Three styryl-substituted tetra­hydro-1,4-epoxy-1-benzazepines: configurations, conformations and hydrogen-bonded chains

(2SR,4RS)-7-Chloro-2-exo-[(E)-styryl]-2,3,4,5-tetra­hydro-1H-1,4-epoxy-1-benzazepine, C₁₈H₁₆ClNO, (I), crystallizes as a racemic twin in the space group P2₁ and the mol­ecules are linked into a chain of edge-fused R₃³(9) rings by a combination of C—H...O and C—H...N hydrogen bonds. The diastereo­isomer (2RS,4RS)-7-chloro-2-endo-[(E)-styryl]-2,3,4,5-tetra­hydro-1H-1,4-epoxy-1-benzazepine, (II), also crystallizes as a racemic twin, but in the space group P2₁2₁2₁, and a two-centre C—H...N hydrogen bond and a three-centre C—H...(O,N) hydrogen bond combine to link the mol­ecules into a complex chain of rings. In (2R,4R)-7-fluoro-2-endo-[(E)-styryl]-2,3,4,5-tetra­hydro-1H-1,4-epoxy-1-benzazepine, C₁₈H₁₆FNO, (III), which is not isomorphous with (II), the mol­ecules are linked by a single C—H...O hydrogen bond into simple chains, but the mol­ecular arrangements in (II) and (III) are nonetheless very similar. The significance of this study lies in its observation of the variations in mol­ecular configuration and conformation, and in the variation in the supra­molecular aggregation, consequent upon modest changes in the peripheral substituents.

S1. Comment

The tetrahydro-1-benzazepine ring is an important pharmacophore in drug discovery and many of its derivatives exhibit a broad spectrum of biological activity (Zuccotto et al., 2001; Fabio et al., 2003; Zhao et al., 2003; Seto et al., 2005; Shimada et al., 2005; Kunick et al., 2006). Accordingly, a number of synthetic methods have recently been developed for the synthesis of new derivatives of this heterocyclic system (Fujita et al., 2004; Ikemoto et al., 2005; Qadir et al., 2005). In this context, we have recently developed a simple and efficient synthetic pathway to obtain new 1,4-epoxy-2-aryltetrahydro-1-benzazepines and 1,4-epoxy-2-aryltetrahydronaphtho[1,2-b]azepines and their reduced amino alcohols from readily available 2-allyl-N-benzyl-substituted anilines or naphthylamines, respectively (Gómez et al., 2006; Yépez et al., 2006). Compounds of this type show promising action against Trypanosoma cruzi and Leishmania chagasi parasites (Palma et al., 2008).

Based on these results, and as part of a programme to identify structurally novel anti-parasitic compounds with new modes of action to combat both T. cruzi and L. chagasi, we have focused our attention on the synthesis of a range of 2-substituted 1,4-epoxy-tetrahydro-1-benzazepines. We report here the structures of three styryl-substituted examples, compounds (I)–(III) (Figs. 1–3); further reports are planned, to deal with aryl-substituted examples and with examples carrying heterocyclic substituents at C2. A search of the Cambridge Structural Database (CSD, Version 5.29, November 2007; Allen, 2002) found 72 examples of the bicyclic perhydro-1-benzazepine skeleton, which is a sub-structural fragment of (I)–(III), but found no examples at all of the 1,4-epoxy-tetrahydro-1-benzazepine skeleton itself.

The synthesis of compounds (I)–(III) involved treating the corresponding 2-allyl-N-cinnamylanilines (A) with an excess of hydrogen peroxide solution in the presence of catalytic amounts of sodium tungstate, and subsequent internal 1,3-dipolar cycloaddition of the resulting nitrones (B) across the terminal C═C bond of the pendant allylic fragment connected to the ortho position, giving the tricyclic product (C) (see scheme). The 1,3-dipolar cycloaddition of these nitrones resulted in the formation of diastereomeric mixtures of both 2-exo- and 2-endo-1,4-epoxy-cycloadducts, which were successfully separated by column chromatography.

Compounds (I) and (II) were both found to crystallize as racemic twins; the reference molecules were selected as those having the R configuration at C4. The absolute configuration of (III) was indeterminate, so again the reference molecule was selected as having the R configuration at C4. On this basis, (I) has the S configuration at C2, while (II) and (III) have the R configuration at C2. Compounds (I) and (II) are thus diastereoisomers. However, despite the close similarity between the constitutions of (II) and (III), they are not isomorphous, crystallizing in space groups P2₁2₁2₁ and P2₁, respectively.

The shapes of the heterobicyclic ring systems in (I)–(III), as defined by the ring-puckering parameters (Cremer & Pople, 1975), are very similar (Table 1). For the five-membered rings, those in (II) and (III) adopt half-chair conformations, for which the ideal puckering angle ϕ is (36k + 18)°, where k represents zero or an integer. For the corresponding ring in (I), the conformation is intermediate between an envelope form, where the ideal value of ϕ is 36k°, and the half-chair form observed in the other examples. In each compound studied here, the conformation of the six-membered heterocyclic ring is intermediate between a half-chair form, where the idealized values of the ring-puckering angles are θ = 50.8° and ϕ = (60k + 30)°, and an envelope form, where the idealized values are θ = 54.7° and ϕ = 60k°.

In the title compounds, the torsion angle N1—C2—C21—C22 (Fig. 1) is 137.8 (3)° in (I), as opposed to -101.4 (3) and -104.56 (10)° in (II) and (III), respectively, possibly associated with the difference in configuration at C2 in (I) on the one hand and in (II) and (III) on the other. In addition, the torsion angle C21—C22—C221—C222 defining the orientation of the terminal aryl group is 22.7 (5)° in (I), as opposed to 3.5 (4)° in (II) and -1.45 (14)° in (III), again highlighting the conformational similarity between (II) and (III).

The hydrogen-bonded supramolecular structures of (I)–(III) are all one-dimensional. In compound (I), molecules related by the 2₁ screw axis along (1/2, y, 1/2) are linked by two hydrogen bonds (Table 2). The C—H···O and C—H···N hydrogen bonds acting individually give rise to C(3) and C(4) (Bernstein et al., 1995) chains, respectively, while the combination of these two hydrogen bonds generates a chain of edge-fused R₃³(9) rings (Fig. 2). Although compounds (II) and (III) are not isomorphous, their supramolecular hydrogen-bonded structures show considerable similarity. In compound (II), molecules related by translation along [100] are linked by a combination of one two-centre C—H···N hydrogen bond and one three-centre C—H···(N,O) hydrogen bond (Table 2). Although several of the individual components are quite long, the cooperative effect of the three individual components is probably significant. Acting individually, these interactions generate C(5), C(4) and C(4) chains, respectively, while in combination they generate an R²₂(7) motif divided into R²₁(3) and R¹₂(6) sectors (Fig. 3). In compound (III), in contrast, molecules related by translation along [100] are linked into simple C(4) chains (Fig. 4) by a single C—H···O hydrogen bond, the donor and acceptor of which correspond exactly to the C—H···O interaction in (III), although this interaction in (III) is characterized by significantly shorter H···O and C···O distances than its counterpart in (II) (Table 2). However, the slightly different mutual orientation of the molecules in (II) and (III) (Figs. 3 and 4) results in H3B···N1ⁱ and H5B···N1ⁱ [symmetry code: (i) 1 + x, y, z] distances in (III) of 3.08 and 2.74 Å, respectively, which are very much longer than the corresponding distances in (II) and well outside the range for effective hydrogen bonding. However, the overall arrangement of the molecules within the chains along [100] is remarkably similar in these two compounds (Figs. 3 and 4).

