Download citation
Download citation
link to html
Two polymorphs of safinamide {systematic name: (2S)-2-[4-(3-fluoro­benzyl­oxy)benzyl­amino]­propionamide}, C17H19FN2O2, a potent selective and reversible monoamine oxidase B (MAO-B) inhibitor, are described. Both forms are ortho­rhom­bic and regarded as conformational polymorphs due to the differences in the orientation of the 3-fluoro­benzyl­oxy and propanamide groups. Both structures pack with layers in the ac plane. In polymorph (I), the layers have discrete wide and narrow regions which are complementary when located next to adjacent layers. In polymorph (II), the layer has long flanges protruding from each side, which inter­digitate when packed with the adjacent layers. N-H...O hydrogen bonds are present in both structures, whereas N-H...F hydrogen bonding is seen in polymorph (I), while N-H...N hydrogen bonding is seen in polymorph (II).

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270110019384/sf3130sup1.cif
Contains datablocks I, II, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270110019384/sf3130Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270110019384/sf3130IIsup3.hkl
Contains datablock II

CCDC references: 782545; 782546

Comment top

Monoamino oxidases (MAOs) are flavin adenine dinucleotide (FAD) containing enzymes localized in the outer mitochondrial membrane. Two different isoenzymatic forms have been identified, namely, MAO-A and MAO-B, which differ in their amino acid sequences, three-dimensional structures, substrate specificity and sensitivity to inhibitors. Safinamide, a derivative of the chemical class of aminoamides, has been developed by Newron Pharmaceuticals, Bresso, Italy, and was initially reported by Pharmacia & Upjohn as a potent anticonvulsant (Pevarello et al., 1998). It acts by means of multiple mechanisms of action that comprise MAO-B and dopamine uptake inhibition, sodium and calcium channel modulation, and reduction of glutamate release in the central nervous system (Caccia et al., 2006). Due to its excellent therapeutic properties and safety margin, safinamide has been developed as an antiparkinsonian and anticonvulsant agent.

Polymorphism is often characterized as the ability of a drug substance to exist as two or more crystalline phases that have different arrangements and/or conformations of the molecules in the crystal lattice (Grant, 1999). The last decade has witnessed many developments in the design and characterization of polymorphs, due to the increased awareness of the possibility of multiple crystal forms of a substance, the utility that may be derived from preparing a crystal form with enhanced properties, and the potential intellectual property implications of new crystal forms.

The present study is a continuation of our investigation of the structural characterization of pharmaceutical compounds (Ravikumar & Sridhar, 2007; Ravikumar et al., 2008; Ravikumar & Sridhar, 2009). We report here the crystal structures of two polymorphic forms of safinamide, (I) and (II).

Both polymorphs (I) and (II) crystallize in space group P212121 and were assigned the known handedness (the asymmetric centre C15 has the S configuration). The molecular structures observed in polymorphs (I) and (II) are composed of a central aromatic ring substituted at C8 by a fluorobenzyloxy group and at C11 by an alaninamide group (Figs. 1 and 2). The bond lengths in the two structures are the same to within 3σ. The exocyclic bond angles involving atom C1 differ by up to 5.3° (Table 3); the sense of these deviations suggests interactions between atoms O1 and C2 [in (I)] or C6 [in (II)], possibly associated with weak intramolecular C—H···O hydrogen bonds. The slight variation in the bond angles involving the amine atom N1 may be attributed to its involvement in different types of hydrogen-bonding interactions. The significant conformational differences between polymorphs (I) and (II) are in the orientations of the fluorobenzyloxy and alaninamide groups in relation to the central aromatic ring. The fluoro-substituted phenyl ring is cisoid [C2—C1—C7—O1 = 16.8 (5)°] to the ether atom O1 in (I), while it is transoid [C2—C1—C7—O1 = 171.2 (3)°] in (II). Similarly, the alaninamide group is in a -sc,-sc,-sp orientation in (I), whereas it is -ap,sc,ac in (II).

It is noteworthy that in the crystal structure of the complex safinamide–human monoamine oxidase [Binda et al., 2007; Protein Data Bank (Berman et al., 2000) entry 2 V5Z], the extracted ligand structure (Fig. 3) shows another significant difference in the orientation of the C8 and C11 substituents (C2—C1—C7—O1 = -44.8°, and the alaninamide group is in an -ap,-ac,-sc orientation). It is interesting to note that the alaninamide chain is in an extended conformation in the extracted ligand structure and perhaps it may be speculated that a third polymorph of the title compound is possible with such features.

Substantial differences in the molecular packing of the polymorphs are observed. Both structures (I) and (II) pack with layers in the ac plane. In (I), the layers have discrete wide and narrow regions which are complementary when located next to adjacent layers. In (II), the layer has long flanges protruding from each side, which interdigitate when packed with the adjacent layers.

