Desvenlafaxine succinate mono­hydrate

The title compound {systematic name: [2-(1-hydroxy­cyclo­hex­yl)-2-(4-hydroxy­phen­yl)eth­yl]dimethyl­ammonium 3-carboxy­propanoate monohydrate}, C₁₆H₂₆NO₂⁺·C₄H₅O₄^-·H₂O, is a succinate salt of O-desmethyl­venlafaxine (desvenlafaxine). The present structure is one of four reported polymorphs of this salt, which is a new anti­depressant drug. The carboxyl group of the succinate anion adopts a rare anti conformation and is engaged in a very short O-H...O^- hydrogen-bond contact. Both cations and anions are involved separately in the formation of distinct O-H...O hydrogen-bonded networks. Desvenlafaxine cations and water mol­ecules self-assemble to generate a honeycomb layer, while the succinate anions form a linear tape structure. These hydrogen-bonded networks are inter­linked via N-H...O and O-H...O hydrogen bonds. The hydrogen-bonding network is so strong that desolvation and melting occur together at approximately 402 K. Thus, the crystal structure may be used to understand the thermal stability and solubility of the compound at the mol­ecular level.

S1. Comment

The title compound, (I), is a monohydrate of the 1:1 salt of 1-[2-dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol with succinic acid. Desvenlafaxine succinate is an antidepressant drug belonging to the class of serotonin–norepinephrine reuptake inhibitors and is expected to be marketed as Pristiq (Deecher et al., 2006). It is a racemic mixture and is reported to exist in four crystalline polymorphs (Hadfield et al., 2004). The crystalline form reported here is Form I.

The asymmetric unit consists of one desvenalfaxine cation, a succinate anion and a water molecule (Fig. 1). The dimethylaminomethyl group of the desvenlafaxine molecule is protonated by succinic acid. The hydroxy group lies perpendicular to the cyclohexane ring, while the bulkier dimethylaminohydroxyphenylethyl group is coplanar with this ring, adopting a rigid T-shaped geometry with the dimethylaminomethyl and cyclohexanol groups representing the arms. The cyclohexyl ring assumes a chair conformation, with the endocyclic bond angles close to the tetrahedral value [109.5 (2)–112.7 (2)°] and with average endocyclic torsion angle values of about ±55°. Interestingly, the carboxyl group adopts the uncommon anti conformation (i.e. the acid H atom points away from the carbonyl O atom). The occurrence and energetics of this conformation have been discussed by DeVita Dufort et al. (2007).

Desvenlafaxine cations and water molecules self-assemble to form a honeycomb-like hydrogen-bonded network parallel to the ab crystallographic plane, in such a way that all the dimethylammonium groups point in one direction perpendicular to the hydrogen-bonded layer, while all the cyclohexane groups point in the opposite direction, generating a series of hydrophilic and hydrophobic grooves on opposite sides of the hydrogen-bonded layer (Fig. 2). The cations and water molecules in this layer are connected by infinite (OH)_phenyl···(OH)_cyclohexyl···(OH)_water···(OH)_phenyl hydrogen-bonded chains running parallel to [100] (entries 1–3, respectively, Table 1). The hydrophilic grooves are lined with the OH and NH⁺ groups of water molecules and desvenlafaxine cations, respectively. Infinite hydrogen-bonded tapes of succinate anions connected by a short O—H···O^- hydrogen bond (entry 4, Table 1) fill these hydrophilic grooves. The succinate anion also forms hydrogen-bonding contacts with both NH⁺ and OH groups, coating the grooves (entries 5–7, Table 1). In addition, there is a C—H···O hydrogen bond with the N-methyl group (entry 8 [or entry 10?], Table 1, Desiraju & Steiner, 1999). Thus, in order to maximize the attractive interactions, the carboxylic acid group must adopt the anti conformation. The inversion-related layers stack to form alternating hydrophobic and hydrophilic layers along [001], with layer thicknesses of about 7 and 11 Å, respectively. The hydrophobic grooves interdigitate with one another, while the hydrophilic grooves filled with the succinate anion tapes do not. As a result, the hydrophobic layer is thinner than the hydrophilic layer.