In summary, we have characterized three compounds containing a heterocyclic ring system whose structural characteristics have not previously been reported, we have analysed the supramolecular aggregation, and we have found that, for compounds (II) and (III), while the crystals are not isomorphous the molecular arrangements within the crystals are nonetheless very similar.

S2. Experimental

For each of compounds (I)–(III), to a stirred solution of the appropriately substituted 2-allylaniline (0.10 mol; see scheme) in methanol (40 ml) was added sodium tungstate dihydrate, Na₂WO₄.2H₂O (5 mol%), followed by 30% aqueous hydrogen peroxide solution (0.30 mol). The resulting mixtures were then stirred at ambient temperature for periods ranging from 8 to 72 h. Each mixture was then filtered and the solvent was removed under reduced pressure. Toluene (50 ml) was added to the solid residue and the resulting solution was heated under reflux for periods ranging from 3 h to 10 h. After cooling the solution to ambient temperature, the solvent was removed under reduced pressure and the crude product was purified by chromatography on silica using heptane–ethyl acetate (compositions ranged from 10:1 to 60:1 v/v) as eluent. Crystallization from heptane gave crystals of compounds (I)–(III) suitable for single-crystal X-ray diffraction.

For (I): colourless crystals, yield 54%, m.p. 415–416 K; MS (70 eV) m/z (%): 297 (M⁺, ³⁵Cl, 75), 296 (7), 280 (36), 267 (11), 164 (32), 139 (71), 138 (100), 130 (96), 129 (77), 128 (41), 112 (25). Analysis, found: C 72.4, H 5.8, N 4.5%; C₁₈H₁₆ClNO requires: C 72.6, H 5.4, N 4.7%.

For (II): colourless crystals, yield 25%, m.p. 403–404 K; MS (70 eV) m/z (%): 297 (M⁺, ³⁵Cl, 67), 296 (11), 280 (36), 267 (11), 164 (27), 139 (72), 138 (100), 130 (95), 129 (76), 128 (44), 112 (23). Analysis, found: C 72.9, H 5.1, N 4.5%; C₁₈H₁₆ClNO requires: C 72.6, H 5.4, N 4.7%.

For (III): orange crystals, yield 20%, m.p. 407–408 K; MS (70 eV) m/z (%): 281 (M⁺, 64), 280 (41), 264 (33), 251 (12), 148 (29), 130 (62), 129 (58), 128 (33), 123 (56), 122 (100), 96 (30). Analysis, found: C 76.6, H 5.9, N 4.8%; C₁₈H₁₆FNO requires: C 76.8, H 5.7, N 5.0%.

S3. Refinement

The space group P2₁2₁2₁ was uniquely assigned from the systematic absences for compound (II). For compounds (I) and (III), the systematic absences permitted P2₁ or P2₁/m as possible space groups; in each case, P2₁ was selected and confirmed by the subsequent structure analyses. All H atoms were located in difference maps and then treated as riding atoms in geometrically idealized positions, with C—H = 0.95 (aromatic, heteroaromatic and alkene), 0.99 (CH₂) or 1.00 Å (aliphatic CH), and with U_iso(H) = 1.2U_eq(C). In the absence of significant resonant scattering in (III), the Flack parameter (Flack, 1983) was indeterminate (Flack & Bernardinelli, 2000), and hence Friedel-equivalent reflections were merged prior to the final refinements; the reference molecule in (III) was set to have the R configuration at C4. Compounds (I) and (II) crystallized as racemic twins and they were refined using the TWIN and BASF instructions in SHELXL97 (Sheldrick, 2008), giving twin fractions of 0.32 (9)/0.68 (9) in (I) and 0.44 (8)/0.56 (8) in (II), and again the reference molecules were chosen as those having the R configuration at C4.

Computing details

For all compounds, data collection: COLLECT (Nonius, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PRPKAPPA (Ferguson, 1999).

Figures

	Fig. 1. The molecular structure of compound (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The molecular structure of compound (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. The molecular structure of compound (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 4. A stereoview of part of the crystal structure of compound (I), showing the formation of a hydrogen-bonded chain of edge-fused R3^3(9) rings along [010]. For the sake of clarity, H atoms bonded to C atoms which are not involved in the motif shown have been omitted.
	Fig. 5. A stereoview of part of the crystal structure of compound (II), showing the formation of a hydrogen-bonded chain of rings along [100]. For the sake of clarity, H atoms bonded to C atoms which are not involved in the motif shown have been omitted.
	Fig. 6. A stereoview of part of the crystal structure of compound (III), showing the formation of a hydrogen-bonded C(4) chain along [100]. For the sake of clarity, only the H atoms bonded to atoms C3 and C5 are shown.

(I) (2SR,4RS)-7-Chloro-2-exo-[(E)-styryl]-2,3,4,5-tetrahydro- 1,4-epoxy-1H-1-benzazepine

Crystal data

C18H16ClNO	F(000) = 312
Mr = 297.77	Dx = 1.359 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 3305 reflections
a = 10.5798 (8) Å	θ = 5.1–27.5°
b = 5.3448 (10) Å	µ = 0.26 mm^−1
c = 12.873 (3) Å	T = 120 K
β = 90.204 (12)°	Lath, colourless
V = 727.9 (2) Å^3	0.45 × 0.15 × 0.08 mm
Z = 2

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	3305 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	2033 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.083
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 5.1°
ϕ and ω scans	h = −13→13
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −6→6
Tmin = 0.924, Tmax = 0.979	l = −16→16
17564 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)] = 0.050	H-atom parameters constrained
wR(F^2) = 0.120	w = 1/[σ^2(Fo^2) + (0.048P)^2 + 0.173P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
3305 reflections	Δρmax = 0.31 e Å^−3
191 parameters	Δρmin = −0.33 e Å^−3
1 restraint	Absolute structure: Flack (1983), with 1460 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.32 (9)

