Three closely related dibenzazepine carb­oxy­lic acids: hydrogen-bonded aggregation in one, two and three dimensions

In the structure of (6R*,11R*)-5-acetyl-11-ethyl-6,11-di­hydro-5H-dibenzo[b,e]azepine-6-carb­oxy­lic acid, C₁₉H₁₉NO₃, (I), the mol­ecules are linked into sheets by a combination of O—H...O and C—H...O hydrogen bonds; in the structure of the monomethyl analogue (6RS,11SR)-5-acetyl-11-ethyl-2-methyl-6,11-di­hydro-5H-dibenzo[b,e]azepine-6-carb­oxy­lic acid, C₂₀H₂₁NO₃, (II), the mol­ecules are linked into simple C(7) chains by O—H...O hydrogen bonds; and in the structure of the di­methyl analogue (6RS,11SR)-5-acetyl-11-ethyl-1,3-di­methyl-6,11-di­hydro-5H-dibenzo[b,e]azepine-6-carb­oxy­lic acid, C₂₁H₂₃NO₃, (III), a combination of O—H...O, C—H...O and C—H...π(arene) hydrogen bonds links the mol­ecules into a three-dimensional framework structure. None of these structures exhibits the R₂²(8) dimer motif characteristic of simple carb­oxy­lic acids.

S1. Introduction

The dibenzo[b,e]azepine ring is an important pharmacophore in drug discovery and many of its derivatives exhibit a broad spectrum of biological activities (Van der Burg et al., 1970; Brogden et al., 1978; Nickolson & Wieringa, 1981; Berger et al., 1989; De Boer et al., 1996; Roeder et al., 1998; Andrés et al., 2002; Wikström et al., 2002). Consequently, a significant number of synthetic methods have been developed for the synthesis of new derivatives of this heterocyclic system (Moriconi & Maniscalco, 1972; Sasakura & Sugasawa, 1981; Stappers et al., 2002). In this context, we have recently developed a simple and practical synthetic route to obtain novel series of 6,11-di­hydro­dibenzo[b,e]azepines from readily available 2-allyl-N-benzyl-substituted anilines (Palma et al., 2004, 2010). To broaden the scope of this route, and in continuation of our research programme on the preparation of new potentially bio-active molecules containing the di­hydro­dibenzo[b,e]azepine nucleus, we have achieved a simple synthesis of three previously unknown 5-acetyl-11-ethyl-6,11-di­hydro-5H-dibenzo[b,e]azepine-6-carb­oxy­lic acids. Here we report the molecular structures and supra­molecular assembly of three closely related compounds, namely (6R*,11R*)-5-acetyl-11-ethyl-6,11-di­hydro-5H-dibenzo[b,e]azepine-6-carb­oxy­lic acid, (I) (Fig. 1), (6RS,11SR)-5-acetyl-11-ethyl-2-methyl-6,11-di­hydro-5H- dibenzo[b,e]azepine-6-carb­oxy­lic acid, (II) (Fig. 2), and (6RS,11SR)-5-acetyl-11-ethyl-1,3-di­methyl-6,11-di­hydro- 5H-dibenzo[b,e]azepine-6-carb­oxy­lic acid, (III) (Fig. 3), the constitutions of which differ only in the presence of one methyl substituent in (II) and two in (III), while there are none in (I). The synthesis of compounds (I)–(III) was achieved by intra­molecular Friedel–Crafts alkyl­ation of the corresponding methyl 2-[N-(2-allyl­aryl)­acetamido]-2-phenyl­acetates using concentrated sulfuric acid at 373 K (see scheme).

S2. Experimental

S2.1. Synthesis and crystallization

For the synthesis of each of (I)–(III), a suspension of the appropriately substituted racemic methyl 2-[N-(2-allyl­aryl)­acetamido]-2-phenyl­acetate (see scheme) (1.0 g) in concentrated sulfuric acid (3 ml) was stirred at 373 K for 7 min. The reaction mixture was cooled to ambient temperature by the addition of ice and then extracted with ethyl acetate (3 × 50 ml). The combined organic extracts were dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting crude products were subjected to column chromatographic purification over silica gel using heptane–ethyl acetate–acetic acid (1:2:0.04 v/v/v). Crystallization from ethyl acetate–ethanol (30:1 v/v) at ambient temperature and in the presence of air gave colourless crystals of (I)–(III), suitable for single-crystal X-ray diffraction. Compound (I): yield 35%, m.p. 449–450 K, HRMS m/z [M]⁺ found 309.1366, C₁₉H₁₉NO₃ requires 309.1365. Compound (II): yield 20%, m.p. 460–462 K, HRMS m/z [M]⁺ found 323.1525, C₂₀H₂₁NO₃ requires 323.1521. Compound (III): yield 41%, m.p. 497–499 K, HRMS m/z [M]⁺ found 337.1653, C₂₁H₂₁NO₃ requires 337.1678.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were located in difference maps and subsequently treated as riding atoms. C-bound H atoms were permitted to ride in geometrically idealized positions, with C—H = 0.95 (aromatic), 0.98 (CH₃), 0.99 (CH₂) or 1.00 Å (aliphatic C—H), and with U_iso(H) = kU_eq(C), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all other C-bound H atoms. O-bound H atoms were permitted to ride at the positions located in difference maps with U_iso(H) = 1.5U_eq(O), giving the O—H distances shown in Table 3. Several low-angle reflections, which had been wholly or partially attenuated by the beam stop, were omitted from the final refinements. The value of the Flack x parameter (Flack, 1983) for (I) was indeterminate (Flack & Bernardinelli, 2000); accordingly, Friedel-equivalent reflections were merged prior to the final refinements. Examination of the refined structures using PLATON (Spek, 2009) showed the presence of two small cavities in the structure of (II), centred at (1/2, 0, 1/2) and (1/2, 1/2, 0) and each of volume 24 ų; these cavities are far too small to contain any plausible solvent molecule but, nonetheless, the largest peak in the difference map, 0.68 e Å^-3 at (0.523, 0.482, 0.064), was very close to one of the cavities. However, application of the SQUEEZE procedure in PLATON revealed only one excess electron per cavity. Accordingly, we regard both the difference peak and the excess electron count as minor artefacts of the data.

S3. Results and discussion

The molecules of (I)–(III) all contain two stereogenic centres at atoms C6 and C11 (Figs. 1–3). In (I), the exocyclcic substituents at atoms C6 and C11 have a cis arrangement relative to the azepine ring, while those in (II) and (III) have a trans arrangement. For each compound, the reference molecule was selected as one having the R configuration at atom C6. On this basis, the reference molecule of (I) has the R configuration at atom C11, while those of (II) and (III) have the S configuration at atom C11. Compounds (II) and (III) crystallize as racemic mixtures, as shown by the centrosymmetric space group, but (I) crystallizes in the Sohnke space group P2₁. Hence in the absence of twinning, for which no evidence was found, each crystal of (I) contains only one enanti­omorph. It was not possible to determine the absolute configuration of the molecules in the crystal of (I) which was selected for data collection, and hence the configuration of the reference molecule was set to have the R configuration at atom C6, just as for (II) and (III).

Since the methyl 2-[N-(2-allyl­aryl)­acetamido]-2-phenyl­acetates used as the precursors to (I)–(III) (see scheme) are all racemic, the crystallization of (II) and (III) as racemic mixtures is unsurprising, and the method of synthesis makes it probable that (I) is formed in solution as a racemic mixture, which then crystallizes as a conglomerate rather than as a racemate. More problematic is the difference in relative configurations at atoms C6 and C11 between (I), (6R*,11R*), on the one hand and (II) and (III), (6RS,11SR), on the other. Since the yields of the purified crystallized products are all significantly less than 50% (see Experimental), it is at least possible that the compounds may be formed as diastereoisomeric mixtures, and that the stereoisomers reported here are simply those which crystallized preferentially. However, it must be emphasized that there is no direct evidence on this point, and so this suggestion must be regarded as speculative.

