3,3-Dimethyl-cis-9a,13a-diphenyl-2,3,9a,11,12,13a-hexa­hydro-1H-benzo[h][1,4]dioxino[2′,3′:5,6][1,4]dioxino[2,3-f]chromene

Bauer O Bernardes; Aurelio B Buarque Ferreira; James L Wardell; Solange M S V Wardell; José C Netto-Ferreira; Edward R T Tiekink

doi:10.1107/S1600536813023660

. 2013 Aug 31;69(Pt 9):o1487–o1488. doi: 10.1107/S1600536813023660

3,3-Dimethyl-cis-9a,13a-diphenyl-2,3,9a,11,12,13a-hexahydro-1H-benzo[h][1,4]dioxino[2′,3′:5,6][1,4]dioxino[2,3-f]chromene

Bauer O Bernardes ^a,^‡, Aurelio B Buarque Ferreira ^a, James L Wardell ^b,^c,^§, Solange M S V Wardell ^d, José C Netto-Ferreira ^a, Edward R T Tiekink ^e,^*

PMCID: PMC3884479 PMID: 24427106

Abstract

In the title dihydrodioxin, C₃₁H₂₈O₅, the dioxane ring has a chair conformation, whereas each of the pyran and dioxine rings has an envelope conformation with methylene and quaternary C atoms, respectively, being the flap atoms. The phenyl rings are cis and form a dihedral angle of 82.11 (10)°. The molecular structure is stabilized by C—H⋯O contacts. In the crystal packing, supramolecular layers parallel to (101) are sustained by C—H⋯π interactions.

Related literature

For the biological activity of lapachol and its isomers, see: de Almeida (2009 ▶); Ferreira et al. (2010 ▶); Medeiros et al. (2010 ▶); Neves-Pinto et al. (2002 ▶). For reactions of the quinone O atoms in lapachol, see: da Silva et al. (2011 ▶); Ferreira et al. (2006 ▶); Neves-Pinto et al. (2002 ▶). For the preparation of dihydrodioxins, see: Schönberg & Mustafa (1944 ▶), and for their DNA photo-cleavage, see: Mack et al. (2004 ▶). For the synthesis, see: Summerbell & Berger (1959 ▶). For the crystal structure of β-lapachone, see: Cunha-Filho et al. (2006 ▶).

Experimental

Crystal data

C₃₁H₂₈O₅
M _r = 480.53
Monoclinic,
a = 15.1335 (6) Å
b = 9.6048 (2) Å
c = 16.9739 (6) Å
β = 97.384 (1)°
V = 2446.77 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 120 K
0.36 × 0.28 × 0.07 mm

Data collection

Bruker-Nonius Roper CCD camera on a κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.831, T _max = 1.000
23103 measured reflections
5549 independent reflections
3390 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.139
S = 1.02
5549 reflections
355 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) general, I. DOI: 10.1107/S1600536813023660/hg5343sup1.cif

e-69-o1487-sup1.cif^{(26.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813023660/hg5343Isup2.hkl

e-69-o1487-Isup2.hkl^{(266.2KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the C4A,C5,C6,C6A,C10A,C10B benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C18—H18⋯O3	0.95	2.36	3.001 (3)	124
C22—H22⋯O4	0.95	2.32	2.683 (3)	102
C24—H24⋯O4	0.95	2.44	3.071 (2)	124
C8—H8⋯Cg1ⁱ	0.95	2.65	3.3134 (19)	128
C15—H15A⋯Cg1ⁱⁱ	0.99	2.39	3.336 (2)	161

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. BB and JLW thank CAPES (Brazil) for support. Dr Maira Fasciotti, Inmetro (Brazil), is gratefuly acknowledged for the HRMS analysis. Support from the Ministry of Higher Education, Malaysia, High-Impact Research scheme (UM.C/HIR-MOHE/SC/12) is also gratefully acknowledged.

supplementary crystallographic information

1. Comment

Isomeric, lapachol, 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone, β-lapachone, 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione, and α-lapachone, 2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione, Fig. 1, are found in the wood of trees of the genus, Tabebuia (family Bignoniaceae), distributed throughout Central and South America. Since their discovery at the end of the 19th century, lapachol and its isomers have attracted much attention due to their biological activities (de Almeida, 2009; Ferreira et al., 2010). Studies have revealed the effectiveness of these compounds and their derivatives as anti-cancer and anti-neoplastic (de Almeida, 2009), anti-fungal (Medeiros et al., 2010) and anti-Trypanosoma cruzi agents (Neves-Pinto et al., 2002), among other activities.