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

	x	y	z	Uiso*/Ueq
Cl7	1.20480 (7)	0.6898 (2)	0.65479 (7)	0.0577 (3)
O14	0.62139 (18)	0.3471 (4)	0.57943 (17)	0.0416 (6)
N1	0.6811 (2)	0.3167 (5)	0.67945 (19)	0.0321 (6)
C2	0.6050 (3)	0.4855 (6)	0.7457 (3)	0.0359 (8)
C3	0.5667 (3)	0.7010 (7)	0.6734 (3)	0.0493 (9)
C4	0.6093 (3)	0.6136 (6)	0.5665 (3)	0.0469 (9)
C5	0.7361 (3)	0.7137 (7)	0.5354 (2)	0.0425 (8)
C5a	0.8373 (3)	0.6060 (5)	0.6031 (2)	0.0309 (7)
C6	0.9611 (3)	0.6886 (7)	0.5988 (2)	0.0355 (7)
C7	1.0508 (3)	0.5803 (6)	0.6613 (2)	0.0361 (8)
C8	1.0234 (3)	0.3899 (7)	0.7272 (2)	0.0382 (8)
C9	0.8999 (3)	0.3028 (6)	0.7310 (2)	0.0354 (8)
C9a	0.8085 (2)	0.4117 (5)	0.6701 (2)	0.0287 (7)
C21	0.4925 (2)	0.3474 (6)	0.7873 (3)	0.0363 (8)
C22	0.4526 (3)	0.3671 (6)	0.8840 (3)	0.0368 (8)
C221	0.3400 (3)	0.2490 (5)	0.9274 (2)	0.0317 (7)
C222	0.2866 (3)	0.0386 (6)	0.8834 (2)	0.0375 (8)
C223	0.1788 (3)	−0.0674 (6)	0.9246 (2)	0.0379 (8)
C224	0.1238 (3)	0.0329 (6)	1.0107 (2)	0.0373 (8)
C225	0.1763 (3)	0.2392 (6)	1.0569 (2)	0.0400 (8)
C226	0.2837 (3)	0.3460 (6)	1.0163 (2)	0.0367 (8)
H2	0.6578	0.5505	0.8043	0.043*
H3A	0.4742	0.7285	0.6748	0.059*
H3B	0.6100	0.8581	0.6934	0.059*
H4	0.5440	0.6539	0.5127	0.056*
H5A	0.7530	0.6701	0.4620	0.051*
H5B	0.7363	0.8983	0.5415	0.051*
H6	0.9838	0.8199	0.5528	0.043*
H8	1.0873	0.3179	0.7698	0.046*
H9	0.8786	0.1679	0.7757	0.043*
H21	0.4476	0.2397	0.7415	0.044*
H22	0.5017	0.4676	0.9297	0.044*
H222	0.3244	−0.0343	0.8238	0.045*
H223	0.1428	−0.2112	0.8928	0.046*
H224	0.0494	−0.0401	1.0385	0.045*
H225	0.1385	0.3087	1.1172	0.048*
H226	0.3199	0.4880	1.0493	0.044*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl7	0.0311 (4)	0.0791 (7)	0.0629 (6)	−0.0168 (5)	0.0110 (4)	−0.0268 (5)
O14	0.0376 (12)	0.0313 (13)	0.0558 (14)	−0.0017 (10)	−0.0188 (10)	−0.0034 (11)
N1	0.0254 (13)	0.0295 (14)	0.0413 (15)	−0.0004 (10)	−0.0063 (11)	−0.0017 (12)
C2	0.0250 (15)	0.0312 (18)	0.051 (2)	−0.0015 (14)	−0.0014 (14)	−0.0104 (15)
C3	0.0222 (15)	0.0321 (18)	0.094 (3)	0.0023 (16)	0.0015 (16)	−0.002 (2)
C4	0.0400 (19)	0.037 (2)	0.064 (2)	0.0040 (15)	−0.0237 (17)	0.0095 (17)
C5	0.0489 (19)	0.0340 (19)	0.0444 (19)	0.0012 (18)	−0.0105 (15)	0.0070 (17)
C5a	0.0347 (17)	0.0266 (17)	0.0315 (17)	0.0013 (13)	−0.0045 (13)	−0.0019 (13)
C6	0.0373 (16)	0.0330 (17)	0.0362 (17)	−0.0094 (17)	0.0052 (13)	−0.0010 (17)
C7	0.0305 (17)	0.043 (2)	0.0347 (18)	−0.0054 (14)	0.0051 (14)	−0.0149 (16)
C8	0.0230 (15)	0.053 (2)	0.0383 (18)	0.0081 (15)	−0.0061 (13)	0.0016 (17)
C9	0.0316 (17)	0.0364 (19)	0.0382 (18)	0.0052 (14)	0.0003 (14)	0.0028 (15)
C9a	0.0268 (15)	0.0261 (17)	0.0331 (17)	0.0021 (13)	−0.0026 (13)	−0.0043 (13)
C21	0.0207 (14)	0.0341 (18)	0.054 (2)	−0.0026 (14)	−0.0040 (14)	−0.0071 (16)
C22	0.0267 (16)	0.0343 (19)	0.049 (2)	0.0000 (14)	−0.0065 (14)	−0.0070 (17)
C221	0.0261 (15)	0.034 (2)	0.0350 (17)	0.0026 (14)	−0.0077 (13)	0.0018 (14)
C222	0.0340 (17)	0.037 (2)	0.0417 (19)	0.0011 (14)	−0.0006 (15)	−0.0028 (16)
C223	0.0366 (17)	0.034 (2)	0.0429 (19)	−0.0046 (15)	−0.0026 (15)	−0.0029 (15)
C224	0.0310 (17)	0.039 (2)	0.0417 (19)	−0.0018 (14)	−0.0036 (15)	0.0022 (17)
C225	0.0366 (17)	0.047 (2)	0.0365 (18)	0.0071 (17)	0.0004 (14)	−0.0036 (16)
C226	0.0362 (17)	0.0325 (19)	0.0414 (19)	0.0009 (15)	−0.0102 (14)	−0.0025 (16)

Geometric parameters (Å, º)

