Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S160053680703749X/at2356sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S160053680703749X/at2356Isup2.hkl |
CCDC reference: 660208
Key indicators
- Single-crystal X-ray study
- T = 203 K
- Mean (C-C) = 0.002 Å
- R factor = 0.032
- wR factor = 0.068
- Data-to-parameter ratio = 24.5
checkCIF/PLATON results
No syntax errors found
Alert level C GOODF01_ALERT_2_C The least squares goodness of fit parameter lies outside the range 0.80 <> 2.00 Goodness of fit given = 0.758 PLAT026_ALERT_3_C Ratio Observed / Unique Reflections too Low .... 42 Perc. PLAT062_ALERT_4_C Rescale T(min) & T(max) by ..................... 0.97 PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) ... 2.80 Ratio PLAT230_ALERT_2_C Hirshfeld Test Diff for C1 - C2 .. 5.19 su PLAT241_ALERT_2_C Check High Ueq as Compared to Neighbors for C21 PLAT242_ALERT_2_C Check Low Ueq as Compared to Neighbors for C19 PLAT318_ALERT_2_C Check Hybridisation of N in Main Residue . ? PLAT414_ALERT_2_C Short Intra D-H..H-X H0A .. H13A .. 1.94 Ang. PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........ 1
Alert level G ABSTM02_ALERT_3_G When printed, the submitted absorption T values will be replaced by the scaled T values. Since the ratio of scaled T's is identical to the ratio of reported T values, the scaling does not imply a change to the absorption corrections used in the study. Ratio of Tmax expected/reported 0.966 Tmax scaled 0.966 Tmin scaled 0.875 REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 32.71 From the CIF: _reflns_number_total 6220 Count of symmetry unique reflns 3880 Completeness (_total/calc) 160.31% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 2340 Fraction of Friedel pairs measured 0.603 Are heavy atom types Z>Si present yes PLAT791_ALERT_1_G Confirm the Absolute Configuration of C15 = . S
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 10 ALERT level C = Check and explain 3 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 7 ALERT type 2 Indicator that the structure model may be wrong or deficient 2 ALERT type 3 Indicator that the structure quality may be low 3 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
A pure sample of the title compound was obtained as a gift sample from Sequent Scientific Ltd., India and was crystallized from a mixture of (1:1) ethylacetate and toluene (m.p.: 427–429 K).
The H atoms were included in the riding model approximation with O—H = 0.83 Å, N—H = 0.87 Å and C—H = 0.94–0.98 Å, and with Uiso(H) = 1.19–1.49Ueq(C, O, N).
The title compound is an intermediate in the preparation of efavirenz, an anti HIV drug. Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regime to prevent HIV transmission for those exposed to materials associated with a high risk for HIV transmission. Efavirenz was approved by the Food and Drug Administration (FDA) in 1998, making it the 14t h approved antiretroviral drug. In recent years fluorinated compounds find much importance in the pharmaceutical field. Fluorinated compounds in general, fluorinated heterocycles in particular, are those focused on much in modern-day medicinal chemistry. Incorporation of a fluorine atom instead of hydrogen one can alter the course of the reaction as well as its biological activities. Further introduction of a fluorine atom as the CF3 group provides a more lipophilically and pharmacologically interesting compound compared to their non fluorinated analogues. The trifluoromethyl substituted compounds have been reported to possess biological activities as herbicides, fungicides and inhibitors for platelet aggregation. In view of the importance of the fluro derivatives, a crystal structure of the title compound, (I), is reported.
The mean planes of the 5-chlorophenyl and 4-methoxybenzyl groups are twisted slightly with the amine group [dihedral angles: N—C7—C8—C13 = -8.4 (2)°; C7—N—C6—C5 = 13.6 (2)°] and 6.2 (7)° with each other forming a nearly planar arrangement (Fig. 1).
