The effect of bromine scanning around the phenyl group of 4-phenyl­quinolone derivatives

Three quinolone compounds were synthesized and crystallized in an effort to study the structure–activity relationship of these calcium-channel antagonists. In all three quinolones, viz. ethyl 4-(4-bromo­phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate, (I), ethyl 4-(3-bromo­phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-car­box­yl­ate, (II), and ethyl 4-(2-bromo­phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate, (III), all C₂₁H₂₄BrNO₃, common structural features such as a flat boat conformation of the 1,4-di­hydro­pyridine (1,4-DHP) ring, an envelope conformation of the fused cyclo­hexa­none ring and a bromo­phenyl ring at the pseudo-axial position and orthogonal to the 1,4-DHP ring are retained. However, due to the different packing inter­actions in each compound, halogen bonds are observed in (I) and (III). Compound (III) crystallizes with two molecules in the asymmetric unit. All of the prepared derivatives satisfy the basic structural requirements to possess moderate activity as calcium-channel antagonists.

S1. Introduction

The 1,4-di­hydro­pyridine (1,4-DHP) heterocycle comprises a large family of medicinally important compounds. The substructure has garnered the most attention as calcium channel antagonists working as slow calcium channel blockers, which have been used in the treatment of angina pectoris and hypertension. The examination of Hantzsch 1,4-di­hydro­pyridine ester derivatives has produced more active and longer acting agents than the prototypical nifedipine molecule. Many other derivatives have been synthesized to yield compounds active as calcium agonists or antagonists (Martin-Leon et al., 1995; Rose, 1990; Rose & Draeger, 1992). A fused cyclo­hexanone ring is one of the modifications to 1,4-DHP compounds and this class has been shown to have moderate calcium antagonistic activity, as well as modest anti-inflammatory and stem cell differentiation properties, and has been implicated in slowing neurodegenerative disorders. Thus, further understanding of the structure–activity relationship of 1,4-DHP compounds and their derivatives will allow for the determination of off-target activity and the reduction of side effects. It has been proven that the flattened boat conformation of the 1,4-DHP ring is one factor that leads to higher calcium channel activity. Atoms N1 and C4 of the DHP ring can be marginally displaced from the mean plane of the boat (Linden et al., 2002). An aryl group in the 4-position of 1,4-DHP is essential for optimal activity. One study showed that an aryl ring with halogen or other electron-withdrawing groups exhibits higher receptor-binding activity (Takahashi et al., 2008). On the 1,4-DHP ring, ester groups are usually substituted at the 3- and 5-positions. It is suggested that at least one cis-ester is required for the calcium antagonistic effect and hydrogen bonding to the receptor (Fossheim, 1986). In an effort to find more active calcium channel antagonists in the 1,4-DHP genre, we have synthesized a series of 1,4-DHP fused-ring derivatives, hexa­hydro­quinolones. In this paper, we report three structures which have bromine substituted at the para-, meta- and ortho-positions on the phenyl ring attached to the 1,4-DHP ring, compounds (I)–(III).

S2. Experimental

S2.1. Synthesis and crystallization

An oven-dried 100 ml round-bottomed flask was charged with dimedone (0.757 g), ethyl aceto­acetate (0.703 g), ytterbium(III) tri­fluoro­methane­sulfonate (0.170 g) and a magenetic stirrer bar. The mixture was then taken up in absolute ethanol (13.5 ml), capped, placed under an inert atmosphere of argon and stirred at room temperature for 20 min. Homologues of bromo­benzaldehyde (1.0 g, 5.405 mmol) and a qu­antity of ammonium acetate (0.419 g) were added to the stirred solution, and it was stirred at room temperature for a further 48 h. Reaction progress was monitored via thin-layer chromatography (TLC). Once the reaction was complete, excess solvent was removed via rotary evaporation. The solution was then purified via silica-column chromatography. The products were recrystallized from hexane and ethyl acetate as white to light-yellow crystalline solids [for (I), yield 1.91 g, 4.57 mmol, 84.00%; for (II), yield 1.86 g, 4.45 mmol, 82.30%; for (III), yield 1.45 g, 3.466 mmol, 63.76%].

S2.2. Characterization information

Melting points were determined in open capillary tubes with a Mel-Temp melting point apparatus (200 W) and are uncorrected. Structures were confirmed with ¹H and ¹³C NMR, and mass spectroscopy. ¹H NMR spectra were obtained in chloro­form-d₁ using a Bruker AMX 400 MHz spectrometer. Chemical shifts are reported as p.p.m. relative to tetra­methyl­silane (TMS). LC–MS (liquid chromatography–mass spectrometry) data were obtained using a Waters LCT Premier XE series spectrometer.

Compound (I). ¹H NMR (CDCl₃, δ, p.p.m.): 7.31 (d, J = 8.28 Hz, 2H), 7.20 (d, J = 8.28 Hz, 2H), 6.01 (bs, 1H), 5.02 (s, 1H), 4.05 (q, J = 7.03 Hz, 2H), 2.38 (s, 3H), 2.21 (s, 2H), 2.17 (s, 2H), 1.20 (t, J = 7.15 Hz, 3H), 1.08 (s, 3H), 0.93 (s, 6H); ¹³C NMR (CDCl₃, δ, p.p.m.): 195.42, 167.19, 148.01, 146.07, 143.60, 130.96, 129.89, 119.82, 111.90, 105.72, 59.94, 50.69, 41.14, 36.33, 32.75, 29.44, 27.15, 19.49, 14.23. HRMS, calculated for C₂₁H₂₄NO₃Br: 418.1018; found: 418.1024. MS, m/z = 418 ([M⁺¹] 100), 419 ([M⁺²] 10), 420 ([M⁺³] 100). m.p. 527–528 K. TLC [SiO₂, hexane–EtOAc (3:2 v/v)]: R_f = 0.19.

Compound (II). ¹H NMR (CDCl₃, δ, p.p.m.): 7.41 (s, 1H), 7.26 (d, J = 7.53 Hz, 1H), 7.22 (d, J = 8.53 Hz, 1H), 7.07 (t, J = 7.78 Hz, 1H), 6.09 (bs, 1H), 5.03 (s, 1H), 4.07 (m, J = 7.15 Hz, 2H), 2.38 (s, 3H), 2.31 (s, 2H), 2.22 (s, 2H), 1.21 (t, J = 7.15 Hz, 3H), 1.09 (s, 3H), 0.96 (s, 6H); ¹³C NMR (CDCl₃, δ, p.p.m.): 195.39, 167.15, 149.30, 148.24, 143.79, 131.09, 129.17, 126.97, 122.10, 111.71, 105.60, 59.96, 50.69, 41.12, 36.64, 32.78, 29.40, 27.22, 19.51, 14.21. HRMS, calculated for C₂₁H₂₄NO₃Br: 418.1018; found: 418.0979. MS, m/z = 418 ([M⁺¹] 100), 419 ([M⁺²] 90). m.p. 508-509 K. TLC [SiO₂, hexane–EtOAc (3:2 v/v)]: R_f = 0.12.

Compound (III). ¹H NMR (CDCl₃, δ, p.p.m.): 7.44 (dd, J = 7.91 Hz, 1H), 7.37 (dd, J = 7.78 Hz, 1H), 7.16 (tt, J = 7.53 Hz, 1H), 6.94 (tt, J = 7.91 Hz, 1H), 5.92 (bs, 1H), 5.37 (s, 1H), 4.08 (m, J = 7.15 Hz, 2H), 2.32 (s, 3H), 2.30 (s, 2H), 2.19 (s, 2H), 1.18 (t, J = 7.03 Hz 3H), 1.08 (s, 3H), 0.96 (s, 6H); ¹³C NMR (CDCl₃, δ, p.p.m.): 195.30, 167.44, 148.04, 145.88, 143.22, 133.08, 132.03, 127.49, 126.97, 123.38, 111.74, 105.86, 59.84, 50.69, 41.29, 37.98, 32.58, 29.28, 27.38, 19.49, 14.36. HRMS, calculated for C₂₁H₂₄NO₃Br: 418.1018; found: 418.1037. MS: m/z = 417 ([M] 100), 418 ([M⁺¹] 100), 419 ([M⁺²] 30). m.p. 473–477 K. TLC [SiO₂, hexane–EtOAc (3:2 v/v)]: R_f = 0.23.

S2.3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. The methyl H atoms were constrained to an ideal geometry, with C—H = 0.98 Å and U_iso(H) = 1.5U_eq(C), and were allowed to rotate freely about their C—C bonds. The remaining C-bound H atoms were placed in calculated positions, with C—H = 0.95–1.00 Å, and refined as riding, with U_iso(H) = 1.2U_eq(C). The positions of the amine H atoms were determined from difference Fourier maps and refined freely along with their isotropic displacement parameters. Two low-angle reflections of (I) and four of (III) were omitted from the refinement because their observed intensities were much lower than the calculated values as a result of being partially obscured by the beam stop.

S3. Results and discussion

Both ethyl 4-(4-bromo­phenyl)-2,7,7-tri­methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3- carboxyl­ate, (I) (Fig. 1), and ethyl 4-(3-bromo­phenyl)-2,7,7-tri­methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3- carboxyl­ate, (II) (Fig. 2), crystallize in the orthorhombic space group Pbcn with one molecule in the asymmetric unit. The asymmetric unit of ethyl 4-(2-bromo­phenyl)-2,7,7-tri­methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3- carboxyl­ate, (III) (Fig. 3), is composed of two enanti­omers of (III), molecules (IIIA) and (IIIB), which crystallize in the monoclinic space group P2₁/c. All three compounds have very similar structural conformations, which accommodate the requirements for calcium channel antagonists.

In all three structures, the 1,4-DHP ring is characterized by a shallow or flattened boat conformation, which is one of the factors that leads to higher calcium channel activity. The boat conformation can be qu­anti­fied by ring puckering parameters (Cremer & Pople, 1975). An ideal boat would have θ = 90° and ϕ = n×60°. In (I), the puckering parameters are Q = 0.196 (2) Å, θ = 106.5 (6)° and ϕ = 5.2 (8)° for the atom sequence N1–C2–C3–C4–C10–C9. The corresponding parameters for (II) are Q = 0.3014 (17) Å, θ = 107.1 (3)° and ϕ = 0.9 (3)°, while for (III), two sets were obtained as Q_A = 0.162 (3) Å, θ_A = 67.3 (10)° and ϕ_A = 197.5 (10)°, and Q_B = 0.279 (3) Å, θ_B = 106.9 (6)° and ϕ_B = 3.9 (6)° for molecules A and B, respectively. The shallowness of the boat conformation is indicated by the marginal displacements of atoms N1 and C4 from the mean plane (the base of the boat) defined by the two double bonds [C2═C3 and C10═ C9]. The deviation of atom N1 from the base of the boat is generally smaller, between 0.00 and 0.19 Å, while the deviation of atom C4 is most frequently found around 0.3 Å (Linden et al., 2004, 2005). These are also observed in the title compounds: the deviations of atom N1 are 0.095 (3), 0.142 (2), 0.047 (3) and 0.134 (3) Å for (I), (II), (IIIA) and (IIIB), respectively; and the deviations of atom C4 are 0.235 (4), 0.365 (2), 0.207 (4) and 0.336 (4) Å for (I), (II), (IIIA) and (IIIB), respectively. The sum of the absolute values of the ring inter­nal torsion angles is also considered a qu­anti­tative measure of the `flatness' of the 1,4-DHP ring. A flattened or unpuckered ring shows a sum of 0° and 240° for an ideal boat conformation of the ring. Here, these sums are 67.74° for (I), 104.39° for (II), 55.72° for (IIIA) and 96.52° for (IIIB) [These vary over a range of nearly 50% - are any conclusions meaningful?], indicating flattened boat conformations, compared with a sum of 72° for nifedipine, the known standard for 1,4-DHPs.

