Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109053906/gg3225sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109053906/gg3225Isup2.hkl |
CCDC reference: 765482
A sample of compound (I) was prepared and crystallized according to the published procedure (Häufel & Breitmaier, 1974). [Recrystallised from which solvent?]
All H atoms were located in difference maps. H atoms bonded to C or N atoms were then treated as riding atoms in geometrically idealized positions, with C—H = 0.95 (aromatic and formyl) or 0.98 Å (methyl), and N—H = 0.88 Å, and with Uiso(H) = kUeq(carrier), where k = 1.5 for the methyl group, which was permitted to rotate but not to tilt, and 1.2 for all other H atoms bonded to C or N atoms. The unique H atom of the water molecule was permitted to ride at the position deduced from a difference map, with Uiso(H) = 1.2Ueq(O), giving an O—H distance of 0.86 Å and an H—O—H angle of 108°.
Data collection: COLLECT (Nonius, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).
C11H11N3O·0.5H2O | F(000) = 888 |
Mr = 210.24 | Dx = 1.397 Mg m−3 |
Orthorhombic, Pbcn | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2n 2ab | Cell parameters from 1842 reflections |
a = 10.8346 (14) Å | θ = 3.3–25.5° |
b = 7.4952 (9) Å | µ = 0.10 mm−1 |
c = 24.621 (3) Å | T = 120 K |
V = 1999.4 (4) Å3 | Block, pale yellow |
Z = 8 | 0.28 × 0.17 × 0.12 mm |
Bruker Nonius KappaCCD area-detector diffractometer | 1842 independent reflections |
Radiation source: Bruker Nonius FR591 rotating anode | 1267 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.091 |
Detector resolution: 9.091 pixels mm-1 | θmax = 25.5°, θmin = 3.3° |
ϕ and ω scans | h = −13→12 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | k = −9→9 |
Tmin = 0.973, Tmax = 0.989 | l = −29→29 |
16503 measured 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)] = 0.055 | H-atom parameters constrained |
wR(F2) = 0.126 | w = 1/[σ2(Fo2) + (0.0215P)2 + 3.0272P] where P = (Fo2 + 2Fc2)/3 |
S = 1.16 | (Δ/σ)max = 0.001 |
1842 reflections | Δρmax = 0.24 e Å−3 |
143 parameters | Δρmin = −0.29 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0044 (7) |
C11H11N3O·0.5H2O | V = 1999.4 (4) Å3 |
Mr = 210.24 | Z = 8 |
Orthorhombic, Pbcn | Mo Kα radiation |
a = 10.8346 (14) Å | µ = 0.10 mm−1 |
b = 7.4952 (9) Å | T = 120 K |
c = 24.621 (3) Å | 0.28 × 0.17 × 0.12 mm |
Bruker Nonius KappaCCD area-detector diffractometer | 1842 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 1267 reflections with I > 2σ(I) |
Tmin = 0.973, Tmax = 0.989 | Rint = 0.091 |
16503 measured reflections |
R[F2 > 2σ(F2)] = 0.055 | 0 restraints |
