organic compounds
2,2,7,7-Tetramethyl-1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione
aDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA, bDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, and cHacettepe University, Faculty of Pharmacy, Dept. of Pharmaceutical Chemistry, 06100 Sihhiye-Ankara, Turkey
*Correspondence e-mail: rbutcher99@yahoo.com
The whole molecule of the title compound, C17H21NO2, is generated by twofold rotational symmetry. The N atom and the C and H atoms in position 4 of the pyridine ring lie on the twofold axis. The cyclohexene ring has a sofa conformation with the CH2 C atom adjacent to the dimethyl-substituted C atom displaced by 0.5949 (16) Å from the mean plane of the other five C atoms. In the crystal, weak C—H⋯O interactions link the molecules into chains parallel to the a axis. In addition, π–π stacking interactions [centroid–centroid distance = 3.8444 (7) Å] contribute to the stabilization of the crystal structure.
Related literature
For background to potassium channels and biological functions and physiological roles, see: Horiuchi et al. (2001); Crestanello et al. (2000). For biological properties of 1,4-dihydropyridines (DHP), see: Simşek et al. (2004); Fincan et al. (2012); Gündüz et al. (2009); Pyrko (2008); Li et al. (2010). For geometric analysis, see: Cremer & Pople (1975). For a description of the Cambridge Structural Database, see: Allen (2002). For hydrogen-bond motifs, see: Bernstein et al. (1995). For similar structures, see: El-Khouly et al. (2012); Öztürk Yildirim et al. (2012, 2013); Gündüz et al. (2012).
Experimental
Crystal data
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Refinement
|
Data collection: CrysAlis PRO (Agilent, 2011); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.
Supporting information
https://doi.org/10.1107/S1600536812048957/mw2098sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812048957/mw2098Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812048957/mw2098Isup3.cml
A mixture of paraformaldehyde (1.0 mmol), 4,4-dimethyl-1,3-cyclohexanedione (2.0 mmol) and 1 mL of glacial acetic acid was refluxed in 5 mL of methanol for 8 h. Ammonium acetate (5.0 mmol) was then added and reflux was continued until the reaction was completed (monitored by TLC). The mixture was evaporated under reduced pressure, the residue was treated with 5 mL of water and 20 mL of dichloromethane. The dichloromethane extract was dried over sodium sulfate and evaporated to give the desired product. Pure crystals suitable for X-ray structure analysis were obtained by slow evaporation method using methanol as a solvent.
H atoms bonded to C atoms were positioned geometrically and treated as riding with C—H = 0.95–0.99 Å and Uiso(H) = 1.2Ueq(C) for H, and C—H = 0.98 Å and Uiso(H) = 1.5Ueq(C) for methyl H. The crystal is a racemic twin with a BASF value of 0.3 (4).
Potassium channels play an important role in cell function in both excitable and non-excitable cells. Potassium channel openers, which open vascular potassium channels, have the potential to restrain or prevent contractile responses to excitatory stimuli or clamp the vessel in a relaxed condition. Their vasorelaxant effect is due to an increase in the potassium efflux through opening plasmalemmal potassium channels, which reduce calcium release from intracellular sources (Horiuchi et al., 2001; Crestanello et al., 2000). It is well known that 1,4-dihydropyridine (DHP) and its bicyclo (quinoline) and tricyclo (acridine) analogs are a well known group of calcium channel blockers that are established in the clinic as having vasodilator and anti-hypertensive functions. Potassium channel opener activities of these compounds are well known (Simşek et al., 2004; Fincan et al., 2012; Gündüz et al., 2009; Pyrko, 2008; Li et al., 2010).
The molecular structure of (I) is shown in Fig. 1. The π conjugation along N1/C1/C6/C7/C6i/C1i [N1—C1 = 1.3423 (18) Å, N1—C1i = 1.3423 (18) Å, C1—C6 = 1.409 (2) Å, C6—C7 = 1.3861 (17) Å, C7—C6i = 1.3861 (17) Å and C1i—C6i = 1.409 (2) Å, symmetry code: (i) = y, x, -z + 5/4] indicates the strong aromaticity in the central ring, which makes all the atoms of the ring lie almost in a plane with the maximum deviation being -0.017 (1) Å for C1. This planarity of the central ring is further supported by the zero value for the puckering amplitude of this ring (Cremer & Pople, 1975). The unique cyclohexene ring (C1–C6) is in a sofa conformation with puckering parameters (Cremer & Pople, 1975) of QT = 0.435 (2) Å, θ = 48.8 (2)° and φ = 123.7 (3)°, respectively. The values of the bond lengths and bond angles are comparable with those of the related structures previously reported (El-Khouly et al., 2012; Öztürk Yildirim et al., 2012, 2013; Gündüz, et al., 2012).
