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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 7| July 2014| Pages o791-o792
https://doi.org/10.1107/S1600536814013294

Di­ethyl 4-(bi­phenyl-4-yl)-2,6-di­methyl-1,4-di­hydro­pyridine-3,5-di­carboxyl­ate

Scott A. Steiger,a Anthony J. Monacelli,b Chun Li,b Janet L. Huntingb and Nicholas R. Natalea*

aDepartment of Biomedical and Pharmaceutical Sciences, The University of Montana, 32 Campus Drive, Missoula, MT 59812, USA, and bDepartment of Chemistry, Ithaca College, 953 Danby Road, Ithaca, NY 14850, USA
*Correspondence e-mail: nicholas.natale@mso.umt.edu

(Received 22 May 2014; accepted 6 June 2014; online 18 June 2014)

The title compound, C25H27NO4, has a flattened di­hydro­pyridine ring. The benzene and phenyl rings are synclinal to one another, forming a dihedral angle of 49.82 (8)°; the axis of the biphenyl rings makes an 81.05 (9)° angle to the plane of the di­hydro­pyridine ring. In the crystal, N—H⋯O hydrogen bonds link the mol­ecules into chain motifs running along the a-axis direction. The chains are cross-linked by C—H⋯O inter­actions, forming sheet motifs running slightly off the (110) plane, together with an intermolecular interaction between head-to tail biphenyl groups, thus making the whole crystal packing a three-dimensional network. Intra­molecular C—H⋯O hydrogen bonds are also observed.

Related literature

For general structure–activity relationship studies of 1,4-di­hydro­pyridines (DHPs) as calcium channel modulators, see: Bossert et al. (1981[Bossert, F., Meyer, H. & Wehinger, E. (1981). Angew. Chem. Int. Ed. Engl. 20, 762-769.]); Triggle (2003[Triggle, D. (2003). Cell. Mol. Neurobiol. 23, 293-303.]). For binding studies of DHPs to multiple drug resistant protein 1 (MDR1), see: Abe et al. (1995[Abe, T., Koike, K., Ohga, T., Kubo, T., Wada, M., Kohno, K., Mori, T., Hidaka, K. & Kuwano, M. (1995). Br. J. Cancer, 72, 418-423.]); Cole et al. (1989[Cole, S., Downes, H. & Slovak, M. (1989). Br. J. Cancer, 59, 42-46.]); Tasaki et al. (1995[Tasaki, Y., Nakagawa, M., Ogata, J., Kiue, A., Tanimura, H., Kuwano, M. & Nomura, Y. (1995). J. Urol. 154, 1210-1216.]); Vanhoefer et al. (1999[Vanhoefer, U., Muller, M., Hilger, R., Lindtner, B., Klaassen, U., Schleucher, N., Rustum, Y., Seeber, S. & Harstrick, A. (1999). Br. J. Cancer, 81, 1304-1310.]); Tolomero et al. (1994[Tolomero, M., Gancitano, R., Musso, M., Porretto, F., Perricone, R., Abbadessa, V. & Cajozzo, A. (1994). Haematologica, 79, 328-333.]); Cindric et al. (2010[Cindric, M., Cipak, A., Serly, J., Plotniece, A., Jaganjac, M., Mrakovcic, L., Lovakovic, T., Dedic, A., Soldo, I., Duburs, G., Zarkovic, N. & Molnar, J. (2010). Anticancer Res. 30, 4063-4070.]).

