cis-(6RS,13RS)-3,3,10,10-Tetra­methyl-6,13-diphenyl-1,8-dioxa-4,11-diaza­cyclo­tetra­decane-2,5,9,12-tetra­one and two of its precursors

The title macrocycle, C₂₆H₃₀N₂O₆, (VI), was obtained by `direct amide cyclization' from the linear precursor 3-hydr­oxy-N-[1-methyl-1-(N-methyl-N-phenyl­carbamoyl)ethyl]-2-phenylpropanamide, the N-methyl­anilide of rac-2-methyl-2-[(3-hydroxy-2-phenyl­propanoyl)­amino]­propanoic acid, C₁₃H₁₇NO₄, (IV). The reaction proceeds via the inter­mediate rac-2-(2-hydroxy-1-phenyl­ethyl)-4,4-dimethyl-1,3-oxazol-5(4H)-one, C₁₃H₁₅NO₃, (V), which was synthesized independently and whose structure was also established. Unlike all previously described analogues, the title macrocycle has the cis-diphenyl configuration. The 14-membered ring has a distorted rect­angular diamond-based [3434] configuration and inter­molecular N—H...O hydrogen bonds link the mol­ecules into a three-dimensional framework. The propanoic acid precursor forms a complex series of inter­molecular hydrogen bonds, each of which involves pairwise association of mol­ecules and which together result in the formation of extended two-dimensional sheets. The oxazole inter­mediate forms centrosymmetric hydrogen-bonded dimers in the solid state.

S1. Comment

Cyclic depsipeptides are renowned for their biological activity, mainly as antibiotics, due to their ability to allow cations selectively to pass through the cell membrane (Ballard et al., 2002). A useful method for the synthesis of some analogues, which contain α,α-disubstituted α-amino acids, from linear precursors is the so-called 'direct amide cyclization' (Obrecht & Heimgartner, 1984, 1987). The starting materials for the cyclization are hydroxy oligoamides, such as compound (III) (see scheme), which possess one or several α,α-disubstituted α-amino acids, and which are conveniently accessible from the corresponding hydroxy acids [e.g. (I)] and 2H-azirin-3-amines [e.g. (II)] via the 'azirine/oxazolone method' (Wipf & Heimgartner, 1990; Heimgartner, 1991). Treatment of the hydroxy oligoamides with HCl gas in toluene at 373 K yields 9–24-membered cyclic depsipeptides in good yields via the formation of 1,3-oxazol-5(4H)-ones as intermediates (Obrecht & Heimgartner, 1987; Koch et al., 2000, 2001; Köttgen et al., 2006).

Our recent studies have shown that, when β-hydroxy acid amides analogous to compound (III) are used, 14-membered cyclodepsipeptides were formed instead of the expected 7-membered monomers. Again, the corresponding 1,3-oxazol-5(4H)-ones were shown to be intermediates (Iliev et al., 2003, 2006). Furthermore, in comparable experiments with racemic starting materials, the cyclodimers obtained were trans-configured and no cis isomers could be detected. Other cyclization methods that started from hydroxy acids [e.g. (IV)], which were derived from α,α-disubstituted analogues of compound (III), led to the same result (Iliev et al., 2003, 2006). Further studies showed that, in order for the reactions to have a practical value, it is a requirement that the β-hydroxy acid is α,α-disubstituted. When that was not the case, water elimination occurred and no cyclic products could be isolated, although the intermediate oxazolone, like compound (V), could be detected by means of IR spectroscopy and its presence proven chemically (Iliev et al., 2006). Only in a single case, when the starting β-hydroxy acid amide, (III), contained the α-phenyl-β-hydroxy acid moiety, could crystals of a 14-membered cyclodepsipeptide be isolated, namely the title compound, (VI). The hydroxy acid, (IV), was obtained after selective hydrolysis of (III) by treatment with 3 N HCl in tetrahydrofuran. The intermediate oxazolone, (V), could be isolated after treatment of (IV) with N,N'-dicyclohexylcarbodiimide in ethyl acetate. As part of the full characterization of the reaction products shown in the scheme, and in order to confirm the stereochemistry of compound (VI), the crystal structures of compounds (IV), (V) and (VI) were determined and are described here.

Compound (IV) crystallizes in a centrosymmetric space group and is therefore a racemate: the selected reference moleule has the (R) configuration at C5 (Fig. 1). The geometric parameters involving the non-H atoms are within normal ranges. The molecule possesses three hydrogen-bond donors, which are all involved in intermolecular interactions (Table 1). These interactions combine to link the molecules into extended two-dimensional sheets which lie parallel to the (001) plane (Fig. 2). Within the sheets, several hydrogen-bonding motifs (Bernstein et al., 1995) can be discerned. The carboxylic acid H atom interacts with the carbonyl O atom of the carboxylic acid group of a neighbouring molecule, which, in turn, acts as a donor for an identical interaction back to the original molecule. These interactions result in pairs of molecules being linked into dimers across crystallographic centres of inversion. This pattern can be described by a graph-set motif of R²₂(8), which is one of the classic motifs found in the crystal structures of carboxylic acids. The H atom of the hydroxy group forms an intermolecular hydrogen bond with the amide O atom of a different neighbouring molecule. Again, this interaction links pairs of molecules into centrosymmetric dimers and the pattern can be described by a graph-set motif of R²₂(12). In a similar fashion, the amide H atom forms an intermolecular hydrogen bond with the hydroxy O atom of a third neighbouring molecule. This interaction also links pairs of molecules into centrosymmetric dimers with the R²₂(12) motif. The interactions involving the H atoms of the hydroxy and amide groups can also be combined in an alternating fashion to yield extended cooperative ···O—H···O═C—N—H···O—H··· chains, which run parallel to the [100] direction and can be described by a binary graph-set motif of C²₂(6).

Free refinement of the carboxylic acid H atom in (IV) resulted in a rather long O2—H2 distance, while the associated hydrogen-bonding H···O and O···O distances in the R²₂(8) motif between the opposing carboxylic acid functions in two adjacent molecules are quite short (Table 2). This indicates that the pairwise intermolecular hydrogen-bonding interactions are quite strong. In such cases, some practitioners have described observations that suggest there may be a tendency for the hydrogen bonds to become more symmetrical, disordered across the O···O vector, or even perfectly symmetrical (Gilli et al., 1994; Alfonso et al., 2001). The refined position of atom H2, at first glance, seems to support the idea of partial symmetricalization of the H-atom position, but other evidence suggests that the refined position may be misleading. Firstly, the refined isotropic atomic displacement parameter of atom H2 is somewhat larger than normal and and larger than those of the hydroxy and amide H atoms, whose positions and atomic displacement parameters were also refined. Secondly, a contoured difference Fourier map produced by PLATON (Spek, 2003), in which the site occupation factor of atom H2 had been set to 0.001, clearly shows that the electron density does indeed extend a low ridge towards the acceptor O atom, but that the maximum of the electron density is quite clearly defined and is located closer to atom O2 than the refined position of atom H2 (Fig. 3). The maximum is estimated to be about 0.83 Å from atom O2, which is surprisingly close to the normally expected O—H distance of 0.84 Å at the temperature of the measurement (160 K). This result suggests that the refined position of atom H2 does not necessarily truly represent the majority of the electron-density distribution in this case and that there may be little, if any, symmetricalization of the hydrogen bond. The result further shows the importance of examining contoured difference Fourier maps whenever potentially unusual H-atom positions are being investigated.

Compound (V) also crystallized as a racemate and again the reference molecule was selected as having the (R) configuration (Fig. 4). The oxazole ring is planar, with this plane making an angle of 87.02 (6)° with the plane of the phenyl ring. The hydroxy H atom forms an intermolecular hydrogen bond with the N atom of the oxazole ring of a neighbouring molecule which, in turn, acts as a donor for an identical interaction back to the original molecule (Table 2). These interactions link centrosymmetrically related pairs of molecules into dimers and can be described by a graph-set motif of R²₂(12).