Within the amide unit, the N5—C51 and C51—O51 distances (Table 2) are typical of those found in N,N-disubstituted amides (Allen et al., 1987), while the C—O distances in the carb­oxy­lic acid units are fully consistent with the locations of the carb­oxy­lic H atoms as found in difference maps. The remaining bond distances present no unusual values. In each of (I)–(III), the azepine ring adopts a conformation inter­mediate between the boat and twist-boat forms (Evans & Boeyens, 1989; Entrena et al., 1997). For (II) and (III), the ring-puckering parameters (Cremer & Pople, 1975) are very similar (Table 2), but the extent of the ring puckering, as shown by the overall puckering amplitude Q, is somewhat larger in (I) than in (II) and (III). This may be associated with the cis stereochemistry at atoms C6 and C11 in (I), compared with the trans arrangement in (II) and (III). The orientation of the amide unit relative to the azepine ring is very similar in all three compounds, as shown by the values of the torsion angles C6—N5—C51—O51 and C6—N5—C51—C52 (Table 2, and Figs. 1–3). By contrast, the orientation of the carb­oxy­lic acid unit varies widely, and this variation may be a consequence of the different hydrogen-bonding arrangements in the three structures. The conformations adopted by the ethyl group also vary widely, and since this substituent plays no part in the supra­molecular assembly it seems likely that these conformations are determined by the methyl groups based on atom C112 finding accommodation in whatever suitable spaces are available within the hydrogen-bonded structure.

Accordingly, despite their very similar constitutions, (I)–(III) differ not only in the relative configurations at their two stereogenic centres but also in their crystallization characteristics, i.e. as a conglomerate for (I) and as a racemate for each of (II) and (III), with Z values of 2, 4 and and 4, respectively, as well as in their molecular conformations. They also differ in their modes of supra­molecular assembly, with the formation of a simple hydrogen-bonded chain in (II), a hydrogen-bonded sheet in (I), and a three-dimensional framework structure in (III). It is convenient to discuss the supra­molecular assembly in the structures of (I)–(III) in the order of increasing complexity.

The O—H···O hydrogen bond in compound (II) (Table 3) links molecules related by the 2₁ screw axis along (1/2, y, 3/4) into a C(7) (Bernstein et al., 1995) chain running parallel to the [010] direction. (Fig. 4). The two shortest inter­molecular C—H···O contacts (Table 3) have H···O distances not significantly less than the sum of the van der Waals radii for H and O (2.61 Å; Bondi, 1964; Rowland & Taylor, 1996). In any event, both contacts have fairly small C—H···O angles (cf. Wood et al., 2009), so that neither can be regarded as structurally significant. Two chains of this type, related to one another by inversion, pass through each unit cell but there are no direction-specific inter­actions between adjacent chains.

The supra­molecular assembly in (I) and (III) can most readily be analysed in terms of a series of one-dimensional substructures (Ferguson et al., 1998a,b; Gregson et al., 2000). In (I), molecules related by a 2₁ screw axis are similarly linked by an O—H···O hydrogen bond to form a C(7) chain running parallel to the [010] direction but, in contrast with (II), chains in (I) which are related by translation along the [101] direction are linked by a C—H···O hydrogen bond to form a sheet of R³₄(26) rings parallel to (101) (Fig. 5). The only other short inter­molecular contact involves a low-acidity C—H bond from a methyl group and is thus unlikely to be structurally significant.

The molecules of (III) are linked into a three-dimensional framework structure by a combination of O—H···O, C—H···O and C—H···π(arene) hydrogen bonds (Table 3). The O—H···O hydrogen bond links molecules related by the n-glide plane at y = 3/4 to form a C(7) chain running parallel to the [101] direction (Fig. 6), and the C—H···O hydrogen bond links molecules related by a 2₁ screw axis along (3/4, y, 1/4) to form a C(8) chain running parallel to the [010] direction (Fig. 6). The combination of these two chains generates a sheet lying parallel to (101) and built from a single type of centrosymmetric R₄⁴(30) ring (Fig. 6). Sheets of this type are linked to form a continuous three-dimensional framework structure by the C—H···π(arene) hydrogen bond, which links molecules related by translation along the [100] direction (Fig. 7). The combination of chains along [100], [010] and [101] is sufficient to form a three-dimensional structure.

It is thus striking that none of (I)–(III) exhibits the R₂²(8) dimer motif so characteristic of simple carb­oxy­lic acids. Instead, all utilize atom O51 of the N-acetyl group as acceptor in an O—H···O hydrogen bond, and it is of inter­est briefly to compare the substructures which can be identified in the supra­molecular assemblies of (I)–(III). In each of the structures, a C(7) chain motif can be identified built from O—H···O hydrogen bonds. However, these chains differ in that those in (I) and (II) contain molecules related by a 2₁ screw axis, whereas that in (III) contains molecules related by an n-glide plane. Similarly, sheets built from a combination of O—H···O and C—H···O hydrogen bonds can be identified in the structures of (I) and (III) (Figs. 5 and 6). Both sheets exhibit (4,4) topology (Batten & Robson, 1998). The ring sizes in the sheets in (I) and (III) differ, as do the numbers of hydrogen-bond acceptors within these rings, since in (I) amide atom O51 acts as a double acceptor of hydrogen bonds, unlike that in (III). However, within the sheet in (III) the constituent rings are centrosymmetric, while those in (I) are not centrosymmetric. Chain formation by means of O—H···O hydrogen bonds has been extensively studied in keto acids, where the chain motif follows directly from the mutual disposition of the carboxyl and keto groups. Thus, γ-keto-acids form C(7) chains (e.g. Thompson et al., 2004; Malak et al., 2006), δ-keto acids form C(8) chains (e.g. Davison, Kikolski et al., 2004) and ε-keto acids form C(9) chains (e.g. Davison, Thompson et al., 2004), while longer chain motifs are generated in steroidal keto acids (e.g. Kikolski et al., 2006).

Related literature

For related literature, see: Allen et al. (1987); Andrés et al. (2002); Batten & Robson (1998); Berger et al. (1989); Bernstein et al. (1995); Bondi (1964); Brogden et al. (1978); Cremer & Pople (1975); Davison, Kikolski, Lalancette & Thompson (2004); Davison, Thompson & Lalancette (2004); De Boer, Nefkens, van Helvoirt & van Delft (1996); Entrena et al. (1997); Evans & Boeyens (1989); Ferguson et al. (1998a, 1998b); Flack (1983); Flack & Bernardinelli (2000); Gregson et al. (2000); Kikolski et al. (2006); Malak et al. (2006); Moriconi & Maniscalco (1972); Nickolson & Wieringa (1981); Palma et al. (2004, 2010); Roeder et al. (1998); Rowland & Taylor (1996); Sasakura & Sugasawa (1981); Spek (2009); Stappers et al. (2002); Thompson et al. (2004); Van der Burg, Bonta, Delobelle, Ramon & Vargaftig (1970); Wikström et al. (2002); Wood et al. (2009).

Computing details

For all compounds, data collection: COLLECT (Nonius, 1998); 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) for (I), (II); SHELXS97 (Sheldrick, 2008) for (III). For all compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of the (6R,11R) enantiomer of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The molecular structure of the (6R,11S) enantiomer of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 3. The molecular structure of the (6R,11S) enantiomer of (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 4. Part of the crystal structure of (II), showing the formation of a hydrogen-bonded (dashed lines) chain parallel to [010]. For the sake of clarity, H atoms not involved in the motifs shown have been omitted. Atoms marked with an asterisk (*), a hash (#), a dollar sign ($) or an ampersand (&) are at the symmetry positions (-x + 1, y + 1/2, -z + 1/2), (-x + 1, y - 1/2, -z + 1/2), (x, y + 1, z) and (x, y - 1, z), respectively.
	Fig. 5. A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded (dashed lines) sheet parallel to (101). For the sake of clarity, H atoms not involved in the motifs shown have been omitted.
	Fig. 6. A stereoview of part of the crystal structure of (III), showing the formation of a hydrogen-bonded (dashed lines) sheet of R4^4(30) rings parallel to (101) and built from a combination of O—H···O and C—H···O hydrogen bonds. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.
	Fig. 7. A stereoview of part of the crystal structure of (III), showing the formation of a chain parallel to [100] built from C—H···π(arene) hydrogen bonds (dashed lines). For the sake of clarity, H atoms not involved in the motif shown have been omitted.