Intramolecular hydrogen bonding occurs between the amine hydrogen, and the hydroxyl oxygen, N—H0A···O2, of the title molecule. In addition, intermolecular hydrogen bonding between the the same amine hydrogen and a fluorine atom, N—H0A···F2, as well as between the methoxy oxygen atom and hydroxyl hydrogen atom, O2—H2B···O1, adds to crystal packing stability (Fig. 2).
For related structures, see: Yathirajan, Sarojini et al. (2007); Yathirajan, Sreevidya et al. (2007). For related literature, see: Whittle et al. (1994); Ren et al. (2002); Jung et al. (2002); Küçükgüzel et al. (2000).
Data collection: CrysAlis PRO (Oxford Diffraction, 2007); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2000); software used to prepare material for publication: SHELXTL.
C21H19ClF3NO2 | F(000) = 848 |
Mr = 409.82 | Dx = 1.450 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 4798 reflections |
a = 8.6400 (19) Å | θ = 4.6–32.6° |
b = 9.7671 (9) Å | µ = 0.25 mm−1 |
c = 22.240 (5) Å | T = 203 K |
V = 1876.8 (6) Å3 | Plate, colourless |
Z = 4 | 0.43 × 0.37 × 0.14 mm |
Oxford Diffraction Gemini R diffractometer | 6220 independent reflections |
Radiation source: fine-focus sealed tube | 2640 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.050 |
Detector resolution: 10.5081 pixels mm-1 | θmax = 32.7°, θmin = 4.8° |
φ and ω scans | h = −12→12 |
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007) | k = −13→14 |
Tmin = 0.906, Tmax = 1.000 | l = −32→32 |
18057 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)] = 0.032 | H-atom parameters constrained |
wR(F2) = 0.069 | w = 1/[σ2(Fo2) + (0.0312P)2] where P = (Fo2 + 2Fc2)/3 |
S = 0.76 | (Δ/σ)max = 0.016 |
6220 reflections | Δρmax = 0.21 e Å−3 |
254 parameters | Δρmin = −0.22 e Å−3 |
0 restraints | Absolute structure: Flack (1983), with 3628 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.02 (4) |
C21H19ClF3NO2 | V = 1876.8 (6) Å3 |
Mr = 409.82 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.6400 (19) Å | µ = 0.25 mm−1 |
b = 9.7671 (9) Å | T = 203 K |
c = 22.240 (5) Å | 0.43 × 0.37 × 0.14 mm |
Oxford Diffraction Gemini R diffractometer | 6220 independent reflections |
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007) | 2640 reflections with I > 2σ(I) |
Tmin = 0.906, Tmax = 1.000 | Rint = 0.050 |
18057 measured reflections |
R[F2 > 2σ(F2)] = 0.032 | H-atom parameters constrained |
wR(F2) = 0.069 | Δρmax = 0.21 e Å−3 |
S = 0.76 | Δρmin = −0.22 e Å−3 |
6220 reflections | Absolute structure: Flack (1983), with 3628 Friedel pairs |
254 parameters | Absolute structure parameter: 0.02 (4) |
