Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010900941X/sk3306sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S010827010900941X/sk3306Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S010827010900941X/sk3306IIsup3.hkl |
CCDC references: 730104; 730105
The title compounds were synthesized in a two-step procedure. 6-(4-Chlorophenyl)-4,6-dioxohexanoic acid was synthesized by a modification of the method dscribed by Murray et al. (1991), using NaHMDS in place of LiHMDS. Next, a mixture of 6-(4-chlorophenyl)-4,6-dioxohexanoic acid (1.27 g, 5 mmol), 4-methoxyphenylhydrazine hydrochloride (873 mg, 5 mmol) and Et3N (506 mg, 5 mmol) were combined in MeOH (40 ml) and stirred at room temperature for 6 h. The mixture was then concentrated in vacuo to a residue, which was partitioned between Et2O (40 ml) and 5% aqueous HCl (37.5 ml). The ether layer was separated, washed with 5% aqueous HCl (2 × 10 ml) and brine 10 ml, dried over Na2SO4, filtered, and concentrated to a residue. The crude residue was flash chromatographed on silica gel with hexane:EtOAc:AcOH (6:2:1) as eluant and separated into the two products (I) and (II). Compound (I) was crystallized by slow evaporation of a diethyl ether solution (yield 70%). Compound (II) was crystallized by slow evaporation of a deuterated methanol solution (yield 30%).
All hydrogen atoms were located from a difference map and constrained to ride on the parent atom, except that the hydroxy H atoms in (I) were freely refined [the O—H distances are 0.84 (3) and 0.90 (3) Å]. H atoms were refined with Uiso(H) values of 1.2Ueq(C) [or 1.5Ueq(C) for methyl H atoms] and fixed C—H distances of 0.95 Å for aryl, 0.98 Å for methyl and 0.99 Å for methylene H atoms.
For both compounds, data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 1999) and Mercury (Version 2.2; Macrae et al., 2008). Software used to prepare material for publication: SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2008) and local programs for (I); SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2008), and local programs for (II).
C19H17ClN2O3 | Z = 4 |
Mr = 356.80 | F(000) = 744 |
Triclinic, P1 | Dx = 1.395 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.131 (2) Å | Cell parameters from 5841 reflections |
b = 13.759 (3) Å | θ = 2.4–28.0° |
c = 14.264 (3) Å | µ = 0.25 mm−1 |
α = 103.733 (3)° | T = 150 K |
β = 96.928 (3)° | Block, colourless |
γ = 98.459 (3)° | 0.32 × 0.21 × 0.11 mm |
V = 1699.2 (6) Å3 |
Bruker APEXII CCD diffractometer | 8218 independent reflections |
Radiation source: sealed tube | 6174 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.025 |
thin–slice ω scans | θmax = 28.3°, θmin = 2.3° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −12→12 |
Tmin = 0.916, Tmax = 0.974 | k = −18→18 |
19183 measured reflections | l = −18→18 |
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)] = 0.043 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.115 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | w = 1/[σ2(Fo2) + (0.050P)2 + 0.4502P] where P = (Fo2 + 2Fc2)/3 |
8218 reflections | (Δ/σ)max = 0.001 |
461 parameters | Δρmax = 0.52 e Å−3 |
0 restraints | Δρmin = −0.32 e Å−3 |
C19H17ClN2O3 | γ = 98.459 (3)° |
Mr = 356.80 | V = 1699.2 (6) Å3 |
Triclinic, P1 | Z = 4 |
a = 9.131 (2) Å | Mo Kα radiation |
b = 13.759 (3) Å | µ = 0.25 mm−1 |
c = 14.264 (3) Å | T = 150 K |
α = 103.733 (3)° | 0.32 × 0.21 × 0.11 mm |
β = 96.928 (3)° |
Bruker APEXII CCD diffractometer | 8218 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 6174 reflections with I > 2σ(I) |
Tmin = 0.916, Tmax = 0.974 | Rint = 0.025 |
19183 measured reflections |
R[F2 > 2σ(F2)] = 0.043 | 0 restraints |
wR(F2) = 0.115 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.52 e Å−3 |
8218 reflections | Δρmin = −0.32 e Å−3 |
461 parameters |
Experimental. Spectroscopic data for compound (I). C19H17ClN2O3, Mass Calculated 356.80, 1H NMR (600 MHz, CDCl3) d 7.25 (d, 2H),7.13 (t, 4H), 6.9 (d, 2H), 6.4 (s, 1H), 3.76 (s, 3H) 2.96 (t, 2H) 2.70 (t, 2H) |
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 | ||
Cl1 | −0.27614 (5) | −0.31833 (3) | 0.67484 (4) | 0.04131 (13) | |
O1 | 0.04617 (17) | 0.19973 (11) | 1.08923 (9) | 0.0449 (3) | |
O2 | 0.62247 (16) | 0.45259 (9) | 0.56095 (10) | 0.0405 (3) | |
H2O | 0.689 (3) | 0.479 (2) | 0.5275 (19) | 0.074 (8)* | |
O3 | 0.63158 (14) | 0.30375 (9) | 0.45893 (9) | 0.0337 (3) | |
N1 | 0.31218 (15) | 0.19334 (10) | 0.69068 (10) | 0.0255 (3) | |
N2 | 0.21733 (15) | 0.12475 (10) | 0.72088 (10) | 0.0244 (3) | |
C1 | 0.31393 (18) | 0.14856 (12) | 0.59717 (11) | 0.0244 (3) | |
C2 | 0.22024 (18) | 0.05316 (12) | 0.56672 (12) | 0.0262 (3) | |
H2 | 0.2024 | 0.0073 | 0.5035 | 0.031* | |
C3 | 0.15901 (17) | 0.03923 (11) | 0.64726 (11) | 0.0234 (3) | |
C4 | 0.18565 (17) | 0.14963 (12) | 0.81879 (11) | 0.0234 (3) | |
C5 | 0.19647 (19) | 0.08145 (13) | 0.87649 (13) | 0.0300 (4) | |
H5 | 0.2357 | 0.0215 | 0.8538 | 0.036* | |
