Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802001265/cf6138sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536802001265/cf6138Isup2.hkl |
CCDC reference: 182625
The title compound, (I), was synthesized for the first time by Paternó (1882). However, the method used here was that of Hooker (1892). This substance is easily prepared, in chloroform solvent, by reaction of lapachol with bromine, followed by evaporation and crystallization from ethanol. It was recrystallized from acetone at room temperature.
H atoms were positioned geometrically and refined with a riding model, with isotropic displacement parameters equal to 1.5 (for methyl H atoms) or 1.2Ueq for the parent atom.
Data collection: COLLECT (Nonius, 1999); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).
Fig. 1. The molecular structure of (I), showing the atom labelling and 50% probability displacement ellipsoids. |
C15H13BrO3 | F(000) = 648 |
Mr = 321.16 | Dx = 1.650 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71070 Å |
a = 11.823 (2) Å | Cell parameters from 3176 reflections |
b = 8.191 (2) Å | θ = 1.0–27.5° |
c = 13.894 (3) Å | µ = 3.18 mm−1 |
β = 106.05 (1)° | T = 120 K |
V = 1293.1 (5) Å3 | Prism, orange |
Z = 4 | 0.22 × 0.15 × 0.12 mm |
Nonius KappaCCD diffractometer | 2971 independent reflections |
Radiation source: fine-focus sealed tube | 2601 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.016 |
Detector resolution: 9 pixels mm-1 | θmax = 27.5°, θmin = 1.8° |
ϕ scans, and ω scans with κ offsets | h = 0→15 |
Absorption correction: multi-scan (Blessing, 1995) | k = 0→10 |
Tmin = 0.541, Tmax = 0.702 | l = −18→17 |
5298 measured reflections |
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)] = 0.039 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.114 | H-atom parameters constrained |
S = 1.09 | w = 1/[σ2(Fo2) + (0.069P)2 + 0.7539P] where P = (Fo2 + 2Fc2)/3 |
2971 reflections | (Δ/σ)max < 0.001 |
175 parameters | Δρmax = 1.05 e Å−3 |
0 restraints | Δρmin = −0.80 e Å−3 |
C15H13BrO3 | V = 1293.1 (5) Å3 |
Mr = 321.16 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 11.823 (2) Å | µ = 3.18 mm−1 |
b = 8.191 (2) Å | T = 120 K |
c = 13.894 (3) Å | 0.22 × 0.15 × 0.12 mm |
β = 106.05 (1)° |
Nonius KappaCCD diffractometer | 2971 independent reflections |
Absorption correction: multi-scan (Blessing, 1995) | 2601 reflections with I > 2σ(I) |
Tmin = 0.541, Tmax = 0.702 | Rint = 0.016 |
5298 measured reflections |
R[F2 > 2σ(F2)] = 0.039 | 0 restraints |
