Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-deca­hydro-3,11b-ep­oxy­azepino[2,1-a]iso­indole-4-carboxyl­ate

Flavien A A Toze; Dmitry S Poplevin; Fedor I Zubkov; Eugeniya V Nikitina; Ciara Porras; Victor N Khrustalev

doi:10.1107/S2056989015016679

. 2015 Sep 12;71(Pt 10):o729–o730. doi: 10.1107/S2056989015016679

Crystal structure of methyl (3RS,4SR,4aRS,11aRS,11bSR)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-decahydro-3,11b-epoxyazepino[2,1-a]isoindole-4-carboxylate

Flavien A A Toze ^a,^*, Dmitry S Poplevin ^b, Fedor I Zubkov ^b, Eugeniya V Nikitina ^b, Ciara Porras ^c, Victor N Khrustalev ^c,^d,^*

PMCID: PMC4647423 PMID: 26594446

Abstract

The title compound, C₁₅H₁₉NO₄, is the a product of the esterification of the corresponding carbonic acid with methanol. The molecule comprises a fused tetracyclic system containing three five-membered rings (2-pyrrolidinone, tetrahydrofuran and dihydrofuran) and one seven-membered ring (azepane). The five-membered rings have the usual envelope conformations, with the quaternary C atom being the flap atom for the 2-pyrrolidinone ring, and the ether O atom being the common flap atom for the remaining rings. The seven-membered azepane ring adopts a chair conformation with the methine and middle methylene C atoms lying above and below the mean plane defined by the remaining five atoms. The carboxylate substituent is rotated by 77.56 (5)° with respect to the base plane of the tetrahydrofuran ring. In the crystal, the molecules are bound by weak C—H⋯O hydrogen-bonding interactions into puckered layers parallel to (001).

Keywords: crystal structure; 3,6a-epoxyisoindoles; azepane; intramolecular cycloaddition; C—H⋯O hydrogen bonds

Related literature

For the synthesis of 2-(furan-2-yl)azepane, see: Asher et al. (1981 ▸); Shono et al. (1981 ▸); Nikolic & Beak (1997 ▸). For intramolecular cycloaddition reactions of α,β-unsaturated acid anhydrides to α-furylamines (IMDAF reactions), see: Vogel et al. (1999 ▸); Zubkov et al. (2005 ▸). For related compounds, see: Zylber et al. (1995 ▸); Evans et al. (1999 ▸); Kachkovskyi & Kolodiazhnyi (2007 ▸); Kharitonov et al. (2009 ▸); Aabid et al. (2010 ▸); Zubkov et al. (2010 ▸, 2011 ▸, 2014 ▸); Toze et al. (2011 ▸); Wang & Li (2012 ▸); Zaytsev, Mikhailova et al. (2012 ▸); Zaytsev, Zubkov et al. 2012 ▸); Zaytsev et al. (2013 ▸); Chen et al. (2013 ▸); Hizartzidis et al. (2014 ▸). graphic file with name e-71-0o729-scheme1.jpg

Experimental

Crystal data

C₁₅H₁₉NO₄
M _r = 277.31
Triclinic,
a = 7.5460 (8) Å
b = 9.6984 (10) Å
c = 10.2894 (10) Å
α = 103.857 (2)°
β = 94.745 (2)°
γ = 106.620 (2)°
V = 691.24 (12) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 290 K
0.30 × 0.25 × 0.25 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2003 ▸) T _min = 0.959, T _max = 0.969
9699 measured reflections
3268 independent reflections
2613 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.141
S = 1.03
3268 reflections
182 parameters
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▸); cell refinement: SAINT (Bruker, 2001 ▸); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: SHELXTL (Sheldrick, 2008 ▸); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015016679/tk5384sup1.cif

e-71-0o729-sup1.cif^{(368.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015016679/tk5384Isup2.hkl

e-71-0o729-Isup2.hkl^{(179.4KB, hkl)}

Click here for additional data file.^{(5.9KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015016679/tk5384Isup3.cml

Click here for additional data file.^{(928.6KB, tif)}

a b a . DOI: 10.1107/S2056989015016679/tk5384fig1.tif

Esterification of 5-oxo-3,4,4a,5,7,8,9,10,11,11a-decahydro-3,11b-epoxyazepino[2,1-a]isoindole-4-carboxylic acid with methanol.

Click here for additional data file.^{(288.1KB, tif)}

. DOI: 10.1107/S2056989015016679/tk5384fig2.tif

Molecular structure of (I). Displacement ellipsoids are shown at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.

Click here for additional data file.^{(777.4KB, tif)}

a . DOI: 10.1107/S2056989015016679/tk5384fig3.tif

Crystal packing of (I) along the a axis demonstrating the H-bonded puckered layers parallel to (001). Dashed lines indicate the weak intermolecular C—H⋯O hydrogen-bonding interactions.