C6 | 0.1502 (2) | 0.10115 (14) | 0.96662 (13) | 0.0339 (4) | |
H6 | 0.1559 | 0.0540 | 1.0054 | 0.041* | |
C7 | 0.09518 (19) | 0.18974 (14) | 1.00096 (12) | 0.0304 (4) | |
C8 | 0.0912 (2) | 0.25997 (13) | 0.94570 (12) | 0.0304 (4) | |
H8 | 0.0583 | 0.3221 | 0.9702 | 0.036* | |
C9 | 0.13575 (19) | 0.23892 (12) | 0.85421 (12) | 0.0285 (4) | |
H9 | 0.1317 | 0.2865 | 0.8158 | 0.034* | |
C10 | −0.0173 (2) | 0.28677 (17) | 1.12500 (14) | 0.0452 (5) | |
H10A | 0.0596 | 0.3482 | 1.1384 | 0.068* | |
H10B | −0.0555 | 0.2820 | 1.1854 | 0.068* | |
H10C | −0.0999 | 0.2902 | 1.0759 | 0.068* | |
C11 | 0.41458 (19) | 0.19607 (12) | 0.53809 (12) | 0.0278 (4) | |
H11A | 0.3594 | 0.1847 | 0.4711 | 0.033* | |
H11B | 0.5022 | 0.1616 | 0.5329 | 0.033* | |
C12 | 0.4701 (2) | 0.30929 (12) | 0.58101 (13) | 0.0311 (4) | |
H12A | 0.3834 | 0.3448 | 0.5800 | 0.037* | |
H12B | 0.5167 | 0.3215 | 0.6501 | 0.037* | |
C13 | 0.58203 (19) | 0.35346 (12) | 0.52660 (13) | 0.0284 (4) | |
C14 | 0.05165 (17) | −0.04738 (12) | 0.65634 (12) | 0.0236 (3) | |
C15 | 0.06232 (19) | −0.14580 (12) | 0.60665 (12) | 0.0293 (4) | |
H15 | 0.1400 | −0.1557 | 0.5686 | 0.035* | |
C16 | −0.0378 (2) | −0.22898 (13) | 0.61177 (12) | 0.0306 (4) | |
H16 | −0.0305 | −0.2956 | 0.5769 | 0.037* | |
C17 | −0.14897 (18) | −0.21383 (12) | 0.66846 (12) | 0.0275 (4) | |
C18 | −0.16246 (18) | −0.11766 (13) | 0.71918 (13) | 0.0294 (4) | |
H18 | −0.2384 | −0.1086 | 0.7588 | 0.035* | |
C19 | −0.06361 (18) | −0.03486 (12) | 0.71130 (12) | 0.0274 (4) | |
H19 | −0.0744 | 0.0318 | 0.7439 | 0.033* | |
Cl51 | 1.58948 (6) | 1.16094 (4) | 0.16067 (5) | 0.05287 (16) | |
O51 | 1.40228 (16) | 0.51734 (10) | −0.16297 (9) | 0.0411 (3) | |
O52 | 0.79956 (16) | 0.38456 (9) | 0.34517 (10) | 0.0391 (3) | |
H52O | 0.747 (3) | 0.357 (2) | 0.379 (2) | 0.076 (9)* | |
O53 | 0.82523 (16) | 0.52788 (9) | 0.46318 (10) | 0.0414 (3) | |
N51 | 1.15524 (15) | 0.62669 (10) | 0.23265 (10) | 0.0275 (3) | |
N52 | 1.24349 (15) | 0.69184 (10) | 0.19441 (10) | 0.0257 (3) | |
C51 | 1.12167 (18) | 0.68508 (12) | 0.31247 (12) | 0.0269 (3) | |
C52 | 1.18747 (19) | 0.78708 (12) | 0.32632 (12) | 0.0279 (4) | |
H52 | 1.1807 | 0.8430 | 0.3785 | 0.034* | |
C53 | 1.26365 (18) | 0.79014 (12) | 0.24948 (12) | 0.0248 (3) | |
C54 | 1.29342 (18) | 0.64860 (12) | 0.10536 (11) | 0.0239 (3) | |
C55 | 1.19538 (19) | 0.57000 (12) | 0.03676 (12) | 0.0289 (4) | |
H55 | 1.0997 | 0.5456 | 0.0507 | 0.035* | |
C56 | 1.2366 (2) | 0.52766 (13) | −0.05103 (13) | 0.0317 (4) | |
H56 | 1.1695 | 0.4736 | −0.0975 | 0.038* | |
C57 | 1.3759 (2) | 0.56322 (12) | −0.07252 (12) | 0.0300 (4) | |
C58 | 1.4763 (2) | 0.63996 (13) | −0.00270 (13) | 0.0318 (4) | |
H58 | 1.5725 | 0.6638 | −0.0163 | 0.038* | |
C59 | 1.43537 (19) | 0.68140 (13) | 0.08681 (12) | 0.0285 (4) | |
H59 | 1.5046 | 0.7322 | 0.1353 | 0.034* | |
C60 | 1.5382 (2) | 0.55308 (15) | −0.19046 (15) | 0.0435 (5) | |
H60A | 1.5470 | 0.6260 | −0.1859 | 0.065* | |
H60B | 1.5407 | 0.5163 | −0.2579 | 0.065* | |
H60C | 1.6219 | 0.5420 | −0.1468 | 0.065* | |
C61 | 1.0217 (2) | 0.63930 (12) | 0.37321 (12) | 0.0292 (4) | |
H61A | 0.9365 | 0.6759 | 0.3806 | 0.035* | |
H61B | 1.0790 | 0.6489 | 0.4393 | 0.035* | |
C62 | 0.9610 (2) | 0.52670 (13) | 0.32904 (13) | 0.0325 (4) | |
H62A | 0.9081 | 0.5169 | 0.2618 | 0.039* | |
H62B | 1.0463 | 0.4898 | 0.3246 | 0.039* | |
C63 | 0.85545 (19) | 0.48111 (12) | 0.38645 (12) | 0.0283 (4) | |
C64 | 1.34394 (18) | 0.87970 (12) | 0.22497 (12) | 0.0247 (3) | |
C65 | 1.32780 (19) | 0.89161 (13) | 0.13001 (12) | 0.0280 (4) | |
H65 | 1.2646 | 0.8403 | 0.0786 | 0.034* | |
C66 | 1.4031 (2) | 0.97761 (13) | 0.10989 (14) | 0.0324 (4) | |
H66 | 1.3925 | 0.9850 | 0.0450 | 0.039* | |
C67 | 1.49379 (19) | 1.05237 (13) | 0.18537 (14) | 0.0320 (4) | |
C68 | 1.50994 (19) | 1.04394 (13) | 0.28041 (14) | 0.0319 (4) | |
H68 | 1.5717 | 1.0962 | 0.3318 | 0.038* | |
C69 | 1.43416 (18) | 0.95756 (12) | 0.29928 (13) | 0.0275 (3) | |
H69 | 1.4440 | 0.9513 | 0.3645 | 0.033* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0426 (3) | 0.0347 (2) | 0.0434 (3) | −0.01198 (19) | 0.0146 (2) | 0.0117 (2) |
O1 | 0.0635 (9) | 0.0533 (8) | 0.0291 (7) | 0.0250 (7) | 0.0201 (6) | 0.0174 (6) |
O2 | 0.0536 (8) | 0.0235 (6) | 0.0442 (8) | −0.0064 (6) | 0.0284 (7) | 0.0064 (5) |
O3 | 0.0410 (7) | 0.0271 (6) | 0.0335 (7) | −0.0018 (5) | 0.0178 (6) | 0.0078 (5) |
N1 | 0.0275 (7) | 0.0233 (7) | 0.0256 (7) | −0.0024 (5) | 0.0076 (6) | 0.0086 (5) |
N2 | 0.0269 (7) | 0.0224 (6) | 0.0234 (7) | −0.0007 (5) | 0.0081 (5) | 0.0063 (5) |
C1 | 0.0280 (8) | 0.0232 (8) | 0.0224 (8) | 0.0009 (6) | 0.0060 (6) | 0.0079 (6) |
C2 | 0.0309 (9) | 0.0231 (8) | 0.0229 (8) | −0.0011 (6) | 0.0063 (6) | 0.0051 (6) |
C3 | 0.0241 (8) | 0.0213 (7) | 0.0242 (8) | 0.0012 (6) | 0.0049 (6) | 0.0062 (6) |
C4 | 0.0218 (7) | 0.0257 (8) | 0.0218 (8) | −0.0006 (6) | 0.0050 (6) | 0.0065 (6) |
C5 | 0.0312 (9) | 0.0331 (9) | 0.0312 (9) | 0.0123 (7) | 0.0096 (7) | 0.0127 (7) |