The relationship between the 1,4-DHP pyridine ring and the aryl group attached at the C4 position is another key factor in the 1,4-DHP structure–activity relationship. It has been reported that the pseudo-axial position of the aryl ring is essential for pharmacological activity (Langs et al., 1987). In the title compounds, the bromo­phenyl rings are almost orthogonal to the base of the 1,4-DHP ring defined by atoms C2, C3, C10 and C9, with angles between the mean planes [plane C2/C3/C10/C9 to plane C17–22] of 86.32 (8), 88.46 (5), 99.37 (8) and 89.36 (9)° for (I), (II), (IIIA) and (IIIB), respectively. Another qu­anti­tative descriptive factor is the torsion angle between the N1—C4 axis and the bond in the phenyl group directly above the 1,4-DHP ring [C17—C18 in compounds (I) and (II), and C17—C22 in compound (III)]. The N1—C4—C17—C18 torsion angles are 6.75 (19) and 7.14 (12)° for (I) and (II), respectively. The corresponding torsion angles in (III) show an even more orthogonal configuration as the values are 1.88 (18) and 3.3 (2)° for (IIIA) and (IIIB), respectively. The ortho-bromo group is placed in a synperiplanar orientation with respect to the C4—H bond. Such an orientation has been observed in other ortho-substituted phenyl rings in 4-aryl-1,4-DHP compounds (Linden et al., 2004). It is worth noting that, although meta-NO₂ substitution has been reported to be syn-periplanar to the H atom on C4 (Morales et al., 1996), the meta-bromine in (II) is in an anti-periplanar position. In the same manner as other reported ortho-substituted structures, compound (III) has the bromine pointing away from the 1,4-DHP.

Due to the electron delocalization of the conjugate system, each ester group on the 1,4-DHP is coplanar and at a cis orientation to the adjacent endocyclic double bond. The coplanes extend out through the ester chains in (I) and (II). However, in (III), because of the different packing pattern, the end methyl group in (IIIA) is curled up in the direction of the aryl group. As a result, it pushes the aryl group slightly away from the orthogonal position, thus making the angle between the 1,4-DHP and the aryl ring the most strongly deviating from 90° – 99.37 (8)° in (IIIA) versus 89.36 (9)° in (IIIB).

Again, Cremer & Pople's ring puckering parameters can be used to qu­antify the conformations of the fused cyclo­hexanone rings. In all three compounds, the cyclo­hexanone rings adopt the envelope conformation, which ideally would have θ = 54.7° (or θ = 125.3° in the case of an absolute configuration change) and ϕ = n×60°. For (I), the puckering parameters are Q = 0.447 (3) Å, θ = 57.4 (4)°, and ϕ = 178.6 (4)° for atom sequence C5–C10. For the same atom sequence in (II), (IIIA) and (IIIB), the corresponding puckering parameters are Q = 0.4595 (18) Å, θ = 59.4 (2)° and ϕ = 122.0 (3)° for (II), Q = 0.462 (3) Å, θ = 122.5 (4)° and ϕ = 2.9 (4)° for (IIIA), and Q = 0.477 (3) Å, θ = 59.4 (4)° and ϕ = 183.4 (4)° for (IIIB). All these parameters are very close to those of the ideal envelope conformation. Because of the almost perfect envelope conformation, atom C7 stands out from the plane formed by the rest of the atoms in the ring and points to the same side as the C4-aryl ring. It is also inter­esting that the axial methyl group on C7 is almost syn-periplanar to the bond that connects C4 and the aryl ring. The relationship can be shown by the C11—C7—C4—C17 torsion angle, which is 13.86 (17)° for (I), 4.51 (13)° for (II), 16.2 (2)° for (IIIA) and 5.5 (2)° for (IIIB).

One feature which has not been previously reported for this type of structure is inter­molecular halogen bonding between Br and the ester carbonyl O atom. A halogen bond is defined as a short C—X···O—Y inter­action, where the X···O distance is less than or equal to the sums of the respective van der Waals radii (3.37 Å for Br···O in this case; [Standard reference?]), with the C—X···O angle ≈ 165° and the X···O—Y angle ≈ 120° (Auffinger et al., 2004). Although (II) has an X···O distance of 3.4837 (14) Å, which is only slightly longer than the sum of the van der Waals radii, the angles of 166.17 (13)° for Br1···O2—C14 and 77.24 (6)° for C19—Br1···O2 are out of range for halogen bonds. However, the Br···O distance is 3.1976 (18) Å in (I), with C20—Br1···O2 = 152.24 (9)° and Br1···O2—C14 = 111.06 (15)°, while in (III), Br1A···O2B = 3.1764 (18) Å and the angles are Br1A···O2B—C14B = 106.79 (16)° and C18A—Br1A···O2B = 160.65 (8)°. These numbers are within the range for halogen bonds. Halogen bonding has been known for decades and has been found in biological systems, where the halogen acts as a Lewis acid and the inter­acting atom can be any electron-donating entity. For example, in addition to the backbone carbonyl O atom as the most prominent Lewis base involved in halogen bonds, hydroxyls and carboxyls in the side-chain groups can also form halogen bonds in protein binding sites (Wilcken et al., 2013). The possibility of halogen bonding from Br in these three compounds needs to be considered during the study of their structure–activity relationships.

In all three compounds, hydrogen bonds are formed between the N—H group of one molecule and the carbonyl O atom in the cyclo­hexanone ring of another molecule (Tables 2, 3, and 4). These hydrogen bonds link the molecules into extended chains running along the c axis in both (I) and (II), but along the a axis in (III) (Figs. 4, 5, and 6). In compound (I), the largest difference hole of -1.21 e Å^-3, which is 0.68 Å away from Br1, may indicate a slight disorder of the Br atom.

In conclusion, the structures reported here demonstrate that the conformational features have been conserved in cyclo­hexanone-fused 1,4-DHP derivatives. As a promising base structure for calcium channel antagonists, different substitutions and more structural modifications are being carried out in our group; progress will be reported in due course.

Related literature

For related literature, see: Auffinger et al. (2004); Cremer & Pople (1975); Fossheim (1986); Langs et al. (1987); Linden et al. (2002, 2004, 2005); Martin-Leon, Quinteiro, Seoane, Soto, Mora, Suarez, Ochoa, Morales & Bosque (1995); Morales et al. (1996); Rose (1990); Rose & Draeger (1992); Takahashi et al. (2008); Wilcken et al. (2013).

Computing details

For all compounds, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures

	Fig. 1. The asymmetric unit of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. The asymmetric unit of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 3. The asymmetric unit of (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 4. Part of the crystal structure of (I), showing the formation of chains of molecules running along the c axis. Hydrogen bonds are indicated by dashed lines. For the sake of clarity, H atoms not involved in hydrogen bonding have been omitted.
	Fig. 5. Part of the crystal structure of (II), showing the formation of chains of molecules running along the c axis. Hydrogen bonds are indicated by dashed lines. For the sake of clarity, H atoms not involved in hydrogen bonding have been omitted.
	Fig. 6. Part of the crystal structure of (III), showing the formation of chains of molecules running along the a axis. Hydrogen bonds are indicated by dashed lines. For the sake of clarity, H atoms not involved in hydrogen bonding have been omitted.

(I) Ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

Crystal data

C21H24BrNO3	Dx = 1.400 Mg m^−3
Mr = 418.32	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbcn	Cell parameters from 9956 reflections
a = 18.0371 (4) Å	θ = 2.3–27.5°
b = 15.4309 (3) Å	µ = 2.09 mm^−1
c = 14.2604 (3) Å	T = 100 K
V = 3969.08 (14) Å^3	Prism, light yellow
Z = 8	0.26 × 0.18 × 0.13 mm
F(000) = 1728

Data collection

Bruker SMART BREEZE CCD area-detector diffractometer	3391 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tube	Rint = 0.038
ϕ and ω scans	θmax = 27.5°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −19→23
Tmin = 0.909, Tmax = 1.000	k = −20→19
35271 measured reflections	l = −18→18
4558 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.042	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.101	w = 1/[σ^2(Fo^2) + (0.0386P)^2 + 5.4149P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
4558 reflections	Δρmax = 1.49 e Å^−3
243 parameters	Δρmin = −1.21 e Å^−3
0 restraints