The amide groups are associated to form the core of the hydrogen-bonding networks in (I) (Table 1). Amide atom N2 connects two adjacent molecules by N—H···OC hydrogen bonding involving only the amide groups, creating an R32(8) motif (Etter, 1990; Etter et al., 1990; Bernstein et al., 1995). The hydrogen-bonded amide groups are coplanar, forming a ribbon-like packing motif along the a axis (Fig. 4). Amine atom N1 forms an N—H···F interaction with an adjacent fluorobenzyl group, developing a helical hydrogen-bonded catemer along the a axis and cross-linking neighbouring ribbon-like motifs along the c axis to give the two-dimensional supramolecular hydrogen-bonded network.

Fig. 5 illustrates the packing for (II), wherein one N2—H forms an N—H···OC interaction with another amide (Table 3). This generates a ribbon-like pattern of R22(9) motifs along the a axis. The second amide H atom bound to N2 forms an N—H···N hydrogen bond to an amine, generating an R43(11) motif in combination with N—H···O hydrogen bonds, resulting in an infinite two-dimensional supramolecular hydrogen-bonded network. A stacking interaction between pairs of aromatic and fluorobenzyl rings [centroid-to-centroid separation = 3.875 (2) Å; symmetry code: -1/2 + x, 3/2 - y, -z] occurs between adjacent layers. The F atom in (II) is involved in an intermolecular C—H···F interaction. Ether atom O1 is not involved in any intermolecular hydrogen-bonding interactions in either polymorph.

In conclusion, it can be seen that the two polymorphic structures, (I) and (II), which differ significantly in the orientation of the two substituents at C8 and C11, give rise to two different modifications of the crystal packing.

Related literature top

For related literature, see: Berman et al. (2000); Bernstein et al. (1995); Binda et al. (2007); Caccia et al. (2006); Etter (1990); Etter, MacDonald & Bernstein (1990); Grant (1999); Pevarello et al. (1998); Ravikumar & Sridhar (2007, 2009); Ravikumar et al. (2008).

Experimental top

Plate-shaped single crystals of polymorph (I) were obtained by slow evaporation of the title compound (25 mg) from benzene (10 ml) and hexane (2 ml) solutions stirred and warmed slightly over a steam bath for 10 min. Needle-shaped crystals of polymorph (II) were obtained by slow evaporation from ethyl acetate (8 ml) and hexane (2 ml) solutions stirred and warmed slightly over a steam bath for 10 min.

Refinement top

All N-bound H atoms were located in difference Fourier maps, and their positions and isotropic displacement parameters were located and refined. All other H atoms were located in a difference density map but were positioned geometrically and included as riding atoms, with C—H = 0.93–0.98 Å, and with Uiso(H) = 1.5Ueq(C) for methyl H or 1.2Ueq(C) for the other H atoms. In the absence of significant anomalous scattering effects, Friedel pairs were merged. The absolute configuration of safinamide was known in advance.