C6 | 0.0393 (10) | 0.0407 (10) | 0.0307 (10) | 0.0139 (8) | 0.0114 (8) | 0.0198 (8) |
C7 | 0.0320 (9) | 0.0393 (10) | 0.0225 (9) | 0.0073 (7) | 0.0083 (7) | 0.0106 (7) |
C8 | 0.0380 (9) | 0.0255 (8) | 0.0267 (9) | 0.0057 (7) | 0.0075 (7) | 0.0039 (7) |
C9 | 0.0357 (9) | 0.0233 (8) | 0.0266 (9) | 0.0012 (7) | 0.0066 (7) | 0.0082 (6) |
C10 | 0.0539 (12) | 0.0585 (13) | 0.0282 (10) | 0.0207 (10) | 0.0190 (9) | 0.0088 (9) |
C11 | 0.0340 (9) | 0.0263 (8) | 0.0226 (8) | −0.0029 (7) | 0.0074 (7) | 0.0093 (6) |
C12 | 0.0365 (9) | 0.0250 (8) | 0.0330 (9) | −0.0011 (7) | 0.0159 (7) | 0.0091 (7) |
C13 | 0.0300 (9) | 0.0254 (8) | 0.0300 (9) | −0.0016 (7) | 0.0082 (7) | 0.0102 (7) |
C14 | 0.0243 (8) | 0.0229 (8) | 0.0238 (8) | 0.0011 (6) | 0.0055 (6) | 0.0079 (6) |
C15 | 0.0335 (9) | 0.0266 (8) | 0.0281 (9) | 0.0010 (7) | 0.0150 (7) | 0.0055 (7) |
C16 | 0.0398 (10) | 0.0225 (8) | 0.0279 (9) | −0.0009 (7) | 0.0137 (7) | 0.0034 (7) |
C17 | 0.0278 (8) | 0.0269 (8) | 0.0273 (9) | −0.0043 (6) | 0.0068 (7) | 0.0103 (7) |
C18 | 0.0229 (8) | 0.0319 (9) | 0.0342 (9) | 0.0025 (7) | 0.0111 (7) | 0.0084 (7) |
C19 | 0.0240 (8) | 0.0238 (8) | 0.0338 (9) | 0.0036 (6) | 0.0082 (7) | 0.0049 (7) |
Cl51 | 0.0598 (3) | 0.0331 (3) | 0.0746 (4) | 0.0013 (2) | 0.0337 (3) | 0.0242 (2) |
O51 | 0.0538 (8) | 0.0369 (7) | 0.0337 (7) | 0.0048 (6) | 0.0231 (6) | 0.0055 (6) |
O52 | 0.0520 (8) | 0.0266 (6) | 0.0360 (7) | −0.0085 (6) | 0.0214 (6) | 0.0052 (5) |
O53 | 0.0556 (8) | 0.0281 (6) | 0.0391 (8) | −0.0069 (6) | 0.0288 (6) | 0.0043 (5) |
N51 | 0.0294 (7) | 0.0269 (7) | 0.0266 (7) | −0.0031 (6) | 0.0101 (6) | 0.0097 (6) |
N52 | 0.0261 (7) | 0.0265 (7) | 0.0247 (7) | −0.0019 (5) | 0.0091 (5) | 0.0085 (5) |
C51 | 0.0281 (8) | 0.0287 (8) | 0.0249 (8) | 0.0012 (7) | 0.0079 (6) | 0.0093 (7) |
C52 | 0.0319 (9) | 0.0273 (8) | 0.0248 (9) | 0.0018 (7) | 0.0101 (7) | 0.0066 (7) |
C53 | 0.0249 (8) | 0.0245 (8) | 0.0259 (8) | 0.0016 (6) | 0.0066 (6) | 0.0088 (6) |
C54 | 0.0270 (8) | 0.0221 (7) | 0.0223 (8) | 0.0006 (6) | 0.0059 (6) | 0.0064 (6) |
C55 | 0.0284 (9) | 0.0283 (8) | 0.0281 (9) | −0.0026 (7) | 0.0069 (7) | 0.0073 (7) |
C56 | 0.0379 (10) | 0.0254 (8) | 0.0285 (9) | −0.0014 (7) | 0.0061 (7) | 0.0048 (7) |
C57 | 0.0431 (10) | 0.0260 (8) | 0.0242 (9) | 0.0097 (7) | 0.0122 (7) | 0.0077 (7) |
C58 | 0.0317 (9) | 0.0314 (9) | 0.0351 (10) | 0.0051 (7) | 0.0143 (7) | 0.0101 (7) |
C59 | 0.0269 (8) | 0.0275 (8) | 0.0279 (9) | −0.0017 (7) | 0.0060 (7) | 0.0040 (7) |
C60 | 0.0593 (13) | 0.0417 (11) | 0.0395 (11) | 0.0142 (9) | 0.0365 (10) | 0.0122 (9) |
C61 | 0.0341 (9) | 0.0280 (8) | 0.0269 (9) | 0.0000 (7) | 0.0147 (7) | 0.0081 (7) |
C62 | 0.0419 (10) | 0.0292 (9) | 0.0253 (9) | −0.0044 (7) | 0.0153 (7) | 0.0071 (7) |
C63 | 0.0324 (9) | 0.0265 (8) | 0.0264 (9) | 0.0001 (7) | 0.0090 (7) | 0.0090 (7) |
C64 | 0.0240 (8) | 0.0240 (8) | 0.0302 (9) | 0.0058 (6) | 0.0113 (6) | 0.0105 (6) |
C65 | 0.0288 (8) | 0.0298 (8) | 0.0279 (9) | 0.0052 (7) | 0.0104 (7) | 0.0097 (7) |
C66 | 0.0366 (10) | 0.0361 (9) | 0.0350 (10) | 0.0136 (8) | 0.0192 (8) | 0.0187 (8) |
C67 | 0.0302 (9) | 0.0251 (8) | 0.0490 (11) | 0.0078 (7) | 0.0212 (8) | 0.0165 (8) |
C68 | 0.0288 (9) | 0.0264 (8) | 0.0411 (10) | 0.0036 (7) | 0.0094 (7) | 0.0086 (7) |
C69 | 0.0285 (8) | 0.0266 (8) | 0.0290 (9) | 0.0049 (7) | 0.0068 (7) | 0.0090 (7) |
Cl1—C17 | 1.7379 (16) | Cl51—C67 | 1.7490 (17) |
O1—C7 | 1.370 (2) | O51—C57 | 1.362 (2) |
O1—C10 | 1.420 (2) | O51—C60 | 1.402 (2) |
O2—H2O | 0.90 (3) | O52—H52O | 0.84 (3) |
O2—C13 | 1.314 (2) | O52—C63 | 1.315 (2) |
O3—C13 | 1.220 (2) | O53—C63 | 1.216 (2) |
N1—N2 | 1.3671 (18) | N51—N52 | 1.3696 (18) |
N1—C1 | 1.333 (2) | N51—C51 | 1.326 (2) |
N2—C3 | 1.366 (2) | N52—C53 | 1.367 (2) |
N2—C4 | 1.432 (2) | N52—C54 | 1.427 (2) |
C1—C2 | 1.397 (2) | C51—C52 | 1.400 (2) |
C1—C11 | 1.501 (2) | C51—C61 | 1.504 (2) |
C2—H2 | 0.950 | C52—H52 | 0.950 |
C2—C3 | 1.377 (2) | C52—C53 | 1.373 (2) |
C3—C14 | 1.469 (2) | C53—C64 | 1.476 (2) |
C4—C5 | 1.393 (2) | C54—C55 | 1.389 (2) |
C4—C9 | 1.378 (2) | C54—C59 | 1.386 (2) |
C5—H5 | 0.950 | C55—H55 | 0.950 |
C5—C6 | 1.380 (2) | C55—C56 | 1.372 (2) |
C6—H6 | 0.950 | C56—H56 | 0.950 |
C6—C7 | 1.391 (2) | C56—C57 | 1.391 (2) |
C7—C8 | 1.386 (2) | C57—C58 | 1.394 (2) |
C8—H8 | 0.950 | C58—H58 | 0.950 |
C8—C9 | 1.391 (2) | C58—C59 | 1.388 (2) |
C9—H9 | 0.950 | C59—H59 | 0.950 |
C10—H10A | 0.980 | C60—H60A | 0.980 |
C10—H10B | 0.980 | C60—H60B | 0.980 |
C10—H10C | 0.980 | C60—H60C | 0.980 |
C11—H11A | 0.990 | C61—H61A | 0.990 |
C11—H11B | 0.990 | C61—H61B | 0.990 |
C11—C12 | 1.516 (2) | C61—C62 | 1.518 (2) |
C12—H12A | 0.990 | C62—H62A | 0.990 |
C12—H12B | 0.990 | C62—H62B | 0.990 |
C12—C13 | 1.500 (2) | C62—C63 | 1.500 (2) |
C14—C15 | 1.395 (2) | C64—C65 | 1.396 (2) |
C14—C19 | 1.393 (2) | C64—C69 | 1.393 (2) |
C15—H15 | 0.950 | C65—H65 | 0.950 |
C15—C16 | 1.378 (2) | C65—C66 | 1.387 (2) |
C16—H16 | 0.950 | C66—H66 | 0.950 |
C16—C17 | 1.381 (2) | C66—C67 | 1.382 (3) |
