The endo and exo isomers of 1-(4-isopropyl-3,5-dioxa-8-aza­bicyclo­[5.1.0]octan-8-yl)pyrrolidine-2,5-dione

The crystal structures of the title compounds, C₁₂H₁₈N₂O₄, have been determined in order to establish the relative configurations. In both structures, the isopropyl substituent strongly prefers the quasi-equatorial position. Therefore, the exo isomer adopts a dioxepanoaziridine pattern of a chair-chair (CC) conformation and the endo isomer a boat-chair (BC) conformation.

S1. Comment

Fused aziridines, e.g. N-arenesulfonyl-protected 1,3-dioxepanoaziridines, are of interest as potent antihypoglycaemic agents (Dumić et al., 1993, 1995; Oresić et al., 2001; Filić et al., 1996). Such compounds have been prepared from trans-acetylaminochlorodioxepanes by ring-closure dehydrohalogenation and subsequent N-protection with arenesulfonylchlorides. Direct aziridination of 4,7-dihydro-1,3-dioxepins using sulfonylazides as the nitrogen source failed (Dumić et al., 1993). The crystal structures of these compounds have been thoroughly studied in order to develop quantitative structure–property and structure–activity relationship models.

Recently, we have developed a new aziridination procedure using N-aminosuccinimide as the nitrogen source and iodosylbenzene diacetate as the oxidizing agent, which directly leads to N-amino-protected fused dioxepanoaziridines (Flock et al., 2005). Thus, a diastereomeric mixture of the title compounds, (I) and (II) (Figs 1 and 2), was obtained from 2-isopropyl-4,7-dihydro-1,3-dioxepin, N-aminosuccinimide and iodosylbenzene diacetate. The relative configurations of these compounds are of interest with respect to their reactivity and stability.

Separation of the diastereomeric mixture by column chromatography afforded (I) and (II) as colourless solids. However, determination of the relative configurations using nuclear Overhauser experiments failed because of the flexibility of the dioxepin moiety in solution. After recrystallization from diethyl ether–acetone and evaporation from acetone, respectively, (I) and (II) crystallized as well formed plate-like colourless crystals.

The exo isomer, (I), crystallizes in the non-centrosymmetric space group P2₁ with Z' = 1, but the absolute configuration could not be determined. The endo isomer, (II), crystallizes in space group P2₁/c with Z' = 2. The difference between the two independent molecules in (II) lies in the conformation of the isopropyl substituent around the C5—C6 and C17—C18 bonds (Fig. 2). Neither isomer shows any strong intermolecular interactions.

In both isomers, the isopropyl substituent at the acetalic unit was found in a quasi-equatorial position. Analysis of the endo isomer, (II), reveals that the dioxepanoaziridine moiety adopts a boat–chair (BC) conformation, while for the exo isomer, (I), the preferred conformation in the solid state is the chair–chair (CC) conformation. The substituent on the aziridine N atom occupies, in both cases, the anti position with respect to the dioxepane ring, which supports previous results found for 8-sulfonyl-protected bicyclooctane derivatives (Dumić et al., 1995).

S2. Experimental

Under a nitrogen atmosphere, small portions of iodosylbenzene diacetate (3.865 g, 12 mmol) were added at room temperature to a solution of 2-isopropyl-4,7-dihydro-1,3-dioxepine (2.560 g, 18 mmol) and N-aminosuccinimide (1.141 g, 10 mmol) in dry acetonitrile (30 ml) over a period of 2.5 h. After stirring for a further 15 h, the reaction mixture was evaporated under reduced pressure. The oily residue was purified by column chromatography (silica gel, cyclohexane 100 → ethylacetate–cyclohexane: 80:20) to give the separated isomers, (I) and (II), as colourless solids (total yield 1.602 g, 6.3 mmol, 63%). Single crystals of isomer (I) (exo) for X-ray diffraction studies were obtained by slow evaporation from acetone (m.p. 413–415 K). Spectroscopic analysis: ¹H NMR (500 MHz, CDCl₃, δ, p.p.m.): 0.90 [d, 6H, J = 6.84 Hz, CH(CH₃)₂], 1.84 [m, 1H, CH(CH₃)₂], 2.63 [s, 4H, CO—(CH₂)₂—CO], 2.82 (m, 2H, CH—N), 3.84 (m, 2H, O—CH₂), 4.12 (d, 1H, J = 6.84 Hz, O—CHR—O), 4.56 (m, 2H, O—CH₂); ¹³C NMR (125 MHz, CDCl₃, δ, p.p.m.): 172.45 (2 C, CO), 112.42 (1 C, O—CHR—O), 66.64 (2 C, O—CH₂), 47.46 (2 C, CH—N), 31.56 [1 C, CH(CH₃)₂], 26.46 [2 C, CO-(CH₂)₂-CO], 17.74 [2 C, CH(CH₃)₂]. Single crystals of isomer (II) (endo) for X-ray diffraction studies were obtained by recrystallization from diethyl ether–acetone (Ratio?) at 253 K (m.p. 415–417 K). Spectroscopic analysis: ¹H NMR (500 MHz, CDCl₃, δ, p.p.m.): 0.88 [d, 6H, J = 6.88 Hz, CH(CH₃)₂], 1.83 [m, 1H, CH(CH₃)₂], 2.62 [s, 4H, CO—(CH₂)₂—CO], 2.71 (m, 2H, CH—N), 3.94 (d, 1H, J = 6.83 Hz, O—CHR—O), 3.98 (m, 2H, O—CH₂), 4.62 (m, 2H, O—CH2); ¹³C NMR (125 MHz, CDCl₃, δ, p.p.m.): 172.70 (2 C, CO), 111.28 (1 C, O—CHR—O), 65.36 (2 C, O—CH₂), 48.15 (2 C, CH—N), 32.23 [1 C, CH(CH₃)₂], 26.60 [2 C, CO—(CH₂)₂—CO], 17.72 [2 C, CH(CH₃)₂]. APCI-MS, mixture of isomers: m/z (%) = 255 (100) [M+H]⁺; 287 (21) [M+H+MeOH]⁺.