wR(F2) = 0.126 | H-atom parameters constrained |
S = 1.16 | Δρmax = 0.24 e Å−3 |
1842 reflections | Δρmin = −0.29 e Å−3 |
143 parameters |
x | y | z | Uiso*/Ueq | ||
N1 | 0.5446 (2) | 0.5822 (3) | 0.61894 (8) | 0.0197 (6) | |
N2 | 0.6141 (2) | 0.5143 (3) | 0.66200 (9) | 0.0212 (6) | |
C3 | 0.7292 (3) | 0.5324 (4) | 0.64687 (10) | 0.0189 (6) | |
C4 | 0.7381 (3) | 0.6100 (4) | 0.59489 (10) | 0.0190 (6) | |
C5 | 0.6158 (3) | 0.6415 (4) | 0.57888 (11) | 0.0196 (6) | |
C31 | 0.8304 (3) | 0.4754 (4) | 0.68343 (11) | 0.0236 (7) | |
H31A | 0.8736 | 0.5809 | 0.6973 | 0.035* | |
H31B | 0.8886 | 0.4003 | 0.6633 | 0.035* | |
H31C | 0.7961 | 0.4075 | 0.7139 | 0.035* | |
C41 | 0.8434 (3) | 0.6523 (4) | 0.56410 (11) | 0.0237 (7) | |
H41 | 0.9218 | 0.6272 | 0.5796 | 0.028* | |
O41 | 0.84151 (18) | 0.7193 (3) | 0.51862 (8) | 0.0281 (5) | |
N51 | 0.5776 (2) | 0.7204 (3) | 0.53345 (9) | 0.0244 (6) | |
H51A | 0.4982 | 0.7374 | 0.5278 | 0.029* | |
H51B | 0.6316 | 0.7555 | 0.5090 | 0.029* | |
C11 | 0.4144 (3) | 0.5973 (4) | 0.62572 (10) | 0.0197 (7) | |
C12 | 0.3700 (3) | 0.6639 (4) | 0.67404 (11) | 0.0216 (7) | |
H12 | 0.4253 | 0.6990 | 0.7020 | 0.026* | |
C13 | 0.2440 (3) | 0.6790 (4) | 0.68123 (11) | 0.0237 (7) | |
H13 | 0.2119 | 0.7256 | 0.7142 | 0.028* | |
C14 | 0.1655 (3) | 0.6263 (4) | 0.64057 (11) | 0.0254 (7) | |
H14 | 0.0789 | 0.6368 | 0.6456 | 0.030* | |
C15 | 0.2105 (3) | 0.5589 (4) | 0.59287 (11) | 0.0243 (7) | |
H15 | 0.1552 | 0.5226 | 0.5650 | 0.029* | |
C16 | 0.3365 (3) | 0.5435 (4) | 0.58515 (11) | 0.0214 (7) | |
H16 | 0.3685 | 0.4963 | 0.5522 | 0.026* | |
O1 | 0.5000 | 0.3101 (4) | 0.7500 | 0.0255 (7) | |
H1 | 0.5124 | 0.3772 | 0.7223 | 0.031* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0137 (14) | 0.0243 (13) | 0.0210 (12) | 0.0001 (11) | 0.0009 (10) | 0.0034 (10) |
N2 | 0.0177 (14) | 0.0232 (13) | 0.0226 (12) | 0.0024 (11) | −0.0018 (10) | 0.0016 (10) |
C3 | 0.0155 (17) | 0.0163 (14) | 0.0248 (14) | 0.0002 (12) | 0.0005 (12) | −0.0014 (12) |
C4 | 0.0128 (16) | 0.0242 (15) | 0.0199 (13) | 0.0012 (12) | −0.0001 (12) | −0.0019 (12) |
C5 | 0.0205 (17) | 0.0189 (15) | 0.0193 (14) | 0.0002 (12) | 0.0018 (12) | −0.0017 (12) |
C31 | 0.0195 (17) | 0.0254 (16) | 0.0260 (15) | 0.0004 (13) | −0.0036 (12) | 0.0011 (12) |
C41 | 0.0155 (17) | 0.0306 (17) | 0.0249 (16) | 0.0008 (13) | 0.0000 (12) | −0.0028 (13) |
O41 | 0.0207 (12) | 0.0386 (13) | 0.0250 (11) | −0.0001 (10) | 0.0028 (9) | 0.0064 (9) |
N51 | 0.0176 (14) | 0.0328 (15) | 0.0228 (12) | 0.0005 (11) | 0.0025 (10) | 0.0059 (11) |
C11 | 0.0159 (17) | 0.0189 (15) | 0.0242 (15) | 0.0003 (12) | 0.0010 (12) | 0.0039 (12) |