Computing details top

For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005) and Mercury (Macrae et al., 2008)'; software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. A perspective drawing of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. A perspective drawing of (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 3] Fig. 3. A superposition of the molecular conformations of safinamide molecules. The overlay was made by making a least-squares fit through the central aromatic ring system (C8–C13) of safinamide polymorph (I). The labels and r.m.s deviations (Å) are as follows: safinamide polymorph (II), 0.012; extracted structure of safinamide from safinamide–human monoamine oxidase complex, (III), 0.025. H atoms have been omitted for clarity.
[Figure 4] Fig. 4. A partial packing diagram for (I), with extracellular molecules, depicting the ribbon-like packing motif generated by the N—H···O hydrogen bonds, along with N—H···F helical hydrogen-bonded catemers. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity. Selected atoms of the molecules present in the asymmetric unit are labelled, primarily to provide a key for the coding of the atoms. [Symmetry codes: (i) x + 3/2, -y + 1/2, -z + 2; (ii) x + 1, y, z; (iii) x + 1/2, -y + 1/2, -z + 1.]
[Figure 5] Fig. 5. A partial packing diagram for (II), with extracellular molecules, depicting the ribbon-like pattern generated by the N—H···O and N—H···N hydrogen bonds (dashed lines). H atoms not involved in hydrogen bonding have been omitted for clarity. Selected atoms of the molecules present in the asymmetric unit are labelled, primarily to provide a key for the coding of the atoms. [Symmetry codes: (i) -x + 1, y - 1/2, -z + 1/2; (ii) -x, y + 1/2, -z + 1/2; (iii) -x + 1, y + 1/2, -z + 1/2 (this atom lies exactly behind atom O2i).]
(I) (2S)-2-[4-(3-fluorobenzyloxy)benzylamino]propionamide top
Crystal data top
C17H19FN2O2F(000) = 640
Mr = 302.34Dx = 1.231 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 1832 reflections
a = 5.1127 (5) Åθ = 2.3–17.4°
b = 17.8516 (16) ŵ = 0.09 mm1
c = 17.8746 (1) ÅT = 294 K
V = 1631.4 (2) Å3Flaky plate, colourless
Z = 40.14 × 0.10 × 0.06 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1179 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.057
Graphite monochromatorθmax = 25.0°, θmin = 1.6°
ω scansh = 66
15763 measured reflectionsk = 2121
1698 independent reflectionsl = 2121
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113H atoms treated by a mixture of independent and constrained refinement
S = 0.97 w = 1/[σ2(Fo2) + (0.0525P)2 + 0.3868P]
where P = (Fo2 + 2Fc2)/3
1698 reflections(Δ/σ)max < 0.001
212 parametersΔρmax = 0.15 e Å3
0 restraintsΔρmin = 0.12 e Å3
Crystal data top
C17H19FN2O2V = 1631.4 (2) Å3
Mr = 302.34Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.1127 (5) ŵ = 0.09 mm1
b = 17.8516 (16) ÅT = 294 K
c = 17.8746 (1) Å0.14 × 0.10 × 0.06 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1179 reflections with I > 2σ(I)
15763 measured reflectionsRint = 0.057
1698 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0420 restraints
wR(F2) = 0.113H atoms treated by a mixture of independent and constrained refinement
S = 0.97Δρmax = 0.15 e Å3
1698 reflectionsΔρmin = 0.12 e Å3
212 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.2831 (8)0.0072 (2)1.01349 (19)0.0624 (9)