S3. Refinement

H atoms were treated as riding, with C—H distances in the range 0.98–1.00 Å and U_iso(H) = 1.2U_eq(C). [Please check added text] The Friedel-equivalent reflections were merged.

Computing details

For both compounds, data collection: Please provide missing details; cell refinement: Please provide missing details; data reduction: Please provide missing details; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: Please provide missing details; software used to prepare material for publication: Please provide missing details.

Figures

	Fig. 1. The exo isomer (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small circles of arbitrary radii.
	Fig. 2. The asymmetric unit of the endo isomer (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small circles of arbitrary radii.

(I) endo- 1-(4-isopropyl-3,5-dioxa-8-azabicyclo[5.1.0]octan-8-yl)pyrrolidine-2,5-dione

Crystal data

C12H18N2O4	F(000) = 272
Mr = 254.28	Dx = 1.363 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 7302 reflections
a = 6.1449 (11) Å	θ = 1.6–26.0°
b = 7.8343 (10) Å	µ = 0.10 mm^−1
c = 13.080 (3) Å	T = 153 K
β = 100.250 (15)°	Plate, colourless
V = 619.6 (2) Å^3	0.47 × 0.41 × 0.05 mm
Z = 2

Data collection

Stoe IPDS 2 diffractometer	1244 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	998 reflections with I > 2σ(I)
Plane graphite monochromator	Rint = 0.057
Detector resolution: 6.67 pixels mm^-1	θmax = 25.5°, θmin = 1.6°
rotation scans	h = −7→7
Absorption correction: integration X-RED32 (Stoe & Cie, 2004)	k = −9→9
Tmin = 0.954, Tmax = 0.995	l = −15→15
8393 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.076	H-atom parameters constrained
S = 1.02	w = 1/[σ^2(Fo^2) + (0.044P)^2] where P = (Fo^2 + 2Fc^2)/3
1244 reflections	(Δ/σ)max = 0.004
165 parameters	Δρmax = 0.14 e Å^−3
1 restraint	Δρmin = −0.21 e Å^−3

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.