The water molecules are so tightly held in the crystal structure that desolvation and melting occur almost simultaneously. The differential scanning calorimetry trace shows a single endotherm with a mid-point temperature of 401.8 K (heating rate 10 K min^-1). The water molecule is involved in the formation of as many as three strong hydrogen bonds, bridging the desvenlafaxine ions and linking the desvenlafaxine cations and succinate anions (Fig. 2 and Table 1). In addition, it also accepts a C—H···O hydrogen bond from atom C14 (entry 9, Table 1). The donor and acceptor groups around the water molecules are in nearly ideal tetrahedral positions. Another interesting feature is the occurrence of a short O—H···O^- hydrogen bond between the indistinguishable carboxylic acid and carboxylate groups. Thus, one C—O bond [C17—O3 = 1.286 (3) Å and C20—O5 = 1.291 (3) Å] is longer than the other [C17—O4 = 1.224 (4) Å and C20—O6 = 1.234 (4) Å] on each acid group. On the other hand, if the acidic H atom were owned completely by one acid group, one would expect two sets of C—O bond distances, one corresponding to the carboxylic acid group (one C—O bond distance much longer than the other) and the other corresponding to a delocalized carboxylate group (nearly equivalent C—O distances). The acidic H atom is actually shared between atoms O3 and O5 in the short hydrogen bond. Such interactions are known as low-barrier hydrogen bonds and are considered to be very strong (Vishweshwar et al., 2004; Hibbert & Emsley, 1990).

Related literature

For related literature, see: Deecher et al. (2006); Desiraju & Steiner (1999); DeVita Dufort et al. (2007); Hadfield et al. (2004); Hibbert & Emsley (1990); Vishweshwar et al. (2004).

S2. Experimental

The title compound was synthesized and purified in our laboratory by following Dr Reddy's Laboratories' (proprietary) process. Diffraction quality single crystals of (I) were obtained by slow evaporation from an isopropyl alcohol solution under ambient conditions.

S3. Refinement

H atoms bound to C atoms were positioned geometrically [C—H = 0.95 Å and U_iso(H) = 1.2U_eq(C)] and refined using a riding model. The positions of H atoms bound to N and O atoms were refined [U_iso(H) = 1.5U_eq(N,O) {please check; values in CIF do not agree with this}].

Computing details

Data collection: CrystalClear (Rigaku, 1999); cell refinement: CrystalClear (Rigaku, 1999); data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), X-SEED (Barbour, 2001) and Mercury (Macrae et al., 2006; software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004).

Figures

	Fig. 1. An ORTEPIII drawing (Burnett & Johnson, 1996) of the title compound, showing the atomic numbering. Displacement ellipsoids of non-H atoms are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The packing of (I), showing a honeycomb layer parallel to the ab crystallographic plane consisting of desvenlafaxine cations and water molecules connected by O—H···O hydrogen bonds (dashed lines). Infinite O—H···O hydrogen-bonded tapes of succinate anions fill the hydrophilic grooves. Also note the bifurcated N—H···O hydrogen bonds between the cations and anions.

[2-(1-hydroxycyclohexyl)-2-(4-hydroxyphenyl)ethyl]dimethylammonium 3-carboxypropanoate monohydrate

Crystal data

C16H26NO2^+·C4H5O4^−·H2O	Z = 2
Mr = 399.48	F(000) = 432.00
Triclinic, P1	Dx = 1.270 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71070 Å
a = 6.542 (5) Å	Cell parameters from 3898 reflections
b = 9.324 (8) Å	θ = 1.2–28.7°
c = 17.631 (14) Å	µ = 0.10 mm^−1
α = 77.594 (17)°	T = 298 K
β = 84.00 (2)°	Block, colorless
γ = 89.39 (2)°	0.50 × 0.30 × 0.12 mm
V = 1044.5 (15) Å^3

