4-[3-(4-Fluoro­benzyl­idene­amino)-2-oxo-1,3-oxazolidin-5-yl­methyl]­morpholin-4-ium chloride mono­hydrate

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, C₁₅H₁₉FN₃O₃⁺·Cl^-·H₂O, is similar to that of 5-morpholino­methyl-3-(4-chloro­benzyl­idene­amino)-2-oxazolidinone. The oxazolidinone ring exists in an almost ideal half-chair conformation. The primary location of molecular interaction with an acid residue within a putative receptor site is at the morpholine N atom. The structure of the title compound is built up from strong and weak intermolecular hydrogen bonds forming a two dimensional infinite hydrogen-bond network.

Key indicators

• Single-crystal X-ray study
• T = 291 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.063
• wR factor = 0.201
• Data-to-parameter ratio = 16.6

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



RADNW_01  Alert C The radiation wavelength lies outside the expected range
          for the supplied radiation type. Expected range 1.54175-1.54180
          Wavelength given =    1.54056

General Notes



RADNW_01  The radiation wavelength given implies that Cu Kalpha1 has
          been used. Please check that this is correct.
          Wavelength given =    1.54056


 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-chlorobenzylidenamino)-2-oxazolidinone, (I) hereafter, 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 the specific, energetically preferred conformation of a compound (so-called bioactive conformation) determines the nature of interactions with its molecular target, the pharmacological receptor. Therefore, it is of fundamental importance to get an insight into such molecular parameters as charge distribution, most preferred conformation or distances between specified points within a molecule (Krzywda et al., 2000). Bartczak et al. (2001) have determined the structure of the chloride monohydrate of (I) and found that the primary location of molecular interaction with an acid residue within a putative receptor site is at the morpholine N atom. The structure of 5-morpholinomethyl-3-(4-fluorobenzylidenamino)-2-oxazolidinone, (II), has also been previously determined (Kruszynski et al., 2001) but the primary location of molecular interaction with an acid residue within a putative receptor site was only supposed on the basis of similar molecular geometry of (II) and the chloride monohydrate of (I).

The perspective view of the title compound, (III), together with the atom-numbering scheme, is shown in Fig. 1. A l l interatomic distances are normal. The molecular geometry of (III) is similar to the chloride monohydrate of (I) (Bartczak et al., 2001) and (II). The weighted r.m.s. deviation for all atoms in (III) and inverted molecule (II) is 0.238 (3) Å; for (III) and (II), it is 0.229 (2) Å. The superposition of the two molecules (III) and (II) is shown in Fig. 2. The molecule of (III) shows signs of disorder, as was noticed in (II), but invoking this model did not improve the quality of structure; therefore the model was not applied.

In (III), a proton transfer takes place from hydrochloric acid to the atom N1. This confirms the presumption (Kruszynski et al., 2001) that the molecule interacts with an acid residue within a putative receptor through the atom N1. The oxazolidinone ring of (III) exists in the same almost ideal half-chair conformation as in (I); this can be detected by the asymmetry parameters (Duax & Norton, 1975). Values and positions of the asymmetry parameters for the oxazolidinone ring are shown in Fig. 3. According to the asymmetry parameters the morpholine ring exists in a slightly distorted chair conformation.

The structure of (III) is built up from strong and weak intermolecular hydrogen bonds to form the two dimensional infinite hydrogen-bond network (Fig. 4 and Table 2). The absence of an intermolecular hydrogen bond linking atoms C1 and O2 in (III) as in (II), which creates a fused three-membered ring system in the chloride monohydrate of (I) (Bartczak et al., 2001), might be one of the reasons for the signs of disorder observed in the molecule.

S2. Experimental

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

S3. Refinement

All H atoms except these of the water molecule and that bonded to atom N1 were placed in calculated positions and were treated as riding on the adjacent C atom. They were refined with individual isotropic displacement parameters equal to 1.2 times the value of the equivalent displacement parameter of the parent C atom for aryl H atoms and equal to 1.5 times for other H atoms. The positional parameters and isotropic displacement parameter of the H atom bonded to atom N1 were free to refine.