[Scheme 1]

Experimental

Crystal data

  • C25H27NO4

  • Mr = 405.47

  • Triclinic, [P \overline 1]

  • a = 7.3431 (3) Å

  • b = 10.6075 (4) Å

  • c = 13.8449 (6) Å

  • α = 85.762 (3)°

  • β = 88.124 (3)°

  • γ = 73.530 (2)°

  • V = 1031.25 (7) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 100 K

  • 0.15 × 0.14 × 0.13 mm
Data collection

  • Bruker SMART BREEZE CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Ins., Madison, Wisconsin, USA.]) Tmin = 0.919, Tmax = 1.000

  • 19956 measured reflections

  • 4752 independent reflections

  • 2983 reflections with I > 2σ(I)

  • Rint = 0.072
Refinement

  • R[F2 > 2σ(F2)] = 0.062

  • wR(F2) = 0.149

  • S = 1.02

  • 4752 reflections

  • 279 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.43 e Å−3

  • Δρmin = −0.37 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C21—H21⋯O2i 0.95 2.50 3.256 (3) 137
C6—H6A⋯O3ii 0.98 2.59 3.452 (3) 147
C19—H19⋯O1 0.95 2.51 3.227 (3) 132
C13—H13B⋯O2 0.98 2.11 2.857 (3) 131
C8—H8A⋯O2iii 0.99 2.55 3.344 (3) 137
N1—H1⋯O3ii 0.91 (3) 2.03 (3) 2.938 (3) 173 (2)
Symmetry codes: (i) x-1, y+1, z; (ii) x+1, y, z; (iii) -x+1, -y+1, -z+2.

Data collection: APEX2 (Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Ins., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Ins., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S1600536814013294/zl2590sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536814013294/zl2590Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536814013294/zl2590Isup3.cml

checkCIF report


Comment top

Hantzsch 1,4-di­hydro­pyridines (DHPs) are an extensively studied class of compounds that are known predominantly for their L-type voltage gated calcium channel modulation. (Bossert et al. 1981, Triggle 2003) There have been extensive structure-activity relationship (SAR) studies done on DHPs that have revealed the basic structural requirements for robust binding affinity to calcium channels. (Triggle 2003) Other studies in the field have shown that DHPs bind to multiple receptors, most notably the multiple drug resistant protein 1 (MDR1) (Abe et al. 1995, Cole et al. 1989, Tasaki et al. 1995, Vanhoefer et al. 1999, Tolomero et al. 1994, Cindric et al. 2010). Using established SAR more selective compounds can be designed for greater selectivity resulting in more clinically relevant compounds.

The title compound, C25H27NO4, has very similar structural features as other DHPs. Such features include a flattened boat conformation of the 1,4-DHP ring and two ester groups coplanar to the double bonds in the 1,4-DHP, with one carbonyl being cis and the other carbonyl being trans to the double bonds (Figure 1). Although the phenyl group attached at C(3) is still orthogonal to the bottom [C(1)—C(2)—C(4)—C(5)] of the 1,4-DHP ring [81.05 (9)°], it twists away from the N(1)—C(3) at an angle of 47.77 (8)°. The next phenyl ring twists again, with 49.82 (8)° from the center phenyl group, and becomes almost orthogonal to the N(1)—C(3) axis [12.97 (9)°]. Inter­molecular hydrogen bonds between N(1) – H(1) and O(3), together with the inter­molecular C(6) – H(6) ··· O(3) inter­actions, link the molecules into chain motifs running along the a axis (Figure 2). Two inter­molecular C – H ··· O inter­actions both from O(2) cross link the molecules into sheet motifs running slightly off the 110 plane (Figure 3). These inter­ations form a three-dimensional network in the cyrstal packing (Figure 4). There are two intra­molecular H-bonds observed in the molecule, C(19) – H(19) ··· O(1) and C(13) – H(13B) ··· O(2).

