Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807041827/hb2523sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807041827/hb2523Isup2.hkl |
CCDC reference: 667274
The title compound was prepared according to the method of Bell et al. (1992). 1-Methyl-3-propyl-1H-pyrazole-5-carboxylic acid ethyl ester (20.2 g, 0.10 mol) was suspended in 6 N aqueous sodium hydroxide solution (50 ml, 0.30 mol). The mixture was heated to 353 K for 2 h then diluted with water (50 ml) and acidified with concentrated hydrochloric acid (25 ml). Filtration gave the carboxylic acid as pale brown crystals (12.3 g, 71%), m.p. 423–427 K. Colourless blocks of (I) suitable for X-ray analysis were obtained by slow evaporation of a methanol/ethyl acetate mixture (1:1 v/v).
The O-bound H atom was located in a difference map·Its position was freely refined, with Uiso(H) = 1.5Ueq(O). The C-bound H atoms were positioned geometrically (C—H = 0.93–0.97 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).
Sidenafil has been found to be particularly useful in the treatment of inter alia, male erectile dysfunction. The structure of the title compound, (I), (Fig. 1) a key intermediate in the synthesis of sidenafil, is reported here.
As shown in Fig. 2, the packing is consolidated by a conbination of O—H···N and C—H···O interactions (Table 1) resulting in molecular chains propagating in [201].
For synthesis, see: Simon et al. (1992).
Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL (Bruker, 1997).
C8H12N2O2 | F(000) = 360 |
Mr = 168.20 | Dx = 1.239 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 1522 reflections |
a = 4.9336 (19) Å | θ = 2.4–26.3° |
b = 19.121 (7) Å | µ = 0.09 mm−1 |
c = 9.568 (4) Å | T = 294 K |
β = 92.136 (7)° | Block, colourless |
V = 902.0 (6) Å3 | 0.50 × 0.20 × 0.10 mm |
Z = 4 |
Bruker SMART 1000 CCD diffractometer | 1585 independent reflections |
Radiation source: fine-focus sealed tube | 1090 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.038 |
ω scans | θmax = 25.0°, θmin = 2.1° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −5→5 |
Tmin = 0.948, Tmax = 0.991 | k = −11→22 |
4542 measured reflections | l = −11→11 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.054 | Hydrogen site location: difmap and geom |
wR(F2) = 0.157 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0772P)2 + 0.3462P] where P = (Fo2 + 2Fc2)/3 |
1585 reflections | (Δ/σ)max = 0.004 |
114 parameters | Δρmax = 0.26 e Å−3 |
0 restraints | Δρmin = −0.23 e Å−3 |
C8H12N2O2 | V = 902.0 (6) Å3 |
Mr = 168.20 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 4.9336 (19) Å | µ = 0.09 mm−1 |
b = 19.121 (7) Å | T = 294 K |
c = 9.568 (4) Å | 0.50 × 0.20 × 0.10 mm |
β = 92.136 (7)° |
Bruker SMART 1000 CCD diffractometer | 1585 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1090 reflections with I > 2σ(I) |
Tmin = 0.948, Tmax = 0.991 | Rint = 0.038 |
4542 measured reflections |
R[F2 > 2σ(F2)] = 0.054 | 0 restraints |