(I) (6R*,11R*)-5-Acetyl-11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxylic acid

Crystal data

C19H19NO3	F(000) = 328
Mr = 309.35	Dx = 1.342 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1853 reflections
a = 8.8053 (3) Å	θ = 3.2–27.5°
b = 10.9821 (4) Å	µ = 0.09 mm^−1
c = 9.0080 (6) Å	T = 120 K
β = 118.510 (3)°	Rod, colourless
V = 765.45 (6) Å^3	0.26 × 0.14 × 0.10 mm
Z = 2

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	1851 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	1638 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.049
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.7°
φ and ω scans	h = −11→11
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −14→14
Tmin = 0.977, Tmax = 0.991	l = −11→11
13276 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) = 0.081	H-atom parameters constrained
S = 1.15	w = 1/[σ^2(Fo^2) + (0.0351P)^2 + 0.1657P] where P = (Fo^2 + 2Fc^2)/3
1851 reflections	(Δ/σ)max = 0.001
210 parameters	Δρmax = 0.21 e Å^−3
1 restraint	Δρmin = −0.24 e Å^−3

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

	x	y	z	Uiso*/Ueq
C1	0.6424 (3)	0.5942 (2)	0.7939 (3)	0.0186 (5)
H1	0.6599	0.6154	0.9031	0.022*
C2	0.7828 (3)	0.5595 (2)	0.7731 (3)	0.0211 (5)
H2	0.8953	0.5589	0.8678	0.025*
C3	0.7604 (3)	0.5255 (2)	0.6149 (3)	0.0202 (5)
H3	0.8563	0.4993	0.6019	0.024*
C4	0.5955 (3)	0.5306 (2)	0.4757 (3)	0.0166 (5)
H4	0.5780	0.5079	0.3669	0.020*
C4a	0.4576 (3)	0.5687 (2)	0.4973 (3)	0.0142 (5)
N5	0.2883 (2)	0.58197 (17)	0.3533 (2)	0.0132 (4)
C6	0.1469 (3)	0.4966 (2)	0.3244 (3)	0.0128 (4)
H6	0.0389	0.5461	0.2831	0.015*
C6a	0.1714 (3)	0.4295 (2)	0.4842 (3)	0.0145 (5)
C7	0.1243 (3)	0.3077 (2)	0.4737 (3)	0.0174 (5)
H7	0.0884	0.2652	0.3704	0.021*
C8	0.1286 (3)	0.2465 (2)	0.6107 (3)	0.0189 (5)
H8	0.0977	0.1628	0.6008	0.023*
C9	0.1780 (3)	0.3073 (2)	0.7616 (3)	0.0188 (5)
H9	0.1759	0.2670	0.8540	0.023*
C10	0.2305 (3)	0.4277 (2)	0.7762 (3)	0.0185 (5)
H10	0.2674	0.4685	0.8808	0.022*
C10a	0.2307 (3)	0.4909 (2)	0.6412 (3)	0.0151 (5)
C11	0.3097 (3)	0.6185 (2)	0.6677 (3)	0.0150 (5)
H11	0.2307	0.6694	0.5686	0.018*
C11a	0.4763 (3)	0.5982 (2)	0.6566 (3)	0.0145 (5)
C51	0.2534 (3)	0.6720 (2)	0.2388 (3)	0.0142 (5)
O51	0.10670 (19)	0.68043 (16)	0.11339 (19)	0.0180 (4)
C52	0.3950 (3)	0.7609 (2)	0.2675 (3)	0.0189 (5)
H52A	0.4784	0.7219	0.2397	0.028*
H52B	0.4537	0.7862	0.3862	0.028*
H52C	0.3452	0.8324	0.1952	0.028*
C61	0.1208 (3)	0.4093 (2)	0.1806 (3)	0.0145 (5)
O61	−0.0387 (2)	0.36474 (17)	0.10291 (19)	0.0186 (4)
H61	−0.0487	0.3107	0.0297	0.028*
O62	0.2327 (2)	0.38608 (17)	0.1438 (2)	0.0224 (4)
C111	0.3325 (3)	0.6837 (2)	0.8280 (3)	0.0202 (5)
H11A	0.2247	0.6761	0.8362	0.024*
H11B	0.4266	0.6440	0.9284	0.024*
C112	0.3752 (3)	0.8181 (2)	0.8272 (3)	0.0229 (5)
H12A	0.4821	0.8260	0.8195	0.034*
H12B	0.3905	0.8565	0.9317	0.034*
H12C	0.2804	0.8583	0.7300	0.034*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0214 (12)	0.0168 (12)	0.0133 (11)	−0.0021 (10)	0.0048 (10)	−0.0003 (10)
C2	0.0163 (12)	0.0170 (13)	0.0222 (13)	−0.0025 (9)	0.0027 (10)	0.0035 (10)
C3	0.0158 (11)	0.0198 (13)	0.0252 (13)	0.0018 (10)	0.0101 (11)	0.0052 (10)
C4	0.0191 (11)	0.0145 (12)	0.0168 (11)	−0.0002 (9)	0.0091 (10)	0.0012 (9)
C4a	0.0138 (11)	0.0128 (12)	0.0136 (11)	−0.0010 (8)	0.0045 (10)	0.0021 (9)
N5	0.0120 (9)	0.0137 (10)	0.0117 (9)	−0.0010 (7)	0.0038 (8)	0.0010 (8)
C6	0.0117 (10)	0.0148 (11)	0.0113 (10)	−0.0006 (8)	0.0049 (9)	−0.0002 (9)
C6a	0.0133 (11)	0.0176 (12)	0.0136 (11)	0.0010 (9)	0.0071 (9)	0.0004 (9)
C7	0.0156 (11)	0.0201 (12)	0.0151 (11)	−0.0004 (9)	0.0061 (9)	−0.0019 (9)
C8	0.0177 (12)	0.0162 (12)	0.0217 (12)	−0.0028 (10)	0.0085 (10)	0.0009 (10)
C9	0.0173 (12)	0.0222 (13)	0.0183 (12)	0.0008 (10)	0.0097 (10)	0.0054 (10)
C10	0.0172 (12)	0.0242 (13)	0.0135 (11)	0.0020 (10)	0.0069 (10)	−0.0006 (10)
C10a	0.0125 (10)	0.0167 (11)	0.0162 (11)	0.0006 (9)	0.0068 (9)	0.0002 (9)
C11	0.0152 (11)	0.0167 (12)	0.0135 (11)	−0.0009 (9)	0.0073 (9)	−0.0015 (9)
C11a	0.0184 (12)	0.0098 (10)	0.0156 (11)	−0.0010 (9)	0.0083 (10)	0.0006 (9)
C51	0.0168 (11)	0.0142 (11)	0.0121 (11)	0.0004 (9)	0.0074 (9)	−0.0020 (9)
O51	0.0161 (8)	0.0186 (9)	0.0150 (8)	0.0005 (7)	0.0040 (7)	0.0025 (7)
C52	0.0207 (12)	0.0162 (12)	0.0194 (12)	−0.0010 (10)	0.0092 (10)	0.0029 (10)
C61	0.0176 (11)	0.0127 (11)	0.0117 (10)	0.0001 (9)	0.0058 (9)	0.0022 (9)
O61	0.0176 (8)	0.0213 (9)	0.0150 (8)	−0.0045 (7)	0.0062 (7)	−0.0065 (7)
O62	0.0221 (9)	0.0252 (10)	0.0241 (9)	−0.0024 (7)	0.0144 (8)	−0.0062 (8)
C111	0.0243 (12)	0.0195 (13)	0.0176 (12)	−0.0018 (11)	0.0106 (10)	−0.0036 (11)
C112	0.0265 (13)	0.0208 (13)	0.0248 (13)	−0.0031 (10)	0.0151 (11)	−0.0065 (10)

Geometric parameters (Å, º)