Compound (VI) crystallized as a racemate, albeit in a non-centrosymmetric space group. The compound has the (6RS,13RS) configuration, which means that the phenyl substituents have a cis relationship: the selected reference molecule has (6R,13R) configuration (Fig. 5). The cis orientation of the phenyl groups was unexpected, as all previous analogous reactions starting from racemic materials had yielded trans-configured cyclodimers (Iliev et al., 2003, 2006). The 14-membered ring conformation, while corrugated, is not folded. When viewed perpendicular to the mean ring plane, the ring appears to have a distorted variant of the rectangular diamond-lattice [3434] conformation often observed for this size of organic macrocycle (Groth, 1979; Chan et al., 1985) and predicted to be slightly more stable than the [3344] and [3335] conformations (Dale, 1973). The lactone and lactam groups sit along the `3' and `4' sides of the rectangle, respectively, while the phenyl and methyl substituents occur at the corners. The torsion angles along the sides of the rectangle (Table 3) are close to the ideal value of 180°, with the greatest deviation of about 6° being observed within the lactam groups. The corners of an ideal [3434] rectangle are characterized by two consecutive torsion angles of the same sign and values of ±60° and it is here that the ring in (VI) shows the greatest deviation from ideality. The dimethyl-substituted corners have a sharper turn, as demonstrated by both torsion angles being up to 17° less than 60°. The phenyl-substituted corners are completely outside the expected pattern, with one torsion angle having a magnitude of about 127° and the following torsion angle being opposite in sign and with a magnitude of about 64°. The five-atom and four-atom planes formed by the lactone and lactam sides of the rectangle, respectively, are reasonably planar, with the maximum deviations in each type of plane being 0.023 (2) and 0.042 (3) Å, respectively. The greater deviation from planarity of the sides containing the lactam groups is in keeping with the greater deviation of the lactam torsion angle from 180°. Most significantly, instead of the planes of opposing flanks being parallel, as in the ideal diamond-based conformation, the planes of the two lactam sides intersect at an angle of 24.4 (4)°, while those of the two lactone sides intersect at an angle of 80.6 (4)°, which means that the lactone carbonyl groups are turned well away from one another. The described distortions may all be a consequence of twists in the macrocyclic ring conformation, induced by the cis-positioned phenyl substituents preferring to occupy equatorial positions. The phenyl ring planes are approximately perpendicular to the mean plane of the macrocyclic ring. One of the phenyl rings is disordered with an approximately 2:1 ratio of orientations, and the two orientations differ by a twist of 22.0 (1)° about the C17···C20 axis.

The lactam groups in the molecules of (VI) are oriented such that their donor H atoms point towards the same side of the macrocyclic ring and, in addition, the molecules pack such that all of the N—H bonds in the structure face in roughly the same direction. The crystallographic c-glide plane does not flip any molecules up the other way, as it lies approximately perpendicular to the mean plane of the macrocyclic ring. In the structures of the previously examined analogues (Iliev et al., 2003, 2006), the centrosymmetric nature of the molecules meant that the amide H atoms pointed to opposite sides of the macrocyclic ring. This difference has consequences for the hydrogen-bonding pattern. In the previous structures, hydrogen bonds formed between the lactam N—H groups and the lactone O atoms of neighbouring molecules and assembled the centrosymmetric molecules into stacks of ladder-like columns, where the macrocycle acted as the ladder rung and the hydrogen bonds were the rung supports, with the directional sense of the support (the N—H → O direction) on opposing sides of a rung being opposite. In (VI), the lactam N—H groups also form intermolecular hydrogen bonds with the lactone O atoms of neighbouring molecules (Table 4), but instead of a ladder-like arrangement, the hydrogen bonds link to diagonally offset neighbouring molecules, with each of the two symmetry-independent interactions going off in different directions (Fig. 6). Taken individually, the interactions link the molecules into extended chains, each of which has a graph-set motif of C(5). The chains involving N4—H and N11—H run in the [101] and [001] directions, respectively. In essence, each molecule donates hydrogen bonds to two neighbouring molecules and accepts two hydrogen bonds from two other molecules, so that, taken together, these interactions serve to link the molecules into an extended three-dimensional framework.

S2. Experimental

Compound (III) was prepared in 88% yield by the reaction of DL-tropic acid, (I) (332 mg, 2 mmol), and 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine, (II) (370 mg, 2.11 mmol), in tetrahydrofuran (20 ml) at room temperature, according to a known protocol (Obrecht & Heimgartner, 1987). Hydroxy acid (IV) was obtained by treatment of (III) (340 mg, 1 mmol) with a 3 N solution of HCl in tetrahydrofuran (3 ml) for 4 h at room temperature and subsequent extraction with ethyl acetate. Suitable crystals of (IV) were obtained by slow recrystallization from a mixture of dichloromethane–2-propanol–hexane (Ratio of solvents?) (m.p. 498–501 K). The treatment of (IV) (126 mg, 0.5 mmol) with N,N'-dicyclohexylcarbodiimide (104 mg, 0.5 mmol) in ethyl acetate (10 ml) overnight at room temperature, followed by filtration, washing with ethyl acetate and recrystallization of the residue from acetonitrile, yielded 93 mg (79%) of (V) (m.p. 392–395 K). The treatment of (IV) (126 mg, 0.5 mmol) with Bu₂SnO (50 mg) in xylene (150 ml) at reflux for 2 d (Iliev et al., 2003), followed by evaporation of the solvent, washing with diethyl ether and recrystallization from acetone–hexane–2-propanol (Ratio of solvents?), yielded 9 mg (5%) of (VI) as colourless crystals. The same compound was isolated in small amounts by treatment of (III) (170 mg, 0.5 mmol) in toluene (100 ml) at 373 K with HCl (gas) for 8 min, followed by chromatographic purification (silica gel, dichloromethane–acetone 20:1).

S3. Refinement

In the structure of compound (VI), one of the phenyl rings is disordered over two orientations which result from a pivot about the C17···C20 axis of the ring. Two positions were defined for each of the other four atoms of this ring and refinement of constrained site occupation factors for the two orientations yielded a value of 0.67 (3) for the major conformation. All C—C bond lengths within both orientations of the disordered ring were restrained to be similar, while neighbouring atoms within and between each conformation of the disordered ring were restrained to have similar atomic displacement parameters. Compound (VI) crystallized in a non-centrosymmetric space group with a polar axis, but the presence of glide planes indicates that the compound in the crystal is racemic. In the absence of significant anomalous dispersion effects, Friedel opposites were merged prior to the final cycles of refinement and the absolute structure was assigned arbitrarily. The amide, hydroxy and carboxylic acid H atoms of (IV), the hydroxy H atom of (V) and the amide H atoms of (VI) were placed in the positions indicated by difference electron-density maps and their positions were allowed to refine together with individual isotropic displacement parameters. In each structure, the methyl H atoms were constrained to an ideal geometry (C—H = 0.98 Å) with U_iso(H) = 1.5U_eq(C), but were allowed to rotate freely about the C—C bonds. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent C atom at distances of 0.95, 0.99 or 1.00 Å for phenyl, methylene or methine groups, respectively, and with U_iso(H) = 1.2U_eq(C). For (IV), (V) and (VI), two, one and four low-angle reflections, respectively, were omitted from the final cycles of refinement, because their observed intensities were much lower than the calculated values as a result of being partially obscured by the beam stop.

Computing details

For all compounds, data collection: COLLECT (Nonius, 2000); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

	Fig. 1. A view of the (R) enantiomer in racemic (IV), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by circles of arbitrary size.
	Fig. 2. A hydrogen-bonded sheet in (IV). The hydrogen bonds are shown by dashed lines and the R^22(8), two R^22(12) and C^22(6) motifs are clearly visible.
	Fig. 3. A contoured difference Fourier map slice in the plane of the carboxylic acid group of (IV), with the site-occupancy factor of atom H2 set to 0.001. The refined positions of the atoms are shown by + marks. The contour intervals are 0.1 e Å^−3. [Symmetry code: (i) 1 − x, 2 − y, −z.]
	Fig. 4. A view of the (R) enantiomer in racemic (V), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by circles of arbitrary size.
	Fig. 5. A view of the (6R,13R) enantiomer in racemic (VI), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by circles of arbitrary size. Only the major conformation of the disordered phenyl ring is shown.
	Fig. 6. The crystal packing in (VI), showing the intermolecular hydrogen bonds as dashed lines.