consists of one half of the molecule and the complete molecule is generated from the by a twofold axis which passes through the N1 and C7 atoms. The keto bond distance (C5—O1) is 1.215 (2) Å and is comparable with those in similar structures obtained from the Cambrige Crystallographic Database (Allen, 2002).The deviation of atom C3 from the mean plane passing through C1, C2, C4, C5, C6 is 0.595 (2) Å. The dihedral angle between the mean planes of C1, C2, C5 and C6 and C1i, C2i, C5i and C6i (related by 2-fold axis) is 6.02 (3)°. TheMolecules of (I) are linked to each other via weak intermolecular C—H···O hydrogen bonds forming D motifs (Bernstein et al., 1995) as chains parallel to the a axis (Table 1, Fig. 2). In the crystal, weak π-π stacking interactions also contribute to the stabilization: [Cg1···Cg1ii (symmetry code: (ii) = 1 - y, x, -1/4 + z) = 3.844 (7) Å; where Cg1 is the centroid of the N1/C1/C6/C7/C6i/C1i (symmetry code: (i) = y, x, -z + 5/4) ring].
For background to potassium channels and biological functions and physiological roles, see: Horiuchi et al. (2001); Crestanello et al. (2000). For biological properties of 1,4-dihydropyridines (DHP), see: Simşek et al. (2004); Fincan et al. (2012); Gündüz et al. (2009); Pyrko (2008); Li et al. (2010). For geometric analysis, see: Cremer & Pople (1975). For a description of the Cambridge Structural Database, see: Allen (2002). For hydrogen-bond motifs, see: Bernstein et al. (1995). For similar structures, see: El-Khouly et al. (2012); Öztürk Yildirim et al. (2012,2013); Gündüz et al. (2012).
Data collection: CrysAlis PRO (Agilent, 2011); cell
CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C17H21NO2 | Dx = 1.245 Mg m−3 |
Mr = 271.35 | Cu Kα radiation, λ = 1.54184 Å |
Tetragonal, P4322 | Cell parameters from 1551 reflections |
Hall symbol: P 4cw 2c | θ = 3.0–75.1° |
a = 9.99077 (19) Å | µ = 0.64 mm−1 |
c = 14.5063 (4) Å | T = 123 K |
V = 1447.95 (6) Å3 | Block, colorless |
Z = 4 | 0.50 × 0.30 × 0.25 mm |
F(000) = 584 |
Agilent Xcalibur (Ruby, Gemini) diffractometer | 1452 independent reflections |
Radiation source: Enhance (Cu) X-ray Source | 1349 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.030 |
Detector resolution: 10.5081 pixels mm-1 | θmax = 75.3°, θmin = 4.4° |
ω scans | h = −11→12 |
Absorption correction: multi-scan [CrysAlis RED (Agilent, 2011), based on expressions derived by Clark & Reid (1995)] | k = −12→7 |
Tmin = 0.740, Tmax = 0.856 | l = −12→18 |
3055 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.043 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.122 | H-atom parameters constrained |
S = 1.09 | w = 1/[σ2(Fo2) + (0.0749P)2 + 0.0669P] where P = (Fo2 + 2Fc2)/3 |
1452 reflections | (Δ/σ)max < 0.001 |
94 parameters | Δρmax = 0.16 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
C17H21NO2 | Z = 4 |
Mr = 271.35 | Cu Kα radiation |
Tetragonal, P4322 | µ = 0.64 mm−1 |
a = 9.99077 (19) Å | T = 123 K |
c = 14.5063 (4) Å | 0.50 × 0.30 × 0.25 mm |
V = 1447.95 (6) Å3 |
Agilent Xcalibur (Ruby, Gemini) diffractometer | 1452 independent reflections |
