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

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ISSN: 2414-3146

Spiro­[cyclo­pentane-1,11′-hexa­cyclo[7.6.0.01,6.06,13.08,12.010,14]penta­deca­ne]-7′,15′-dione

aDepartment of Chemistry, Indian Institute of Technology - Bombay, Powai, Mumbai, 400 076, India
*Correspondence e-mail: srk@chem.iitb.ac.in

Edited by I. Brito, University of Antofagasta, Chile (Received 18 September 2018; accepted 9 November 2018; online 27 November 2018)

An unusual rearrangement of spiro cage dione to a tris­homocubane derivatives is reported by acid-catalysed rearrangement with the aid of BF3·OEt2 in benzene (solvent) reflux conditions. Here, the mol­ecular structure of cage mol­ecule C19H22O2 (major product) consists of five-membered rings, which adopt an envelope conformation and six-membered rings adopt a chair or boat conformation. The Cremer & Pople puckering parameters of all four six-membered rings are calculated.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

D3-Trishomocubane and its derivatives are of inter­est for their use as targets for pharmaceutical applications (Liu et al., 2001[Liu, X., Nuwayhid, S., Christie, M. J., Kassiou, M. & Werling, L. L. (2001). Eur. J. Pharmacol. 422, 39-45.]), in medicinal chemistry (Oliver et al., 1991[Oliver, D. W., Dekker, T. G., Snyckers, F. O. & Fourie, T. G. (1991). J. Med. Chem. 34, 851-854.]) as well as in asymmetric catalysis (Levandovsky et al., 2010[Levandovsky, I. A., Sharapa, D. I., Cherenkova, O. A., Gaidai, A. V. & Shubina, T. E. (2010). Russ. Chem. Rev. 79, 1005-1026.]; Sharapa et al., 2012[Sharapa, D. I., Levandovskiy, I. A. & Shubina, T. E. (2012). Curr. Org. Chem. 16, 2632-2660.]). Several amino functionalized D3-tris­homocubane derivatives show significant biological activity and are NMDA receptor antagonists. In addition, some of them exhibit potent anti-TB activity, act as P2X7 receptor antagonists and exhibit anti-Parkinson's activity (Geldenhuys et al., 2005[Geldenhuys, W. J., Malan, S. F., Bloomquist, J. R., Marchand, A. P. & Van der Schyf, C. J. (2005). Med. Res. Rev. 25, 21-48.]).

As part of our major program on cage mol­ecules, which involves the design of unusual polycyclic cage frameworks, for example, D3-tris­homocubanes by the rearrangement approach (Kotha et al., 2018[Kotha, S., Cheekatla, S. R. & Gunta, R. (2018). IUCrData, 3, x180090.]) and we present herein the synthesis of the title cage compound II (Fig. 1[link]), which was prepared (Fig. 2[link]) from cheap and commercially available starting materials such as 1,4-hydro­quinone in eight steps via Claisen rearrangement, Diels–Alder reaction and ring-closing metathesis (RCM) followed by acid-promoted rearrangement with Lewis acid (Kotha & Dipak, 2006[Kotha, S. & Dipak, M. K. (2006). Chem. Eur. J. 12, 4446-4450.]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound II with displacement ellipsoids drawn at the 50% probability level.
[Figure 2]
Figure 2
Lewis acid-promoted rearrangement of the cage dione I.

The mol­ecular structure of II is made up of fused five- and six-membered rings that are joined into a compact cage system. All five-membered rings adopt an envelope conformation, whereas the six-membered rings are in chair or boat conformations. The Cremer & Pople puckering parameters of three six-membered rings, namely, C2–C7, C2/C3/C9/C10/C6/C7 and C3–C6/C10/C9 are Q = 1.110 (2) Å, θ = 89.25 (10)° and φ = 15.37 (12)°; Q = 1.112 (2) Å, θ = 89.98 (10)° and φ = 285.71 (12)°; and Q = 1.114 (2) Å, θ = 90.57 (10)° and φ = 44.48 (12)° respectively. These six-membered rings all exhibit a boat conformation. The other six-membered ring C4/C5/C12–C15 is in a chair conformation with puckering parameters Q = 0.530 (3) Å. θ = 7.1 (3)° and φ = 216 (2)°.