C20.1661 (9)0.0617 (2)1.0556 (2)0.0774 (12)
H20.20990.11181.04910.093*
C30.0151 (10)0.0411 (3)1.1070 (3)0.0911 (14)
C40.0915 (10)0.0304 (3)1.1186 (3)0.0955 (15)
H40.21940.04201.15380.115*
C50.0249 (10)0.0846 (3)1.0772 (3)0.0917 (14)
H50.02160.13451.08420.110*
C60.2108 (9)0.0663 (2)1.0250 (2)0.0808 (12)
H60.28920.10400.99700.097*
C70.4762 (9)0.0250 (2)0.9525 (2)0.0747 (11)
H7A0.62220.00960.95490.090*
H7B0.39320.01970.90400.090*
C80.7410 (8)0.1249 (2)0.9092 (2)0.0636 (10)
C90.8390 (9)0.1955 (2)0.9215 (2)0.0745 (12)
H90.78490.22260.96320.089*
C101.0159 (9)0.2264 (2)0.8728 (2)0.0758 (11)
H101.08100.27410.88240.091*
C111.1003 (7)0.1884 (2)0.8094 (2)0.0639 (10)
C121.0019 (9)0.1185 (2)0.7984 (2)0.0753 (11)
H121.05760.09140.75700.090*
C130.8210 (8)0.0858 (2)0.8468 (2)0.0755 (11)
H130.75530.03820.83710.091*
C141.2953 (8)0.2220 (2)0.7559 (2)0.0771 (12)
H14A1.46320.22460.78110.093*
H14B1.31470.18810.71390.093*
C150.9785 (7)0.30437 (19)0.69276 (18)0.0531 (9)
H150.85470.27260.72010.064*
C160.9790 (6)0.28013 (19)0.61121 (18)0.0485 (8)
C170.8823 (10)0.3847 (2)0.6968 (3)0.0930 (15)
H17A0.86870.39980.74820.140*
H17B0.71380.38830.67340.140*
H17C1.00360.41690.67140.140*
F10.1339 (8)0.09638 (19)1.14651 (19)0.1656 (16)
N11.2348 (6)0.2958 (2)0.72683 (16)0.0657 (9)
H1N1.261 (10)0.328 (2)0.763 (2)0.110 (17)*
N21.2062 (6)0.2778 (2)0.57748 (18)0.0611 (8)
H2N1.344 (8)0.285 (2)0.607 (2)0.067 (11)*
H3N1.219 (7)0.2644 (16)0.5328 (17)0.056 (10)*
O10.5665 (6)0.09873 (14)0.96168 (14)0.0758 (8)
O20.7690 (4)0.26650 (14)0.57990 (12)0.0624 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.067 (2)0.064 (2)0.056 (2)0.001 (2)0.002 (2)0.0046 (18)
C20.092 (3)0.061 (2)0.080 (3)0.010 (2)0.012 (3)0.006 (2)
C30.102 (4)0.088 (3)0.083 (3)0.005 (3)0.031 (3)0.022 (3)
C40.099 (4)0.116 (4)0.072 (3)0.021 (3)0.023 (3)0.008 (3)
C50.112 (4)0.074 (3)0.089 (3)0.025 (3)0.007 (3)0.009 (3)
C60.097 (3)0.069 (3)0.077 (3)0.005 (3)0.008 (3)0.005 (2)
C70.081 (3)0.069 (2)0.074 (2)0.005 (2)0.012 (3)0.007 (2)
C80.061 (2)0.077 (3)0.053 (2)0.003 (2)0.005 (2)0.0117 (19)
C90.089 (3)0.079 (3)0.055 (2)0.016 (2)0.014 (2)0.003 (2)
C100.083 (3)0.084 (3)0.060 (2)0.022 (3)0.003 (2)0.001 (2)
C110.053 (2)0.090 (3)0.048 (2)0.003 (2)0.0041 (19)0.008 (2)
C120.069 (3)0.099 (3)0.058 (2)0.010 (3)0.010 (2)0.007 (2)
C130.076 (3)0.074 (3)0.076 (3)0.002 (2)0.011 (3)0.007 (2)
C140.050 (2)0.127 (3)0.054 (2)0.001 (3)0.0032 (19)0.019 (2)
C150.0468 (19)0.068 (2)0.0442 (18)0.0126 (19)0.0045 (18)0.0015 (16)
C160.0349 (18)0.064 (2)0.0464 (17)0.0063 (17)0.0023 (17)0.0032 (16)
C170.108 (4)0.083 (3)0.088 (3)0.001 (3)0.008 (3)0.017 (2)
F10.199 (4)0.140 (3)0.158 (3)0.003 (3)0.095 (3)0.049 (2)
N10.0521 (18)0.101 (3)0.0444 (16)0.025 (2)0.0038 (16)0.0012 (17)
N20.0380 (16)0.104 (3)0.0412 (18)0.0050 (17)0.0007 (17)0.0040 (17)
O10.090 (2)0.0674 (17)0.0704 (16)0.0125 (15)0.0170 (16)0.0035 (13)
O20.0353 (13)0.0974 (18)0.0545 (14)0.0076 (13)0.0045 (12)0.0080 (13)
Geometric parameters (Å, º) top
C1—C21.368 (5)C10—H100.9300
C1—C61.379 (5)C11—C121.360 (5)
C1—C71.504 (5)C11—C141.506 (5)
C2—C31.356 (6)C12—C131.394 (5)
C2—H20.9300C12—H120.9300
C3—C41.350 (6)C13—H130.9300
C3—F11.357 (5)C14—N11.450 (5)
C4—C51.357 (6)C14—H14A0.9700
C4—H40.9300C14—H14B0.9700
C5—C61.371 (6)C15—N11.453 (5)
C5—H50.9300C15—C171.518 (5)
C6—H60.9300C15—C161.521 (5)
C7—O11.405 (4)C15—H150.9800