wR(F2) = 0.114 | H-atom parameters constrained |
S = 1.09 | Δρmax = 1.05 e Å−3 |
2971 reflections | Δρmin = −0.80 e Å−3 |
175 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 | ||
Br | 0.02654 (2) | 0.10427 (4) | 0.17914 (2) | 0.03901 (13) | |
C10 | 0.5407 (2) | 0.3889 (3) | 0.10681 (18) | 0.0239 (5) | |
H10 | 0.4857 | 0.4731 | 0.1075 | 0.029* | |
C7 | 0.7053 (2) | 0.1448 (3) | 0.10824 (17) | 0.0255 (5) | |
H7 | 0.7617 | 0.0616 | 0.1097 | 0.031* | |
O1 | 0.32160 (15) | 0.31129 (19) | 0.11720 (13) | 0.0253 (3) | |
C6A | 0.5942 (2) | 0.1036 (3) | 0.11613 (17) | 0.0225 (5) | |
C4A | 0.3568 (2) | 0.0233 (3) | 0.12886 (17) | 0.0247 (5) | |
O3 | 0.41395 (17) | −0.2531 (2) | 0.14410 (13) | 0.0316 (4) | |
O2 | 0.63408 (16) | −0.1795 (2) | 0.12945 (14) | 0.0319 (4) | |
C11 | 0.1356 (2) | 0.2586 (3) | −0.00585 (19) | 0.0320 (5) | |
H11A | 0.1774 | 0.1724 | −0.0310 | 0.048* | |
H11B | 0.1376 | 0.3598 | −0.0430 | 0.048* | |
H11C | 0.0536 | 0.2255 | −0.0149 | 0.048* | |
C3 | 0.1879 (2) | 0.1403 (3) | 0.17233 (19) | 0.0273 (5) | |
H3 | 0.2373 | 0.1660 | 0.2416 | 0.033* | |
C5 | 0.4390 (2) | −0.1098 (3) | 0.13378 (17) | 0.0247 (5) | |
C2 | 0.1950 (2) | 0.2868 (3) | 0.10532 (18) | 0.0261 (5) | |
C4 | 0.2359 (2) | −0.0142 (3) | 0.13876 (18) | 0.0272 (5) | |
H4A | 0.2404 | −0.1021 | 0.1886 | 0.033* | |
H4B | 0.1839 | −0.0510 | 0.0736 | 0.033* | |
C10A | 0.5101 (2) | 0.2262 (3) | 0.11514 (16) | 0.0218 (4) | |
C6 | 0.5640 (2) | −0.0693 (3) | 0.12655 (17) | 0.0247 (5) | |
C1 | 0.3918 (2) | 0.1800 (3) | 0.12090 (16) | 0.0229 (4) | |
C8 | 0.7343 (2) | 0.3067 (3) | 0.09834 (18) | 0.0279 (5) | |
H8 | 0.8100 | 0.3345 | 0.0922 | 0.034* | |
C12 | 0.1566 (2) | 0.4462 (3) | 0.1419 (2) | 0.0329 (5) | |
H12A | 0.1842 | 0.5377 | 0.1089 | 0.049* | |
H12C | 0.1904 | 0.4549 | 0.2145 | 0.049* | |
H12B | 0.0706 | 0.4491 | 0.1259 | 0.049* | |
C9 | 0.6517 (2) | 0.4282 (3) | 0.09743 (18) | 0.0269 (5) | |
H9 | 0.6713 | 0.5392 | 0.0903 | 0.032* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br | 0.02618 (18) | 0.0457 (2) | 0.0482 (2) | −0.00395 (10) | 0.01535 (13) | −0.00299 (11) |
C10 | 0.0260 (11) | 0.0201 (11) | 0.0240 (11) | 0.0046 (8) | 0.0042 (9) | 0.0000 (8) |
C7 | 0.0252 (11) | 0.0262 (11) | 0.0236 (11) | 0.0053 (9) | 0.0046 (9) | −0.0011 (9) |
O1 | 0.0233 (8) | 0.0197 (8) | 0.0337 (8) | 0.0046 (6) | 0.0092 (7) | −0.0006 (6) |
C6A | 0.0253 (11) | 0.0218 (11) | 0.0187 (10) | 0.0048 (8) | 0.0031 (8) | −0.0009 (8) |
C4A | 0.0277 (11) | 0.0225 (11) | 0.0234 (10) | 0.0014 (9) | 0.0065 (9) | −0.0001 (8) |