Data collection

Rigaku Mercury diffractometer	2265 reflections with F^2 > 2σ(F^2)
Detector resolution: 7.31 pixels mm^-1	Rint = 0.045
ω scans	θmax = 29.3°
Absorption correction: multi-scan (Jacobson, 1998)	h = −8→6
Tmin = 0.964, Tmax = 0.989	k = −12→12
11016 measured reflections	l = −22→22
3995 independent reflections

Refinement

Refinement on F^2	Chebychev polynomial with 3 parameters: 4182.1300 5759.2800 1682.9900 [Carruthers, J. R. & Watkin, D. J. (1979). Acta Cryst. A35, 698–699]
R[F^2 > 2σ(F^2)] = 0.065	(Δ/σ)max < 0.001
wR(F^2) = 0.101	Δρmax = 0.36 e Å^−3
S = 1.25	Δρmin = −0.34 e Å^−3
3875 reflections	Extinction correction: Larson, A. C. (1970). Crystallographic Computing, edited by F. R. Ahmed, p. 291-294. Munksgaard: Copenhagen.
299 parameters	Extinction coefficient: 410 (24)
H atoms treated by a mixture of independent and constrained refinement

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement was performed using reflections with F² > 0.5 σ(F²). The weighted R-factor (wR) and goodness of fit (S) are based on F². R-factor (gt) are based on F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