C1—C2	1.388 (4)	C9—C10	1.386 (3)
C1—C11a	1.395 (3)	C9—H9	0.9500
C1—H1	0.9500	C10—C10a	1.401 (3)
C2—C3	1.393 (4)	C10—H10	0.9500
C2—H2	0.9500	C10a—C11	1.532 (3)
C3—C4	1.395 (3)	C11—C11a	1.533 (3)
C3—H3	0.9500	C11—C111	1.536 (3)
C4—C4a	1.383 (3)	C11—H11	1.0000
C4—H4	0.9500	C51—O51	1.249 (3)
C4a—C11a	1.402 (3)	C51—C52	1.506 (3)
C4a—N5	1.442 (3)	C52—H52A	0.9800
N5—C51	1.354 (3)	C52—H52B	0.9800
N5—C6	1.479 (3)	C52—H52C	0.9800
C6—C6a	1.538 (3)	C61—O62	1.207 (3)
C6—C61	1.538 (3)	C61—O61	1.328 (3)
C6—H6	1.0000	O61—H61	0.8602
C6a—C7	1.390 (3)	C111—C112	1.523 (4)
C6a—C10a	1.423 (3)	C111—H11A	0.9900
C7—C8	1.390 (3)	C111—H11B	0.9900
C7—H7	0.9500	C112—H12A	0.9800
C8—C9	1.386 (3)	C112—H12B	0.9800
C8—H8	0.9500	C112—H12C	0.9800
C2—C1—C11a	120.9 (2)	C10a—C10—H10	119.0
C2—C1—H1	119.5	C10—C10a—C6a	118.4 (2)
C11a—C1—H1	119.5	C10—C10a—C11	120.5 (2)
C1—C2—C3	120.7 (2)	C6a—C10a—C11	120.8 (2)
C1—C2—H2	119.6	C10a—C11—C11a	103.51 (18)
C3—C2—H2	119.6	C10a—C11—C111	114.78 (19)
C2—C3—C4	119.1 (2)	C11a—C11—C111	115.41 (19)
C2—C3—H3	120.4	C10a—C11—H11	107.6
C4—C3—H3	120.4	C11a—C11—H11	107.6
C4a—C4—C3	119.6 (2)	C111—C11—H11	107.6
C4a—C4—H4	120.2	C1—C11a—C4a	117.4 (2)
C3—C4—H4	120.2	C1—C11a—C11	125.3 (2)
C4—C4a—C11a	122.1 (2)	C4a—C11a—C11	116.87 (19)
C4—C4a—N5	120.27 (19)	O51—C51—N5	120.3 (2)
C11a—C4a—N5	117.61 (19)	O51—C51—C52	121.4 (2)
C51—N5—C4a	121.36 (18)	N5—C51—C52	118.30 (19)
C51—N5—C6	117.57 (18)	C51—C52—H52A	109.5
C4a—N5—C6	121.06 (17)	C51—C52—H52B	109.5
N5—C6—C6a	114.16 (18)	H52A—C52—H52B	109.5
N5—C6—C61	108.54 (17)	C51—C52—H52C	109.5
C6a—C6—C61	112.80 (19)	H52A—C52—H52C	109.5
N5—C6—H6	107.0	H52B—C52—H52C	109.5
C6a—C6—H6	107.0	O62—C61—O61	125.0 (2)
C61—C6—H6	107.0	O62—C61—C6	123.3 (2)
C7—C6a—C10a	118.7 (2)	O61—C61—C6	111.64 (18)
C7—C6a—C6	119.6 (2)	C61—O61—H61	110.7
C10a—C6a—C6	121.6 (2)	C112—C111—C11	111.7 (2)
C8—C7—C6a	121.6 (2)	C112—C111—H11A	109.3
C8—C7—H7	119.2	C11—C111—H11A	109.3
C6a—C7—H7	119.2	C112—C111—H11B	109.3
C9—C8—C7	120.0 (2)	C11—C111—H11B	109.3
C9—C8—H8	120.0	H11A—C111—H11B	108.0
C7—C8—H8	120.0	C111—C112—H12A	109.5
C8—C9—C10	119.2 (2)	C111—C112—H12B	109.5
C8—C9—H9	120.4	H12A—C112—H12B	109.5
C10—C9—H9	120.4	C111—C112—H12C	109.5
C9—C10—C10a	122.0 (2)	H12A—C112—H12C	109.5
C9—C10—H10	119.0	H12B—C112—H12C	109.5
C11a—C1—C2—C3	−1.3 (4)	C7—C6a—C10a—C11	170.7 (2)
C1—C2—C3—C4	2.1 (4)	C6—C6a—C10a—C11	−13.4 (3)
C2—C3—C4—C4a	−0.1 (4)	C10—C10a—C11—C11a	108.4 (2)
C3—C4—C4a—C11a	−2.7 (4)	C6a—C10a—C11—C11a	−65.6 (3)
C3—C4—C4a—N5	176.0 (2)	C10—C10a—C11—C111	−18.3 (3)
C4—C4a—N5—C51	−70.0 (3)	C6a—C10a—C11—C111	167.7 (2)
C11a—C4a—N5—C51	108.7 (2)	C2—C1—C11a—C4a	−1.4 (3)
C4—C4a—N5—C6	109.3 (2)	C2—C1—C11a—C11	171.5 (2)
C11a—C4a—N5—C6	−72.0 (3)	C4—C4a—C11a—C1	3.4 (3)
C51—N5—C6—C6a	−158.55 (19)	N5—C4a—C11a—C1	−175.3 (2)
C4a—N5—C6—C6a	22.1 (3)	C4—C4a—C11a—C11	−170.1 (2)
C51—N5—C6—C61	74.7 (2)	N5—C4a—C11a—C11	11.2 (3)
C4a—N5—C6—C61	−104.7 (2)	C10a—C11—C11a—C1	−103.1 (3)
N5—C6—C6a—C7	−141.2 (2)	C111—C11—C11a—C1	23.1 (4)
C61—C6—C6a—C7	−16.7 (3)	C10a—C11—C11a—C4a	69.8 (2)
N5—C6—C6a—C10a	42.9 (3)	C111—C11—C11a—C4a	−163.9 (2)
C61—C6—C6a—C10a	167.43 (19)	C4a—N5—C51—O51	178.7 (2)
C10a—C6a—C7—C8	2.2 (3)	C6—N5—C51—O51	−0.7 (3)
C6—C6a—C7—C8	−173.8 (2)	C4a—N5—C51—C52	−1.5 (3)
C6a—C7—C8—C9	1.0 (4)	C6—N5—C51—C52	179.1 (2)
C7—C8—C9—C10	−3.0 (3)	N5—C6—C61—O62	24.4 (3)
C8—C9—C10—C10a	1.8 (3)	C6a—C6—C61—O62	−103.1 (3)
C9—C10—C10a—C6a	1.4 (3)	N5—C6—C61—O61	−155.01 (18)
C9—C10—C10a—C11	−172.7 (2)	C6a—C6—C61—O61	77.5 (2)
C7—C6a—C10a—C10	−3.4 (3)	C10a—C11—C111—C112	−168.0 (2)
C6—C6a—C10a—C10	172.6 (2)	C11a—C11—C111—C112	71.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O61—H61···O51^i	0.86	1.83	2.672 (2)	167
C2—H2···O51^ii	0.95	2.49	3.309 (3)	144
C112—H12A···O62^iii	0.98	2.46	3.418 (4)	165

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

(II) (6RS,11SR)-5-Acetyl-11-ethyl-2-methyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxylic acid

Crystal data

C20H21NO3	F(000) = 688
Mr = 323.38	Dx = 1.262 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3906 reflections
a = 15.2894 (16) Å	θ = 2.7–27.5°
b = 10.760 (2) Å	µ = 0.09 mm^−1
c = 10.538 (2) Å	T = 120 K
β = 100.990 (11)°	Block, colourless
V = 1701.9 (5) Å^3	0.41 × 0.30 × 0.24 mm
Z = 4

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	3903 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	2589 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.092
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.3°
φ and ω scans	h = −19→19
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −13→13
Tmin = 0.966, Tmax = 0.980	l = −13→13
28096 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)] = 0.059	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.155	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0624P)^2 + 1.5377P] where P = (Fo^2 + 2Fc^2)/3
3903 reflections	(Δ/σ)max = 0.001
220 parameters	Δρmax = 0.68 e Å^−3
0 restraints	Δρmin = −0.29 e Å^−3