Cl7—C7	1.733 (3)	C7—C8	1.357 (5)
O14—C4	1.439 (4)	C8—C9	1.389 (4)
O14—N1	1.441 (3)	C8—H8	0.95
N1—C9a	1.446 (4)	C9—C9a	1.372 (4)
N1—C2	1.481 (4)	C9—H9	0.95
C2—C21	1.500 (4)	C21—C22	1.321 (4)
C2—C3	1.534 (5)	C21—H21	0.95
C2—H2	1.00	C22—C221	1.461 (4)
C3—C4	1.522 (5)	C22—H22	0.95
C3—H3A	0.99	C221—C222	1.379 (4)
C3—H3B	0.99	C221—C226	1.391 (4)
C4—C5	1.501 (4)	C222—C223	1.381 (4)
C4—H4	1.00	C222—H222	0.95
C5—C5a	1.494 (4)	C223—C224	1.363 (4)
C5—H5A	0.99	C223—H223	0.95
C5—H5B	0.99	C224—C225	1.370 (4)
C5a—C6	1.384 (4)	C224—H224	0.95
C5a—C9a	1.384 (4)	C225—C226	1.377 (4)
C6—C7	1.370 (4)	C225—H225	0.95
C6—H6	0.95	C226—H226	0.95
C4—O14—N1	104.7 (2)	C8—C7—Cl7	119.1 (3)
O14—N1—C9a	107.0 (2)	C6—C7—Cl7	118.6 (3)
O14—N1—C2	102.0 (2)	C7—C8—C9	118.5 (3)
C9a—N1—C2	110.0 (2)	C7—C8—H8	120.8
N1—C2—C21	109.8 (2)	C9—C8—H8	120.8
N1—C2—C3	104.5 (3)	C9a—C9—C8	119.9 (3)
C21—C2—C3	112.3 (2)	C9a—C9—H9	120.0
N1—C2—H2	110.0	C8—C9—H9	120.0
C21—C2—H2	110.0	C9—C9a—C5a	121.2 (3)
C3—C2—H2	110.0	C9—C9a—N1	117.3 (3)
C4—C3—C2	103.9 (3)	C5a—C9a—N1	121.5 (2)
C4—C3—H3A	111.0	C22—C21—C2	123.7 (3)
C2—C3—H3A	111.0	C22—C21—H21	118.2
C4—C3—H3B	111.0	C2—C21—H21	118.2
C2—C3—H3B	111.0	C21—C22—C221	126.2 (3)
H3A—C3—H3B	109.0	C21—C22—H22	116.9
O14—C4—C5	107.7 (3)	C221—C22—H22	116.9
O14—C4—C3	103.1 (3)	C222—C221—C226	117.8 (3)
C5—C4—C3	113.6 (3)	C222—C221—C22	121.9 (3)
O14—C4—H4	110.7	C226—C221—C22	120.3 (3)
C5—C4—H4	110.7	C221—C222—C223	121.0 (3)
C3—C4—H4	110.7	C221—C222—H222	119.5
C5a—C5—C4	110.2 (3)	C223—C222—H222	119.5
C5a—C5—H5A	109.6	C224—C223—C222	120.4 (3)
C4—C5—H5A	109.6	C224—C223—H223	119.8
C5a—C5—H5B	109.6	C222—C223—H223	119.8
C4—C5—H5B	109.6	C223—C224—C225	119.8 (3)
H5A—C5—H5B	108.1	C223—C224—H224	120.1
C6—C5a—C9a	118.3 (3)	C225—C224—H224	120.1
C6—C5a—C5	122.0 (3)	C224—C225—C226	120.2 (3)
C9a—C5a—C5	119.6 (3)	C224—C225—H225	119.9
C7—C6—C5a	119.7 (3)	C226—C225—H225	119.9
C7—C6—H6	120.1	C225—C226—C221	120.9 (3)
C5a—C6—H6	120.1	C225—C226—H226	119.5
C8—C7—C6	122.3 (3)	C221—C226—H226	119.5
C4—O14—N1—C9a	−67.9 (3)	C8—C9—C9a—C5a	1.0 (4)
C4—O14—N1—C2	47.6 (3)	C8—C9—C9a—N1	−178.5 (3)
O14—N1—C2—C21	87.4 (3)	C6—C5a—C9a—C9	0.0 (4)
C9a—N1—C2—C21	−159.3 (2)	C5—C5a—C9a—C9	177.8 (3)
O14—N1—C2—C3	−33.2 (3)	C6—C5a—C9a—N1	179.5 (3)
C9a—N1—C2—C3	80.1 (3)	C5—C5a—C9a—N1	−2.7 (4)
N1—C2—C3—C4	8.2 (3)	O14—N1—C9a—C9	−149.2 (2)
C21—C2—C3—C4	−110.7 (3)	C2—N1—C9a—C9	100.8 (3)
N1—O14—C4—C5	78.3 (3)	O14—N1—C9a—C5a	31.3 (3)
N1—O14—C4—C3	−42.0 (3)	C2—N1—C9a—C5a	−78.7 (3)
C2—C3—C4—O14	19.8 (3)	N1—C2—C21—C22	137.8 (3)
C2—C3—C4—C5	−96.5 (3)	C3—C2—C21—C22	−106.4 (4)
O14—C4—C5—C5a	−46.3 (4)	C2—C21—C22—C221	176.3 (3)
C3—C4—C5—C5a	67.1 (4)	C21—C22—C221—C222	22.7 (5)
C4—C5—C5a—C6	−172.5 (3)	C21—C22—C221—C226	−158.0 (3)
C4—C5—C5a—C9a	9.8 (4)	C226—C221—C222—C223	1.8 (4)
C9a—C5a—C6—C7	−1.0 (4)	C22—C221—C222—C223	−178.8 (3)
C5—C5a—C6—C7	−178.8 (3)	C221—C222—C223—C224	−0.7 (5)
C5a—C6—C7—C8	1.0 (5)	C222—C223—C224—C225	−0.4 (5)
C5a—C6—C7—Cl7	−179.5 (2)	C223—C224—C225—C226	0.5 (4)
C6—C7—C8—C9	0.0 (5)	C224—C225—C226—C221	0.7 (4)
Cl7—C7—C8—C9	−179.5 (2)	C222—C221—C226—C225	−1.8 (4)
C7—C8—C9—C9a	−1.0 (5)	C22—C221—C226—C225	178.9 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3B···N1^i	0.99	2.57	3.507 (5)	158
C4—H4···O14^ii	1.00	2.35	3.318 (4)	163

Symmetry codes: (i) x, y+1, z; (ii) −x+1, y+1/2, −z+1.