O3 | 0.0406 (10) | 0.0203 (8) | 0.0341 (9) | 0.0003 (7) | 0.0106 (8) | 0.0012 (7) |
O2 | 0.0319 (9) | 0.0231 (8) | 0.0378 (9) | 0.0088 (7) | 0.0048 (8) | −0.0012 (7) |
C11 | 0.0305 (12) | 0.0333 (13) | 0.0301 (12) | 0.0033 (11) | 0.0050 (10) | −0.0014 (10) |
C3 | 0.0210 (11) | 0.0330 (12) | 0.0282 (11) | −0.0003 (9) | 0.0074 (9) | −0.0032 (9) |
C5 | 0.0325 (13) | 0.0203 (11) | 0.0204 (10) | 0.0018 (9) | 0.0057 (9) | −0.0002 (8) |
C2 | 0.0205 (11) | 0.0286 (12) | 0.0293 (11) | 0.0016 (9) | 0.0068 (9) | −0.0022 (9) |
C4 | 0.0277 (12) | 0.0255 (11) | 0.0292 (11) | −0.0017 (9) | 0.0089 (9) | −0.0009 (9) |
C10A | 0.0227 (11) | 0.0216 (10) | 0.0203 (10) | 0.0040 (8) | 0.0048 (8) | −0.0006 (8) |
C6 | 0.0282 (12) | 0.0221 (10) | 0.0216 (10) | 0.0059 (9) | 0.0030 (9) | 0.0002 (8) |
C1 | 0.0262 (11) | 0.0208 (11) | 0.0209 (10) | 0.0042 (9) | 0.0048 (8) | −0.0008 (8) |
C8 | 0.0238 (11) | 0.0308 (13) | 0.0292 (11) | 0.0018 (9) | 0.0072 (9) | 0.0006 (9) |
C12 | 0.0266 (12) | 0.0318 (13) | 0.0401 (14) | 0.0060 (10) | 0.0090 (10) | −0.0053 (11) |
C9 | 0.0284 (12) | 0.0236 (11) | 0.0270 (11) | −0.0008 (9) | 0.0052 (9) | 0.0000 (9) |
Br—C3 | 1.958 (2) | C11—H11A | 0.980 |
C10—C9 | 1.393 (4) | C11—H11B | 0.980 |
C10—C10A | 1.394 (3) | C11—H11C | 0.980 |
C10—H10 | 0.950 | C3—C4 | 1.513 (3) |
C7—C8 | 1.385 (3) | C3—C2 | 1.536 (4) |
C7—C6A | 1.390 (4) | C3—H3 | 1.000 |
C7—H7 | 0.950 | C5—C6 | 1.545 (4) |
O1—C1 | 1.351 (3) | C2—C12 | 1.515 (3) |
O1—C2 | 1.473 (3) | C4—H4A | 0.990 |
C6A—C10A | 1.411 (3) | C4—H4B | 0.990 |
C6A—C6 | 1.478 (3) | C10A—C1 | 1.472 (3) |
C4A—C1 | 1.363 (3) | C8—C9 | 1.392 (3) |
C4A—C5 | 1.449 (3) | C8—H8 | 0.950 |
C4A—C4 | 1.505 (3) | C12—H12A | 0.980 |
O3—C5 | 1.229 (3) | C12—H12C | 0.980 |
O2—C6 | 1.219 (3) | C12—H12B | 0.980 |
C11—C2 | 1.527 (3) | C9—H9 | 0.950 |
C9—C10—C10A | 120.1 (2) | O1—C2—C3 | 105.23 (18) |
C9—C10—H10 | 119.9 | C12—C2—C3 | 113.5 (2) |
C10A—C10—H10 | 119.9 | C11—C2—C3 | 114.1 (2) |
C8—C7—C6A | 120.3 (2) | C4A—C4—C3 | 107.7 (2) |
C8—C7—H7 | 119.8 | C4A—C4—H4A | 110.2 |
C6A—C7—H7 | 119.8 | C3—C4—H4A | 110.2 |
C1—O1—C2 | 119.39 (18) | C4A—C4—H4B | 110.2 |
C7—C6A—C10A | 120.4 (2) | C3—C4—H4B | 110.2 |
C7—C6A—C6 | 120.0 (2) | H4A—C4—H4B | 108.5 |
C10A—C6A—C6 | 119.6 (2) | C10—C10A—C6A | 118.9 (2) |
C1—C4A—C5 | 119.8 (2) | C10—C10A—C1 | 121.5 (2) |
C1—C4A—C4 | 121.2 (2) | C6A—C10A—C1 | 119.6 (2) |
C5—C4A—C4 | 118.9 (2) | O2—C6—C6A | 122.2 (2) |
C2—C11—H11A | 109.5 | O2—C6—C5 | 119.5 (2) |
C2—C11—H11B | 109.5 | C6A—C6—C5 | 118.3 (2) |
H11A—C11—H11B | 109.5 | O1—C1—C4A | 123.8 (2) |