0 restraints |
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 | ||
Cl | 0.82991 (6) | 0.66081 (4) | 0.14333 (2) | 0.05311 (14) | |
F1 | 0.90703 (12) | 0.15349 (10) | 0.23407 (4) | 0.0495 (3) | |
F2 | 0.85448 (12) | 0.01133 (9) | 0.16359 (4) | 0.0507 (3) | |
F3 | 1.06136 (12) | −0.01341 (9) | 0.21520 (4) | 0.0485 (3) | |
O1 | 0.89852 (13) | −0.45246 (10) | −0.11680 (5) | 0.0395 (3) | |
O2 | 1.12304 (12) | 0.08094 (11) | 0.10175 (4) | 0.0355 (3) | |
H2B | 1.2016 | 0.0439 | 0.1158 | 0.053* | |
N | 0.86626 (16) | 0.10757 (13) | 0.03665 (5) | 0.0332 (3) | |
H0A | 0.9088 | 0.0411 | 0.0568 | 0.040* | |
C1 | 0.94820 (17) | 0.26983 (14) | 0.11402 (6) | 0.0260 (3) | |
C2 | 0.93451 (18) | 0.40036 (16) | 0.13820 (7) | 0.0306 (4) | |
H2A | 0.9913 | 0.4230 | 0.1729 | 0.037* | |
C3 | 0.8395 (2) | 0.49753 (14) | 0.11254 (7) | 0.0339 (4) | |
C4 | 0.7563 (2) | 0.46620 (17) | 0.06224 (8) | 0.0398 (4) | |
H4A | 0.6919 | 0.5325 | 0.0446 | 0.048* | |
C5 | 0.76666 (19) | 0.33727 (17) | 0.03738 (7) | 0.0360 (4) | |
H5A | 0.7083 | 0.3168 | 0.0029 | 0.043* | |
C6 | 0.86196 (18) | 0.23591 (15) | 0.06223 (6) | 0.0282 (4) | |
C7 | 0.8037 (2) | 0.07891 (15) | −0.02165 (7) | 0.0364 (4) | |
H7A | 0.8517 | 0.1405 | −0.0510 | 0.044* | |
H7B | 0.6924 | 0.0981 | −0.0212 | 0.044* | |
C8 | 0.82856 (19) | −0.06668 (15) | −0.04160 (7) | 0.0306 (4) | |
C9 | 0.7601 (2) | −0.10854 (17) | −0.09471 (8) | 0.0424 (4) | |
H9A | 0.6951 | −0.0473 | −0.1153 | 0.051* | |
C10 | 0.7839 (2) | −0.23590 (17) | −0.11818 (8) | 0.0434 (4) | |
H10A | 0.7357 | −0.2614 | −0.1544 | 0.052* | |
C11 | 0.87869 (18) | −0.32664 (16) | −0.08862 (7) | 0.0311 (4) | |
C12 | 0.9456 (2) | −0.29100 (16) | −0.03566 (8) | 0.0392 (4) | |
H12A | 1.0091 | −0.3535 | −0.0150 | 0.047* | |
C13 | 0.9191 (2) | −0.16095 (17) | −0.01221 (7) | 0.0390 (4) | |
H13A | 0.9643 | −0.1370 | 0.0248 | 0.047* | |
C14 | 1.0172 (2) | −0.54038 (17) | −0.09373 (9) | 0.0514 (5) | |
H14A | 1.0199 | −0.6244 | −0.1170 | 0.077* | |
H14B | 0.9956 | −0.5617 | −0.0520 | 0.077* | |
H14C | 1.1166 | −0.4946 | −0.0966 | 0.077* | |
C15 | 1.05879 (17) | 0.16978 (15) | 0.14503 (6) | 0.0274 (3) | |
C16 | 0.9694 (2) | 0.07957 (17) | 0.18995 (8) | 0.0345 (4) | |
C17 | 1.18271 (19) | 0.23895 (15) | 0.17881 (7) | 0.0311 (4) | |
C18 | 1.28762 (19) | 0.28546 (15) | 0.20665 (7) | 0.0342 (4) | |
C19 | 1.4148 (2) | 0.34007 (18) | 0.24111 (8) | 0.0411 (4) | |
H19A | 1.4228 | 0.3049 | 0.2827 | 0.049* | |
C20 | 1.4705 (3) | 0.4811 (2) | 0.23272 (10) | 0.0676 (7) | |
H20A | 1.4182 | 0.5378 | 0.2026 | 0.081* | |
H20B | 1.5066 | 0.5308 | 0.2683 | 0.081* | |
