(2E,4E)-8-Methyl-2,4-bis(3-thienylmethyl­ene)-8-aza­bicyclo­[3.2.1]octan-3-one

The title compound, C₁₈H₁₇NOS₂, was prepared by the base-catalyzed Aldol condensation of tropinone with thio­phene-3-carboxaldehyde. It crystallizes with the molecule on a mirror plane. Both double bonds linking the tropinone and thio­phene rings adopt the E configuration, with the thienyl-ring flip and the H atoms of the N-methyl group disordered.

Key indicators

• Single-crystal X-ray study
• T = 90 K
• Mean [sigma](C-C) = 0.002 Å
• Disorder in main residue
• R factor = 0.031
• wR factor = 0.074
• Data-to-parameter ratio = 11.6

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT301_ALERT_3_B Main Residue  Disorder .........................      31.00 Perc.

Alert level C
STRVA01_ALERT_4_C           Flack test results are ambiguous.
           From the CIF: _refine_ls_abs_structure_Flack    0.470
           From the CIF: _refine_ls_abs_structure_Flack_su    0.090
PLAT033_ALERT_2_C Flack Parameter Value Deviates from Zero .......       0.47
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT366_ALERT_2_C Short? C(sp?)-C(sp?) Bond  C2     -   C6     ...       1.35 Ang.

Alert level G
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           27.49
           From the CIF: _reflns_number_total               1668
           Count of symmetry unique reflns          960
           Completeness (_total/calc)            173.75%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       708
           Fraction of Friedel pairs measured     0.738
           Are heavy atom types Z>Si present        yes

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion

---

S1. Comment

Tropane alkaloids comprise a large group of bases occurring predominantly in the family Solanaceae. Many of these compounds have interesting biological properties. A series of tropanes have showed anticonvulsant activity against pentylenetetrazol-induced convulsions in mice and antiarrhythmic activity in rabbit previously treated with ouabain (Trigo et al., 1981). The title compound, (I), is a synthetic precursor of a drug candidate with defined double-bond geometry and was prepared by the base-catalyzed Aldol condensation of tropinone with thiophene-3-carboxaldehyde to afford a single geometric isomer. The product, the title compound, (I), was identified by NMR spectroscopy. In order to confirm the double-bond geometries and to study the structural conformation of the molecule in the solid state, its X-ray structure determination has been carried out and the results are presented here.

Fig. 1 illustrates a displacement ellipsoid plot of (I), and selected geometric parameters are presented in Table 1. The molecule is symmetric, with both C═C double-bonds adopting the E configuration. Deviations from the ideal bond-angle geometry around the sp² C atoms of the double bonds are observed. The angles C6═C2—C1, C2═C6—C7 and C8═C7—C6 are distorted because of steric hindrance, due to the double bonds linking the thiophene rings on both sides of the tropinone moiety. These angles have values of 116.60 (15), 130.07 (14) and 128.6 (5)° respectively. The C2═ C6—C7═C8 torsion angle [−21.6 (12)°] indicates a deviation of the plane of the thiophene rings from the plane of the double bonds connecting the rings. The C6—C7 bond length [1.458 (2) Å] is slightly shorter than typical C—C single bonds, suggesting extended conjugation of the thiophene ring π-electron systems with the C2═C6 double bond (Wilson, 1992). The molecule has thienyl-ring flip disorder, the thiophene rings being disordered over two conformations about the C6–C7 bond. The N-methyl group is also disordered.

S2. Experimental

Potassium hydroxide (1.25 g) dissolved in water (5 ml) was added to tropinone (0.418 g, 3 mmol) and thiophene-3-carboxaldehyde (0.673 g, 6 mmol) dissolved in alcohol Ethanol? (20 ml), and the solution was then boiled under reflux for 1 h. After cooling the reaction mixture to room temperature, crystals separated and were collected by filtration and washed with water. Recrystallization from ethyl acetate afforded (I) as brown needles which were suitable for X-ray analysis. Spectroscopic analysis: ¹H NMR (CDCl₃, δ, p.p.m.): 1.94 (m, 2H), 2.38 (s, 3H), 2.61 (m, 2H), 4.48 (m, 2H), 7.23 (dd, 2H), 7.39 (q, 2H), 7.45 (m, 2H), 7.77 (s, 2H); ¹³C NMR (CDCl₃, δ, p.p.m.): 30.3, 36.4, 61.5, 126.3, 128.3, 129.2, 130.1, 136.9, 137.1, 187.5.