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

	x	y	z	Uiso*/Ueq
C1	0.1562 (5)	0.8397 (4)	0.6551 (2)	0.0359 (7)
H1A	0.2998	0.8933	0.6500	0.043*
H1B	0.1719	0.7149	0.6472	0.043*
C2	0.1003 (5)	0.8771 (4)	0.7606 (2)	0.0310 (6)
H2A	0.1520	0.9890	0.7930	0.037*
C3	−0.1000 (4)	0.8033 (4)	0.7901 (2)	0.0314 (6)
H3A	−0.1692	0.8701	0.8411	0.038*
C4	−0.2544 (5)	0.6976 (4)	0.7130 (2)	0.0345 (7)
H4B	−0.1758	0.5945	0.6951	0.041*
H4A	−0.3809	0.6599	0.7448	0.041*
C5	−0.1931 (4)	0.7912 (4)	0.5452 (2)	0.0314 (6)
H5A	−0.1396	0.6725	0.5364	0.038*
C6	−0.3220 (5)	0.8561 (4)	0.4427 (2)	0.0341 (6)
H6A	−0.3517	0.9805	0.4504	0.041*
C7	−0.1823 (5)	0.8357 (4)	0.3577 (2)	0.0403 (7)
H7A	−0.1594	0.7141	0.3457	0.048*
H7B	−0.0389	0.8916	0.3796	0.048*
H7C	−0.2592	0.8885	0.2933	0.048*
C8	−0.5429 (5)	0.7652 (4)	0.4124 (2)	0.0421 (8)
H8C	−0.6164	0.8051	0.3439	0.051*
H8B	−0.6364	0.7902	0.4639	0.051*
H8A	−0.5180	0.6418	0.4100	0.051*
C9	0.3970 (5)	0.8568 (4)	0.9687 (2)	0.0357 (7)
C10	0.4386 (5)	0.8615 (4)	1.0854 (2)	0.0403 (7)
H10A	0.4573	0.9805	1.1109	0.048*
H10B	0.5731	0.7958	1.1143	0.048*
C11	0.2335 (5)	0.7804 (4)	1.1162 (2)	0.0398 (7)
H11B	0.2757	0.6853	1.1656	0.048*
H11A	0.1492	0.8658	1.1490	0.048*
C12	0.0983 (5)	0.7156 (4)	1.0165 (2)	0.0354 (7)
N1	0.1217 (4)	0.7252 (3)	0.83085 (17)	0.0313 (5)
N2	0.2005 (4)	0.7706 (3)	0.93619 (15)	0.0299 (5)
O1	0.5120 (3)	0.9170 (3)	0.91070 (15)	0.0453 (6)
O2	−0.0704 (4)	0.6317 (3)	1.00440 (16)	0.0455 (6)
O3	−0.0102 (3)	0.9024 (3)	0.57294 (13)	0.0347 (5)
O4	−0.3350 (3)	0.7922 (3)	0.62015 (13)	0.0341 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0300 (14)	0.0462 (19)	0.0319 (14)	0.0004 (14)	0.0061 (12)	−0.0008 (14)
C2	0.0335 (15)	0.0281 (15)	0.0319 (14)	−0.0004 (13)	0.0070 (11)	−0.0002 (13)
C3	0.0298 (14)	0.0342 (15)	0.0304 (14)	0.0046 (13)	0.0061 (12)	0.0005 (12)
C4	0.0354 (17)	0.0419 (18)	0.0264 (15)	−0.0042 (13)	0.0060 (12)	0.0062 (12)
C5	0.0313 (14)	0.0350 (15)	0.0297 (14)	−0.0041 (14)	0.0100 (11)	−0.0007 (12)
C6	0.0385 (15)	0.0330 (15)	0.0312 (14)	−0.0001 (14)	0.0071 (12)	−0.0014 (13)
C7	0.0489 (18)	0.0394 (18)	0.0337 (15)	0.0013 (15)	0.0105 (13)	0.0011 (14)
C8	0.0404 (18)	0.048 (2)	0.0363 (16)	−0.0014 (16)	0.0033 (13)	0.0020 (15)
C9	0.0326 (15)	0.0352 (16)	0.0390 (15)	0.0023 (14)	0.0056 (13)	−0.0040 (14)
C10	0.0422 (17)	0.0441 (18)	0.0325 (16)	−0.0001 (15)	0.0008 (12)	−0.0032 (15)
C11	0.0488 (18)	0.0388 (17)	0.0308 (14)	−0.0048 (16)	0.0042 (13)	−0.0029 (14)
C12	0.0452 (19)	0.0292 (15)	0.0311 (15)	0.0009 (15)	0.0048 (13)	0.0017 (13)
N1	0.0355 (13)	0.0292 (12)	0.0289 (12)	0.0022 (10)	0.0045 (10)	−0.0009 (10)
N2	0.0345 (13)	0.0311 (13)	0.0235 (11)	−0.0004 (11)	0.0031 (10)	−0.0034 (11)
O1	0.0347 (11)	0.0612 (14)	0.0418 (12)	−0.0036 (11)	0.0113 (10)	−0.0026 (11)
O2	0.0491 (14)	0.0462 (13)	0.0404 (11)	−0.0146 (12)	0.0059 (10)	0.0044 (11)
O3	0.0346 (11)	0.0390 (12)	0.0304 (10)	−0.0033 (10)	0.0057 (8)	0.0040 (9)
O4	0.0307 (10)	0.0428 (11)	0.0295 (10)	0.0019 (9)	0.0072 (8)	0.0045 (9)

Geometric parameters (Å, º)

