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The structure of the title benzovesamicol analogue, C21H27N3O2, an important compound for the diagnosis of Alzheimer's disease, has been determined by X-ray powder diffraction. The title compound was firstly synthesized and characterized by spectroscopic methods (FT–IR, and 13C and 1H NMR). The compound is a racemic mixture of enantio­mers which crystallizes in the monoclinic system in a centrosymmetric space group (P21/c). Crystallography, in particular powder X-ray diffraction, was pivotal in revealing that the enantio-resolution did not succeed. The piperazine ring is in a chair conformation, while the cyclo­hexene ring assumes a half-chair conformation. The crystal packing is dominated by inter­molecular O—H...N hydrogen bonding which links molecules along the c direction.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270111040844/cu3006sup1.cif
Contains datablocks global, I

rtv

Rietveld powder data file (CIF format) https://doi.org/10.1107/S0108270111040844/cu3006Isup2.rtv
Contains datablock I

CCDC reference: 813007

Comment top

(2RS,3RS)-5-Amino-3-[4-(3-methoxyphenyl)piperazin-1-yl]-1,2,3,4-tetrahydronaphthalen-2-ol, (2RS,3RS)-(I), is a benzovezamicol derivative, which is used in cholinergic nerve imaging for the diagnosis of Alzheimer's disease. Radiolabelled benzovesamicol analogues have been widely used as imaging probes in single photon emission computer tomography (SPECT) and positron emission tomography (PET), aimed at both in vitro and in vivo studies of Alzheimer's disease (Alfonso et al., 1993; Efange et al., 1997). For this aim, many efforts have focused on developing vesamicol derivatives as radiotracers using SPECT and PET (Rogers et al., 1989; Jung et al., 1990; Mulholland & Jung, 1992; Mulholland et al., 1993; Van Dort et al., 1993; Kuhl et al., 1996; Sorger et al., 2000; Bando et al., 2000; Bando et al., 2001; Auld et al., 2002; Zea-Ponce et al., 2005).

The title compound, (2RS,3RS)-(I), was prepared as presented in the reaction scheme. The synthesis was started with the addition of 1-(3-methoxyphenyl)piperazine to 2,2,2-trifluoro-N-(1a,2,7,7a-tetrahydronaphtho[2,3-b]oxiren-3-yl)acetamide (Rogers et al., 1989; Zea-Ponce et al., 2005) to obtain two regioisomers, which were separated by flash chromatography (silica gel; Et2O and Et3N, 10:1 v/v). Compound (2RS,3RS)-(I) was characterized by FT–IR and 13C and 1H NMR spectroscopy and showed results consistent with the assigned structures. Moreover, since the specific binding of benzovezamicol derivatives is known to be highly enantioselective, enantiomeric resolution of racemic (2RS,3RS)-(I) was performed using (1S)-(+)-camphor-10-sulphonic acid [(+)-CSA] (see Experimental). The resulting compound, supposedly a pure enantiomer, crystallizes in the form of very fine white powder. It seems impossible, to our knowledge, to grow single crystals of sufficient thickness and quality for single-crystal X-ray diffraction experiments. Thus, a crystal structure determination by powder X-ray diffraction was attempted for this compound.

We employed in-house powder X-ray diffraction data to solve and refine the crystal structure of (2RS,3RS)-(I). This involves a 26-atom (non-H) problem, which requires careful measurement and interpretation of the data in order to optimize the quality of the results. In recent years, the crystal structures of a number of compounds of pharmaceutical interest have been determined by powder X-ray diffraction data as a last resort in the absence of single crystals of sufficient quality (Chan et al., 1999; Shankland et al., 2004; Chernyshev et al., 2003; Kiang et al., 2003; Rukiah et al., 2004; Van der Lee et al., 2005; Rukiah & Assaad, 2010; Al-Ktaifani & Rukiah, 2010; Rukiah & Al-Ktaifani, 2011).