C7—H7A0.9700C16—O21.235 (4)
C7—H7B0.9700C16—N21.309 (4)
C8—C91.374 (5)C17—H17A0.9600
C8—O11.376 (4)C17—H17B0.9600
C8—C131.378 (5)C17—H17C0.9600
C9—C101.371 (5)N1—H1N0.88 (4)
C9—H90.9300N2—H2N0.88 (4)
C10—C111.389 (5)N2—H3N0.84 (3)
C2—C1—C6118.5 (4)C10—C11—C14121.9 (4)
C2—C1—C7122.4 (4)C11—C12—C13122.7 (4)
C6—C1—C7119.0 (4)C11—C12—H12118.6
C3—C2—C1118.6 (4)C13—C12—H12118.6
C3—C2—H2120.7C8—C13—C12119.1 (4)
C1—C2—H2120.7C8—C13—H13120.5
C4—C3—C2124.0 (4)C12—C13—H13120.5
C4—C3—F1118.6 (5)N1—C14—C11116.7 (3)
C2—C3—F1117.4 (4)N1—C14—H14A108.1
C3—C4—C5117.6 (4)C11—C14—H14A108.1
C3—C4—H4121.2N1—C14—H14B108.1
C5—C4—H4121.2C11—C14—H14B108.1
C4—C5—C6120.3 (4)H14A—C14—H14B107.3
C4—C5—H5119.8N1—C15—C17111.8 (3)
C6—C5—H5119.8N1—C15—C16111.7 (3)
C5—C6—C1121.0 (4)C17—C15—C16108.4 (3)
C5—C6—H6119.5N1—C15—H15108.3
C1—C6—H6119.5C17—C15—H15108.3
O1—C7—C1109.2 (3)C16—C15—H15108.3
O1—C7—H7A109.8O2—C16—N2123.8 (3)
C1—C7—H7A109.8O2—C16—C15119.3 (3)
O1—C7—H7B109.8N2—C16—C15116.9 (3)
C1—C7—H7B109.8C15—C17—H17A109.5
H7A—C7—H7B108.3C15—C17—H17B109.5
C9—C8—O1116.0 (3)H17A—C17—H17B109.5
C9—C8—C13119.1 (4)C15—C17—H17C109.5
O1—C8—C13124.9 (4)H17A—C17—H17C109.5
C8—C9—C10120.5 (4)H17B—C17—H17C109.5
C8—C9—H9119.7C14—N1—C15116.0 (3)
C10—C9—H9119.7C14—N1—H1N107 (3)
C9—C10—C11121.7 (4)C15—N1—H1N112 (3)
C9—C10—H10119.1C16—N2—H2N115 (2)
C11—C10—H10119.1C16—N2—H3N121 (3)
C12—C11—C10116.8 (4)H2N—N2—H3N123 (4)
C12—C11—C14121.2 (4)C8—O1—C7116.9 (3)
C6—C1—C2—C30.2 (6)C10—C11—C12—C131.2 (6)
C7—C1—C2—C3176.9 (4)C14—C11—C12—C13179.9 (3)
C1—C2—C3—C41.2 (8)C9—C8—C13—C120.8 (6)
C1—C2—C3—F1178.1 (4)O1—C8—C13—C12179.2 (3)
C2—C3—C4—C51.4 (8)C11—C12—C13—C81.2 (6)
F1—C3—C4—C5178.3 (5)C12—C11—C14—N1128.0 (4)
C3—C4—C5—C60.8 (7)C10—C11—C14—N153.1 (5)
C4—C5—C6—C10.0 (7)N1—C15—C16—O2162.4 (3)
C2—C1—C6—C50.3 (6)C17—C15—C16—O274.0 (4)
C7—C1—C6—C5176.5 (4)N1—C15—C16—N220.1 (5)
C2—C1—C7—O116.8 (5)C17—C15—C16—N2103.5 (4)
C6—C1—C7—O1166.5 (4)C11—C14—N1—C1552.8 (5)
O1—C8—C9—C10179.4 (4)C17—C15—N1—C14153.6 (3)
C13—C8—C9—C100.6 (6)C16—C15—N1—C1484.7 (4)
C8—C9—C10—C110.6 (6)C9—C8—O1—C7176.3 (4)
C9—C10—C11—C120.9 (6)C13—C8—O1—C73.7 (5)
C9—C10—C11—C14179.8 (4)C1—C7—O1—C8178.4 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···F1i0.88 (4)2.17 (4)3.046 (4)174 (5)
N2—H2N···N10.88 (4)2.23 (4)2.693 (4)113 (3)
N2—H2N···O2ii0.88 (4)2.25 (4)2.885 (4)128 (3)
N2—H3N···O2iii0.84 (3)2.10 (3)2.940 (3)177 (3)
C2—H2···O10.932.412.729 (5)100
C14—H14A···Cg2ii0.972.983.873 (4)153
Symmetry codes: (i) x+3/2, y+1/2, z+2; (ii) x+1, y, z; (iii) x+1/2, y+1/2, z+1.
(II) 2(S)-[4-(3-Fluorobenzyloxy) benzylamino] propionamide top
Crystal data top
C17H19FN2O2F(000) = 640
Mr = 302.34Dx = 1.277 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 5921 reflections
a = 6.6297 (9) Åθ = 2.8–26.1°
b = 8.1015 (12) ŵ = 0.09 mm1
c = 29.268 (4) ÅT = 294 K
V = 1572.0 (4) Å3Needle, colourless
Z = 40.15 × 0.10 × 0.05 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1573 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.025
Graphite monochromatorθmax = 25.0°, θmin = 1.4°
ω scansh = 77
15166 measured reflectionsk = 99
1636 independent reflectionsl = 3434
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.121H atoms treated by a mixture of independent and constrained refinement
S = 1.22 w = 1/[σ2(Fo2) + (0.0658P)2 + 0.2636P]
where P = (Fo2 + 2Fc2)/3
1636 reflections(Δ/σ)max < 0.001