(IV) rac-3-hydroxy-N-[1-methyl-1-(N-methyl-N-phenylcarbamoyl)ethyl]- 2-phenylpropanamide

Crystal data

C13H17NO4	Z = 2
Mr = 251.28	F(000) = 268
Triclinic, P1	Dx = 1.320 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.6567 (2) Å	Cell parameters from 2837 reflections
b = 9.1317 (3) Å	θ = 2.0–27.5°
c = 10.8486 (3) Å	µ = 0.10 mm^−1
α = 99.2298 (16)°	T = 160 K
β = 98.278 (2)°	Tablet, colourless
γ = 99.5405 (19)°	0.25 × 0.17 × 0.10 mm
V = 631.98 (3) Å^3

Data collection

Nonius KappaCCD area-detector diffractometer	2129 reflections with I > 2σ(I)
Radiation source: Nonius FR590 sealed tube generator	Rint = 0.061
Horizontally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 3.2°
Detector resolution: 9 pixels mm^-1	h = 0→8
ϕ and ω scans with κ offsets	k = −11→11
15315 measured reflections	l = −14→13
2900 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.052	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.139	w = 1/[σ^2(Fo^2) + (0.0656P)^2 + 0.1385P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max = 0.001
2898 reflections	Δρmax = 0.31 e Å^−3
178 parameters	Δρmin = −0.30 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.067 (12)

Special details

Experimental. Solvent used: acetonitrile–methanol Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.548 (2) Frames collected: 681 Seconds exposure per frame: 12 Degrees rotation per frame: 1.0 Crystal-Detector distance (mm): 30.0

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.49870 (19)	1.03820 (13)	0.15522 (12)	0.0377 (3)
O2	0.2869 (2)	0.85713 (14)	0.00834 (11)	0.0374 (3)
H2	0.379 (5)	0.906 (4)	−0.054 (3)	0.119 (11)*
O4	0.45972 (16)	0.66054 (12)	0.19945 (11)	0.0297 (3)
O7	0.26448 (17)	0.40646 (13)	−0.05294 (11)	0.0290 (3)
H7	0.377 (4)	0.386 (3)	−0.094 (3)	0.079 (8)*
N3	0.1425 (2)	0.71929 (14)	0.19032 (12)	0.0241 (3)
H3	0.008 (4)	0.685 (2)	0.160 (2)	0.051 (6)*
C1	0.3509 (2)	0.92984 (17)	0.12373 (15)	0.0273 (4)
C2	0.2204 (2)	0.88278 (17)	0.22064 (15)	0.0256 (4)
C4	0.2691 (2)	0.61981 (17)	0.17993 (14)	0.0235 (4)
C5	0.1632 (2)	0.45320 (17)	0.14904 (15)	0.0244 (4)
H5	0.0219	0.4454	0.0993	0.029*
C6	0.2818 (2)	0.36091 (18)	0.06740 (15)	0.0268 (4)
H61	0.4290	0.3790	0.1080	0.032*
H62	0.2233	0.2517	0.0567	0.032*
C8	0.0327 (3)	0.96027 (19)	0.20649 (17)	0.0339 (4)
H81	−0.0422	0.9309	0.1189	0.051*
H82	0.0799	1.0702	0.2272	0.051*
H83	−0.0593	0.9291	0.2643	0.051*
C9	0.3445 (3)	0.93276 (19)	0.35500 (15)	0.0312 (4)
H91	0.2557	0.9068	0.4161	0.047*
H92	0.3951	1.0424	0.3718	0.047*
H93	0.4623	0.8812	0.3634	0.047*
C10	0.1384 (2)	0.39679 (17)	0.27110 (15)	0.0258 (4)
C11	−0.0576 (3)	0.35727 (19)	0.29991 (17)	0.0327 (4)
H11	−0.1756	0.3656	0.2427	0.039*
C12	−0.0830 (3)	0.3059 (2)	0.41111 (18)	0.0413 (5)
H12	−0.2179	0.2789	0.4297	0.050*
C13	0.0881 (3)	0.2939 (2)	0.49516 (18)	0.0410 (5)
H13	0.0708	0.2591	0.5716	0.049*
C14	0.2840 (3)	0.33251 (19)	0.46771 (17)	0.0367 (4)
H14	0.4016	0.3244	0.5254	0.044*
C15	0.3093 (3)	0.38321 (18)	0.35583 (16)	0.0307 (4)
H15	0.4443	0.4088	0.3370	0.037*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0413 (7)	0.0313 (7)	0.0367 (7)	−0.0050 (6)	0.0084 (6)	0.0065 (5)
O2	0.0483 (8)	0.0332 (7)	0.0274 (6)	−0.0014 (6)	0.0068 (6)	0.0053 (5)
O4	0.0231 (6)	0.0283 (6)	0.0368 (7)	0.0050 (5)	0.0055 (5)	0.0032 (5)
O7	0.0272 (6)	0.0329 (6)	0.0293 (6)	0.0092 (5)	0.0074 (5)	0.0070 (5)
N3	0.0240 (7)	0.0188 (7)	0.0301 (7)	0.0051 (5)	0.0050 (6)	0.0059 (5)
C1	0.0316 (9)	0.0217 (8)	0.0286 (8)	0.0061 (7)	0.0032 (7)	0.0058 (7)
C2	0.0308 (9)	0.0186 (8)	0.0284 (8)	0.0059 (6)	0.0062 (7)	0.0049 (6)
C4	0.0253 (8)	0.0244 (8)	0.0226 (8)	0.0061 (6)	0.0062 (6)	0.0070 (6)
C5	0.0236 (8)	0.0214 (8)	0.0282 (8)	0.0058 (6)	0.0028 (6)	0.0050 (6)
C6	0.0296 (8)	0.0225 (8)	0.0287 (8)	0.0077 (6)	0.0036 (7)	0.0045 (7)
C8	0.0363 (10)	0.0237 (8)	0.0444 (10)	0.0113 (7)	0.0089 (8)	0.0074 (7)
C9	0.0373 (9)	0.0278 (9)	0.0277 (9)	0.0037 (7)	0.0060 (7)	0.0055 (7)
C10	0.0317 (9)	0.0181 (7)	0.0283 (8)	0.0061 (6)	0.0061 (7)	0.0041 (6)
C11	0.0323 (9)	0.0298 (9)	0.0385 (10)	0.0083 (7)	0.0091 (7)	0.0090 (7)
C12	0.0460 (11)	0.0386 (10)	0.0469 (11)	0.0104 (8)	0.0217 (9)	0.0158 (9)
C13	0.0591 (12)	0.0326 (10)	0.0345 (10)	0.0084 (9)	0.0141 (9)	0.0112 (8)
C14	0.0480 (11)	0.0276 (9)	0.0329 (9)	0.0079 (8)	−0.0017 (8)	0.0079 (7)
C15	0.0327 (9)	0.0240 (8)	0.0345 (9)	0.0061 (7)	0.0029 (7)	0.0051 (7)

Geometric parameters (Å, º)