C1—O3	1.432 (3)	C6—H6A	1.0000
C1—C2	1.509 (4)	C7—H7A	0.9800
C1—H1A	0.9900	C7—H7B	0.9800
C1—H1B	0.9900	C7—H7C	0.9800
C2—C3	1.472 (4)	C8—H8C	0.9800
C2—N1	1.495 (3)	C8—H8B	0.9800
C2—H2A	1.0000	C8—H8A	0.9800
C3—N1	1.502 (4)	C9—O1	1.219 (3)
C3—C4	1.504 (4)	C9—N2	1.382 (4)
C3—H3A	1.0000	C9—C10	1.503 (4)
C4—O4	1.434 (3)	C10—C11	1.528 (4)
C4—H4B	0.9900	C10—H10A	0.9900
C4—H4A	0.9900	C10—H10B	0.9900
C5—O3	1.417 (3)	C11—C12	1.504 (4)
C5—O4	1.423 (3)	C11—H11B	0.9900
C5—C6	1.519 (4)	C11—H11A	0.9900
C5—H5A	1.0000	C12—O2	1.213 (3)
C6—C8	1.521 (4)	C12—N2	1.385 (4)
C6—C7	1.529 (4)	N1—N2	1.422 (3)
O3—C1—C2	111.8 (2)	C6—C7—H7B	109.5
O3—C1—H1A	109.3	H7A—C7—H7B	109.5
C2—C1—H1A	109.3	C6—C7—H7C	109.5
O3—C1—H1B	109.3	H7A—C7—H7C	109.5
C2—C1—H1B	109.3	H7B—C7—H7C	109.5
H1A—C1—H1B	107.9	C6—C8—H8C	109.5
C3—C2—N1	60.83 (18)	C6—C8—H8B	109.5
C3—C2—C1	120.0 (2)	H8C—C8—H8B	109.5
N1—C2—C1	113.4 (2)	C6—C8—H8A	109.5
C3—C2—H2A	116.8	H8C—C8—H8A	109.5
N1—C2—H2A	116.8	H8B—C8—H8A	109.5
C1—C2—H2A	116.8	O1—C9—N2	124.7 (3)
C2—C3—N1	60.33 (17)	O1—C9—C10	127.5 (3)
C2—C3—C4	119.8 (2)	N2—C9—C10	107.8 (2)
N1—C3—C4	116.0 (2)	C9—C10—C11	104.9 (2)
C2—C3—H3A	116.3	C9—C10—H10A	110.8
N1—C3—H3A	116.3	C11—C10—H10A	110.8
C4—C3—H3A	116.3	C9—C10—H10B	110.8
O4—C4—C3	111.4 (2)	C11—C10—H10B	110.8
O4—C4—H4B	109.3	H10A—C10—H10B	108.8
C3—C4—H4B	109.3	C12—C11—C10	105.5 (2)
O4—C4—H4A	109.3	C12—C11—H11B	110.7
C3—C4—H4A	109.3	C10—C11—H11B	110.7
H4B—C4—H4A	108.0	C12—C11—H11A	110.7
O3—C5—O4	112.1 (2)	C10—C11—H11A	110.7
O3—C5—C6	106.6 (2)	H11B—C11—H11A	108.8
O4—C5—C6	108.6 (2)	O2—C12—N2	124.2 (3)
O3—C5—H5A	109.8	O2—C12—C11	128.6 (3)
O4—C5—H5A	109.8	N2—C12—C11	107.3 (3)
C6—C5—H5A	109.8	N2—N1—C2	112.0 (2)
C5—C6—C8	112.0 (2)	N2—N1—C3	111.9 (2)
C5—C6—C7	109.6 (2)	C2—N1—C3	58.84 (17)
C8—C6—C7	110.7 (2)	C9—N2—C12	114.1 (2)
C5—C6—H6A	108.2	C9—N2—N1	123.2 (2)
C8—C6—H6A	108.2	C12—N2—N1	122.3 (2)
C7—C6—H6A	108.2	C5—O3—C1	114.2 (2)
C6—C7—H7A	109.5	C5—O4—C4	114.8 (2)

(II) exo- 1-(4-isopropyl-3,5-dioxa-8-azabicyclo[5.1.0]octan-8-yl)pyrrolidine-2,5-dione

Crystal data

C12H18N2O4	F(000) = 1088
Mr = 254.28	Dx = 1.330 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 10318 reflections
a = 24.470 (3) Å	θ = 1.7–25.6°
b = 8.8444 (8) Å	µ = 0.10 mm^−1
c = 11.8252 (14) Å	T = 153 K
β = 97.119 (9)°	Plate, colourless
V = 2539.6 (5) Å^3	0.66 × 0.65 × 0.25 mm
Z = 8

Data collection

Stoe IPDS 2 diffractometer	4465 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	2623 reflections with I > 2σ(I)
Plane graphite monochromator	Rint = 0.033
Detector resolution: 6.67 pixels mm^-1	θmax = 25.0°, θmin = 1.7°
rotation scans	h = −29→29
Absorption correction: integration X-RED32 (Stoe & Cie, 2004)	k = −10→10
Tmin = 0.914, Tmax = 0.972	l = −13→14
18062 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) = 0.084	w = 1/[σ^2(Fo^2) + (0.0484P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.90	(Δ/σ)max < 0.001
4465 reflections	Δρmax = 0.21 e Å^−3
330 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0028 (4)

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.