212 parametersΔρmax = 0.19 e Å3
0 restraintsΔρmin = 0.17 e Å3
Crystal data top
C17H19FN2O2V = 1572.0 (4) Å3
Mr = 302.34Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 6.6297 (9) ŵ = 0.09 mm1
b = 8.1015 (12) ÅT = 294 K
c = 29.268 (4) Å0.15 × 0.10 × 0.05 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1573 reflections with I > 2σ(I)
15166 measured reflectionsRint = 0.025
1636 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0430 restraints
wR(F2) = 0.121H atoms treated by a mixture of independent and constrained refinement
S = 1.22Δρmax = 0.19 e Å3
1636 reflectionsΔρmin = 0.17 e Å3
212 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.1171 (5)0.4371 (4)0.02528 (9)0.0495 (7)
C20.2923 (5)0.3716 (4)0.04292 (9)0.0520 (7)
H20.41620.39480.02950.062*
C30.2811 (5)0.2712 (4)0.08073 (10)0.0541 (8)
C40.1047 (6)0.2333 (4)0.10173 (11)0.0619 (9)
H40.10170.16540.12730.074*
C50.0688 (6)0.2983 (5)0.08393 (12)0.0687 (10)
H50.19210.27380.09750.082*
C60.0627 (5)0.4006 (5)0.04589 (11)0.0630 (9)
H60.18170.44460.03430.076*
C70.1350 (5)0.5511 (4)0.01517 (10)0.0561 (8)
H7A0.20030.65290.00600.067*
H7B0.21690.49960.03870.067*
C80.0697 (5)0.6838 (4)0.07106 (10)0.0524 (8)
C90.2585 (6)0.6969 (4)0.09069 (11)0.0621 (9)
H90.36670.63830.07860.074*
C100.2863 (6)0.7973 (4)0.12828 (11)0.0632 (9)
H100.41380.80530.14130.076*
C110.1288 (6)0.8859 (4)0.14691 (9)0.0548 (8)
C120.0589 (5)0.8686 (4)0.12731 (10)0.0580 (8)
H120.16750.92560.13980.070*
C130.0904 (5)0.7689 (4)0.08958 (10)0.0570 (8)
H130.21850.75950.07690.068*
C140.1626 (6)1.0039 (4)0.18580 (9)0.0611 (9)
H14A0.29141.05850.18160.073*
H14B0.05841.08790.18510.073*
C150.1719 (4)1.0422 (3)0.26796 (9)0.0375 (6)
H150.04131.09830.27030.045*
C160.3358 (4)1.1737 (3)0.26122 (8)0.0339 (5)
C170.2095 (7)0.9497 (4)0.31239 (9)0.0648 (10)
H17A0.10370.87060.31720.097*
H17B0.21161.02660.33730.097*
H17C0.33680.89360.31070.097*
F10.4535 (3)0.2103 (3)0.09842 (8)0.0809 (7)
N10.1607 (3)0.9244 (3)0.23036 (7)0.0337 (5)
H1N0.262 (4)0.853 (3)0.2338 (8)0.027 (6)*
N20.2709 (4)1.3273 (3)0.25989 (9)0.0446 (6)
H2N0.144 (6)1.344 (4)0.2631 (10)0.049 (8)*
H3N0.359 (5)1.402 (4)0.2545 (9)0.038 (7)*
O10.0592 (3)0.5858 (3)0.03269 (7)0.0640 (6)
O20.5132 (3)1.1349 (2)0.25693 (8)0.0516 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0547 (17)0.0506 (16)0.0433 (14)0.0022 (15)0.0081 (12)0.0073 (13)
C20.0493 (16)0.0571 (17)0.0494 (15)0.0001 (16)0.0037 (13)0.0053 (14)
C30.0588 (19)0.0533 (17)0.0503 (16)0.0040 (16)0.0146 (14)0.0018 (14)
C40.075 (2)0.0593 (19)0.0518 (16)0.0074 (19)0.0025 (16)0.0040 (15)
C50.061 (2)0.076 (2)0.070 (2)0.007 (2)0.0067 (17)0.0030 (19)
C60.0503 (17)0.072 (2)0.0667 (19)0.0060 (18)0.0071 (15)0.0006 (17)
C70.0550 (18)0.0638 (19)0.0495 (15)0.0036 (17)0.0088 (14)0.0007 (15)
C80.0618 (19)0.0500 (16)0.0455 (14)0.0076 (16)0.0086 (14)0.0056 (13)
C90.062 (2)0.0597 (19)0.0650 (18)0.0002 (18)0.0130 (17)0.0039 (16)
C100.068 (2)0.0573 (18)0.0643 (18)0.0047 (18)0.0253 (17)0.0024 (16)
C110.077 (2)0.0401 (14)0.0472 (15)0.0121 (16)0.0145 (15)0.0089 (13)
C120.070 (2)0.0553 (17)0.0488 (15)0.0038 (17)0.0002 (15)0.0003 (15)
C130.0548 (19)0.0652 (19)0.0510 (16)0.0104 (17)0.0089 (14)0.0022 (14)
C140.093 (3)0.0394 (14)0.0510 (15)0.0149 (18)0.0150 (17)0.0076 (12)
C150.0326 (13)0.0297 (12)0.0502 (13)0.0001 (10)0.0053 (12)0.0002 (11)
C160.0304 (12)0.0290 (11)0.0423 (12)0.0010 (10)0.0028 (10)0.0031 (10)