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
Br1	0.01835 (2)	0.08589 (2)	0.60206 (2)	0.03911 (12)
O1	0.39646 (10)	−0.02836 (11)	0.63323 (11)	0.0200 (4)
O2	0.35587 (10)	0.33300 (11)	0.41638 (12)	0.0213 (4)
O3	0.34556 (10)	0.27791 (11)	0.56159 (11)	0.0213 (4)
N1	0.39491 (12)	0.07392 (13)	0.32412 (14)	0.0190 (5)
H1	0.4013 (16)	0.0634 (19)	0.264 (2)	0.027 (8)*
C2	0.38319 (14)	0.15957 (16)	0.35057 (16)	0.0178 (5)
C3	0.36618 (13)	0.17953 (15)	0.44025 (16)	0.0148 (5)
C4	0.35425 (13)	0.10862 (15)	0.51345 (15)	0.0137 (5)
H4	0.3808	0.1260	0.5721	0.016*
C5	0.40247 (13)	−0.04303 (16)	0.54818 (16)	0.0145 (5)
C6	0.43032 (14)	−0.13027 (15)	0.51443 (16)	0.0158 (5)
H6A	0.4101	−0.1757	0.5562	0.019*
H6B	0.4850	−0.1314	0.5207	0.019*
C7	0.41033 (14)	−0.15326 (16)	0.41315 (15)	0.0149 (5)
C8	0.42990 (14)	−0.07570 (15)	0.35066 (16)	0.0158 (5)
H8A	0.4845	−0.0721	0.3445	0.019*
H8B	0.4090	−0.0854	0.2873	0.019*
C9	0.40135 (13)	0.00865 (15)	0.38786 (15)	0.0140 (5)
C10	0.38685 (13)	0.02328 (15)	0.47985 (15)	0.0132 (5)
C11	0.32747 (14)	−0.17399 (17)	0.40568 (17)	0.0203 (5)
H11A	0.2985	−0.1230	0.4240	0.030*
H11B	0.3154	−0.2225	0.4474	0.030*
H11C	0.3154	−0.1898	0.3409	0.030*
C12	0.45589 (15)	−0.23200 (16)	0.38188 (17)	0.0210 (5)
H12A	0.4444	−0.2455	0.3163	0.031*
H12B	0.4435	−0.2819	0.4214	0.031*
H12C	0.5088	−0.2189	0.3879	0.031*
C13	0.39310 (19)	0.22252 (18)	0.27089 (17)	0.0323 (7)
H13A	0.4131	0.1919	0.2163	0.048*
H13B	0.4275	0.2684	0.2898	0.048*
H13C	0.3451	0.2482	0.2547	0.048*
C14	0.35600 (13)	0.27062 (16)	0.46787 (17)	0.0166 (5)
C15	0.33581 (17)	0.36583 (17)	0.59609 (18)	0.0254 (6)
H15A	0.2975	0.3962	0.5588	0.030*
H15B	0.3829	0.3984	0.5907	0.030*
C16	0.3126 (3)	0.3606 (2)	0.6959 (2)	0.0582 (12)
H16A	0.2656	0.3291	0.7004	0.087*
H16B	0.3062	0.4193	0.7210	0.087*
H16C	0.3507	0.3301	0.7321	0.087*
C17	0.27210 (13)	0.09825 (14)	0.53660 (16)	0.0149 (5)
C18	0.22092 (14)	0.08222 (16)	0.46580 (17)	0.0182 (5)
H18	0.2378	0.0755	0.4031	0.022*
C19	0.14545 (15)	0.07577 (16)	0.48494 (19)	0.0226 (6)
H19	0.1109	0.0648	0.4361	0.027*
C20	0.12180 (15)	0.08566 (17)	0.5767 (2)	0.0247 (6)
C21	0.17150 (15)	0.09807 (17)	0.64941 (19)	0.0243 (6)
H21	0.1546	0.1021	0.7123	0.029*
C22	0.24660 (15)	0.10459 (16)	0.62882 (17)	0.0204 (5)
H22	0.2811	0.1135	0.6782	0.025*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.02137 (16)	0.03688 (19)	0.0591 (2)	−0.00082 (14)	0.01586 (14)	−0.01140 (15)
O1	0.0306 (10)	0.0199 (10)	0.0094 (7)	0.0029 (8)	−0.0012 (7)	0.0007 (7)
O2	0.0221 (10)	0.0143 (9)	0.0274 (9)	0.0020 (8)	0.0039 (7)	0.0039 (8)
O3	0.0328 (11)	0.0115 (9)	0.0194 (8)	0.0013 (8)	−0.0009 (8)	−0.0020 (7)
N1	0.0314 (12)	0.0157 (11)	0.0098 (9)	−0.0012 (9)	0.0002 (8)	−0.0005 (8)
C2	0.0234 (13)	0.0134 (12)	0.0166 (11)	−0.0016 (10)	−0.0033 (10)	0.0016 (10)
C3	0.0143 (12)	0.0123 (12)	0.0179 (11)	−0.0008 (10)	−0.0022 (9)	0.0003 (9)
C4	0.0171 (12)	0.0128 (12)	0.0113 (10)	0.0000 (10)	−0.0005 (9)	0.0009 (9)
C5	0.0114 (11)	0.0165 (12)	0.0156 (11)	−0.0018 (10)	−0.0006 (9)	0.0013 (10)
C6	0.0187 (12)	0.0137 (12)	0.0150 (11)	0.0020 (10)	0.0013 (9)	0.0004 (9)
C7	0.0177 (12)	0.0135 (12)	0.0134 (11)	−0.0004 (10)	0.0006 (9)	−0.0006 (9)
C8	0.0193 (12)	0.0147 (13)	0.0135 (11)	−0.0018 (10)	0.0026 (9)	−0.0012 (9)
C9	0.0142 (11)	0.0135 (12)	0.0143 (11)	−0.0022 (10)	−0.0005 (9)	−0.0002 (9)
C10	0.0132 (11)	0.0117 (12)	0.0146 (11)	−0.0001 (9)	0.0009 (9)	0.0000 (9)
C11	0.0204 (13)	0.0188 (13)	0.0217 (12)	−0.0041 (11)	0.0006 (10)	−0.0036 (11)
C12	0.0258 (13)	0.0152 (13)	0.0219 (12)	0.0009 (11)	0.0045 (10)	−0.0026 (10)
C13	0.062 (2)	0.0193 (15)	0.0159 (12)	−0.0038 (14)	0.0004 (13)	0.0046 (11)
C14	0.0108 (11)	0.0176 (13)	0.0214 (12)	−0.0017 (10)	−0.0014 (9)	0.0011 (10)
C15	0.0377 (16)	0.0134 (13)	0.0250 (13)	0.0011 (12)	0.0002 (12)	−0.0038 (11)
C16	0.117 (4)	0.0214 (17)	0.0365 (18)	0.014 (2)	0.020 (2)	−0.0008 (15)
C17	0.0198 (12)	0.0070 (11)	0.0178 (11)	0.0016 (10)	0.0031 (9)	−0.0003 (9)
C18	0.0209 (13)	0.0155 (12)	0.0183 (11)	0.0025 (11)	0.0014 (10)	0.0018 (10)
C19	0.0197 (13)	0.0170 (13)	0.0310 (14)	0.0018 (11)	−0.0007 (11)	0.0003 (11)
C20	0.0180 (13)	0.0157 (13)	0.0403 (15)	0.0010 (11)	0.0094 (11)	−0.0013 (12)
C21	0.0300 (15)	0.0180 (14)	0.0248 (13)	0.0016 (11)	0.0127 (11)	−0.0039 (11)
C22	0.0265 (14)	0.0163 (13)	0.0185 (11)	0.0021 (11)	0.0025 (10)	−0.0024 (10)

Geometric parameters (Å, º)

Br1—C20	1.901 (3)	C9—C10	1.357 (3)
O1—C5	1.239 (3)	C11—H11A	0.9800
O2—C14	1.211 (3)	C11—H11B	0.9800
O3—C14	1.354 (3)	C11—H11C	0.9800
O3—C15	1.454 (3)	C12—H12A	0.9800
N1—H1	0.89 (3)	C12—H12B	0.9800
N1—C2	1.391 (3)	C12—H12C	0.9800
N1—C9	1.362 (3)	C13—H13A	0.9800
C2—C3	1.351 (3)	C13—H13B	0.9800
C2—C13	1.505 (3)	C13—H13C	0.9800
C3—C4	1.528 (3)	C15—H15A	0.9900
C3—C14	1.471 (3)	C15—H15B	0.9900
C4—H4	1.0000	C15—C16	1.485 (4)
C4—C10	1.520 (3)	C16—H16A	0.9800
C4—C17	1.526 (3)	C16—H16B	0.9800
C5—C6	1.515 (3)	C16—H16C	0.9800
C5—C10	1.441 (3)	C17—C18	1.390 (3)
C6—H6A	0.9900	C17—C22	1.397 (3)
C6—H6B	0.9900	C18—H18	0.9500
C6—C7	1.530 (3)	C18—C19	1.392 (4)
C7—C8	1.533 (3)	C19—H19	0.9500
C7—C11	1.532 (3)	C19—C20	1.385 (4)
C7—C12	1.533 (3)	C20—C21	1.384 (4)
C8—H8A	0.9900	C21—H21	0.9500
C8—H8B	0.9900	C21—C22	1.390 (4)
C8—C9	1.497 (3)	C22—H22	0.9500
C14—O3—C15	115.35 (19)	H11A—C11—H11C	109.5
C2—N1—H1	117.3 (19)	H11B—C11—H11C	109.5
C9—N1—H1	120.2 (19)	C7—C12—H12A	109.5
C9—N1—C2	122.3 (2)	C7—C12—H12B	109.5
N1—C2—C13	113.0 (2)	C7—C12—H12C	109.5
C3—C2—N1	120.5 (2)	H12A—C12—H12B	109.5
C3—C2—C13	126.5 (2)	H12A—C12—H12C	109.5
C2—C3—C4	121.0 (2)	H12B—C12—H12C	109.5
C2—C3—C14	120.0 (2)	C2—C13—H13A	109.5
C14—C3—C4	118.9 (2)	C2—C13—H13B	109.5
C3—C4—H4	108.1	C2—C13—H13C	109.5
C10—C4—C3	110.53 (18)	H13A—C13—H13B	109.5
C10—C4—H4	108.1	H13A—C13—H13C	109.5
C10—C4—C17	110.66 (19)	H13B—C13—H13C	109.5
C17—C4—C3	111.08 (19)	O2—C14—O3	122.2 (2)
C17—C4—H4	108.1	O2—C14—C3	126.7 (2)
O1—C5—C6	120.2 (2)	O3—C14—C3	111.2 (2)
O1—C5—C10	121.0 (2)	O3—C15—H15A	110.1
C10—C5—C6	118.74 (19)	O3—C15—H15B	110.1
C5—C6—H6A	108.4	O3—C15—C16	107.9 (2)
C5—C6—H6B	108.4	H15A—C15—H15B	108.4
C5—C6—C7	115.32 (19)	C16—C15—H15A	110.1
H6A—C6—H6B	107.5	C16—C15—H15B	110.1
C7—C6—H6A	108.4	C15—C16—H16A	109.5
C7—C6—H6B	108.4	C15—C16—H16B	109.5
C6—C7—C8	108.26 (19)	C15—C16—H16C	109.5
C6—C7—C11	110.12 (19)	H16A—C16—H16B	109.5
C6—C7—C12	109.4 (2)	H16A—C16—H16C	109.5
C11—C7—C8	110.3 (2)	H16B—C16—H16C	109.5
C11—C7—C12	109.7 (2)	C18—C17—C4	120.4 (2)
C12—C7—C8	109.03 (19)	C18—C17—C22	118.5 (2)
C7—C8—H8A	108.9	C22—C17—C4	121.1 (2)
C7—C8—H8B	108.9	C17—C18—H18	119.3
H8A—C8—H8B	107.8	C17—C18—C19	121.3 (2)
C9—C8—C7	113.18 (19)	C19—C18—H18	119.3
C9—C8—H8A	108.9	C18—C19—H19	120.7
C9—C8—H8B	108.9	C20—C19—C18	118.6 (2)
N1—C9—C8	115.85 (19)	C20—C19—H19	120.7
C10—C9—N1	120.4 (2)	C19—C20—Br1	118.8 (2)
C10—C9—C8	123.6 (2)	C21—C20—Br1	119.6 (2)
C5—C10—C4	118.5 (2)	C21—C20—C19	121.6 (2)
C9—C10—C4	121.6 (2)	C20—C21—H21	120.5
C9—C10—C5	119.9 (2)	C20—C21—C22	118.9 (2)
C7—C11—H11A	109.5	C22—C21—H21	120.5
C7—C11—H11B	109.5	C17—C22—H22	119.5
C7—C11—H11C	109.5	C21—C22—C17	121.0 (2)
H11A—C11—H11B	109.5	C21—C22—H22	119.5
Br1—C20—C21—C22	−174.96 (19)	C7—C8—C9—N1	−159.3 (2)
O1—C5—C6—C7	159.3 (2)	C7—C8—C9—C10	24.9 (3)
O1—C5—C10—C4	−7.0 (3)	C8—C9—C10—C4	−176.9 (2)
O1—C5—C10—C9	173.0 (2)	C8—C9—C10—C5	3.2 (4)
N1—C2—C3—C4	−4.1 (4)	C9—N1—C2—C3	−10.4 (4)
N1—C2—C3—C14	178.3 (2)	C9—N1—C2—C13	168.4 (2)
N1—C9—C10—C4	7.5 (4)	C10—C4—C17—C18	−67.8 (3)
N1—C9—C10—C5	−172.4 (2)	C10—C4—C17—C22	112.2 (2)
C2—N1—C9—C8	−167.3 (2)	C10—C5—C6—C7	−23.8 (3)
C2—N1—C9—C10	8.7 (4)	C11—C7—C8—C9	72.0 (2)
C2—C3—C4—C10	17.6 (3)	C12—C7—C8—C9	−167.4 (2)
C2—C3—C4—C17	−105.7 (3)	C13—C2—C3—C4	177.2 (3)
C2—C3—C14—O2	5.8 (4)	C13—C2—C3—C14	−0.4 (4)
C2—C3—C14—O3	−174.8 (2)	C14—O3—C15—C16	170.6 (3)
C3—C4—C10—C5	160.6 (2)	C14—C3—C4—C10	−164.8 (2)
C3—C4—C10—C9	−19.4 (3)	C14—C3—C4—C17	72.0 (3)
C3—C4—C17—C18	55.4 (3)	C15—O3—C14—O2	−1.3 (3)
C3—C4—C17—C22	−124.6 (2)	C15—O3—C14—C3	179.3 (2)
C4—C3—C14—O2	−171.8 (2)	C17—C4—C10—C5	−75.9 (3)
C4—C3—C14—O3	7.6 (3)	C17—C4—C10—C9	104.1 (2)
C4—C17—C18—C19	−177.6 (2)	C17—C18—C19—C20	0.0 (4)
C4—C17—C22—C21	177.8 (2)	C18—C17—C22—C21	−2.2 (4)
C5—C6—C7—C8	48.7 (3)	C18—C19—C20—Br1	175.19 (19)
C5—C6—C7—C11	−72.0 (3)	C18—C19—C20—C21	−2.7 (4)
C5—C6—C7—C12	167.4 (2)	C19—C20—C21—C22	2.9 (4)
C6—C5—C10—C4	176.1 (2)	C20—C21—C22—C17	−0.4 (4)
C6—C5—C10—C9	−3.9 (3)	C22—C17—C18—C19	2.4 (4)
C6—C7—C8—C9	−48.5 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.89 (3)	1.94 (3)	2.812 (2)	168 (3)