S3. Refinement

H atoms were placed in idealized positions and were constrained, with C—H distances of 0.99, 0.98 and 0.95 Å for methyl, sp and sp² C atoms, respectively, and with U_iso(H) = 1.2U_eq(C), or 1.5U_eq(C) for methyl H atoms. The Flack x(u) parameter (Flack, 1983) refined to 0.47 (9) and was subsequently fixed at 0.5. The crystals are inversion twins. Disorder of the thiophene ring is common in this sort of molecule. The geometries of the two PARTs were kept similar using the SAME restraint and displacement parameters in these disordered pieces were restrained using both ISOR and SIMU. In addition, the components of anisotropic displacement for disordered atoms occupying approximately the same site were made equal using the EADP constraint.

Computing details

Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1995); software used to prepare material for publication: SHELXL97 and local procedures.

Figures

Fig. 1. A view of (I), after application of the mirror symmetry operation (2 − x, y, z) to generate the full molecule. H atoms and the disorder of the thienyl rings have been omitted for clarity. Displacement ellipsoids are drawn at the 50% probability level.

(2E,4E)-8-Methyl-2,4-bis-thiophen-3-ylmethylene-8-azabicyclo[3.2.1]octan-3-one

Crystal data

C18H17NOS2	F(000) = 688
Mr = 327.45	Dx = 1.450 Mg m^−3
Orthorhombic, Cmc21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2c -2	Cell parameters from 994 reflections
a = 19.3783 (4) Å	θ = 1.0–27.5°
b = 10.5680 (6) Å	µ = 0.36 mm^−1
c = 7.3257 (3) Å	T = 90 K
V = 1500.23 (11) Å^3	Irregular fragment, brown
Z = 4	0.25 × 0.20 × 0.15 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1668 independent reflections
Radiation source: fine-focus sealed tube	1551 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
Detector resolution: 18 pixels mm^-1	θmax = 27.5°, θmin = 2.1°
ω scans at fixed χ = 55°	h = −24→25
Absorption correction: multi-scan (SCALEPACK, Version 0.95.373; Otwinowski & Minor, 1997)	k = −13→13
Tmin = 0.916, Tmax = 0.949	l = −9→9
1668 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.031	H-atom parameters constrained
wR(F^2) = 0.074	w = 1/[σ^2(Fo^2) + (0.0376P)^2 + 0.3768P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max = 0.001
1668 reflections	Δρmax = 0.23 e Å^−3
144 parameters	Δρmin = −0.20 e Å^−3
186 restraints	Absolute structure: Flack (1983), with how many Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.47 (9)

Special details

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.