C170.103 (3)0.0461 (16)0.0452 (15)0.016 (2)0.0050 (17)0.0025 (13)
F10.0726 (13)0.0881 (15)0.0820 (13)0.0113 (12)0.0212 (11)0.0177 (12)
N10.0293 (10)0.0271 (9)0.0447 (11)0.0036 (9)0.0022 (9)0.0033 (9)
N20.0288 (12)0.0276 (11)0.0774 (16)0.0024 (9)0.0038 (11)0.0032 (11)
O10.0612 (13)0.0750 (15)0.0559 (12)0.0052 (13)0.0101 (10)0.0126 (11)
O20.0314 (9)0.0310 (9)0.0925 (15)0.0028 (8)0.0001 (9)0.0058 (10)
Geometric parameters (Å, º) top
C1—C61.368 (5)C10—H100.9300
C1—C21.378 (4)C11—C121.378 (5)
C1—C71.506 (4)C11—C141.503 (4)
C2—C31.375 (4)C12—C131.384 (4)
C2—H20.9300C12—H120.9300
C3—F11.348 (4)C13—H130.9300
C3—C41.357 (5)C14—N11.454 (3)
C4—C51.368 (5)C14—H14A0.9700
C4—H40.9300C14—H14B0.9700
C5—C61.388 (5)C15—N11.458 (3)
C5—H50.9300C15—C171.521 (4)
C6—H60.9300C15—C161.535 (3)
C7—O11.414 (4)C15—H150.9800
C7—H7A0.9700C16—O21.223 (3)
C7—H7B0.9700C16—N21.318 (3)
C8—C131.377 (5)C17—H17A0.9600
C8—O11.377 (4)C17—H17B0.9600
C8—C91.382 (5)C17—H17C0.9600
C9—C101.380 (5)N1—H1N0.89 (3)
C9—H90.9300N2—H2N0.86 (4)
C10—C111.379 (5)N2—H3N0.85 (3)
C6—C1—C2119.1 (3)C10—C11—C14121.2 (3)
C6—C1—C7123.2 (3)C11—C12—C13121.9 (3)
C2—C1—C7117.7 (3)C11—C12—H12119.1
C3—C2—C1118.9 (3)C13—C12—H12119.1
C3—C2—H2120.5C8—C13—C12119.3 (3)
C1—C2—H2120.5C8—C13—H13120.3
F1—C3—C4118.3 (3)C12—C13—H13120.3
F1—C3—C2118.6 (3)N1—C14—C11113.3 (2)
C4—C3—C2123.0 (3)N1—C14—H14A108.9
C3—C4—C5117.7 (3)C11—C14—H14A108.9
C3—C4—H4121.1N1—C14—H14B108.9
C5—C4—H4121.1C11—C14—H14B108.9
C4—C5—C6120.7 (3)H14A—C14—H14B107.7
C4—C5—H5119.6N1—C15—C17109.4 (2)
C6—C5—H5119.6N1—C15—C16113.1 (2)
C1—C6—C5120.5 (3)C17—C15—C16109.6 (2)
C1—C6—H6119.7N1—C15—H15108.2
C5—C6—H6119.7C17—C15—H15108.2
O1—C7—C1109.6 (3)C16—C15—H15108.2
O1—C7—H7A109.8O2—C16—N2123.6 (2)
C1—C7—H7A109.8O2—C16—C15121.1 (2)
O1—C7—H7B109.8N2—C16—C15115.4 (2)
C1—C7—H7B109.8C15—C17—H17A109.5
H7A—C7—H7B108.2C15—C17—H17B109.5
C13—C8—O1124.8 (3)H17A—C17—H17B109.5
C13—C8—C9119.8 (3)C15—C17—H17C109.5
O1—C8—C9115.4 (3)H17A—C17—H17C109.5
C10—C9—C8119.8 (3)H17B—C17—H17C109.5
C10—C9—H9120.1C14—N1—C15112.8 (2)
C8—C9—H9120.1C14—N1—H1N112.3 (16)
C11—C10—C9121.4 (3)C15—N1—H1N107.4 (16)
C11—C10—H10119.3C16—N2—H2N118 (2)
C9—C10—H10119.3C16—N2—H3N116.6 (19)
C12—C11—C10117.8 (3)H2N—N2—H3N125 (3)
C12—C11—C14121.0 (3)C8—O1—C7117.1 (2)
C6—C1—C2—C30.0 (4)C10—C11—C12—C131.4 (5)
C7—C1—C2—C3178.0 (3)C14—C11—C12—C13175.7 (3)
C1—C2—C3—F1178.6 (3)O1—C8—C13—C12177.5 (3)
C1—C2—C3—C40.0 (5)C9—C8—C13—C121.0 (5)
F1—C3—C4—C5178.8 (3)C11—C12—C13—C80.2 (5)
C2—C3—C4—C50.3 (5)C12—C11—C14—N198.5 (4)
C3—C4—C5—C60.5 (5)C10—C11—C14—N184.5 (4)
C2—C1—C6—C50.3 (5)N1—C15—C16—O259.6 (3)
C7—C1—C6—C5178.1 (3)C17—C15—C16—O262.8 (3)
C4—C5—C6—C10.5 (6)N1—C15—C16—N2119.6 (3)
C6—C1—C7—O110.9 (5)C17—C15—C16—N2118.0 (3)
C2—C1—C7—O1171.2 (3)C11—C14—N1—C15173.8 (3)
C13—C8—C9—C101.0 (5)C17—C15—N1—C14169.3 (3)
O1—C8—C9—C10177.6 (3)C16—C15—N1—C1446.8 (3)
C8—C9—C10—C110.1 (5)C13—C8—O1—C79.8 (4)
C9—C10—C11—C121.3 (5)C9—C8—O1—C7171.7 (3)
C9—C10—C11—C14175.7 (3)C1—C7—O1—C8177.6 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O2i0.89 (3)2.33 (3)3.212 (3)171 (2)
N2—H2N···N1ii0.86 (4)2.13 (4)2.981 (3)171 (3)
N2—H3N···O2iii0.85 (3)2.10 (3)2.916 (3)160 (3)
C6—H6···O10.932.412.746 (4)101
C5—H5···F1iv0.932.413.274 (4)155
Symmetry codes: (i) x+1, y1/2, z+1/2; (ii) x, y+1/2, z+1/2; (iii) x+1, y+1/2, z+1/2; (iv) x+1, y, z.