C2—C11—H11C | 109.5 | O1—C1—C10A | 112.1 (2) |
H11A—C11—H11C | 109.5 | C4A—C1—C10A | 124.2 (2) |
H11B—C11—H11C | 109.5 | C7—C8—C9 | 119.6 (2) |
C4—C3—C2 | 112.2 (2) | C7—C8—H8 | 120.2 |
C4—C3—Br | 110.05 (17) | C9—C8—H8 | 120.2 |
C2—C3—Br | 111.39 (16) | C2—C12—H12A | 109.5 |
C4—C3—H3 | 107.6 | C2—C12—H12C | 109.5 |
C2—C3—H3 | 107.6 | H12A—C12—H12C | 109.5 |
Br—C3—H3 | 107.6 | C2—C12—H12B | 109.5 |
O3—C5—C4A | 123.0 (2) | H12A—C12—H12B | 109.5 |
O3—C5—C6 | 118.6 (2) | H12C—C12—H12B | 109.5 |
C4A—C5—C6 | 118.5 (2) | C8—C9—C10 | 120.7 (2) |
O1—C2—C12 | 103.55 (19) | C8—C9—H9 | 119.6 |
O1—C2—C11 | 107.63 (19) | C10—C9—H9 | 119.6 |
C12—C2—C11 | 111.9 (2) | ||
C8—C7—C6A—C10A | −0.6 (4) | C7—C6A—C10A—C1 | 178.4 (2) |
C8—C7—C6A—C6 | 179.9 (2) | C6—C6A—C10A—C1 | −2.2 (3) |
C1—C4A—C5—O3 | 177.7 (2) | C7—C6A—C6—O2 | 0.7 (4) |
C4—C4A—C5—O3 | 1.2 (3) | C10A—C6A—C6—O2 | −178.8 (2) |
C1—C4A—C5—C6 | −1.8 (3) | C7—C6A—C6—C5 | −179.3 (2) |
C4—C4A—C5—C6 | −178.3 (2) | C10A—C6A—C6—C5 | 1.3 (3) |
C1—O1—C2—C12 | 160.0 (2) | O3—C5—C6—O2 | 1.3 (3) |
C1—O1—C2—C11 | −81.4 (2) | C4A—C5—C6—O2 | −179.2 (2) |
C1—O1—C2—C3 | 40.6 (3) | O3—C5—C6—C6A | −178.8 (2) |
C4—C3—C2—O1 | −62.8 (2) | C4A—C5—C6—C6A | 0.7 (3) |
Br—C3—C2—O1 | 173.26 (14) | C2—O1—C1—C4A | −9.9 (3) |
C4—C3—C2—C12 | −175.3 (2) | C2—O1—C1—C10A | 170.00 (18) |
Br—C3—C2—C12 | 60.7 (2) | C5—C4A—C1—O1 | −179.1 (2) |
C4—C3—C2—C11 | 54.9 (3) | C4—C4A—C1—O1 | −2.7 (3) |
Br—C3—C2—C11 | −69.0 (2) | C5—C4A—C1—C10A | 1.0 (3) |
C1—C4A—C4—C3 | −18.7 (3) | C4—C4A—C1—C10A | 177.4 (2) |
C5—C4A—C4—C3 | 157.7 (2) | C10—C10A—C1—O1 | −0.1 (3) |
C2—C3—C4—C4A | 52.0 (3) | C6A—C10A—C1—O1 | −178.84 (19) |
Br—C3—C4—C4A | 176.63 (15) | C10—C10A—C1—C4A | 179.8 (2) |
C9—C10—C10A—C6A | 1.4 (3) | C6A—C10A—C1—C4A | 1.1 (3) |
C9—C10—C10A—C1 | −177.4 (2) | C6A—C7—C8—C9 | 0.7 (4) |
C7—C6A—C10A—C10 | −0.4 (3) | C7—C8—C9—C10 | 0.3 (4) |
C6—C6A—C10A—C10 | 179.0 (2) | C10A—C10—C9—C8 | −1.3 (4) |
Experimental details
Crystal data | |
Chemical formula | C15H13BrO3 |
Mr | 321.16 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 120 |
a, b, c (Å) | 11.823 (2), 8.191 (2), 13.894 (3) |
β (°) | 106.05 (1) |
V (Å3) | 1293.1 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 3.18 |
Crystal size (mm) | 0.22 × 0.15 × 0.12 |
Data collection | |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | Multi-scan (Blessing, 1995) |
Tmin, Tmax | 0.541, 0.702 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5298, 2971, 2601 |
Rint | 0.016 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.114, 1.09 |