The title compound crystallizes in the achiral centrosymmetric space group P21/c. A chiral compound must necessarily pack in a motif such that other molecules in the unit cell can not be superimposed on their own mirror images. In crystals, this condition for chirality excludes both the inversion centre and the mirror-plane symmetry elements. Thus, chiral molecules can not belong to space groups having these symmetry elements. However, crystal structure determination in the chiral space group P21 in the monoclinic system with two molecules in the asymmetric unit was unsuccessful. On the other hand, crystal structure determination in the achiral space group P21/c did give a structure suitable for Rietveld refinement. Consequently, the sample was most likely racemic. To confirm this result, an analysis of the optical purity of the bulk material was performed by high-performance liquid chromatography (HPLC) and polarimetry. We used chiral HPLC to analyze the isolated product, (2R,3R)-(I). The analysis of the optical purity was performed using semipreparative HPLC and a Chiracel column (4.6 × 150 mm; 5 µm, Zorpax, SPAO) and acetonitrile–H2O–TFA (80/20/0.1 v/v) as eluant at a flow rate of 1 ml min-1. HPLC–UV absorption was observed at 254 nm, which gave two peaks (retention times at 3.5 and 4.5 min) instead of one. A polarimeter was also used to measure the rotation of plane-polarized light. The net rotation of plane-polarized light is 0°, which means that the compound was optically inactive. These results mean that the enantiomeric resolution was not successful and the compound was indeed racemic.

An ORTEP-3 (Farrugia, 1997) view of compound (2RS,3RS)-(I) with atomic labelling is shown in Fig. 1. Selected bond lengths and bond and torsion angles are reported in Table 2. Bond lengths and angles in compound (2RS,3RS)-(I) are in their normal ranges (Allen et al., 1987). The molecule contains four six-membered rings (two benzene, a piperazine and a cyclohexene). The piperazine ring adopts a chair conformation, as shown by its puckering parameters (Cremer & Pople, 1975) Q = 0.578 (13) Å, θ = 3.5 (13)° and ϕ = 82 (19)°. The bond lengths and angles around atoms C6 and C5 clearly confirm the presence of an aromatic bond length. The cyclohexene ring assumes a conformation very similar to a half-chair [puckering parameters Q = 0.560 (14) Å, θ = 33.6 (15)° and ϕ = 228 (3)°], with the C5/C6/C7/C10 atoms nearly coplanar (the maximum deviation from the mean plane is 0.0157 Å for atom C5) and atoms C8 and C9 situated below and above this mean plane, respectively. The cyclohexene ring is trans-fused to the first benzene ring (C1–C6) through atoms C5 and C6 to form a ten-membered ring system which is a tetrahydronaphthalene.

The crystal packing is characterized by an intermolecular head-to-tail O—H···N hydrogen bond involving the hydroxy H atom and the amine H atom. The hydrogen bond forms a one-dimensional chain in the [001] direction (Fig. 2).

Related literature top

For related literature, see: Al-Ktaifani & Rukiah (2010); Alfonso et al. (1993); Allen et al. (1987); Altomare et al. (1999); Auld et al. (2002); Bando et al. (2000, 2001); Boultif & Louër (2004); Chan et al. (1999); Chernyshev et al. (2003); Cremer & Pople (1975); Dollase (1986); Efange et al. (1997); Farrugia (1997); Favre-Nicolin & Černý (2002); Finger et al. (1994); Jung et al. (1990); Kiang et al. (2003); Kuhl et al. (1996); Larson & Von Dreele (2004); Le Bail, Duroy & Fourquet (1988); March (1932); Mulholland & Jung (1992); Mulholland et al. (1993); Rodriguez-Carvajal (2001); Rogers et al. (1989); Roisnel & Rodriguez-Carvajal (2001); Rukiah & Al-Ktaifani (2011); Rukiah & Assaad (2010); Rukiah et al. (2004); Shankland et al. (2004); Sorger et al. (2000); Stephens (1999); Thompson et al. (1987); Toby (2001); Van Dort, Jung, Gildersleeve, Hagen, Kuhl & Wieland (1993); Van der Lee, Richez & Tapiero (2005); Von Dreele (1997); Zea-Ponce, Mavel, Assaad, Kruse, Parsons, Emond, Chalon, Kruse, Giboureau, Kassiou & Guilloteau (2005).

Experimental top

2,2,2-Trifluoro-N-(1a,2,7,7a-tetrahydronaphtho[2,3-b]oxiren-3-yl)acetamide was prepared according to a previously reported method (Rukiah & Assaad, 2010). The powder sample of compound (2RS,3RS)-(I) was ground lightly in a mortar, loaded between two Mylar foils and fixed in the sample holder with a mask of suitable internal diameter (8.0 mm). X-ray powder diffraction data were collected at room temperature with a Stoe transmission Stadi P diffractometer using monochromatic Cu Kα1 radiation (λ = 1.54060 Å) selected with an incident-beam curved-crystal germanium(111) monochromator, using the Stoe transmission geometry (horizontal set-up) with a linear position-sensitive detector (PSD). The pattern was scanned over the angular range 5–85° (2θ).