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

	x	y	z	Uiso*/Ueq
O1	0.3698 (3)	0.8465 (2)	0.18421 (13)	0.0558 (7)
O2	0.0718 (3)	0.04218 (18)	0.16404 (11)	0.0443 (6)
N1	0.2141 (3)	0.1799 (2)	0.36417 (13)	0.0483 (8)
C1	0.1866 (4)	0.4083 (2)	0.21436 (14)	0.0374 (8)
C2	0.0427 (4)	0.5173 (2)	0.21364 (15)	0.0416 (8)
C3	0.0986 (4)	0.6638 (2)	0.20413 (15)	0.0424 (8)
C4	0.3048 (4)	0.7023 (2)	0.19388 (15)	0.0422 (8)
C5	0.4512 (4)	0.5960 (2)	0.19441 (16)	0.0467 (9)
C6	0.3923 (4)	0.4499 (2)	0.20530 (15)	0.0446 (9)
C7	0.1178 (4)	0.2495 (2)	0.22566 (15)	0.0412 (8)
C8	0.1227 (3)	0.1966 (2)	0.14596 (15)	0.0374 (8)
C9	0.3308 (4)	0.2116 (3)	0.09773 (15)	0.0447 (9)
C10	0.3262 (4)	0.1621 (3)	0.02144 (17)	0.0584 (11)
C11	0.1667 (5)	0.2455 (4)	−0.02677 (18)	0.0714 (11)
C12	−0.0456 (5)	0.2316 (3)	0.01962 (18)	0.0653 (12)
C13	−0.0377 (4)	0.2802 (2)	0.09704 (16)	0.0495 (9)
C14	0.2282 (4)	0.1421 (2)	0.28475 (15)	0.0458 (9)
C15	0.3259 (5)	0.0671 (3)	0.41607 (18)	0.0654 (11)
C16	0.0015 (5)	0.1928 (3)	0.39983 (18)	0.0619 (11)
O3	0.2483 (3)	0.4888 (2)	0.39876 (12)	0.0591 (8)
O4	0.5369 (3)	0.3750 (2)	0.37900 (14)	0.0642 (8)
O5	1.1001 (3)	0.7299 (2)	0.40258 (14)	0.0662 (8)
O6	0.8204 (3)	0.8619 (2)	0.38551 (14)	0.0655 (8)
C17	0.4458 (4)	0.4846 (3)	0.39106 (16)	0.0458 (9)
C18	0.5596 (4)	0.6220 (2)	0.39617 (18)	0.0493 (9)
C19	0.7874 (3)	0.6023 (2)	0.39817 (16)	0.0445 (8)
C20	0.9061 (4)	0.7418 (3)	0.39506 (17)	0.0478 (10)
O7	0.6943 (3)	0.9781 (2)	0.24101 (16)	0.0718 (10)
H1	0.265 (4)	0.916 (3)	0.1776 (16)	0.0658*
H2	−0.09900	0.49100	0.22020	0.0510*
H3	−0.00320	0.73720	0.20430	0.0520*
H5	0.59260	0.62310	0.18770	0.0560*
H6	0.49460	0.37650	0.20660	0.0540*
H7	−0.02240	0.24520	0.24660	0.0500*
H11	0.282 (4)	0.270 (3)	0.3644 (16)	0.0604*
H21	−0.056 (4)	0.028 (2)	0.1848 (15)	0.0479*
H91	0.37260	0.31190	0.08550	0.0540*
H92	0.42760	0.15480	0.12760	0.0540*
H101	0.45800	0.17500	−0.00760	0.0700*
H102	0.28900	0.06090	0.03360	0.0700*
H111	0.20620	0.34620	−0.04070	0.0870*
H112	0.16100	0.20860	−0.07270	0.0870*
H121	−0.08820	0.13160	0.03100	0.0810*
H122	−0.14130	0.28970	−0.01030	0.0810*
H131	−0.16870	0.26440	0.12650	0.0600*
H132	−0.00420	0.38200	0.08530	0.0600*
H141	0.36890	0.14260	0.26490	0.0560*
H142	0.17140	0.04650	0.29060	0.0550*
H151	0.23340	−0.01030	0.44150	0.0790*
H152	0.38140	0.10940	0.45410	0.0790*
H153	0.43420	0.02950	0.38600	0.0790*
H161	−0.04150	0.29150	0.38450	0.0760*
H162	−0.00220	0.16690	0.45510	0.0760*
H163	−0.08800	0.12950	0.38280	0.0760*