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

	x	y	z	Uiso*/Ueq
C1	0.13853 (6)	0.1498 (2)	0.37970 (13)	0.0339 (4)
H1A	0.1338	0.0495	0.3427	0.041*
H1B	0.1604	0.2128	0.3327	0.041*
C2	0.08288 (6)	0.22056 (18)	0.37812 (14)	0.0284 (4)
H2A	0.0625	0.2297	0.2997	0.034*
C3	0.06445 (6)	0.33025 (18)	0.45939 (13)	0.0269 (4)
H3A	0.0343	0.3984	0.4248	0.032*
C4	0.09820 (6)	0.39655 (18)	0.56193 (13)	0.0302 (4)
H4B	0.1149	0.4918	0.5387	0.036*
H4A	0.0732	0.4228	0.6186	0.036*
C5	0.18282 (6)	0.26653 (17)	0.54868 (13)	0.0274 (4)
H5A	0.1868	0.3502	0.4934	0.033*
C6	0.23653 (7)	0.24463 (19)	0.62595 (15)	0.0335 (4)
H6A	0.2313	0.1617	0.6811	0.040*
C7	0.28230 (7)	0.1981 (2)	0.55652 (17)	0.0496 (5)
H7A	0.2880	0.2782	0.5020	0.060*
H7B	0.2719	0.1043	0.5152	0.060*
H7C	0.3164	0.1818	0.6078	0.060*
C8	0.25272 (7)	0.3879 (2)	0.69348 (14)	0.0403 (4)
H8A	0.2229	0.4171	0.7372	0.048*
H8B	0.2594	0.4696	0.6409	0.048*
H8C	0.2863	0.3692	0.7458	0.048*
C9	−0.02191 (7)	0.04486 (18)	0.32502 (13)	0.0291 (4)
C10	−0.08362 (6)	0.04812 (19)	0.29875 (14)	0.0332 (4)
H10A	−0.0992	−0.0543	0.3057	0.040*
H10B	−0.0948	0.0859	0.2205	0.040*
C11	−0.10334 (7)	0.15492 (19)	0.38645 (14)	0.0352 (4)
H11B	−0.1242	0.2404	0.3482	0.042*
H11A	−0.1274	0.1009	0.4344	0.042*
C12	−0.05208 (7)	0.21086 (18)	0.45773 (14)	0.0290 (4)
C13	0.40029 (6)	0.88727 (18)	0.43325 (13)	0.0295 (4)
H13A	0.3829	0.9826	0.4541	0.035*
H13B	0.4260	0.9128	0.3776	0.035*
C14	0.43315 (6)	0.82396 (18)	0.53816 (13)	0.0269 (4)
H14A	0.4622	0.8944	0.5743	0.032*
C15	0.41454 (6)	0.71207 (18)	0.61837 (13)	0.0277 (4)
H15A	0.4339	0.7225	0.6975	0.033*
C16	0.35980 (6)	0.6350 (2)	0.61452 (12)	0.0316 (4)
H16B	0.3660	0.5331	0.6484	0.038*
H16A	0.3372	0.6924	0.6636	0.038*
C17	0.31634 (7)	0.75532 (17)	0.44628 (13)	0.0270 (4)
H17A	0.3132	0.8384	0.5025	0.032*
C18	0.26201 (7)	0.73858 (18)	0.36962 (15)	0.0322 (4)
H18A	0.2577	0.8290	0.3185	0.039*
C19	0.26088 (7)	0.5990 (2)	0.29422 (14)	0.0411 (4)
H19A	0.2618	0.5080	0.3417	0.049*
H19B	0.2930	0.5999	0.2522	0.049*
H19C	0.2271	0.5993	0.2402	0.049*
C20	0.21412 (7)	0.7386 (2)	0.44041 (17)	0.0441 (5)
H20C	0.1794	0.7304	0.3898	0.053*
H20B	0.2144	0.8329	0.4840	0.053*
H20A	0.2178	0.6525	0.4930	0.053*
C21	0.55121 (7)	0.71403 (18)	0.54804 (14)	0.0288 (4)
C22	0.60214 (7)	0.6605 (2)	0.62166 (15)	0.0358 (4)
H22A	0.6218	0.7467	0.6616	0.043*
H22B	0.6274	0.6090	0.5749	0.043*
C23	0.58212 (6)	0.55098 (19)	0.70676 (14)	0.0337 (4)
H23A	0.5988	0.4499	0.7000	0.040*
H23B	0.5919	0.5881	0.7857	0.040*
C24	0.52063 (6)	0.54374 (18)	0.67696 (13)	0.0284 (4)
N1	0.04750 (5)	0.16772 (14)	0.46420 (10)	0.0262 (3)
N2	−0.00770 (5)	0.14746 (14)	0.41301 (10)	0.0265 (3)
N3	0.45186 (5)	0.66313 (14)	0.53454 (10)	0.0257 (3)
N4	0.50663 (5)	0.64627 (14)	0.58886 (10)	0.0256 (3)
O1	0.01112 (5)	−0.02834 (13)	0.27952 (9)	0.0359 (3)
O2	−0.04824 (5)	0.29651 (13)	0.53843 (10)	0.0366 (3)
O3	0.16959 (4)	0.13044 (12)	0.48916 (8)	0.0310 (3)