For synthesis and enantiomeric resolution of (2RS,3RS)-(I), 1-(3-methoxyphenyl)piperazine (9.44 g, 49 mmol) was added to a solution of 1-amino-N-triflouroacetyl-5,8-dihydronaphthalene oxide (4 g, 16 mmol) in ethanol (25 ml). The solution was refluxed for 16 h, and then kept for 24 h at room temperature to produce a powder solid. The solid was filtered and dried under vacuum, then dissolved in methanol (25 ml) and treated with 1 N NaOH (15 ml). The mixture was stirred at room temperature for 16 h and then extracted with CH2Cl2 (3 × 25 ml). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting regioisomers were separated by silica-gel chromatography with ethyl acetate–hexane (7:3 v/v) to give 900 mg (64%) of (2RS,3RS)-(I) (RF = 0.65; m.p. 478–484 K).

The racemic mixture of (2RS,3RS)-(I) was separated into its enantiomers by complexation with (1S)-(+)-camphor-10-sulphonic acid [(+)-CSA]. Racemic (2RS,3RS)-(I) (500 mg, 1.41 mmol) and [(+)-CSA] (300 mg, 1.29 mmol) were dissolved in boiling acetonitrile. The mixture was stirred at room temperature for 16 h. The precipitate obtained on standing was filtered and treated with 1 N NaOH and CHCl3 (25 ml), while the aqueous layer was treated with CHCl3 (3 × 25 ml). The combined organic extracts were washed with saturated brine, dried over anhydrous Na2SO4 and evaporated to dryness to obtain (2R,3R)-(I) (m.p. 476–479 K) in 70% overall yield (350 mg). The filtrate was concentrated and the residue worked up as outlined above to obtain (2R,3R)-(I) in 30% overall yield (150 mg).

Spectroscopic data for (2RS,3RS)-(I): 1H NMR (CDCl3, δ, p.p.m.): 2.48–2.55 (m, 2H, 2 H10), 2.71–3.00 (m, 6H, 2 H1, 2 H4, 2 H10), 3.25–3.35 ([Peak strength/type? 6H?] 4 H9, H3, OH), 3.60 (s, 2H, NH2), 3.83 (s, 3H, CH3), 3.88–3.92 (m, 1H, H2), 6.64–6.63 (m, 5H, 5HAr), 7.02 (t, 2H, 3J = 8 Hz), 7.22 (t, 2H, 3J = 8 Hz, 2HAr); 13C NMR (CDCl3, δ, p.p.m.): 20.9 (2 C10), 38.0 (C1), 48.0 (C4), 49.8 (C3), 55.2 (CH3), 65.2 (C2), 66.2 (2 C9), 95.58 (CHAr), 102.76 (CHAr), 104.64 (CHAr), 104.82 (CHAr), 109.1 (CHAr), 112.1(CHAr), 129.82 (CHAr), 129.86 (CHAr), 134.78 (CHAr), 136.83 (CHAr), 144.41 (CHAr), 162.2 (C—CH3); IR (KBr, ν, cm-1): 3466.2 (OH), 3368.6 (NH2), 3050 (CHCH, Ar), 2910.4–2835.7 (CH2, aliphatic), 1203 (OCH3).

Refinement top

For pattern indexing, the extraction of the peak positions was carried out using the program WinPLOTR (Roisnel & Rodriguez-Carvajal, 2001). Pattern indexing was performed using the program DICVOL4.0 (Boultif & Louër, 2004). The first 20 lines of the powder pattern were completely indexed on the basis of a monoclinic cell. The absolute error on each observed line was fixed at 0.02° (2θ). The figures of merit are sufficient to support the obtained indexing results [M(20) = 23.1 and F(20) = 53.4(0.0071, 53)]. The whole powder diffraction pattern from 5 to 85° (2θ) was subsequently refined with cell and resolution constraints (Le Bail et al., 1988) in a space group without systematic extinctions in the monoclinic system, P2/m, using the `profile matching' option of the program FULLPROF (Rodriguez-Carvajal, 2001). The best estimated space group in the monoclinic system was P21/c, which was determined with the help of the program CHECKGROUP interfaced by WinPLOTR. The number of molecules per unit cell was estimated to be Z = 4, and it can be concluded that the number of molecules in the asymmetric unit is Z' = 1 for space group P21/c.