O1—C1	1.2392 (19)	C8—H81	0.9800
O2—C1	1.294 (2)	C8—H82	0.9800
O2—H2	1.08 (3)	C8—H83	0.9800
O4—C4	1.2385 (18)	C9—H91	0.9800
O7—C6	1.4273 (19)	C9—H92	0.9800
O7—H7	0.95 (3)	C9—H93	0.9800
N3—C4	1.3406 (19)	C10—C11	1.389 (2)
N3—C2	1.4638 (19)	C10—C15	1.392 (2)
N3—H3	0.89 (2)	C11—C12	1.385 (2)
C1—C2	1.526 (2)	C11—H11	0.9500
C2—C9	1.527 (2)	C12—C13	1.384 (3)
C2—C8	1.535 (2)	C12—H12	0.9500
C4—C5	1.529 (2)	C13—C14	1.381 (3)
C5—C10	1.516 (2)	C13—H13	0.9500
C5—C6	1.517 (2)	C14—C15	1.389 (2)
C5—H5	1.0000	C14—H14	0.9500
C6—H61	0.9900	C15—H15	0.9500
C6—H62	0.9900
C1—O2—H2	109.9 (17)	C2—C8—H82	109.5
C6—O7—H7	110.6 (15)	H81—C8—H82	109.5
C4—N3—C2	122.12 (13)	C2—C8—H83	109.5
C4—N3—H3	117.6 (14)	H81—C8—H83	109.5
C2—N3—H3	118.6 (14)	H82—C8—H83	109.5
O1—C1—O2	123.80 (15)	C2—C9—H91	109.5
O1—C1—C2	120.43 (14)	C2—C9—H92	109.5
O2—C1—C2	115.57 (14)	H91—C9—H92	109.5
N3—C2—C1	109.91 (12)	C2—C9—H93	109.5
N3—C2—C9	111.65 (13)	H91—C9—H93	109.5
C1—C2—C9	110.70 (13)	H92—C9—H93	109.5
N3—C2—C8	107.52 (13)	C11—C10—C15	118.78 (15)
C1—C2—C8	106.69 (13)	C11—C10—C5	119.98 (14)
C9—C2—C8	110.19 (13)	C15—C10—C5	121.24 (14)
O4—C4—N3	121.99 (14)	C12—C11—C10	120.75 (16)
O4—C4—C5	122.38 (13)	C12—C11—H11	119.6
N3—C4—C5	115.56 (13)	C10—C11—H11	119.6
C10—C5—C6	112.77 (13)	C13—C12—C11	120.00 (17)
C10—C5—C4	109.57 (12)	C13—C12—H12	120.0
C6—C5—C4	110.43 (13)	C11—C12—H12	120.0
C10—C5—H5	108.0	C14—C13—C12	119.93 (17)
C6—C5—H5	108.0	C14—C13—H13	120.0
C4—C5—H5	108.0	C12—C13—H13	120.0
O7—C6—C5	107.77 (12)	C13—C14—C15	120.04 (16)
O7—C6—H61	110.2	C13—C14—H14	120.0
C5—C6—H61	110.2	C15—C14—H14	120.0
O7—C6—H62	110.2	C14—C15—C10	120.50 (16)
C5—C6—H62	110.2	C14—C15—H15	119.7
H61—C6—H62	108.5	C10—C15—H15	119.7
C2—C8—H81	109.5
C4—N3—C2—C1	56.53 (18)	C10—C5—C6—O7	170.06 (12)
C4—N3—C2—C9	−66.72 (18)	C4—C5—C6—O7	−66.99 (15)
C4—N3—C2—C8	172.30 (14)	C6—C5—C10—C11	−124.04 (16)
O1—C1—C2—N3	−148.38 (15)	C4—C5—C10—C11	112.53 (16)
O2—C1—C2—N3	36.52 (19)	C6—C5—C10—C15	55.83 (19)
O1—C1—C2—C9	−24.6 (2)	C4—C5—C10—C15	−67.60 (18)
O2—C1—C2—C9	160.32 (14)	C15—C10—C11—C12	0.3 (2)
O1—C1—C2—C8	95.33 (17)	C5—C10—C11—C12	−179.83 (15)
O2—C1—C2—C8	−79.77 (17)	C10—C11—C12—C13	0.2 (3)
C2—N3—C4—O4	2.4 (2)	C11—C12—C13—C14	−0.3 (3)
C2—N3—C4—C5	179.44 (13)	C12—C13—C14—C15	−0.1 (3)
O4—C4—C5—C10	88.59 (17)	C13—C14—C15—C10	0.5 (3)
N3—C4—C5—C10	−88.45 (15)	C11—C10—C15—C14	−0.7 (2)
O4—C4—C5—C6	−36.2 (2)	C5—C10—C15—C14	179.47 (14)
N3—C4—C5—C6	146.75 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1^i	1.08 (3)	1.55 (4)	2.6307 (16)	174 (3)
O7—H7···O4^ii	0.95 (3)	1.74 (3)	2.6780 (16)	167 (2)
N3—H3···O7^iii	0.89 (2)	1.98 (2)	2.8523 (18)	166 (2)

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

(V) rac-2-(2-hydroxy-1-phenylethyl)-4,4-dimethyl-1,3-oxazol-5(4H)-one

Crystal data

C13H15NO3	F(000) = 496
Mr = 233.27	Dx = 1.316 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3606 reflections
a = 10.1934 (2) Å	θ = 2.0–30.0°
b = 9.9466 (2) Å	µ = 0.09 mm^−1
c = 11.9331 (3) Å	T = 160 K
β = 103.3915 (9)°	Prism, colourless
V = 1177.00 (4) Å^3	0.35 × 0.20 × 0.20 mm
Z = 4

Data collection

Nonius KappaCCD area-detector diffractometer	2638 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.047
Horizontally mounted graphite crystal monochromator	θmax = 30.0°, θmin = 2.7°
Detector resolution: 9 pixels mm^-1	h = 0→14
ϕ and ω scans with κ offsets	k = 0→13
28758 measured reflections	l = −16→16
3422 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.042	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.108	w = 1/[σ^2(Fo^2) + (0.0472P)^2 + 0.2303P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
3421 reflections	Δρmax = 0.23 e Å^−3
161 parameters	Δρmin = −0.21 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.020 (4)

Special details

Experimental. Solvent used: acetonitrile Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.611 (2) Frames collected: 345 Seconds exposure per frame: 60 Degrees rotation per frame: 2.0 Crystal-Detector distance (mm): 30.0