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

	x	y	z	Uiso*/Ueq
C1	0.11423 (15)	0.5736 (2)	0.1081 (2)	0.0183 (5)
H1	0.0551	0.5673	0.1234	0.022*
C2	0.13034 (15)	0.6464 (2)	0.0050 (2)	0.0200 (5)
C3	0.21783 (16)	0.6576 (2)	−0.0142 (2)	0.0203 (5)
H3	0.2303	0.7089	−0.0819	0.024*
C4	0.28655 (15)	0.5946 (2)	0.0642 (2)	0.0189 (5)
H4	0.3459	0.6025	0.0502	0.023*
C4a	0.26855 (14)	0.5197 (2)	0.1637 (2)	0.0160 (5)
N5	0.33846 (12)	0.45422 (17)	0.24821 (17)	0.0153 (4)
C6	0.36955 (15)	0.5095 (2)	0.3762 (2)	0.0164 (5)
H6	0.4184	0.4543	0.4213	0.020*
C6a	0.30137 (15)	0.5169 (2)	0.4643 (2)	0.0166 (5)
C7	0.33741 (16)	0.5563 (2)	0.5908 (2)	0.0216 (5)
H7	0.3989	0.5765	0.6123	0.026*
C8	0.28551 (17)	0.5662 (2)	0.6846 (2)	0.0257 (5)
H8	0.3111	0.5930	0.7694	0.031*
C9	0.19597 (18)	0.5366 (2)	0.6534 (2)	0.0267 (6)
H9	0.1594	0.5439	0.7165	0.032*
C10	0.15979 (16)	0.4962 (2)	0.5295 (2)	0.0220 (5)
H10	0.0983	0.4754	0.5094	0.026*
C10a	0.21130 (15)	0.4849 (2)	0.4325 (2)	0.0176 (5)
C11	0.16359 (14)	0.4346 (2)	0.3022 (2)	0.0180 (5)
H11	0.0985	0.4447	0.3014	0.022*
C11a	0.18239 (15)	0.5102 (2)	0.1891 (2)	0.0166 (5)
C21	0.05529 (16)	0.7126 (2)	−0.0825 (2)	0.0279 (6)
H21A	0.0756	0.7409	−0.1604	0.042*
H21B	0.0366	0.7844	−0.0371	0.042*
H21C	0.0049	0.6556	−0.1069	0.042*
C51	0.38517 (14)	0.3587 (2)	0.2100 (2)	0.0182 (5)
O51	0.44856 (11)	0.31255 (16)	0.28673 (15)	0.0231 (4)
C52	0.35754 (17)	0.3077 (2)	0.0754 (2)	0.0265 (6)
H52A	0.4064	0.3181	0.0282	0.040*
H52B	0.3049	0.3526	0.0305	0.040*
H52C	0.3433	0.2192	0.0800	0.040*
C61	0.41375 (15)	0.6350 (2)	0.3559 (2)	0.0188 (5)
O61	0.47155 (11)	0.61912 (15)	0.27831 (17)	0.0259 (4)
H61	0.4981	0.6936	0.2657	0.039*
O62	0.39924 (12)	0.73197 (15)	0.40492 (16)	0.0270 (4)
C111	0.17878 (16)	0.2930 (2)	0.2890 (2)	0.0204 (5)
H11A	0.1583	0.2681	0.1977	0.024*
H11B	0.2434	0.2751	0.3125	0.024*
C112	0.12941 (17)	0.2163 (2)	0.3747 (2)	0.0254 (5)
H12A	0.1478	0.2429	0.4648	0.038*
H12B	0.1437	0.1281	0.3673	0.038*
H12C	0.0651	0.2286	0.3472	0.038*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0180 (11)	0.0202 (11)	0.0166 (11)	0.0000 (9)	0.0034 (9)	−0.0008 (9)
C2	0.0249 (12)	0.0211 (12)	0.0128 (11)	0.0011 (9)	0.0008 (9)	−0.0013 (9)
C3	0.0278 (12)	0.0210 (11)	0.0117 (10)	−0.0006 (10)	0.0026 (9)	0.0011 (9)
C4	0.0209 (11)	0.0231 (12)	0.0137 (10)	−0.0016 (9)	0.0063 (9)	−0.0007 (9)
C4a	0.0189 (11)	0.0173 (11)	0.0117 (10)	0.0005 (9)	0.0026 (9)	−0.0007 (9)
N5	0.0161 (9)	0.0180 (9)	0.0118 (9)	0.0001 (7)	0.0026 (7)	0.0007 (7)
C6	0.0189 (11)	0.0188 (11)	0.0110 (10)	0.0003 (9)	0.0012 (8)	−0.0014 (9)
C6a	0.0236 (11)	0.0138 (10)	0.0134 (10)	0.0017 (9)	0.0057 (9)	0.0013 (8)
C7	0.0279 (12)	0.0214 (12)	0.0150 (11)	−0.0016 (10)	0.0028 (9)	−0.0002 (9)
C8	0.0385 (14)	0.0260 (13)	0.0129 (11)	−0.0029 (11)	0.0055 (10)	−0.0007 (10)
C9	0.0374 (14)	0.0294 (13)	0.0170 (12)	−0.0032 (11)	0.0144 (11)	−0.0013 (10)
C10	0.0256 (12)	0.0234 (12)	0.0190 (12)	−0.0039 (10)	0.0092 (10)	−0.0008 (10)
C10a	0.0230 (11)	0.0164 (11)	0.0139 (10)	0.0005 (9)	0.0049 (9)	0.0004 (9)
C11	0.0168 (11)	0.0241 (12)	0.0128 (10)	0.0001 (9)	0.0026 (9)	0.0025 (9)
C11a	0.0198 (11)	0.0185 (11)	0.0117 (10)	−0.0024 (9)	0.0032 (9)	−0.0015 (9)
C21	0.0264 (13)	0.0319 (14)	0.0240 (13)	0.0011 (11)	0.0008 (10)	0.0079 (11)
C51	0.0175 (11)	0.0200 (11)	0.0181 (11)	−0.0007 (9)	0.0055 (9)	0.0001 (9)
O51	0.0236 (9)	0.0262 (9)	0.0190 (8)	0.0066 (7)	0.0026 (7)	−0.0024 (7)
C52	0.0298 (13)	0.0286 (13)	0.0216 (12)	0.0045 (11)	0.0058 (10)	−0.0070 (11)
C61	0.0197 (11)	0.0220 (12)	0.0141 (10)	0.0007 (9)	0.0018 (9)	0.0018 (9)
O61	0.0279 (9)	0.0218 (9)	0.0323 (10)	−0.0053 (7)	0.0166 (8)	−0.0036 (7)
O62	0.0377 (10)	0.0196 (9)	0.0256 (9)	−0.0007 (7)	0.0111 (8)	−0.0024 (7)
C111	0.0246 (12)	0.0239 (12)	0.0132 (11)	−0.0057 (10)	0.0048 (9)	−0.0011 (9)
C112	0.0310 (13)	0.0257 (13)	0.0197 (12)	−0.0060 (10)	0.0054 (10)	0.0040 (10)

Geometric parameters (Å, º)