Some details of the solution and refinement of (2RS,3RS)-(I) merit a brief comment. Firstly, the structure was solved ab initio by direct methods using the program EXPO2009 (Altomare et al., 1999), but with no success. Therefore, the direct space method was used with the program FOX (Favre-Nicolin & Černý, 2002) to find the starting model, using the `parallel tempering' algorithm of the Monte Carlo simulated-annealing method. The 2θ angular range was restricted from 5.0 to 55.0° in order to speed up the Monte Carlo calculations. The profile parameter needed for the program was calculated from preliminary profile-matching refinements carried out using FOX itself. The molecule of (2RS,3RS)-(I) has three independent torsion angles, so there are nine degrees of freedom to determine the starting model. The H atoms were not introduced in these calculations because they do not contribute significantly to the powder diffraction pattern, due to their low X-ray scattering power. After approximately 2000000 cycles, the agreement factor Rwp was near to 0.12. The calculations were continued with respect to preferred orientation in the (100) direction, and Rwp decreased rapidly to 0.09 for a solution corresponding to a configuration which could constitute a relevant starting structural model in terms of crystal packing, the lowest contact distance between neighbouring molecules being 2.94 Å between the hydroxy group and the amine group to form a hydrogen bond. The parameter G1 of the March–Dollase (March, 1932; Dollase, 1986) function is 1.19 at the end of the calculations.

The model found by this program was introduced into the program GSAS (Larson & Von Dreele, 2004) implemented in EXPGUI (Toby, 2001) for Rietveld refinement. During Rietveld refinement, the effect of the asymmetry of the low-order peaks was corrected using a pseudo-Voigt description of the peak shape (Thompson et al., 1987) which allows for angle-dependent asymmetry with axial divergence (Finger et al., 1994). [Microstrain broadening by Stephens (1999)? Otherwise uncited.] The two asymmetry parameters of this function, S/L and D/L, were both fixed at 0.0225 during Rietveld refinement. Soft restraints were imposed on bond lengths for the coordinates of the 26 non-H atoms to their normal values for similar compounds (Allen et al., 1987). A global isotropic atomic displacement parameter was introduced for C, N and O atoms. Intensities were corrected from absorption effects with a µd value of 0.446. Before the final refinement, aromatic, methylene, methine and methyl H atoms were introduced from geometric arguments. The coordinates of these H atoms were refined with constraints to normal values on bond lengths and angles to the parent atoms (C—H = 0.99 for CH, 0.98 for CH2 and 0.97 for CH3). H atoms of hydroxy and amine groups were located in a Fourier difference synthesis and refined with constraints on their bond lengths (O—H = 0.82 Å and N—H = 0.87 Å for NH2) and angles. A spherical harmonic correction for preferred orientation (Von Dreele, 1997) was used with 14 coefficients. The use of the preferred orientation correction leads to better molecular geometry with better agreement factors. The final Rietveld agreement factors are Rp = 0.021, Rwp = 0.027, Rexp = 0.017, χ2 = 2.722 and RF2 = 0.0548. The final Rietveld plot of the X-ray diffraction pattern is given in Fig. 3.