C21 | 1.5639 (3) | 0.3671 (2) | 0.21144 (10) | 0.0727 (7) | |
H21A | 1.6586 | 0.3453 | 0.2337 | 0.087* | |
H21B | 1.5703 | 0.3523 | 0.1679 | 0.087* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl | 0.0663 (3) | 0.0375 (2) | 0.0555 (3) | 0.0118 (2) | −0.0040 (3) | −0.0080 (2) |
F1 | 0.0513 (6) | 0.0649 (6) | 0.0323 (5) | 0.0004 (6) | 0.0132 (5) | 0.0022 (5) |
F2 | 0.0472 (6) | 0.0591 (6) | 0.0459 (6) | −0.0258 (5) | −0.0090 (5) | 0.0130 (5) |
F3 | 0.0560 (6) | 0.0459 (5) | 0.0435 (6) | 0.0030 (5) | −0.0096 (5) | 0.0180 (5) |
O1 | 0.0334 (7) | 0.0377 (6) | 0.0475 (7) | 0.0026 (5) | −0.0007 (6) | −0.0050 (5) |
O2 | 0.0313 (7) | 0.0436 (6) | 0.0318 (6) | 0.0099 (5) | −0.0045 (6) | −0.0058 (5) |
N | 0.0399 (8) | 0.0319 (7) | 0.0279 (7) | 0.0000 (6) | −0.0098 (7) | 0.0025 (6) |
C1 | 0.0241 (8) | 0.0308 (8) | 0.0231 (8) | −0.0018 (7) | 0.0014 (7) | 0.0032 (7) |
C2 | 0.0271 (8) | 0.0395 (9) | 0.0253 (8) | −0.0024 (7) | 0.0023 (8) | 0.0011 (7) |
C3 | 0.0369 (9) | 0.0301 (8) | 0.0346 (9) | 0.0007 (8) | 0.0026 (9) | −0.0014 (7) |
C4 | 0.0395 (10) | 0.0391 (10) | 0.0408 (10) | 0.0071 (8) | −0.0050 (9) | 0.0071 (8) |
C5 | 0.0354 (9) | 0.0442 (10) | 0.0283 (8) | 0.0001 (9) | −0.0076 (8) | 0.0031 (8) |
C6 | 0.0253 (9) | 0.0327 (9) | 0.0267 (8) | −0.0027 (7) | 0.0000 (8) | 0.0040 (7) |
C7 | 0.0432 (11) | 0.0394 (9) | 0.0267 (9) | −0.0005 (8) | −0.0059 (8) | 0.0035 (7) |
C8 | 0.0297 (9) | 0.0359 (9) | 0.0263 (8) | −0.0044 (8) | 0.0014 (8) | 0.0011 (7) |
C9 | 0.0461 (11) | 0.0441 (10) | 0.0370 (10) | 0.0112 (8) | −0.0180 (9) | −0.0045 (8) |
C10 | 0.0467 (11) | 0.0488 (11) | 0.0347 (10) | 0.0033 (9) | −0.0119 (9) | −0.0059 (9) |
C11 | 0.0258 (9) | 0.0333 (9) | 0.0342 (9) | −0.0062 (8) | 0.0019 (8) | −0.0013 (8) |
C12 | 0.0432 (11) | 0.0382 (10) | 0.0361 (10) | −0.0038 (8) | −0.0113 (9) | 0.0066 (8) |
C13 | 0.0497 (11) | 0.0368 (9) | 0.0306 (9) | −0.0082 (9) | −0.0137 (9) | 0.0004 (8) |
C14 | 0.0415 (11) | 0.0500 (11) | 0.0628 (13) | 0.0093 (9) | −0.0033 (10) | −0.0051 (10) |
C15 | 0.0267 (8) | 0.0306 (7) | 0.0248 (8) | 0.0001 (8) | 0.0003 (8) | −0.0030 (7) |
C16 | 0.0368 (10) | 0.0356 (9) | 0.0312 (9) | −0.0032 (9) | −0.0025 (9) | 0.0044 (8) |
C17 | 0.0275 (9) | 0.0320 (8) | 0.0337 (9) | −0.0003 (8) | −0.0023 (8) | 0.0037 (7) |
C18 | 0.0304 (10) | 0.0337 (9) | 0.0386 (10) | 0.0016 (8) | 0.0010 (8) | −0.0005 (7) |
C19 | 0.0359 (10) | 0.0465 (10) | 0.0408 (10) | −0.0044 (9) | −0.0069 (9) | 0.0017 (9) |
C20 | 0.0816 (17) | 0.0393 (11) | 0.0818 (15) | −0.0179 (12) | −0.0386 (14) | 0.0011 (11) |