Synthesis and crystallization

Compound II can be prepared via Lewis acid-promoted rearrangement (Fig. 2[link]) of the cage [4.4.2]propellane I with the aid of BF3·OEt2 in the presence of benzene as a solvent. Spiro cage dione I (200 mg, 0.70 mmol) was added to a stirred solution of anhydrous BF3·OEt2 (1 mL) in dry benzene (10 mL) at room temperature. Next, the resulting reaction mixture was refluxed for two days. After completion of the reaction (TLC monitoring), the reaction mixture was quenched with a saturated aqueous NaHCO3 solution and extracted with benzene. The combined organic layers were washed with water and brine solution then dried over anhydrous Na2SO4. After removal of the solvent under vacuum, the resulting crude residue was subjected to silica gel column chromatography by using 5% ethyl acetate in petroleum ether as an eluent to deliver the desired rearranged cage ketone III (57 mg, 23%) containing a phenyl group as a colourless liquid. Continuous elution with 10% ethyl acetate in petroleum ether delivered the rearranged cage dione II (82 mg, 41%) as a colourless crystalline solid. Recrystallization of a column-purified II from a mixture of ethyl acetate and hexane (1:2) solvents gave crystals suitable for X-ray analysis. M.p. 409–411 K. IR (neat, cm−1) 2926, 2857, 1751, 1450, 1294, 1076; 1H NMR (500 MHz, CDCl3 p.p.m.): δ 2.23–2.26 (m, 6H), 1.83 (d, J = 13.5 Hz, 2H), 1.69–1.62 (m, 2H), 1.49–1.42 (m, 10H), 1.15–1.12 (m, 2H); 13C NMR (125 MHz, CDCl3, p.p.m.): δ 213.1, 60.5, 50.6, 48.6, 48.4, 42.8, 32.5, 26.1, 22.2, 21.9; HRMS (ESI, Q-TOF) m/z calculated for C19H22O2 [M + Na] + 305.1512; found: 305.1514.

Melting points were recorded on a Veego VMP–CMP melting point apparatus and are uncorrected. Nuclear Magnetic Resonance (NMR) spectra were recorded on a Bruker (Avance IIITM500) spectrometer operated at 500 MHz for 1H and 125.7 MHz for 13C nuclei.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link].

Table 1
Experimental details

Crystal data
Chemical formula C19H22O2
Mr 282.36
Crystal system, space group Monoclinic, P21/c
Temperature (K) 150
a, b, c (Å) 10.8650 (8), 14.3936 (9), 9.8008 (8)
β (°) 111.680 (9)
V3) 1424.3 (2)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.14 × 0.11 × 0.09
 
Data collection
Diffractometer Rigaku Saturn724+
Absorption correction Multi-scan (CrysAlis PRO; Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.])
Tmin, Tmax 0.740, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 4407, 2470, 1877
Rint 0.050
(sin θ/λ)max−1) 0.594
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.052, 0.140, 1.05
No. of reflections 2470
No. of parameters 190
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.25, −0.28
Computer programs: CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and 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.]).

