Crystal structures of the two epimers from the unusual thermal C6-epimerization of 5-oxo-1,2,3,5,5a,6,7,9b-octa-hydro-7,9a-ep-oxy-pyrrolo-[2,1-a]iso-indole-6-carb-oxy-lic acid, 5a(RS),6(SR),7(RS),9a(SR),9b(SR) and 5a(RS),6(RS),7(RS),9a(SR),9b(SR).

The isomeric title compounds, C12H13NO4 (Ia) and C12H13NO4 (IIa), the products of an usual thermal C6-epimerization of 5-oxo-1,2,3,5,5a,6,7,9b-octa-hydro-7,9a-ep-oxy-pyrrolo-[2,1-a]iso-indole-6-carb-oxy-lic acid, represent the two different diastereomers and have very similar mol-ecular geometries. The mol-ecules of both compounds comprise a fused tetra-cyclic system containing four five-membered rings (pyrrolidine, pyrrolidinone, di-hydro-furan and tetra-hydro-furan), all of which adopt the usual envelope conformations. The dihedral angle between the basal planes of the pyrrolidine and pyrrolidinone rings are 14.3 (2) and 16.50 (11)°, respectively, for (Ia) and (IIa). The nitro-gen atom has a slightly pyramidalized geometry [bond-angle sum = 355.9 and 355.3°, for (Ia) and (IIa)], respectively. In the crystal of (Ia), mol-ecules form zigzag-like hydrogen-bonded chains along [010] through strong O-H⋯O hydrogen bonds and are further linked by weak C-H⋯O hydrogen bonds into complex two-tier layers parallel to (100). Unlike (Ia), the crystal of (IIa) contains centrosymmetric cyclic hydrogen-bonded dimers [graph set R22(14)], formed through strong O-H⋯O hydrogen bonds and are further linked by weak C-H⋯O hydrogen bonds into ribbons extending across [101].

Chemical context

The intra­molecular Diels–Alder furan (IMDAF) reaction between α,β-unsaturated acid anhydrides and hydrogenated heterocycles, containing a furfuryl­amine moiety, has been studied for a long time (see, for example, Parker & Adamchuk, 1978 ▸; Blokzijl et al., 1991 ▸; Varlamov et al., 2006 ▸; Groenendaal et al., 2008 ▸; Nakamura et al., 2011 ▸; Zubkov et al., 2011 ▸, 2012 ▸, 2014 ▸; Toze et al., 2015 ▸) and used for diastereospecific synthesis of diverse fused-ring systems. It is arguable that the pathway with a simultaneous controlled formation of four or five new stereogenic centers is the best approach to ep­oxy­iso­indoles and affords target adducts under mild conditions with satisfactory yields. However, the simplest 2-furyl aza­heterocycles (azetidine, pyrrolidine, piperidine, perhydro­azepine) have not yet been studied in this reaction. One of the goals of our work is to fill the gap. Here we report on the utilization of 2-furyl pyrrolidine as an initial reagent in the IMDAF reaction.

The inter­action between 2-furyl pyrrolidine and maleic anhydride at room temperature leads to the mixture of cyclic (Ia) and open-chain (Ib) tautomers, the crystallization of which results in the cyclic form (Ia) only (Fig. 1 ▸). In contrast, the same reaction at 413 K leads to the maleic amide fragment isomerization and affords a mixture of the adduct (IIa) and the amide (IIb) (Fig. 2 ▸). Similarly, the mixture crystallization gives rise the cyclic tautomer (IIa) only. The crystal structures of both (Ia) and (IIa) using synchrotron X-ray diffraction data have been determined and are reported herein.

Figure 1

Reaction of 2-furyl pyrrolidine and maleic anhydride at room temperature.

Figure 2

Reaction of 2-furyl pyrrolidine and maleic anhydride at 413 K.

Structural commentary

Compounds (Ia) and (IIa) represent two different diastereo­mers of 5-oxo-1,2,3,5,5a,6,7,9b-octa­hydro-7,9a-ep­oxy­pyrrolo[2,1-a]iso­indole-6-carb­oxy­lic acid and have very similar mol­ecular geometries (Figs. 3 ▸, 4 ▸). The mol­ecules of (Ia) and (IIa) each comprise a fused tetra­cyclic system containing four five-membered rings (pyrrolidine, pyrrolidinone, di­hydro­furan and tetra­hydro­furan), all of which adopt the usual envelope conformations. The dihedral angles between the basal planes of the pyrrolidine and pyrrolidinone rings are 14.3 (2) and 16.50 (11)°, respectively, for (Ia) and (IIa). The nitro­gen N4 atom has a slightly pyramidalized geometry [sum of the bond angles = 355.9 and 355.3°, respectively, for (Ia) and (IIa)]. The bond lengths and angles in both epimers are in good agreement with those observed in a related structure (Lu et al., 2013 ▸).

Figure 3

Mol­ecular structure and atom-numbering scheme for epimer (Ia). Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.

Figure 4

Mol­ecular structure and atom-numbering scheme for epimer (IIa). Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.