C21 | 0.0464 (12) | 0.0994 (18) | 0.0723 (15) | −0.0318 (13) | 0.0111 (13) | −0.0185 (13) |
Cl—C3 | 1.7375 (15) | C8—C9 | 1.383 (2) |
F1—C16 | 1.3321 (18) | C9—C10 | 1.365 (2) |
F2—C16 | 1.3317 (19) | C9—H9A | 0.9400 |
F3—C16 | 1.3311 (18) | C10—C11 | 1.374 (2) |
O1—C11 | 1.3901 (18) | C10—H10A | 0.9400 |
O1—C14 | 1.4327 (19) | C11—C12 | 1.357 (2) |
O2—C15 | 1.4097 (16) | C12—C13 | 1.392 (2) |
O2—H2B | 0.8300 | C12—H12A | 0.9400 |
N—C6 | 1.3771 (18) | C13—H13A | 0.9400 |
N—C7 | 1.4323 (18) | C14—H14A | 0.9700 |
N—H0A | 0.8700 | C14—H14B | 0.9700 |
C1—C2 | 1.389 (2) | C14—H14C | 0.9700 |
C1—C6 | 1.411 (2) | C15—C17 | 1.472 (2) |
C1—C15 | 1.531 (2) | C15—C16 | 1.540 (2) |
C2—C3 | 1.379 (2) | C17—C18 | 1.188 (2) |
C2—H2A | 0.9400 | C18—C19 | 1.442 (2) |
C3—C4 | 1.365 (2) | C19—C20 | 1.471 (3) |
C4—C5 | 1.378 (2) | C19—C21 | 1.471 (3) |
C4—H4A | 0.9400 | C19—H19A | 0.9900 |
C5—C6 | 1.401 (2) | C20—C21 | 1.454 (3) |
C5—H5A | 0.9400 | C20—H20A | 0.9800 |
C7—C8 | 1.505 (2) | C20—H20B | 0.9800 |
C7—H7A | 0.9800 | C21—H21A | 0.9800 |
C7—H7B | 0.9800 | C21—H21B | 0.9800 |
C8—C13 | 1.373 (2) | ||
C11—O1—C14 | 117.17 (13) | C13—C12—H12A | 120.4 |
C15—O2—H2B | 109.5 | C8—C13—C12 | 121.81 (15) |
C6—N—C7 | 122.80 (12) | C8—C13—H13A | 119.1 |
C6—N—H0A | 118.6 | C12—C13—H13A | 119.1 |
C7—N—H0A | 118.6 | O1—C14—H14A | 109.5 |
C2—C1—C6 | 119.12 (14) | O1—C14—H14B | 109.5 |
C2—C1—C15 | 117.70 (13) | H14A—C14—H14B | 109.5 |
C6—C1—C15 | 123.18 (13) | O1—C14—H14C | 109.5 |
C3—C2—C1 | 121.49 (14) | H14A—C14—H14C | 109.5 |
C3—C2—H2A | 119.3 | H14B—C14—H14C | 109.5 |
C1—C2—H2A | 119.3 | O2—C15—C17 | 110.16 (12) |
C4—C3—C2 | 119.92 (14) | O2—C15—C1 | 109.34 (11) |
C4—C3—Cl | 120.25 (13) | C17—C15—C1 | 113.01 (12) |
C2—C3—Cl | 119.81 (12) | O2—C15—C16 | 106.76 (12) |
C3—C4—C5 | 119.96 (15) | C17—C15—C16 | 107.23 (12) |
C3—C4—H4A | 120.0 | C1—C15—C16 | 110.14 (12) |
C5—C4—H4A | 120.0 | F2—C16—F3 | 106.82 (13) |
C4—C5—C6 | 121.71 (15) | F2—C16—F1 | 107.11 (14) |
C4—C5—H5A | 119.1 | F3—C16—F1 | 107.48 (13) |
C6—C5—H5A | 119.1 | F2—C16—C15 | 112.00 (13) |
N—C6—C5 | 119.73 (14) | F3—C16—C15 | 111.38 (14) |
N—C6—C1 | 122.46 (14) | F1—C16—C15 | 111.76 (13) |
C5—C6—C1 | 117.80 (14) | C18—C17—C15 | 175.12 (16) |
N—C7—C8 | 113.44 (13) | C17—C18—C19 | 179.06 (18) |
N—C7—H7A | 108.9 | C18—C19—C20 | 121.87 (15) |
C8—C7—H7A | 108.9 | C18—C19—C21 | 119.69 (15) |
N—C7—H7B | 108.9 | C20—C19—C21 | 59.26 (13) |
C8—C7—H7B | 108.9 | C18—C19—H19A | 114.9 |
H7A—C7—H7B | 107.7 | C20—C19—H19A | 114.9 |
C13—C8—C9 | 116.86 (14) | C21—C19—H19A | 114.9 |
C13—C8—C7 | 125.05 (15) | C21—C20—C19 | 60.39 (12) |