(II) (2RS,4RS)-7-Chloro-2-endo-[(E)-styryl]-2,3,4,5-tetrahydro- 1,4-epoxy-1H-1-benzazepine

Crystal data

C18H16ClNO	F(000) = 624
Mr = 297.77	Dx = 1.337 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3384 reflections
a = 5.2855 (10) Å	θ = 3.5–27.5°
b = 15.649 (2) Å	µ = 0.26 mm^−1
c = 17.880 (3) Å	T = 120 K
V = 1478.9 (4) Å^3	Block, colourless
Z = 4	0.36 × 0.27 × 0.14 mm

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	3384 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	2525 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.063
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.5°
ϕ and ω scans	h = −6→6
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −20→20
Tmin = 0.929, Tmax = 0.965	l = −23→23
32581 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)] = 0.047	H-atom parameters constrained
wR(F^2) = 0.084	w = 1/[σ^2(Fo^2) + (0.0236P)^2 + 0.5604P] where P = (Fo^2 + 2Fc^2)/3
S = 1.12	(Δ/σ)max = 0.001
3384 reflections	Δρmax = 0.24 e Å^−3
191 parameters	Δρmin = −0.22 e Å^−3
0 restraints	Absolute structure: Flack (1983), with 1401 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.44 (8)

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

	x	y	z	Uiso*/Ueq
Cl7	0.26769 (16)	0.37935 (4)	0.83238 (3)	0.04339 (19)
O14	0.5908 (3)	0.69616 (9)	0.61265 (10)	0.0305 (4)
N1	0.6466 (3)	0.60833 (11)	0.59337 (11)	0.0271 (5)
C2	0.5013 (5)	0.59945 (15)	0.52196 (13)	0.0269 (6)
C3	0.2559 (5)	0.65030 (13)	0.53609 (12)	0.0255 (5)
C4	0.3163 (4)	0.70133 (14)	0.60672 (13)	0.0264 (5)
C5	0.2071 (5)	0.66351 (12)	0.67763 (11)	0.0240 (5)
C5a	0.3357 (4)	0.57909 (13)	0.69370 (12)	0.0209 (5)
C6	0.2514 (5)	0.52469 (13)	0.75038 (12)	0.0238 (5)
C7	0.3772 (5)	0.44850 (14)	0.76345 (12)	0.0261 (6)
C8	0.5868 (5)	0.42502 (14)	0.72237 (13)	0.0277 (6)
C9	0.6709 (4)	0.47882 (13)	0.66638 (14)	0.0271 (5)
C9a	0.5462 (4)	0.55505 (13)	0.65238 (12)	0.0211 (5)
C21	0.4707 (5)	0.50834 (15)	0.49879 (13)	0.0261 (6)
C22	0.6092 (5)	0.47215 (15)	0.44635 (13)	0.0274 (6)
C221	0.5971 (4)	0.38406 (15)	0.41849 (12)	0.0232 (5)
C222	0.4196 (5)	0.32487 (16)	0.44247 (13)	0.0317 (6)
C223	0.4147 (5)	0.24267 (17)	0.41448 (14)	0.0343 (6)
C224	0.5891 (5)	0.21790 (16)	0.36117 (14)	0.0326 (6)
C225	0.7634 (6)	0.27566 (15)	0.33536 (15)	0.0405 (6)
C226	0.7685 (5)	0.35768 (14)	0.36393 (14)	0.0359 (6)
H2	0.5982	0.6295	0.4818	0.032*
H3A	0.2174	0.6887	0.4936	0.031*
H3B	0.1106	0.6115	0.5443	0.031*
H4	0.2614	0.7621	0.6008	0.032*
H5A	0.2341	0.7033	0.7199	0.029*
H5B	0.0228	0.6546	0.6716	0.029*
H6	0.1085	0.5398	0.7798	0.029*
H8	0.6718	0.3728	0.7324	0.033*
H9	0.8146	0.4635	0.6374	0.033*
H21	0.3453	0.4748	0.5231	0.031*
H22	0.7329	0.5077	0.4236	0.033*
H222	0.2985	0.3413	0.4790	0.038*
H223	0.2915	0.2032	0.4319	0.041*
H224	0.5883	0.1611	0.3425	0.039*
H225	0.8808	0.2593	0.2978	0.049*
H226	0.8915	0.3969	0.3460	0.043*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl7	0.0695 (5)	0.0337 (3)	0.0270 (3)	0.0059 (4)	0.0102 (4)	0.0102 (3)
O14	0.0242 (9)	0.0181 (8)	0.0493 (10)	−0.0046 (7)	−0.0068 (8)	0.0023 (8)
N1	0.0228 (11)	0.0182 (10)	0.0403 (12)	−0.0024 (8)	−0.0018 (9)	0.0027 (9)
C2	0.0239 (13)	0.0279 (13)	0.0290 (13)	−0.0012 (11)	0.0056 (11)	0.0070 (10)
C3	0.0254 (13)	0.0267 (11)	0.0244 (11)	0.0031 (12)	−0.0014 (12)	0.0050 (9)
C4	0.0248 (14)	0.0191 (11)	0.0353 (13)	0.0052 (10)	−0.0060 (11)	0.0037 (10)
C5	0.0255 (13)	0.0208 (11)	0.0257 (12)	0.0056 (10)	−0.0060 (11)	−0.0045 (9)
C5a	0.0242 (13)	0.0191 (11)	0.0194 (10)	−0.0025 (10)	−0.0084 (9)	−0.0063 (9)
C6	0.0264 (13)	0.0259 (11)	0.0191 (10)	0.0019 (12)	−0.0025 (11)	−0.0041 (9)
C7	0.0394 (16)	0.0209 (12)	0.0179 (12)	−0.0036 (11)	−0.0047 (11)	−0.0002 (9)
C8	0.0319 (14)	0.0182 (11)	0.0330 (13)	0.0036 (11)	−0.0069 (12)	−0.0001 (10)
C9	0.0213 (13)	0.0241 (12)	0.0360 (13)	−0.0009 (9)	−0.0006 (11)	−0.0004 (11)
C9a	0.0191 (12)	0.0164 (11)	0.0279 (13)	−0.0043 (10)	−0.0048 (10)	0.0012 (9)
C21	0.0276 (14)	0.0263 (13)	0.0245 (12)	−0.0038 (12)	0.0063 (12)	0.0065 (10)
C22	0.0265 (14)	0.0284 (13)	0.0274 (13)	−0.0011 (11)	0.0041 (11)	0.0091 (11)
C221	0.0202 (12)	0.0290 (12)	0.0205 (11)	0.0002 (11)	−0.0014 (10)	0.0062 (10)
C222	0.0282 (14)	0.0408 (15)	0.0260 (12)	−0.0057 (13)	0.0068 (12)	−0.0040 (11)
C223	0.0313 (15)	0.0389 (15)	0.0327 (14)	−0.0102 (13)	0.0024 (13)	−0.0026 (12)
C224	0.0301 (15)	0.0350 (14)	0.0329 (14)	−0.0021 (12)	−0.0013 (13)	−0.0058 (11)
C225	0.0344 (15)	0.0406 (14)	0.0467 (15)	0.0007 (14)	0.0189 (16)	−0.0082 (13)
C226	0.0274 (14)	0.0327 (13)	0.0477 (15)	−0.0060 (13)	0.0144 (14)	0.0019 (11)

Geometric parameters (Å, º)