The mol­ecules possess five asymmetric centers at the C5, C6, C7, C9a and C9b carbon atoms. The crystals of (Ia) and (IIa) are racemic and consist of enanti­omeric pairs with the following relative configurations of the centers: 5a(RS),6(SR),7(RS),9a(SR),9b(SR) and 5a(RS),6(RS),7(RS),9a(SR),9b(SR)

Supra­molecular features

Although the similarity of the mol­ecular geometries might lead to similar packing motifs, this is not found in the case of (Ia) and (IIa). The inter­molecular inter­actions, namely strong O—H⋯O and weak C—H⋯O hydrogen bonding, combined in a different way, give rise to different packing networks. In the crystal of (Ia), mol­ecules form zigzag-like hydrogen-bonded chains extending along [010] through strong O12—H12⋯O5i hydrogen bonds, which are further linked by weak C5A—H5A⋯O12ii hydrogen bonds into complex two-tier layers lying parallel to (100) (Table 1 ▸, Fig. 5 ▸).

Table 1

Hydrogen-bond geometry (Å, °) for (Ia)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O12—H12⋯O5i	0.90 (3)	1.75 (3)	2.613 (2)	157 (3)
C5A—H5A⋯O12ii	1.00	2.51	3.234 (3)	129

Symmetry codes: (i) ; (ii) .

Figure 5

Crystal structure of (Ia) showing the two-tier layers parallel to (100). Dashed lines indicate the inter­molecular O—H⋯O and C—H⋯O hydrogen bonds.

However, unlike (Ia), the crystal of (IIa) contains centrosymmetric hydrogen-bonded cyclic dimers [graph set (14), formed through two strong O12—H12⋯O5i hydrogen bonds (Table 2 ▸, Fig. 6 ▸). The dimers are further linked by weak C9—H9⋯O11ii hydrogen bonds into ribbons extending across [101] (Table 2 ▸, Figs. 6 ▸ and 7 ▸).

Table 2

Hydrogen-bond geometry (Å, °) for (IIa)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O12—H12⋯O5i	0.92	1.70	2.607 (2)	165
C9—H9⋯O11ii	0.95	2.42	3.362 (3)	172

Symmetry codes: (i) ; (ii) .

Figure 6

The hydrogen-bonded chains of (IIa). Dashed lines indicate the inter­molecular O—H⋯O and C—H⋯O hydrogen bonds.

Figure 7

Crystal structure of (IIa) along [101]. Dashed lines indicate the inter­molecular O—H⋯O and C—H⋯O hydrogen bonds.

Synthesis and crystallization

The initial 2-furyl pyrrolidine was synthesized according to the procedure described previously (Acher et al., 1981 ▸; Shono et al., 1981 ▸; Nikolic & Beak, 1997 ▸).

Synthesis of (I ). A mixture of the initial 2-furyl pyrrolidine (0.30 g, 2.2 mmol) and maleic anhydride (0.23 g, 2.3 mmol) in di­chloro­methane (6 mL) was stirred for 5 h at r.t. [monitoring by TLC until disappearance of the starting compound spot, eluent–EtOAc: hexane (1:3), Sorbfil]. On completion of the reaction, the solvent was evaporated. The isomer (Ia) was isolated as fine needles by slow recrystallization of the residue from a mixture of EtOAc–EtOH. Yield 39%: m.p. = 413–414 K. IR (KBr), ν (cm−1): 1734, 1654. 1H NMR (CDCl3, 400 MHz, 300 K): δ = 1.98–1.69 (m, 4H, H1a, H1b, H2a, H2b), 2.42 (d, 1H, H6, J 6,5a = 9.1), 2.94–2.88 (m, 2H, H3a, H3b), 3.10 (d, 1H, H5a, J 5a,6 = 9.1), 4.41 (t, 1H, H9b, J 9b,1a = 7.5, J 9b,1 b = 7.5), 4.97 (d, 1H, H7, J 7,8 = 1.6), 6.44 (dd, 1H, H8, J 8,9 = 5.5, J 8,7 = 1.6), 6.54 (d, 1H, H9, J 9,8 = 5.5). 13C NMR (CDCl3, 100 MHz, 300 K): δ = 23.5, 26.2, 41.9 (C1, C2, C3), 46.9, 53.8 (C6, C5a), 60.0 (C9b), 80.5 (C7), 93.5 (C9a), 133.9 (C9), 137.1 (C8), 171.7, 173.2 (NCO, COOH). EI–MS (70 eV), m/z (rel. intensity): 235 (22), 217 (91), 137 (41), 136 (100), 108 (39), 80 (45), 70 (32), 54 (38), 45 (29), 42 (25).