C9—C8—C7 | 118.05 (15) | C21—C20—H20A | 117.7 |
C10—C9—C8 | 122.13 (16) | C19—C20—H20A | 117.7 |
C10—C9—H9A | 118.9 | C21—C20—H20B | 117.7 |
C8—C9—H9A | 118.9 | C19—C20—H20B | 117.7 |
C9—C10—C11 | 119.65 (16) | H20A—C20—H20B | 114.9 |
C9—C10—H10A | 120.2 | C20—C21—C19 | 60.35 (14) |
C11—C10—H10A | 120.2 | C20—C21—H21A | 117.7 |
C12—C11—C10 | 120.23 (15) | C19—C21—H21A | 117.7 |
C12—C11—O1 | 124.44 (14) | C20—C21—H21B | 117.7 |
C10—C11—O1 | 115.33 (14) | C19—C21—H21B | 117.7 |
C11—C12—C13 | 119.28 (15) | H21A—C21—H21B | 114.9 |
C11—C12—H12A | 120.4 | ||
C6—C1—C2—C3 | −0.4 (2) | C14—O1—C11—C10 | 168.93 (14) |
C15—C1—C2—C3 | 178.93 (13) | C10—C11—C12—C13 | −1.0 (2) |
C1—C2—C3—C4 | 0.0 (2) | O1—C11—C12—C13 | 178.99 (14) |
C1—C2—C3—Cl | −178.38 (12) | C9—C8—C13—C12 | 2.2 (2) |
C2—C3—C4—C5 | 0.4 (2) | C7—C8—C13—C12 | −175.29 (16) |
Cl—C3—C4—C5 | 178.77 (13) | C11—C12—C13—C8 | −0.9 (3) |
C3—C4—C5—C6 | −0.3 (2) | C2—C1—C15—O2 | −148.07 (13) |
C7—N—C6—C5 | 13.6 (2) | C6—C1—C15—O2 | 31.26 (18) |
C7—N—C6—C1 | −167.77 (15) | C2—C1—C15—C17 | −24.99 (18) |
C4—C5—C6—N | 178.61 (15) | C6—C1—C15—C17 | 154.34 (14) |
C4—C5—C6—C1 | −0.1 (2) | C2—C1—C15—C16 | 94.91 (16) |
C2—C1—C6—N | −178.20 (14) | C6—C1—C15—C16 | −85.76 (17) |
C15—C1—C6—N | 2.5 (2) | O2—C15—C16—F2 | −61.54 (16) |
C2—C1—C6—C5 | 0.4 (2) | C17—C15—C16—F2 | −179.58 (13) |
C15—C1—C6—C5 | −178.89 (13) | C1—C15—C16—F2 | 57.07 (17) |
C6—N—C7—C8 | 177.15 (14) | O2—C15—C16—F3 | 58.03 (16) |
N—C7—C8—C13 | −8.4 (2) | C17—C15—C16—F3 | −60.02 (16) |
N—C7—C8—C9 | 174.05 (15) | C1—C15—C16—F3 | 176.64 (12) |
C13—C8—C9—C10 | −1.8 (3) | O2—C15—C16—F1 | 178.27 (12) |
C7—C8—C9—C10 | 175.92 (16) | C17—C15—C16—F1 | 60.23 (16) |
C8—C9—C10—C11 | 0.0 (3) | C1—C15—C16—F1 | −63.12 (16) |
C9—C10—C11—C12 | 1.5 (2) | C18—C19—C20—C21 | −107.99 (19) |
C9—C10—C11—O1 | −178.54 (15) | C18—C19—C21—C20 | 111.60 (19) |
C14—O1—C11—C12 | −11.1 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2B···O1i | 0.83 | 1.92 | 2.7114 (15) | 159 |
N—H0A···O2 | 0.87 | 2.14 | 2.6620 (17) | 118 |
N—H0A···F2 | 0.87 | 2.44 | 2.9773 (16) | 121 |
Symmetry code: (i) x+1/2, −y−1/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C21H19ClF3NO2 |
Mr | 409.82 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 203 |
a, b, c (Å) | 8.6400 (19), 9.7671 (9), 22.240 (5) |
V (Å3) | 1876.8 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.25 |
Crystal size (mm) | 0.43 × 0.37 × 0.14 |
Data collection | |
Diffractometer | Oxford Diffraction Gemini R |
Absorption correction | Multi-scan (CrysAlis RED; Oxford Diffraction, 2007) |