Computing details top

Data collection: WinXPOW (Stoe & Cie, 1999); cell refinement: GSAS (Larson & Von Dreele, 2004); data reduction: WinXPOW (Stoe & Cie, 1999); program(s) used to solve structure: FOX (Favre-Nicolin & Černý, 2002); program(s) used to refine structure: GSAS (Larson & Von Dreele, 2004); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of (2RS,3RS)-(I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitary radii.
[Figure 2] Fig. 2. The crystal packing of (2RS,3RS)-(I), viewed normal to the b axis. O—H···N hydrogen bonds are shown as dashed lines. H atoms have been omitted for clarity. [Symmetry code: (i) x, -y - 1/2, z - 1/2.]
[Figure 3] Fig. 3. Final Rietveld plot for (2RS,3RS)-(I). Observed data points are indicated by dots, the best-fit profile (upper trace) and the difference pattern (lower trace) are solid lines. The vertical bars indicate the positions of Bragg peaks.
(2RS,3RS)-5-amino-3-[4-(3-methoxyphenyl)piperazin-1-yl]- 1,2,3,4-tetrahydronaphthalen-2-ol top
Crystal data top
C21H27N3O2F(000) = 760
Mr = 353.47Dx = 1.239 Mg m3
Monoclinic, P21/cCu Kα1 radiation, λ = 1.54060 Å
Hall symbol: -P 2ybcµ = 0.64 mm1
a = 12.6234 (3) ÅT = 298 K
b = 8.90929 (16) ÅParticle morphology: fine powder
c = 17.2752 (3) Åwhite
β = 102.8536 (11)°flat sheet, 8 × 8 mm
V = 1894.18 (7) Å3Specimen preparation: Prepared at 298 K and 101.3 kPa
Z = 4
Data collection top
Transmission Stoe STADI P
diffractometer
Scan method: step
Radiation source: sealed X-ray tube, 1.5406Absorption correction: for a cylinder mounted on the ϕ axis
(GSAS; Larson & Von Dreele, 2004)
Ge 111 monochromatorTmin = 0.391, Tmax = 0.502
Specimen mounting: powder loaded between two Mylar foils2θmin = 4.998°, 2θmax = 84.978°, 2θstep = 0.02°
Data collection mode: transmission
Refinement top
Least-squares matrix: fullProfile function: CW Profile function number 4 with 21 terms Pseudo-voigt profile coefficients as parameterized in (Thompson, et al., 1987). Asymmetry correction of (Finger et al., 1994). Microstrain broadening by (Stephens, 1999). #1(GU) = 0.000 #2(GV) = 0.000 #3(GW) = 7.766 #4(GP) = 0.000 #5(LX) = 1.857 #6(ptec) = 0.00 #7(trns) = 0.00 #8(shft) = 0.0000 #9(sfec) = 0.00 #10(S/L) = 0.0230 #11(H/L) = 0.0230 #12(eta) = 0.6000 #13(S400 ) = 1.3E-01 #14(S040 ) = 9.9E-02 #15(S004 ) = 1.4E-02 #16(S220 ) = -1.5E-02 #17(S202 ) = 2.5E-02 #18(S022 ) = 1.8E-02 #19(S301 ) = -1.7E-02 #20(S103 ) = 3.1E-02 #21(S121 ) = 3.9E-03 Peak tails are ignored where the intensity is below 0.0010 times the peak Aniso. broadening axis 0.0 0.0 1.0
Rp = 0.019115 parameters
Rwp = 0.02429 restraints
Rexp = 0.017H-atom parameters constrained
R(F2) = 0.03232(Δ/σ)max = 0.01
χ2 = 2.722Background function: GSAS Background function number 1 with 20 terms. Shifted Chebyshev function of 1st kind 1: 2554.25 2: -2039.65 3: 718.920 4: 109.607 5: -289.817 6: 191.958 7: -40.7231 8: -116.523 9: 113.592 10: 19.7866 11: -99.1759 12: 72.3448 13: -3.45975 14: -24.3312 15: -3.96068 16: 5.86789 17: 6.99931 18: -6.30464 19: -5.20851 20: 7.35489
4000 data pointsPreferred orientation correction: March-Dollase AXIS 1 Ratio = 1.18166 h = 1.000 k = 0.000 l = 0.000 Preferred orientation correction range: Min = 0.60606, Max = 1.28452
Excluded region(s): none
Crystal data top
C21H27N3O2V = 1894.18 (7) Å3
Mr = 353.47Z = 4
Monoclinic, P21/cCu Kα1 radiation, λ = 1.54060 Å
a = 12.6234 (3) ŵ = 0.64 mm1
b = 8.90929 (16) ÅT = 298 K
c = 17.2752 (3) Åflat sheet, 8 × 8 mm
β = 102.8536 (11)°
Data collection top
Transmission Stoe STADI P
diffractometer
Absorption correction: for a cylinder mounted on the ϕ axis
(GSAS; Larson & Von Dreele, 2004)
Specimen mounting: powder loaded between two Mylar foilsTmin = 0.391, Tmax = 0.502
Data collection mode: transmission2θmin = 4.998°, 2θmax = 84.978°, 2θstep = 0.02°
Scan method: step
Refinement top
Rp = 0.0194000 data points
Rwp = 0.024115 parameters
Rexp = 0.01729 restraints
R(F2) = 0.03232H-atom parameters constrained
χ2 = 2.722
Special details top

Experimental. The sample was ground lightly in a mortar, loaded between two Mylar foils and fixed in the sample holder with a mask of 7.0 mm internal diameter.