Synthesis of (II ). A mixture of the initial 2-furyl pyrrolidine (0.3 g, 2.2 mmol) and maleic anhydride (0.23 g, 2.3 mmol) in o-xylene (6 mL) was heated at reflux for 3 h. At the end of the reaction, the solvent was evaporated. The isomer (IIa) was isolated as fine needles by slow recrystallization of the residue from a mixture of EtOAc–EtOH. Yield: 0.33 45%; m.p. = 414–416 K. IR (KBr), ν (cm−1): 1738, 1658. 1H NMR (CDCl3, 400 MHz, 300 K): δ = 1.82–1.64 (m, 4H, H1a, H1b, H2a, H2b), 3.02 (d, 1H, H5a, J 5a,6 = 3.4), 3.17 (dd, 1H, H6, J 6,5a = 3.4, J 6,5a = 3.4), 3.36–3.32 (m, 2H, H3a, H3b), 4.52 (t, 1H, H9b, J 9b,1a = 7.6, J 9b,1b = 7.6), 5.20 (dd, 1H, H7, J 7,8 = 1.6, J 7,6 = 4.8), 6.34 (dd, 1H, H8, J 8,9 = 5.8, J 8,7 = 1.6), 6.66 (d, 1H, H9, J 9,8 = 5.8). 13C NMR (CDCl3, 100 MHz, 300 K): δ = 23.5, 26.2, 42.1 (C1, C2, C3), 47.0, 55.1 (C6, C5a), 61.0 (C9b), 79.2 (C7), 93.5 (C9a), 133.9 (C8), 135.2 (C9), 171.7, 173.2 (NCO, COOH). EI–MS (70 eV), m/z (rel. intensity): 235 (22), 217 (91), 137 (41), 136 (100), 108 (39), 80 (45), 70 (32), 54 (38), 45 (29), 42 (25).

Refinement

Crystal data, data collection and refinement details are summarized in Table 3 ▸. X-ray diffraction studies were carried out on the ‘Belok’ beamline (λ = 0.96990 Å) of the National Research Center "Kurchatov Institute" (Moscow, Russian Federation) using a MAR CCD detector.

Table 3

Experimental details

	(Ia)	(IIa)
Crystal data
Chemical formula	C12H13NO4	C12H13NO4
M r	235.23	235.23
Crystal system, space group	Monoclinic, P21/c	Triclinic, P
Temperature (K)	100	100
a, b, c (Å)	11.045 (2), 9.2023 (18), 11.062 (2)	8.4700 (17), 8.5100 (17), 8.5900 (17)
α, β, γ (°)	90, 100.91 (3), 90	94.04 (3), 111.12 (3), 105.17 (3)
V (Å3)	1104.1 (4)	548.0 (2)
Z	4	2
Radiation type	Synchrotron, λ = 0.96990 Å	Synchrotron, λ = 0.96990 Å
μ (mm−1)	0.23	0.23
Crystal size (mm)	0.20 × 0.15 × 0.15	0.15 × 0.10 × 0.10
Data collection
Diffractometer	MAR CCD	MAR CCD
Absorption correction	Multi-scan (SCALA; Evans, 2006 ▸)	Multi-scan (SCALA; Evans, 2006 ▸)
T min, T max	0.950, 0.960	0.960, 0.969
No. of measured, independent and observed [I > 2σ(I)] reflections	12183, 2329, 1864	7090, 2104, 1402
R int	0.085	0.061
(sin θ/λ)max (Å−1)	0.641	0.637
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.072, 0.189, 1.02	0.099, 0.240, 0.93
No. of reflections	2329	2104
No. of parameters	158	155
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.43, −0.43	0.45, −0.36

Computer programs: Automar (MarXperts, 2015 ▸), i MOSFLM (Battye et al., 2011 ▸), SHELXS97 and SHELXTL (Sheldrick, 2008 ▸) and SHELXL2014 (Sheldrick, 2015 ▸).

The hydrogen atoms of the hydroxyl groups were localized in the difference-Fourier maps and refined in an isotropic approximation with fixed displacement parameters [U iso(H) = 1.5U eq(O)] [for (Ia)] or included in the refinement with fixed positional (riding model) and isotropic displacement parameters [U iso(H) = 1.5U eq(O)] [for (IIa)]. Other hydrogen atoms were placed in calculated positions with C—H = 0.95–1.00 Å and refined in the riding model with fixed isotropic displacement parameters [U iso(H) = 1.2U eq(C)].

The insufficient data completeness of 94.1% in the case of (IIa) is the result of the low (triclinic) crystal symmetry, making it very difficult to obtain good data completeness using the φ scan mode only (‘Belok’ beamline limitation), even though we have used the two different crystal orientations.

Crystal structure: contains datablock(s) global, Ia, IIa. DOI: 10.1107/S2056989016014420/zs2368sup1.cif

Structure factors: contains datablock(s) Ia. DOI: 10.1107/S2056989016014420/zs2368Iasup2.hkl

Structure factors: contains datablock(s) IIa. DOI: 10.1107/S2056989016014420/zs2368IIasup3.hkl

CCDC references: 1503860, 1503859

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

C12H13NO4	Dx = 1.415 Mg m−3
Mr = 235.23	Melting point = 413–414 K
Monoclinic, P21/c	Synchrotron radiation, λ = 0.96990 Å
a = 11.045 (2) Å	Cell parameters from 600 reflections
b = 9.2023 (18) Å	θ = 4.5–38.0°
c = 11.062 (2) Å	µ = 0.23 mm−1
β = 100.91 (3)°	T = 100 K
V = 1104.1 (4) Å3	Prism, colourless
Z = 4	0.20 × 0.15 × 0.15 mm
F(000) = 496