C12 | 0.0200 (17) | 0.0228 (15) | 0.0219 (14) | −0.0017 (13) | −0.0001 (12) | 0.0006 (12) |
C13 | 0.0230 (18) | 0.0233 (15) | 0.0249 (15) | 0.0035 (14) | 0.0056 (13) | 0.0014 (13) |
C14 | 0.0163 (17) | 0.0287 (17) | 0.0311 (16) | 0.0008 (13) | 0.0022 (13) | 0.0067 (13) |
C15 | 0.0209 (18) | 0.0253 (16) | 0.0268 (16) | −0.0051 (13) | −0.0056 (12) | 0.0057 (13) |
C16 | 0.0207 (17) | 0.0216 (16) | 0.0218 (14) | −0.0025 (13) | 0.0009 (12) | 0.0022 (12) |
O1 | 0.0267 (18) | 0.0257 (16) | 0.0242 (14) | 0.000 | −0.0002 (12) | 0.000 |
N1—N2 | 1.396 (3) | N51—H51A | 0.8800 |
N2—C3 | 1.309 (4) | N51—H51B | 0.8800 |
C3—C4 | 1.409 (4) | C11—C16 | 1.368 (4) |
C4—C5 | 1.403 (4) | C11—C12 | 1.377 (4) |
C5—N1 | 1.328 (3) | C12—C13 | 1.381 (4) |
N1—C11 | 1.425 (4) | C12—H12 | 0.9500 |
C3—C31 | 1.482 (4) | C13—C14 | 1.372 (4) |
C4—C41 | 1.406 (4) | C13—H13 | 0.9500 |
C41—O41 | 1.228 (3) | C14—C15 | 1.369 (4) |
C5—N51 | 1.331 (3) | C14—H14 | 0.9500 |
C31—H31A | 0.9800 | C15—C16 | 1.383 (4) |
C31—H31B | 0.9800 | C15—H15 | 0.9500 |
C31—H31C | 0.9800 | C16—H16 | 0.9500 |
C41—H41 | 0.9500 | O1—H1 | 0.8600 |
C5—N1—N2 | 111.9 (2) | C5—N51—H51A | 120.0 |
C5—N1—C11 | 129.4 (2) | C5—N51—H51B | 120.0 |
N2—N1—C11 | 118.3 (2) | H51A—N51—H51B | 120.0 |
C3—N2—N1 | 105.1 (2) | C16—C11—C12 | 121.5 (3) |
N2—C3—C4 | 111.5 (2) | C16—C11—N1 | 120.1 (2) |
N2—C3—C31 | 120.2 (2) | C12—C11—N1 | 118.4 (2) |
C4—C3—C31 | 128.3 (3) | C11—C12—C13 | 119.1 (3) |
C5—C4—C41 | 125.3 (2) | C11—C12—H12 | 120.5 |
C5—C4—C3 | 105.0 (2) | C13—C12—H12 | 120.5 |
C41—C4—C3 | 129.7 (3) | C14—C13—C12 | 119.7 (3) |
N1—C5—N51 | 126.3 (3) | C14—C13—H13 | 120.1 |
N1—C5—C4 | 106.4 (2) | C12—C13—H13 | 120.1 |
N51—C5—C4 | 127.2 (3) | C15—C14—C13 | 120.7 (3) |
C3—C31—H31A | 109.5 | C15—C14—H14 | 119.6 |
C3—C31—H31B | 109.5 | C13—C14—H14 | 119.6 |
H31A—C31—H31B | 109.5 | C14—C15—C16 | 120.0 (3) |
C3—C31—H31C | 109.5 | C14—C15—H15 | 120.0 |
H31A—C31—H31C | 109.5 | C16—C15—H15 | 120.0 |
H31B—C31—H31C | 109.5 | C11—C16—C15 | 118.9 (3) |
O41—C41—C4 | 124.8 (3) | C11—C16—H16 | 120.5 |
O41—C41—H41 | 117.6 | C15—C16—H16 | 120.5 |
C4—C41—H41 | 117.6 | ||
C5—N1—N2—C3 | −0.6 (3) | C3—C4—C5—N51 | 177.0 (3) |
C11—N1—N2—C3 | −173.8 (2) | C5—C4—C41—O41 | −1.5 (5) |
N1—N2—C3—C4 | −0.2 (3) | C3—C4—C41—O41 | 179.5 (3) |
N1—N2—C3—C31 | 179.3 (2) | C5—N1—C11—C16 | 52.9 (4) |
N2—C3—C4—C5 | 0.8 (3) | N2—N1—C11—C16 | −135.3 (3) |
C31—C3—C4—C5 | −178.6 (3) | C5—N1—C11—C12 | −128.3 (3) |
N2—C3—C4—C41 | 179.9 (3) | N2—N1—C11—C12 | 43.6 (4) |
C31—C3—C4—C41 | 0.5 (5) | C16—C11—C12—C13 | −1.0 (4) |
N2—N1—C5—N51 | −177.0 (2) | N1—C11—C12—C13 | −179.8 (3) |