Absorption correction: multi-scan [CrysAlis RED (Agilent, 2011), based on expressions derived by Clark & Reid (1995)] | 1349 reflections with I > 2σ(I) |
Tmin = 0.740, Tmax = 0.856 | Rint = 0.030 |
3055 measured reflections |
R[F2 > 2σ(F2)] = 0.043 | 0 restraints |
wR(F2) = 0.122 | H-atom parameters constrained |
S = 1.09 | Δρmax = 0.16 e Å−3 |
1452 reflections | Δρmin = −0.24 e Å−3 |
94 parameters |
Experimental. Absorption correction: CrysAlis RED, (Agilent, 2011) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. (Clark & Reid, 1995). |
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 | ||
O1 | 0.54930 (12) | 0.19920 (12) | 0.62530 (9) | 0.0345 (3) | |
N1 | 0.66208 (13) | 0.66208 (13) | 0.6250 | 0.0259 (4) | |
C1 | 0.69529 (15) | 0.53223 (15) | 0.61859 (10) | 0.0231 (3) | |
C2 | 0.84076 (15) | 0.49870 (18) | 0.60647 (12) | 0.0288 (4) | |
H2A | 0.8957 | 0.5649 | 0.6403 | 0.035* | |
H2B | 0.8643 | 0.5049 | 0.5403 | 0.035* | |
C3 | 0.87361 (17) | 0.35818 (18) | 0.64155 (11) | 0.0297 (4) | |
H3A | 0.8671 | 0.3579 | 0.7096 | 0.036* | |
H3B | 0.9674 | 0.3368 | 0.6251 | 0.036* | |
C4 | 0.78234 (16) | 0.24795 (17) | 0.60323 (11) | 0.0254 (4) | |
C5 | 0.63570 (16) | 0.28413 (16) | 0.61821 (11) | 0.0240 (3) | |
C6 | 0.59904 (15) | 0.42923 (15) | 0.62063 (10) | 0.0218 (3) | |
C7 | 0.46519 (15) | 0.46519 (15) | 0.6250 | 0.0223 (4) | |
H7A | 0.3980 | 0.3980 | 0.6250 | 0.027* | |
C8 | 0.79805 (17) | 0.23165 (17) | 0.49808 (12) | 0.0319 (4) | |
H8A | 0.7307 | 0.1685 | 0.4752 | 0.048* | |
H8B | 0.8877 | 0.1974 | 0.4842 | 0.048* | |
H8C | 0.7856 | 0.3186 | 0.4680 | 0.048* | |
C9 | 0.8130 (2) | 0.1153 (2) | 0.65133 (18) | 0.0458 (6) | |
H9A | 0.7559 | 0.0448 | 0.6257 | 0.069* | |
H9B | 0.7955 | 0.1242 | 0.7175 | 0.069* | |
H9C | 0.9072 | 0.0920 | 0.6416 | 0.069* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0283 (6) | 0.0225 (5) | 0.0527 (8) | −0.0016 (5) | 0.0096 (6) | 0.0026 (6) |
N1 | 0.0238 (6) | 0.0238 (6) | 0.0300 (9) | −0.0034 (7) | 0.0020 (6) | −0.0020 (6) |
C1 | 0.0220 (7) | 0.0265 (8) | 0.0209 (7) | −0.0006 (7) | 0.0003 (6) | −0.0011 (6) |
C2 | 0.0202 (7) | 0.0309 (9) | 0.0352 (8) | −0.0030 (6) | 0.0014 (6) | −0.0046 (7) |
C3 | 0.0222 (7) | 0.0388 (9) | 0.0283 (8) | 0.0035 (7) | −0.0034 (7) | −0.0007 (7) |
C4 | 0.0222 (8) | 0.0251 (7) | 0.0288 (8) | 0.0040 (6) | 0.0006 (6) | 0.0038 (6) |
C5 | 0.0233 (8) | 0.0229 (8) | 0.0257 (7) | 0.0013 (6) | 0.0033 (7) | 0.0031 (6) |
C6 | 0.0229 (7) | 0.0227 (7) | 0.0197 (7) | 0.0001 (6) | 0.0007 (6) | 0.0020 (6) |
C7 | 0.0213 (6) | 0.0213 (6) | 0.0243 (10) | −0.0026 (8) | −0.0004 (6) | 0.0004 (6) |
C8 | 0.0263 (8) | 0.0357 (9) | 0.0338 (9) | 0.0008 (7) | 0.0036 (7) | −0.0065 (8) |
C9 | 0.0353 (10) | 0.0389 (10) | 0.0631 (13) | 0.0080 (8) | −0.0002 (9) | 0.0204 (10) |
O1—C5 | 1.215 (2) | C4—C9 | 1.528 (2) |
N1—C1 | 1.3423 (18) | C4—C8 | 1.542 (2) |
N1—C1i | 1.3423 (18) | C5—C6 | 1.496 (2) |
C1—C6 | 1.409 (2) | C6—C7 | 1.3861 (17) |
C1—C2 | 1.502 (2) | C7—C6i | 1.3861 (17) |
C2—C3 | 1.529 (2) | C7—H7A | 0.9500 |
C2—H2A | 0.9900 | C8—H8A | 0.9800 |
C2—H2B | 0.9900 | C8—H8B | 0.9800 |
C3—C4 | 1.534 (2) | C8—H8C | 0.9800 |
C3—H3A | 0.9900 | C9—H9A | 0.9800 |
C3—H3B | 0.9900 | C9—H9B | 0.9800 |
C4—C5 | 1.525 (2) | C9—H9C | 0.9800 |
C1—N1—C1i | 118.85 (19) | O1—C5—C6 | 120.07 (15) |
N1—C1—C6 | 122.40 (14) | O1—C5—C4 | 121.96 (15) |
N1—C1—C2 | 117.57 (14) | C6—C5—C4 | 117.93 (13) |
C6—C1—C2 | 120.01 (14) | C7—C6—C1 | 118.05 (15) |
C1—C2—C3 | 111.93 (14) | C7—C6—C5 | 119.24 (14) |
C1—C2—H2A | 109.2 | C1—C6—C5 | 122.71 (14) |
C3—C2—H2A | 109.2 | C6i—C7—C6 | 120.1 (2) |
C1—C2—H2B | 109.2 | C6i—C7—H7A | 119.9 |
C3—C2—H2B | 109.2 | C6—C7—H7A | 119.9 |
H2A—C2—H2B | 107.9 | C4—C8—H8A | 109.5 |
C2—C3—C4 | 114.27 (13) | C4—C8—H8B | 109.5 |
C2—C3—H3A | 108.7 | H8A—C8—H8B | 109.5 |
C4—C3—H3A | 108.7 | C4—C8—H8C | 109.5 |
C2—C3—H3B | 108.7 | H8A—C8—H8C | 109.5 |
C4—C3—H3B | 108.7 | H8B—C8—H8C | 109.5 |
H3A—C3—H3B | 107.6 | C4—C9—H9A | 109.5 |
C5—C4—C9 | 109.45 (15) | C4—C9—H9B | 109.5 |
C5—C4—C3 | 110.45 (13) | H9A—C9—H9B | 109.5 |
C9—C4—C3 | 109.74 (15) | C4—C9—H9C | 109.5 |
C5—C4—C8 | 105.29 (13) | H9A—C9—H9C | 109.5 |
C9—C4—C8 | 109.85 (16) | H9B—C9—H9C | 109.5 |
C3—C4—C8 | 111.95 (14) | ||
C1i—N1—C1—C6 | −1.60 (11) | C3—C4—C5—C6 | 29.2 (2) |
C1i—N1—C1—C2 | 176.83 (16) | C8—C4—C5—C6 | −91.81 (16) |
N1—C1—C2—C3 | 154.89 (12) | N1—C1—C6—C7 | 3.1 (2) |
C6—C1—C2—C3 | −26.6 (2) | C2—C1—C6—C7 | −175.25 (13) |
C1—C2—C3—C4 | 51.52 (19) | N1—C1—C6—C5 | −176.91 (12) |
C2—C3—C4—C5 | −52.49 (18) | C2—C1—C6—C5 | 4.7 (2) |
C2—C3—C4—C9 | −173.25 (15) | O1—C5—C6—C7 | −4.2 (2) |
C2—C3—C4—C8 | 64.49 (18) | C4—C5—C6—C7 | 173.69 (12) |
C9—C4—C5—O1 | −32.0 (2) | O1—C5—C6—C1 | 175.89 (15) |
C3—C4—C5—O1 | −152.98 (16) | C4—C5—C6—C1 | −6.3 (2) |
C8—C4—C5—O1 | 85.99 (19) | C1—C6—C7—C6i | −1.48 (10) |
C9—C4—C5—C6 | 150.15 (17) | C5—C6—C7—C6i | 178.57 (16) |
Symmetry code: (i) y, x, −z+5/4. |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2B···O1ii | 0.99 | 2.52 | 3.415 (2) | 151 |
Symmetry code: (ii) −y+1, x, z−1/4. |
Experimental details
Crystal data | |
Chemical formula | C17H21NO2 |
Mr | 271.35 |
Crystal system, space group | Tetragonal, P4322 |
Temperature (K) | 123 |
a, c (Å) | 9.99077 (19), 14.5063 (4) |
V (Å3) | 1447.95 (6) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.64 |
Crystal size (mm) | 0.50 × 0.30 × 0.25 |
Data collection | |
Diffractometer | Agilent Xcalibur (Ruby, Gemini) |
Absorption correction | Multi-scan [CrysAlis RED (Agilent, 2011), based on expressions derived by Clark & Reid (1995)] |
Tmin, Tmax | 0.740, 0.856 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3055, 1452, 1349 |
Rint | 0.030 |
(sin θ/λ)max (Å−1) | 0.627 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.122, 1.09 |
No. of reflections | 1452 |
No. of parameters | 94 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.16, −0.24 |
Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2B···O1i | 0.99 | 2.52 | 3.415 (2) | 151 |
Symmetry code: (i) −y+1, x, z−1/4. |
Acknowledgements
RJB acknowledges the NSF–MRI program (grant No. CHE-0619278) for funds to purchase the diffractometer.
