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Acta Cryst. (2013). E69, o927    [ doi:10.1107/S1600536813013391 ]

[(2R,3R)-3-(4-Nitrophenyl)aziridin-2-yl]methanol monohydrate

V. Gaumet, C. Denis, F. Leal, M. Madesclaire and V. P. Zaitsev

Abstract top

The title monohydrate, C9H10N2O3·H2O, contains an aziridine ring including two contiguous stereocenters, both of which exhibit an R configuration. The methylhydroxy and nitrophenyl groups are cis-disposed about the aziridine ring. The mean plane of the benzene ring is tilted to the aziridine ring by 66.65 (8)°. The nitro group is nearly coplanar with the benzene ring [dihedral angle = 2.5 (2)°]. In the crystal, the components are linked by N-H...O, O-H...N and O-H...O hydrogen bonds, generating supramolecular layers parallel to (001).

Comment top

Because of their powerful alkylating properties (Li et al., 1995), aziridine-containing natural products such as mitomycin C, dibenzyl aziridine-2,3-dicarboxylate, N-(diethylphosphonopropionyl)-2-hydroxymethylaziridine, aziridinylbenzoquinones are potent antitumor and antibiotic agents (Sheldon et al., 1999; Danshiitsoodol et al.,2006; Vicik et al., 2006; Keniche et al., 2011; Lee et al.,1992; Ngo et al., 1998). Furthermore chiral aziridine derivatives offer a combination of reactivity, synthetic flexibility, and atom economy that is commonly employed in heterocyclic chemistry for the preparation of important pharmaceutical products like effective antiretroviral drugs used in the treatment of the human immunodeficiency virus (Kim et al., 2001).

Dimensions of aziridine cycles highlight a pronounced C—C bond shortening [1.487 (2) Å] and a little C—N bond lengthening [1.478 (2) Å on average] when compared to normal open chain C—C (1.54 Å) and C—N (1.46 Å) bond lengths. Aziridine endocyclic angles are close to 60° [59.7 (1) - 60.4 (1)°] and the geometry at nitrogen is pyramidal (Zhu et al., 2006). Methyl hydroxyl and nitrophenyl groups are cis-disposed about the aziridine ring (Fig. 1) and only one invertomer was found that has the NH proton on the least hindered ring side. The nitro group is nearly coplanar with the benzene ring [C8—C9—N12—O13 = 2.5 (2)°]. The mean N—O bond lengths are in an usual range [1.216 (2) - 1.223 (2) Å] for aromatic nitro groups.

C9H10N2O3 molecules are linked into infinite chains via N1—H1···O5 intermolecular hydrogen bonds (Table 1). Along these chains, the nitro phenyl groups are located on the same side in an isotactic way (Fig. 2). Accordingly, the chain structure is additionally stabilized by an intermolecular NO2···π interaction, namely N12—O14···Cg iv [symmetry code: iv: x, y + 1, z], with distance of 3.539 (1) Å between O14 atom and centroid, Cg, of (C6—C11) aromatic ring. Chains are running parallel to the [0 1 0] direction and define hydrophilic channels occupied by water molecules.The water oxygen atom O1w acts as both donor and acceptor in four hydrogen bonds. The dihedral angle between the acceptor plane (defined by O1wv, O1w and O5vi) and the donor plane (defined by O1wiii, O1w and N1) is 86.67 (4)°. O1wv lies 0,216 (6) Å below the donor plane (Fig. 3). The hydrogen bonds lie in the lone-pair plane of the O1w atom but no preference could be discerned for the sp3 (i.e. tetrahedral) lone pair directions within that plane. The strong H-bond network between chains and water molecules builds up [(C9H10N2O3)2(H2O)2] layers parallel to the (0 0 1) plane (Fig. 2).

Related literature top

For the biological activity of aziridine derivatives, see: Li et al. (1995); Sheldon et al. (1999); Danshiitsoodol et al. (2006); Vicik et al. (2006); Keniche et al. (2011); Lee et al. (1992); Ngo et al. (1998). For the use of chiral aziridines as precursors for pharmaceutical products, see: Kim et al. (2001). For related structures, see: Zhu et al. (2006). For details of the synthesis, see: Madesclaire et al. (2013). For determination of the absolute configuration, see: Hooft et al. (2008).