MAR CCD diffractometer	1864 reflections with I > 2σ(I)
φ scan	Rint = 0.085
Absorption correction: multi-scan (SCALA; Evans, 2006)	θmax = 38.5°, θmin = 4.5°
Tmin = 0.950, Tmax = 0.960	h = −13→14
12183 measured reflections	k = −11→10
2329 independent reflections	l = −13→13

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.072	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.189	w = 1/[σ2(Fo2) + (0.08P)2 + 1.P] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max < 0.001
2329 reflections	Δρmax = 0.43 e Å−3
158 parameters	Δρmin = −0.43 e Å−3
0 restraints	Extinction correction: SHELXL-2014/7 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: difference Fourier map	Extinction coefficient: 0.104 (9)

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.

	x	y	z	Uiso*/Ueq
C1	0.8345 (2)	0.9330 (3)	0.5467 (2)	0.0330 (6)
H1A	0.8888	0.8929	0.4933	0.040*
H1B	0.8859	0.9780	0.6202	0.040*
C2	0.7415 (2)	1.0430 (3)	0.4762 (2)	0.0349 (6)
H2A	0.7799	1.1002	0.4177	0.042*
H2B	0.7123	1.1106	0.5341	0.042*
C3	0.6333 (2)	0.9507 (3)	0.4064 (2)	0.0312 (6)
H3A	0.5531	0.9989	0.4059	0.037*
H3B	0.6426	0.9320	0.3205	0.037*
N4	0.64418 (17)	0.8166 (2)	0.47832 (17)	0.0272 (5)
C5	0.60154 (19)	0.6839 (2)	0.4418 (2)	0.0253 (5)
O5	0.52224 (14)	0.65677 (18)	0.34888 (14)	0.0280 (5)
C5A	0.66529 (19)	0.5736 (2)	0.53586 (19)	0.0236 (5)
H5A	0.6166	0.5553	0.6019	0.028*
C6	0.7153 (2)	0.4306 (2)	0.4908 (2)	0.0254 (5)
H6	0.7007	0.3500	0.5470	0.030*
C7	0.8561 (2)	0.4655 (3)	0.5143 (2)	0.0296 (6)
H7	0.9050	0.4068	0.4645	0.035*
C8	0.9021 (2)	0.4591 (3)	0.6528 (2)	0.0330 (6)
H8	0.9504	0.3847	0.6980	0.040*
C9	0.8604 (2)	0.5799 (3)	0.6976 (2)	0.0302 (6)
H9	0.8737	0.6103	0.7812	0.036*
C9A	0.7874 (2)	0.6583 (2)	0.5868 (2)	0.0251 (5)
C9B	0.7500 (2)	0.8164 (3)	0.5827 (2)	0.0291 (6)
H9B	0.7224	0.8442	0.6606	0.035*
O10	0.85603 (14)	0.62038 (18)	0.49215 (14)	0.0276 (4)
C11	0.6649 (2)	0.3852 (2)	0.3585 (2)	0.0251 (5)
O11	0.71540 (16)	0.4123 (2)	0.27256 (16)	0.0374 (5)
O12	0.56401 (14)	0.30469 (18)	0.35042 (15)	0.0265 (4)
H12	0.539 (3)	0.275 (3)	0.272 (3)	0.040*

	U11	U22	U33	U12	U13	U23
C1	0.0350 (13)	0.0293 (13)	0.0289 (12)	−0.0063 (9)	−0.0086 (10)	−0.0015 (9)
C2	0.0433 (15)	0.0252 (13)	0.0318 (14)	−0.0031 (10)	−0.0039 (11)	0.0009 (9)
C3	0.0333 (13)	0.0261 (13)	0.0304 (13)	0.0025 (9)	−0.0033 (10)	0.0043 (9)
N4	0.0257 (10)	0.0236 (11)	0.0278 (10)	0.0004 (7)	−0.0064 (8)	0.0017 (7)
C5	0.0192 (10)	0.0290 (12)	0.0246 (11)	−0.0003 (8)	−0.0036 (8)	0.0016 (8)
O5	0.0233 (8)	0.0293 (9)	0.0259 (9)	−0.0010 (6)	−0.0098 (6)	0.0025 (6)
C5A	0.0190 (10)	0.0270 (12)	0.0214 (11)	−0.0001 (8)	−0.0052 (8)	0.0018 (8)
C6	0.0229 (11)	0.0254 (12)	0.0235 (11)	−0.0011 (8)	−0.0066 (8)	0.0011 (8)
C7	0.0215 (11)	0.0309 (13)	0.0314 (13)	0.0017 (9)	−0.0075 (9)	−0.0039 (9)
C8	0.0252 (11)	0.0324 (13)	0.0334 (14)	0.0030 (9)	−0.0148 (9)	0.0008 (9)
C9	0.0268 (12)	0.0341 (14)	0.0237 (12)	−0.0021 (9)	−0.0102 (9)	0.0011 (9)
C9A	0.0231 (11)	0.0260 (12)	0.0226 (11)	−0.0001 (8)	−0.0045 (8)	−0.0008 (8)
C9B	0.0269 (12)	0.0323 (14)	0.0236 (11)	0.0001 (9)	−0.0066 (9)	−0.0003 (9)
O10	0.0222 (8)	0.0303 (9)	0.0276 (9)	−0.0023 (6)	−0.0023 (6)	−0.0015 (7)
C11	0.0221 (11)	0.0246 (12)	0.0254 (12)	0.0003 (8)	−0.0036 (8)	0.0000 (8)
O11	0.0352 (10)	0.0471 (12)	0.0276 (10)	−0.0085 (8)	0.0004 (7)	−0.0016 (7)
O12	0.0205 (8)	0.0301 (9)	0.0251 (9)	−0.0027 (6)	−0.0053 (6)	−0.0030 (6)