O4	0.14114 (4)	0.30286 (12)	0.61645 (8)	0.0291 (3)
O5	0.54759 (5)	0.80150 (13)	0.46811 (10)	0.0367 (3)
O6	0.48765 (4)	0.46768 (13)	0.72011 (9)	0.0360 (3)
O7	0.35839 (4)	0.79079 (12)	0.37859 (8)	0.0290 (3)
O8	0.32862 (4)	0.61822 (12)	0.50495 (8)	0.0285 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0327 (9)	0.0431 (11)	0.0256 (8)	−0.0001 (8)	0.0026 (7)	−0.0043 (7)
C2	0.0280 (9)	0.0323 (9)	0.0245 (8)	−0.0021 (7)	0.0025 (7)	0.0017 (7)
C3	0.0273 (9)	0.0253 (8)	0.0277 (8)	−0.0012 (7)	0.0021 (7)	0.0023 (7)
C4	0.0285 (8)	0.0296 (9)	0.0322 (9)	0.0027 (8)	0.0025 (7)	−0.0020 (7)
C5	0.0272 (8)	0.0275 (9)	0.0275 (9)	−0.0015 (7)	0.0031 (7)	0.0017 (7)
C6	0.0315 (9)	0.0331 (10)	0.0348 (10)	−0.0024 (7)	0.0006 (7)	0.0060 (7)
C7	0.0306 (10)	0.0551 (13)	0.0618 (13)	0.0070 (9)	0.0002 (9)	−0.0058 (10)
C8	0.0321 (8)	0.0484 (11)	0.0396 (9)	−0.0089 (8)	0.0021 (7)	0.0000 (8)
C9	0.0330 (9)	0.0267 (9)	0.0272 (9)	−0.0019 (8)	0.0021 (7)	0.0010 (7)
C10	0.0285 (9)	0.0352 (10)	0.0346 (9)	−0.0015 (8)	−0.0013 (7)	−0.0014 (7)
C11	0.0287 (9)	0.0338 (10)	0.0426 (10)	0.0033 (8)	0.0022 (7)	−0.0018 (7)
C12	0.0302 (9)	0.0267 (9)	0.0305 (9)	0.0012 (7)	0.0053 (7)	0.0029 (7)
C13	0.0308 (9)	0.0284 (9)	0.0290 (8)	−0.0033 (8)	0.0028 (7)	0.0015 (7)
C14	0.0269 (9)	0.0257 (9)	0.0282 (9)	−0.0014 (7)	0.0043 (7)	−0.0035 (7)
C15	0.0297 (9)	0.0327 (9)	0.0208 (8)	0.0023 (7)	0.0026 (7)	−0.0007 (7)
C16	0.0276 (8)	0.0439 (11)	0.0231 (8)	−0.0020 (7)	0.0024 (6)	0.0034 (7)
C17	0.0283 (9)	0.0256 (9)	0.0275 (9)	0.0012 (7)	0.0045 (7)	−0.0016 (6)
C18	0.0297 (9)	0.0302 (10)	0.0350 (10)	0.0007 (7)	−0.0031 (7)	0.0006 (7)
C19	0.0391 (9)	0.0425 (10)	0.0389 (9)	−0.0016 (8)	−0.0059 (7)	−0.0065 (8)
C20	0.0293 (9)	0.0461 (12)	0.0561 (12)	0.0022 (8)	0.0018 (8)	−0.0037 (8)
C21	0.0294 (9)	0.0269 (9)	0.0305 (9)	−0.0022 (7)	0.0052 (7)	−0.0041 (7)
C22	0.0268 (9)	0.0369 (10)	0.0433 (10)	−0.0032 (8)	0.0023 (7)	0.0009 (8)
C23	0.0300 (9)	0.0357 (10)	0.0343 (9)	0.0012 (8)	−0.0006 (7)	0.0019 (7)
C24	0.0286 (9)	0.0281 (9)	0.0286 (9)	−0.0001 (7)	0.0032 (7)	−0.0016 (7)
N1	0.0246 (7)	0.0275 (7)	0.0261 (7)	−0.0008 (6)	0.0015 (5)	0.0013 (5)
N2	0.0253 (7)	0.0268 (8)	0.0267 (7)	0.0001 (6)	0.0004 (5)	0.0001 (5)
N3	0.0244 (7)	0.0273 (7)	0.0251 (7)	0.0003 (6)	0.0016 (5)	−0.0019 (5)
N4	0.0229 (7)	0.0263 (8)	0.0272 (7)	−0.0017 (6)	0.0017 (5)	−0.0007 (5)
O1	0.0332 (7)	0.0366 (7)	0.0377 (7)	0.0031 (6)	0.0030 (5)	−0.0079 (5)
O2	0.0392 (7)	0.0354 (7)	0.0355 (7)	0.0037 (6)	0.0062 (5)	−0.0055 (5)
O3	0.0302 (6)	0.0304 (6)	0.0314 (6)	0.0013 (5)	0.0004 (5)	−0.0010 (5)
O4	0.0281 (6)	0.0346 (6)	0.0246 (6)	0.0008 (5)	0.0035 (5)	0.0006 (5)
O5	0.0377 (7)	0.0366 (7)	0.0364 (7)	−0.0050 (6)	0.0074 (5)	0.0052 (6)
O6	0.0329 (7)	0.0368 (7)	0.0380 (7)	−0.0040 (6)	0.0034 (5)	0.0075 (5)
O7	0.0289 (6)	0.0333 (6)	0.0247 (6)	−0.0041 (5)	0.0022 (5)	−0.0009 (5)
O8	0.0288 (6)	0.0296 (6)	0.0263 (6)	−0.0012 (5)	−0.0001 (4)	0.0025 (5)