Experimental top

(2R,3R)-3-(4-Nitrophenyl)aziridin-2-yl]methanol was synthesized from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propandiol by the four-step method developped by Madesclaire et al. (2013). Plate and colourless crystals of the title coumpund were obtained by slow evaporation in air of a 1:10 (v/v) methanol-ethyl acetate solution. The formation of the monohydrated compound is certainly favored by the high hygroscopicity of methanol which absorbs moisture from the air. Once formed, monocrystals are stable in air for several weeks.

Refinement top

All C-bound H atoms were positioned geometrically [C—H = 0.97 Å for methanediyl, C—H = 0.98 Å for methanetriyl and C—H = 0.93 Å for aromatic H atoms] and included in the refinement in the riding-model approximation with Uiso(H) = 1.2Ueq(C). The N– and O–bound H atoms were located from difference-Fourier maps and refined freely. O—H distances in water molecule were restrained to be equal with standard deviation 0.02, the actual value of these distances was free to refine. The absolute structure was set by reference to the known chirality of the carbon atom bearing the hydroxymethyl group, namely C2 (note that the Cahn-Ingold-Prelog designation at C2 atom is reversed by comparison with that of the starting material due to the change in priority of the substituents). Hooft parameter is poorly defined 0.1 (6), however examination of the Bijvoet pairs using the likelihood methods (Hooft et al., 2008) confirms that the absolute configuration had been correctly assigned with probability higher than 0.816.

Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. Molecular structure showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by spheres of arbitrary radius.
[Figure 2] Fig. 2. Structure projections for the title compound. Dashed lines represent intermolecular H-bond and nitro-group···π interactions. Left: projection along a, the centroids Cg are denoted by small black spheres. Right: projection along b, intra-chain interactions have been omited for clarity.
[Figure 3] Fig. 3. Two orthogonal views of hydrogen bonding around water oxygen atom O1w. Thermal ellipsoids are drawn at the 50% probability level. [Symmetry codes: (iii) -x + 2, y - 1/2, -z + 1; (v) -x + 2, y + 1/2, -z + 1; (vi) -x + 1, y - 1/2, -z + 1]
[(2R,3R)-3-(4-Nitrophenyl)aziridin-2-yl]methanol monohydrate top
Crystal data top
C9H10N2O3·H2OF(000) = 224
Mr = 212.21Dx = 1.399 Mg m3
Monoclinic, P21Melting point: 379 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 6.3064 (2) ÅCell parameters from 98 reflections
b = 5.4695 (2) Åθ = 5.1–26.3°
c = 14.6481 (5) ŵ = 0.11 mm1
β = 94.303 (2)°T = 296 K
V = 503.83 (3) Å3Plate, colourless
Z = 20.68 × 0.44 × 0.06 mm
Data collection top
Bruker APEXII CCD
diffractometer
2383 independent reflections
Radiation source: fine-focus sealed tube2031 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.020
φ and ω scansθmax = 29.1°, θmin = 4.0°
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
h = 87
Tmin = 0.944, Tmax = 1.000k = 76
5357 measured reflectionsl = 2019
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.035H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086 w = 1/[σ2(Fo2) + (0.0435P)2 + 0.0307P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
2383 reflectionsΔρmax = 0.13 e Å3
152 parametersΔρmin = 0.19 e Å3
2 restraintsAbsolute structure: The absolute configuration was assigned to agree with that of its precusor at the chiral center C2.
Primary atom site location: structure-invariant direct methods
Crystal data top
C9H10N2O3·H2OV = 503.83 (3) Å3
Mr = 212.21Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.3064 (2) ŵ = 0.11 mm1
b = 5.4695 (2) ÅT = 296 K
c = 14.6481 (5) Å0.68 × 0.44 × 0.06 mm
β = 94.303 (2)°
Data collection top
Bruker APEXII CCD
diffractometer
2383 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
2031 reflections with I > 2σ(I)
Tmin = 0.944, Tmax = 1.000Rint = 0.020
5357 measured reflectionsθmax = 29.1°
Refinement top
R[F2 > 2σ(F2)] = 0.035H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086Δρmax = 0.13 e Å3
S = 1.04Δρmin = 0.19 e Å3
2383 reflectionsAbsolute structure: The absolute configuration was assigned to agree with that of its precusor at the chiral center C2.
152 parametersFlack parameter: ?
2 restraintsRogers parameter: ?
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.

