31.2 (3)
C1—N1—C5B	114.3 (3)	C9—N3—N2	118.0 (2)
C4—N1—C5B	129.0 (4)	N3—C9—C10	120.5 (2)
C1—N1—C5A	111.2 (3)	N3—C9—H9	119.8
C4—N1—C5A	97.3 (3)	C10—C9—H9	119.8
C5B—N1—C5A	43.6 (3)	C15—C10—C11	118.4 (2)
C6A—C5A—N1	108.6 (5)	C15—C10—C9	120.2 (2)
C6A—C5A—H5A1	110.0	C11—C10—C9	121.3 (2)
N1—C5A—H5A1	110.0	C12—C11—C10	121.5 (3)
C6A—C5A—H5A2	110.0	C12—C11—H11	119.3
N1—C5A—H5A2	110.0	C10—C11—H11	119.3
H5A1—C5A—H5A2	108.3	C13—C12—C11	117.9 (3)
O2—C6A—C5A	104.4 (6)	C13—C12—H12	121.1
O2—C6A—C8	102.0 (4)	C11—C12—H12	121.1
C5A—C6A—C8	109.4 (5)	C14—C13—F1	118.4 (3)
O2—C6A—H6A	113.4	C14—C13—C12	123.2 (3)
C5A—C6A—H6A	113.4	F1—C13—C12	118.4 (3)
C8—C6A—H6A	113.4	C13—C14—C15	118.4 (3)
C6B—C5B—N1	111.0 (6)	C13—C14—H14	120.8
C6B—C5B—H5B1	109.4	C15—C14—H14	120.8
N1—C5B—H5B1	109.4	C10—C15—C14	120.7 (3)
C6B—C5B—H5B2	109.4	C10—C15—H15	119.7
N1—C5B—H5B2	109.4	C14—C15—H15	119.7
O2—C7—N2—C8	−2.9 (4)	N1—C5A—C6A—C8	156.2 (4)
C7—N2—C8—C6A	−6.8 (5)	C1—N1—C5B—C6B	−71.8 (7)
N2—C8—C6A—O2	12.9 (5)	N1—C5B—C6B—O2	85.4 (7)
C8—C6A—O2—C7	−15.9 (6)	N1—C5B—C6B—C8	−171.1 (4)
C6A—O2—C7—N2	12.6 (5)	C1—C2—O1—C3	58.1 (4)
C7—N2—C8—C6B	24.1 (6)	C2—O1—C3—C4	−56.6 (4)
N2—C8—C6B—O2	−32.0 (6)	O1—C3—C4—N1	56.1 (4)
C8—C6B—O2—C7	32.9 (6)	C3—C4—N1—C1	−55.9 (4)
C6B—O2—C7—N2	−20.1 (5)	C4—N1—C1—C2	56.7 (4)
C1—N1—C5A—C6A	70.5 (5)	N1—C1—C2—O1	−58.3 (4)
N1—C5A—C6A—O2	−95.2 (6)	N2—N3—C9—C10	178.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5A—H5A1···O3^i	0.97	2.40	3.314 (5)	157
C8—H8B···O3^i	0.97	2.47	3.143 (3)	126
C14—H14···O1^ii	0.93	2.54	3.375 (4)	150

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