Symmetry code: (i) x, −y, z−1/2.

(II) Ethyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

Crystal data

C21H24BrNO3	Dx = 1.474 Mg m^−3
Mr = 418.32	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbcn	Cell parameters from 9015 reflections
a = 17.0813 (5) Å	θ = 2.3–29.1°
b = 15.4877 (5) Å	µ = 2.20 mm^−1
c = 14.2544 (5) Å	T = 100 K
V = 3771.0 (2) Å^3	Prism, light yellow
Z = 8	0.40 × 0.21 × 0.19 mm
F(000) = 1728

Data collection

Bruker SMART BREEZE CCD area-detector diffractometer	5055 independent reflections
Radiation source: 2 kW sealed X-ray tube	4278 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
ϕ and ω scans	θmax = 29.1°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −23→23
Tmin = 0.839, Tmax = 1.000	k = −21→21
55070 measured reflections	l = −19→19

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.032	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.084	w = 1/[σ^2(Fo^2) + (0.0428P)^2 + 3.6244P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.002
5055 reflections	Δρmax = 1.31 e Å^−3
243 parameters	Δρmin = −0.38 e Å^−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
Br1	0.92434 (2)	0.52663 (2)	0.66172 (2)	0.01998 (7)
O1	0.61002 (8)	0.46449 (8)	0.36349 (9)	0.0170 (3)
O2	0.60547 (9)	0.83120 (9)	0.54611 (11)	0.0273 (3)
O3	0.66301 (8)	0.77388 (8)	0.41978 (10)	0.0235 (3)
N1	0.61112 (9)	0.58166 (9)	0.66708 (10)	0.0132 (3)
C2	0.61780 (9)	0.66563 (11)	0.63433 (12)	0.0132 (3)
C3	0.63546 (9)	0.67997 (11)	0.54285 (12)	0.0132 (3)
C4	0.65961 (9)	0.60546 (10)	0.47927 (11)	0.0117 (3)
H4	0.6397	0.6174	0.4146	0.014*
C10	0.62185 (9)	0.52300 (10)	0.51443 (11)	0.0105 (3)
C9	0.60504 (9)	0.51293 (10)	0.60705 (11)	0.0105 (3)
C8	0.57528 (9)	0.43036 (11)	0.64894 (11)	0.0126 (3)
H8A	0.5176	0.4335	0.6542	0.015*
H8B	0.5968	0.4240	0.7130	0.015*
C7	0.59747 (10)	0.35080 (10)	0.59090 (12)	0.0129 (3)
C6	0.57615 (10)	0.36838 (11)	0.48787 (12)	0.0143 (3)
H6A	0.5981	0.3214	0.4489	0.017*
H6B	0.5185	0.3662	0.4816	0.017*
C5	0.60455 (9)	0.45362 (11)	0.44924 (11)	0.0112 (3)
C11	0.68524 (11)	0.33164 (12)	0.59932 (14)	0.0208 (4)
H11A	0.6988	0.3228	0.6654	0.031*
H11B	0.7152	0.3804	0.5743	0.031*
H11C	0.6978	0.2794	0.5636	0.031*
C12	0.55061 (12)	0.27318 (12)	0.62687 (14)	0.0217 (4)
H12A	0.4946	0.2868	0.6252	0.033*
H12B	0.5663	0.2602	0.6915	0.033*
H12C	0.5610	0.2230	0.5869	0.033*
C13	0.60140 (11)	0.73340 (12)	0.70714 (13)	0.0193 (4)
H13A	0.5964	0.7060	0.7688	0.029*
H13B	0.5525	0.7633	0.6916	0.029*
H13C	0.6446	0.7751	0.7085	0.029*
C14	0.63211 (10)	0.76888 (11)	0.50625 (13)	0.0172 (3)
C15	0.66536 (13)	0.86167 (13)	0.38140 (16)	0.0281 (4)
H15A	0.6813	0.9033	0.4305	0.034*
H15B	0.6131	0.8785	0.3577	0.034*
C16	0.72312 (12)	0.86129 (14)	0.30382 (16)	0.0285 (4)
H16A	0.7739	0.8415	0.3275	0.043*
H16B	0.7285	0.9198	0.2785	0.043*
H16C	0.7052	0.8223	0.2541	0.043*
C17	0.74878 (10)	0.59554 (10)	0.47466 (11)	0.0124 (3)
C18	0.78958 (9)	0.56824 (11)	0.55396 (11)	0.0130 (3)
H18	0.7620	0.5547	0.6099	0.016*
C19	0.87044 (10)	0.56085 (11)	0.55114 (12)	0.0137 (3)
C20	0.91306 (10)	0.57960 (11)	0.47084 (13)	0.0161 (3)
H20	0.9685	0.5752	0.4702	0.019*
C21	0.87189 (11)	0.60498 (12)	0.39144 (13)	0.0199 (4)
H21	0.8996	0.6168	0.3351	0.024*
C22	0.79094 (10)	0.61342 (12)	0.39305 (12)	0.0177 (3)
H22	0.7640	0.6315	0.3381	0.021*
H1	0.6037 (14)	0.5739 (15)	0.7262 (18)	0.021 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.01611 (10)	0.02866 (11)	0.01518 (10)	0.00677 (7)	−0.00292 (6)	−0.00298 (7)
O1	0.0224 (6)	0.0199 (6)	0.0087 (5)	0.0009 (5)	−0.0005 (5)	−0.0006 (5)
O2	0.0349 (8)	0.0137 (6)	0.0332 (8)	0.0049 (6)	0.0042 (6)	0.0020 (6)
O3	0.0262 (7)	0.0184 (6)	0.0259 (7)	0.0052 (5)	0.0088 (6)	0.0111 (5)
N1	0.0179 (7)	0.0137 (7)	0.0079 (6)	−0.0008 (5)	0.0009 (5)	−0.0009 (5)
C2	0.0113 (7)	0.0122 (7)	0.0162 (8)	0.0000 (6)	−0.0011 (6)	−0.0025 (6)
C3	0.0111 (7)	0.0124 (7)	0.0161 (8)	−0.0007 (6)	−0.0011 (6)	0.0009 (6)
C4	0.0122 (7)	0.0129 (7)	0.0101 (7)	−0.0011 (6)	−0.0003 (6)	0.0027 (6)
C10	0.0108 (7)	0.0119 (7)	0.0088 (7)	0.0000 (5)	−0.0003 (5)	0.0012 (6)
C9	0.0098 (7)	0.0116 (7)	0.0101 (7)	0.0006 (5)	−0.0004 (5)	0.0001 (6)
C8	0.0140 (7)	0.0132 (8)	0.0105 (7)	0.0001 (6)	0.0022 (6)	0.0021 (6)
C7	0.0144 (7)	0.0116 (7)	0.0126 (8)	0.0008 (6)	0.0014 (6)	0.0010 (6)
C6	0.0167 (8)	0.0127 (7)	0.0135 (8)	−0.0009 (6)	−0.0002 (6)	−0.0017 (6)
C5	0.0095 (7)	0.0143 (7)	0.0097 (7)	0.0024 (6)	−0.0013 (6)	−0.0011 (6)
C11	0.0193 (8)	0.0209 (9)	0.0223 (9)	0.0069 (7)	0.0020 (7)	0.0047 (7)
C12	0.0283 (9)	0.0139 (8)	0.0228 (9)	−0.0023 (7)	0.0063 (8)	0.0020 (7)
C13	0.0218 (9)	0.0165 (8)	0.0196 (9)	0.0005 (7)	0.0027 (7)	−0.0065 (7)
C14	0.0120 (7)	0.0159 (8)	0.0235 (9)	−0.0019 (6)	−0.0006 (7)	0.0047 (7)
C15	0.0332 (11)	0.0183 (9)	0.0327 (11)	0.0053 (8)	0.0059 (9)	0.0103 (8)
C16	0.0278 (10)	0.0272 (10)	0.0306 (11)	−0.0017 (8)	0.0012 (9)	0.0088 (9)
C17	0.0149 (7)	0.0104 (7)	0.0120 (7)	−0.0011 (6)	0.0025 (6)	−0.0008 (6)
C18	0.0132 (7)	0.0151 (8)	0.0106 (7)	−0.0014 (6)	0.0023 (6)	−0.0019 (6)
C19	0.0155 (7)	0.0119 (7)	0.0137 (8)	0.0003 (6)	−0.0016 (6)	−0.0033 (6)
C20	0.0139 (8)	0.0141 (8)	0.0203 (9)	0.0006 (6)	0.0040 (6)	−0.0014 (6)
C21	0.0213 (9)	0.0221 (9)	0.0164 (8)	0.0002 (7)	0.0084 (7)	0.0043 (7)
C22	0.0195 (8)	0.0200 (8)	0.0134 (8)	0.0012 (7)	0.0033 (6)	0.0051 (6)