C1—C11a	1.393 (3)	C10—C10a	1.409 (3)
C1—C2	1.398 (3)	C10—H10	0.9500
C1—H1	0.9500	C10a—C11	1.527 (3)
C2—C3	1.396 (3)	C11—C11a	1.515 (3)
C2—C21	1.507 (3)	C11—C111	1.551 (3)
C3—C4	1.384 (3)	C11—H11	1.0000
C3—H3	0.9500	C21—H21A	0.9800
C4—C4a	1.390 (3)	C21—H21B	0.9800
C4—H4	0.9500	C21—H21C	0.9800
C4a—C11a	1.397 (3)	C51—O51	1.241 (3)
C4a—N5	1.439 (3)	C51—C52	1.504 (3)
N5—C51	1.356 (3)	C52—H52A	0.9800
N5—C6	1.468 (3)	C52—H52B	0.9800
C6—C6a	1.524 (3)	C52—H52C	0.9800
C6—C61	1.543 (3)	C61—O62	1.204 (3)
C6—H6	1.0000	C61—O61	1.325 (3)
C6a—C10a	1.397 (3)	O61—H61	0.9200
C6a—C7	1.407 (3)	C111—C112	1.526 (3)
C7—C8	1.385 (3)	C111—H11A	0.9900
C7—H7	0.9500	C111—H11B	0.9900
C8—C9	1.383 (4)	C112—H12A	0.9800
C8—H8	0.9500	C112—H12B	0.9800
C9—C10	1.387 (3)	C112—H12C	0.9800
C9—H9	0.9500
C11a—C1—C2	121.9 (2)	C10—C10a—C11	116.5 (2)
C11a—C1—H1	119.1	C11a—C11—C10a	112.81 (19)
C2—C1—H1	119.1	C11a—C11—C111	113.73 (18)
C3—C2—C1	118.5 (2)	C10a—C11—C111	112.05 (18)
C3—C2—C21	120.6 (2)	C11a—C11—H11	105.8
C1—C2—C21	120.9 (2)	C10a—C11—H11	105.8
C4—C3—C2	120.7 (2)	C111—C11—H11	105.8
C4—C3—H3	119.7	C1—C11a—C4a	118.0 (2)
C2—C3—H3	119.7	C1—C11a—C11	120.9 (2)
C3—C4—C4a	119.8 (2)	C4a—C11a—C11	121.1 (2)
C3—C4—H4	120.1	C2—C21—H21A	109.5
C4a—C4—H4	120.1	C2—C21—H21B	109.5
C4—C4a—C11a	121.1 (2)	H21A—C21—H21B	109.5
C4—C4a—N5	121.3 (2)	C2—C21—H21C	109.5
C11a—C4a—N5	117.50 (19)	H21A—C21—H21C	109.5
C51—N5—C4a	123.97 (18)	H21B—C21—H21C	109.5
C51—N5—C6	118.90 (18)	O51—C51—N5	120.0 (2)
C4a—N5—C6	116.29 (17)	O51—C51—C52	120.8 (2)
N5—C6—C6a	116.21 (18)	N5—C51—C52	119.2 (2)
N5—C6—C61	107.51 (17)	C51—C52—H52A	109.5
C6a—C6—C61	113.99 (18)	C51—C52—H52B	109.5
N5—C6—H6	106.1	H52A—C52—H52B	109.5
C6a—C6—H6	106.1	C51—C52—H52C	109.5
C61—C6—H6	106.1	H52A—C52—H52C	109.5
C10a—C6a—C7	119.4 (2)	H52B—C52—H52C	109.5
C10a—C6a—C6	126.77 (19)	O62—C61—O61	125.2 (2)
C7—C6a—C6	113.8 (2)	O62—C61—C6	125.3 (2)
C8—C7—C6a	121.7 (2)	O61—C61—C6	109.52 (18)
C8—C7—H7	119.2	C61—O61—H61	110.0
C6a—C7—H7	119.2	C112—C111—C11	112.24 (19)
C9—C8—C7	119.2 (2)	C112—C111—H11A	109.2
C9—C8—H8	120.4	C11—C111—H11A	109.2
C7—C8—H8	120.4	C112—C111—H11B	109.2
C8—C9—C10	119.7 (2)	C11—C111—H11B	109.2
C8—C9—H9	120.2	H11A—C111—H11B	107.9
C10—C9—H9	120.2	C111—C112—H12A	109.5
C9—C10—C10a	122.1 (2)	C111—C112—H12B	109.5
C9—C10—H10	118.9	H12A—C112—H12B	109.5
C10a—C10—H10	118.9	C111—C112—H12C	109.5
C6a—C10a—C10	117.8 (2)	H12A—C112—H12C	109.5
C6a—C10a—C11	125.67 (19)	H12B—C112—H12C	109.5
C11a—C1—C2—C3	−1.7 (3)	C6—C6a—C10a—C11	0.6 (4)
C11a—C1—C2—C21	179.1 (2)	C9—C10—C10a—C6a	−0.5 (3)
C1—C2—C3—C4	2.2 (3)	C9—C10—C10a—C11	177.7 (2)
C21—C2—C3—C4	−178.5 (2)	C6a—C10a—C11—C11a	−48.5 (3)
C2—C3—C4—C4a	−0.3 (3)	C10—C10a—C11—C11a	133.4 (2)
C3—C4—C4a—C11a	−2.3 (3)	C6a—C10a—C11—C111	81.4 (3)
C3—C4—C4a—N5	−179.1 (2)	C10—C10a—C11—C111	−96.7 (2)
C4—C4a—N5—C51	−67.9 (3)	C2—C1—C11a—C4a	−0.8 (3)
C11a—C4a—N5—C51	115.2 (2)	C2—C1—C11a—C11	178.4 (2)
C4—C4a—N5—C6	101.4 (2)	C4—C4a—C11a—C1	2.8 (3)
C11a—C4a—N5—C6	−75.5 (2)	N5—C4a—C11a—C1	179.75 (19)
C51—N5—C6—C6a	−126.5 (2)	C4—C4a—C11a—C11	−176.4 (2)
C4a—N5—C6—C6a	63.6 (2)	N5—C4a—C11a—C11	0.5 (3)
C51—N5—C6—C61	104.4 (2)	C10a—C11—C11a—C1	−116.4 (2)
C4a—N5—C6—C61	−65.5 (2)	C111—C11—C11a—C1	114.6 (2)
N5—C6—C6a—C10a	−4.9 (3)	C10a—C11—C11a—C4a	62.8 (3)
C61—C6—C6a—C10a	121.0 (2)	C111—C11—C11a—C4a	−66.2 (3)
N5—C6—C6a—C7	172.59 (19)	C4a—N5—C51—O51	175.1 (2)
C61—C6—C6a—C7	−61.5 (3)	C6—N5—C51—O51	6.0 (3)
C10a—C6a—C7—C8	−1.1 (3)	C4a—N5—C51—C52	−6.6 (3)
C6—C6a—C7—C8	−178.8 (2)	C6—N5—C51—C52	−175.6 (2)
C6a—C7—C8—C9	0.0 (4)	N5—C6—C61—O62	131.7 (2)
C7—C8—C9—C10	0.8 (4)	C6a—C6—C61—O62	1.4 (3)
C8—C9—C10—C10a	−0.6 (4)	N5—C6—C61—O61	−49.6 (2)
C7—C6a—C10a—C10	1.3 (3)	C6a—C6—C61—O61	−179.92 (18)
C6—C6a—C10a—C10	178.6 (2)	C11a—C11—C111—C112	−159.48 (19)
C7—C6a—C10a—C11	−176.7 (2)	C10a—C11—C111—C112	71.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O61—H61···O51^i	0.92	1.67	2.572 (2)	167
C4—H4···O62^ii	0.95	2.58	3.220 (3)	125
C8—H8···O62^iii	0.95	2.58	3.405 (3)	145

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x, −y+3/2, z−1/2; (iii) x, −y+3/2, z+1/2.