Experimental top

Synthesis and crystallization top

An oven-dried 100 mL round bottom flask was charged with 1.90g of bi­phenyl-4-carbaldehyde, 2.86 g of ethyl aceto­acetate, 2.49 mL of 14.8M ammonium hydroxide, and a magenetic stir bar. The mixture was taken up in 50 mL of absolute ethanol, and the round bottom flask was fitted with a dean stark trap and heated to reflux while stirring. Reaction progress was monitored via TLC. Once the reaction was complete, excess solvent was removed via rotary evaporation. The solution was then purified via a silica column chromatography. The product was re-crystallized into white to yellow crystalline clumps with hexane and di­chloro­methane (yield = 1.24g , 3.06 mmol, 29.31%).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. The methyl H atoms were constrained to an ideal geometry, with C – H = 0.98 Å and Uiso(H) = 1.5Ueq(C), and were allowed to rotate freely about the C – C bonds. The rest of the H atoms were placed in calculated positions with C – H = 0.95 ~ 1.00 Å and refined as riding on their carrier atoms with Uiso(H) = 1.2Ueq(C). The positions of amine H atoms were determined from difference Fourier maps and refined freely along with their isotropic displacement parameters. One low-angle reflection was omitted from the refinement because its observed intensity was much lower than the calculated value as a result of being partially obscured by the beam stop.

Related literature top

For general structure–activity relationship studies of 1,4-dihydropyridines (DHPs) as calcium channel modulators, see: Bossert et al. (1981); Triggle (2003). For binding studies of DHPs to multiple drug resistant protein 1 (MDR1), see: Abe et al. (1995), Cole et al. (1989); Tasaki et al. (1995); Vanhoefer et al. (1999); Tolomero et al. (1994); and Cindric et al. (2010).

Structure description top

Hantzsch 1,4-di­hydro­pyridines (DHPs) are an extensively studied class of compounds that are known predominantly for their L-type voltage gated calcium channel modulation. (Bossert et al. 1981, Triggle 2003) There have been extensive structure-activity relationship (SAR) studies done on DHPs that have revealed the basic structural requirements for robust binding affinity to calcium channels. (Triggle 2003) Other studies in the field have shown that DHPs bind to multiple receptors, most notably the multiple drug resistant protein 1 (MDR1) (Abe et al. 1995, Cole et al. 1989, Tasaki et al. 1995, Vanhoefer et al. 1999, Tolomero et al. 1994, Cindric et al. 2010). Using established SAR more selective compounds can be designed for greater selectivity resulting in more clinically relevant compounds.

The title compound, C25H27NO4, has very similar structural features as other DHPs. Such features include a flattened boat conformation of the 1,4-DHP ring and two ester groups coplanar to the double bonds in the 1,4-DHP, with one carbonyl being cis and the other carbonyl being trans to the double bonds (Figure 1). Although the phenyl group attached at C(3) is still orthogonal to the bottom [C(1)—C(2)—C(4)—C(5)] of the 1,4-DHP ring [81.05 (9)°], it twists away from the N(1)—C(3) at an angle of 47.77 (8)°. The next phenyl ring twists again, with 49.82 (8)° from the center phenyl group, and becomes almost orthogonal to the N(1)—C(3) axis [12.97 (9)°]. Inter­molecular hydrogen bonds between N(1) – H(1) and O(3), together with the inter­molecular C(6) – H(6) ··· O(3) inter­actions, link the molecules into chain motifs running along the a axis (Figure 2). Two inter­molecular C – H ··· O inter­actions both from O(2) cross link the molecules into sheet motifs running slightly off the 110 plane (Figure 3). These inter­ations form a three-dimensional network in the cyrstal packing (Figure 4). There are two intra­molecular H-bonds observed in the molecule, C(19) – H(19) ··· O(1) and C(13) – H(13B) ··· O(2).

For general structure–activity relationship studies of 1,4-dihydropyridines (DHPs) as calcium channel modulators, see: Bossert et al. (1981); Triggle (2003). For binding studies of DHPs to multiple drug resistant protein 1 (MDR1), see: Abe et al. (1995), Cole et al. (1989); Tasaki et al. (1995); Vanhoefer et al. (1999); Tolomero et al. (1994); and Cindric et al. (2010).