Geometric parameters (Å, º)

Br1—C19	1.9009 (17)	C6—C5	1.510 (2)
O1—C5	1.237 (2)	C11—H11A	0.9800
O2—C14	1.209 (2)	C11—H11B	0.9800
O3—C14	1.343 (2)	C11—H11C	0.9800
O3—C15	1.466 (2)	C12—H12A	0.9800
N1—C2	1.386 (2)	C12—H12B	0.9800
N1—C9	1.370 (2)	C12—H12C	0.9800
N1—H1	0.86 (2)	C13—H13A	0.9800
C2—C3	1.357 (2)	C13—H13B	0.9800
C2—C13	1.502 (2)	C13—H13C	0.9800
C3—C4	1.524 (2)	C15—H15A	0.9900
C3—C14	1.474 (2)	C15—H15B	0.9900
C4—H4	1.0000	C15—C16	1.482 (3)
C4—C10	1.516 (2)	C16—H16A	0.9800
C4—C17	1.532 (2)	C16—H16B	0.9800
C10—C9	1.360 (2)	C16—H16C	0.9800
C10—C5	1.451 (2)	C17—C18	1.394 (2)
C9—C8	1.500 (2)	C17—C22	1.396 (2)
C8—H8A	0.9900	C18—H18	0.9500
C8—H8B	0.9900	C18—C19	1.386 (2)
C8—C7	1.532 (2)	C19—C20	1.387 (2)
C7—C6	1.537 (2)	C20—H20	0.9500
C7—C11	1.533 (2)	C20—C21	1.389 (3)
C7—C12	1.533 (2)	C21—H21	0.9500
C6—H6A	0.9900	C21—C22	1.389 (3)
C6—H6B	0.9900	C22—H22	0.9500
C14—O3—C15	113.99 (15)	H11A—C11—H11C	109.5
C2—N1—H1	118.2 (16)	H11B—C11—H11C	109.5
C9—N1—C2	121.67 (14)	C7—C12—H12A	109.5
C9—N1—H1	119.5 (16)	C7—C12—H12B	109.5
N1—C2—C13	114.04 (15)	C7—C12—H12C	109.5
C3—C2—N1	119.69 (15)	H12A—C12—H12B	109.5
C3—C2—C13	126.23 (16)	H12A—C12—H12C	109.5
C2—C3—C4	120.52 (15)	H12B—C12—H12C	109.5
C2—C3—C14	118.99 (16)	C2—C13—H13A	109.5
C14—C3—C4	120.49 (15)	C2—C13—H13B	109.5
C3—C4—H4	108.4	C2—C13—H13C	109.5
C3—C4—C17	111.75 (13)	H13A—C13—H13B	109.5
C10—C4—C3	109.02 (13)	H13A—C13—H13C	109.5
C10—C4—H4	108.4	H13B—C13—H13C	109.5
C10—C4—C17	110.65 (13)	O2—C14—O3	122.23 (16)
C17—C4—H4	108.4	O2—C14—C3	126.45 (17)
C9—C10—C4	120.49 (14)	O3—C14—C3	111.32 (15)
C9—C10—C5	119.58 (14)	O3—C15—H15A	110.3
C5—C10—C4	119.92 (14)	O3—C15—H15B	110.3
N1—C9—C8	116.08 (14)	O3—C15—C16	107.04 (16)
C10—C9—N1	120.08 (15)	H15A—C15—H15B	108.6
C10—C9—C8	123.76 (15)	C16—C15—H15A	110.3
C9—C8—H8A	109.0	C16—C15—H15B	110.3
C9—C8—H8B	109.0	C15—C16—H16A	109.5
C9—C8—C7	112.76 (13)	C15—C16—H16B	109.5
H8A—C8—H8B	107.8	C15—C16—H16C	109.5
C7—C8—H8A	109.0	H16A—C16—H16B	109.5
C7—C8—H8B	109.0	H16A—C16—H16C	109.5
C8—C7—C6	108.35 (13)	H16B—C16—H16C	109.5
C8—C7—C11	110.82 (14)	C18—C17—C4	119.53 (14)
C8—C7—C12	108.72 (14)	C18—C17—C22	118.56 (15)
C11—C7—C6	109.92 (14)	C22—C17—C4	121.91 (15)
C12—C7—C6	109.56 (14)	C17—C18—H18	120.0
C12—C7—C11	109.43 (14)	C19—C18—C17	119.98 (15)
C7—C6—H6A	108.5	C19—C18—H18	120.0
C7—C6—H6B	108.5	C18—C19—Br1	118.78 (13)
H6A—C6—H6B	107.5	C18—C19—C20	121.97 (16)
C5—C6—C7	115.28 (14)	C20—C19—Br1	119.24 (13)
C5—C6—H6A	108.5	C19—C20—H20	121.1
C5—C6—H6B	108.5	C19—C20—C21	117.76 (16)
O1—C5—C10	121.10 (15)	C21—C20—H20	121.1
O1—C5—C6	120.22 (15)	C20—C21—H21	119.4
C10—C5—C6	118.63 (14)	C22—C21—C20	121.13 (16)
C7—C11—H11A	109.5	C22—C21—H21	119.4
C7—C11—H11B	109.5	C17—C22—H22	119.7
C7—C11—H11C	109.5	C21—C22—C17	120.58 (17)
H11A—C11—H11B	109.5	C21—C22—H22	119.7
Br1—C19—C20—C21	−179.58 (13)	C9—C10—C5—C6	−6.4 (2)
N1—C2—C3—C4	−8.9 (2)	C9—C8—C7—C6	−49.12 (18)
N1—C2—C3—C14	171.99 (15)	C9—C8—C7—C11	71.56 (18)
N1—C9—C8—C7	−159.09 (14)	C9—C8—C7—C12	−168.13 (14)
C2—N1—C9—C10	13.9 (2)	C8—C7—C6—C5	49.17 (18)
C2—N1—C9—C8	−162.93 (14)	C7—C6—C5—O1	160.14 (15)
C2—C3—C4—C10	28.5 (2)	C7—C6—C5—C10	−22.5 (2)
C2—C3—C4—C17	−94.13 (18)	C5—C10—C9—N1	−171.17 (14)
C2—C3—C14—O2	−10.1 (3)	C5—C10—C9—C8	5.4 (2)
C2—C3—C14—O3	170.08 (15)	C11—C7—C6—C5	−72.07 (18)
C3—C4—C10—C9	−28.9 (2)	C12—C7—C6—C5	167.65 (14)
C3—C4—C10—C5	152.04 (14)	C13—C2—C3—C4	173.19 (16)
C3—C4—C17—C18	68.23 (19)	C13—C2—C3—C14	−5.9 (3)
C3—C4—C17—C22	−111.52 (18)	C14—O3—C15—C16	161.23 (17)
C4—C3—C14—O2	170.86 (17)	C14—C3—C4—C10	−152.46 (14)
C4—C3—C14—O3	−9.0 (2)	C14—C3—C4—C17	84.92 (18)
C4—C10—C9—N1	9.8 (2)	C15—O3—C14—O2	3.3 (3)
C4—C10—C9—C8	−173.61 (14)	C15—O3—C14—C3	−176.83 (15)
C4—C10—C5—O1	−10.0 (2)	C17—C4—C10—C9	94.34 (18)
C4—C10—C5—C6	172.64 (14)	C17—C4—C10—C5	−84.68 (17)
C4—C17—C18—C19	−178.60 (15)	C17—C18—C19—Br1	178.21 (12)
C4—C17—C22—C21	179.09 (16)	C17—C18—C19—C20	−0.3 (3)
C10—C4—C17—C18	−53.5 (2)	C18—C17—C22—C21	−0.7 (3)
C10—C4—C17—C22	126.79 (17)	C18—C19—C20—C21	−1.1 (3)
C10—C9—C8—C7	24.2 (2)	C19—C20—C21—C22	1.6 (3)
C9—N1—C2—C3	−14.3 (2)	C20—C21—C22—C17	−0.7 (3)
C9—N1—C2—C13	163.81 (15)	C22—C17—C18—C19	1.1 (2)
C9—C10—C5—O1	170.98 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.86 (2)	2.05 (2)	2.8896 (19)	166 (2)

Symmetry code: (i) x, −y+1, z+1/2.

(III) Ethyl 4-(2-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

Crystal data

C21H24BrNO3	F(000) = 1728
Mr = 418.32	Dx = 1.445 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 14.5012 (18) Å	Cell parameters from 9934 reflections
b = 18.299 (2) Å	θ = 2.2–27.7°
c = 15.1952 (19) Å	µ = 2.16 mm^−1
β = 107.5262 (15)°	T = 100 K
V = 3844.9 (8) Å^3	Prism, translucent yellow
Z = 8	0.34 × 0.16 × 0.08 mm

Data collection

Bruker SMART BREEZE CCD area-detector diffractometer	6859 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tube	Rint = 0.065
ϕ and ω scans	θmax = 27.7°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −18→18
Tmin = 0.866, Tmax = 1.000	k = −23→23
45465 measured reflections	l = −19→19
8935 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.081	w = 1/[σ^2(Fo^2) + (0.0324P)^2 + 2.2792P] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max = 0.001
8935 reflections	Δρmax = 1.46 e Å^−3
485 parameters	Δρmin = −0.47 e Å^−3
0 restraints