C1—C9B	1.524 (4)	C6—C11	1.522 (3)
C1—C2	1.544 (3)	C6—C7	1.561 (3)
C1—H1A	0.9900	C6—H6	1.0000
C1—H1B	0.9900	C7—O10	1.446 (3)
C2—C3	1.548 (3)	C7—C8	1.522 (3)
C2—H2A	0.9900	C7—H7	1.0000
C2—H2B	0.9900	C8—C9	1.334 (4)
C3—N4	1.461 (3)	C8—H8	0.9500
C3—H3A	0.9900	C9—C9A	1.516 (3)
C3—H3B	0.9900	C9—H9	0.9500
N4—C5	1.343 (3)	C9A—O10	1.447 (3)
N4—C9B	1.480 (3)	C9A—C9B	1.511 (3)
C5—O5	1.243 (3)	C9B—H9B	1.0000
C5—C5A	1.527 (3)	C11—O11	1.216 (3)
C5A—C6	1.546 (3)	C11—O12	1.327 (3)
C5A—C9A	1.568 (3)	O12—H12	0.90 (3)
C5A—H5A	1.0000
C9B—C1—C2	102.2 (2)	C11—C6—H6	108.8
C9B—C1—H1A	111.3	C5A—C6—H6	108.8
C2—C1—H1A	111.3	C7—C6—H6	108.8
C9B—C1—H1B	111.3	O10—C7—C8	101.44 (18)
C2—C1—H1B	111.3	O10—C7—C6	101.91 (17)
H1A—C1—H1B	109.2	C8—C7—C6	107.0 (2)
C1—C2—C3	105.63 (19)	O10—C7—H7	115.0
C1—C2—H2A	110.6	C8—C7—H7	115.0
C3—C2—H2A	110.6	C6—C7—H7	115.0
C1—C2—H2B	110.6	C9—C8—C7	105.6 (2)
C3—C2—H2B	110.6	C9—C8—H8	127.2
H2A—C2—H2B	108.7	C7—C8—H8	127.2
N4—C3—C2	102.45 (18)	C8—C9—C9A	105.3 (2)
N4—C3—H3A	111.3	C8—C9—H9	127.3
C2—C3—H3A	111.3	C9A—C9—H9	127.3
N4—C3—H3B	111.3	O10—C9A—C9B	112.83 (19)
C2—C3—H3B	111.3	O10—C9A—C9	101.49 (18)
H3A—C3—H3B	109.2	C9B—C9A—C9	125.67 (19)
C5—N4—C3	128.07 (19)	O10—C9A—C5A	98.78 (16)
C5—N4—C9B	114.43 (18)	C9B—C9A—C5A	104.85 (17)
C3—N4—C9B	113.42 (18)	C9—C9A—C5A	110.12 (18)
O5—C5—N4	125.7 (2)	N4—C9B—C9A	101.29 (17)
O5—C5—C5A	126.3 (2)	N4—C9B—C1	103.16 (18)
N4—C5—C5A	108.04 (17)	C9A—C9B—C1	120.6 (2)
C5—C5A—C6	119.56 (18)	N4—C9B—H9B	110.3
C5—C5A—C9A	99.73 (17)	C9A—C9B—H9B	110.3
C6—C5A—C9A	101.74 (17)	C1—C9B—H9B	110.3
C5—C5A—H5A	111.5	C7—O10—C9A	95.65 (17)
C6—C5A—H5A	111.5	O11—C11—O12	124.4 (2)
C9A—C5A—H5A	111.5	O11—C11—C6	123.9 (2)
C11—C6—C5A	117.10 (17)	O12—C11—C6	111.56 (19)
C11—C6—C7	112.8 (2)	C11—O12—H12	109.4 (19)
C5A—C6—C7	100.16 (17)
C9B—C1—C2—C3	−35.5 (3)	C6—C5A—C9A—O10	40.32 (19)
C1—C2—C3—N4	23.1 (3)	C5—C5A—C9A—C9B	33.7 (2)
C2—C3—N4—C5	−157.3 (2)	C6—C5A—C9A—C9B	156.88 (18)
C2—C3—N4—C9B	−1.6 (3)	C5—C5A—C9A—C9	171.42 (19)
C3—N4—C5—O5	−16.7 (4)	C6—C5A—C9A—C9	−65.4 (2)
C9B—N4—C5—O5	−172.2 (2)	C5—N4—C9B—C9A	13.2 (3)
C3—N4—C5—C5A	164.6 (2)	C3—N4—C9B—C9A	−146.0 (2)
C9B—N4—C5—C5A	9.0 (3)	C5—N4—C9B—C1	138.6 (2)
O5—C5—C5A—C6	45.6 (3)	C3—N4—C9B—C1	−20.6 (3)
N4—C5—C5A—C6	−135.7 (2)	O10—C9A—C9B—N4	77.5 (2)
O5—C5—C5A—C9A	155.1 (2)	C9—C9A—C9B—N4	−157.9 (2)
N4—C5—C5A—C9A	−26.1 (2)	C5A—C9A—C9B—N4	−29.0 (2)
C5—C5A—C6—C11	−18.4 (3)	O10—C9A—C9B—C1	−35.3 (3)
C9A—C5A—C6—C11	−126.8 (2)	C9—C9A—C9B—C1	89.3 (3)
C5—C5A—C6—C7	103.9 (2)	C5A—C9A—C9B—C1	−141.8 (2)
C9A—C5A—C6—C7	−4.5 (2)	C2—C1—C9B—N4	33.3 (2)
C11—C6—C7—O10	92.5 (2)	C2—C1—C9B—C9A	145.2 (2)
C5A—C6—C7—O10	−32.8 (2)	C8—C7—O10—C9A	−50.66 (19)
C11—C6—C7—C8	−161.48 (19)	C6—C7—O10—C9A	59.66 (18)
C5A—C6—C7—C8	73.2 (2)	C9B—C9A—O10—C7	−171.63 (16)
O10—C7—C8—C9	32.0 (3)	C9—C9A—O10—C7	51.38 (18)
C6—C7—C8—C9	−74.4 (2)	C5A—C9A—O10—C7	−61.36 (16)
C7—C8—C9—C9A	0.9 (3)	C5A—C6—C11—O11	95.3 (3)
C8—C9—C9A—O10	−33.6 (2)	C7—C6—C11—O11	−20.2 (3)
C8—C9—C9A—C9B	−162.9 (2)	C5A—C6—C11—O12	−88.8 (2)
C8—C9—C9A—C5A	70.3 (3)	C7—C6—C11—O12	155.70 (19)
C5—C5A—C9A—O10	−82.84 (18)