Structural data


Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Spiro[cyclopentane-1,11'-hexacyclo[7.6.0.01,6.06,13.08,12.010,14]pentadecane]-7',15'-dione top
Crystal data top
C19H22O2Dx = 1.317 Mg m3
Mr = 282.36Melting point = 409–411 K
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 10.8650 (8) ÅCell parameters from 2620 reflections
b = 14.3936 (9) Åθ = 2.5–31.0°
c = 9.8008 (8) ŵ = 0.08 mm1
β = 111.680 (9)°T = 150 K
V = 1424.3 (2) Å3Block, colourless
Z = 40.14 × 0.11 × 0.09 mm
F(000) = 608
Data collection top
Rigaku Saturn724+
diffractometer
2470 independent reflections
Radiation source: fine-focus sealed X-ray tube1877 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.050
ω scansθmax = 25.0°, θmin = 2.7°
Absorption correction: multi-scan
(CrysAlisPro; Rigaku OD, 2018)
h = 128
Tmin = 0.740, Tmax = 1.000k = 1117
4407 measured reflectionsl = 1011
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.140 w = 1/[σ2(Fo2) + (0.0668P)2 + 0.4068P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2470 reflectionsΔρmax = 0.25 e Å3
190 parametersΔρmin = 0.28 e Å3
0 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. All H atoms were placed in geometrically calculated positions and refined using a riding model with C–H distances of 1.00 Å for all H atoms bound to tertiary C(sp3) atoms and 0.99 Å for H atoms bound to secondary C(sp3) atoms. Isotropic displacement parameters for H atoms were calculated as Uiso(H) = 1.2Ueq(C).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.66123 (15)0.57866 (10)0.78083 (19)0.0336 (4)
O20.67492 (16)0.18936 (11)0.86490 (19)0.0361 (5)
C10.6053 (2)0.50462 (15)0.7681 (2)0.0228 (5)
C20.4704 (2)0.48099 (15)0.7682 (2)0.0236 (5)
H20.4201160.5320320.7935680.028*
C30.4940 (2)0.39008 (14)0.8618 (3)0.0250 (5)
H30.4813130.3974900.9572030.030*
C40.6387 (2)0.35801 (14)0.8782 (2)0.0252 (5)
C50.6500 (2)0.40821 (14)0.7433 (2)0.0217 (5)
C60.5219 (2)0.36927 (14)0.6173 (2)0.0218 (5)
H60.5311070.3618610.5201020.026*
C70.4066 (2)0.43687 (14)0.6154 (2)0.0224 (5)
H70.3759030.4816310.5314430.027*
C80.2984 (2)0.37374 (15)0.6313 (3)0.0254 (5)
C90.3986 (2)0.31667 (15)0.7546 (2)0.0269 (6)
H90.3593050.2699250.8022990.032*
C100.4915 (2)0.27694 (14)0.6830 (3)0.0251 (5)
H100.4572450.2237420.6136110.030*
C110.6139 (2)0.25960 (15)0.8169 (2)0.0259 (5)
C120.7534 (2)0.37557 (16)1.0209 (3)0.0313 (6)
H12A0.7470010.3331891.0976010.038*
H12B0.7491620.4402251.0534100.038*
C130.8851 (2)0.35997 (18)1.0017 (3)0.0364 (6)
H13A0.9587310.3763791.0940510.044*
H13B0.8938590.2933520.9817740.044*
C140.8961 (2)0.41781 (17)0.8765 (3)0.0335 (6)
H14A0.9820370.4046820.8669800.040*
H14B0.8943830.4845670.9000560.040*
C150.7839 (2)0.39734 (16)0.7303 (3)0.0273 (5)
H15A0.7900350.4403860.6543100.033*