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O3	1.19102 (8)	0.01235 (8)	0.30826 (7)	0.0314 (2)
O4	1.02125 (7)	0.09096 (7)	0.38170 (7)	0.02467 (19)
N1	1.05564 (9)	0.31591 (9)	0.38349 (8)	0.0231 (2)
C2	1.16760 (10)	0.25549 (10)	0.34192 (9)	0.0222 (2)
C3	1.13445 (10)	0.10658 (11)	0.33784 (9)	0.0232 (2)
C5	0.98238 (10)	0.22086 (10)	0.40437 (9)	0.0212 (2)
C6	0.85930 (10)	0.22667 (11)	0.45235 (9)	0.0223 (2)
H6	0.8770	0.1690	0.5229	0.027*
C7	0.73591 (10)	0.16956 (10)	0.36896 (9)	0.0222 (2)
C8	0.70194 (11)	0.20797 (12)	0.25370 (10)	0.0278 (3)
H8	0.7581	0.2687	0.2249	0.033*
C9	0.58591 (12)	0.15755 (13)	0.18064 (10)	0.0325 (3)
H9	0.5627	0.1850	0.1023	0.039*
C10	0.50412 (11)	0.06801 (13)	0.22096 (11)	0.0342 (3)
H10	0.4254	0.0333	0.1704	0.041*
C11	0.53726 (11)	0.02898 (13)	0.33533 (11)	0.0331 (3)
H11	0.4813	−0.0326	0.3635	0.040*
C12	0.65245 (11)	0.07985 (11)	0.40904 (10)	0.0269 (2)
H12	0.6745	0.0531	0.4876	0.032*
C13	1.17464 (12)	0.30969 (12)	0.22417 (10)	0.0311 (3)
H131	1.0898	0.2903	0.1685	0.047*
H132	1.2494	0.2665	0.1991	0.047*
H133	1.1893	0.4071	0.2291	0.047*
C14	1.30048 (11)	0.27985 (13)	0.43026 (10)	0.0295 (3)
H141	1.3186	0.3766	0.4373	0.044*
H142	1.3741	0.2348	0.4049	0.044*
H143	1.2939	0.2438	0.5052	0.044*
O15	0.93363 (8)	0.40103 (8)	0.59066 (7)	0.0309 (2)
H15	0.9390 (17)	0.493 (2)	0.5950 (15)	0.063 (5)*
C15	0.83426 (11)	0.36989 (11)	0.48989 (10)	0.0252 (2)
H151	0.8394	0.4343	0.4278	0.030*
H152	0.7433	0.3763	0.5057	0.030*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O3	0.0316 (4)	0.0257 (4)	0.0374 (5)	0.0052 (3)	0.0089 (4)	−0.0047 (3)
O4	0.0254 (4)	0.0181 (4)	0.0312 (4)	0.0002 (3)	0.0080 (3)	−0.0016 (3)
N1	0.0212 (4)	0.0205 (4)	0.0273 (4)	0.0004 (3)	0.0052 (4)	−0.0020 (3)
C2	0.0204 (5)	0.0218 (5)	0.0239 (5)	−0.0002 (4)	0.0043 (4)	−0.0020 (4)
C3	0.0217 (5)	0.0244 (5)	0.0221 (5)	0.0020 (4)	0.0021 (4)	−0.0017 (4)
C5	0.0216 (5)	0.0182 (5)	0.0221 (5)	0.0012 (4)	0.0013 (4)	−0.0015 (4)
C6	0.0223 (5)	0.0209 (5)	0.0237 (5)	−0.0008 (4)	0.0053 (4)	0.0002 (4)
C7	0.0201 (5)	0.0195 (5)	0.0273 (5)	0.0009 (4)	0.0061 (4)	−0.0015 (4)
C8	0.0247 (5)	0.0290 (6)	0.0299 (6)	−0.0013 (4)	0.0065 (5)	0.0039 (4)
C9	0.0276 (6)	0.0398 (7)	0.0282 (6)	0.0026 (5)	0.0024 (5)	−0.0001 (5)
C10	0.0206 (5)	0.0385 (7)	0.0411 (7)	−0.0022 (5)	0.0019 (5)	−0.0096 (5)
C11	0.0231 (5)	0.0321 (6)	0.0455 (7)	−0.0063 (5)	0.0110 (5)	−0.0011 (5)
C12	0.0249 (5)	0.0274 (6)	0.0297 (6)	−0.0005 (4)	0.0093 (4)	0.0013 (4)
C13	0.0330 (6)	0.0325 (6)	0.0278 (6)	−0.0009 (5)	0.0070 (5)	0.0031 (5)
C14	0.0226 (5)	0.0342 (6)	0.0302 (6)	−0.0018 (5)	0.0027 (4)	−0.0049 (5)
O15	0.0374 (5)	0.0227 (4)	0.0297 (4)	−0.0010 (3)	0.0018 (4)	−0.0046 (3)
C15	0.0236 (5)	0.0239 (5)	0.0286 (5)	0.0003 (4)	0.0069 (4)	−0.0026 (4)

Geometric parameters (Å, º)

O3—C3	1.1957 (13)	C9—H9	0.9500
O4—C3	1.3818 (13)	C10—C11	1.3834 (18)
O4—C5	1.3961 (12)	C10—H10	0.9500
N1—C5	1.2648 (13)	C11—C12	1.3892 (16)
N1—C2	1.4737 (13)	C11—H11	0.9500
C2—C3	1.5174 (15)	C12—H12	0.9500
C2—C13	1.5222 (15)	C13—H131	0.9800
C2—C14	1.5308 (15)	C13—H132	0.9800
C5—C6	1.4960 (14)	C13—H133	0.9800
C6—C7	1.5215 (15)	C14—H141	0.9800
C6—C15	1.5324 (15)	C14—H142	0.9800
C6—H6	1.0000	C14—H143	0.9800
C7—C12	1.3918 (15)	O15—C15	1.4155 (13)
C7—C8	1.3918 (16)	O15—H15	0.915 (19)
C8—C9	1.3902 (17)	C15—H151	0.9900
C8—H8	0.9500	C15—H152	0.9900
C9—C10	1.3804 (18)
C3—O4—C5	105.59 (8)	C9—C10—C11	119.72 (11)
C5—N1—C2	107.46 (8)	C9—C10—H10	120.1
N1—C2—C3	103.00 (8)	C11—C10—H10	120.1
N1—C2—C13	111.84 (9)	C10—C11—C12	119.99 (11)
C3—C2—C13	111.95 (9)	C10—C11—H11	120.0
N1—C2—C14	109.53 (8)	C12—C11—H11	120.0
C3—C2—C14	109.36 (9)	C11—C12—C7	120.68 (11)
C13—C2—C14	110.87 (9)	C11—C12—H12	119.7
O3—C3—O4	121.72 (10)	C7—C12—H12	119.7
O3—C3—C2	130.96 (10)	C2—C13—H131	109.5
O4—C3—C2	107.27 (8)	C2—C13—H132	109.5
N1—C5—O4	116.53 (9)	H131—C13—H132	109.5
N1—C5—C6	129.21 (9)	C2—C13—H133	109.5
O4—C5—C6	114.25 (9)	H131—C13—H133	109.5
C5—C6—C7	112.01 (8)	H132—C13—H133	109.5
C5—C6—C15	111.04 (9)	C2—C14—H141	109.5
C7—C6—C15	111.71 (8)	C2—C14—H142	109.5
C5—C6—H6	107.3	H141—C14—H142	109.5
C7—C6—H6	107.3	C2—C14—H143	109.5
C15—C6—H6	107.3	H141—C14—H143	109.5
C12—C7—C8	118.92 (10)	H142—C14—H143	109.5
C12—C7—C6	119.55 (9)	C15—O15—H15	106.7 (11)
C8—C7—C6	121.51 (9)	O15—C15—C6	108.48 (9)
C9—C8—C7	120.10 (10)	O15—C15—H151	110.0
C9—C8—H8	120.0	C6—C15—H151	110.0
C7—C8—H8	120.0	O15—C15—H152	110.0
C10—C9—C8	120.59 (11)	C6—C15—H152	110.0
C10—C9—H9	119.7	H151—C15—H152	108.4
C8—C9—H9	119.7
C5—N1—C2—C3	3.31 (11)	N1—C5—C6—C15	−6.53 (15)
C5—N1—C2—C13	123.69 (10)	O4—C5—C6—C15	172.39 (8)
C5—N1—C2—C14	−112.98 (10)	C5—C6—C7—C12	133.53 (10)
C5—O4—C3—O3	−178.95 (10)	C15—C6—C7—C12	−101.18 (11)
C5—O4—C3—C2	3.38 (10)	C5—C6—C7—C8	−48.41 (13)
N1—C2—C3—O3	178.52 (11)	C15—C6—C7—C8	76.88 (12)
C13—C2—C3—O3	58.21 (15)	C12—C7—C8—C9	0.34 (16)
C14—C2—C3—O3	−65.07 (15)	C6—C7—C8—C9	−177.73 (10)
N1—C2—C3—O4	−4.11 (10)	C7—C8—C9—C10	−0.73 (18)
C13—C2—C3—O4	−124.42 (9)	C8—C9—C10—C11	0.56 (18)
C14—C2—C3—O4	112.30 (9)	C9—C10—C11—C12	−0.02 (18)
C2—N1—C5—O4	−1.43 (12)	C10—C11—C12—C7	−0.37 (18)
C2—N1—C5—C6	177.47 (10)	C8—C7—C12—C11	0.20 (16)
C3—O4—C5—N1	−1.34 (12)	C6—C7—C12—C11	178.31 (10)
C3—O4—C5—C6	179.59 (8)	C5—C6—C15—O15	−71.64 (11)
N1—C5—C6—C7	119.13 (12)	C7—C6—C15—O15	162.53 (9)
O4—C5—C6—C7	−61.95 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O15—H15···N1^i	0.915 (19)	1.92 (2)	2.8316 (12)	174.8 (16)

Symmetry code: (i) −x+2, −y+1, −z+1.