D—H···A	D—H	H···A	D···A	D—H···A
O12—H12···O5i	0.90 (3)	1.75 (3)	2.613 (2)	157 (3)
C5A—H5A···O12ii	1.00	2.51	3.234 (3)	129

C12H13NO4	F(000) = 248
Mr = 235.23	Dx = 1.426 Mg m−3
Triclinic, P1	Melting point = 414–416 K
a = 8.4700 (17) Å	Synchrotron radiation, λ = 0.96990 Å
b = 8.5100 (17) Å	Cell parameters from 500 reflections
c = 8.5900 (17) Å	θ = 3.6–36.0°
α = 94.04 (3)°	µ = 0.23 mm−1
β = 111.12 (3)°	T = 100 K
γ = 105.17 (3)°	Prism, colourless
V = 548.0 (2) Å3	0.15 × 0.10 × 0.10 mm
Z = 2

MAR CCD diffractometer	1402 reflections with I > 2σ(I)
φ scan	Rint = 0.061
Absorption correction: multi-scan (SCALA; Evans, 2006)	θmax = 38.1°, θmin = 3.4°
Tmin = 0.960, Tmax = 0.969	h = −10→10
7090 measured reflections	k = −10→10
2104 independent reflections	l = −10→10

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.099	H-atom parameters constrained
wR(F2) = 0.240	w = 1/[σ2(Fo2) + (0.06P)2] where P = (Fo2 + 2Fc2)/3
S = 0.93	(Δ/σ)max < 0.001
2104 reflections	Δρmax = 0.45 e Å−3
155 parameters	Δρmin = −0.36 e Å−3
0 restraints	Extinction correction: SHELXL-2014/7 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: difference Fourier map	Extinction coefficient: 0.138 (11)

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.

	x	y	z	Uiso*/Ueq
C1	0.1779 (3)	0.0068 (2)	0.2264 (2)	0.0322 (5)
H1A	0.0733	−0.0331	0.1171	0.039*
H1B	0.2531	−0.0668	0.2374	0.039*
C2	0.1215 (3)	0.0169 (2)	0.3765 (2)	0.0324 (5)
H2A	0.0900	−0.0932	0.4081	0.039*
H2B	0.0181	0.0592	0.3486	0.039*
C3	0.2874 (2)	0.1392 (2)	0.5222 (2)	0.0288 (5)
H3A	0.2529	0.2089	0.5934	0.035*
H3B	0.3628	0.0797	0.5949	0.035*
N4	0.37879 (19)	0.23864 (17)	0.42848 (16)	0.0261 (4)
C5	0.5531 (2)	0.3199 (2)	0.4832 (2)	0.0250 (4)
O5	0.65982 (17)	0.35299 (15)	0.63512 (13)	0.0299 (3)
C5A	0.5950 (2)	0.3619 (2)	0.3297 (2)	0.0233 (4)
H5A	0.5949	0.4769	0.3127	0.028*
C6	0.7574 (2)	0.32415 (19)	0.3142 (2)	0.0245 (4)
H6	0.8150	0.2754	0.4140	0.029*
C7	0.6593 (3)	0.1818 (2)	0.1503 (2)	0.0276 (5)
H7	0.7338	0.1138	0.1333	0.033*
C8	0.5722 (2)	0.2548 (2)	−0.0027 (2)	0.0264 (5)
H8	0.6108	0.2775	−0.0921	0.032*
C9	0.4292 (3)	0.2805 (2)	0.0152 (2)	0.0284 (5)
H9	0.3431	0.3223	−0.0598	0.034*
C9A	0.4358 (2)	0.2276 (2)	0.1826 (2)	0.0256 (5)
C9B	0.2840 (2)	0.1875 (2)	0.24142 (19)	0.0267 (5)
H9B	0.2022	0.2541	0.1950	0.032*
O10	0.51146 (16)	0.09341 (13)	0.18544 (14)	0.0258 (3)
C11	0.8967 (2)	0.4657 (2)	0.2990 (2)	0.0259 (5)
O11	0.88416 (17)	0.60281 (15)	0.27854 (15)	0.0338 (4)
O12	1.04071 (16)	0.42233 (14)	0.31124 (15)	0.0312 (4)
H12	1.1355	0.5093	0.3163	0.047*