No. of reflections | 2971 |
No. of parameters | 175 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 1.05, −0.80 |
Computer programs: COLLECT (Nonius, 1999), HKL SCALEPACK (Otwinowski & Minor, 1997), HKL DENZO (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
Br—C3 | 1.958 (2) | C4A—C4 | 1.505 (3) |
O1—C1 | 1.351 (3) | C3—C4 | 1.513 (3) |
O1—C2 | 1.473 (3) | C3—C2 | 1.536 (4) |
C4A—C1 | 1.363 (3) | ||
C1—O1—C2 | 119.39 (18) | O1—C2—C3 | 105.23 (18) |
C4—C3—C2 | 112.2 (2) | C4A—C4—C3 | 107.7 (2) |
C2—C3—Br | 111.39 (16) |
Naphthoquinonic compounds are often found in nature and their biological activity has been associated with various medicinal applications. Their action ranges from antibiotic to antineoplastic activity, although some of them do not presently have a defined function (Pinto et al., 1980). Among the naphthoquinonic compounds, lapachol, lapachones and their derivatives have been of interest to the scientific communities of several countries for more than 100 years because of the large range of biological activities found for these compounds (Subramanian, 1996). Among these activities are: antiviral (Pinto, Pinto et al., 1987), antimalarial (Fieser et al., 1967), antitumor (Li et al., 1999), and activity against trypanosoma cruzi, the protozoan of Chagas disease (Gonçalves et al., 1980; Pinto, Ferreira et al., 1987). As part of a search for compounds with therapeutic activity against a number of parasitic diseases endemic to Brazil, a series of derivatives has been prepared from lapachol (Cruz et al., 1977).
The title compound, (I), is a derivative of lapachol. It was tested in two biological assays, against trypanosoma cruzi (Lopes et al., 1978), and as a protection against the penetration of Schistosomiasis mansoni cercariae in tails of mice (Pinto et al., 1977), and showed, in both tests, discrete biological activity.
The crystal structure of (I) (Fig. 1) shows that the atoms comprising rings A and B and the adjacent C and O atoms are essentially coplanar, with an r.m.s. deviation of 0.039 Å for the 14 atoms. Atoms C2 and C3 are 0.256 (2) and 0.519 (3) Å out of this plane, respectively. Therefore, the C ring assumes a distorted half-chair conformation, the Cremer & Pople (1975) ring-puckering parameters being q2 = 0.407 (2), q3 = 0.314 (2) Å, Q = 0.514 (2) Å, θ = 52.4 (2)° and ϕ = 160.8 (3)°. The overall geometry of both B and C rings is in good agreement with that found for this moiety in a similar compound (Pereira, 1989).