Cl7—C7	1.739 (2)	C7—C8	1.379 (3)
O14—N1	1.447 (2)	C8—C9	1.382 (3)
O14—C4	1.457 (3)	C8—H8	0.95
N1—C9a	1.446 (3)	C9—C9a	1.386 (3)
N1—C2	1.497 (3)	C9—H9	0.95
C2—C21	1.494 (3)	C21—C22	1.317 (3)
C2—C3	1.542 (3)	C21—H21	0.95
C2—H2	1.00	C22—C221	1.467 (3)
C3—C4	1.528 (3)	C22—H22	0.95
C3—H3A	0.99	C221—C222	1.386 (3)
C3—H3B	0.99	C221—C226	1.394 (3)
C4—C5	1.513 (3)	C222—C223	1.381 (4)
C4—H4	1.00	C222—H222	0.95
C5—C5a	1.513 (3)	C223—C224	1.381 (4)
C5—H5A	0.99	C223—H223	0.95
C5—H5B	0.99	C224—C225	1.371 (4)
C5a—C9a	1.387 (3)	C224—H224	0.95
C5a—C6	1.397 (3)	C225—C226	1.382 (3)
C6—C7	1.385 (3)	C225—H225	0.95
C6—H6	0.95	C226—H226	0.95
N1—O14—C4	103.78 (15)	C8—C7—Cl7	118.61 (18)
C9a—N1—O14	107.40 (17)	C6—C7—Cl7	119.70 (19)
C9a—N1—C2	112.37 (17)	C7—C8—C9	118.8 (2)
O14—N1—C2	100.76 (16)	C7—C8—H8	120.6
C21—C2—N1	112.38 (19)	C9—C8—H8	120.6
C21—C2—C3	116.6 (2)	C8—C9—C9a	120.2 (2)
N1—C2—C3	104.12 (18)	C8—C9—H9	119.9
C21—C2—H2	107.8	C9a—C9—H9	119.9
N1—C2—H2	107.8	C9—C9a—C5a	121.2 (2)
C3—C2—H2	107.8	C9—C9a—N1	117.0 (2)
C4—C3—C2	103.26 (19)	C5a—C9a—N1	121.78 (19)
C4—C3—H3A	111.1	C22—C21—C2	123.2 (2)
C2—C3—H3A	111.1	C22—C21—H21	118.4
C4—C3—H3B	111.1	C2—C21—H21	118.4
C2—C3—H3B	111.1	C21—C22—C221	128.4 (2)
H3A—C3—H3B	109.1	C21—C22—H22	115.8
O14—C4—C5	107.28 (18)	C221—C22—H22	115.8
O14—C4—C3	103.85 (19)	C222—C221—C226	117.3 (2)
C5—C4—C3	114.10 (18)	C222—C221—C22	123.5 (2)
O14—C4—H4	110.5	C226—C221—C22	119.2 (2)
C5—C4—H4	110.5	C223—C222—C221	121.5 (2)
C3—C4—H4	110.5	C223—C222—H222	119.2
C5a—C5—C4	109.22 (18)	C221—C222—H222	119.2
C5a—C5—H5A	109.8	C222—C223—C224	119.9 (2)
C4—C5—H5A	109.8	C222—C223—H223	120.0
C5a—C5—H5B	109.8	C224—C223—H223	120.0
C4—C5—H5B	109.8	C225—C224—C223	119.7 (2)
H5A—C5—H5B	108.3	C225—C224—H224	120.1
C9a—C5a—C6	118.5 (2)	C223—C224—H224	120.1
C9a—C5a—C5	119.7 (2)	C224—C225—C226	120.1 (2)
C6—C5a—C5	121.8 (2)	C224—C225—H225	120.0
C7—C6—C5a	119.6 (2)	C226—C225—H225	120.0
C7—C6—H6	120.2	C225—C226—C221	121.4 (2)
C5a—C6—H6	120.2	C225—C226—H226	119.3
C8—C7—C6	121.7 (2)	C221—C226—H226	119.3
C4—O14—N1—C9a	−67.7 (2)	C8—C9—C9a—C5a	−0.1 (3)
C4—O14—N1—C2	50.05 (19)	C8—C9—C9a—N1	179.5 (2)
C9a—N1—C2—C21	−51.5 (3)	C6—C5a—C9a—C9	0.2 (3)
O14—N1—C2—C21	−165.50 (18)	C5—C5a—C9a—C9	179.0 (2)
C9a—N1—C2—C3	75.6 (2)	C6—C5a—C9a—N1	−179.3 (2)
O14—N1—C2—C3	−38.5 (2)	C5—C5a—C9a—N1	−0.5 (3)
C21—C2—C3—C4	138.1 (2)	O14—N1—C9a—C9	−149.90 (19)
N1—C2—C3—C4	13.7 (2)	C2—N1—C9a—C9	100.2 (2)
N1—O14—C4—C5	79.8 (2)	O14—N1—C9a—C5a	29.6 (3)
N1—O14—C4—C3	−41.4 (2)	C2—N1—C9a—C5a	−80.3 (2)
C2—C3—C4—O14	15.9 (2)	N1—C2—C21—C22	−101.4 (3)
C2—C3—C4—C5	−100.5 (2)	C3—C2—C21—C22	138.5 (2)
O14—C4—C5—C5a	−47.7 (2)	C2—C21—C22—C221	−179.7 (2)
C3—C4—C5—C5a	66.8 (2)	C21—C22—C221—C222	3.5 (4)
C4—C5—C5a—C9a	9.4 (3)	C21—C22—C221—C226	−177.8 (3)
C4—C5—C5a—C6	−171.8 (2)	C226—C221—C222—C223	1.0 (4)
C9a—C5a—C6—C7	−0.5 (3)	C22—C221—C222—C223	179.8 (2)
C5—C5a—C6—C7	−179.3 (2)	C221—C222—C223—C224	−0.2 (4)
C5a—C6—C7—C8	0.7 (3)	C222—C223—C224—C225	−1.2 (4)
C5a—C6—C7—Cl7	−178.36 (17)	C223—C224—C225—C226	1.6 (4)
C6—C7—C8—C9	−0.6 (3)	C224—C225—C226—C221	−0.7 (4)
Cl7—C7—C8—C9	178.51 (18)	C222—C221—C226—C225	−0.6 (4)
C7—C8—C9—C9a	0.3 (3)	C22—C221—C226—C225	−179.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3B···N1^i	0.99	2.61	3.443 (3)	142
C5—H5B···N1^i	0.99	2.54	3.434 (3)	151
C5—H5B···O14^i	0.99	2.60	3.496 (3)	151

Symmetry code: (i) x−1, y, z.