CCDC reference: 1422681

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C1H1O5ⁱ	0.93	2.59	3.4576(19)	156
C3H3O13ⁱⁱ	0.98	2.55	3.5259(19)	174
C4AH4AO14ⁱⁱⁱ	0.98	2.51	3.4190(17)	154
C14H14AO5^iv	0.96	2.56	3.279(2)	132

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

Acknowledgments

Funding from the US National Science Foundation (PREM DMR-0934212 and EPSCoR IIA-1301346) is gratefully acknowledged.

supplementary crystallographic information

S1. Structural commentary

In the last decade our synthetic group has published some effective strategies for the synthesis of 3,6a-epoxyisoindoles annulated with various heterocycles (Zubkov et al. 2010, 2011, 2014; Zaytsev, Mikhailova et al. 2012; Zaytsev, Zubkov et al. 2012; Zaytsev et al. 2013). These strategies were based on the intramolecular cycloaddition reaction of α,β-unsaturated acid anhydrides to the heterocycles containing an α-furfurylamine fragment (IMDAF reaction) (Vogel et al., 1999; Zubkov et al., 2005). Therefore, within the scope of this investigation, the initial carboxylic acid was easily synthesized by the treatment of 2-(2-furyl)perhydroazepine (Asher et al., 1981; Shono et al., 1981; Nikolic et al., 1997) with maleic anhydride.

This work reports the structural characterization of 3,6a-epoxyisoindole annulated with perhydroazepine ring. The esterification of the initial carboxylic acid obtained as fine-crystalline powder is due to its poor solubility in most common organic solvents (Fig. 1).

The molecule of the title compound, C₁₅H₁₉NO₄, (I) comprises a fused tetracyclic system containing three five-membered rings (2-pyrrolidinone, tetrahydrofuran and dihydrofuran) and one seven-membered ring (1,4-diazepine) (Fig. 2). The 2-pyrrolidinone, tetrahydrofuran and dihydrofuran five-membered rings have the usual envelope conformations (Zylber et al., 1995; Evans et al., 1999; Kachkovskyi et al., 2007; Kharitonov et al., 2009; Aabid et al., 2010; Toze et al., 2011; Wang et al., 2012; Chen et al., 2013; Hizartzidis et al., 2014). The seven-membered diazepine ring adopts a chair conformation. The nitrogen N6 atom has the slightly pyramidalized geometry (sum of the bond angles is 359.7 (4)°). The dihedral angle between the basal plane of the diazepine ring (C8—C9/C11—C11A) and the base plane of the pyrrolidinone ring (C4—C5—N6—C11A) is 66.55 (9)°). The carboxylate substituent is rotated by 77.56 (5)° to the base plane of the tetrahydrofuran ring.

The molecule of (I) possesses five asymmetric centers at the C3, C4, C4A, C11A and C11B carbon atoms and can have potentially numerous diastereomers. The crystal of (I) is racemic and consists of enantiomeric pairs with the following relative configuration of the centers: rac-3R*,4S*,4AR*,11AR*,11BS*.

In the crystal, the molecules of (I) are bound by the weak intermolecular C—H···O hydrogen bonding interactions into puckered layers parallel to (001) (Fig. 3, Table 1).

S2. Synthesis and crystallization

A solution of the initial acid – (3R*,4S*,4aR*,11aR*,11bS*)-5-oxo-3,4,4a,5,7,8,9,10,11,11a-decahydro-3,11b-epoxyazepino[2,1-a]isoindole-4-carboxylic acid (0.5 g, 1.8 mmol) in methanol (30 mL) was refluxed for 3 h in the presence of catalytic amount of concentrated H₂SO₄ (monitoring by TLC until disappearance of the starting compound (eluent – EtOAc:hexane (1:3), Sorbfil). Then the solvent was evaporated. The residual oil was passed through a thin layer of aluminum oxide (eluent – chloroform). Chloroform was removed under reduced pressure. The crude ester was recrystallized from a mixture of EtOAc-EtOH to give the target compound I as white crystals. Yield is 0.31 g (58%). Single-crystals were isolated as fine needles by slow re-crystallization from EtOAc-EtOH. M.pt = 388–389 K. IR (KBr), ν/cm^-1: 1741 (C=O), 1693 (C=O). Mass spectrum, EI–MS (70 eV), m/z (I_r(%)): 230 (5), 189 (52), 146 (96), 118 (19), 96 (100), 91 (17), 77 (18), 70 (17), 44 (33), 42 (25), 41 (18). ¹H NMR (CDCl₃, 400 MHz, 300 K): δ = 1.64–1.25 (m, 3H, H9B, H10A, H10B), 2.00–1.92 (m, 4H, H11B, H8A, H8B, H9A), 2.25–2.22 (m, 1H, H11A), 2.71 (d, 1H, H4, J_4,4a = 9.0), 2.86 (d, 1H, H4a, J_4a,4 = 9.0), 3.18–3.14 (m, 1H, H7B), 3.78–3.73 (m, 1H, H11A), 3.79 (s, 3H, CO₂Me), 3.96 (m, 1H, H7A), 5.15 (d, 1H, H3, J_3,2 = 1.7), 6.47 (dd, 1H, H2, J_2,1 = 6.5, J_2,3 = 1.7), 6.53 (d, 1H, H1, J_1,2 = 6.5). ¹³C NMR (CDCl₃, 100 MHz, 300 K): δ = 26.6, 27.6, 29.2, 33.6 (C8, C9, C10, C11), 43.5, 45.4, 49.6, 52.1 (C7, C4A, C13, C4), 59.6 (C11A), 81.2 (C3), 92.1 (C11B), 135.2, 137.4 (C1, C2), 170.5, 172.5 (CO₂Me, NCO).

S3. Refinement

The hydrogen atoms were placed in calculated positions with C—H = 0.93–0.98 Å and refined in the riding model with fixed isotropic displacement parameters [U_iso(H) = 1.5U_eq(C) for CH₃ and U_iso(H) = 1.2U_eq(C) for remaining H].