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Potassium channels play an important role in cell function in both excitable and non-excitable cells. Potassium channel openers, which open vascular potassium channels, have the potential to restrain or prevent contractile responses to excitatory stimuli or clamp the vessel in a relaxed condition. Their vasorelaxant effect is due to an increase in the potassium efflux through opening plasmalemmal potassium channels, which reduce calcium release from intracellular sources (Horiuchi et al., 2001; Crestanello et al., 2000). It is well known that 1,4-dihydropyridine (DHP) and its bicyclo (quinoline) and tricyclo (acridine) analogs are a well known group of calcium channel blockers that are established in the clinic as having vasodilator and anti-hypertensive functions. Potassium channel opener activities of these compounds are well known (Simşek et al., 2004; Fincan et al., 2012; Gündüz et al., 2009; Pyrko, 2008; Li et al., 2010).
The molecular structure of (I) is shown in Fig. 1. The asymmetric unit consists of one half of the molecule and the complete molecule is generated from the asymmetric unit by a twofold axis which passes through the N1 and C7 atoms. The keto bond distance (C5—O1) is 1.215 (2) Å and is comparable with those in similar structures obtained from the Cambrige Crystallographic Database (Allen, 2002).The deviation of atom C3 from the mean plane passing through C1, C2, C4, C5, C6 is 0.595 (2) Å. The dihedral angle between the mean planes of C1, C2, C5 and C6 and C1i, C2i, C5i and C6i (related by 2-fold axis) is 6.02 (3)°. The π conjugation along N1/C1/C6/C7/C6i/C1i [N1—C1 = 1.3423 (18) Å, N1—C1i = 1.3423 (18) Å, C1—C6 = 1.409 (2) Å, C6—C7 = 1.3861 (17) Å, C7—C6i = 1.3861 (17) Å and C1i—C6i = 1.409 (2) Å, symmetry code: (i) = y, x, -z + 5/4] indicates the strong aromaticity in the central ring, which makes all the atoms of the ring lie almost in a plane with the maximum deviation being -0.017 (1) Å for C1. This planarity of the central ring is further supported by the zero value for the puckering amplitude of this ring (Cremer & Pople, 1975). The unique cyclohexene ring (C1–C6) is in a sofa conformation with puckering parameters (Cremer & Pople, 1975) of QT = 0.435 (2) Å, θ = 48.8 (2)° and φ = 123.7 (3)°, respectively. The values of the bond lengths and bond angles are comparable with those of the related structures previously reported (El-Khouly et al., 2012; Öztürk Yildirim et al., 2012, 2013; Gündüz, et al., 2012).
Molecules of (I) are linked to each other via weak intermolecular C—H···O hydrogen bonds forming D motifs (Bernstein et al., 1995) as chains parallel to the a axis (Table 1, Fig. 2). In the crystal, weak π-π stacking interactions also contribute to the stabilization: [Cg1···Cg1ii (symmetry code: (ii) = 1 - y, x, -1/4 + z) = 3.844 (7) Å; where Cg1 is the centroid of the N1/C1/C6/C7/C6i/C1i (symmetry code: (i) = y, x, -z + 5/4) ring].