H15B0.7931400.3331310.6991640.033*
C160.2179 (2)0.31748 (16)0.4922 (3)0.0308 (6)
H16A0.2550170.3260490.4147840.037*
H16B0.2193470.2504480.5154390.037*
C170.0770 (2)0.35547 (18)0.4420 (3)0.0346 (6)
H17A0.0668010.4116730.3805290.041*
H17B0.0115470.3082450.3859710.041*
C180.0616 (2)0.37849 (18)0.5865 (3)0.0366 (6)
H18A0.0484150.3215210.6360870.044*
H18B0.0138080.4211800.5710850.044*
C190.1933 (2)0.42530 (17)0.6750 (3)0.0320 (6)
H19A0.2132100.4191460.7816670.038*
H19B0.1907430.4921090.6501380.038*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0352 (10)0.0194 (9)0.0443 (11)0.0054 (7)0.0125 (8)0.0020 (7)
O20.0463 (10)0.0204 (9)0.0435 (11)0.0061 (8)0.0188 (8)0.0057 (8)
C10.0275 (12)0.0199 (12)0.0184 (12)0.0011 (9)0.0057 (9)0.0006 (9)
C20.0281 (12)0.0189 (11)0.0262 (12)0.0020 (9)0.0127 (10)0.0013 (9)
C30.0349 (13)0.0208 (11)0.0242 (12)0.0009 (9)0.0168 (10)0.0018 (9)
C40.0339 (13)0.0193 (11)0.0246 (13)0.0014 (9)0.0132 (10)0.0019 (9)
C50.0245 (12)0.0215 (11)0.0194 (12)0.0000 (9)0.0083 (9)0.0006 (9)
C60.0246 (11)0.0214 (11)0.0209 (12)0.0015 (9)0.0102 (10)0.0010 (9)
C70.0223 (11)0.0219 (11)0.0242 (12)0.0001 (9)0.0100 (9)0.0006 (9)
C80.0256 (12)0.0253 (12)0.0294 (13)0.0034 (9)0.0150 (10)0.0055 (10)
C90.0336 (13)0.0234 (12)0.0309 (14)0.0071 (10)0.0203 (11)0.0031 (10)
C100.0304 (12)0.0187 (11)0.0297 (13)0.0029 (9)0.0154 (10)0.0031 (9)
C110.0358 (13)0.0186 (12)0.0283 (13)0.0004 (10)0.0177 (11)0.0033 (10)
C120.0409 (14)0.0274 (12)0.0225 (13)0.0024 (10)0.0082 (11)0.0015 (10)
C130.0333 (13)0.0368 (14)0.0301 (15)0.0059 (11)0.0012 (11)0.0015 (11)
C140.0246 (13)0.0370 (14)0.0339 (14)0.0003 (10)0.0051 (11)0.0046 (11)
C150.0262 (12)0.0287 (12)0.0278 (13)0.0004 (10)0.0108 (10)0.0001 (10)
C160.0291 (13)0.0308 (13)0.0360 (14)0.0068 (10)0.0161 (11)0.0080 (11)
C170.0302 (13)0.0396 (14)0.0362 (15)0.0073 (11)0.0150 (11)0.0056 (11)
C180.0279 (13)0.0429 (15)0.0438 (16)0.0055 (11)0.0190 (12)0.0070 (12)
C190.0297 (13)0.0350 (13)0.0364 (15)0.0006 (10)0.0181 (11)0.0052 (11)
Geometric parameters (Å, º) top
O1—C11.210 (3)C12—H12A0.9900
O2—C111.205 (3)C12—H12B0.9900
C1—C21.505 (3)C12—C131.528 (3)
C1—C51.519 (3)C13—H13A0.9900
C2—H21.0000C13—H13B0.9900
C2—C31.564 (3)C14—C131.523 (3)
C2—C71.536 (3)C14—H14A0.9900
C3—H31.0000C14—H14B0.9900
C3—C41.589 (3)C15—C51.514 (3)
C3—C91.578 (3)C15—C141.528 (3)
C4—C121.512 (3)C15—H15A0.9900
C5—C41.550 (3)C15—H15B0.9900
C5—C61.583 (3)C16—H16A0.9900
C6—H61.0000C16—H16B0.9900
C6—C71.580 (3)C16—C171.527 (3)
C6—C101.564 (3)C17—H17A0.9900
C7—H71.0000C17—H17B0.9900
C7—C81.538 (3)C18—C171.523 (3)
C8—C91.532 (3)C18—H18A0.9900
C8—C161.548 (3)C18—H18B0.9900
C9—H91.0000C19—C81.550 (3)
C10—C91.538 (3)C19—C181.528 (3)
C10—H101.0000C19—H19A0.9900
C11—C41.523 (3)C19—H19B0.9900
C11—C101.505 (3)