C17—C18 | 1.380 (2) | C67—C68 | 1.380 (3) |
C18—H18 | 0.950 | C68—H68 | 0.950 |
C18—C19 | 1.381 (2) | C68—C69 | 1.385 (2) |
C19—H19 | 0.950 | C69—H69 | 0.950 |
C7—O1—C10 | 117.50 (15) | C57—O51—C60 | 117.74 (15) |
H2O—O2—C13 | 111.6 (16) | H52O—O52—C63 | 113.1 (19) |
N2—N1—C1 | 104.60 (12) | N52—N51—C51 | 105.06 (13) |
N1—N2—C3 | 111.96 (13) | N51—N52—C53 | 111.68 (13) |
N1—N2—C4 | 119.75 (12) | N51—N52—C54 | 116.90 (13) |
C3—N2—C4 | 128.23 (13) | C53—N52—C54 | 131.39 (13) |
N1—C1—C2 | 111.54 (14) | N51—C51—C52 | 111.09 (14) |
N1—C1—C11 | 121.68 (14) | N51—C51—C61 | 120.17 (14) |
C2—C1—C11 | 126.66 (14) | C52—C51—C61 | 128.72 (15) |
C1—C2—H2 | 127.1 | C51—C52—H52 | 126.9 |
C1—C2—C3 | 105.87 (14) | C51—C52—C53 | 106.29 (14) |
H2—C2—C3 | 127.1 | H52—C52—C53 | 126.9 |
N2—C3—C2 | 106.02 (13) | N52—C53—C52 | 105.87 (14) |
N2—C3—C14 | 124.92 (14) | N52—C53—C64 | 125.40 (14) |
C2—C3—C14 | 129.06 (14) | C52—C53—C64 | 128.63 (15) |
N2—C4—C5 | 120.45 (14) | N52—C54—C55 | 117.81 (14) |
N2—C4—C9 | 119.76 (14) | N52—C54—C59 | 122.19 (14) |
C5—C4—C9 | 119.68 (15) | C55—C54—C59 | 119.99 (15) |
C4—C5—H5 | 120.0 | C54—C55—H55 | 120.0 |
C4—C5—C6 | 119.95 (16) | C54—C55—C56 | 120.04 (15) |
H5—C5—C6 | 120.0 | H55—C55—C56 | 120.0 |
C5—C6—H6 | 119.9 | C55—C56—H56 | 119.7 |
C5—C6—C7 | 120.27 (16) | C55—C56—C57 | 120.53 (16) |
H6—C6—C7 | 119.9 | H56—C56—C57 | 119.7 |
O1—C7—C6 | 115.56 (15) | O51—C57—C56 | 115.14 (15) |
O1—C7—C8 | 124.64 (16) | O51—C57—C58 | 125.30 (16) |
C6—C7—C8 | 119.79 (16) | C56—C57—C58 | 119.56 (15) |
C7—C8—H8 | 120.2 | C57—C58—H58 | 120.1 |
C7—C8—C9 | 119.62 (16) | C57—C58—C59 | 119.76 (16) |
H8—C8—C9 | 120.2 | H58—C58—C59 | 120.1 |
C4—C9—C8 | 120.57 (16) | C54—C59—C58 | 119.99 (15) |
C4—C9—H9 | 119.7 | C54—C59—H59 | 120.0 |
C8—C9—H9 | 119.7 | C58—C59—H59 | 120.0 |
O1—C10—H10A | 109.5 | O51—C60—H60A | 109.5 |
O1—C10—H10B | 109.5 | O51—C60—H60B | 109.5 |
O1—C10—H10C | 109.5 | O51—C60—H60C | 109.5 |
H10A—C10—H10B | 109.5 | H60A—C60—H60B | 109.5 |
H10A—C10—H10C | 109.5 | H60A—C60—H60C | 109.5 |
H10B—C10—H10C | 109.5 | H60B—C60—H60C | 109.5 |
C1—C11—H11A | 108.9 | C51—C61—H61A | 109.0 |
C1—C11—H11B | 108.9 | C51—C61—H61B | 109.0 |
C1—C11—C12 | 113.55 (14) | C51—C61—C62 | 112.94 (14) |
H11A—C11—H11B | 107.7 | H61A—C61—H61B | 107.8 |
H11A—C11—C12 | 108.9 | H61A—C61—C62 | 109.0 |
H11B—C11—C12 | 108.9 | H61B—C61—C62 | 109.0 |
C11—C12—H12A | 109.0 | C61—C62—H62A | 108.9 |
C11—C12—H12B | 109.0 | C61—C62—H62B | 108.9 |
C11—C12—C13 | 112.79 (14) | C61—C62—C63 | 113.51 (14) |
H12A—C12—H12B | 107.8 | H62A—C62—H62B | 107.7 |
H12A—C12—C13 | 109.0 | H62A—C62—C63 | 108.9 |
H12B—C12—C13 | 109.0 | H62B—C62—C63 | 108.9 |
O2—C13—O3 | 123.46 (15) | O52—C63—O53 | 123.44 (15) |
O2—C13—C12 | 112.14 (15) | O52—C63—C62 | 112.68 (14) |
O3—C13—C12 | 124.40 (15) | O53—C63—C62 | 123.88 (15) |
C3—C14—C15 | 119.34 (14) | C53—C64—C65 | 122.27 (15) |
C3—C14—C19 | 122.32 (14) | C53—C64—C69 | 119.37 (15) |
C15—C14—C19 | 118.33 (14) | C65—C64—C69 | 118.30 (15) |
C14—C15—H15 | 119.4 | C64—C65—H65 | 119.6 |
C14—C15—C16 | 121.17 (15) | C64—C65—C66 | 120.72 (16) |
H15—C15—C16 | 119.4 | H65—C65—C66 | 119.6 |
C15—C16—H16 | 120.5 | C65—C66—H66 | 120.4 |
C15—C16—C17 | 118.91 (15) | C65—C66—C67 | 119.22 (17) |
H16—C16—C17 | 120.5 | H66—C66—C67 | 120.4 |
Cl1—C17—C16 | 119.15 (13) | Cl51—C67—C66 | 119.55 (14) |
Cl1—C17—C18 | 119.27 (13) | Cl51—C67—C68 | 118.90 (14) |
C16—C17—C18 | 121.57 (15) | C66—C67—C68 | 121.55 (16) |
C17—C18—H18 | 120.6 | C67—C68—H68 | 120.7 |
C17—C18—C19 | 118.83 (15) | C67—C68—C69 | 118.53 (17) |
H18—C18—C19 | 120.6 | H68—C68—C69 | 120.7 |
C14—C19—C18 | 121.15 (15) | C64—C69—C68 | 121.65 (16) |
C14—C19—H19 | 119.4 | C64—C69—H69 | 119.2 |
C18—C19—H19 | 119.4 | C68—C69—H69 | 119.2 |
C1—N1—N2—C3 | −0.89 (18) | C51—N51—N52—C53 | −0.54 (18) |
C1—N1—N2—C4 | −178.32 (14) | C51—N51—N52—C54 | −178.54 (14) |
N2—N1—C1—C2 | 0.83 (18) | N52—N51—C51—C52 | −0.13 (19) |
N2—N1—C1—C11 | −175.47 (14) | N52—N51—C51—C61 | 178.58 (15) |
N1—C1—C2—C3 | −0.5 (2) | N51—C51—C52—C53 | 0.7 (2) |
C11—C1—C2—C3 | 175.59 (16) | C61—C51—C52—C53 | −177.84 (17) |
N1—N2—C3—C2 | 0.61 (18) | N51—N52—C53—C52 | 0.99 (19) |
N1—N2—C3—C14 | −178.85 (14) | N51—N52—C53—C64 | −175.58 (15) |
C4—N2—C3—C2 | 177.77 (15) | C54—N52—C53—C52 | 178.62 (16) |
C4—N2—C3—C14 | −1.7 (3) | C54—N52—C53—C64 | 2.1 (3) |
C1—C2—C3—N2 | −0.08 (18) | C51—C52—C53—N52 | −1.00 (19) |
C1—C2—C3—C14 | 179.35 (16) | C51—C52—C53—C64 | 175.41 (16) |
N1—N2—C4—C5 | −130.75 (16) | N51—N52—C54—C55 | 36.4 (2) |
N1—N2—C4—C9 | 53.0 (2) | N51—N52—C54—C59 | −142.53 (16) |
C3—N2—C4—C5 | 52.3 (2) | C53—N52—C54—C55 | −141.13 (18) |
C3—N2—C4—C9 | −123.94 (18) | C53—N52—C54—C59 | 39.9 (3) |
N2—C4—C5—C6 | −172.97 (16) | N52—C54—C55—C56 | 178.33 (15) |
C9—C4—C5—C6 | 3.3 (3) | C59—C54—C55—C56 | −2.7 (3) |
C4—C5—C6—C7 | −1.2 (3) | C54—C55—C56—C57 | −0.4 (3) |
C10—O1—C7—C6 | −177.16 (17) | C60—O51—C57—C56 | 177.24 (16) |