Experimental details

(I)(II)
Crystal data
Chemical formulaC17H19FN2O2C17H19FN2O2
Mr302.34302.34
Crystal system, space groupOrthorhombic, P212121Orthorhombic, P212121
Temperature (K)294294
a, b, c (Å)5.1127 (5), 17.8516 (16), 17.8746 (1)6.6297 (9), 8.1015 (12), 29.268 (4)
V3)1631.4 (2)1572.0 (4)
Z44
Radiation typeMo KαMo Kα
µ (mm1)0.090.09
Crystal size (mm)0.14 × 0.10 × 0.060.15 × 0.10 × 0.05
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Bruker SMART APEX CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
15763, 1698, 1179 15166, 1636, 1573
Rint0.0570.025
(sin θ/λ)max1)0.5950.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.113, 0.97 0.043, 0.121, 1.22
No. of reflections16981636
No. of parameters212212
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.15, 0.120.19, 0.17

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg & Putz, 2005) and Mercury (Macrae et al., 2008)'.

Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···F1i0.88 (4)2.17 (4)3.046 (4)174 (5)
N2—H2N···N10.88 (4)2.23 (4)2.693 (4)113 (3)
N2—H2N···O2ii0.88 (4)2.25 (4)2.885 (4)128 (3)
N2—H3N···O2iii0.84 (3)2.10 (3)2.940 (3)177 (3)
C2—H2···O10.932.412.729 (5)100
C14—H14A···Cg2ii0.972.983.873 (4)153
Symmetry codes: (i) x+3/2, y+1/2, z+2; (ii) x+1, y, z; (iii) x+1/2, y+1/2, z+1.
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O2i0.89 (3)2.33 (3)3.212 (3)171 (2)
N2—H2N···N1ii0.86 (4)2.13 (4)2.981 (3)171 (3)
N2—H3N···O2iii0.85 (3)2.10 (3)2.916 (3)160 (3)
C6—H6···O10.932.412.746 (4)101
C5—H5···F1iv0.932.413.274 (4)155
Symmetry codes: (i) x+1, y1/2, z+1/2; (ii) x, y+1/2, z+1/2; (iii) x+1, y+1/2, z+1/2; (iv) x+1, y, z.
Selected geometric parameters (Å ,° ) for polymorphs (I) and (II) top
(I)(II)
C2-C1-C6118.5 (4)119.1 (3)
C2-C1-C7122.4 (4)117.7 (3)
C6-C1-C7119.0 (4)123.2 (3)
N1-C14-C11116.7 (3)113.3 (2)
N1-C15-C16111.7 (3)113.1 (2)
N1-C15-C17111.8 (3)109.4 (2)
C14-N1-C15116.0 (3)112.8 (2)
C11-C14-N1-C15-52.8 (5)-173.8 (3)
C16-C15-N1-C14-84.7 (4)-46.8 (3)
N1-C15-C16-N2-20.1 (5)119.6 (3)
 

Follow Acta Cryst. C
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds