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In the title compound, C16H19ClN2O4, the pyridine ring is nearly planar, the piperidine ring is non-planar and the cyclo­hexane ring adopts a screw-boat conformation. The carboxyl­ate group makes a dihedral angle of 80.9 (2)° with the least-squares plane through the cyclo­hexane ring.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270101010770/sk1492sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270101010770/sk1492Isup2.hkl
Contains datablock I

CCDC reference: 173392

Comment top

The synthesis and biological evaluation of conformationally restricted analogues of nicotine and anabasine have attracted much attention (Catka & Leete, 1978; Kanne et al., 1986; Kanne & Abood, 1988; Vernier et al., 1998). The anabasine analogue with a piperidine ring has recently been screened as one of the agonists of neuronal acetylcholine receptors (nAChRs) and, more interestingly, the anabasine analogue with a pyrrolidine ring is currently under clinical trial for the treatment of Parkinson's disease and pain (Vernier et al., 1998). In this context, Sarkar et al. (2000) recently reported a domino reaction-based flexible strategy for the synthesis of the two analogues and synthesized the title compound, (I). The presence of a methoxy group at a proper position in the pyridine ring of the bridged analogues is the key to better selectivity as nAChR agonists. An X-ray crystal-structure determination of (I) was undertaken to assist in the understanding of its properties and the results are presented here. \sch

In compound (I), the bond lengths and angles show normal values and are comparable with those of the related structure previously studied by Sarkar et al. (1999). The pyridine ring is nearly planar, with a maximum deviation of -0.039 (3) Å for C2. The chloro group deviates by 0.252 (1) Å, and the methoxy group is twisted through 2.2 (3)°, relative to the least-squares plane of the pyridine ring.

The piperidine ring is not planar, with atoms C4 and C5 deviating by 0.196 (7) and -0.223 (8) Å, respectively. The puckering parameters (Cremer & Pople, 1975) are Q2 = 0.265 (5) and Q3 = 0.188 (5) Å, ϕ2 = 260.8 (10)°, QT = 0.325 (6) Å, and θ2 = 54.7 (9)°. The methyl group, C13, deviates by 0.802 (5) Å from the least-squares plane of the piperidine ring.

The cyclohexane ring adopts a screw-boat conformation, with the following deviations of atoms from their least-squares plane: C10 - 0.071 (3), C2 - 0.202 (3), C8 - 0.365 (4), C7 0.063 (3), C3 0.212 (3) and C9 0.363 (3) Å. This is also confirmed by the puckering parameters Q2 = 0.571 (3) and Q3 = 0.182 (3) Å, ϕ2 = 210.8 (3)°, QT = 0.600 (3) Å, and θ2 = 72.3 (3)°.

The hydroxy group is in the least-squares plane through the cyclohexane ring, while this plane makes dihedral angles of 20.1 (2), 23.5 (2) and 80.9 (2)° with the least-squares planes through the pyridine ring, piperidine ring and carboxylate group, respectively.

Experimental top

To a stirred solution of α-diazoester 1 (140 mg, 0.38 mmol) in dry benzene under an argon atmosphere at ambient temperature, a catalytic amount of Rh2(OAc)4 was added. After stirring the mixture for 24 h, the solvent was removed in vacuo and the residue was purified by flash chromatography (alumina, ethyl acetate/petroleum ether 20:80). Recrystallization from a dichloromethane:diethyl ether:petroleum ether (3:3:1) solution afforded 80 mg (62%) of (I) as yellowish-green crystals.

Refinement top

After checking their presence in the difference map, all H atoms were geometrically fixed and allowed to ride on their attached atoms, with C—H = 0.93–0.97 Å and O—H = 0.82 Å, and Uiso(H) = 1.5Ueq(O) and 1.2Ueq(C). Query.

Computing details top

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL, PARST95 (Nardelli, 1995) and PLATON (Spek, 1990).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing 30% probability displacement ellipsoids and the atom-numbering scheme. H atoms are drawn as small spheres of arbitrary radii.
Methyl (SR)-10-chloro-1,2,3,4,5,6-hexahydro-6-hydroxy-8-methoxy-1-methyl- 1,9-phenanthroline-6-carboxylate top
Crystal data top
C16H19ClN2O4F(000) = 356
Mr = 338.78Dx = 1.330 Mg m3
Triclinic, P1Melting point: 426K K
a = 9.2081 (4) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.4835 (4) ÅCell parameters from 3323 reflections
c = 11.1287 (6) Åθ = 2.0–28.3°
α = 100.574 (1)°µ = 0.25 mm1
β = 101.751 (1)°T = 293 K
γ = 111.882 (1)°Slab, yellowish green
V = 846.14 (7) Å30.46 × 0.36 × 0.22 mm
Z = 2
Data collection top
Siemens SMART CCD area-detector
diffractometer
3990 independent reflections
Radiation source: fine-focus sealed tube2299 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.057
Detector resolution: 8.33 pixels mm-1θmax = 28.2°, θmin = 2.0°
ω scansh = 1212
Absorption correction: empirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
k = 1212
Tmin = 0.895, Tmax = 0.948l = 1214
6088 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.076Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.209H-atom parameters constrained
S = 0.94 w = 1/[σ2(Fo2) + (0.1071P)2]
where P = (Fo2 + 2Fc2)/3
3990 reflections(Δ/σ)max < 0.001
212 parametersΔρmax = 0.63 e Å3
2 restraintsΔρmin = 0.62 e Å3
Crystal data top
C16H19ClN2O4γ = 111.882 (1)°
Mr = 338.78V = 846.14 (7) Å3
Triclinic, P1Z = 2
a = 9.2081 (4) ÅMo Kα radiation
b = 9.4835 (4) ŵ = 0.25 mm1
c = 11.1287 (6) ÅT = 293 K
α = 100.574 (1)°0.46 × 0.36 × 0.22 mm
β = 101.751 (1)°
Data collection top
Siemens SMART CCD area-detector
diffractometer
3990 independent reflections
Absorption correction: empirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
2299 reflections with I > 2σ(I)
Tmin = 0.895, Tmax = 0.948Rint = 0.057
6088 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0762 restraints
wR(F2) = 0.209H-atom parameters constrained
S = 0.94Δρmax = 0.63 e Å3
3990 reflectionsΔρmin = 0.62 e Å3
212 parameters
Special details top

Experimental. The data collection covered over a hemisphere of reciprocal space by a combination of three sets of exposures; each set had a different ϕ angle (0, 88 and 180°) for the crystal and each exposure of 10 s covered 0.3° in ω. The crystal-to-detector distance was 4 cm and the detector swing angle was -35°. Crystal decay was monitored by repeating fifty initial frames at the end of data collection and analysing the intensity of duplicate reflections, and was found to be negligible.