C11—N1—C5—N51 | −4.8 (5) | C11—C12—C13—C14 | 0.5 (4) |
N2—N1—C5—C4 | 1.0 (3) | C12—C13—C14—C15 | 0.0 (4) |
C11—N1—C5—C4 | 173.3 (3) | C13—C14—C15—C16 | −0.2 (4) |
C41—C4—C5—N1 | 179.8 (3) | C12—C11—C16—C15 | 0.9 (4) |
C3—C4—C5—N1 | −1.0 (3) | N1—C11—C16—C15 | 179.7 (3) |
C41—C4—C5—N51 | −2.2 (5) | C14—C15—C16—C11 | −0.3 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N2 | 0.86 | 2.12 | 2.927 (3) | 158 |
N51—H51A···O41i | 0.88 | 2.07 | 2.897 (3) | 156 |
N51—H51B···O41 | 0.88 | 2.30 | 2.883 (3) | 123 |
Symmetry code: (i) x−1/2, −y+3/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C11H11N3O·0.5H2O |
Mr | 210.24 |
Crystal system, space group | Orthorhombic, Pbcn |
Temperature (K) | 120 |
a, b, c (Å) | 10.8346 (14), 7.4952 (9), 24.621 (3) |
V (Å3) | 1999.4 (4) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.28 × 0.17 × 0.12 |
Data collection | |
Diffractometer | Bruker Nonius KappaCCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.973, 0.989 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 16503, 1842, 1267 |
Rint | 0.091 |
(sin θ/λ)max (Å−1) | 0.606 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.055, 0.126, 1.16 |
No. of reflections | 1842 |
No. of parameters | 143 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.29 |
Computer programs: COLLECT (Nonius, 1999), DIRAX/LSQ (Duisenberg et al., 2000), EVALCCD (Duisenberg et al., 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).
N1—N2 | 1.396 (3) | N1—C11 | 1.425 (4) |
N2—C3 | 1.309 (4) | C4—C41 | 1.406 (4) |
C3—C4 | 1.409 (4) | C41—O41 | 1.228 (3) |
C4—C5 | 1.403 (4) | C5—N51 | 1.331 (3) |
C5—N1 | 1.328 (3) | ||
C5—C4—C41—O41 | −1.5 (5) | N2—N1—C11—C12 | 43.6 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N2 | 0.86 | 2.12 | 2.927 (3) | 158 |
N51—H51A···O41i | 0.88 | 2.07 | 2.897 (3) | 156 |
N51—H51B···O41 | 0.88 | 2.30 | 2.883 (3) | 123 |
Symmetry code: (i) x−1/2, −y+3/2, −z+1. |
The Vilsmeier–Haack formylation reaction allows access to a large variety of heterocyclic carbaldehyde derivatives, all of which permit a wide range of functional elaboration, acting in particular as extremely valuable intermediates for the synthesis of new fused heterocyclic systems. Accordingly, we have now prepared the title compound, (I) (Häufel & Breitmaier, 1974), as a versatile precursor for the synthesis of fused pyrazole derivatives of potential pharmaceutical interest, and here we report its molecular and supramolecular structure, which we briefly compare with those of the fused analogues (II) (Trilleras et al., 2008) and (III) (Low et al., 2006) (see scheme).