(III) (6RS,11SR)-5-Acetyl-11-ethyl-1,3-dimethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxylic acid

Crystal data

C21H23NO3	F(000) = 720
Mr = 337.40	Dx = 1.250 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3320 reflections
a = 9.2283 (11) Å	θ = 2.8–25.5°
b = 16.691 (2) Å	µ = 0.08 mm^−1
c = 11.9824 (18) Å	T = 120 K
β = 103.820 (11)°	Block, colourless
V = 1792.2 (4) Å^3	0.23 × 0.20 × 0.20 mm
Z = 4

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	3316 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	2090 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.139
Detector resolution: 9.091 pixels mm^-1	θmax = 25.5°, θmin = 3.9°
φ and ω scans	h = −11→11
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −20→19
Tmin = 0.981, Tmax = 0.984	l = −14→14
27558 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)] = 0.058	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.120	H-atom parameters constrained
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0317P)^2 + 1.5359P] where P = (Fo^2 + 2Fc^2)/3
3316 reflections	(Δ/σ)max = 0.001
230 parameters	Δρmax = 0.25 e Å^−3
0 restraints	Δρmin = −0.29 e Å^−3

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

	x	y	z	Uiso*/Ueq
C1	0.3227 (3)	0.48561 (16)	0.3898 (2)	0.0174 (6)
C2	0.2439 (3)	0.53647 (17)	0.4458 (2)	0.0197 (6)
H2	0.2072	0.5158	0.5076	0.024*
C3	0.2165 (3)	0.61670 (17)	0.4150 (2)	0.0205 (6)
C4	0.2709 (3)	0.64561 (17)	0.3246 (2)	0.0174 (6)
H4	0.2549	0.7001	0.3020	0.021*
C4a	0.3486 (3)	0.59547 (15)	0.2670 (2)	0.0141 (6)
N5	0.4052 (2)	0.62796 (12)	0.17360 (17)	0.0132 (5)
C6	0.5661 (3)	0.64307 (15)	0.1962 (2)	0.0146 (6)
H6	0.5817	0.6680	0.1241	0.018*
C6a	0.6650 (3)	0.56840 (16)	0.2147 (2)	0.0155 (6)
C7	0.8137 (3)	0.58138 (16)	0.2103 (2)	0.0172 (6)
H7	0.8446	0.6342	0.1972	0.021*
C8	0.9167 (3)	0.51994 (17)	0.2243 (2)	0.0206 (6)
H8	1.0173	0.5308	0.2228	0.025*
C9	0.8724 (3)	0.44232 (17)	0.2404 (2)	0.0225 (7)
H9	0.9418	0.3993	0.2503	0.027*
C10	0.7248 (3)	0.42871 (16)	0.2419 (2)	0.0194 (6)
H10	0.6940	0.3753	0.2510	0.023*
C10a	0.6187 (3)	0.49019 (16)	0.2306 (2)	0.0149 (6)
C11	0.4610 (3)	0.46222 (16)	0.2309 (2)	0.0161 (6)
H11	0.4741	0.4097	0.2723	0.019*
C11a	0.3770 (3)	0.51523 (16)	0.2974 (2)	0.0148 (6)
C12	0.3465 (3)	0.39932 (17)	0.4299 (2)	0.0256 (7)
H12A	0.2968	0.3901	0.4925	0.038*
H12B	0.4536	0.3889	0.4575	0.038*
H12C	0.3045	0.3633	0.3658	0.038*
C31	0.1284 (4)	0.67011 (19)	0.4762 (3)	0.0313 (8)
H31A	0.0923	0.7169	0.4282	0.047*
H31B	0.1925	0.6878	0.5495	0.047*
H31C	0.0432	0.6403	0.4905	0.047*
C51	0.3141 (3)	0.65751 (16)	0.0762 (2)	0.0163 (6)
O51	0.3684 (2)	0.69395 (11)	0.00503 (15)	0.0212 (5)
C52	0.1502 (3)	0.64286 (18)	0.0543 (2)	0.0231 (7)
H52A	0.1063	0.6805	0.0997	0.035*
H52B	0.1325	0.5879	0.0764	0.035*
H52C	0.1042	0.6506	−0.0275	0.035*
C61	0.6070 (3)	0.70912 (16)	0.2882 (2)	0.0160 (6)
O61	0.7497 (2)	0.70908 (11)	0.34155 (16)	0.0223 (5)
H61	0.7652	0.7474	0.3911	0.034*
O62	0.5169 (2)	0.75766 (11)	0.30369 (18)	0.0268 (5)
C111	0.3721 (3)	0.44278 (17)	0.1067 (2)	0.0190 (6)
H11A	0.3513	0.4933	0.0626	0.023*
H11B	0.4343	0.4087	0.0691	0.023*
C112	0.2253 (3)	0.40005 (18)	0.1024 (3)	0.0273 (7)
H11C	0.2449	0.3498	0.1457	0.041*
H11D	0.1752	0.3885	0.0223	0.041*
H11E	0.1612	0.4344	0.1365	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0145 (15)	0.0211 (15)	0.0154 (13)	−0.0016 (12)	0.0008 (11)	0.0038 (12)
C2	0.0160 (16)	0.0306 (17)	0.0129 (13)	−0.0002 (12)	0.0044 (11)	0.0035 (12)
C3	0.0161 (16)	0.0286 (17)	0.0157 (14)	0.0010 (12)	0.0016 (12)	−0.0018 (12)
C4	0.0174 (16)	0.0171 (15)	0.0165 (13)	0.0010 (12)	0.0017 (11)	−0.0019 (11)
C4a	0.0119 (14)	0.0192 (14)	0.0095 (13)	−0.0024 (11)	−0.0011 (11)	0.0001 (11)
N5	0.0127 (12)	0.0133 (11)	0.0129 (11)	−0.0004 (9)	0.0014 (9)	0.0021 (9)
C6	0.0131 (15)	0.0160 (14)	0.0142 (13)	−0.0015 (11)	0.0022 (11)	0.0026 (11)
C6a	0.0185 (15)	0.0173 (14)	0.0103 (13)	0.0000 (12)	0.0026 (11)	−0.0020 (11)
C7	0.0188 (16)	0.0189 (15)	0.0151 (14)	−0.0031 (12)	0.0063 (12)	−0.0019 (11)
C8	0.0163 (16)	0.0257 (16)	0.0199 (14)	−0.0034 (13)	0.0048 (12)	−0.0067 (12)
C9	0.0192 (16)	0.0247 (16)	0.0232 (15)	0.0058 (12)	0.0040 (12)	−0.0013 (13)
C10	0.0230 (17)	0.0159 (15)	0.0199 (14)	−0.0009 (12)	0.0063 (12)	−0.0012 (12)
C10a	0.0176 (15)	0.0166 (14)	0.0102 (12)	−0.0011 (11)	0.0026 (11)	0.0008 (11)
C11	0.0177 (16)	0.0137 (14)	0.0165 (14)	−0.0002 (11)	0.0032 (11)	0.0002 (11)
C11a	0.0123 (15)	0.0176 (14)	0.0134 (13)	−0.0004 (11)	0.0011 (11)	−0.0003 (11)
C12	0.0296 (18)	0.0251 (16)	0.0242 (16)	−0.0015 (14)	0.0101 (14)	0.0099 (13)
C31	0.035 (2)	0.0386 (19)	0.0241 (16)	0.0080 (15)	0.0154 (14)	−0.0010 (14)
C51	0.0174 (16)	0.0154 (14)	0.0162 (14)	−0.0002 (11)	0.0040 (12)	−0.0008 (11)
O51	0.0179 (11)	0.0247 (11)	0.0200 (10)	0.0004 (9)	0.0027 (8)	0.0088 (9)
C52	0.0161 (16)	0.0306 (17)	0.0209 (15)	−0.0009 (13)	0.0012 (12)	0.0046 (13)
C61	0.0154 (16)	0.0144 (14)	0.0167 (14)	−0.0036 (12)	0.0011 (11)	0.0019 (11)
O61	0.0175 (11)	0.0236 (11)	0.0233 (10)	0.0012 (8)	−0.0005 (8)	−0.0111 (9)
O62	0.0214 (12)	0.0189 (11)	0.0375 (12)	0.0027 (9)	0.0020 (9)	−0.0101 (9)
C111	0.0190 (16)	0.0210 (15)	0.0175 (14)	−0.0034 (12)	0.0051 (12)	−0.0051 (12)
C112	0.0257 (18)	0.0274 (17)	0.0284 (17)	−0.0079 (14)	0.0057 (14)	−0.0074 (13)

Geometric parameters (Å, º)