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
Cl10.45819 (11)0.21311 (9)0.18714 (8)0.0550 (3)
O10.3028 (2)0.7970 (3)0.3657 (2)0.0503 (6)
H1A0.34110.88390.41880.075*
O20.0171 (3)0.3112 (3)0.0170 (2)0.0575 (6)
O30.5669 (3)0.8382 (2)0.2006 (2)0.0521 (6)
O40.6409 (3)1.0135 (3)0.3897 (2)0.0564 (7)
N10.2167 (3)0.2805 (3)0.0998 (2)0.0391 (6)
N20.7440 (3)0.5413 (3)0.3051 (3)0.0481 (7)
C10.3702 (4)0.3479 (3)0.1796 (3)0.0362 (6)
C20.4532 (3)0.5035 (3)0.2557 (3)0.0323 (6)
C30.6239 (3)0.5831 (3)0.3428 (3)0.0361 (6)
C40.9080 (5)0.6318 (8)0.3933 (5)0.108 (2)
H4A0.96690.56580.38790.130*
H4B0.96320.72190.36400.130*
C50.9225 (6)0.6899 (9)0.5249 (5)0.149 (3)
H5A1.03570.76480.56820.179*
H5B0.90020.60150.56140.179*
C60.8205 (4)0.7653 (5)0.5543 (4)0.0600 (10)
H6A0.87350.87660.55870.072*
H6B0.80650.75870.63740.072*
C70.6541 (3)0.6888 (3)0.4544 (3)0.0372 (7)
C80.5202 (4)0.7338 (4)0.4785 (3)0.0398 (7)
H8A0.56680.83310.54590.048*
H8B0.44440.65260.50560.048*
C90.4305 (3)0.7510 (3)0.3549 (3)0.0362 (7)
C100.3563 (3)0.5894 (3)0.2559 (3)0.0315 (6)
C110.1993 (4)0.5246 (4)0.1770 (3)0.0401 (7)
H11A0.13620.58160.17610.048*
C120.1361 (3)0.3693 (4)0.0974 (3)0.0392 (7)
C130.7499 (5)0.5374 (5)0.1754 (4)0.0674 (11)
H13A0.80910.47770.15150.101*
H13B0.80430.64370.17080.101*
H13C0.64040.48830.11790.101*
C140.5584 (4)0.8815 (3)0.3185 (3)0.0375 (7)
C150.6896 (6)0.9556 (5)0.1650 (4)0.0739 (12)
H15A0.69010.91100.08050.111*
H15B0.79540.98840.22470.111*
H15C0.66501.04560.16630.111*
C160.0894 (5)0.1510 (4)0.0618 (4)0.0714 (12)
H16A0.19650.12650.11550.107*
H16B0.09840.08100.00860.107*
H16C0.02190.13790.11420.107*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0605 (6)0.0455 (5)0.0550 (5)0.0324 (4)0.0027 (4)0.0000 (4)
O10.0399 (12)0.0559 (13)0.0524 (14)0.0288 (11)0.0101 (10)0.0046 (11)
O20.0366 (12)0.0470 (13)0.0606 (15)0.0086 (11)0.0128 (11)0.0016 (12)
O30.0679 (15)0.0448 (12)0.0315 (12)0.0122 (11)0.0191 (11)0.0043 (10)
O40.0703 (16)0.0379 (12)0.0477 (14)0.0123 (12)0.0257 (13)0.0042 (11)
N10.0363 (14)0.0359 (13)0.0331 (13)0.0101 (11)0.0022 (11)0.0029 (11)
N20.0299 (13)0.0573 (16)0.0555 (17)0.0235 (13)0.0066 (12)0.0089 (14)
C10.0380 (16)0.0395 (16)0.0313 (15)0.0188 (14)0.0098 (13)0.0060 (13)
C20.0310 (15)0.0369 (15)0.0265 (14)0.0137 (12)0.0079 (11)0.0059 (12)
C30.0298 (15)0.0398 (16)0.0372 (16)0.0155 (13)0.0062 (12)0.0109 (13)
C40.044 (2)0.158 (5)0.109 (4)0.061 (3)0.002 (3)0.006 (4)
C50.052 (3)0.231 (8)0.113 (5)0.076 (4)0.029 (3)0.041 (5)
C60.0373 (19)0.068 (2)0.051 (2)0.0119 (18)0.0048 (16)0.0042 (18)
C70.0302 (15)0.0411 (16)0.0306 (15)0.0094 (13)0.0028 (12)0.0078 (13)
C80.0418 (17)0.0426 (17)0.0276 (15)0.0138 (14)0.0092 (13)0.0037 (13)
C90.0316 (15)0.0411 (16)0.0328 (15)0.0173 (13)0.0082 (12)0.0013 (13)
C100.0270 (14)0.0334 (14)0.0286 (14)0.0108 (12)0.0065 (11)0.0029 (11)
C110.0320 (15)0.0415 (16)0.0411 (17)0.0167 (13)0.0045 (13)0.0040 (14)
C120.0260 (15)0.0419 (17)0.0378 (16)0.0066 (13)0.0030 (12)0.0086 (14)
C130.060 (2)0.089 (3)0.072 (3)0.040 (2)0.040 (2)0.026 (2)
C140.0399 (16)0.0383 (16)0.0356 (16)0.0211 (14)0.0090 (13)0.0066 (14)
C150.098 (3)0.060 (2)0.059 (2)0.019 (2)0.047 (2)0.015 (2)
C160.050 (2)0.045 (2)0.077 (3)0.0012 (18)0.016 (2)0.009 (2)