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 (Å2) top
xyzUiso*/Ueq
N10.6266 (2)0.3667 (2)0.33556 (10)0.0457 (3)
H10.573 (3)0.212 (5)0.3340 (14)0.063 (6)*
C20.4417 (2)0.5260 (3)0.34835 (10)0.0394 (3)
H20.30690.44230.35630.047*
C30.5261 (2)0.5024 (3)0.25666 (9)0.0394 (3)
H30.43880.40180.21310.047*
C40.4863 (3)0.7468 (3)0.40646 (10)0.0397 (3)
H4A0.47450.70510.47020.048*
H4B0.63030.80240.39980.048*
O50.3410 (2)0.9368 (2)0.38063 (8)0.0489 (3)
H50.256 (3)0.927 (4)0.4181 (12)0.051 (5)*
C60.6449 (2)0.7016 (3)0.21394 (9)0.0357 (3)
C70.8526 (2)0.7649 (3)0.24213 (10)0.0426 (4)
H70.92500.67820.28940.051*
C80.9530 (2)0.9552 (3)0.20089 (9)0.0422 (4)
H81.09150.99900.22050.051*
C90.8439 (2)1.0790 (3)0.13006 (9)0.0361 (3)
C100.6386 (2)1.0188 (3)0.09979 (9)0.0408 (4)
H100.56761.10430.05190.049*
C110.5409 (2)0.8300 (3)0.14185 (9)0.0401 (4)
H110.40250.78710.12180.048*
N120.9485 (2)1.2823 (3)0.08617 (8)0.0438 (3)
O131.13280 (19)1.3298 (3)0.11207 (9)0.0642 (4)
O140.8479 (2)1.3952 (3)0.02591 (8)0.0611 (4)
O1W0.9400 (2)0.4031 (3)0.47803 (9)0.0568 (3)
H1W0.856 (4)0.392 (5)0.4262 (14)0.089 (8)*
H2W0.990 (4)0.252 (4)0.491 (2)0.092 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0548 (8)0.0273 (7)0.0541 (8)0.0025 (6)0.0019 (6)0.0015 (6)
C20.0401 (8)0.0322 (8)0.0459 (7)0.0037 (6)0.0026 (6)0.0051 (7)
C30.0425 (8)0.0338 (8)0.0408 (7)0.0033 (7)0.0047 (6)0.0053 (6)
C40.0506 (9)0.0344 (8)0.0341 (7)0.0016 (7)0.0025 (6)0.0029 (6)
O50.0594 (7)0.0371 (6)0.0511 (6)0.0079 (6)0.0090 (6)0.0079 (6)
C60.0374 (7)0.0395 (8)0.0298 (6)0.0015 (6)0.0000 (5)0.0076 (6)
C70.0364 (7)0.0519 (10)0.0384 (7)0.0040 (7)0.0054 (6)0.0057 (8)
C80.0305 (7)0.0553 (10)0.0399 (7)0.0006 (7)0.0035 (5)0.0013 (8)
C90.0368 (7)0.0430 (8)0.0288 (6)0.0017 (6)0.0048 (5)0.0038 (6)
C100.0390 (8)0.0537 (10)0.0288 (6)0.0047 (7)0.0030 (5)0.0015 (7)
C110.0325 (7)0.0546 (10)0.0322 (7)0.0012 (7)0.0044 (5)0.0036 (7)
N120.0453 (7)0.0488 (9)0.0373 (6)0.0046 (6)0.0044 (5)0.0043 (6)
O130.0530 (7)0.0721 (9)0.0658 (8)0.0226 (7)0.0060 (6)0.0051 (7)
O140.0650 (8)0.0656 (9)0.0518 (6)0.0047 (7)0.0025 (5)0.0195 (6)
O1W0.0527 (7)0.0553 (8)0.0612 (7)0.0004 (6)0.0036 (6)0.0010 (7)
Geometric parameters (Å, º) top
N1—C31.476 (2)C7—C81.381 (2)
N1—C21.479 (2)C7—H70.9300
N1—H10.91 (2)C8—C91.379 (2)
C2—C31.487 (2)C8—H80.9300