Synthesis and crystallization top

An oven-dried 100 mL round bottom flask was charged with 1.90g of bi­phenyl-4-carbaldehyde, 2.86 g of ethyl aceto­acetate, 2.49 mL of 14.8M ammonium hydroxide, and a magenetic stir bar. The mixture was taken up in 50 mL of absolute ethanol, and the round bottom flask was fitted with a dean stark trap and heated to reflux while stirring. Reaction progress was monitored via TLC. Once the reaction was complete, excess solvent was removed via rotary evaporation. The solution was then purified via a silica column chromatography. The product was re-crystallized into white to yellow crystalline clumps with hexane and di­chloro­methane (yield = 1.24g , 3.06 mmol, 29.31%).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 1. The methyl H atoms were constrained to an ideal geometry, with C – H = 0.98 Å and Uiso(H) = 1.5Ueq(C), and were allowed to rotate freely about the C – C bonds. The rest of the H atoms were placed in calculated positions with C – H = 0.95 ~ 1.00 Å and refined as riding on their carrier atoms with Uiso(H) = 1.2Ueq(C). The positions of amine H atoms were determined from difference Fourier maps and refined freely along with their isotropic displacement parameters. One low-angle reflection was omitted from the refinement because its observed intensity was much lower than the calculated value as a result of being partially obscured by the beam stop.

Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. Packing diagram of the title compound, showing the intermolecular hydrogen bonds which form chain motifs running along the a axis. For the sake of clarity, H atoms not involved in H-bonds are removed.
[Figure 3] Fig. 3. Packing diagram of the title compound, showing intermolecular C – H ··· O interactions in dashed lines which cross link the molecules into a sheet motif running slightly off the 110 plane. For the sake of clarity, H atoms not involved in the interactions are removed.
[Figure 4] Fig. 4. Packing diagram of the title compound. The intermolecular interactions form a three-dimensional network in the crystal packing. For the sake of clarity, H atoms not involved in the interactions are removed.
Diethyl 4-(biphenyl-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate top
Crystal data top
C25H27NO4Z = 2
Mr = 405.47F(000) = 432
Triclinic, P1Dx = 1.306 Mg m−3
a = 7.3431 (3) ÅMo Kα radiation, λ = 0.71073 Å
b = 10.6075 (4) ÅCell parameters from 5122 reflections
c = 13.8449 (6) Åθ = 2.4–27.4°
α = 85.762 (3)°µ = 0.09 mm−1
β = 88.124 (3)°T = 100 K
γ = 73.530 (2)°Prism, pale white
V = 1031.25 (7) Å30.15 × 0.14 × 0.13 mm
Data collection top
Bruker SMART BREEZE CCD
diffractometer		2983 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tubeRint = 0.072
φ and ω scansθmax = 27.6°, θmin = 2.0°
Absorption correction: multi-scan
(SADABS; Bruker, 2012)		h = −9→9
Tmin = 0.919, Tmax = 1.000k = −13→13
19956 measured reflectionsl = −17→18
4752 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.062H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.149 w = 1/[σ2(Fo2) + (0.0537P)2 + 0.8331P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.001
4752 reflectionsΔρmax = 0.43 e Å−3
279 parametersΔρmin = −0.37 e Å−3
0 restraints
Crystal data top
C25H27NO4γ = 73.530 (2)°
Mr = 405.47V = 1031.25 (7) Å3
Triclinic, P1Z = 2
a = 7.3431 (3) ÅMo Kα radiation
b = 10.6075 (4) ŵ = 0.09 mm−1
c = 13.8449 (6) ÅT = 100 K
α = 85.762 (3)°0.15 × 0.14 × 0.13 mm
β = 88.124 (3)°
Data collection top
Bruker SMART BREEZE CCD
diffractometer		4752 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2012)		2983 reflections with I > 2σ(I)
Tmin = 0.919, Tmax = 1.000Rint = 0.072
19956 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0620 restraints
wR(F2) = 0.149H atoms treated by a mixture of independent and constrained refinement
S = 1.02Δρmax = 0.43 e Å−3
4752 reflectionsΔρmin = −0.37 e Å−3
279 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O30.1263 (2)0.73985 (17)0.98682 (13)0.0183 (4)
O10.4574 (2)0.44644 (15)0.75695 (12)0.0149 (4)
O40.2751 (2)0.84869 (17)1.07429 (13)0.0191 (4)
N10.7805 (3)0.68215 (19)0.92579 (15)0.0127 (5)
O20.7739 (2)0.38137 (18)0.73785 (14)0.0248 (5)
C30.4394 (3)0.6641 (2)0.85636 (17)0.0111 (5)
H30.34080.61530.86190.013*
C40.4521 (3)0.7191 (2)0.95378 (17)0.0115 (5)