C10—O1—C7—C8 | 2.0 (3) | C60—O51—C57—C58 | −3.3 (3) |
C5—C6—C7—O1 | 177.24 (17) | C55—C56—C57—O51 | −178.10 (16) |
C5—C6—C7—C8 | −2.0 (3) | C55—C56—C57—C58 | 2.4 (3) |
O1—C7—C8—C9 | −176.12 (17) | O51—C57—C58—C59 | 179.35 (16) |
C6—C7—C8—C9 | 3.0 (3) | C56—C57—C58—C59 | −1.2 (3) |
N2—C4—C9—C8 | 174.04 (15) | N52—C54—C59—C58 | −177.20 (16) |
C5—C4—C9—C8 | −2.2 (2) | C55—C54—C59—C58 | 3.9 (3) |
C7—C8—C9—C4 | −0.9 (3) | C57—C58—C59—C54 | −1.9 (3) |
N1—C1—C11—C12 | −19.4 (2) | N51—C51—C61—C62 | −3.8 (2) |
C2—C1—C11—C12 | 164.86 (17) | C52—C51—C61—C62 | 174.66 (18) |
C1—C11—C12—C13 | 174.43 (15) | C51—C61—C62—C63 | −177.32 (15) |
C11—C12—C13—O2 | 176.23 (16) | C61—C62—C63—O52 | 177.55 (16) |
C11—C12—C13—O3 | −4.4 (3) | C61—C62—C63—O53 | −2.9 (3) |
N2—C3—C14—C15 | −143.44 (17) | N52—C53—C64—C65 | 41.4 (2) |
N2—C3—C14—C19 | 38.1 (2) | N52—C53—C64—C69 | −141.46 (17) |
C2—C3—C14—C15 | 37.2 (3) | C52—C53—C64—C65 | −134.38 (19) |
C2—C3—C14—C19 | −141.24 (18) | C52—C53—C64—C69 | 42.8 (2) |
C3—C14—C15—C16 | −178.80 (16) | C53—C64—C65—C66 | 178.92 (15) |
C19—C14—C15—C16 | −0.3 (3) | C69—C64—C65—C66 | 1.7 (2) |
C14—C15—C16—C17 | −0.9 (3) | C64—C65—C66—C67 | −0.6 (2) |
C15—C16—C17—Cl1 | 179.73 (14) | C65—C66—C67—Cl51 | 179.87 (13) |
C15—C16—C17—C18 | 0.5 (3) | C65—C66—C67—C68 | −0.7 (3) |
Cl1—C17—C18—C19 | −178.08 (13) | Cl51—C67—C68—C69 | −179.79 (13) |
C16—C17—C18—C19 | 1.1 (3) | C66—C67—C68—C69 | 0.8 (3) |
C17—C18—C19—C14 | −2.4 (3) | C67—C68—C69—C64 | 0.5 (3) |
C3—C14—C19—C18 | −179.55 (16) | C53—C64—C69—C68 | −178.95 (15) |
C15—C14—C19—C18 | 2.0 (3) | C65—C64—C69—C68 | −1.7 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2O···O53 | 0.90 (3) | 1.78 (3) | 2.6815 (18) | 178 (3) |
O52—H52O···O3 | 0.84 (3) | 1.84 (3) | 2.6790 (18) | 177 (3) |
C20H19ClN2O3 | F(000) = 1552 |
Mr = 370.82 | Dx = 1.383 Mg m−3 |
Monoclinic, C2/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -C 2yc | Cell parameters from 8767 reflections |
a = 22.174 (5) Å | θ = 2.6–28.3° |
b = 5.1352 (11) Å | µ = 0.24 mm−1 |
c = 31.884 (7) Å | T = 150 K |
β = 101.126 (2)° | Rod, colourless |
V = 3562.4 (13) Å3 | 0.27 × 0.15 × 0.09 mm |
Z = 8 |
Bruker APEXII CCD diffractometer | 4351 independent reflections |
Radiation source: fine-focus sealed tube | 3788 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.022 |
thin–slice ω scans | θmax = 28.3°, θmin = 2.1° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −29→29 |
Tmin = 0.919, Tmax = 0.979 | k = −6→6 |
18813 measured reflections | l = −42→42 |
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)] = 0.034 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.087 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0391P)2 + 2.9658P] where P = (Fo2 + 2Fc2)/3 |
4351 reflections | (Δ/σ)max < 0.001 |
237 parameters | Δρmax = 0.28 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
C20H19ClN2O3 | V = 3562.4 (13) Å3 |
Mr = 370.82 | Z = 8 |
Monoclinic, C2/c | Mo Kα radiation |
a = 22.174 (5) Å | µ = 0.24 mm−1 |
b = 5.1352 (11) Å | T = 150 K |
c = 31.884 (7) Å | 0.27 × 0.15 × 0.09 mm |
β = 101.126 (2)° |
Bruker APEXII CCD diffractometer | 4351 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 3788 reflections with I > 2σ(I) |
Tmin = 0.919, Tmax = 0.979 | Rint = 0.022 |
18813 measured reflections |
R[F2 > 2σ(F2)] = 0.034 | 0 restraints |
wR(F2) = 0.087 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.28 e Å−3 |
4351 reflections | Δρmin = −0.24 e Å−3 |
237 parameters |
Experimental. Spectroscopic data for compound (2) C20H19ClN2O3, Mass Calculated; 370.83, LCQ MSm/z 371.1. 1HNMR (500 MHz, MeOD) δ 7.2 (d, 2H), 7.1 (t, 4H), 6.85 (d, 2H), 6.35(s, 1H) 3.75 (s, 3H) 3.6 (s, 3H) 2.9 (t, 2H), 2.70 (t, 2H) 13C NMR δ (500 MHz, MeOD) 24.481,34.604, 107.262, 115.465, 128.453, 129.802,130.394, 131.310, 134.047, 135.525, 144.604, 153.476, 161.048, 174.982 LCQ MSm/z 371.1 |
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 F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ 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 | ||
Cl1 | 0.494947 (15) | 0.89824 (7) | 0.183985 (11) | 0.03867 (10) | |
O1 | 0.13992 (4) | 0.7107 (2) | 0.25101 (3) | 0.0336 (2) | |
O2 | 0.01512 (4) | −0.2309 (2) | −0.03747 (3) | 0.0344 (2) | |
O3 | 0.10061 (4) | −0.45884 (18) | −0.03784 (3) | 0.0313 (2) | |
N1 | 0.17275 (4) | 0.1843 (2) | 0.07866 (3) | 0.0235 (2) | |
N2 | 0.21372 (4) | 0.3414 (2) | 0.10458 (3) | 0.0218 (2) | |
C1 | 0.20409 (5) | 0.0851 (2) | 0.05067 (3) | 0.0213 (2) | |
C2 | 0.26488 (5) | 0.1765 (2) | 0.05832 (4) | 0.0222 (2) | |
H2 | 0.2960 | 0.1342 | 0.0427 | 0.027* | |
C3 | 0.27019 (5) | 0.3404 (2) | 0.09317 (3) | 0.0207 (2) | |
C4 | 0.19538 (5) | 0.4461 (2) | 0.14193 (3) | 0.0209 (2) | |
C5 | 0.21951 (5) | 0.3419 (2) | 0.18183 (4) | 0.0254 (2) | |
H5 | 0.2490 | 0.2058 | 0.1845 | 0.030* | |
C6 | 0.20032 (6) | 0.4373 (3) | 0.21763 (4) | 0.0272 (3) | |
H6 | 0.2169 | 0.3673 | 0.2450 | 0.033* | |
C7 | 0.15672 (5) | 0.6359 (2) | 0.21368 (4) | 0.0236 (2) | |