Computing details

Data collection: KM-4 Software (Kuma, 1993); cell refinement: KM-4 Software; data reduction: DATAPROC (Kuma 1998); 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) and ORTEP-3 (Farrugia 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of the title compound (III). Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Superposition of two molecules, i.e. inverted (II) and (III). Molecule (II) is indicated by dashed lines. The disordered atoms of (II) have been omitted for clarity.
	Fig. 3. The values and positions of asymmetry parameters for the oxazolidinone ring of the title compound.
	Fig. 4. Part of the molecular packing of (III) showing intermolecular hydrogen bonds creating an infinite two-dimensional net structure. Hydrogen bonds are indicated by dashed lines.

4-[3-(4-fluorobenzylidenamino)-2-oxooxazolidin-5-ylmethyl]morpholin-4-ium chloride monohydrate

Crystal data

C15H19FN3O3^+·Cl^−·H2O	Dx = 1.390 Mg m^−3
Mr = 361.80	Melting point: 501.2-502.1 K K
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54056 Å
a = 8.9570 (9) Å	Cell parameters from 99 reflections
b = 27.968 (3) Å	θ = 5–60°
c = 7.137 (1) Å	µ = 2.28 mm^−1
β = 104.820 (9)°	T = 291 K
V = 1728.4 (4) Å^3	Plate, colourless
Z = 4	0.39 × 0.35 × 0.17 mm
F(000) = 760

Data collection

Kuma KM-4 diffractometer	2689 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Graphite monochromator	θmax = 81.5°, θmin = 3.2°
ω–2θ scans	h = −11→11
Absorption correction: numerical (X-RED; Stoe & Cie, 1999)	k = 0→35
Tmin = 0.471, Tmax = 0.698	l = 0→9
3674 measured reflections	3 standard reflections every 100 reflections
3674 independent reflections	intensity decay: 1.7%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.201	H atoms treated by a mixture of independent and constrained refinement
S = 1.12	w = 1/[σ^2(Fo^2) + (0.1136P)^2 + 0.499P] where P = (Fo^2 + 2Fc^2)/3
3674 reflections	(Δ/σ)max < 0.001
221 parameters	Δρmax = 0.87 e Å^−3
0 restraints	Δρmin = −0.42 e Å^−3