H31	0.172 (5)	0.603 (4)	0.400 (2)	0.0979*
H181	0.50590	0.65310	0.44210	0.0600*
H182	0.53930	0.69650	0.35160	0.0600*
H191	0.80860	0.53510	0.44540	0.0540*
H192	0.83820	0.56170	0.35500	0.0540*
H71	0.735 (6)	0.958 (4)	0.292 (2)	0.1089*
H72	0.638 (5)	0.918 (4)	0.225 (2)	0.0796*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0507 (12)	0.0283 (9)	0.0887 (15)	−0.0013 (8)	−0.0156 (10)	−0.0091 (9)
O2	0.0476 (10)	0.0280 (8)	0.0590 (12)	−0.0020 (8)	−0.0055 (9)	−0.0129 (8)
N1	0.0640 (15)	0.0383 (12)	0.0442 (13)	−0.0139 (11)	−0.0043 (11)	−0.0124 (10)
C1	0.0466 (15)	0.0294 (12)	0.0381 (13)	0.0007 (10)	−0.0075 (11)	−0.0099 (10)
C2	0.0416 (14)	0.0313 (12)	0.0541 (16)	−0.0015 (11)	−0.0113 (12)	−0.0108 (11)
C3	0.0434 (15)	0.0304 (12)	0.0556 (16)	0.0072 (11)	−0.0110 (12)	−0.0116 (11)
C4	0.0526 (16)	0.0249 (12)	0.0494 (15)	−0.0002 (11)	−0.0094 (12)	−0.0064 (10)
C5	0.0391 (15)	0.0368 (14)	0.0643 (18)	0.0027 (11)	−0.0069 (12)	−0.0108 (12)
C6	0.0500 (16)	0.0289 (12)	0.0564 (17)	0.0083 (11)	−0.0081 (13)	−0.0114 (11)
C7	0.0504 (16)	0.0273 (12)	0.0465 (15)	0.0000 (11)	−0.0032 (12)	−0.0103 (10)
C8	0.0422 (14)	0.0241 (11)	0.0469 (14)	0.0018 (10)	−0.0083 (11)	−0.0080 (10)
C9	0.0429 (15)	0.0438 (15)	0.0481 (15)	0.0025 (11)	−0.0018 (12)	−0.0129 (12)
C10	0.062 (2)	0.0628 (19)	0.0514 (18)	0.0045 (15)	0.0032 (14)	−0.0192 (14)
C11	0.093 (2)	0.077 (2)	0.0484 (18)	0.011 (2)	−0.0175 (18)	−0.0182 (16)
C12	0.071 (2)	0.065 (2)	0.066 (2)	0.0111 (17)	−0.0308 (17)	−0.0170 (16)
C13	0.0532 (17)	0.0400 (15)	0.0570 (17)	0.0069 (12)	−0.0135 (13)	−0.0107 (12)
C14	0.0564 (17)	0.0340 (13)	0.0487 (15)	−0.0016 (12)	−0.0077 (13)	−0.0118 (11)
C15	0.086 (2)	0.0531 (18)	0.0587 (19)	−0.0045 (17)	−0.0212 (17)	−0.0085 (15)
C16	0.070 (2)	0.0548 (18)	0.065 (2)	−0.0037 (15)	−0.0028 (16)	−0.0238 (15)
O3	0.0453 (12)	0.0586 (13)	0.0761 (15)	−0.0156 (9)	−0.0085 (10)	−0.0184 (11)
O4	0.0614 (13)	0.0407 (11)	0.0961 (17)	−0.0066 (10)	−0.0211 (11)	−0.0204 (11)
O5	0.0439 (12)	0.0608 (13)	0.1017 (18)	−0.0105 (10)	−0.0107 (11)	−0.0330 (12)
O6	0.0616 (13)	0.0435 (12)	0.0986 (17)	−0.0073 (10)	−0.0204 (12)	−0.0250 (11)
C17	0.0504 (17)	0.0394 (14)	0.0483 (16)	−0.0081 (12)	−0.0122 (12)	−0.0069 (12)
C18	0.0446 (15)	0.0401 (14)	0.0663 (19)	−0.0092 (12)	−0.0084 (13)	−0.0165 (13)
C19	0.0413 (14)	0.0423 (14)	0.0515 (16)	−0.0067 (11)	−0.0007 (12)	−0.0150 (12)
C20	0.0495 (17)	0.0439 (16)	0.0543 (17)	−0.0096 (13)	−0.0056 (13)	−0.0194 (12)
O7	0.0540 (14)	0.0689 (16)	0.0901 (19)	−0.0141 (11)	−0.0125 (12)	−0.0088 (13)