Flack's x(u) parameter refined to 0.47 (9) and was subsequently fixed at 0.5. The crystals are inversion twins.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	1.0000	1.04922 (15)	0.7913 (3)	0.0239 (4)
N1	1.0000	0.67138 (18)	0.8054 (3)	0.0157 (4)
C1	1.0000	0.9364 (2)	0.7552 (3)	0.0165 (5)
C2	0.93431 (8)	0.86450 (14)	0.7290 (3)	0.0155 (3)
C3	0.94082 (8)	0.72283 (14)	0.7042 (3)	0.0152 (3)
H3	0.8972	0.6795	0.7421	0.018*
C4	0.95997 (8)	0.68646 (16)	0.5066 (3)	0.0182 (4)
H4A	0.9417	0.7492	0.4186	0.022*
H4B	0.9417	0.6018	0.4751	0.022*
C5	1.0000	0.6941 (2)	1.0032 (3)	0.0201 (5)
H5A	0.9933	0.7846	1.0268	0.030*	0.50
H5B	1.0442	0.6669	1.0549	0.030*	0.50
H5C	0.9625	0.6460	1.0599	0.030*	0.50
C6	0.87556 (8)	0.93268 (15)	0.7284 (2)	0.0160 (3)
H6	0.8813	1.0203	0.7532	0.019*
C7	0.80459 (7)	0.89298 (15)	0.6955 (3)	0.0144 (3)	0.604 (2)
C8	0.7817 (6)	0.7892 (12)	0.607 (3)	0.0135 (13)	0.604 (2)
H8	0.8119	0.7276	0.5566	0.016*	0.604 (2)
S1	0.69352 (6)	0.77756 (15)	0.5917 (2)	0.0162 (3)	0.604 (2)
C9	0.6851 (4)	0.9185 (10)	0.7108 (17)	0.0176 (16)	0.604 (2)
H9	0.6420	0.9539	0.7448	0.021*	0.604 (2)
C10	0.7459 (4)	0.9719 (11)	0.7496 (19)	0.0136 (12)	0.604 (2)
H10	0.7505	1.0523	0.8062	0.016*	0.604 (2)
C7'	0.80459 (7)	0.89298 (15)	0.6955 (3)	0.0144 (3)	0.396 (2)
C8'	0.7535 (6)	0.9653 (16)	0.754 (3)	0.0143 (18)	0.396 (2)
H8'	0.7607	1.0396	0.8246	0.017*	0.396 (2)
S1'	0.67364 (15)	0.9136 (4)	0.6918 (6)	0.0170 (5)	0.396 (2)
C9'	0.7115 (4)	0.7811 (11)	0.593 (2)	0.0203 (18)	0.396 (2)
H9'	0.6852	0.7156	0.5374	0.024*	0.396 (2)
C10'	0.7801 (9)	0.7786 (19)	0.600 (4)	0.0135 (18)	0.396 (2)
H10'	0.8087	0.7136	0.5522	0.016*	0.396 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0190 (8)	0.0157 (8)	0.0368 (10)	0.000	0.000	−0.0037 (7)
N1	0.0137 (8)	0.0159 (9)	0.0176 (10)	0.000	0.000	0.0012 (8)
C1	0.0157 (10)	0.0143 (9)	0.0195 (12)	0.000	0.000	−0.0001 (9)
C2	0.0155 (7)	0.0157 (7)	0.0152 (9)	−0.0010 (6)	0.0005 (6)	0.0005 (6)
C3	0.0126 (7)	0.0141 (7)	0.0188 (9)	−0.0009 (5)	−0.0010 (7)	0.0001 (7)
C4	0.0211 (9)	0.0151 (7)	0.0183 (9)	−0.0001 (6)	−0.0028 (7)	−0.0012 (7)
C5	0.0194 (11)	0.0224 (11)	0.0185 (12)	0.000	0.000	0.0005 (10)
C6	0.0175 (7)	0.0141 (7)	0.0165 (9)	−0.0011 (6)	0.0004 (6)	0.0016 (7)
C7	0.0154 (7)	0.0144 (7)	0.0135 (8)	0.0017 (5)	−0.0004 (7)	0.0037 (6)
C8	0.0128 (16)	0.014 (2)	0.014 (2)	0.0028 (15)	0.0004 (16)	0.0019 (19)
S1	0.0143 (5)	0.0170 (4)	0.0172 (4)	−0.0009 (4)	−0.0013 (5)	0.0000 (3)
C9	0.021 (2)	0.016 (2)	0.016 (3)	0.0041 (19)	0.002 (2)	−0.0008 (16)
C10	0.0132 (19)	0.0127 (18)	0.015 (2)	0.0085 (14)	−0.0019 (17)	−0.0005 (15)
C7'	0.0154 (7)	0.0144 (7)	0.0135 (8)	0.0017 (5)	−0.0004 (7)	0.0037 (6)
C8'	0.014 (2)	0.015 (3)	0.014 (3)	−0.003 (2)	−0.002 (2)	0.002 (2)
S1'	0.0120 (8)	0.0204 (8)	0.0186 (11)	−0.0020 (7)	−0.0007 (8)	0.0004 (7)
C9'	0.025 (3)	0.018 (2)	0.018 (3)	−0.001 (2)	0.002 (3)	−0.0030 (18)
C10'	0.017 (2)	0.013 (3)	0.011 (3)	−0.0022 (19)	0.000 (2)	−0.002 (2)

Geometric parameters (Å, º)