Geometric parameters (Å, º) top
Cl1—C11.755 (3)C5—H5B0.9700
O1—C91.417 (3)C6—C71.514 (4)
O1—H1A0.8200C6—H6A0.9700
O2—C121.348 (3)C6—H6B0.9700
O2—C161.428 (4)C7—C81.503 (4)
O3—C141.329 (3)C8—C91.524 (4)
O3—C151.442 (4)C8—H8A0.9700
O4—C141.206 (3)C8—H8B0.9700
N1—C121.314 (4)C9—C101.524 (4)
N1—C11.343 (4)C9—C141.541 (4)
N2—C31.418 (4)C10—C111.364 (4)
N2—C41.450 (5)C11—C121.402 (4)
N2—C131.451 (5)C11—H11A0.9300
C1—C21.385 (4)C13—H13A0.9600
C2—C101.415 (4)C13—H13B0.9600
C2—C31.485 (4)C13—H13C0.9600
C3—C71.349 (4)C15—H15A0.9600
C4—C51.426 (4)C15—H15B0.9600
C4—H4A0.9700C15—H15C0.9600
C4—H4B0.9700C16—H16A0.9600
C5—C61.429 (4)C16—H16B0.9600
C5—H5A0.9700C16—H16C0.9600
C9—O1—H1A109.5C7—C8—H8B110.0
C12—O2—C16118.4 (3)C9—C8—H8B110.0
C14—O3—C15115.9 (3)H8A—C8—H8B108.4
C12—N1—C1116.7 (2)O1—C9—C8114.1 (2)
C3—N2—C4113.9 (3)O1—C9—C10108.4 (2)
C3—N2—C13116.8 (3)C8—C9—C10106.8 (2)
C4—N2—C13109.3 (3)O1—C9—C14107.7 (2)
N1—C1—C2126.0 (3)C8—C9—C14106.9 (2)
N1—C1—Cl1112.8 (2)C10—C9—C14113.2 (2)
C2—C1—Cl1121.1 (2)C11—C10—C2121.0 (3)
C1—C2—C10114.3 (2)C11—C10—C9121.9 (2)
C1—C2—C3127.6 (3)C2—C10—C9116.9 (2)
C10—C2—C3117.9 (2)C10—C11—C12117.9 (3)
C7—C3—N2124.0 (3)C10—C11—H11A121.0
C7—C3—C2117.7 (2)C12—C11—H11A121.0
N2—C3—C2118.3 (2)N1—C12—O2120.1 (3)
C5—C4—N2117.4 (4)N1—C12—C11123.5 (3)
C5—C4—H4A108.0O2—C12—C11116.4 (3)
N2—C4—H4A108.0N2—C13—H13A109.5
C5—C4—H4B108.0N2—C13—H13B109.5
N2—C4—H4B108.0H13A—C13—H13B109.5
H4A—C4—H4B107.2N2—C13—H13C109.5
C4—C5—C6117.8 (5)H13A—C13—H13C109.5
C4—C5—H5A107.9H13B—C13—H13C109.5
C6—C5—H5A107.9O4—C14—O3122.6 (3)
C4—C5—H5B107.9O4—C14—C9122.9 (3)
C6—C5—H5B107.9O3—C14—C9114.5 (2)
H5A—C5—H5B107.2O3—C15—H15A109.5
C5—C6—C7111.4 (3)O3—C15—H15B109.5
C5—C6—H6A109.3H15A—C15—H15B109.5
C7—C6—H6A109.3O3—C15—H15C109.5
C5—C6—H6B109.3H15A—C15—H15C109.5
C7—C6—H6B109.3H15B—C15—H15C109.5
H6A—C6—H6B108.0O2—C16—H16A109.5
C3—C7—C8119.0 (3)O2—C16—H16B109.5
C3—C7—C6121.5 (3)H16A—C16—H16B109.5
C8—C7—C6119.5 (3)O2—C16—H16C109.5
C7—C8—C9108.4 (2)H16A—C16—H16C109.5
C7—C8—H8A110.0H16B—C16—H16C109.5
C9—C8—H8A110.0
C12—N1—C1—C22.6 (4)C7—C8—C9—C1459.7 (3)
C12—N1—C1—Cl1173.8 (2)C1—C2—C10—C115.8 (4)
N1—C1—C2—C106.8 (4)C3—C2—C10—C11179.1 (3)
Cl1—C1—C2—C10169.3 (2)C1—C2—C10—C9169.5 (2)
N1—C1—C2—C3178.5 (3)C3—C2—C10—C95.6 (4)
Cl1—C1—C2—C35.4 (4)O1—C9—C10—C1112.0 (4)
C4—N2—C3—C74.5 (5)C8—C9—C10—C11135.3 (3)
C13—N2—C3—C7133.5 (3)C14—C9—C10—C11107.4 (3)
C4—N2—C3—C2176.8 (4)O1—C9—C10—C2163.3 (2)
C13—N2—C3—C247.8 (4)C8—C9—C10—C240.0 (3)
C1—C2—C3—C7142.8 (3)C14—C9—C10—C277.4 (3)
C10—C2—C3—C731.6 (4)C2—C10—C11—C121.0 (4)
C1—C2—C3—N235.9 (4)C9—C10—C11—C12174.0 (3)
C10—C2—C3—N2149.6 (3)C1—N1—C12—O2178.1 (3)
C3—N2—C4—C528.8 (8)C1—N1—C12—C113.1 (4)
C13—N2—C4—C5161.4 (6)C16—O2—C12—N11.7 (4)
N2—C4—C5—C646.3 (10)C16—O2—C12—C11177.2 (3)
C4—C5—C6—C735.1 (9)C10—C11—C12—N13.8 (5)
N2—C3—C7—C8174.7 (3)C10—C11—C12—O2177.4 (3)
C2—C3—C7—C86.6 (4)C15—O3—C14—O44.1 (5)
N2—C3—C7—C64.0 (5)C15—O3—C14—C9177.8 (3)
C2—C3—C7—C6174.7 (3)O1—C9—C14—O467.0 (3)
C5—C6—C7—C310.9 (6)C8—C9—C14—O456.0 (3)
C5—C6—C7—C8170.4 (4)C10—C9—C14—O4173.2 (3)
C3—C7—C8—C940.5 (4)O1—C9—C14—O3111.1 (3)
C6—C7—C8—C9138.3 (3)C8—C9—C14—O3125.9 (3)
C7—C8—C9—O1178.6 (2)C10—C9—C14—O38.7 (3)
C7—C8—C9—C1061.6 (3)