C200.1965 (3)1.0952 (2)0.55708 (17)0.0118 (5)
C140.3787 (3)0.7763 (2)0.77713 (17)0.0107 (5)
C250.2602 (3)1.0854 (2)0.46091 (18)0.0156 (5)
H250.33841.00370.44060.019*
C10.7918 (3)0.5861 (2)0.86166 (17)0.0122 (5)
C180.2529 (3)0.8563 (2)0.61659 (18)0.0141 (5)
H180.20850.83830.55690.017*
C50.6197 (3)0.7352 (2)0.98050 (17)0.0112 (5)
C20.6293 (3)0.5673 (2)0.83079 (17)0.0118 (5)
C70.2713 (3)0.7670 (2)1.00548 (18)0.0136 (5)
C210.0758 (3)1.2152 (2)0.58379 (18)0.0138 (5)
H210.02901.22310.64850.017*
C220.0236 (3)1.3226 (2)0.51739 (19)0.0167 (6)
H22−0.06011.40310.53650.020*
C170.2607 (3)0.9835 (2)0.63075 (17)0.0107 (5)
C160.3313 (3)1.0043 (2)0.71876 (18)0.0144 (5)
H160.33981.08970.73010.017*
C60.6587 (3)0.8067 (2)1.06364 (18)0.0163 (6)
H6A0.79620.78831.07110.025*
H6B0.60330.77681.12330.025*
H6C0.60210.90171.05080.025*
C190.3093 (3)0.7555 (2)0.68872 (18)0.0139 (5)
H190.30040.67010.67760.017*
C150.3893 (3)0.9031 (2)0.78989 (18)0.0125 (5)
H150.43740.92040.84880.015*
C130.9930 (3)0.5135 (3)0.8374 (2)0.0204 (6)
H13A1.05060.57170.79650.031*
H13B0.99460.43600.80250.031*
H13C1.06540.48530.89720.031*
C80.0994 (3)0.9041 (2)1.12773 (18)0.0152 (5)
H8A0.06080.83371.16670.018*
H8B−0.00410.94961.08250.018*
C100.6336 (3)0.4574 (2)0.77147 (18)0.0146 (5)
C90.1404 (4)1.0005 (2)1.19262 (19)0.0195 (6)
H9A0.18381.06721.15320.029*
H9B0.23950.95351.23860.029*
H9C0.02461.04331.22830.029*
C230.0929 (4)1.3132 (2)0.42313 (19)0.0177 (6)
H230.06031.38780.37810.021*
C240.2102 (3)1.1940 (2)0.39484 (19)0.0168 (6)
H240.25641.18680.33000.020*
C110.4471 (4)0.3420 (2)0.69640 (18)0.0176 (6)
H11A0.32490.32130.70910.021*
H11B0.55070.26160.71410.021*
C120.4631 (4)0.3793 (3)0.59046 (19)0.0245 (6)
H12A0.44540.30930.55260.037*
H12B0.58910.39120.57630.037*
H12C0.36540.46180.57330.037*
H10.893 (4)0.696 (3)0.9411 (19)0.023 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O30.0103 (9)0.0255 (10)0.0221 (11)−0.0085 (8)0.0015 (7)−0.0084 (8)
O10.0152 (9)0.0113 (9)0.0194 (10)−0.0046 (7)0.0007 (7)−0.0057 (7)
O40.0115 (9)0.0269 (10)0.0210 (10)−0.0064 (8)0.0055 (7)−0.0145 (8)
N10.0078 (10)0.0152 (11)0.0168 (12)−0.0054 (9)0.0013 (8)−0.0049 (9)
O20.0154 (9)0.0238 (10)0.0328 (12)0.0018 (8)−0.0007 (8)−0.0158 (9)
C30.0091 (11)0.0108 (12)0.0145 (13)−0.0040 (9)−0.0004 (10)−0.0026 (10)
C40.0122 (12)0.0108 (12)0.0110 (13)−0.0026 (9)0.0003 (9)0.0000 (9)
C200.0106 (12)0.0127 (12)0.0127 (13)−0.0044 (10)−0.0018 (10)−0.0002 (10)
C140.0068 (11)0.0106 (12)0.0130 (13)0.0005 (9)0.0019 (9)−0.0018 (10)
C250.0126 (12)0.0170 (13)0.0181 (14)−0.0047 (10)−0.0010 (10)−0.0039 (11)
C10.0108 (12)0.0119 (12)0.0126 (13)−0.0016 (10)−0.0005 (10)0.0021 (10)
C180.0143 (12)0.0145 (13)0.0128 (14)−0.0018 (10)−0.0022 (10)−0.0052 (10)
C50.0126 (12)0.0093 (11)0.0118 (13)−0.0038 (9)−0.0001 (10)0.0011 (10)
C20.0131 (12)0.0111 (12)0.0120 (13)−0.0050 (10)0.0003 (10)0.0006 (10)
C70.0142 (12)0.0131 (12)0.0136 (14)−0.0044 (10)−0.0007 (10)0.0012 (10)