All other chemicals were commercially available and used without further purification. The title compound, (2RS,3RS)-(I), was prepared by a procedure similar to that reported in the literature (Bando et al., 2000, 2001). Thin-layer chromatographic (TLC) analysis was performed using Merck 60 F254 silica-gel plates. Flash chromatography was used for routine purification of reaction products using silica gel (70–230 mesh). Visualization was accomplished under UV or in an iodine chamber. NMR spectra were recorded on a Bruker Bio spin 400 spectrometer (400 MHz for 1H, 100 MHz for 13C). Chemical shifts (δ) were expressed in p.p.m. relative to trimethylsilane (TMS) as an internal standard. FT–IR spectra were recorded on an FTIR–JASCO 300E. Melting-point determinations were performed with a digital melting-point instrument from Stuart, model SMP3. An analysis of the optical purity of the product was performed using semi-preparative HPLC and a Chiracel column.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.3419 (14)0.8169 (17)0.8004 (9)0.0363 (12)*
C20.3894 (15)0.9586 (16)0.8101 (8)0.0363 (12)*
C30.4379 (12)1.0149 (12)0.7509 (10)0.0363 (12)*
C40.4236 (13)0.9405 (18)0.6779 (9)0.0363 (12)*
C50.3568 (14)0.8134 (16)0.6636 (7)0.0363 (12)*
C60.3209 (13)0.7453 (13)0.7266 (11)0.0363 (12)*
C70.3467 (15)0.7340 (15)0.5850 (7)0.0363 (12)*
C80.2493 (14)0.6265 (16)0.5682 (8)0.0363 (12)*
C90.2616 (10)0.5156 (15)0.6385 (8)0.0363 (12)*
C100.2606 (16)0.5945 (13)0.7172 (8)0.0363 (12)*
C110.0674 (11)0.4221 (15)0.6115 (9)0.0363 (12)*
C120.0067 (14)0.2775 (15)0.5781 (9)0.0363 (12)*
C130.2275 (12)0.2770 (16)0.6670 (8)0.0363 (12)*
C140.1633 (12)0.1332 (14)0.6359 (9)0.0363 (12)*
C150.0221 (12)0.0171 (13)0.6240 (10)0.0363 (12)*
C160.1261 (14)0.0144 (15)0.5755 (8)0.0363 (12)*
C170.1961 (8)0.105 (2)0.5815 (7)0.0363 (12)*
C180.1592 (12)0.2302 (14)0.6280 (11)0.0363 (12)*
C190.0538 (13)0.2298 (14)0.6747 (9)0.0363 (12)*
C200.0152 (10)0.1072 (19)0.6725 (8)0.0363 (12)*
C210.3753 (12)0.1874 (15)0.5335 (9)0.0363 (12)*
N10.2925 (11)0.7702 (13)0.8590 (7)0.0363 (12)*
N20.1818 (10)0.3962 (12)0.6113 (8)0.0363 (12)*
N30.0467 (12)0.1504 (12)0.6307 (9)0.0363 (12)*
O10.2538 (11)0.5412 (10)0.4990 (6)0.0363 (12)*
O20.2926 (8)0.0804 (10)0.5304 (5)0.0363 (12)*
H20.404351.002450.865170.05*
H30.475841.113680.760410.05*
H40.448540.990090.633970.05*
H7a0.34070.808720.546290.05*
H7b0.414430.674640.589810.05*
H80.181710.681610.560810.05*
H90.337320.471630.644980.05*
H10a0.180120.610090.715890.05*
H10b0.28630.523060.760980.05*
H11a0.040920.506150.575220.05*
H11b0.057570.443030.66390.05*
H12a0.017260.254740.524740.05*
H12b0.071540.291770.575240.05*
H13a0.304260.256880.666720.05*
H13b0.21890.295730.720530.05*
H14a0.170890.110540.580860.05*
H14b0.188820.046390.669030.05*
H160.155370.100770.542940.05*
H180.21040.317020.631340.05*
H190.027460.318520.708950.05*
H200.09040.114030.702390.05*
H21a0.408460.168110.574980.05*
H21b0.42880.177120.480950.05*
H21c0.343820.28630.534560.05*
H1o10.26350.608930.458010.05*
H1n10.221250.768320.844820.05*
H2n10.319990.68720.880.05*
Geometric parameters (Å, º) top
C1—C21.39 (2)C12—H12a0.98
C1—C61.40 (2)C12—H12b0.99
C1—N11.37 (2)C13—C141.55 (2)
C2—C31.40 (2)C13—N21.463 (18)
C2—H21.01C13—H13a0.99
C3—C41.40 (2)C13—H13b0.97
C3—H31.00C14—N31.46 (2)
C4—C51.40 (2)C14—H14a1.00
C4—H40.99C14—H14b0.97
C5—C61.41 (2)C15—C161.39 (2)
C5—C71.511 (18)C15—C201.41 (2)
C6—C101.535 (19)C15—N31.461 (18)
C7—C81.53 (2)C16—C171.40 (2)
C7—H7a0.94C16—H160.98