	U11	U22	U33	U12	U13	U23
C1	0.0352 (10)	0.0244 (9)	0.0294 (8)	−0.0016 (8)	0.0132 (7)	−0.0032 (7)
C2	0.0364 (10)	0.0254 (9)	0.0311 (8)	−0.0003 (8)	0.0158 (7)	0.0030 (7)
C3	0.0365 (9)	0.0234 (9)	0.0290 (8)	0.0035 (8)	0.0201 (6)	0.0019 (7)
N4	0.0308 (8)	0.0214 (7)	0.0246 (6)	0.0012 (6)	0.0152 (5)	−0.0014 (5)
C5	0.0316 (9)	0.0159 (7)	0.0263 (8)	0.0045 (7)	0.0131 (6)	−0.0028 (6)
O5	0.0364 (7)	0.0281 (6)	0.0205 (5)	0.0017 (5)	0.0130 (4)	−0.0033 (5)
C5A	0.0284 (9)	0.0177 (8)	0.0227 (7)	0.0022 (7)	0.0131 (6)	−0.0005 (6)
C6	0.0355 (9)	0.0164 (8)	0.0232 (7)	0.0043 (7)	0.0165 (6)	0.0005 (6)
C7	0.0335 (9)	0.0192 (8)	0.0277 (8)	−0.0004 (7)	0.0169 (6)	−0.0048 (6)
C8	0.0373 (10)	0.0199 (8)	0.0209 (7)	0.0025 (7)	0.0158 (6)	−0.0026 (6)
C9	0.0368 (10)	0.0211 (8)	0.0229 (8)	0.0029 (8)	0.0118 (7)	−0.0001 (6)
C9A	0.0344 (9)	0.0168 (8)	0.0239 (7)	0.0043 (7)	0.0128 (6)	0.0000 (6)
C9B	0.0327 (9)	0.0214 (8)	0.0240 (8)	0.0032 (7)	0.0134 (6)	−0.0021 (6)
O10	0.0337 (6)	0.0164 (5)	0.0277 (5)	0.0033 (5)	0.0165 (4)	−0.0009 (4)
C11	0.0316 (9)	0.0227 (9)	0.0204 (7)	0.0024 (7)	0.0126 (6)	−0.0045 (6)
O11	0.0375 (7)	0.0228 (6)	0.0390 (6)	0.0042 (6)	0.0170 (5)	0.0031 (5)
O12	0.0309 (7)	0.0232 (6)	0.0403 (6)	0.0040 (5)	0.0189 (5)	0.0015 (5)