wR(F2) = 0.157 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.26 e Å−3 |
1585 reflections | Δρmin = −0.23 e Å−3 |
114 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.7756 (3) | 0.22535 (10) | −0.19643 (18) | 0.0556 (6) | |
H1 | 0.887 (7) | 0.2471 (16) | −0.245 (3) | 0.083* | |
O2 | 0.6976 (4) | 0.33056 (10) | −0.1072 (2) | 0.0638 (6) | |
N1 | 0.2945 (4) | 0.26597 (10) | 0.06131 (19) | 0.0405 (5) | |
N2 | 0.1416 (4) | 0.21980 (10) | 0.1296 (2) | 0.0448 (5) | |
C1 | 0.6546 (5) | 0.26908 (13) | −0.1126 (2) | 0.0434 (6) | |
C2 | 0.4590 (4) | 0.23211 (12) | −0.0261 (2) | 0.0394 (6) | |
C3 | 0.4085 (5) | 0.16227 (12) | −0.0133 (2) | 0.0458 (6) | |
H3 | 0.4905 | 0.1260 | −0.0607 | 0.055* | |
C4 | 0.2087 (5) | 0.15646 (12) | 0.0855 (2) | 0.0452 (6) | |
C5 | 0.0766 (5) | 0.09284 (13) | 0.1413 (3) | 0.0594 (8) | |
H5A | −0.0493 | 0.1070 | 0.2115 | 0.071* | |
H5B | −0.0278 | 0.0706 | 0.0658 | 0.071* | |
C6 | 0.2655 (7) | 0.04127 (16) | 0.2037 (4) | 0.0884 (11) | |
H6A | 0.3816 | 0.0643 | 0.2737 | 0.106* | |
H6B | 0.3800 | 0.0234 | 0.1317 | 0.106* | |
C7 | 0.1225 (9) | −0.01936 (19) | 0.2712 (5) | 0.1121 (15) | |
H7A | 0.0049 | −0.0019 | 0.3409 | 0.168* | |
H7B | 0.2545 | −0.0502 | 0.3143 | 0.168* | |
H7C | 0.0173 | −0.0444 | 0.2012 | 0.168* | |
C8 | 0.2658 (5) | 0.33973 (12) | 0.0891 (3) | 0.0549 (7) | |
H8A | 0.4412 | 0.3597 | 0.1098 | 0.082* | |
H8B | 0.1528 | 0.3462 | 0.1677 | 0.082* | |
H8C | 0.1842 | 0.3624 | 0.0085 | 0.082* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0502 (11) | 0.0624 (12) | 0.0563 (11) | −0.0052 (8) | 0.0315 (9) | −0.0021 (9) |
O2 | 0.0663 (13) | 0.0528 (12) | 0.0744 (13) | −0.0101 (9) | 0.0330 (10) | 0.0005 (9) |
N1 | 0.0359 (10) | 0.0442 (11) | 0.0423 (11) | 0.0006 (8) | 0.0138 (9) | −0.0002 (8) |
N2 | 0.0406 (11) | 0.0489 (12) | 0.0462 (12) | −0.0010 (9) | 0.0193 (9) | 0.0035 (9) |
C1 | 0.0354 (13) | 0.0546 (16) | 0.0409 (13) | 0.0004 (11) | 0.0102 (10) | 0.0029 (11) |
C2 | 0.0328 (12) | 0.0492 (14) | 0.0370 (12) | 0.0008 (10) | 0.0124 (10) | −0.0005 (10) |
C3 | 0.0421 (14) | 0.0479 (15) | 0.0485 (14) | 0.0058 (10) | 0.0176 (11) | −0.0010 (11) |
C4 | 0.0403 (13) | 0.0466 (14) | 0.0498 (15) | 0.0019 (10) | 0.0158 (11) | 0.0032 (11) |
C5 | 0.0573 (17) | 0.0537 (16) | 0.0690 (18) | −0.0030 (12) | 0.0266 (14) | 0.0048 (13) |
C6 | 0.081 (2) | 0.063 (2) | 0.122 (3) | −0.0029 (17) | 0.015 (2) | 0.0266 (19) |
C7 | 0.121 (3) | 0.070 (2) | 0.147 (4) | −0.003 (2) | 0.024 (3) | 0.045 (2) |
C8 | 0.0584 (17) | 0.0454 (15) | 0.0622 (17) | −0.0001 (12) | 0.0198 (13) | −0.0057 (12) |
O1—C1 | 1.317 (3) | C5—C6 | 1.468 (4) |
O1—H1 | 0.84 (3) | C5—H5A | 0.9700 |
O2—C1 | 1.195 (3) | C5—H5B | 0.9700 |
N1—N2 | 1.346 (2) | C6—C7 | 1.514 (4) |
N1—C2 | 1.352 (3) | C6—H6A | 0.9700 |
N1—C8 | 1.443 (3) | C6—H6B | 0.9700 |
N2—C4 | 1.328 (3) | C7—H7A | 0.9600 |
C1—C2 | 1.475 (3) | C7—H7B | 0.9600 |
C2—C3 | 1.365 (3) | C7—H7C | 0.9600 |
C3—C4 | 1.396 (3) | C8—H8A | 0.9600 |
C3—H3 | 0.9300 | C8—H8B | 0.9600 |