C7—H7b0.99C17—C181.39 (2)
C8—C91.546 (19)C17—O21.354 (15)
C8—O11.428 (17)C18—C191.39 (2)
C8—H80.97C18—H181.02
C9—C101.533 (19)C19—C201.40 (2)
C9—N21.469 (18)C19—H191.00
C9—H91.02C20—H200.98
C10—H10a1.02C21—O21.424 (17)
C10—H10b0.99C21—H21a0.92
C11—C121.54 (2)C21—H21b1.01
C11—N21.463 (19)C21—H21c0.97
C11—H11a0.99N1—H1n10.88
C11—H11b0.96N1—H2n10.86
C12—N31.469 (19)O1—H1o10.96
C2—C1—C6120.8 (7)N3—C12—H12a108.8
C2—C1—N1116.3 (16)N3—C12—H12b109.5
C6—C1—N1120.7 (16)H12a—C12—H12b108.9
C1—C2—C3119.0 (13)C14—C13—N2105.8 (11)
C1—C2—H2116.7C14—C13—H13a106.7
C3—C2—H2122.2C14—C13—H13b108.3
C2—C3—C4120.0 (13)N2—C13—H13a111.8
C2—C3—H3117.9N2—C13—H13b113.0
C4—C3—H3121.8H13a—C13—H13b110.8
C3—C4—C5119.6 (14)C13—C14—N3112.1 (12)
C3—C4—H4118.7C13—C14—H14a110.2
C5—C4—H4120.6C13—C14—H14b112.0
C4—C5—C6119.8 (7)N3—C14—H14a105.7
C4—C5—C7117.7 (14)N3—C14—H14b108.4
C6—C5—C7121.1 (14)H14a—C14—H14b108.1
C1—C6—C5118.7 (13)C16—C15—C20119.4 (12)
C1—C6—C10119.0 (14)C16—C15—N3121.7 (14)
C5—C6—C10122.3 (14)C20—C15—N3118.6 (14)
C5—C7—C8111.5 (12)C15—C16—C17119.6 (13)
C5—C7—H7a106.6C15—C16—H16121.3
C5—C7—H7b106.0C17—C16—H16118.6
C8—C7—H7a112.1C16—C17—C18121.1 (6)
C8—C7—H7b108.8C16—C17—O2108.5 (16)
H7a—C7—H7b111.8C18—C17—O2130.1 (16)
C7—C8—C9108.3 (13)C17—C18—C19119.0 (12)
C7—C8—O1108.1 (11)C17—C18—H18120.4
C7—C8—H8110.7C19—C18—H18120.4
C9—C8—O1107.6 (11)C18—C19—C20120.3 (12)
C9—C8—H8111.1C18—C19—H19119.3
O1—C8—H8110.9C20—C19—H19120.3
C8—C9—C10112.6 (12)C15—C20—C19120.1 (13)
C8—C9—N2105.7 (11)C15—C20—H20121.5
C8—C9—H9105.1C19—C20—H20118.3
C10—C9—N2118.4 (11)O2—C21—H21a111.6
C10—C9—H9105.8O2—C21—H21b104.8
N2—C9—H9108.5O2—C21—H21c108.1
C6—C10—C9113.1 (11)H21a—C21—H21b110.6
C6—C10—H10a110.6H21a—C21—H21c114.3
C6—C10—H10b114.4H21b—C21—H21c106.9
C9—C10—H10a104.3C1—N1—H1n1114.1
C9—C10—H10b108.5C1—N1—H2n1111.5
H10a—C10—H10b105.2H1n1—N1—H2n1113.2
C12—C11—N2106.0 (12)C9—N2—C11119.5 (12)
C12—C11—H11a109.1C9—N2—C13100.0 (13)
C12—C11—H11b111.0C11—N2—C13110.9 (12)
N2—C11—H11a108.2C12—N3—C14108.8 (13)
N2—C11—H11b111.6C12—N3—C15117.4 (14)
H11a—C11—H11b110.8C14—N3—C15119.5 (12)
C11—C12—N3109.8 (11)C8—O1—H1o1108.6
C11—C12—H12a111.3C17—O2—C21115.2 (12)
C11—C12—H12b108.6
C21—O2—C17—C16175.8 (11)C4—C5—C7—C8164.4 (14)
C21—O2—C17—C1811 (2)C7—C5—C6—C106 (2)
C13—N2—C11—C1265.8 (14)C6—C5—C7—C829 (2)
C13—N2—C9—C8159.8 (11)C7—C5—C6—C1173.7 (15)
C9—N2—C11—C12178.8 (12)C4—C5—C6—C10171.6 (15)
C11—N2—C9—C879.1 (15)C4—C5—C6—C18 (2)
C11—N2—C13—C1463.0 (14)C1—C6—C10—C9169.5 (14)
C9—N2—C13—C14169.9 (11)C5—C6—C10—C910 (2)
C11—N2—C9—C1048.1 (18)C5—C7—C8—C955.9 (16)
C13—N2—C9—C1073.0 (14)C5—C7—C8—O1172.2 (11)
C12—N3—C14—C1358.1 (16)C7—C8—C9—N2167.3 (11)
C15—N3—C14—C13163.2 (13)O1—C8—C9—C10178.7 (13)
C14—N3—C12—C1159.4 (16)O1—C8—C9—N250.6 (15)
C15—N3—C12—C11160.9 (13)C7—C8—C9—C1062.1 (16)
C12—N3—C15—C166 (2)C8—C9—C10—C638.2 (19)
C14—N3—C15—C16141.3 (15)N2—C9—C10—C6162.1 (13)
C14—N3—C15—C2044 (2)N2—C11—C12—N362.6 (16)
C12—N3—C15—C20178.8 (14)N2—C13—C14—N358.6 (15)
C6—C1—C2—C314 (3)C20—C15—C16—C177 (2)
N1—C1—C2—C3177.8 (15)N3—C15—C20—C19172.3 (14)
C2—C1—C6—C55 (3)N3—C15—C16—C17168.7 (14)
N1—C1—C6—C1012 (2)C16—C15—C20—C193 (2)
N1—C1—C6—C5168.2 (15)C15—C16—C17—C188 (2)
C2—C1—C6—C10175.4 (16)C15—C16—C17—O2178.3 (13)
C1—C2—C3—C410 (2)O2—C17—C18—C19178.1 (13)
C2—C3—C4—C53 (2)C16—C17—C18—C196 (2)
C3—C4—C5—C7178.1 (14)C17—C18—C19—C202 (2)
C3—C4—C5—C612 (2)C18—C19—C20—C151 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O1···N1i0.962.123.072 (16)171
Symmetry code: (i) x, y+3/2, z1/2.