Geometric parameters (Å, º)

O1—C4	1.384 (3)	C2—H2	0.9500
O2—C8	1.441 (3)	C3—H3	0.9500
O1—H1	0.94 (3)	C5—H5	0.9500
O2—H21	0.88 (3)	C6—H6	0.9500
O3—C17	1.286 (3)	C7—H7	0.9500
O4—C17	1.224 (4)	C9—H92	0.9500
O5—C20	1.291 (3)	C9—H91	0.9500
O6—C20	1.234 (4)	C10—H101	0.9500
O3—H31	1.18 (4)	C10—H102	0.9500
O5—H31^i	1.28 (4)	C11—H112	0.9500
O7—H71	0.94 (4)	C11—H111	0.9500
O7—H72	0.79 (4)	C12—H122	0.9500
N1—C16	1.480 (4)	C12—H121	0.9500
N1—C14	1.509 (4)	C13—H132	0.9500
N1—C15	1.479 (4)	C13—H131	0.9500
N1—H11	0.96 (3)	C14—H142	0.9500
C1—C6	1.388 (4)	C14—H141	0.9500
C1—C2	1.377 (3)	C15—H153	0.9500
C1—C7	1.518 (3)	C15—H152	0.9500
C2—C3	1.388 (3)	C15—H151	0.9500
C3—C4	1.383 (4)	C16—H161	0.9500
C4—C5	1.370 (3)	C16—H162	0.9500
C5—C6	1.387 (3)	C16—H163	0.9500
C7—C14	1.518 (4)	C17—C18	1.513 (4)
C7—C8	1.583 (4)	C18—C19	1.503 (4)
C8—C13	1.528 (4)	C19—C20	1.510 (4)
C8—C9	1.519 (4)	C18—H181	0.9500
C9—C10	1.516 (4)	C18—H182	0.9500
C10—C11	1.517 (5)	C19—H192	0.9500
C11—C12	1.528 (5)	C19—H191	0.9500
C12—C13	1.534 (4)
C4—O1—H1	114.7 (17)	C9—C10—H101	110.00
C8—O2—H21	110.2 (13)	C9—C10—H102	108.00
C17—O3—H31	117.4 (17)	H101—C10—H102	109.00
C20—O5—H31^i	114.1 (15)	C10—C11—H112	110.00
H71—O7—H72	121 (3)	H111—C11—H112	110.00
C15—N1—C16	110.2 (2)	C10—C11—H111	108.00
C14—N1—C16	114.3 (2)	C12—C11—H112	109.00
C14—N1—C15	108.22 (19)	C12—C11—H111	109.00
C15—N1—H11	104.2 (16)	C11—C12—H121	109.00
C14—N1—H11	113.7 (17)	C13—C12—H122	110.00
C16—N1—H11	105.8 (16)	C13—C12—H121	108.00
C2—C1—C7	120.0 (2)	H121—C12—H122	109.00
C6—C1—C7	122.5 (2)	C11—C12—H122	110.00
C2—C1—C6	117.48 (19)	C12—C13—H131	109.00
C1—C2—C3	122.0 (2)	C12—C13—H132	108.00
C2—C3—C4	119.3 (2)	C8—C13—H132	109.00
O1—C4—C3	121.9 (2)	C8—C13—H131	109.00
C3—C4—C5	120.0 (2)	H131—C13—H132	109.00
O1—C4—C5	118.2 (2)	C7—C14—H141	108.00
C4—C5—C6	119.9 (2)	N1—C14—H142	108.00
C1—C6—C5	121.4 (2)	H141—C14—H142	109.00
C8—C7—C14	111.01 (17)	N1—C14—H141	109.00
C1—C7—C14	114.4 (2)	C7—C14—H142	109.00
C1—C7—C8	112.78 (19)	N1—C15—H151	109.00
O2—C8—C7	107.97 (19)	H151—C15—H153	110.00
O2—C8—C9	105.90 (18)	N1—C15—H153	110.00
C7—C8—C13	109.48 (18)	H151—C15—H152	109.00
O2—C8—C13	109.06 (17)	N1—C15—H152	110.00
C9—C8—C13	109.5 (2)	H152—C15—H153	109.00
C7—C8—C9	114.77 (19)	N1—C16—H163	110.00
C8—C9—C10	112.7 (2)	H161—C16—H162	109.00
C9—C10—C11	111.2 (2)	H162—C16—H163	109.00
C10—C11—C12	111.2 (3)	N1—C16—H162	110.00