C1—C2	1.532 (3)	C6—C11	1.500 (3)
C1—C9B	1.534 (3)	C6—C7	1.590 (2)
C1—H1A	0.9900	C6—H6	1.0000
C1—H1B	0.9900	C7—O10	1.427 (2)
C2—C3	1.552 (2)	C7—C8	1.521 (3)
C2—H2A	0.9900	C7—H7	1.0000
C2—H2B	0.9900	C8—C9	1.344 (3)
C3—N4	1.472 (2)	C8—H8	0.9500
C3—H3A	0.9900	C9—C9A	1.522 (2)
C3—H3B	0.9900	C9—H9	0.9500
N4—C5	1.341 (2)	C9A—O10	1.446 (2)
N4—C9B	1.485 (2)	C9A—C9B	1.513 (3)
C5—O5	1.250 (2)	C9B—H9B	1.0000
C5—C5A	1.526 (3)	C11—O11	1.218 (2)
C5A—C6	1.540 (3)	C11—O12	1.336 (2)
C5A—C9A	1.576 (2)	O12—H12	0.9239
C5A—H5A	1.0000
C2—C1—C9B	102.15 (14)	C11—C6—H6	108.7
C2—C1—H1A	111.3	C5A—C6—H6	108.7
C9B—C1—H1A	111.3	C7—C6—H6	108.7
C2—C1—H1B	111.3	O10—C7—C8	102.71 (15)
C9B—C1—H1B	111.3	O10—C7—C6	99.48 (13)
H1A—C1—H1B	109.2	C8—C7—C6	109.15 (14)
C1—C2—C3	104.39 (16)	O10—C7—H7	114.6
C1—C2—H2A	110.9	C8—C7—H7	114.6
C3—C2—H2A	110.9	C6—C7—H7	114.6
C1—C2—H2B	110.9	C9—C8—C7	105.52 (17)
C3—C2—H2B	110.9	C9—C8—H8	127.2
H2A—C2—H2B	108.9	C7—C8—H8	127.2
N4—C3—C2	102.16 (13)	C8—C9—C9A	104.59 (17)
N4—C3—H3A	111.3	C8—C9—H9	127.7
C2—C3—H3A	111.3	C9A—C9—H9	127.7
N4—C3—H3B	111.3	O10—C9A—C9B	111.77 (14)
C2—C3—H3B	111.3	O10—C9A—C9	102.12 (14)
H3A—C3—H3B	109.2	C9B—C9A—C9	126.44 (16)
C5—N4—C3	127.10 (15)	O10—C9A—C5A	100.18 (14)
C5—N4—C9B	115.10 (15)	C9B—C9A—C5A	105.83 (13)
C3—N4—C9B	113.07 (13)	C9—C9A—C5A	107.50 (14)
O5—C5—N4	124.50 (18)	N4—C9B—C9A	102.11 (13)
O5—C5—C5A	127.21 (17)	N4—C9B—C1	101.06 (14)
N4—C5—C5A	108.28 (14)	C9A—C9B—C1	120.38 (16)
C5—C5A—C6	117.75 (15)	N4—C9B—H9B	110.7
C5—C5A—C9A	101.00 (14)	C9A—C9B—H9B	110.7
C6—C5A—C9A	101.86 (13)	C1—C9B—H9B	110.7
C5—C5A—H5A	111.7	C7—O10—C9A	96.02 (13)
C6—C5A—H5A	111.7	O11—C11—O12	123.30 (17)
C9A—C5A—H5A	111.7	O11—C11—C6	125.93 (18)
C11—C6—C5A	117.00 (15)	O12—C11—C6	110.77 (15)
C11—C6—C7	113.55 (15)	C11—O12—H12	113.8
C5A—C6—C7	99.72 (13)
C9B—C1—C2—C3	−40.2 (2)	C6—C5A—C9A—O10	32.99 (16)
C1—C2—C3—N4	24.99 (19)	C5—C5A—C9A—C9B	27.56 (18)
C2—C3—N4—C5	−154.32 (18)	C6—C5A—C9A—C9B	149.26 (14)
C2—C3—N4—C9B	−0.1 (2)	C5—C5A—C9A—C9	165.01 (15)
C3—N4—C5—O5	−16.0 (3)	C6—C5A—C9A—C9	−73.29 (18)
C9B—N4—C5—O5	−169.80 (16)	C5—N4—C9B—C9A	8.4 (2)
C3—N4—C5—C5A	163.66 (15)	C3—N4—C9B—C9A	−149.09 (15)
C9B—N4—C5—C5A	9.9 (2)	C5—N4—C9B—C1	133.04 (17)
O5—C5—C5A—C6	47.1 (2)	C3—N4—C9B—C1	−24.4 (2)
N4—C5—C5A—C6	−132.62 (15)	O10—C9A—C9B—N4	85.85 (15)
O5—C5—C5A—C9A	156.89 (18)	C9—C9A—C9B—N4	−148.99 (15)
N4—C5—C5A—C9A	−22.81 (19)	C5A—C9A—C9B—N4	−22.27 (18)
C5—C5A—C6—C11	−123.93 (16)	O10—C9A—C9B—C1	−24.8 (2)
C9A—C5A—C6—C11	126.75 (15)	C9—C9A—C9B—C1	100.3 (2)
C5—C5A—C6—C7	113.23 (14)	C5A—C9A—C9B—C1	−132.96 (15)
C9A—C5A—C6—C7	3.91 (16)	C2—C1—C9B—N4	38.51 (18)
C11—C6—C7—O10	−165.65 (15)	C2—C1—C9B—C9A	149.76 (16)
C5A—C6—C7—O10	−40.40 (16)	C8—C7—O10—C9A	−49.46 (13)
C11—C6—C7—C8	−58.5 (2)	C6—C7—O10—C9A	62.79 (14)
C5A—C6—C7—C8	66.71 (18)	C9B—C9A—O10—C7	−171.68 (12)
O10—C7—C8—C9	30.75 (16)	C9—C9A—O10—C7	50.59 (14)
C6—C7—C8—C9	−74.15 (18)	C5A—C9A—O10—C7	−59.96 (14)
C7—C8—C9—C9A	1.83 (16)	C5A—C6—C11—O11	−8.9 (2)
C8—C9—C9A—O10	−33.38 (16)	C7—C6—C11—O11	106.5 (2)
C8—C9—C9A—C9B	−162.43 (15)	C5A—C6—C11—O12	171.02 (12)
C8—C9—C9A—C5A	71.53 (17)	C7—C6—C11—O12	−73.58 (19)
C5—C5A—C9A—O10	−88.71 (15)

D—H···A	D—H	H···A	D···A	D—H···A
O12—H12···O5i	0.92	1.70	2.607 (2)	165
C9—H9···O11ii	0.95	2.42	3.362 (3)	172