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
N1	0.4961 (3)	0.37889 (7)	1.2497 (4)	0.0536 (5)
C4	0.6564 (3)	0.37213 (11)	1.3677 (5)	0.0672 (7)
H4A	0.7196	0.3979	1.3434	0.101*
H4B	0.6574	0.3718	1.5025	0.101*
C3	0.7197 (4)	0.32576 (12)	1.3176 (5)	0.0752 (8)
H3A	0.8228	0.3217	1.3973	0.113*
H3B	0.7216	0.3267	1.1838	0.113*
O1	0.6284 (3)	0.28678 (8)	1.3449 (4)	0.0831 (7)
C2	0.4785 (4)	0.29185 (11)	1.2224 (6)	0.0820 (10)
H2A	0.4857	0.2934	1.0906	0.123*
H2B	0.4179	0.2646	1.2384	0.123*
C1	0.3994 (4)	0.33671 (9)	1.2671 (5)	0.0654 (7)
H1A	0.3871	0.3349	1.3967	0.098*
H1B	0.2998	0.3397	1.1772	0.098*
C5	0.4372 (3)	0.42510 (9)	1.3088 (4)	0.0597 (6)
H5A	0.5114	0.4496	1.3052	0.090*
H5B	0.4273	0.4216	1.4389	0.090*
C6	0.2843 (3)	0.44029 (9)	1.1820 (4)	0.0559 (6)
H6	0.2817	0.4293	1.0538	0.084*
O2	0.1574 (2)	0.42051 (6)	1.2498 (3)	0.0595 (5)
C7	0.0536 (3)	0.45548 (9)	1.2555 (4)	0.0546 (6)
O3	−0.0693 (2)	0.44726 (7)	1.2881 (3)	0.0688 (6)
N2	0.1095 (2)	0.49766 (7)	1.2124 (3)	0.0540 (5)
C8	0.2657 (3)	0.49440 (9)	1.1912 (4)	0.0571 (6)
H8A	0.2752	0.5095	1.0740	0.086*
H8B	0.3393	0.5081	1.2999	0.086*
N3	0.0318 (2)	0.53915 (7)	1.2260 (3)	0.0511 (5)
C9	0.1007 (3)	0.57767 (8)	1.2022 (4)	0.0520 (5)
H9	0.1908	0.5764	1.1904	0.078*
C10	0.0335 (3)	0.62494 (9)	1.2104 (4)	0.0509 (5)
C11	−0.0999 (3)	0.63272 (9)	1.2703 (4)	0.0580 (6)
H11	−0.1512	0.6063	1.3128	0.070*
C12	−0.1591 (4)	0.67820 (10)	1.2690 (5)	0.0685 (8)
H12	−0.2519	0.6837	1.3095	0.082*
C13	−0.0838 (4)	0.71510 (10)	1.2095 (5)	0.0690 (8)
C14	0.0503 (4)	0.70938 (10)	1.1538 (5)	0.0727 (8)
H14	0.1018	0.7361	1.1138	0.087*
C15	0.1081 (3)	0.66366 (9)	1.1551 (5)	0.0630 (7)
H15	0.2012	0.6618	1.1223	0.076*
F1	−0.1430 (3)	0.75989 (6)	1.2068 (4)	0.0998 (7)
Cl1	0.50494 (8)	0.39291 (3)	0.82881 (11)	0.0705 (3)
O4	0.6843 (3)	0.51101 (9)	1.3309 (4)	0.0908 (8)
H41	0.6610	0.5395	1.2889	0.136*
H42	0.7563	0.4973	1.2938	0.136*