Geometric parameters (Å, º)

C1—O3	1.4279 (18)	C13—C14	1.501 (2)
C1—C2	1.497 (2)	C13—H13A	0.9900
C1—H1A	0.9900	C13—H13B	0.9900
C1—H1B	0.9900	C14—C15	1.481 (2)
C2—C3	1.475 (2)	C14—N3	1.497 (2)
C2—N1	1.4908 (19)	C14—H14A	1.0000
C2—H2A	1.0000	C15—N3	1.4928 (19)
C3—N1	1.499 (2)	C15—C16	1.499 (2)
C3—C4	1.499 (2)	C15—H15A	1.0000
C3—H3A	1.0000	C16—O8	1.4276 (17)
C4—O4	1.4277 (18)	C16—H16B	0.9900
C4—H4B	0.9900	C16—H16A	0.9900
C4—H4A	0.9900	C17—O8	1.4108 (18)
C5—O4	1.4101 (18)	C17—O7	1.4149 (18)
C5—O3	1.4115 (18)	C17—C18	1.521 (2)
C5—C6	1.517 (2)	C17—H17A	1.0000
C5—H5A	1.0000	C18—C19	1.521 (2)
C6—C8	1.524 (2)	C18—C20	1.522 (2)
C6—C7	1.525 (2)	C18—H18A	1.0000
C6—H6A	1.0000	C19—H19A	0.9800
C7—H7A	0.9800	C19—H19B	0.9800
C7—H7B	0.9800	C19—H19C	0.9800
C7—H7C	0.9800	C20—H20C	0.9800
C8—H8A	0.9800	C20—H20B	0.9800
C8—H8B	0.9800	C20—H20A	0.9800
C8—H8C	0.9800	C21—O5	1.2161 (19)
C9—O1	1.2125 (18)	C21—N4	1.383 (2)
C9—N2	1.392 (2)	C21—C22	1.506 (2)
C9—C10	1.504 (2)	C22—C23	1.521 (2)
C10—C11	1.525 (2)	C22—H22A	0.9900
C10—H10A	0.9900	C22—H22B	0.9900
C10—H10B	0.9900	C23—C24	1.504 (2)
C11—C12	1.506 (2)	C23—H23A	0.9900
C11—H11B	0.9900	C23—H23B	0.9900
C11—H11A	0.9900	C24—O6	1.2109 (18)
C12—O2	1.2129 (19)	C24—N4	1.3915 (19)
C12—N2	1.384 (2)	N1—N2	1.4215 (17)
C13—O7	1.4259 (18)	N3—N4	1.4205 (17)
O3—C1—C2	116.29 (13)	N3—C14—C13	117.74 (12)
O3—C1—H1A	108.2	C15—C14—H14A	113.6
C2—C1—H1A	108.2	N3—C14—H14A	113.6
O3—C1—H1B	108.2	C13—C14—H14A	113.6
C2—C1—H1B	108.2	C14—C15—N3	60.43 (10)
H1A—C1—H1B	107.4	C14—C15—C16	128.99 (13)
C3—C2—N1	60.72 (10)	N3—C15—C16	117.77 (13)
C3—C2—C1	128.17 (14)	C14—C15—H15A	112.9
N1—C2—C1	117.71 (13)	N3—C15—H15A	112.9
C3—C2—H2A	113.2	C16—C15—H15A	112.9
N1—C2—H2A	113.2	O8—C16—C15	116.74 (12)
C1—C2—H2A	113.2	O8—C16—H16B	108.1
C2—C3—N1	60.16 (10)	C15—C16—H16B	108.1
C2—C3—C4	127.00 (13)	O8—C16—H16A	108.1
N1—C3—C4	118.14 (12)	C15—C16—H16A	108.1
C2—C3—H3A	113.6	H16B—C16—H16A	107.3
N1—C3—H3A	113.6	O8—C17—O7	110.08 (12)
C4—C3—H3A	113.6	O8—C17—C18	109.06 (13)
O4—C4—C3	116.04 (13)	O7—C17—C18	109.13 (13)
O4—C4—H4B	108.3	O8—C17—H17A	109.5
C3—C4—H4B	108.3	O7—C17—H17A	109.5