C4—C5 | 1.488 (3) | C8—H8C | 0.9600 |
C1—O1—H1 | 110 (2) | C4—C5—H5B | 108.6 |
N2—N1—C2 | 110.26 (19) | H5A—C5—H5B | 107.6 |
N2—N1—C8 | 119.39 (17) | C5—C6—C7 | 112.9 (3) |
C2—N1—C8 | 130.34 (19) | C5—C6—H6A | 109.0 |
C4—N2—N1 | 107.06 (17) | C7—C6—H6A | 109.0 |
O2—C1—O1 | 124.6 (2) | C5—C6—H6B | 109.0 |
O2—C1—C2 | 124.5 (2) | C7—C6—H6B | 109.0 |
O1—C1—C2 | 111.0 (2) | H6A—C6—H6B | 107.8 |
N1—C2—C3 | 107.28 (18) | C6—C7—H7A | 109.5 |
N1—C2—C1 | 122.6 (2) | C6—C7—H7B | 109.5 |
C3—C2—C1 | 130.2 (2) | H7A—C7—H7B | 109.5 |
C2—C3—C4 | 105.9 (2) | C6—C7—H7C | 109.5 |
C2—C3—H3 | 127.0 | H7A—C7—H7C | 109.5 |
C4—C3—H3 | 127.0 | H7B—C7—H7C | 109.5 |
N2—C4—C3 | 109.5 (2) | N1—C8—H8A | 109.5 |
N2—C4—C5 | 120.9 (2) | N1—C8—H8B | 109.5 |
C3—C4—C5 | 129.6 (2) | H8A—C8—H8B | 109.5 |
C6—C5—C4 | 114.5 (2) | N1—C8—H8C | 109.5 |
C6—C5—H5A | 108.6 | H8A—C8—H8C | 109.5 |
C4—C5—H5A | 108.6 | H8B—C8—H8C | 109.5 |
C6—C5—H5B | 108.6 | ||
C2—N1—N2—C4 | 0.0 (2) | N1—C2—C3—C4 | −0.2 (3) |
C8—N1—N2—C4 | −179.6 (2) | C1—C2—C3—C4 | 178.4 (2) |
N2—N1—C2—C3 | 0.2 (2) | N1—N2—C4—C3 | −0.1 (3) |
C8—N1—C2—C3 | 179.7 (2) | N1—N2—C4—C5 | 179.8 (2) |
N2—N1—C2—C1 | −178.6 (2) | C2—C3—C4—N2 | 0.2 (3) |
C8—N1—C2—C1 | 1.0 (4) | C2—C3—C4—C5 | −179.6 (3) |
O2—C1—C2—N1 | 4.9 (4) | N2—C4—C5—C6 | −123.6 (3) |
O1—C1—C2—N1 | −175.1 (2) | C3—C4—C5—C6 | 56.3 (4) |
O2—C1—C2—C3 | −173.5 (3) | C4—C5—C6—C7 | 174.6 (3) |
O1—C1—C2—C3 | 6.4 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N2i | 0.84 (3) | 1.88 (3) | 2.712 (3) | 169 (3) |
C5—H5A···O2ii | 0.97 | 2.48 | 3.430 (4) | 166 |
Symmetry codes: (i) x+1, −y+1/2, z−1/2; (ii) x−1, −y+1/2, z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H12N2O2 |
Mr | 168.20 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 294 |
a, b, c (Å) | 4.9336 (19), 19.121 (7), 9.568 (4) |
β (°) | 92.136 (7) |
V (Å3) | 902.0 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.50 × 0.20 × 0.10 |
Data collection | |
Diffractometer | Bruker SMART 1000 CCD |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.948, 0.991 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4542, 1585, 1090 |
Rint | 0.038 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.054, 0.157, 1.03 |
No. of reflections | 1585 |
No. of parameters | 114 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.26, −0.23 |
Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997).
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N2i | 0.84 (3) | 1.88 (3) | 2.712 (3) | 169 (3) |
C5—H5A···O2ii | 0.97 | 2.48 | 3.430 (4) | 166 |
Symmetry codes: (i) x+1, −y+1/2, z−1/2; (ii) x−1, −y+1/2, z+1/2. |
Sidenafil has been found to be particularly useful in the treatment of inter alia, male erectile dysfunction. The structure of the title compound, (I), (Fig. 1) a key intermediate in the synthesis of sidenafil, is reported here.
As shown in Fig. 2, the packing is consolidated by a conbination of O—H···N and C—H···O interactions (Table 1) resulting in molecular chains propagating in [201].