Compound (I) is a stoichiometric hemihydrate (Fig. 1) and the asymmetric unit consists of one molecule of the organic component in a general position with a water molecule lying across a twofold rotation axis. Within the selected asymmetric unit, the water molecule lies across the axis along (1/2, y, 3/4) and the two molecular components are linked by an O—H···N hydrogen bond (Fig. 1, Table 2).
The formyl group is almost coplanar with the pyrazole ring, as shown by the value of the torsion angle C5—C4—C41—O41 = -1.5 (5)°. The displacement of the formyl atom O41 from the mean plane of the pyrazole ring is only 0.020 (2) Å. This coplanarity may be a consequence of both the intramolecular N—H···O hydrogen bond (Table 2), which forms an S(6) motif (Bernstein et al., 1995), and the electronic delocalization (see discussion below). The two rings, however, are very far from being coplanar, and their planes make a dihedral angle of 47.5 (2)°, possibly as a consequence of H···H repulsion between the H atoms bonded to atoms C16 and N51.
The bond distances (Table 1) within the organic component provide evidence for electronic polarization. The C5—N51 bond is short for its type [mean value (Allen et al., 1987) 1.355 Å; lower quartile value 1.340 Å], as is the C4—C41 bond (mean value 1.464 Å, lower quartile value 1.453 Å). However, the C4—C5 bond is long for its type (mean value 1.369 Å, upper quartile value 1.383 Å), as is the C41—O41 bond (mean value 1.192 Å, upper quartile value 1.197 Å). These values provide evidence for an important contribution to the electronic structure of the polarized form (Ib), in addition to the unpolarized form (Ia). A significant contribution from form (Ib) effectively precludes any aromatic-type delocalization within the pyrazole ring. Consistent with this deduction, the N2—C3 and N1—C5 bonds are both short for their types (mean values 1.329 and 1.357 Å, respectively), while the N1—N2 bond is long for its type (mean value 1.366 Å), indicating significant bond fixation, as opposed to electronic delocalization, within the pyrazole ring. The electronic polarization deduced (Trilleras et al., 2008) for compounds (II) and (III) is more extensive than that in (I), but one of the canonical forms proposed for compounds (II) and (III) is exactly analogous to form (Ia).
In addition to the intramolecular hydrogen bond formed via atom H51B (Table 2), the amino atom N51 at (x, y, z) also acts as a hydrogen-bond donor, via atom H51A, to atom O41 in a second pyrazole molecule at (-1/2 + x, 1.5 - y, 1 - z). The combination of this N—H···O hydrogen bond and the two symmetry-related O—H···N hydrogen bonds formed by the water molecule links the molecular components into a deeply-puckered sheet lying parallel to (010) and containing only a single type of ring, of R108(34) type, in addition to the S(6) rings within the pyrazole component (Fig. 2). Two sheets of this type, related to one another by inversion, pass through each unit cell. The only direction-specific interactions between adjacent sheets are weak aromatic π–π stacking interactions between the phenyl rings at (x, y, z), lying in the reference sheet, and the corresponding rings at (1/2 - x, 1/2 + y, z) and (1/2 - x, -1/2 + y, z), which lie in the two adjacent sheets. For each interaction, the ring planes make a dihedral angle of 2.67 (2)° with an interplanar spacing of ca 3.457 Å; the ring-centroid separation is 3.847 (2) Å and the ring-centroid offset is ca 1.72 Å. By this means, the hydrogen-bonded sheets are weakly linked into a three-dimensional structure.
In contrast with the sheet formation in (I), the crystal structure of (II) is determined by the formation of a chain of rings built from a combination of N—H···O and C—H···O hydrogen bonds (Trilleras et al., 2008), while in (III) centrosymmetric dimers built from paired N—H···O hydrogen bonds are linked into sheets by the combined action of two C—H···O hydrogen bonds (Low et al., 2006).