O1—C1—C2130.6 (2)C11—C10—C6104.29 (17)
O1—C1—C5130.0 (2)C11—C10—C9100.46 (18)
C2—C1—C599.37 (17)C11—C10—H10116.9
C1—C2—H2117.1O2—C11—C4129.4 (2)
C1—C2—C3103.90 (17)O2—C11—C10131.4 (2)
C1—C2—C7100.46 (17)C10—C11—C499.23 (17)
C3—C2—H2117.1C4—C12—H12A109.5
C7—C2—H2117.1C4—C12—H12B109.5
C7—C2—C398.24 (16)C4—C12—C13110.5 (2)
C2—C3—H3114.2H12A—C12—H12B108.1
C2—C3—C4104.15 (16)C13—C12—H12A109.5
C2—C3—C9104.15 (18)C13—C12—H12B109.5
C4—C3—H3114.2C12—C13—H13A109.2
C9—C3—H3114.2C12—C13—H13B109.2
C9—C3—C4104.79 (17)H13A—C13—H13B107.9
C5—C4—C399.51 (16)C14—C13—C12112.02 (19)
C11—C4—C3101.89 (17)C14—C13—H13A109.2
C11—C4—C598.93 (17)C14—C13—H13B109.2
C12—C4—C3119.41 (19)C13—C14—H14A109.2
C12—C4—C5114.43 (18)C13—C14—H14B109.2
C12—C4—C11119.06 (18)C13—C14—C15112.13 (19)
C1—C5—C499.11 (17)H14A—C14—H14B107.9
C1—C5—C6101.95 (16)C15—C14—H14A109.2
C4—C5—C6100.16 (16)C15—C14—H14B109.2
C15—C5—C1118.81 (18)C5—C15—C14111.09 (19)
C15—C5—C4113.84 (18)C5—C15—H15A109.4
C15—C5—C6119.54 (18)C5—C15—H15B109.4
C5—C6—H6114.3C14—C15—H15A109.4
C7—C6—C5104.84 (16)C14—C15—H15B109.4
C7—C6—H6114.3H15A—C15—H15B108.0
C10—C6—C5103.79 (17)C8—C16—H16A110.6
C10—C6—H6114.3C8—C16—H16B110.6
C10—C6—C7103.97 (16)H16A—C16—H16B108.7
C2—C7—C699.94 (16)C17—C16—C8105.67 (18)
C2—C7—H7115.4C17—C16—H16A110.6
C2—C7—C8103.39 (17)C17—C16—H16B110.6
C6—C7—H7115.4C16—C17—H17A111.2
C8—C7—C6105.47 (16)C16—C17—H17B111.2
C8—C7—H7115.4H17A—C17—H17B109.1
C7—C8—C16115.11 (18)C18—C17—C16102.7 (2)
C7—C8—C19114.46 (18)C18—C17—H17A111.2
C9—C8—C792.90 (17)C18—C17—H17B111.2
C9—C8—C16114.81 (19)C17—C18—H18A111.2
C9—C8—C19114.79 (19)C17—C18—H18B111.2
C16—C8—C19105.03 (18)C17—C18—C19102.85 (19)
C3—C9—H9115.4H18A—C18—H18B109.1
C8—C9—C3105.47 (18)C19—C18—H18A111.2
C8—C9—H9115.4C19—C18—H18B111.2
C8—C9—C10103.50 (18)C8—C19—H19A110.7
C10—C9—C399.90 (17)C8—C19—H19B110.7
C10—C9—H9115.4C18—C19—C8105.26 (19)
C6—C10—H10116.9C18—C19—H19A110.7
C9—C10—C698.38 (16)C18—C19—H19B110.7
C9—C10—H10116.9H19A—C19—H19B108.8
 

Funding information

We thank the Defence Research and Development Organization (DRDO, No. ARDB/01/1041849/M/1), New Delhi, for financial assistance. SK thanks the Department of Science and Technology (DST, No. SR/S2/JCB-33/2010) for the award of a J. C. Bose fellowship and Praj industries for the Pramod Chaudhari Chair Professorship (Green Chemistry). RG thanks Indian Institute of Technology (IIT) - Bombay, Mumbai for financial support as an Institute Research Associate (RA) and SRC thanks the University Grants Commission (UGC), New Delhi, for the award of a research fellowship.

References

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First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar

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