O4—C4—H4A	108.3	C18—C17—H17A	109.5
C3—C4—H4A	108.3	C17—C18—C19	112.30 (13)
H4B—C4—H4A	107.4	C17—C18—C20	110.36 (14)
O4—C5—O3	109.90 (12)	C19—C18—C20	111.29 (14)
O4—C5—C6	108.69 (13)	C17—C18—H18A	107.6
O3—C5—C6	108.63 (13)	C19—C18—H18A	107.6
O4—C5—H5A	109.9	C20—C18—H18A	107.6
O3—C5—H5A	109.9	C18—C19—H19A	109.5
C6—C5—H5A	109.9	C18—C19—H19B	109.5
C5—C6—C8	111.03 (14)	H19A—C19—H19B	109.5
C5—C6—C7	110.45 (14)	C18—C19—H19C	109.5
C8—C6—C7	110.25 (15)	H19A—C19—H19C	109.5
C5—C6—H6A	108.3	H19B—C19—H19C	109.5
C8—C6—H6A	108.3	C18—C20—H20C	109.5
C7—C6—H6A	108.3	C18—C20—H20B	109.5
C6—C7—H7A	109.5	H20C—C20—H20B	109.5
C6—C7—H7B	109.5	C18—C20—H20A	109.5
H7A—C7—H7B	109.5	H20C—C20—H20A	109.5
C6—C7—H7C	109.5	H20B—C20—H20A	109.5
H7A—C7—H7C	109.5	O5—C21—N4	124.22 (15)
H7B—C7—H7C	109.5	O5—C21—C22	128.67 (16)
C6—C8—H8A	109.5	N4—C21—C22	107.11 (13)
C6—C8—H8B	109.5	C21—C22—C23	105.75 (13)
H8A—C8—H8B	109.5	C21—C22—H22A	110.6
C6—C8—H8C	109.5	C23—C22—H22A	110.6
H8A—C8—H8C	109.5	C21—C22—H22B	110.6
H8B—C8—H8C	109.5	C23—C22—H22B	110.6
O1—C9—N2	124.16 (15)	H22A—C22—H22B	108.7
O1—C9—C10	128.77 (15)	C24—C23—C22	105.49 (13)
N2—C9—C10	107.06 (14)	C24—C23—H23A	110.6
C9—C10—C11	105.41 (13)	C22—C23—H23A	110.6
C9—C10—H10A	110.7	C24—C23—H23B	110.6
C11—C10—H10A	110.7	C22—C23—H23B	110.6
C9—C10—H10B	110.7	H23A—C23—H23B	108.8
C11—C10—H10B	110.7	O6—C24—N4	124.22 (14)
H10A—C10—H10B	108.8	O6—C24—C23	128.66 (15)
C12—C11—C10	105.81 (13)	N4—C24—C23	107.10 (13)
C12—C11—H11B	110.6	N2—N1—C2	110.51 (12)
C10—C11—H11B	110.6	N2—N1—C3	110.94 (11)
C12—C11—H11A	110.6	C2—N1—C3	59.12 (10)
C10—C11—H11A	110.6	C12—N2—C9	114.50 (13)
H11B—C11—H11A	108.7	C12—N2—N1	122.38 (12)
O2—C12—N2	124.45 (15)	C9—N2—N1	122.46 (13)
O2—C12—C11	128.59 (15)	N4—N3—C15	110.54 (11)
N2—C12—C11	106.96 (13)	N4—N3—C14	111.20 (11)
O7—C13—C14	115.66 (13)	C15—N3—C14	59.40 (9)
O7—C13—H13A	108.4	C21—N4—C24	114.33 (13)
C14—C13—H13A	108.4	C21—N4—N3	122.52 (12)
O7—C13—H13B	108.4	C24—N4—N3	122.54 (12)
C14—C13—H13B	108.4	C5—O3—C1	114.39 (12)
H13A—C13—H13B	107.4	C5—O4—C4	114.79 (11)
C15—C14—N3	60.17 (10)	C17—O7—C13	114.12 (12)
C15—C14—C13	127.08 (13)	C17—O8—C16	114.48 (12)