H1N	0.486 (3)	0.3783 (10)	1.129 (5)	0.055 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0571 (12)	0.0474 (10)	0.0609 (13)	0.0011 (8)	0.0235 (10)	0.0030 (9)
C4	0.0591 (15)	0.0639 (16)	0.0797 (19)	−0.0027 (12)	0.0199 (14)	−0.0039 (13)
C3	0.0697 (18)	0.0774 (19)	0.080 (2)	0.0126 (15)	0.0226 (16)	0.0052 (15)
O1	0.0876 (16)	0.0604 (12)	0.0974 (17)	0.0152 (11)	0.0166 (13)	0.0108 (11)
C2	0.085 (2)	0.0521 (15)	0.107 (3)	0.0010 (14)	0.022 (2)	−0.0083 (16)
C1	0.0662 (17)	0.0505 (14)	0.0836 (19)	−0.0060 (11)	0.0268 (15)	0.0026 (12)
C5	0.0632 (15)	0.0523 (13)	0.0636 (15)	−0.0010 (11)	0.0161 (12)	−0.0054 (11)
C6	0.0587 (14)	0.0528 (13)	0.0597 (14)	−0.0012 (11)	0.0215 (12)	−0.0016 (10)
O2	0.0569 (10)	0.0470 (9)	0.0793 (12)	−0.0006 (7)	0.0260 (9)	0.0026 (8)
C7	0.0532 (13)	0.0506 (12)	0.0615 (14)	−0.0009 (10)	0.0174 (11)	−0.0029 (10)
O3	0.0567 (11)	0.0628 (11)	0.0952 (15)	−0.0075 (9)	0.0345 (11)	0.0000 (10)
N2	0.0495 (11)	0.0471 (10)	0.0691 (13)	0.0014 (8)	0.0220 (10)	0.0013 (9)
C8	0.0538 (14)	0.0510 (13)	0.0727 (16)	0.0015 (10)	0.0276 (12)	0.0040 (11)
N3	0.0517 (11)	0.0467 (10)	0.0560 (11)	0.0021 (8)	0.0158 (9)	−0.0026 (8)
C9	0.0472 (12)	0.0507 (12)	0.0591 (14)	0.0014 (9)	0.0155 (10)	−0.0001 (10)
C10	0.0505 (12)	0.0502 (12)	0.0513 (12)	0.0006 (10)	0.0121 (10)	−0.0016 (9)
C11	0.0535 (14)	0.0525 (13)	0.0708 (16)	−0.0020 (10)	0.0209 (12)	−0.0052 (11)
C12	0.0597 (16)	0.0604 (15)	0.089 (2)	0.0070 (13)	0.0249 (15)	−0.0065 (14)
C13	0.0705 (17)	0.0474 (13)	0.087 (2)	0.0110 (12)	0.0161 (15)	−0.0010 (13)
C14	0.0778 (19)	0.0514 (14)	0.092 (2)	−0.0023 (13)	0.0283 (17)	0.0108 (14)
C15	0.0616 (15)	0.0571 (14)	0.0764 (18)	0.0010 (12)	0.0286 (14)	0.0059 (12)
F1	0.1079 (16)	0.0534 (10)	0.141 (2)	0.0213 (10)	0.0375 (15)	0.0041 (11)
Cl1	0.0562 (4)	0.0926 (5)	0.0674 (4)	0.0033 (3)	0.0241 (3)	0.0171 (3)
O4	0.0851 (16)	0.0808 (15)	0.121 (2)	0.0081 (12)	0.0527 (15)	0.0094 (14)