O1—C1	1.221 (3)	C6—C7	1.458 (2)
N1—C5	1.469 (3)	C6—H6	0.9500
N1—C3^i	1.470 (2)	C7—C8	1.350 (10)
N1—C3	1.470 (2)	C7—C10	1.465 (8)
C1—C2^i	1.4951 (19)	C8—S1	1.716 (11)
C1—C2	1.4952 (19)	C8—H8	0.9500
C2—C6	1.347 (2)	S1—C9	1.733 (9)
C2—C3	1.513 (2)	C9—C10	1.337 (12)
C3—C4	1.543 (3)	C9—H9	0.9500
C3—H3	1.0000	C10—H10	0.9500
C4—C4^i	1.552 (3)	C8'—S1'	1.704 (14)
C4—H4A	0.9900	C8'—H8'	0.9500
C4—H4B	0.9900	S1'—C9'	1.740 (10)
C5—H5A	0.9800	C9'—C10'	1.331 (18)
C5—H5B	0.9800	C9'—H9'	0.9500
C5—H5C	0.9800	C10'—H10'	0.9500
C5—N1—C3^i	115.92 (13)	H5A—C5—H5C	109.5
C5—N1—C3	115.92 (13)	H5B—C5—H5C	109.5
C3^i—N1—C3	102.55 (18)	C2—C6—C7	130.07 (14)
O1—C1—C2^i	121.63 (9)	C2—C6—H6	115.0
O1—C1—C2	121.62 (9)	C7—C6—H6	115.0
C2^i—C1—C2	116.72 (19)	C8—C7—C6	128.6 (5)
C6—C2—C1	116.60 (15)	C8—C7—C10	109.7 (4)
C6—C2—C3	126.81 (14)	C6—C7—C10	121.6 (4)
C1—C2—C3	116.58 (14)	C7—C8—S1	114.6 (7)
N1—C3—C2	111.75 (15)	C7—C8—H8	122.7
N1—C3—C4	101.15 (13)	S1—C8—H8	122.7
C2—C3—C4	112.28 (14)	C8—S1—C9	90.0 (4)
N1—C3—H3	110.4	C10—C9—S1	112.8 (7)
C2—C3—H3	110.4	C10—C9—H9	123.6
C4—C3—H3	110.4	S1—C9—H9	123.6
C3—C4—C4^i	103.92 (8)	C9—C10—C7	112.7 (8)
C3—C4—H4A	111.0	C9—C10—H10	123.7
C4^i—C4—H4A	111.0	C7—C10—H10	123.7
C3—C4—H4B	111.0	S1'—C8'—H8'	123.0
C4^i—C4—H4B	111.0	C8'—S1'—C9'	89.2 (6)
H4A—C4—H4B	109.0	C10'—C9'—S1'	114.8 (9)
N1—C5—H5A	109.5	C10'—C9'—H9'	122.6
N1—C5—H5B	109.5	S1'—C9'—H9'	122.6
H5A—C5—H5B	109.5	C9'—C10'—H10'	125.5
N1—C5—H5C	109.5
O1—C1—C2—C6	6.6 (3)	C2—C3—C4—C4^i	89.51 (11)
C2^i—C1—C2—C6	−171.36 (13)	C1—C2—C6—C7	175.88 (18)
O1—C1—C2—C3	−173.9 (2)	C3—C2—C6—C7	−3.5 (3)
C2^i—C1—C2—C3	8.1 (3)	C2—C6—C7—C8	−21.6 (12)
C5—N1—C3—C2	58.0 (2)	C2—C6—C7—C10	162.7 (7)
C3^i—N1—C3—C2	−69.3 (2)	C6—C7—C8—S1	−178.5 (5)
C5—N1—C3—C4	177.69 (15)	C10—C7—C8—S1	−2.3 (17)
C3^i—N1—C3—C4	50.38 (18)	C7—C8—S1—C9	−0.2 (14)
C6—C2—C3—N1	−148.89 (17)	C8—S1—C9—C10	2.9 (13)
C1—C2—C3—N1	31.7 (2)	S1—C9—C10—C7	−4.8 (15)
C6—C2—C3—C4	98.2 (2)	C8—C7—C10—C9	4.6 (17)
C1—C2—C3—C4	−81.18 (19)	C6—C7—C10—C9	−178.9 (9)
N1—C3—C4—C4^i	−29.76 (11)	C8'—S1'—C9'—C10'	−2 (2)

Symmetry code: (i) −x+2, y, z.