C11—C12—C13	110.7 (3)	N1—C16—H161	109.00
C8—C13—C12	112.4 (2)	H161—C16—H163	109.00
N1—C14—C7	113.58 (18)	O3—C17—O4	121.4 (3)
C1—C2—H2	119.00	O4—C17—C18	121.7 (2)
C3—C2—H2	119.00	O3—C17—C18	116.9 (2)
C4—C3—H3	120.00	C17—C18—C19	113.85 (19)
C2—C3—H3	121.00	C18—C19—C20	114.53 (18)
C4—C5—H5	120.00	O6—C20—C19	121.1 (2)
C6—C5—H5	121.00	O5—C20—C19	117.3 (2)
C1—C6—H6	119.00	O5—C20—O6	121.7 (3)
C5—C6—H6	120.00	C17—C18—H182	109.00
C14—C7—H7	106.00	C19—C18—H181	108.00
C1—C7—H7	106.00	C17—C18—H181	109.00
C8—C7—H7	106.00	H181—C18—H182	110.00
C10—C9—H92	109.00	C19—C18—H182	107.00
C8—C9—H92	109.00	C18—C19—H191	108.00
C10—C9—H91	108.00	C18—C19—H192	108.00
C8—C9—H91	109.00	C20—C19—H192	109.00
H91—C9—H92	109.00	H191—C19—H192	109.00
C11—C10—H101	110.00	C20—C19—H191	108.00
C11—C10—H102	108.00
C15—N1—C14—C7	179.6 (2)	C14—C7—C8—C9	−72.5 (3)
C16—N1—C14—C7	56.5 (3)	C14—C7—C8—C13	164.0 (2)
C6—C1—C2—C3	0.1 (4)	C1—C7—C14—N1	55.7 (3)
C7—C1—C2—C3	179.5 (2)	C8—C7—C14—N1	−175.30 (18)
C2—C1—C6—C5	−1.2 (4)	O2—C8—C9—C10	62.1 (3)
C7—C1—C6—C5	179.5 (2)	C7—C8—C9—C10	−179.0 (2)
C2—C1—C7—C8	98.4 (3)	C13—C8—C9—C10	−55.4 (3)
C2—C1—C7—C14	−133.5 (2)	O2—C8—C13—C12	−60.6 (3)
C6—C1—C7—C8	−82.3 (3)	C7—C8—C13—C12	−178.5 (2)
C6—C1—C7—C14	45.8 (3)	C9—C8—C13—C12	54.9 (3)
C1—C2—C3—C4	1.0 (4)	C8—C9—C10—C11	56.5 (3)
C2—C3—C4—O1	−179.9 (2)	C9—C10—C11—C12	−55.4 (3)
C2—C3—C4—C5	−1.0 (4)	C10—C11—C12—C13	54.8 (3)
O1—C4—C5—C6	178.9 (2)	C11—C12—C13—C8	−55.3 (3)
C3—C4—C5—C6	−0.1 (4)	O3—C17—C18—C19	171.7 (2)
C4—C5—C6—C1	1.2 (4)	O4—C17—C18—C19	−9.3 (4)
C1—C7—C8—O2	175.20 (19)	C17—C18—C19—C20	174.1 (2)
C1—C7—C8—C9	57.4 (3)	C18—C19—C20—O5	174.9 (3)
C1—C7—C8—C13	−66.2 (3)	C18—C19—C20—O6	−5.3 (4)
C14—C7—C8—O2	45.4 (2)

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

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2^ii	0.94 (3)	1.72 (3)	2.655 (4)	179 (3)
O2—H21···O7^iii	0.88 (3)	1.83 (3)	2.698 (4)	171 (2)
O7—H72···O1	0.79 (4)	2.13 (3)	2.836 (4)	149 (3)
O3—H31···O5^iv	1.18 (4)	1.28 (4)	2.450 (3)	176 (3)
N1—H11···O3	0.96 (3)	2.25 (3)	3.085 (4)	145 (2)
N1—H11···O4	0.96 (3)	2.01 (3)	2.870 (4)	149 (2)
O7—H71···O6	0.94 (4)	1.84 (4)	2.753 (4)	162 (3)
C10—H102···O2	0.95	2.55	2.881 (4)	101
C14—H142···O2	0.95	2.40	2.788 (4)	104
C16—H163···O6^iii	0.95	2.56	3.386 (5)	145
C14—H141···O7^v	0.95	2.66	3.485 (4)	145

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