Geometric parameters (Å, º)

N1—C4	1.480 (4)	C7—O3	1.203 (3)
N1—C1	1.487 (3)	C7—N2	1.347 (3)
N1—C5	1.497 (3)	N2—N3	1.369 (3)
N1—H1N	0.84 (3)	N2—C8	1.448 (3)
C4—C3	1.495 (4)	C8—H8A	0.9601
C4—H4A	0.9600	C8—H8B	0.9600
C4—H4B	0.9600	N3—C9	1.274 (3)
C3—O1	1.406 (4)	C9—C10	1.460 (3)
C3—H3A	0.9600	C9—H9	0.8338
C3—H3B	0.9600	C10—C15	1.382 (4)
O1—C2	1.410 (4)	C10—C11	1.385 (4)
C2—C1	1.515 (4)	C11—C12	1.377 (4)
C2—H2A	0.9599	C11—H11	0.9599
C2—H2B	0.9600	C12—C13	1.359 (4)
C1—H1A	0.9600	C12—H12	0.9600
C1—H1B	0.9600	C13—F1	1.358 (3)
C5—C6	1.497 (4)	C13—C14	1.368 (5)
C5—H5A	0.9599	C14—C15	1.379 (4)
C5—H5B	0.9600	C14—H14	0.9600
C6—O2	1.453 (3)	C15—H15	0.9234
C6—C8	1.526 (3)	O4—H41	0.8579
C6—H6	0.9600	O4—H42	0.8485
O2—C7	1.357 (3)
C4—N1—C1	110.6 (2)	O2—C6—H6	111.5
C4—N1—C5	108.1 (2)	C5—C6—H6	106.3
C1—N1—C5	114.0 (2)	C8—C6—H6	112.4
C4—N1—H1N	114 (2)	C7—O2—C6	109.63 (19)
C1—N1—H1N	99 (2)	O3—C7—N2	128.5 (2)
C5—N1—H1N	110.7 (19)	O3—C7—O2	122.4 (2)
N1—C4—C3	110.3 (3)	N2—C7—O2	109.0 (2)
N1—C4—H4A	109.4	C7—N2—N3	120.0 (2)
C3—C4—H4A	109.4	C7—N2—C8	113.2 (2)
N1—C4—H4B	109.3	N3—N2—C8	125.65 (19)
C3—C4—H4B	109.0	N2—C8—C6	100.7 (2)
H4A—C4—H4B	109.5	N2—C8—H8A	111.5
O1—C3—C4	111.7 (3)	C6—C8—H8A	111.3
O1—C3—H3A	109.3	N2—C8—H8B	111.8
C4—C3—H3A	109.1	C6—C8—H8B	111.8
O1—C3—H3B	108.6	H8A—C8—H8B	109.5
C4—C3—H3B	108.5	C9—N3—N2	115.8 (2)
H3A—C3—H3B	109.5	N3—C9—C10	122.8 (2)
C3—O1—C2	109.4 (2)	N3—C9—H9	119.5
O1—C2—C1	112.1 (3)	C10—C9—H9	117.5
O1—C2—H2A	108.6	C15—C10—C11	118.9 (2)
C1—C2—H2A	108.8	C15—C10—C9	117.6 (2)
O1—C2—H2B	108.9	C11—C10—C9	123.5 (2)
C1—C2—H2B	108.9	C12—C11—C10	120.3 (3)
H2A—C2—H2B	109.5	C12—C11—H11	119.9
N1—C1—C2	109.0 (2)	C10—C11—H11	119.9
N1—C1—H1A	109.6	C13—C12—C11	118.8 (3)
C2—C1—H1A	109.5	C13—C12—H12	120.7
N1—C1—H1B	109.7	C11—C12—H12	120.5
C2—C1—H1B	109.6	F1—C13—C12	118.8 (3)
H1A—C1—H1B	109.5	F1—C13—C14	118.2 (3)
N1—C5—C6	114.1 (2)	C12—C13—C14	123.0 (3)
N1—C5—H5A	108.3	C13—C14—C15	117.5 (3)
C6—C5—H5A	108.3	C13—C14—H14	121.3
N1—C5—H5B	108.2	C15—C14—H14	121.1
C6—C5—H5B	108.4	C14—C15—C10	121.4 (3)
H5A—C5—H5B	109.5	C14—C15—H15	114.3
O2—C6—C5	111.3 (2)	C10—C15—H15	124.2
O2—C6—C8	105.1 (2)	H41—O4—H42	116.5
C5—C6—C8	110.4 (2)
C1—C2—O1—C3	−61.5 (4)	C7—N2—C8—C6	12.7 (3)
C2—O1—C3—C4	61.3 (4)	N2—C8—C6—O2	−14.7 (3)
O1—C3—C4—N1	−57.8 (4)	C8—C6—O2—C7	13.0 (3)
C3—C4—N1—C1	53.2 (3)	N2—N3—C9—C10	179.5 (2)
C4—N1—C1—C2	−52.5 (3)	C4—N1—C5—C6	171.6 (2)
N1—C1—C2—O1	57.3 (4)	N1—C5—C6—C8	−155.2 (2)
C6—O2—C7—N2	−5.3 (3)	C1—N1—C5—C6	−64.9 (3)
O2—C7—N2—C8	−5.4 (3)	N1—C5—C6—O2	88.5 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H41···Cl1^i	0.86	2.42	3.225 (3)	157
O4—H42···O3^ii	0.85	2.11	2.914 (3)	159
O4—H42···N3^ii	0.85	2.88	3.473 (3)	128
N1—H1N···Cl1	0.84 (3)	2.23 (3)	3.051 (3)	165 (3)
C4—H4A···O3^ii	0.96	2.45	3.390 (4)	165
C5—H5A···O4	0.96	2.29	3.243 (4)	173
C5—H5B···Cl1^iii	0.96	2.81	3.715 (3)	158

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