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
Br1A	0.39565 (2)	0.30789 (2)	0.25454 (2)	0.01430 (7)
O1A	0.28043 (11)	0.45760 (9)	0.12019 (11)	0.0122 (4)
O2A	0.04711 (13)	0.20468 (10)	0.24987 (15)	0.0262 (5)
O3A	0.20232 (12)	0.23877 (9)	0.29061 (12)	0.0148 (4)
N1A	−0.01715 (15)	0.42917 (11)	0.17929 (14)	0.0110 (4)
C2A	0.00080 (17)	0.35786 (13)	0.21030 (16)	0.0117 (5)
C3A	0.08940 (16)	0.32797 (13)	0.22333 (16)	0.0100 (5)
C4A	0.17328 (16)	0.37166 (13)	0.20857 (16)	0.0096 (5)
H4A	0.2055	0.3416	0.1714	0.012*
C10A	0.13654 (16)	0.44210 (13)	0.15653 (16)	0.0094 (5)
C9A	0.04751 (17)	0.46991 (13)	0.15143 (16)	0.0099 (5)
C8A	0.01507 (17)	0.54547 (13)	0.11637 (17)	0.0113 (5)
H8AA	−0.0255	0.5659	0.1524	0.014*
H8AB	−0.0254	0.5422	0.0511	0.014*
C7A	0.10023 (17)	0.59772 (13)	0.12310 (17)	0.0114 (5)
C6A	0.17181 (17)	0.55891 (13)	0.08212 (16)	0.0111 (5)
H6AA	0.1422	0.5549	0.0145	0.013*
H6AB	0.2305	0.5895	0.0934	0.013*
C5A	0.20149 (17)	0.48342 (13)	0.12076 (16)	0.0104 (5)
C11A	0.15088 (18)	0.61815 (14)	0.22402 (17)	0.0160 (5)
H11A	0.1035	0.6387	0.2515	0.024*
H11B	0.2014	0.6544	0.2267	0.024*
H11C	0.1801	0.5744	0.2584	0.024*
C12A	0.06180 (18)	0.66689 (14)	0.06839 (18)	0.0168 (6)
H12A	0.0299	0.6541	0.0037	0.025*
H12B	0.1156	0.7003	0.0720	0.025*
H12C	0.0152	0.6907	0.0942	0.025*
C13A	−0.08558 (18)	0.32166 (14)	0.22696 (19)	0.0171 (6)
H13A	−0.1282	0.3590	0.2398	0.026*
H13B	−0.0639	0.2885	0.2799	0.026*
H13C	−0.1209	0.2938	0.1720	0.026*
C14A	0.10710 (17)	0.25154 (14)	0.25480 (17)	0.0133 (5)
C15A	0.23069 (18)	0.16497 (13)	0.32241 (18)	0.0155 (5)
H15A	0.2953	0.1544	0.3160	0.019*
H15B	0.1841	0.1298	0.2833	0.019*
C16A	0.2338 (2)	0.15485 (15)	0.42185 (18)	0.0205 (6)
H16A	0.1693	0.1633	0.4279	0.031*
H16B	0.2796	0.1898	0.4607	0.031*
H16C	0.2547	0.1049	0.4415	0.031*
C17A	0.24881 (17)	0.39335 (13)	0.29969 (16)	0.0099 (5)
C18A	0.34612 (17)	0.37375 (14)	0.32615 (16)	0.0129 (5)
C19A	0.41183 (18)	0.40080 (14)	0.40664 (17)	0.0155 (5)
H19A	0.4777	0.3862	0.4236	0.019*
C20A	0.38027 (19)	0.44895 (15)	0.46146 (17)	0.0181 (6)
H20A	0.4250	0.4683	0.5156	0.022*
C21A	0.28354 (19)	0.46919 (14)	0.43783 (17)	0.0167 (6)
H21A	0.2619	0.5022	0.4757	0.020*
C22A	0.21920 (18)	0.44091 (13)	0.35874 (17)	0.0142 (5)
H22A	0.1529	0.4540	0.3437	0.017*
Br1B	0.08223 (2)	0.00989 (2)	0.13780 (2)	0.01685 (7)
O1B	0.21907 (11)	−0.03473 (9)	0.35984 (12)	0.0139 (4)
O2B	0.41353 (12)	0.16979 (9)	0.13408 (12)	0.0158 (4)
O3B	0.26479 (11)	0.12336 (9)	0.11364 (11)	0.0130 (4)
N1B	0.51999 (15)	−0.01424 (12)	0.30637 (14)	0.0116 (4)
C2B	0.48978 (17)	0.04219 (13)	0.24329 (16)	0.0104 (5)
C3B	0.39436 (17)	0.05815 (13)	0.21022 (16)	0.0094 (5)
C4B	0.31871 (16)	0.01002 (13)	0.23282 (16)	0.0090 (5)
H4B	0.2658	0.0421	0.2405	0.011*
C10B	0.36467 (16)	−0.02951 (13)	0.32331 (16)	0.0090 (5)
C9B	0.46114 (17)	−0.04440 (13)	0.35161 (16)	0.0096 (5)
C8B	0.50953 (17)	−0.09235 (13)	0.43263 (16)	0.0114 (5)
H8BA	0.5407	−0.0612	0.4867	0.014*
H8BB	0.5607	−0.1214	0.4182	0.014*
C7B	0.43782 (17)	−0.14455 (13)	0.45732 (16)	0.0117 (5)
C6B	0.35073 (17)	−0.09960 (13)	0.46295 (16)	0.0109 (5)
H6BA	0.3012	−0.1333	0.4724	0.013*
H6BB	0.3715	−0.0673	0.5176	0.013*
C5B	0.30492 (17)	−0.05315 (13)	0.37865 (16)	0.0110 (5)
C12B	0.48777 (19)	−0.17893 (15)	0.55204 (18)	0.0182 (6)
H12D	0.5411	−0.2101	0.5476	0.027*
H12E	0.4409	−0.2084	0.5715	0.027*
H12F	0.5131	−0.1402	0.5974	0.027*
C11B	0.40569 (19)	−0.20507 (14)	0.38480 (18)	0.0165 (6)
H11D	0.3742	−0.1832	0.3243	0.025*
H11E	0.3601	−0.2376	0.4017	0.025*
H11F	0.4623	−0.2332	0.3820	0.025*
C13B	0.57203 (17)	0.07931 (14)	0.22026 (18)	0.0155 (5)
H13D	0.5937	0.1214	0.2611	0.023*
H13E	0.5504	0.0959	0.1559	0.023*
H13F	0.6257	0.0448	0.2287	0.023*
C14B	0.36205 (17)	0.12248 (13)	0.15021 (16)	0.0112 (5)
C15B	0.22766 (18)	0.18339 (14)	0.05020 (18)	0.0164 (6)
H15C	0.2565	0.1822	−0.0011	0.020*
H15D	0.2440	0.2307	0.0827	0.020*
C16B	0.11964 (19)	0.17455 (16)	0.0134 (2)	0.0240 (6)
H16D	0.0924	0.2141	−0.0301	0.036*
H16E	0.0918	0.1763	0.0647	0.036*
H16F	0.1043	0.1274	−0.0183	0.036*
C17B	0.27431 (17)	−0.04582 (13)	0.15652 (16)	0.0107 (5)
C18B	0.17577 (17)	−0.05192 (14)	0.10999 (17)	0.0128 (5)
C19B	0.13963 (19)	−0.10322 (15)	0.04075 (18)	0.0196 (6)
H19B	0.0721	−0.1060	0.0103	0.023*
C20B	0.2024 (2)	−0.15016 (15)	0.01647 (19)	0.0233 (6)
H20B	0.1784	−0.1847	−0.0317	0.028*
C21B	0.3010 (2)	−0.14683 (15)	0.06268 (18)	0.0200 (6)
H21B	0.3444	−0.1797	0.0471	0.024*
C22B	0.33544 (18)	−0.09546 (13)	0.13130 (17)	0.0136 (5)
H22B	0.4029	−0.0937	0.1625	0.016*
H1B	0.576 (2)	−0.0236 (14)	0.3237 (18)	0.011 (7)*
H1A	−0.0714 (19)	0.4467 (14)	0.1738 (17)	0.006 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1A	0.01041 (12)	0.01685 (13)	0.01641 (13)	0.00394 (10)	0.00521 (10)	0.00192 (10)
O1A	0.0075 (8)	0.0155 (9)	0.0138 (9)	−0.0009 (7)	0.0033 (7)	−0.0011 (7)
O2A	0.0129 (10)	0.0128 (10)	0.0512 (14)	−0.0007 (8)	0.0070 (9)	0.0065 (9)
O3A	0.0091 (8)	0.0111 (9)	0.0223 (10)	0.0021 (7)	0.0019 (7)	0.0042 (7)
N1A	0.0059 (10)	0.0129 (11)	0.0156 (11)	0.0031 (9)	0.0054 (8)	0.0037 (9)
C2A	0.0118 (12)	0.0130 (13)	0.0102 (12)	−0.0011 (10)	0.0031 (10)	0.0002 (10)
C3A	0.0080 (11)	0.0102 (12)	0.0113 (12)	−0.0009 (9)	0.0021 (9)	−0.0012 (9)
C4A	0.0079 (11)	0.0107 (12)	0.0100 (11)	0.0023 (9)	0.0024 (9)	−0.0006 (10)
C10A	0.0079 (11)	0.0115 (12)	0.0080 (11)	0.0007 (9)	0.0012 (9)	−0.0011 (9)
C9A	0.0096 (11)	0.0125 (12)	0.0068 (11)	0.0006 (10)	0.0013 (9)	−0.0010 (9)
C8A	0.0088 (12)	0.0124 (13)	0.0134 (12)	0.0021 (10)	0.0044 (10)	0.0008 (10)
C7A	0.0093 (12)	0.0105 (12)	0.0147 (13)	−0.0007 (10)	0.0041 (10)	0.0012 (10)
C6A	0.0125 (12)	0.0100 (12)	0.0118 (12)	−0.0008 (10)	0.0049 (10)	0.0004 (10)
C5A	0.0083 (11)	0.0148 (13)	0.0067 (11)	−0.0008 (10)	0.0004 (9)	−0.0027 (10)
C11A	0.0143 (13)	0.0136 (13)	0.0193 (14)	0.0028 (11)	0.0040 (11)	−0.0018 (11)
C12A	0.0154 (13)	0.0129 (13)	0.0230 (14)	0.0012 (11)	0.0069 (11)	0.0046 (11)
C13A	0.0121 (13)	0.0152 (14)	0.0261 (15)	0.0030 (10)	0.0092 (11)	0.0059 (11)
C14A	0.0087 (12)	0.0153 (13)	0.0173 (13)	0.0011 (10)	0.0063 (10)	−0.0013 (11)
C15A	0.0124 (12)	0.0077 (12)	0.0257 (15)	0.0040 (10)	0.0044 (11)	0.0003 (11)
C16A	0.0233 (15)	0.0165 (14)	0.0209 (15)	0.0048 (12)	0.0052 (12)	0.0017 (11)
C17A	0.0123 (12)	0.0083 (12)	0.0094 (12)	−0.0016 (10)	0.0036 (9)	0.0037 (9)
C18A	0.0135 (12)	0.0143 (13)	0.0123 (12)	−0.0007 (10)	0.0062 (10)	0.0023 (10)
C19A	0.0103 (12)	0.0217 (14)	0.0133 (13)	−0.0039 (11)	0.0017 (10)	0.0050 (11)
C20A	0.0200 (14)	0.0240 (15)	0.0092 (12)	−0.0067 (12)	0.0028 (11)	0.0015 (11)
C21A	0.0222 (14)	0.0181 (14)	0.0111 (13)	−0.0026 (11)	0.0069 (11)	−0.0020 (11)
C22A	0.0152 (13)	0.0125 (13)	0.0145 (13)	−0.0009 (10)	0.0038 (10)	0.0037 (10)
Br1B	0.00708 (12)	0.02538 (15)	0.01687 (13)	0.00182 (10)	0.00179 (9)	0.00505 (11)
O1B	0.0066 (8)	0.0185 (10)	0.0172 (9)	−0.0003 (7)	0.0046 (7)	0.0005 (8)
O2B	0.0155 (9)	0.0108 (9)	0.0220 (10)	−0.0021 (7)	0.0071 (8)	0.0020 (7)
O3B	0.0105 (8)	0.0124 (9)	0.0145 (9)	0.0021 (7)	0.0014 (7)	0.0051 (7)
N1B	0.0045 (10)	0.0172 (12)	0.0133 (11)	0.0020 (9)	0.0031 (8)	0.0025 (9)
C2B	0.0103 (12)	0.0105 (12)	0.0115 (12)	0.0000 (10)	0.0049 (10)	0.0003 (10)
C3B	0.0104 (12)	0.0095 (12)	0.0074 (11)	−0.0011 (9)	0.0010 (9)	−0.0026 (9)
C4B	0.0072 (11)	0.0101 (12)	0.0092 (11)	0.0012 (9)	0.0018 (9)	0.0009 (9)
C10B	0.0077 (11)	0.0101 (12)	0.0092 (11)	0.0006 (9)	0.0023 (9)	−0.0001 (9)
C9B	0.0116 (12)	0.0084 (12)	0.0095 (12)	−0.0002 (10)	0.0040 (9)	−0.0016 (9)
C8B	0.0100 (12)	0.0125 (13)	0.0117 (12)	0.0011 (10)	0.0034 (10)	0.0030 (10)
C7B	0.0124 (12)	0.0122 (13)	0.0106 (12)	0.0005 (10)	0.0036 (10)	0.0027 (10)
C6B	0.0109 (12)	0.0125 (13)	0.0101 (12)	−0.0016 (10)	0.0043 (10)	−0.0009 (10)
C5B	0.0102 (12)	0.0117 (13)	0.0104 (12)	−0.0034 (10)	0.0022 (9)	−0.0062 (10)
C12B	0.0170 (13)	0.0199 (15)	0.0177 (14)	−0.0014 (11)	0.0052 (11)	0.0069 (11)
C11B	0.0175 (13)	0.0140 (14)	0.0183 (14)	0.0002 (11)	0.0057 (11)	0.0022 (11)
C13B	0.0111 (12)	0.0193 (14)	0.0177 (13)	−0.0011 (11)	0.0070 (10)	0.0042 (11)
C14B	0.0109 (12)	0.0128 (13)	0.0105 (12)	0.0011 (10)	0.0041 (9)	−0.0031 (10)
C15B	0.0195 (14)	0.0107 (13)	0.0177 (13)	0.0029 (11)	0.0035 (11)	0.0055 (11)
C16B	0.0187 (14)	0.0223 (15)	0.0276 (16)	0.0073 (12)	0.0016 (12)	0.0115 (12)
C17B	0.0122 (12)	0.0105 (12)	0.0095 (12)	−0.0029 (10)	0.0033 (10)	0.0031 (10)
C18B	0.0104 (12)	0.0137 (13)	0.0145 (13)	0.0002 (10)	0.0041 (10)	0.0044 (10)
C19B	0.0163 (14)	0.0196 (15)	0.0190 (14)	−0.0071 (11)	−0.0005 (11)	0.0015 (11)
C20B	0.0330 (16)	0.0161 (14)	0.0178 (14)	−0.0082 (12)	0.0032 (12)	−0.0046 (11)
C21B	0.0263 (15)	0.0146 (14)	0.0191 (14)	0.0030 (12)	0.0069 (12)	−0.0027 (11)
C22B	0.0133 (12)	0.0121 (13)	0.0137 (13)	0.0017 (10)	0.0013 (10)	0.0026 (10)