Experimental details

Crystal data
Chemical formulaC16H19ClN2O4
Mr338.78
Crystal system, space groupTriclinic, P1
Temperature (K)293
a, b, c (Å)9.2081 (4), 9.4835 (4), 11.1287 (6)
α, β, γ (°)100.574 (1), 101.751 (1), 111.882 (1)
V3)846.14 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.25
Crystal size (mm)0.46 × 0.36 × 0.22
Data collection
DiffractometerSiemens SMART CCD area-detector
diffractometer
Absorption correctionEmpirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.895, 0.948
No. of measured, independent and
observed [I > 2σ(I)] reflections
6088, 3990, 2299
Rint0.057
(sin θ/λ)max1)0.666
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.076, 0.209, 0.94
No. of reflections3990
No. of parameters212
No. of restraints2
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.63, 0.62

Computer programs: SMART (Siemens, 1996), SAINT (Siemens, 1996), SAINT, SHELXTL (Sheldrick, 1997), SHELXTL, PARST95 (Nardelli, 1995) and PLATON (Spek, 1990).

Selected geometric parameters (Å, º) top
N1—C121.314 (4)C3—C71.349 (4)
N1—C11.343 (4)C6—C71.514 (4)
N2—C31.418 (4)C7—C81.503 (4)
N2—C41.450 (5)C8—C91.524 (4)
C2—C101.415 (4)C9—C101.524 (4)
C2—C31.485 (4)
C3—N2—C4113.9 (3)O1—C9—C10108.4 (2)
C7—C3—N2124.0 (3)C8—C9—C10106.8 (2)
C3—C7—C8119.0 (3)O1—C9—C14107.7 (2)
C7—C8—C9108.4 (2)
C10—C2—C3—C731.6 (4)C1—N1—C12—C113.1 (4)
C1—C2—C3—N235.9 (4)C16—O2—C12—N11.7 (4)
C10—C2—C3—N2149.6 (3)C10—C9—C14—O4173.2 (3)
 

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