Experimental details

Crystal data
Chemical formulaC21H27N3O2
Mr353.47
Crystal system, space groupMonoclinic, P21/c
Temperature (K)298
a, b, c (Å)12.6234 (3), 8.90929 (16), 17.2752 (3)
β (°) 102.8536 (11)
V3)1894.18 (7)
Z4
Radiation typeCu Kα1, λ = 1.54060 Å
µ (mm1)0.64
Specimen shape, size (mm)Flat sheet, 8 × 8
Data collection
DiffractometerTransmission Stoe STADI P
diffractometer
Specimen mountingPowder loaded between two Mylar foils
Data collection modeTransmission
Scan methodStep
Absorption correctionFor a cylinder mounted on the ϕ axis
(GSAS; Larson & Von Dreele, 2004)
Tmin, Tmax0.391, 0.502
2θ values (°)2θmin = 4.998 2θmax = 84.978 2θstep = 0.02
Refinement
R factors and goodness of fitRp = 0.019, Rwp = 0.024, Rexp = 0.017, R(F2) = 0.03232, χ2 = 2.722
No. of data points4000
No. of parameters115
No. of restraints29
H-atom treatmentH-atom parameters constrained

Computer programs: WinXPOW (Stoe & Cie, 1999), GSAS (Larson & Von Dreele, 2004), FOX (Favre-Nicolin & Černý, 2002), ORTEP-3 (Farrugia, 1997), publCIF (Westrip, 2010).

Selected geometric parameters (Å, º) top
C5—C61.41 (2)C7—C81.53 (2)
C5—C71.511 (18)C8—C91.546 (19)
C6—C101.535 (19)C9—C101.533 (19)
C4—C5—C6119.8 (7)C1—C6—C5118.7 (13)
C4—C5—C7117.7 (14)C1—C6—C10119.0 (14)
C6—C5—C7121.1 (14)C5—C6—C10122.3 (14)
C7—C5—C6—C1173.7 (15)C5—C6—C10—C910 (2)
C4—C5—C6—C10171.6 (15)C5—C7—C8—C955.9 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O1···N1i0.962.123.072 (16)171
Symmetry code: (i) x, y+3/2, z1/2.
 

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