C210.0149 (12)0.0138 (12)0.0126 (13)−0.0033 (10)−0.0010 (10)−0.0028 (10)
C220.0154 (13)0.0113 (12)0.0229 (15)−0.0020 (10)−0.0035 (11)−0.0040 (11)
C170.0076 (11)0.0116 (12)0.0119 (13)−0.0013 (9)0.0018 (9)−0.0011 (10)
C160.0161 (13)0.0114 (12)0.0168 (14)−0.0051 (10)0.0004 (10)−0.0032 (10)
C60.0125 (12)0.0205 (13)0.0167 (14)−0.0050 (10)−0.0001 (10)−0.0040 (11)
C190.0129 (12)0.0091 (12)0.0191 (14)−0.0017 (10)0.0003 (10)−0.0020 (10)
C150.0131 (12)0.0147 (12)0.0109 (13)−0.0050 (10)−0.0022 (10)−0.0033 (10)
C130.0133 (13)0.0238 (14)0.0220 (15)−0.0003 (11)0.0000 (11)−0.0078 (12)
C80.0102 (12)0.0200 (13)0.0145 (14)−0.0024 (10)0.0040 (10)−0.0048 (11)
C100.0147 (13)0.0121 (12)0.0156 (14)−0.0016 (10)−0.0009 (10)0.0002 (10)
C90.0163 (13)0.0194 (14)0.0230 (16)−0.0041 (11)0.0036 (11)−0.0089 (11)
C230.0221 (14)0.0155 (13)0.0163 (14)−0.0075 (11)−0.0065 (11)0.0048 (11)
C240.0172 (13)0.0244 (14)0.0108 (13)−0.0091 (11)−0.0004 (10)−0.0011 (11)
C110.0228 (14)0.0110 (12)0.0203 (15)−0.0052 (11)0.0002 (11)−0.0081 (11)
C120.0253 (15)0.0329 (16)0.0195 (15)−0.0135 (13)−0.0007 (12)−0.0067 (12)
Geometric parameters (Å, º) top
O3—C71.219 (3)C21—C221.382 (3)
O1—C101.354 (3)C22—H220.9500
O1—C111.458 (3)C22—C231.385 (4)
O4—C71.340 (3)C17—C161.396 (3)
O4—C81.459 (3)C16—H160.9500
N1—C11.383 (3)C16—C151.385 (3)
N1—C51.383 (3)C6—H6A0.9800
N1—H10.91 (3)C6—H6B0.9800
O2—C101.217 (3)C6—H6C0.9800
C3—H31.0000C19—H190.9500
C3—C41.525 (3)C15—H150.9500
C3—C141.536 (3)C13—H13A0.9800
C3—C21.527 (3)C13—H13B0.9800
C4—C51.356 (3)C13—H13C0.9800
C4—C71.464 (3)C8—H8A0.9900
C20—C251.398 (3)C8—H8B0.9900
C20—C211.396 (3)C8—C91.506 (3)
C20—C171.484 (3)C9—H9A0.9800
C14—C191.397 (3)C9—H9B0.9800
C14—C151.392 (3)C9—H9C0.9800
C25—H250.9500C23—H230.9500
C25—C241.388 (4)C23—C241.388 (3)
C1—C21.352 (3)C24—H240.9500
C1—C131.500 (3)C11—H11A0.9900
C18—H180.9500C11—H11B0.9900
C18—C171.395 (3)C11—C121.500 (4)
C18—C191.389 (3)C12—H12A0.9800
C5—C61.502 (3)C12—H12B0.9800
C2—C101.468 (3)C12—H12C0.9800
C21—H210.9500
C10—O1—C11115.95 (18)C5—C6—H6B109.5
C7—O4—C8117.92 (18)C5—C6—H6C109.5
C1—N1—H1115.9 (17)H6A—C6—H6B109.5
C5—N1—C1123.2 (2)H6A—C6—H6C109.5
C5—N1—H1119.4 (17)H6B—C6—H6C109.5
C4—C3—H3108.3C14—C19—H19119.1
C4—C3—C14110.48 (18)C18—C19—C14121.8 (2)
C4—C3—C2110.09 (19)C18—C19—H19119.1
C14—C3—H3108.3C14—C15—H15119.2
C2—C3—H3108.3C16—C15—C14121.6 (2)
C2—C3—C14111.20 (19)C16—C15—H15119.2
C5—C4—C3119.3 (2)C1—C13—H13A109.5
C5—C4—C7124.8 (2)C1—C13—H13B109.5
C7—C4—C3115.4 (2)C1—C13—H13C109.5
C25—C20—C17121.4 (2)H13A—C13—H13B109.5
C21—C20—C25118.4 (2)H13A—C13—H13C109.5
C21—C20—C17120.2 (2)H13B—C13—H13C109.5
C19—C14—C3121.1 (2)O4—C8—H8A110.5
C15—C14—C3121.9 (2)O4—C8—H8B110.5
C15—C14—C19117.0 (2)O4—C8—C9106.34 (19)
C20—C25—H25119.7H8A—C8—H8B108.7
C24—C25—C20120.5 (2)C9—C8—H8A110.5
C24—C25—H25119.7C9—C8—H8B110.5
N1—C1—C13112.5 (2)O1—C10—C2112.0 (2)
C2—C1—N1118.8 (2)O2—C10—O1121.3 (2)
C2—C1—C13128.7 (2)O2—C10—C2126.7 (2)