(III) (2R,4R)-7-fluoro-2-endo-[(E)-styryl]-2,3,4,5-tetrahydro- 1,4-epoxy-1H-1-benzazepine

Crystal data

C18H16FNO	F(000) = 296
Mr = 281.32	Dx = 1.335 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1715 reflections
a = 5.4172 (2) Å	θ = 3.6–27.5°
b = 8.0164 (6) Å	µ = 0.09 mm^−1
c = 16.2310 (11) Å	T = 120 K
β = 96.745 (4)°	Block, orange
V = 699.98 (8) Å^3	0.23 × 0.21 × 0.15 mm
Z = 2

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	1715 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	1510 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.6°
ϕ and ω scans	h = −6→7
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −10→10
Tmin = 0.970, Tmax = 0.986	l = −21→20
16046 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)] = 0.035	H-atom parameters constrained
wR(F^2) = 0.083	w = 1/[σ^2(Fo^2) + (0.0366P)^2 + 0.1566P] where P = (Fo^2 + 2Fc^2)/3
S = 1.17	(Δ/σ)max < 0.001
1715 reflections	Δρmax = 0.17 e Å^−3
190 parameters	Δρmin = −0.22 e Å^−3
1 restraint	Absolute structure: Flack (1983), with Friedel pairs merged
Primary atom site location: structure-invariant direct methods

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

	x	y	z	Uiso*/Ueq
F7	1.0264 (3)	−0.14342 (19)	0.23347 (10)	0.0409 (4)
O14	0.3957 (3)	0.4145 (2)	0.04915 (8)	0.0253 (3)
N1	0.4135 (3)	0.3925 (3)	0.13836 (10)	0.0220 (4)
C2	0.5376 (4)	0.5523 (3)	0.16776 (13)	0.0239 (4)
C3	0.7282 (4)	0.5844 (3)	0.10512 (13)	0.0269 (5)
C4	0.6459 (4)	0.4639 (3)	0.03407 (13)	0.0262 (5)
C5	0.8014 (4)	0.3069 (3)	0.03615 (13)	0.0261 (5)
C5a	0.7630 (4)	0.2072 (3)	0.11269 (13)	0.0225 (5)
C6	0.9128 (4)	0.0705 (3)	0.13801 (14)	0.0271 (5)
C7	0.8722 (4)	−0.0146 (3)	0.20819 (15)	0.0287 (5)
C8	0.6846 (4)	0.0262 (3)	0.25577 (14)	0.0285 (5)
C9	0.5330 (4)	0.1600 (3)	0.22982 (13)	0.0242 (5)
C9a	0.5735 (4)	0.2502 (3)	0.15977 (13)	0.0201 (4)
C21	0.6481 (4)	0.5455 (3)	0.25676 (13)	0.0235 (4)
C22	0.5467 (4)	0.6184 (3)	0.31775 (13)	0.0225 (4)
C221	0.6475 (4)	0.6221 (3)	0.40601 (13)	0.0201 (4)
C222	0.8684 (4)	0.5415 (3)	0.43665 (13)	0.0247 (5)
C223	0.9548 (4)	0.5455 (3)	0.52044 (13)	0.0271 (5)
C224	0.8224 (4)	0.6303 (3)	0.57557 (14)	0.0265 (5)
C225	0.6038 (4)	0.7116 (3)	0.54635 (14)	0.0286 (5)
C226	0.5178 (4)	0.7069 (3)	0.46232 (13)	0.0246 (5)
H2	0.4107	0.6435	0.1616	0.029*
H3A	0.7203	0.7015	0.0856	0.032*
H3B	0.8996	0.5595	0.1303	0.032*
H4	0.6426	0.5213	−0.0208	0.031*
H5A	0.7518	0.2395	−0.0142	0.031*
H5B	0.9791	0.3365	0.0372	0.031*
H6	1.0419	0.0369	0.1067	0.033*
H8	0.6609	−0.0351	0.3043	0.034*
H9	0.4002	0.1900	0.2602	0.029*
H21	0.7989	0.4857	0.2701	0.028*
H22	0.3930	0.6740	0.3031	0.027*
H222	0.9605	0.4831	0.3995	0.030*
H223	1.1052	0.4901	0.5402	0.032*
H224	0.8814	0.6326	0.6330	0.032*
H225	0.5129	0.7704	0.5837	0.034*
H226	0.3675	0.7627	0.4428	0.030*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F7	0.0382 (8)	0.0273 (8)	0.0544 (10)	0.0067 (6)	−0.0062 (7)	0.0031 (7)
O14	0.0168 (7)	0.0414 (9)	0.0168 (7)	−0.0031 (7)	−0.0014 (5)	0.0034 (7)
N1	0.0205 (8)	0.0307 (10)	0.0145 (8)	−0.0012 (8)	0.0000 (6)	0.0005 (8)
C2	0.0231 (10)	0.0259 (11)	0.0218 (10)	0.0006 (9)	−0.0012 (8)	0.0017 (9)
C3	0.0256 (11)	0.0305 (13)	0.0236 (11)	−0.0061 (9)	−0.0010 (9)	0.0057 (9)
C4	0.0205 (10)	0.0390 (13)	0.0184 (10)	−0.0066 (9)	0.0001 (8)	0.0051 (9)
C5	0.0200 (10)	0.0398 (13)	0.0184 (10)	−0.0061 (10)	0.0021 (8)	−0.0019 (10)
C5a	0.0194 (10)	0.0280 (11)	0.0194 (10)	−0.0054 (9)	−0.0011 (8)	−0.0048 (9)
C6	0.0211 (10)	0.0300 (12)	0.0299 (12)	−0.0007 (9)	0.0009 (8)	−0.0080 (10)
C7	0.0264 (11)	0.0230 (11)	0.0342 (12)	−0.0004 (10)	−0.0070 (9)	−0.0036 (10)
C8	0.0342 (12)	0.0257 (13)	0.0242 (11)	−0.0072 (10)	−0.0031 (9)	0.0014 (9)
C9	0.0235 (10)	0.0280 (12)	0.0207 (10)	−0.0048 (9)	0.0014 (8)	−0.0022 (9)
C9a	0.0158 (9)	0.0249 (11)	0.0187 (10)	−0.0049 (8)	−0.0019 (8)	−0.0027 (9)
C21	0.0245 (10)	0.0210 (11)	0.0238 (11)	0.0006 (9)	−0.0015 (8)	0.0007 (9)
C22	0.0215 (10)	0.0208 (10)	0.0245 (10)	0.0003 (9)	0.0000 (8)	0.0037 (9)
C221	0.0200 (10)	0.0183 (10)	0.0223 (10)	−0.0019 (8)	0.0034 (7)	0.0006 (9)
C222	0.0235 (10)	0.0278 (11)	0.0231 (10)	0.0030 (10)	0.0040 (8)	−0.0014 (10)
C223	0.0231 (10)	0.0322 (13)	0.0254 (11)	0.0029 (10)	0.0005 (8)	0.0029 (10)
C224	0.0284 (11)	0.0303 (12)	0.0209 (10)	−0.0016 (10)	0.0028 (8)	0.0014 (10)
C225	0.0328 (12)	0.0274 (12)	0.0271 (11)	0.0037 (10)	0.0100 (9)	−0.0026 (10)
C226	0.0237 (10)	0.0224 (11)	0.0279 (11)	0.0034 (9)	0.0042 (8)	0.0032 (9)