Geometric parameters (Å, º)

Br1A—C18A	1.904 (2)	Br1B—C18B	1.909 (2)
O1A—C5A	1.241 (3)	O1B—C5B	1.237 (3)
O2A—C14A	1.208 (3)	O2B—C14B	1.215 (3)
O3A—C14A	1.343 (3)	O3B—C14B	1.351 (3)
O3A—C15A	1.451 (3)	O3B—C15B	1.454 (3)
N1A—C2A	1.385 (3)	N1B—C2B	1.387 (3)
N1A—C9A	1.361 (3)	N1B—C9B	1.363 (3)
N1A—H1A	0.83 (3)	N1B—H1B	0.80 (3)
C2A—C3A	1.355 (3)	C2B—C3B	1.354 (3)
C2A—C13A	1.504 (3)	C2B—C13B	1.503 (3)
C3A—C4A	1.528 (3)	C3B—C4B	1.524 (3)
C3A—C14A	1.475 (3)	C3B—C14B	1.476 (3)
C4A—H4A	1.0000	C4B—H4B	1.0000
C4A—C10A	1.522 (3)	C4B—C10B	1.519 (3)
C4A—C17A	1.537 (3)	C4B—C17B	1.534 (3)
C10A—C9A	1.368 (3)	C10B—C9B	1.362 (3)
C10A—C5A	1.436 (3)	C10B—C5B	1.443 (3)
C9A—C8A	1.505 (3)	C9B—C8B	1.503 (3)
C8A—H8AA	0.9900	C8B—H8BA	0.9900
C8A—H8AB	0.9900	C8B—H8BB	0.9900
C8A—C7A	1.541 (3)	C8B—C7B	1.539 (3)
C7A—C6A	1.536 (3)	C7B—C6B	1.531 (3)
C7A—C11A	1.534 (3)	C7B—C12B	1.538 (3)
C7A—C12A	1.525 (3)	C7B—C11B	1.532 (3)
C6A—H6AA	0.9900	C6B—H6BA	0.9900
C6A—H6AB	0.9900	C6B—H6BB	0.9900
C6A—C5A	1.512 (3)	C6B—C5B	1.514 (3)
C11A—H11A	0.9800	C12B—H12D	0.9800
C11A—H11B	0.9800	C12B—H12E	0.9800
C11A—H11C	0.9800	C12B—H12F	0.9800
C12A—H12A	0.9800	C11B—H11D	0.9800
C12A—H12B	0.9800	C11B—H11E	0.9800
C12A—H12C	0.9800	C11B—H11F	0.9800
C13A—H13A	0.9800	C13B—H13D	0.9800
C13A—H13B	0.9800	C13B—H13E	0.9800
C13A—H13C	0.9800	C13B—H13F	0.9800
C15A—H15A	0.9900	C15B—H15C	0.9900
C15A—H15B	0.9900	C15B—H15D	0.9900
C15A—C16A	1.509 (4)	C15B—C16B	1.505 (4)
C16A—H16A	0.9800	C16B—H16D	0.9800
C16A—H16B	0.9800	C16B—H16E	0.9800
C16A—H16C	0.9800	C16B—H16F	0.9800
C17A—C18A	1.393 (3)	C17B—C18B	1.395 (3)
C17A—C22A	1.407 (3)	C17B—C22B	1.401 (3)
C18A—C19A	1.395 (3)	C18B—C19B	1.390 (4)
C19A—H19A	0.9500	C19B—H19B	0.9500
C19A—C20A	1.382 (4)	C19B—C20B	1.381 (4)
C20A—H20A	0.9500	C20B—H20B	0.9500
C20A—C21A	1.389 (4)	C20B—C21B	1.391 (4)
C21A—H21A	0.9500	C21B—H21B	0.9500
C21A—C22A	1.381 (3)	C21B—C22B	1.381 (4)
C22A—H22A	0.9500	C22B—H22B	0.9500
C14A—O3A—C15A	116.77 (19)	C14B—O3B—C15B	114.45 (19)
C2A—N1A—H1A	118.2 (17)	C2B—N1B—H1B	117.8 (19)
C9A—N1A—C2A	123.0 (2)	C9B—N1B—C2B	122.3 (2)
C9A—N1A—H1A	118.6 (17)	C9B—N1B—H1B	118.8 (19)
N1A—C2A—C13A	113.0 (2)	N1B—C2B—C13B	112.9 (2)
C3A—C2A—N1A	120.2 (2)	C3B—C2B—N1B	119.5 (2)
C3A—C2A—C13A	126.8 (2)	C3B—C2B—C13B	127.6 (2)
C2A—C3A—C4A	121.9 (2)	C2B—C3B—C4B	121.1 (2)
C2A—C3A—C14A	119.7 (2)	C2B—C3B—C14B	120.0 (2)
C14A—C3A—C4A	118.4 (2)	C14B—C3B—C4B	118.9 (2)
C3A—C4A—H4A	108.9	C3B—C4B—H4B	108.5
C3A—C4A—C17A	112.70 (19)	C3B—C4B—C17B	112.42 (19)
C10A—C4A—C3A	110.48 (19)	C10B—C4B—C3B	109.25 (19)
C10A—C4A—H4A	108.9	C10B—C4B—H4B	108.5
C10A—C4A—C17A	107.00 (19)	C10B—C4B—C17B	109.69 (19)
C17A—C4A—H4A	108.9	C17B—C4B—H4B	108.5
C9A—C10A—C4A	121.4 (2)	C9B—C10B—C4B	120.7 (2)
C9A—C10A—C5A	119.9 (2)	C9B—C10B—C5B	119.7 (2)
C5A—C10A—C4A	118.4 (2)	C5B—C10B—C4B	119.6 (2)
N1A—C9A—C10A	120.4 (2)	N1B—C9B—C8B	116.2 (2)
N1A—C9A—C8A	116.2 (2)	C10B—C9B—N1B	120.0 (2)
C10A—C9A—C8A	123.4 (2)	C10B—C9B—C8B	123.9 (2)
C9A—C8A—H8AA	109.0	C9B—C8B—H8BA	109.1
C9A—C8A—H8AB	109.0	C9B—C8B—H8BB	109.1
C9A—C8A—C7A	112.81 (19)	C9B—C8B—C7B	112.27 (19)
H8AA—C8A—H8AB	107.8	H8BA—C8B—H8BB	107.9
C7A—C8A—H8AA	109.0	C7B—C8B—H8BA	109.1
C7A—C8A—H8AB	109.0	C7B—C8B—H8BB	109.1
C6A—C7A—C8A	108.19 (19)	C6B—C7B—C8B	108.03 (19)
C11A—C7A—C8A	110.5 (2)	C6B—C7B—C12B	109.36 (19)
C11A—C7A—C6A	109.8 (2)	C6B—C7B—C11B	110.6 (2)
C12A—C7A—C8A	108.96 (19)	C12B—C7B—C8B	108.64 (19)
C12A—C7A—C6A	110.1 (2)	C11B—C7B—C8B	110.8 (2)
C12A—C7A—C11A	109.2 (2)	C11B—C7B—C12B	109.4 (2)
C7A—C6A—H6AA	108.7	C7B—C6B—H6BA	108.7
C7A—C6A—H6AB	108.7	C7B—C6B—H6BB	108.7
H6AA—C6A—H6AB	107.6	H6BA—C6B—H6BB	107.6
C5A—C6A—C7A	114.4 (2)	C5B—C6B—C7B	114.42 (19)
C5A—C6A—H6AA	108.7	C5B—C6B—H6BA	108.7
C5A—C6A—H6AB	108.7	C5B—C6B—H6BB	108.7
O1A—C5A—C10A	120.9 (2)	O1B—C5B—C10B	121.5 (2)
O1A—C5A—C6A	120.0 (2)	O1B—C5B—C6B	120.2 (2)
C10A—C5A—C6A	119.1 (2)	C10B—C5B—C6B	118.3 (2)
C7A—C11A—H11A	109.5	C7B—C12B—H12D	109.5
C7A—C11A—H11B	109.5	C7B—C12B—H12E	109.5
C7A—C11A—H11C	109.5	C7B—C12B—H12F	109.5
H11A—C11A—H11B	109.5	H12D—C12B—H12E	109.5
H11A—C11A—H11C	109.5	H12D—C12B—H12F	109.5
H11B—C11A—H11C	109.5	H12E—C12B—H12F	109.5
C7A—C12A—H12A	109.5	C7B—C11B—H11D	109.5
C7A—C12A—H12B	109.5	C7B—C11B—H11E	109.5
C7A—C12A—H12C	109.5	C7B—C11B—H11F	109.5
H12A—C12A—H12B	109.5	H11D—C11B—H11E	109.5
H12A—C12A—H12C	109.5	H11D—C11B—H11F	109.5
H12B—C12A—H12C	109.5	H11E—C11B—H11F	109.5
C2A—C13A—H13A	109.5	C2B—C13B—H13D	109.5
C2A—C13A—H13B	109.5	C2B—C13B—H13E	109.5
C2A—C13A—H13C	109.5	C2B—C13B—H13F	109.5
H13A—C13A—H13B	109.5	H13D—C13B—H13E	109.5
H13A—C13A—H13C	109.5	H13D—C13B—H13F	109.5
H13B—C13A—H13C	109.5	H13E—C13B—H13F	109.5
O2A—C14A—O3A	122.3 (2)	O2B—C14B—O3B	122.5 (2)
O2A—C14A—C3A	127.0 (2)	O2B—C14B—C3B	126.3 (2)
O3A—C14A—C3A	110.7 (2)	O3B—C14B—C3B	111.2 (2)