Tmin, Tmax | 0.906, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 18057, 6220, 2640 |
Rint | 0.050 |
(sin θ/λ)max (Å−1) | 0.760 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.032, 0.069, 0.76 |
No. of reflections | 6220 |
No. of parameters | 254 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.22 |
Absolute structure | Flack (1983), with 3628 Friedel pairs |
Absolute structure parameter | 0.02 (4) |
Computer programs: CrysAlis PRO (Oxford Diffraction, 2007), CrysAlis PRO, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 2000), SHELXTL.
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2B···O1i | 0.83 | 1.92 | 2.7114 (15) | 158.6 |
N—H0A···O2 | 0.87 | 2.14 | 2.6620 (17) | 118.0 |
N—H0A···F2 | 0.87 | 2.44 | 2.9773 (16) | 120.6 |
Symmetry code: (i) x+1/2, −y−1/2, −z. |
The title compound is an intermediate in the preparation of efavirenz, an anti HIV drug. Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regime to prevent HIV transmission for those exposed to materials associated with a high risk for HIV transmission. Efavirenz was approved by the Food and Drug Administration (FDA) in 1998, making it the 14t h approved antiretroviral drug. In recent years fluorinated compounds find much importance in the pharmaceutical field. Fluorinated compounds in general, fluorinated heterocycles in particular, are those focused on much in modern-day medicinal chemistry. Incorporation of a fluorine atom instead of hydrogen one can alter the course of the reaction as well as its biological activities. Further introduction of a fluorine atom as the CF3 group provides a more lipophilically and pharmacologically interesting compound compared to their non fluorinated analogues. The trifluoromethyl substituted compounds have been reported to possess biological activities as herbicides, fungicides and inhibitors for platelet aggregation. In view of the importance of the fluro derivatives, a crystal structure of the title compound, (I), is reported.
The mean planes of the 5-chlorophenyl and 4-methoxybenzyl groups are twisted slightly with the amine group [dihedral angles: N—C7—C8—C13 = -8.4 (2)°; C7—N—C6—C5 = 13.6 (2)°] and 6.2 (7)° with each other forming a nearly planar arrangement (Fig. 1).
Intramolecular hydrogen bonding occurs between the amine hydrogen, and the hydroxyl oxygen, N—H0A···O2, of the title molecule. In addition, intermolecular hydrogen bonding between the the same amine hydrogen and a fluorine atom, N—H0A···F2, as well as between the methoxy oxygen atom and hydroxyl hydrogen atom, O2—H2B···O1, adds to crystal packing stability (Fig. 2).