(VI) (6RS,13RS)-3,3,10,10-Tetramethyl-6,13-diphenyl-1,8-dioxa- 4,11-diazacyclotetradecane-2,5,9,12-tetraone

Crystal data

C26H30N2O6	F(000) = 992
Mr = 466.53	Dx = 1.228 Mg m^−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 2291 reflections
a = 15.9437 (2) Å	θ = 2.0–25.0°
b = 19.1979 (4) Å	µ = 0.09 mm^−1
c = 11.2587 (2) Å	T = 160 K
β = 132.9182 (7)°	Prism, colourless
V = 2523.69 (8) Å^3	0.15 × 0.15 × 0.10 mm
Z = 4

Data collection

Nonius KappaCCD area-detector diffractometer	1883 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.058
Horizontally mounted graphite crystal monochromator	θmax = 25.0°, θmin = 2.1°
Detector resolution: 9 pixels mm^-1	h = −18→18
ω scans with κ offsets	k = −22→22
16028 measured reflections	l = −13→13
2217 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.097	w = 1/[σ^2(Fo^2) + (0.0575P)^2 + 0.2754P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
2215 reflections	Δρmax = 0.22 e Å^−3
357 parameters	Δρmin = −0.17 e Å^−3
152 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0056 (10)

Special details

Experimental. Solvent used: acetone / hexane / 2-propanol Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.680 (1) Frames collected: 709 Seconds exposure per frame: 60 Degrees rotation per frame: 0.5 Crystal-Detector distance (mm): 28.0

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.63873 (17)	0.88207 (10)	0.5609 (2)	0.0356 (5)
O2	0.80326 (18)	0.82304 (10)	0.7413 (3)	0.0388 (5)
O5	0.65079 (18)	0.78036 (12)	0.3756 (3)	0.0443 (6)
O8	0.40110 (18)	0.86611 (10)	0.0797 (3)	0.0356 (5)
O9	0.3745 (2)	0.92609 (11)	−0.1143 (3)	0.0424 (5)
O12	0.58311 (19)	0.97036 (11)	0.2525 (3)	0.0426 (5)
N4	0.5346 (2)	0.75546 (13)	0.4173 (3)	0.0365 (6)
H4	0.471 (3)	0.7449 (17)	0.375 (4)	0.034 (9)*
N11	0.4320 (2)	0.99212 (13)	0.2239 (3)	0.0353 (6)
H11	0.407 (3)	1.0067 (18)	0.267 (4)	0.039 (9)*
C2	0.7001 (3)	0.82438 (15)	0.6390 (4)	0.0331 (7)
C3	0.6227 (3)	0.76193 (15)	0.5924 (4)	0.0367 (7)
C5	0.5564 (3)	0.76283 (15)	0.3228 (4)	0.0368 (7)
C6	0.4560 (3)	0.74659 (15)	0.1430 (4)	0.0375 (7)
H6	0.3859	0.7389	0.1247	0.045*
C7	0.4339 (3)	0.80668 (15)	0.0386 (4)	0.0396 (7)
H71	0.5039	0.8176	0.0599	0.048*
H72	0.3717	0.7948	−0.0776	0.048*
C9	0.3785 (3)	0.92425 (15)	−0.0029 (4)	0.0349 (7)
C10	0.3482 (3)	0.98561 (15)	0.0487 (4)	0.0352 (7)
C12	0.5439 (3)	0.98707 (14)	0.3125 (4)	0.0343 (7)
C13	0.6218 (3)	1.00266 (14)	0.4933 (4)	0.0347 (7)
H13	0.5735	1.0079	0.5197	0.042*
C14	0.7057 (3)	0.94338 (15)	0.5933 (4)	0.0395 (7)
H141	0.7497	0.9345	0.5622	0.047*
H142	0.7601	0.9552	0.7102	0.047*
C15	0.5638 (3)	0.77458 (19)	0.6548 (4)	0.0471 (8)
H151	0.5187	0.8176	0.6071	0.071*
H152	0.6218	0.7790	0.7732	0.071*
H153	0.5131	0.7353	0.6241	0.071*
C16	0.6964 (3)	0.69614 (17)	0.6686 (4)	0.0495 (9)
H161	0.6478	0.6558	0.6393	0.074*
H162	0.7544	0.7012	0.7868	0.074*
H163	0.7343	0.6893	0.6284	0.074*
C17	0.4821 (2)	0.67979 (15)	0.1000 (4)	0.0400 (7)
C18A	0.4419 (11)	0.6168 (4)	0.1028 (19)	0.053 (3)	0.67 (3)
H181	0.4007	0.6160	0.1357	0.063*	0.67 (3)
C19A	0.4590 (10)	0.5550 (7)	0.0597 (17)	0.058 (3)	0.67 (3)
H191	0.4292	0.5124	0.0610	0.069*	0.67 (3)
C18B	0.410 (2)	0.6243 (8)	0.048 (4)	0.043 (5)	0.33 (3)
H182	0.3485	0.6270	0.0447	0.051*	0.33 (3)
C19B	0.429 (2)	0.5647 (15)	0.002 (4)	0.067 (6)	0.33 (3)
H192	0.3758	0.5273	−0.0420	0.080*	0.33 (3)
C20	0.5205 (3)	0.55663 (18)	0.0148 (5)	0.0623 (11)
H201	0.5318	0.5145	−0.0168	0.075*	0.67 (3)
H202	0.5353	0.5143	−0.0117	0.075*	0.33 (3)
C21A	0.5661 (12)	0.6173 (4)	0.0141 (19)	0.057 (3)	0.67 (3)
H211	0.6096	0.6178	−0.0153	0.068*	0.67 (3)
C22A	0.5457 (12)	0.6774 (9)	0.058 (2)	0.056 (4)	0.67 (3)
H221	0.5774	0.7198	0.0600	0.067*	0.67 (3)
C21B	0.589 (3)	0.6144 (10)	0.069 (4)	0.061 (7)	0.33 (3)
H212	0.6551	0.6101	0.0837	0.073*	0.33 (3)