C8 | 0.13346 (5) | 0.7432 (2) | 0.17394 (4) | 0.0244 (2) | |
H8 | 0.1044 | 0.8811 | 0.1713 | 0.029* | |
C9 | 0.15308 (5) | 0.6466 (2) | 0.13799 (4) | 0.0235 (2) | |
H9 | 0.1373 | 0.7190 | 0.1107 | 0.028* | |
C10 | 0.09370 (7) | 0.9065 (3) | 0.24853 (5) | 0.0356 (3) | |
H10A | 0.1090 | 1.0701 | 0.2387 | 0.053* | |
H10B | 0.0836 | 0.9323 | 0.2768 | 0.053* | |
H10C | 0.0568 | 0.8514 | 0.2284 | 0.053* | |
C11 | 0.17471 (5) | −0.1098 (2) | 0.01787 (4) | 0.0232 (2) | |
H11A | 0.1819 | −0.2873 | 0.0299 | 0.028* | |
H11B | 0.1944 | −0.0985 | −0.0074 | 0.028* | |
C12 | 0.10599 (5) | −0.0662 (2) | 0.00385 (4) | 0.0240 (2) | |
H12A | 0.0868 | −0.0612 | 0.0294 | 0.029* | |
H12B | 0.0989 | 0.1048 | −0.0106 | 0.029* | |
C13 | 0.07555 (5) | −0.2740 (2) | −0.02584 (4) | 0.0219 (2) | |
C14 | 0.32387 (5) | 0.4880 (2) | 0.11504 (3) | 0.0205 (2) | |
C15 | 0.38242 (5) | 0.4002 (2) | 0.11127 (4) | 0.0236 (2) | |
H15 | 0.3862 | 0.2509 | 0.0944 | 0.028* | |
C16 | 0.43483 (5) | 0.5284 (2) | 0.13181 (4) | 0.0258 (2) | |
H16 | 0.4744 | 0.4681 | 0.1290 | 0.031* | |
C17 | 0.42894 (5) | 0.7448 (2) | 0.15644 (4) | 0.0250 (2) | |
C18 | 0.37196 (6) | 0.8398 (2) | 0.16025 (4) | 0.0259 (2) | |
H18 | 0.3687 | 0.9899 | 0.1771 | 0.031* | |
C19 | 0.31958 (5) | 0.7130 (2) | 0.13915 (4) | 0.0240 (2) | |
H19 | 0.2802 | 0.7797 | 0.1411 | 0.029* | |
C20 | −0.01904 (6) | −0.4267 (3) | −0.06480 (5) | 0.0366 (3) | |
H20A | −0.0050 | −0.4314 | −0.0921 | 0.055* | |
H20B | −0.0629 | −0.3841 | −0.0699 | 0.055* | |
H20C | −0.0124 | −0.5973 | −0.0509 | 0.055* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.03250 (17) | 0.03609 (19) | 0.04210 (19) | −0.01208 (13) | −0.00606 (14) | −0.00251 (14) |
O1 | 0.0399 (5) | 0.0400 (5) | 0.0234 (4) | 0.0048 (4) | 0.0122 (4) | −0.0045 (4) |
O2 | 0.0201 (4) | 0.0384 (5) | 0.0426 (5) | 0.0006 (4) | 0.0004 (4) | −0.0196 (4) |
O3 | 0.0272 (4) | 0.0258 (5) | 0.0400 (5) | 0.0020 (4) | 0.0039 (4) | −0.0119 (4) |
N1 | 0.0221 (5) | 0.0258 (5) | 0.0222 (5) | −0.0028 (4) | 0.0035 (4) | −0.0050 (4) |
N2 | 0.0205 (4) | 0.0246 (5) | 0.0206 (4) | −0.0027 (4) | 0.0046 (4) | −0.0046 (4) |
C1 | 0.0221 (5) | 0.0208 (5) | 0.0209 (5) | 0.0004 (4) | 0.0039 (4) | −0.0004 (4) |
C2 | 0.0216 (5) | 0.0228 (6) | 0.0226 (5) | −0.0003 (4) | 0.0053 (4) | −0.0020 (4) |
C3 | 0.0210 (5) | 0.0198 (5) | 0.0216 (5) | −0.0001 (4) | 0.0049 (4) | 0.0009 (4) |
C4 | 0.0201 (5) | 0.0232 (6) | 0.0200 (5) | −0.0036 (4) | 0.0054 (4) | −0.0035 (4) |
C5 | 0.0245 (5) | 0.0253 (6) | 0.0257 (6) | 0.0033 (4) | 0.0033 (4) | −0.0007 (5) |
C6 | 0.0308 (6) | 0.0300 (6) | 0.0200 (5) | 0.0020 (5) | 0.0034 (5) | 0.0015 (5) |
C7 | 0.0244 (5) | 0.0257 (6) | 0.0217 (5) | −0.0046 (4) | 0.0071 (4) | −0.0046 (4) |
C8 | 0.0223 (5) | 0.0246 (6) | 0.0265 (6) | 0.0011 (4) | 0.0053 (4) | −0.0025 (5) |
C9 | 0.0240 (5) | 0.0259 (6) | 0.0203 (5) | −0.0008 (4) | 0.0034 (4) | 0.0006 (4) |
C10 | 0.0398 (7) | 0.0350 (7) | 0.0357 (7) | 0.0001 (6) | 0.0169 (6) | −0.0121 (6) |
C11 | 0.0219 (5) | 0.0232 (6) | 0.0243 (5) | −0.0007 (4) | 0.0039 (4) | −0.0049 (4) |
C12 | 0.0222 (5) | 0.0211 (6) | 0.0282 (6) | 0.0004 (4) | 0.0032 (4) | −0.0066 (4) |
C13 | 0.0216 (5) | 0.0218 (5) | 0.0228 (5) | −0.0014 (4) | 0.0059 (4) | −0.0016 (4) |
C14 | 0.0223 (5) | 0.0201 (5) | 0.0193 (5) | −0.0025 (4) | 0.0042 (4) | 0.0012 (4) |
C15 | 0.0253 (6) | 0.0215 (6) | 0.0247 (5) | −0.0018 (4) | 0.0068 (4) | −0.0005 (4) |
C16 | 0.0227 (5) | 0.0257 (6) | 0.0291 (6) | −0.0016 (5) | 0.0050 (5) | 0.0034 (5) |
C17 | 0.0265 (6) | 0.0242 (6) | 0.0224 (5) | −0.0088 (5) | −0.0003 (4) | 0.0035 (4) |
C18 | 0.0329 (6) | 0.0213 (6) | 0.0238 (5) | −0.0056 (5) | 0.0064 (5) | −0.0019 (4) |
C19 | 0.0248 (5) | 0.0215 (6) | 0.0265 (5) | −0.0020 (4) | 0.0072 (4) | −0.0007 (4) |
C20 | 0.0248 (6) | 0.0432 (8) | 0.0400 (7) | −0.0069 (6) | 0.0021 (5) | −0.0174 (6) |
Cl1—C17 | 1.7431 (12) | C9—H9 | 0.950 |
O1—C7 | 1.3690 (14) | C10—H10A | 0.980 |
O1—C10 | 1.4271 (17) | C10—H10B | 0.980 |
O2—C13 | 1.3380 (14) | C10—H10C | 0.980 |
O2—C20 | 1.4453 (15) | C11—H11A | 0.990 |
O3—C13 | 1.1992 (14) | C11—H11B | 0.990 |
N1—N2 | 1.3672 (13) | C11—C12 | 1.5196 (16) |
N1—C1 | 1.3334 (15) | C12—H12A | 0.990 |
N2—C3 | 1.3697 (14) | C12—H12B | 0.990 |
N2—C4 | 1.4350 (14) | C12—C13 | 1.4978 (16) |
C1—C2 | 1.4035 (16) | C14—C15 | 1.4012 (16) |
C1—C11 | 1.5026 (16) | C14—C19 | 1.4013 (16) |
C2—H2 | 0.950 | C15—H15 | 0.950 |
C2—C3 | 1.3807 (15) | C15—C16 | 1.3852 (17) |
C3—C14 | 1.4689 (15) | C16—H16 | 0.950 |
C4—C5 | 1.3887 (16) | C16—C17 | 1.3817 (18) |
C4—C9 | 1.3822 (16) | C17—C18 | 1.3813 (18) |
C5—H5 | 0.950 | C18—H18 | 0.950 |
C5—C6 | 1.3828 (17) | C18—C19 | 1.3872 (17) |
C6—H6 | 0.950 | C19—H19 | 0.950 |
C6—C7 | 1.3941 (17) | C20—H20A | 0.980 |
C7—C8 | 1.3866 (17) | C20—H20B | 0.980 |
C8—H8 | 0.950 | C20—H20C | 0.980 |
C8—C9 | 1.3934 (16) | ||
C7—O1—C10 | 117.55 (10) | C1—C11—H11A | 109.1 |
C13—O2—C20 | 115.62 (10) | C1—C11—H11B | 109.1 |
N2—N1—C1 | 104.99 (9) | C1—C11—C12 | 112.46 (9) |