The quinone O atoms in lapachol and the lapachones are active sites and reactions at these sites have led to various derivatives, including oximes (da Silva et al., 2011), α-diazocarbonyls (Ferreira et al., 2006), phenazines (Neves-Pinto et al., 2002) and as we report here, a dihydrodioxin, (I), which was obtained by photoaddition of β-lapachone to 5,6-diphenyl-2,3-dihydro-1,4-dioxine, Fig. 2. Dihydrodioxins, most readily formed by a photochemical reaction between ortho-quinones and alkenes (Schönberg & Mustafa, 1944), are able to perform efficient DNA photo-cleavage (Mack et al., 2004). The crystal structure of β-lapachone has been reported (Cunha-Filho et al., 2006).

In (I), Fig. 3, the pyran ring approximates an envelope conformation with the C3 atom being the flap atom. The dioxine ring also has an envelope conformation where the C16 atom is the flap. With respect to this ring, the C17- and C23-bound phenyl rings are in axial and equatorial positions, respectively, and make a dihedral angle of 82.11 (10)° with each other. The orientation of these rings is such to facilitate the formation of intramolecular C—H···O interactions, Table 1. Finally, a chair conformation is found for the dioxane ring.

The major feature of the crystal packing is the formation of supramolecular layers parallel to (1 0 1) and sustained by C—H···π interactions, Table 1. These stack with no specific intermolecular interactions between them, Fig. 4.

2. Experimental

β-Lapachone (0.242 g, 1 mmol) was added to a solution of 2,3-diphenyl-1,4-diox-2-ene (0.476 g, 2 mmol) in benzene (20 ml) (Summerbell & Berger, 1959). The solution was deaerated using oxygen-free nitrogen and irradiated using a medium-pressure Hg lamp (500 W; irradiation time = 15 h). The solvent was removed under reduced pressure to leave a residue, to which was added methanol (20 ml). This mixture was filtered under reduced pressure, the colourless solid was collected, and recrystallized from ethanol; M.pt: 482–484 K, yield 69%. Colourless blocks were obtained by slow evaporation of a 1:9 dichloromethane:acetonitrile solution at room temperature. UV (acetonitrile, λ_max. (ε) - nm, L.mol^-1.cm^-1): 212 (3.9x10⁴), 245.5 (3.08x10⁴), 317 (5.8x10³). IR (KBr) (cm^-1): 3065.4, 2972.7, 2935.9, 1646.2, 1586.0, 1495.4, 1450.1, 1413.3, 1389.4, 1326.2, 1264.9, 1240.4, 1180.6, 1160.1, 1105.0, 1068.7, 1042.0, 1018.4, 953.3, 914.2, 854.2, 765.1, 725.9. GC—MS m/z (abundance): 480 (<1%), 238 (11%), 214 (1%), 199 (1%), 181 (1%), 159 (1%), 130 (1%), 105 (100%), 77 (17%), 51 (2%). HRMS: m/z 480.2020 (theoretical 480.2036) ¹H NMR (CDCl₃) δ (p.p.m.): 8.16 (1H, m); 8.12 (1H, m); 7.77–7.68 (4H, m); 7.44 (1H, dt, J = 7.02 and 1.36 Hz); 7.32 (1H, dt, J = 6.20 and 1.36 Hz); 7.24–7.18 (6H, m); 4.34–4.14 (2H, m); 3.96–3.89 (2H, m); 3.02–2.76 (2H, m), 1.87 (2H, J = 6.48 and 1.62 Hz); 1.42 (3H, s); 1.38 (3H, s). ¹³C NMR (CDCl₃) δ (p.p.m.): 17.39; 26.63; 26.82; 32.09; 61.41; 61.78; 74.03; 94.43; 95.10; 106.6; 119.75; 121.54; 123.27; 123.99. 125.57; 127.27; 127.67; 128.52; 134.46. 137.46; 137.79; 144.10.