C22B	0.571 (2)	0.6779 (17)	0.105 (4)	0.055 (7)	0.33 (3)
H222	0.6158	0.7177	0.1307	0.066*	0.33 (3)
C23	0.2314 (3)	0.9701 (2)	−0.0081 (4)	0.0490 (8)
H231	0.2365	0.9276	0.0446	0.074*
H232	0.1744	0.9638	−0.1260	0.074*
H233	0.2087	1.0092	0.0208	0.074*
C24	0.3435 (3)	1.05232 (17)	−0.0303 (5)	0.0505 (9)
H241	0.3261	1.0920	0.0044	0.076*
H242	0.2837	1.0478	−0.1486	0.076*
H243	0.4177	1.0598	0.0026	0.076*
C25	0.6891 (2)	1.06968 (15)	0.5388 (4)	0.0357 (7)
C26	0.7492 (3)	1.0826 (2)	0.4930 (4)	0.0493 (9)
H26	0.7465	1.0499	0.4271	0.059*
C27	0.8135 (3)	1.1431 (2)	0.5430 (5)	0.0600 (11)
H27	0.8553	1.1513	0.5123	0.072*
C28	0.8169 (3)	1.19103 (19)	0.6369 (5)	0.0575 (10)
H28	0.8595	1.2328	0.6689	0.069*
C29	0.7583 (3)	1.17820 (17)	0.6844 (5)	0.0518 (9)
H29	0.7612	1.2111	0.7502	0.062*
C30	0.6951 (3)	1.11764 (16)	0.6366 (4)	0.0436 (8)
H30	0.6557	1.1089	0.6710	0.052*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0366 (11)	0.0263 (10)	0.0417 (12)	−0.0012 (9)	0.0258 (10)	−0.0001 (9)
O2	0.0348 (12)	0.0387 (11)	0.0391 (12)	−0.0004 (9)	0.0237 (11)	0.0002 (10)
O5	0.0442 (13)	0.0454 (13)	0.0493 (14)	−0.0053 (10)	0.0342 (12)	−0.0067 (10)
O8	0.0453 (11)	0.0256 (10)	0.0395 (12)	−0.0001 (9)	0.0303 (10)	−0.0005 (9)
O9	0.0523 (12)	0.0420 (12)	0.0400 (12)	−0.0032 (10)	0.0342 (11)	−0.0019 (10)
O12	0.0461 (12)	0.0419 (12)	0.0489 (13)	−0.0063 (10)	0.0359 (11)	−0.0087 (10)
N4	0.0351 (14)	0.0318 (13)	0.0421 (15)	−0.0019 (12)	0.0262 (13)	−0.0012 (11)
N11	0.0408 (15)	0.0316 (13)	0.0406 (15)	0.0018 (11)	0.0305 (13)	0.0000 (11)
C2	0.0359 (17)	0.0334 (16)	0.0334 (16)	0.0051 (14)	0.0249 (15)	0.0029 (13)
C3	0.0382 (16)	0.0290 (15)	0.0412 (18)	−0.0003 (13)	0.0264 (15)	0.0014 (13)
C5	0.0400 (18)	0.0275 (15)	0.0446 (18)	0.0021 (13)	0.0295 (16)	−0.0020 (14)
C6	0.0405 (17)	0.0297 (15)	0.0446 (19)	−0.0005 (13)	0.0299 (16)	−0.0021 (13)
C7	0.0478 (18)	0.0303 (15)	0.0415 (18)	0.0012 (14)	0.0307 (16)	−0.0043 (13)
C9	0.0355 (15)	0.0315 (15)	0.0353 (17)	−0.0042 (13)	0.0231 (14)	−0.0007 (13)
C10	0.0385 (16)	0.0310 (15)	0.0374 (17)	0.0044 (13)	0.0264 (15)	0.0037 (13)
C12	0.0443 (19)	0.0245 (14)	0.0420 (17)	−0.0034 (13)	0.0325 (16)	−0.0021 (13)
C13	0.0389 (16)	0.0307 (15)	0.0391 (18)	−0.0037 (13)	0.0284 (15)	−0.0028 (13)
C14	0.0411 (17)	0.0300 (16)	0.0470 (19)	−0.0071 (14)	0.0299 (16)	−0.0010 (14)
C15	0.0523 (19)	0.0461 (19)	0.053 (2)	−0.0084 (16)	0.0400 (18)	−0.0024 (16)
C16	0.053 (2)	0.0331 (17)	0.054 (2)	0.0045 (15)	0.0330 (18)	0.0076 (16)
C17	0.0374 (17)	0.0346 (16)	0.0385 (17)	0.0030 (13)	0.0221 (15)	−0.0030 (13)
C18A	0.035 (5)	0.046 (5)	0.060 (7)	0.003 (3)	0.025 (5)	−0.005 (4)
C19A	0.040 (4)	0.036 (4)	0.077 (7)	0.001 (4)	0.032 (5)	−0.008 (5)
C18B	0.043 (10)	0.026 (6)	0.068 (13)	0.004 (6)	0.041 (10)	0.000 (7)
C19B	0.077 (12)	0.039 (10)	0.075 (13)	−0.018 (9)	0.048 (11)	−0.015 (10)
C20	0.063 (2)	0.042 (2)	0.068 (3)	0.0100 (18)	0.039 (2)	−0.0121 (18)
C21A	0.074 (6)	0.051 (4)	0.061 (7)	0.020 (4)	0.052 (6)	0.001 (4)
C22A	0.061 (7)	0.043 (5)	0.070 (7)	0.000 (5)	0.047 (6)	−0.004 (5)
C21B	0.063 (9)	0.052 (9)	0.066 (14)	0.009 (7)	0.044 (10)	0.001 (8)
C22B	0.037 (8)	0.033 (9)	0.086 (15)	−0.008 (7)	0.038 (10)	−0.027 (10)
C23	0.0424 (18)	0.053 (2)	0.051 (2)	0.0082 (17)	0.0314 (17)	0.0049 (17)
C24	0.068 (2)	0.0320 (17)	0.058 (2)	0.0073 (16)	0.046 (2)	0.0081 (16)
C25	0.0379 (16)	0.0328 (15)	0.0338 (17)	−0.0009 (13)	0.0234 (15)	0.0015 (12)
C26	0.053 (2)	0.054 (2)	0.0443 (19)	−0.0145 (17)	0.0343 (18)	−0.0080 (16)
C27	0.063 (2)	0.066 (3)	0.049 (2)	−0.027 (2)	0.037 (2)	−0.0050 (19)
C28	0.056 (2)	0.0435 (19)	0.048 (2)	−0.0199 (18)	0.0251 (19)	−0.0034 (17)
C29	0.052 (2)	0.0373 (18)	0.056 (2)	−0.0072 (16)	0.0323 (19)	−0.0106 (16)
C30	0.0399 (17)	0.0379 (17)	0.050 (2)	−0.0033 (15)	0.0294 (16)	−0.0050 (16)