C17—C18—H18119.6C8—C9—H9A109.5
C19—C18—H18119.6C8—C9—H9B109.5
C19—C18—C17120.8 (2)C8—C9—H9C109.5
N1—C5—C6112.8 (2)H9A—C9—H9B109.5
C4—C5—N1118.6 (2)H9A—C9—H9C109.5
C4—C5—C6128.6 (2)H9B—C9—H9C109.5
C1—C2—C3119.2 (2)C22—C23—H23120.2
C1—C2—C10120.9 (2)C22—C23—C24119.6 (2)
C10—C2—C3119.9 (2)C24—C23—H23120.2
O3—C7—O4121.7 (2)C25—C24—C23120.3 (2)
O3—C7—C4124.1 (2)C25—C24—H24119.9
O4—C7—C4114.2 (2)C23—C24—H24119.9
C20—C21—H21119.5O1—C11—H11A109.1
C22—C21—C20120.9 (2)O1—C11—H11B109.1
C22—C21—H21119.5O1—C11—C12112.4 (2)
C21—C22—H22119.9H11A—C11—H11B107.9
C21—C22—C23120.2 (2)C12—C11—H11A109.1
C23—C22—H22119.9C12—C11—H11B109.1
C18—C17—C20122.8 (2)C11—C12—H12A109.5
C18—C17—C16117.5 (2)C11—C12—H12B109.5
C16—C17—C20119.7 (2)C11—C12—H12C109.5
C17—C16—H16119.3H12A—C12—H12B109.5
C15—C16—C17121.3 (2)H12A—C12—H12C109.5
C15—C16—H16119.3H12B—C12—H12C109.5
C5—C6—H6A109.5
N1—C1—C2—C38.3 (3)C14—C3—C2—C10−87.0 (3)
N1—C1—C2—C10−173.2 (2)C25—C20—C21—C22−1.3 (3)
C3—C4—C5—N1−10.0 (3)C25—C20—C17—C18−50.9 (3)
C3—C4—C5—C6169.1 (2)C25—C20—C17—C16129.5 (2)
C3—C4—C7—O316.6 (3)C1—N1—C5—C4−17.3 (3)
C3—C4—C7—O4−161.2 (2)C1—N1—C5—C6163.4 (2)
C3—C14—C19—C18179.7 (2)C1—C2—C10—O1173.1 (2)
C3—C14—C15—C16−178.9 (2)C1—C2—C10—O2−6.4 (4)
C3—C2—C10—O1−8.3 (3)C18—C17—C16—C15−0.8 (3)
C3—C2—C10—O2172.2 (2)C5—N1—C1—C218.3 (4)
C4—C3—C14—C19−163.0 (2)C5—N1—C1—C13−160.6 (2)
C4—C3—C14—C1516.7 (3)C5—C4—C7—O3−171.8 (2)
C4—C3—C2—C1−31.2 (3)C5—C4—C7—O410.5 (3)
C4—C3—C2—C10150.2 (2)C2—C3—C4—C532.1 (3)
C20—C25—C24—C23−1.3 (4)C2—C3—C4—C7−155.7 (2)
C20—C21—C22—C23−0.9 (4)C2—C3—C14—C1974.4 (3)
C20—C17—C16—C15178.8 (2)C2—C3—C14—C15−105.9 (2)
C14—C3—C4—C5−91.1 (3)C7—O4—C8—C9−174.9 (2)
C14—C3—C4—C781.1 (2)C7—C4—C5—N1178.6 (2)
C14—C3—C2—C191.6 (3)C7—C4—C5—C6−2.3 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C21—H21···O2i0.952.503.256 (3)137
C6—H6A···O3ii0.982.593.452 (3)147
C19—H19···O10.952.513.227 (3)132
C13—H13B···O20.982.112.857 (3)131
C8—H8A···O2iii0.992.553.344 (3)137
N1—H1···O3ii0.91 (3)2.03 (3)2.938 (3)173 (2)
Symmetry codes: (i) x−1, y+1, z; (ii) x+1, y, z; (iii) −x+1, −y+1, −z+2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C21—H21···O2i0.952.503.256 (3)137.0
C6—H6A···O3ii0.982.593.452 (3)147.0
C19—H19···O10.952.513.227 (3)132.0
C13—H13B···O20.982.112.857 (3)131.2
C8—H8A···O2iii0.992.553.344 (3)136.9
N1—H1···O3ii0.91 (3)2.03 (3)2.938 (3)173 (2)
Symmetry codes: (i) x−1, y+1, z; (ii) x+1, y, z; (iii) −x+1, −y+1, −z+2.
 

Acknowledgements

SS and NRN thank the National Institutes of Health for grants NINDS P20RR015583 Center for Structural and Functional Neuroscience (CSFN) and P20 RR017670 Center for Environmental Health Sciences (CEHS).

References

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ISSN: 2056-9890
Volume 70| Part 7| July 2014| Pages o791-o792
https://doi.org/10.1107/S1600536814013294
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