N1—N2—C3 | 111.85 (9) | H11A—C11—H11B | 107.8 |
N1—N2—C4 | 117.46 (9) | H11A—C11—C12 | 109.1 |
C3—N2—C4 | 129.92 (9) | H11B—C11—C12 | 109.1 |
N1—C1—C2 | 111.29 (10) | C11—C12—H12A | 109.1 |
N1—C1—C11 | 120.56 (10) | C11—C12—H12B | 109.1 |
C2—C1—C11 | 128.06 (10) | C11—C12—C13 | 112.64 (9) |
C1—C2—H2 | 127.1 | H12A—C12—H12B | 107.8 |
C1—C2—C3 | 105.87 (10) | H12A—C12—C13 | 109.1 |
H2—C2—C3 | 127.1 | H12B—C12—C13 | 109.1 |
N2—C3—C2 | 106.00 (10) | O2—C13—O3 | 122.91 (11) |
N2—C3—C14 | 124.79 (10) | O2—C13—C12 | 111.25 (10) |
C2—C3—C14 | 129.21 (10) | O3—C13—C12 | 125.83 (11) |
N2—C4—C5 | 119.66 (11) | C3—C14—C15 | 118.20 (10) |
N2—C4—C9 | 119.99 (10) | C3—C14—C19 | 123.46 (10) |
C5—C4—C9 | 120.34 (10) | C15—C14—C19 | 118.33 (10) |
C4—C5—H5 | 120.2 | C14—C15—H15 | 119.6 |
C4—C5—C6 | 119.61 (11) | C14—C15—C16 | 120.89 (11) |
H5—C5—C6 | 120.2 | H15—C15—C16 | 119.6 |
C5—C6—H6 | 119.9 | C15—C16—H16 | 120.4 |
C5—C6—C7 | 120.22 (11) | C15—C16—C17 | 119.22 (11) |
H6—C6—C7 | 119.9 | H16—C16—C17 | 120.4 |
O1—C7—C6 | 115.28 (11) | Cl1—C17—C16 | 119.19 (10) |
O1—C7—C8 | 124.56 (11) | Cl1—C17—C18 | 119.30 (10) |
C6—C7—C8 | 120.16 (11) | C16—C17—C18 | 121.50 (11) |
C7—C8—H8 | 120.3 | C17—C18—H18 | 120.5 |
C7—C8—C9 | 119.35 (11) | C17—C18—C19 | 119.08 (11) |
H8—C8—C9 | 120.3 | H18—C18—C19 | 120.5 |
C4—C9—C8 | 120.30 (11) | C14—C19—C18 | 120.92 (11) |
C4—C9—H9 | 119.8 | C14—C19—H19 | 119.5 |
C8—C9—H9 | 119.8 | C18—C19—H19 | 119.5 |
O1—C10—H10A | 109.5 | O2—C20—H20A | 109.5 |
O1—C10—H10B | 109.5 | O2—C20—H20B | 109.5 |
O1—C10—H10C | 109.5 | O2—C20—H20C | 109.5 |
H10A—C10—H10B | 109.5 | H20A—C20—H20B | 109.5 |
H10A—C10—H10C | 109.5 | H20A—C20—H20C | 109.5 |
H10B—C10—H10C | 109.5 | H20B—C20—H20C | 109.5 |
C1—N1—N2—C3 | −0.23 (13) | N2—C4—C9—C8 | 177.76 (10) |
C1—N1—N2—C4 | −171.15 (10) | C5—C4—C9—C8 | −1.09 (18) |
N2—N1—C1—C2 | 0.06 (13) | C7—C8—C9—C4 | −0.08 (18) |
N2—N1—C1—C11 | 177.00 (10) | N1—C1—C11—C12 | 31.81 (15) |
N1—C1—C2—C3 | 0.12 (14) | C2—C1—C11—C12 | −151.81 (12) |
C11—C1—C2—C3 | −176.53 (11) | C1—C11—C12—C13 | −174.82 (10) |
N1—N2—C3—C2 | 0.31 (13) | C20—O2—C13—O3 | 1.67 (18) |
N1—N2—C3—C14 | −179.55 (10) | C20—O2—C13—C12 | −177.57 (11) |
C4—N2—C3—C2 | 169.78 (11) | C11—C12—C13—O2 | 179.75 (10) |
C4—N2—C3—C14 | −10.08 (19) | C11—C12—C13—O3 | 0.54 (18) |
C1—C2—C3—N2 | −0.25 (13) | N2—C3—C14—C15 | 156.57 (11) |
C1—C2—C3—C14 | 179.60 (11) | N2—C3—C14—C19 | −24.02 (18) |
N1—N2—C4—C5 | 104.40 (13) | C2—C3—C14—C15 | −23.26 (18) |
N1—N2—C4—C9 | −74.45 (14) | C2—C3—C14—C19 | 156.15 (12) |
C3—N2—C4—C5 | −64.58 (17) | C3—C14—C15—C16 | −178.78 (11) |
C3—N2—C4—C9 | 116.56 (14) | C19—C14—C15—C16 | 1.78 (17) |
N2—C4—C5—C6 | −177.92 (11) | C14—C15—C16—C17 | 0.27 (18) |
C9—C4—C5—C6 | 0.94 (18) | C15—C16—C17—Cl1 | 177.47 (9) |
C4—C5—C6—C7 | 0.38 (19) | C15—C16—C17—C18 | −1.51 (18) |
C10—O1—C7—C6 | −177.67 (11) | Cl1—C17—C18—C19 | −178.35 (9) |
C10—O1—C7—C8 | 2.26 (18) | C16—C17—C18—C19 | 0.62 (18) |
C5—C6—C7—O1 | 178.38 (11) | C17—C18—C19—C14 | 1.52 (18) |
C5—C6—C7—C8 | −1.55 (19) | C3—C14—C19—C18 | 177.91 (11) |
O1—C7—C8—C9 | −178.53 (11) | C15—C14—C19—C18 | −2.68 (17) |
C6—C7—C8—C9 | 1.39 (18) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O3i | 0.95 | 2.50 | 3.3651 (15) | 152 |
C15—H15···O3i | 0.95 | 2.41 | 3.3317 (15) | 165 |
C18—H18···O1ii | 0.95 | 2.60 | 3.4625 (16) | 152 |
C20—H20B···N1iii | 0.98 | 2.61 | 3.5750 (18) | 169 |
C10—H10C···Cl1iv | 0.98 | 2.92 | 3.7554 (15) | 143 |
Symmetry codes: (i) −x+1/2, −y−1/2, −z; (ii) −x+1/2, y+1/2, −z+1/2; (iii) −x, −y, −z; (iv) x−1/2, y−1/2, z. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C19H17ClN2O3 | C20H19ClN2O3 |
Mr | 356.80 | 370.82 |
Crystal system, space group | Triclinic, P1 | Monoclinic, C2/c |
Temperature (K) | 150 | 150 |
a, b, c (Å) | 9.131 (2), 13.759 (3), 14.264 (3) | 22.174 (5), 5.1352 (11), 31.884 (7) |
α, β, γ (°) | 103.733 (3), 96.928 (3), 98.459 (3) | 90, 101.126 (2), 90 |
V (Å3) | 1699.2 (6) | 3562.4 (13) |
Z | 4 | 8 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.25 | 0.24 |
Crystal size (mm) | 0.32 × 0.21 × 0.11 | 0.27 × 0.15 × 0.09 |
Data collection | ||
Diffractometer | Bruker APEXII CCD diffractometer | Bruker APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.916, 0.974 | 0.919, 0.979 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19183, 8218, 6174 | 18813, 4351, 3788 |
Rint | 0.025 | 0.022 |
(sin θ/λ)max (Å−1) | 0.666 | 0.666 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.115, 1.07 | 0.034, 0.087, 1.02 |
No. of reflections | 8218 | 4351 |
No. of parameters | 461 | 237 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.52, −0.32 | 0.28, −0.24 |
Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), DIAMOND (Brandenburg & Putz, 1999) and Mercury (Version 2.2; Macrae et al., 2008), SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2008) and local programs, SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2008), and local programs.