Geometric parameters (Å, º)

O1—C2	1.336 (3)	C17—C22B	1.376 (13)
O1—C14	1.459 (3)	C17—C18A	1.378 (8)
O2—C2	1.205 (4)	C17—C22A	1.379 (7)
O5—C5	1.230 (4)	C18A—C19A	1.379 (8)
O8—C9	1.336 (3)	C18A—H181	0.9500
O8—C7	1.456 (3)	C19A—C20	1.376 (8)
O9—C9	1.212 (4)	C19A—H191	0.9500
O12—C12	1.235 (4)	C18B—C19B	1.376 (13)
N4—C5	1.333 (4)	C18B—H182	0.9500
N4—C3	1.451 (4)	C19B—C20	1.375 (13)
N4—H4	0.80 (3)	C19B—H192	0.9500
N11—C12	1.328 (4)	C20—C21B	1.376 (13)
N11—C10	1.450 (4)	C20—C21A	1.377 (8)
N11—H11	0.85 (4)	C20—H201	0.9500
C2—C3	1.535 (4)	C20—H202	0.9500
C3—C15	1.527 (4)	C21A—C22A	1.380 (7)
C3—C16	1.530 (4)	C21A—H211	0.9500
C5—C6	1.531 (5)	C22A—H221	0.9500
C6—C7	1.507 (4)	C21B—C22B	1.377 (13)
C6—C17	1.525 (4)	C21B—H212	0.9500
C6—H6	1.0000	C22B—H222	0.9500
C7—H71	0.9900	C23—H231	0.9800
C7—H72	0.9900	C23—H232	0.9800
C9—C10	1.529 (4)	C23—H233	0.9800
C10—C23	1.531 (5)	C24—H241	0.9800
C10—C24	1.532 (4)	C24—H242	0.9800
C12—C13	1.528 (4)	C24—H243	0.9800
C13—C14	1.517 (4)	C25—C26	1.385 (4)
C13—C25	1.524 (4)	C25—C30	1.388 (4)
C13—H13	1.0000	C26—C27	1.390 (5)
C14—H141	0.9900	C26—H26	0.9500
C14—H142	0.9900	C27—C28	1.374 (6)
C15—H151	0.9800	C27—H27	0.9500
C15—H152	0.9800	C28—C29	1.379 (6)
C15—H153	0.9800	C28—H28	0.9500
C16—H161	0.9800	C29—C30	1.385 (5)
C16—H162	0.9800	C29—H29	0.9500
C16—H163	0.9800	C30—H30	0.9500
C17—C18B	1.375 (13)
C2—O1—C14	114.9 (2)	H162—C16—H163	109.5
C9—O8—C7	114.7 (2)	C18B—C17—C22B	123 (2)
C5—N4—C3	122.6 (3)	C18A—C17—C22A	116.1 (11)
C5—N4—H4	118 (2)	C18B—C17—C6	117.1 (11)
C3—N4—H4	119 (2)	C22B—C17—C6	120.3 (13)
C12—N11—C10	122.5 (3)	C18A—C17—C6	120.0 (7)
C12—N11—H11	120 (2)	C22A—C17—C6	123.9 (7)
C10—N11—H11	117 (2)	C17—C18A—C19A	122.8 (12)
O2—C2—O1	123.9 (3)	C17—C18A—H181	118.6
O2—C2—C3	124.5 (3)	C19A—C18A—H181	118.6
O1—C2—C3	111.4 (2)	C20—C19A—C18A	118.0 (11)
N4—C3—C15	108.0 (3)	C20—C19A—H191	121.0
N4—C3—C16	110.7 (3)	C18A—C19A—H191	121.0
C15—C3—C16	110.6 (3)	C17—C18B—C19B	118 (2)
N4—C3—C2	109.9 (2)	C17—C18B—H182	121.1
C15—C3—C2	108.8 (2)	C19B—C18B—H182	121.1
C16—C3—C2	108.7 (2)	C20—C19B—C18B	123 (2)
O5—C5—N4	122.8 (3)	C20—C19B—H192	118.4
O5—C5—C6	121.9 (3)	C18B—C19B—H192	118.4
N4—C5—C6	115.3 (3)	C19B—C20—C21B	115 (2)
C7—C6—C17	111.5 (3)	C19A—C20—C21A	122.3 (10)
C7—C6—C5	110.7 (3)	C19A—C20—H201	118.9
C17—C6—C5	109.0 (2)	C21A—C20—H201	118.9
C7—C6—H6	108.5	C19B—C20—H202	122.4
C17—C6—H6	108.5	C21B—C20—H202	122.4
C5—C6—H6	108.5	C20—C21A—C22A	116.8 (12)
O8—C7—C6	107.2 (2)	C20—C21A—H211	121.6
O8—C7—H71	110.3	C22A—C21A—H211	121.6
C6—C7—H71	110.3	C17—C22A—C21A	124.0 (13)
O8—C7—H72	110.3	C17—C22A—H221	118.0
C6—C7—H72	110.3	C21A—C22A—H221	118.0
H71—C7—H72	108.5	C20—C21B—C22B	125 (3)
O9—C9—O8	122.9 (3)	C20—C21B—H212	117.4
O9—C9—C10	124.2 (3)	C22B—C21B—H212	117.4
O8—C9—C10	112.6 (3)	C17—C22B—C21B	116 (3)
N11—C10—C9	110.3 (2)	C17—C22B—H222	122.2
N11—C10—C23	108.4 (3)	C21B—C22B—H222	122.2
C9—C10—C23	107.5 (3)	C10—C23—H231	109.5
N11—C10—C24	110.7 (3)	C10—C23—H232	109.5
C9—C10—C24	109.1 (3)	H231—C23—H232	109.5
C23—C10—C24	110.8 (3)	C10—C23—H233	109.5
O12—C12—N11	122.0 (3)	H231—C23—H233	109.5
O12—C12—C13	121.7 (3)	H232—C23—H233	109.5
N11—C12—C13	116.3 (3)	C10—C24—H241	109.5
C14—C13—C25	108.7 (2)	C10—C24—H242	109.5
C14—C13—C12	110.3 (2)	H241—C24—H242	109.5
C25—C13—C12	111.1 (2)	C10—C24—H243	109.5
C14—C13—H13	108.9	H241—C24—H243	109.5
C25—C13—H13	108.9	H242—C24—H243	109.5
C12—C13—H13	108.9	C26—C25—C30	119.1 (3)
O1—C14—C13	107.1 (2)	C26—C25—C13	122.3 (3)
O1—C14—H141	110.3	C30—C25—C13	118.6 (3)
C13—C14—H141	110.3	C25—C26—C27	120.3 (3)
O1—C14—H142	110.3	C25—C26—H26	119.8
C13—C14—H142	110.3	C27—C26—H26	119.8
H141—C14—H142	108.5	C28—C27—C26	120.2 (3)
C3—C15—H151	109.5	C28—C27—H27	119.9
C3—C15—H152	109.5	C26—C27—H27	119.9
H151—C15—H152	109.5	C27—C28—C29	119.8 (3)
C3—C15—H153	109.5	C27—C28—H28	120.1
H151—C15—H153	109.5	C29—C28—H28	120.1
H152—C15—H153	109.5	C28—C29—C30	120.4 (3)
C3—C16—H161	109.5	C28—C29—H29	119.8
C3—C16—H162	109.5	C30—C29—H29	119.8
H161—C16—H162	109.5	C29—C30—C25	120.2 (3)
C3—C16—H163	109.5	C29—C30—H30	119.9
H161—C16—H163	109.5	C25—C30—H30	119.9
C14—O1—C2—O2	7.3 (4)	N11—C12—C13—C25	−111.7 (3)
O1—C2—C3—N4	51.6 (3)	C25—C13—C14—O1	173.4 (2)
C2—C3—N4—C5	42.9 (4)	C7—C6—C17—C18B	−119.9 (15)
C3—N4—C5—C6	173.7 (2)	C5—C6—C17—C18B	117.6 (15)
N4—C5—C6—C7	126.5 (3)	C7—C6—C17—C22B	56.4 (19)
C5—C6—C7—O8	−63.0 (3)	C5—C6—C17—C22B	−66.1 (19)
C6—C7—O8—C9	179.9 (2)	C7—C6—C17—C18A	−142.6 (8)
C7—O8—C9—C10	−178.2 (2)	C5—C6—C17—C18A	94.9 (8)
O8—C9—C10—N11	48.8 (3)	C7—C6—C17—C22A	37.9 (9)
C9—C10—N11—C12	44.2 (3)	C5—C6—C17—C22A	−84.6 (9)
C10—N11—C12—C13	173.8 (3)	C22A—C17—C18A—C19A	−2.8 (12)
N11—C12—C13—C14	127.6 (3)	C6—C17—C18A—C19A	177.6 (6)
C12—C13—C14—O1	−64.5 (3)	C17—C18A—C19A—C20	1.1 (12)
C13—C14—O1—C2	179.3 (2)	C22B—C17—C18B—C19B	1 (3)
C14—O1—C2—C3	−177.6 (2)	C6—C17—C18B—C19B	176.9 (15)
C5—N4—C3—C15	161.5 (3)	C17—C18B—C19B—C20	5 (3)
C5—N4—C3—C16	−77.2 (4)	C18B—C19B—C20—C21B	−4 (3)
O2—C2—C3—N4	−133.4 (3)	C18A—C19A—C20—C21A	1.0 (11)
O2—C2—C3—C15	108.5 (3)	C19A—C20—C21A—C22A	−1.1 (12)
O1—C2—C3—C15	−66.5 (3)	C18A—C17—C22A—C21A	2.7 (14)
O2—C2—C3—C16	−12.1 (4)	C6—C17—C22A—C21A	−177.8 (8)
O1—C2—C3—C16	172.9 (3)	C20—C21A—C22A—C17	−0.8 (15)
C3—N4—C5—O5	−5.2 (4)	C19B—C20—C21B—C22B	−2 (3)
O5—C5—C6—C7	−54.6 (4)	C18B—C17—C22B—C21B	−6 (3)
O5—C5—C6—C17	68.4 (4)	C6—C17—C22B—C21B	177.8 (17)
N4—C5—C6—C17	−110.6 (3)	C20—C21B—C22B—C17	7 (4)
C17—C6—C7—O8	175.5 (2)	C14—C13—C25—C26	72.2 (4)
C7—O8—C9—O9	6.9 (4)	C12—C13—C25—C26	−49.4 (4)
C12—N11—C10—C23	161.7 (3)	C14—C13—C25—C30	−104.4 (3)
C12—N11—C10—C24	−76.6 (3)	C12—C13—C25—C30	134.0 (3)
O9—C9—C10—N11	−136.3 (3)	C30—C25—C26—C27	−0.7 (5)
O9—C9—C10—C23	105.6 (3)	C13—C25—C26—C27	−177.2 (3)
O8—C9—C10—C23	−69.2 (3)	C25—C26—C27—C28	−0.7 (6)
O9—C9—C10—C24	−14.5 (4)	C26—C27—C28—C29	1.4 (6)
O8—C9—C10—C24	170.6 (3)	C27—C28—C29—C30	−0.7 (6)
C10—N11—C12—O12	−6.6 (4)	C28—C29—C30—C25	−0.8 (5)
O12—C12—C13—C14	−52.0 (3)	C26—C25—C30—C29	1.5 (5)
O12—C12—C13—C25	68.6 (4)	C13—C25—C30—C29	178.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4···O2^i	0.80 (3)	2.37 (3)	3.138 (3)	160 (3)
N11—H11···O9^ii	0.85 (4)	2.16 (4)	2.983 (4)	161 (3)

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