O3A—C15A—H15A	109.3	O3B—C15B—H15C	110.2
O3A—C15A—H15B	109.3	O3B—C15B—H15D	110.2
O3A—C15A—C16A	111.6 (2)	O3B—C15B—C16B	107.5 (2)
H15A—C15A—H15B	108.0	H15C—C15B—H15D	108.5
C16A—C15A—H15A	109.3	C16B—C15B—H15C	110.2
C16A—C15A—H15B	109.3	C16B—C15B—H15D	110.2
C15A—C16A—H16A	109.5	C15B—C16B—H16D	109.5
C15A—C16A—H16B	109.5	C15B—C16B—H16E	109.5
C15A—C16A—H16C	109.5	C15B—C16B—H16F	109.5
H16A—C16A—H16B	109.5	H16D—C16B—H16E	109.5
H16A—C16A—H16C	109.5	H16D—C16B—H16F	109.5
H16B—C16A—H16C	109.5	H16E—C16B—H16F	109.5
C18A—C17A—C4A	125.4 (2)	C18B—C17B—C4B	124.7 (2)
C18A—C17A—C22A	116.9 (2)	C18B—C17B—C22B	116.4 (2)
C22A—C17A—C4A	117.6 (2)	C22B—C17B—C4B	118.9 (2)
C17A—C18A—Br1A	121.46 (18)	C17B—C18B—Br1B	121.88 (19)
C17A—C18A—C19A	121.8 (2)	C19B—C18B—Br1B	115.91 (19)
C19A—C18A—Br1A	116.74 (18)	C19B—C18B—C17B	122.2 (2)
C18A—C19A—H19A	120.3	C18B—C19B—H19B	120.2
C20A—C19A—C18A	119.5 (2)	C20B—C19B—C18B	119.6 (2)
C20A—C19A—H19A	120.3	C20B—C19B—H19B	120.2
C19A—C20A—H20A	119.8	C19B—C20B—H20B	120.1
C19A—C20A—C21A	120.4 (2)	C19B—C20B—C21B	119.9 (2)
C21A—C20A—H20A	119.8	C21B—C20B—H20B	120.1
C20A—C21A—H21A	120.3	C20B—C21B—H21B	120.2
C22A—C21A—C20A	119.3 (2)	C22B—C21B—C20B	119.6 (2)
C22A—C21A—H21A	120.3	C22B—C21B—H21B	120.2
C17A—C22A—H22A	119.0	C17B—C22B—H22B	118.9
C21A—C22A—C17A	122.1 (2)	C21B—C22B—C17B	122.2 (2)
C21A—C22A—H22A	119.0	C21B—C22B—H22B	118.9
Br1A—C18A—C19A—C20A	179.88 (19)	Br1B—C18B—C19B—C20B	−179.9 (2)
N1A—C2A—C3A—C4A	2.6 (4)	N1B—C2B—C3B—C4B	−6.8 (3)
N1A—C2A—C3A—C14A	−178.9 (2)	N1B—C2B—C3B—C14B	174.0 (2)
N1A—C9A—C8A—C7A	157.0 (2)	N1B—C9B—C8B—C7B	−159.6 (2)
C2A—N1A—C9A—C10A	−2.6 (4)	C2B—N1B—C9B—C10B	12.6 (4)
C2A—N1A—C9A—C8A	177.8 (2)	C2B—N1B—C9B—C8B	−166.5 (2)
C2A—C3A—C4A—C10A	−14.1 (3)	C2B—C3B—C4B—C10B	25.5 (3)
C2A—C3A—C4A—C17A	105.6 (3)	C2B—C3B—C4B—C17B	−96.5 (3)
C2A—C3A—C14A—O2A	19.8 (4)	C2B—C3B—C14B—O2B	−9.1 (4)
C2A—C3A—C14A—O3A	−160.9 (2)	C2B—C3B—C14B—O3B	171.1 (2)
C3A—C4A—C10A—C9A	18.3 (3)	C3B—C4B—C10B—C9B	−27.2 (3)
C3A—C4A—C10A—C5A	−168.2 (2)	C3B—C4B—C10B—C5B	154.4 (2)
C3A—C4A—C17A—C18A	120.5 (2)	C3B—C4B—C17B—C18B	−122.8 (2)
C3A—C4A—C17A—C22A	−64.0 (3)	C3B—C4B—C17B—C22B	58.0 (3)
C4A—C3A—C14A—O2A	−161.7 (2)	C4B—C3B—C14B—O2B	171.8 (2)
C4A—C3A—C14A—O3A	17.7 (3)	C4B—C3B—C14B—O3B	−8.1 (3)
C4A—C10A—C9A—N1A	−11.2 (3)	C4B—C10B—C9B—N1B	10.1 (3)
C4A—C10A—C9A—C8A	168.4 (2)	C4B—C10B—C9B—C8B	−170.9 (2)
C4A—C10A—C5A—O1A	10.3 (3)	C4B—C10B—C5B—O1B	−8.5 (3)
C4A—C10A—C5A—C6A	−170.6 (2)	C4B—C10B—C5B—C6B	173.4 (2)
C4A—C17A—C18A—Br1A	−6.1 (3)	C4B—C17B—C18B—Br1B	−0.6 (3)
C4A—C17A—C18A—C19A	174.5 (2)	C4B—C17B—C18B—C19B	179.4 (2)
C4A—C17A—C22A—C21A	−173.7 (2)	C4B—C17B—C22B—C21B	−179.4 (2)
C10A—C4A—C17A—C18A	−117.9 (2)	C10B—C4B—C17B—C18B	115.4 (2)
C10A—C4A—C17A—C22A	57.6 (3)	C10B—C4B—C17B—C22B	−63.7 (3)
C10A—C9A—C8A—C7A	−22.6 (3)	C10B—C9B—C8B—C7B	21.4 (3)
C9A—N1A—C2A—C3A	7.0 (4)	C9B—N1B—C2B—C3B	−14.3 (4)
C9A—N1A—C2A—C13A	−173.5 (2)	C9B—N1B—C2B—C13B	165.5 (2)
C9A—C10A—C5A—O1A	−176.1 (2)	C9B—C10B—C5B—O1B	173.1 (2)
C9A—C10A—C5A—C6A	3.0 (3)	C9B—C10B—C5B—C6B	−5.0 (3)
C9A—C8A—C7A—C6A	48.6 (3)	C9B—C8B—C7B—C6B	−49.2 (3)
C9A—C8A—C7A—C11A	−71.7 (3)	C9B—C8B—C7B—C12B	−167.8 (2)
C9A—C8A—C7A—C12A	168.2 (2)	C9B—C8B—C7B—C11B	72.0 (3)
C8A—C7A—C6A—C5A	−51.3 (3)	C8B—C7B—C6B—C5B	52.6 (3)
C7A—C6A—C5A—O1A	−154.2 (2)	C7B—C6B—C5B—O1B	155.3 (2)
C7A—C6A—C5A—C10A	26.7 (3)	C7B—C6B—C5B—C10B	−26.5 (3)
C5A—C10A—C9A—N1A	175.5 (2)	C5B—C10B—C9B—N1B	−171.5 (2)
C5A—C10A—C9A—C8A	−4.9 (4)	C5B—C10B—C9B—C8B	7.5 (4)
C11A—C7A—C6A—C5A	69.5 (3)	C12B—C7B—C6B—C5B	170.7 (2)
C12A—C7A—C6A—C5A	−170.2 (2)	C11B—C7B—C6B—C5B	−68.8 (3)
C13A—C2A—C3A—C4A	−176.8 (2)	C13B—C2B—C3B—C4B	173.5 (2)
C13A—C2A—C3A—C14A	1.7 (4)	C13B—C2B—C3B—C14B	−5.7 (4)
C14A—O3A—C15A—C16A	−88.5 (3)	C14B—O3B—C15B—C16B	177.9 (2)
C14A—C3A—C4A—C10A	167.4 (2)	C14B—C3B—C4B—C10B	−155.3 (2)
C14A—C3A—C4A—C17A	−73.0 (3)	C14B—C3B—C4B—C17B	82.7 (3)
C15A—O3A—C14A—O2A	0.9 (3)	C15B—O3B—C14B—O2B	2.9 (3)
C15A—O3A—C14A—C3A	−178.5 (2)	C15B—O3B—C14B—C3B	−177.29 (19)
C17A—C4A—C10A—C9A	−104.7 (2)	C17B—C4B—C10B—C9B	96.4 (3)
C17A—C4A—C10A—C5A	68.8 (3)	C17B—C4B—C10B—C5B	−82.0 (3)
C17A—C18A—C19A—C20A	−0.7 (4)	C17B—C18B—C19B—C20B	0.1 (4)
C18A—C17A—C22A—C21A	2.2 (4)	C18B—C17B—C22B—C21B	1.4 (4)
C18A—C19A—C20A—C21A	1.3 (4)	C18B—C19B—C20B—C21B	1.3 (4)
C19A—C20A—C21A—C22A	−0.2 (4)	C19B—C20B—C21B—C22B	−1.3 (4)
C20A—C21A—C22A—C17A	−1.6 (4)	C20B—C21B—C22B—C17B	−0.1 (4)
C22A—C17A—C18A—Br1A	178.40 (17)	C22B—C17B—C18B—Br1B	178.55 (17)
C22A—C17A—C18A—C19A	−1.0 (3)	C22B—C17B—C18B—C19B	−1.4 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1B—H1B···O1A^i	0.80 (3)	2.02 (3)	2.818 (3)	174 (3)
N1A—H1A···O1B^ii	0.83 (3)	2.07 (3)	2.884 (3)	165 (2)

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