C2—C41.492 (2)C9—C101.377 (2)
C2—H20.9800C9—N121.466 (2)
C3—C61.487 (2)C10—C111.372 (2)
C3—H30.9800C10—H100.9300
C4—O51.4181 (19)C11—H110.9300
C4—H4A0.9700N12—O141.2161 (17)
C4—H4B0.9700N12—O131.2231 (16)
O5—H50.798 (19)O1W—H1W0.895 (19)
C6—C71.387 (2)O1W—H2W0.90 (2)
C6—C111.3907 (19)
C3—N1—C260.44 (10)C7—C6—C11118.73 (14)
C3—N1—H1108.1 (13)C7—C6—C3123.49 (13)
C2—N1—H1104.8 (14)C11—C6—C3117.77 (13)
N1—C2—C359.67 (10)C8—C7—C6120.79 (13)
N1—C2—C4115.62 (13)C8—C7—H7119.6
C3—C2—C4121.37 (12)C6—C7—H7119.6
N1—C2—H2116.0C9—C8—C7118.67 (13)
C3—C2—H2116.0C9—C8—H8120.7
C4—C2—H2116.0C7—C8—H8120.7
N1—C3—C6119.88 (13)C10—C9—C8121.95 (14)
N1—C3—C259.88 (10)C10—C9—N12118.91 (13)
C6—C3—C2122.85 (12)C8—C9—N12119.14 (13)
N1—C3—H3114.5C11—C10—C9118.58 (13)
C6—C3—H3114.5C11—C10—H10120.7
C2—C3—H3114.5C9—C10—H10120.7
O5—C4—C2110.52 (12)C10—C11—C6121.27 (13)
O5—C4—H4A109.5C10—C11—H11119.4
C2—C4—H4A109.5C6—C11—H11119.4
O5—C4—H4B109.5O14—N12—O13123.31 (15)
C2—C4—H4B109.5O14—N12—C9118.43 (13)
H4A—C4—H4B108.1O13—N12—C9118.25 (13)
C4—O5—H5102.8 (15)H1W—O1W—H2W107 (2)
C3—N1—C2—C4112.85 (14)C6—C7—C8—C91.0 (2)
C2—N1—C3—C6112.95 (15)C7—C8—C9—C100.2 (2)
C4—C2—C3—N1103.31 (15)C7—C8—C9—N12179.60 (14)
N1—C2—C3—C6108.12 (15)C8—C9—C10—C110.1 (2)
C4—C2—C3—C64.8 (2)N12—C9—C10—C11179.30 (13)
N1—C2—C4—O5152.10 (12)C9—C10—C11—C60.4 (2)
C3—C2—C4—O583.41 (17)C7—C6—C11—C101.1 (2)
N1—C3—C6—C72.3 (2)C3—C6—C11—C10178.98 (14)
C2—C3—C6—C773.8 (2)C10—C9—N12—O141.9 (2)
N1—C3—C6—C11177.77 (13)C8—C9—N12—O14177.50 (14)
C2—C3—C6—C11106.31 (16)C10—C9—N12—O13178.12 (14)
C11—C6—C7—C81.4 (2)C8—C9—N12—O132.5 (2)
C3—C6—C7—C8178.68 (14)C2—C4—O5—H599.5 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O5i0.91 (2)2.24 (2)3.064 (2)150.0 (19)
O5—H5···O1Wii0.798 (19)2.03 (2)2.8303 (19)175.0 (17)
O1W—H1W···N10.90 (2)1.89 (2)2.772 (2)167 (2)
O1W—H2W···O1Wiii0.90 (2)2.00 (2)2.8971 (9)172 (3)
Symmetry codes: (i) x, y1, z; (ii) x+1, y+1/2, z+1; (iii) x+2, y1/2, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O5i0.91 (2)2.24 (2)3.064 (2)150.0 (19)
O5—H5···O1Wii0.798 (19)2.03 (2)2.8303 (19)175.0 (17)
O1W—H1W···N10.895 (19)1.89 (2)2.772 (2)167 (2)
O1W—H2W···O1Wiii0.90 (2)2.00 (2)2.8971 (9)172 (3)
Symmetry codes: (i) x, y1, z; (ii) x+1, y+1/2, z+1; (iii) x+2, y1/2, z+1.
references
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