Geometric parameters (Å, º)

F7—C7	1.361 (3)	C7—C8	1.386 (3)
O14—N1	1.451 (2)	C8—C9	1.386 (3)
O14—C4	1.460 (2)	C8—H8	0.95
N1—C9a	1.450 (3)	C9—C9a	1.387 (3)
N1—C2	1.498 (3)	C9—H9	0.95
C2—C21	1.498 (3)	C21—C22	1.323 (3)
C2—C3	1.553 (3)	C21—H21	0.95
C2—H2	1.00	C22—C221	1.472 (3)
C3—C4	1.530 (3)	C22—H22	0.95
C3—H3A	0.99	C221—C226	1.394 (3)
C3—H3B	0.99	C221—C222	1.399 (3)
C4—C5	1.513 (3)	C222—C223	1.386 (3)
C4—H4	1.00	C222—H222	0.95
C5—C5a	1.512 (3)	C223—C224	1.388 (3)
C5—H5A	0.99	C223—H223	0.95
C5—H5B	0.99	C224—C225	1.386 (3)
C5a—C9a	1.393 (3)	C224—H224	0.95
C5a—C6	1.396 (3)	C225—C226	1.389 (3)
C6—C7	1.367 (3)	C225—H225	0.95
C6—H6	0.95	C226—H226	0.95
N1—O14—C4	104.26 (13)	F7—C7—C8	118.4 (2)
C9a—N1—O14	107.61 (16)	C6—C7—C8	123.2 (2)
C9a—N1—C2	111.29 (14)	C9—C8—C7	117.4 (2)
O14—N1—C2	100.88 (16)	C9—C8—H8	121.3
C21—C2—N1	112.91 (18)	C7—C8—H8	121.3
C21—C2—C3	114.60 (18)	C8—C9—C9a	120.5 (2)
N1—C2—C3	103.94 (17)	C8—C9—H9	119.8
C21—C2—H2	108.4	C9a—C9—H9	119.8
N1—C2—H2	108.4	C9—C9a—C5a	121.2 (2)
C3—C2—H2	108.4	C9—C9a—N1	117.32 (18)
C4—C3—C2	103.40 (17)	C5a—C9a—N1	121.44 (19)
C4—C3—H3A	111.1	C22—C21—C2	123.4 (2)
C2—C3—H3A	111.1	C22—C21—H21	118.3
C4—C3—H3B	111.1	C2—C21—H21	118.3
C2—C3—H3B	111.1	C21—C22—C221	126.7 (2)
H3A—C3—H3B	109.0	C21—C22—H22	116.7
O14—C4—C5	107.21 (18)	C221—C22—H22	116.7
O14—C4—C3	103.82 (17)	C226—C221—C222	117.93 (19)
C5—C4—C3	113.35 (18)	C226—C221—C22	119.34 (18)
O14—C4—H4	110.7	C222—C221—C22	122.72 (19)
C5—C4—H4	110.7	C223—C222—C221	120.9 (2)
C3—C4—H4	110.7	C223—C222—H222	119.5
C5a—C5—C4	109.17 (18)	C221—C222—H222	119.5
C5a—C5—H5A	109.8	C222—C223—C224	120.2 (2)
C4—C5—H5A	109.8	C222—C223—H223	119.9
C5a—C5—H5B	109.8	C224—C223—H223	119.9
C4—C5—H5B	109.8	C225—C224—C223	119.7 (2)
H5A—C5—H5B	108.3	C225—C224—H224	120.2
C9a—C5a—C6	118.2 (2)	C223—C224—H224	120.2
C9a—C5a—C5	120.1 (2)	C224—C225—C226	119.9 (2)
C6—C5a—C5	121.70 (19)	C224—C225—H225	120.1
C7—C6—C5a	119.4 (2)	C226—C225—H225	120.1
C7—C6—H6	120.3	C225—C226—C221	121.4 (2)
C5a—C6—H6	120.3	C225—C226—H226	119.3
F7—C7—C6	118.5 (2)	C221—C226—H226	119.3
C4—O14—N1—C9a	−67.0 (2)	C8—C9—C9a—C5a	1.5 (3)
C4—O14—N1—C2	49.69 (19)	C8—C9—C9a—N1	−177.58 (19)
C9a—N1—C2—C21	−49.2 (2)	C6—C5a—C9a—C9	−0.3 (3)
O14—N1—C2—C21	−163.11 (17)	C5—C5a—C9a—C9	179.44 (19)
C9a—N1—C2—C3	75.61 (19)	C6—C5a—C9a—N1	178.75 (18)
O14—N1—C2—C3	−38.31 (19)	C5—C5a—C9a—N1	−1.6 (3)
C21—C2—C3—C4	137.8 (2)	O14—N1—C9a—C9	−151.55 (17)
N1—C2—C3—C4	14.1 (2)	C2—N1—C9a—C9	98.8 (2)
N1—O14—C4—C5	79.56 (19)	O14—N1—C9a—C5a	29.4 (2)
N1—O14—C4—C3	−40.7 (2)	C2—N1—C9a—C5a	−80.2 (2)
C2—C3—C4—O14	15.2 (2)	N1—C2—C21—C22	−104.4 (3)
C2—C3—C4—C5	−100.8 (2)	C3—C2—C21—C22	136.8 (2)
O14—C4—C5—C5a	−48.5 (2)	C2—C21—C22—C221	−177.8 (2)
C3—C4—C5—C5a	65.5 (2)	C21—C22—C221—C226	179.1 (2)
C4—C5—C5a—C9a	11.0 (3)	C21—C22—C221—C222	−1.8 (4)
C4—C5—C5a—C6	−169.35 (19)	C226—C221—C222—C223	0.2 (3)
C9a—C5a—C6—C7	−1.0 (3)	C22—C221—C222—C223	−178.8 (2)
C5—C5a—C6—C7	179.3 (2)	C221—C222—C223—C224	0.0 (4)
C5a—C6—C7—F7	−177.54 (19)	C222—C223—C224—C225	−0.3 (4)
C5a—C6—C7—C8	1.1 (3)	C223—C224—C225—C226	0.4 (4)
F7—C7—C8—C9	178.72 (19)	C224—C225—C226—C221	−0.2 (4)
C6—C7—C8—C9	0.1 (3)	C222—C221—C226—C225	−0.1 (3)
C7—C8—C9—C9a	−1.3 (3)	C22—C221—C226—C225	179.0 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5B···O14^i	0.99	2.33	3.316 (3)	176

Symmetry code: (i) x+1, y, z.