C1—C2	1.390 (4)	C10—H10	0.9500
C1—C11a	1.408 (4)	C10a—C11	1.529 (4)
C1—C12	1.518 (4)	C11—C11a	1.522 (4)
C2—C3	1.396 (4)	C11—C111	1.552 (4)
C2—H2	0.9500	C11—H11	1.0000
C3—C4	1.384 (4)	C12—H12A	0.9800
C3—C31	1.509 (4)	C12—H12B	0.9800
C4—C4a	1.389 (4)	C12—H12C	0.9800
C4—H4	0.9500	C31—H31A	0.9800
C4a—C11a	1.396 (4)	C31—H31B	0.9800
C4a—N5	1.448 (3)	C31—H31C	0.9800
N5—C51	1.358 (3)	C51—O51	1.246 (3)
N5—C6	1.466 (3)	C51—C52	1.492 (4)
C6—C6a	1.529 (4)	C52—H52A	0.9800
C6—C61	1.541 (4)	C52—H52B	0.9800
C6—H6	1.0000	C52—H52C	0.9800
C6a—C10a	1.400 (4)	C61—O62	1.207 (3)
C6a—C7	1.403 (4)	C61—O61	1.319 (3)
C7—C8	1.381 (4)	O61—H61	0.8604
C7—H7	0.9500	C111—C112	1.521 (4)
C8—C9	1.386 (4)	C111—H11A	0.9900
C8—H8	0.9500	C111—H11B	0.9900
C9—C10	1.385 (4)	C112—H11C	0.9800
C9—H9	0.9500	C112—H11D	0.9800
C10—C10a	1.402 (4)	C112—H11E	0.9800
C2—C1—C11a	119.3 (2)	C10a—C11—C111	110.3 (2)
C2—C1—C12	118.6 (2)	C11a—C11—H11	105.4
C11a—C1—C12	122.1 (2)	C10a—C11—H11	105.4
C1—C2—C3	122.8 (3)	C111—C11—H11	105.4
C1—C2—H2	118.6	C4a—C11a—C1	117.6 (2)
C3—C2—H2	118.6	C4a—C11a—C11	120.5 (2)
C4—C3—C2	117.7 (3)	C1—C11a—C11	121.9 (2)
C4—C3—C31	120.8 (3)	C1—C12—H12A	109.5
C2—C3—C31	121.5 (3)	C1—C12—H12B	109.5
C3—C4—C4a	120.4 (3)	H12A—C12—H12B	109.5
C3—C4—H4	119.8	C1—C12—H12C	109.5
C4a—C4—H4	119.8	H12A—C12—H12C	109.5
C4—C4a—C11a	122.3 (2)	H12B—C12—H12C	109.5
C4—C4a—N5	118.9 (2)	C3—C31—H31A	109.5
C11a—C4a—N5	118.8 (2)	C3—C31—H31B	109.5
C51—N5—C4a	122.4 (2)	H31A—C31—H31B	109.5
C51—N5—C6	119.2 (2)	C3—C31—H31C	109.5
C4a—N5—C6	117.2 (2)	H31A—C31—H31C	109.5
N5—C6—C6a	115.4 (2)	H31B—C31—H31C	109.5
N5—C6—C61	108.6 (2)	O51—C51—N5	119.8 (2)
C6a—C6—C61	116.3 (2)	O51—C51—C52	121.1 (2)
N5—C6—H6	105.1	N5—C51—C52	119.0 (2)
C6a—C6—H6	105.1	C51—C52—H52A	109.5
C61—C6—H6	105.1	C51—C52—H52B	109.5
C10a—C6a—C7	118.8 (2)	H52A—C52—H52B	109.5
C10a—C6a—C6	126.1 (2)	C51—C52—H52C	109.5
C7—C6a—C6	115.1 (2)	H52A—C52—H52C	109.5
C8—C7—C6a	122.1 (3)	H52B—C52—H52C	109.5
C8—C7—H7	118.9	O62—C61—O61	124.8 (2)
C6a—C7—H7	118.9	O62—C61—C6	122.0 (2)
C7—C8—C9	119.6 (3)	O61—C61—C6	113.1 (2)
C7—C8—H8	120.2	C61—O61—H61	108.4
C9—C8—H8	120.2	C112—C111—C11	113.2 (2)
C10—C9—C8	118.6 (3)	C112—C111—H11A	108.9
C10—C9—H9	120.7	C11—C111—H11A	108.9
C8—C9—H9	120.7	C112—C111—H11B	108.9
C9—C10—C10a	123.0 (3)	C11—C111—H11B	108.9
C9—C10—H10	118.5	H11A—C111—H11B	107.8
C10a—C10—H10	118.5	C111—C112—H11C	109.5
C6a—C10a—C10	117.8 (2)	C111—C112—H11D	109.5
C6a—C10a—C11	127.3 (2)	H11C—C112—H11D	109.5
C10—C10a—C11	114.8 (2)	C111—C112—H11E	109.5
C11a—C11—C10a	115.4 (2)	H11C—C112—H11E	109.5
C11a—C11—C111	113.9 (2)	H11D—C112—H11E	109.5
C11a—C1—C2—C3	−0.5 (4)	C9—C10—C10a—C6a	1.4 (4)
C12—C1—C2—C3	180.0 (3)	C9—C10—C10a—C11	178.3 (2)
C1—C2—C3—C4	0.0 (4)	C6a—C10a—C11—C11a	−43.6 (4)
C1—C2—C3—C31	179.0 (3)	C10—C10a—C11—C11a	139.8 (2)
C2—C3—C4—C4a	0.6 (4)	C6a—C10a—C11—C111	87.1 (3)
C31—C3—C4—C4a	−178.4 (3)	C10—C10a—C11—C111	−89.4 (3)
C3—C4—C4a—C11a	−0.8 (4)	C4—C4a—C11a—C1	0.4 (4)
C3—C4—C4a—N5	−179.4 (2)	N5—C4a—C11a—C1	179.0 (2)
C4—C4a—N5—C51	−62.8 (3)	C4—C4a—C11a—C11	179.3 (2)
C11a—C4a—N5—C51	118.6 (3)	N5—C4a—C11a—C11	−2.1 (4)
C4—C4a—N5—C6	105.2 (3)	C2—C1—C11a—C4a	0.2 (4)
C11a—C4a—N5—C6	−73.5 (3)	C12—C1—C11a—C4a	179.8 (2)
C51—N5—C6—C6a	−123.6 (2)	C2—C1—C11a—C11	−178.6 (2)
C4a—N5—C6—C6a	68.0 (3)	C12—C1—C11a—C11	0.9 (4)
C51—N5—C6—C61	103.6 (3)	C10a—C11—C11a—C4a	59.8 (3)
C4a—N5—C6—C61	−64.8 (3)	C111—C11—C11a—C4a	−69.3 (3)
N5—C6—C6a—C10a	−11.2 (4)	C10a—C11—C11a—C1	−121.4 (3)
C61—C6—C6a—C10a	117.9 (3)	C111—C11—C11a—C1	109.5 (3)
N5—C6—C6a—C7	166.2 (2)	C4a—N5—C51—O51	170.9 (2)
C61—C6—C6a—C7	−64.7 (3)	C6—N5—C51—O51	3.1 (4)
C10a—C6a—C7—C8	−1.8 (4)	C4a—N5—C51—C52	−11.5 (4)
C6—C6a—C7—C8	−179.4 (2)	C6—N5—C51—C52	−179.2 (2)
C6a—C7—C8—C9	1.6 (4)	N5—C6—C61—O62	−24.6 (3)
C7—C8—C9—C10	0.1 (4)	C6a—C6—C61—O62	−156.9 (2)
C8—C9—C10—C10a	−1.6 (4)	N5—C6—C61—O61	159.0 (2)
C7—C6a—C10a—C10	0.4 (4)	C6a—C6—C61—O61	26.7 (3)
C6—C6a—C10a—C10	177.6 (2)	C11a—C11—C111—C112	−59.2 (3)
C7—C6a—C10a—C11	−176.1 (2)	C10a—C11—C111—C112	169.2 (2)
C6—C6a—C10a—C11	1.1 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O61—H61···O51^i	0.86	1.76	2.575 (3)	156
C9—H9···O62^ii	0.95	2.50	3.329 (3)	145
C8—H8···Cg1^iii	0.95	2.75	3.569 (3)	144

Symmetry codes: (i) x+1/2, −y+3/2, z+1/2; (ii) −x+3/2, y−1/2, −z+1/2; (iii) x+1, y, z.