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2O···O53 | 0.90 (3) | 1.78 (3) | 2.6815 (18) | 178 (3) |
O52—H52O···O3 | 0.84 (3) | 1.84 (3) | 2.6790 (18) | 177 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O3i | 0.95 | 2.50 | 3.3651 (15) | 152 |
C15—H15···O3i | 0.95 | 2.41 | 3.3317 (15) | 165 |
C18—H18···O1ii | 0.95 | 2.60 | 3.4625 (16) | 152 |
C20—H20B···N1iii | 0.98 | 2.61 | 3.5750 (18) | 169 |
C10—H10C···Cl1iv | 0.98 | 2.92 | 3.7554 (15) | 143 |
Symmetry codes: (i) −x+1/2, −y−1/2, −z; (ii) −x+1/2, y+1/2, −z+1/2; (iii) −x, −y, −z; (iv) x−1/2, y−1/2, z. |
Non-steroidal anti-inflammatory drugs (NSAIDs) are the oldest and most widely accepted way to treat mild to moderate pain. One possible side-effect of NSAIDs is bronchial constriction in patients (Charlier & Michaux, 2003; Young, 1999) and so they are not therapeutically advisable for asthma patients. In addition, prolonged treatment may result in gastric irritation and renal impairment. In order to increase the analgesic efficacy and reduce the side effects, we are investigating the synthesis and properties of a range of bifunctional NSAID precursors containing amino acid groups. In the process of synthesizing a precursor to the NSAID tepoxalin, we found that a mixture of regioisomers were possible, identified as I and II in the scheme. Efforts to identify unambiguously the correct regioisomer by NMR spectroscopy, using one-dimensional nuclear Overhauser effect or heteronuclear multiple bond correlation experiments, were not successful, leaving single-crystal X-ray diffraction as the only possible means of unambiguous identification. We report here the structure of the tepoxalin precursor 3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]propionic acid, (I), and the corresponding methyl ester, (II).
The asymmetric unit of (I) is shown in Fig. 1. The compound crystallizes in space group P1 with two crystallographically unique molecules in the asymmetric unit and no solvent of crystallization. The compound is unambiguously regioisomer I. Discussion is restricted to the molecule containing atoms Cl1 to H19 (hereafter `molecule A') with relevant results for the molecule containing atoms Cl51 to H69 (hereafter `molecule B') presented in square brackets. The propionic acid groups of the two crystallographically unique molecules form a hydrogen-bonded dimer with a graph set motif R22(8), as is typical of carboxylic acid groups in the solid state (Bernstein et al., 1995).
The conformational differences that give rise to two unique molecules can be easily appreciated by considering an overlay of the two unique molecules, formed by fitting together the five atoms of each pyrazole ring (r.m.s. deviation 0.0062 Å; Fig. 2). From this it is clear that although there are some small differences between the conformations of the propionic acid and chlorobenzene rings in molecules A and B the most striking difference is found in the methoxybenzene group. Although it first seems that the differences are due to methoxy group orientation, we show by careful systematic numbering that it is the angle between the methyoxybenzene and pyrazole rings which gives rise to two different conformations. The methoxy group is essentially coplanar with the benzyl ring to which it is bonded, and a mean plane fitted through all six ring C atoms and the two methoxy atoms has an r.m.s. deviation of 0.0350 Å [0.0288 Å]. This plane is rotated by 53.51 (5)° [37.32 (8)°] from the central pyrazole ring. In molecule A, the N1—N2—C4—C5 torsion angle is -130.75 (16)°, yet using the same numbering system for B the N51—N52—C54—C55 torsion angle is 36.4 (2)°. The related compound 1-(4-methoxyphenyl)-5-phenylpyrazole (Spivey et al., 2000) also features two molecules in the asymmetric unit. In both cases the methoxy group is coplanar with the benzyl ring to which it is bonded, but the torsion angles corresponding to the atoms named above are approximately 54.34° for one molecule and -53.12° for the other.
The chlorophenol ring is rotated by 37.07 (8)° [42.10 (6)°] from the pyrazole ring. The propionic acid unit has an extended conformation, and a mean plane fitted through atoms O2, O3, C1, C11, C12 and C13 has an r.m.s. deviation of 0.230 Å [0.0148 Å]. The covalent molecular geometry is unexceptional, as is the crystal packing, which consists principally of van der Waals interactions and some minor C—H···π interactions. In some parts of the structure there is evidence of favourable δ+ and δ- alignment (for example C59—H59···N1). The geometry of these interactions is such that we do not believe that these are formal weak hydrogen bonds but rather they result from simple electrostatic attraction.
Obtained as a reaction side-product in the synthesis of (I) was the corresponding methyl ester (II). This was isolated by flash chromatography and crystallized separately. The molecular structure of (II) is shown in Fig. 3 and as with molecule (I) matches that of the predicted regioisomer I; there is only one molecule in the asymmetric unit of this compound. The molecule adopts an extended conformation with the ester group essentially planar (a mean plane fitted through atoms C1, C11, C12, C13, C14 [or C20?], O2 and O3 has an r.m.s. deviation of 0.0406 Å) and that plane is rotated by 31.79 (5)° from the pyrazole ring plane. As with (I), the methoxy group is essentially coplanar with the benzyl ring to which it is bonded, and a mean plane fitted through all six ring C atoms and the two methoxy atoms has an r.m.s. deviation of 0.0323 Å. This plane is rotated by 71.01 (3)° from the pyrazole ring. Finally the chlorobenzene group is rotated by 22.93 (5)° from the central pyrazole ring. The covalent molecular geometry is unexceptional.
The crystal packing of (II) is more complex than that of (I), despite the lack of any functional groups for classical hydrogen bonding. A b-axis projection of (II) (Fig. 4) shows that the ester carbonyl atom O3 is not involved in the O—H···O hydrogen bond found in (I) and is available to form weak C—H···O hydrogen bonds to atoms H2 and H15, generating an R12(7) motif. Furthermore, one of the methyl H atoms (H20B) of the ester function is also able to participate in a weak C—H···N bond, as opposed to a purely favourable electrostatic interation by virtue of the way the atoms are oriented, with the pyrazole ring of an adjacent group. Overall the crystal packing can be most easily described as rippled, stacked sheets, as shown by a projection along the ab diagonal.