(S,S,S,S)-Nebivolol hydro-chloride hemihydrate.

The asymmetric unit of the title hydrated salt, C22H26F2NO4(+)·Cl(-)·0.5H2O, consists of an (S,S,S,S)-nebivolol {nebivol = bis-[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hy-droxy-eth-yl]ammonium} cation, a chloride anion and a half-occupancy water mol-ecule. The dihedral angle between the mean planes of the benzene rings is 50.34 (12)°. The pyran rings adopt half-chair conformations. The crystal packing features O-H⋯O hydrogen bonds and weak N-H⋯Cl, O-H⋯Cl, and O-H⋯Cl inter-actions, producing layers along (010).

Related literature

For the synthesis of the enanti­opure title product, see: Jas et al. (2011 ▶). For a study of related isomers, see: Cini et al. (1990 ▶); Peeters et al. (1993 ▶); Tuchalski et al. (2006 ▶, 2008 ▶). For pharmacological properties of nebivolol, see: Van Lommen et al., (1990 ▶). For distance computations in water mol­ecules, see: Stewart (2009 ▶). For puckering parameters, see: Cremer & Pople, (1975 ▶).

Experimental

Crystal data

C22H26F2NO4 +·Cl−·0.5H2O

M = 450.89

Orthorhombic,

a = 7.5173 (3) Å

b = 8.1495 (3) Å

c = 34.1660 (11) Å

V = 2093.09 (13) Å3

Z = 4

Mo Kα radiation

μ = 0.23 mm−1

T = 115 K

0.10 × 0.07 × 0.02 mm

Data collection

Nonius Kappa APEXII diffractometer

4782 measured reflections

4782 independent reflections

4271 reflections with I > 2σ(I)

R int = 0.000

Refinement

R[F 2 > 2σ(F 2)] = 0.072

wR(F 2) = 0.137

S = 1.27

4782 reflections

290 parameters

3 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.43 e Å−3

Δρmin = −0.31 e Å−3

Absolute structure: Flack (2003 ▶), 1998 Friedel pairs

Flack parameter: 0.02 (12)

Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶); data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 2012 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶).

Click here for additional data file.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812045813/jj2154sup1.cif

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812045813/jj2154Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536812045813/jj2154Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C22H26F2NO4+·Cl−·0.5H2O	F(000) = 948
Mr = 450.89	Dx = 1.431 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2753 reflections
a = 7.5173 (3) Å	θ = 1.0–27.5°
b = 8.1495 (3) Å	µ = 0.23 mm−1
c = 34.1660 (11) Å	T = 115 K
V = 2093.09 (13) Å3	Needle, colourless
Z = 4	0.10 × 0.07 × 0.02 mm

Nonius Kappa APEXII diffractometer	4271 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Horizonally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.6°
Detector resolution: 9 pixels mm-1	h = −9→9
CCD rotation images, thick slices scans	k = −10→10
4782 measured reflections	l = −43→44
4782 independent reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.072	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.137	w = 1/[σ2(Fo2) + (0.P)2 + 4.746P] where P = (Fo2 + 2Fc2)/3
S = 1.27	(Δ/σ)max < 0.001
4782 reflections	Δρmax = 0.43 e Å−3
290 parameters	Δρmin = −0.31 e Å−3
3 restraints	Absolute structure: Flack (2003), 1998 Friedel pairs
0 constraints	Flack parameter: 0.02 (12)
Primary atom site location: structure-invariant direct methods

Experimental. The X-ray, mass spectrometry and NMR analyzes was recorded in the "Pôle Chimie Moléculaire", the technological platform for chemical analysis and molecular synthesis (http://www.wpcm.fr) which relies on the Institute of the Molecular Chemistry of University of Burgundy and Welience"TM", a Burgundy University private subsidiary.The analytical results concerning identity (NMR and optical rotation) and purity (HPLC and chiral HPLC) are listed below.1H and 13C NMR measurements were performed in deuterated DMSO on Bruker Avance III, recorded at 500 MHz and 125 MHz, respectively. DMSO-d6 has been used as internal reference. Chemical shifts (δ) and coupling constants are reported respectively in p.p.m. and hertz (Hz).The optical rotation was measured using a UV Visible Perkin Elmer Lambda 12, polarimeter at 589 nm. High-resolution mass spectrometry (HRMS) was performed in ESI a positive mode. The infrared spectrum (IR) was generated by ATR using a Spectrometer Infrared Avatar 370. A scan range of 4000 - 400 cm-1 was used.(S,S,S,S)-Nebivolol hydrochloride characterization:δ(1H, DMSO-d6, 500 MHz, p.p.m.): 1.77 (2H, m); 1.95 (2H, m); 2.78 (4H, m); 3.21 (4H, m); 4.00 (2H, m); 4.14 (2H, m); 5.79 (2H, bs); 6.76 (2H, dd); 6.92 (4H, m); 8.58 (2H, bs).δ(13C DMSO-d6, 125.76 MHz, p.p.m.): 22.2; 24.1; 49.5; 67.4; 76.8; 113.6 (23.7); 115.2 (22.5); 117.4 (7.5); 123.7 (7.5); 150.5; 155.9 (235.0).[α]29D69.6° (c =0.1, THF/water = 4/1)HRMS (ESI) calcd for C22H25F2NO4[M+H]+ m/z = 406.18244, found m/z = 406.18222.IR (cm-1) 3381, 1492, 1215, 812.

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.4811 (6)	0.0821 (5)	0.97619 (12)	0.0242 (9)
C2	0.3245 (6)	0.1358 (5)	0.96076 (12)	0.0243 (9)
H2	0.2368	0.1833	0.9773	0.029*
C3	0.2926 (5)	0.1210 (5)	0.92044 (12)	0.0211 (8)
C4	0.4248 (5)	0.0511 (5)	0.89753 (11)	0.0199 (8)
C5	0.5850 (5)	0.0016 (5)	0.91376 (12)	0.0230 (8)
H5	0.6748	−0.0436	0.8974	0.028*
C6	0.6152 (5)	0.0173 (5)	0.95347 (12)	0.0264 (9)
H6	0.7250	−0.0156	0.9648	0.032*
C7	0.1216 (5)	0.1825 (5)	0.90272 (12)	0.0237 (8)
H7A	0.0900	0.2896	0.9145	0.028*
H7B	0.0245	0.1041	0.9085	0.028*
C8	0.1409 (6)	0.2016 (5)	0.85853 (11)	0.0209 (8)
H8A	0.0220	0.2149	0.8465	0.025*
H8B	0.2119	0.3008	0.8526	0.025*
C9	0.2313 (5)	0.0525 (5)	0.84167 (11)	0.0212 (8)
H9	0.1593	−0.0468	0.8483	0.025*
C10	0.2528 (6)	0.0615 (5)	0.79760 (12)	0.0202 (8)
H10	0.1331	0.0811	0.7857	0.024*
C11	0.3266 (6)	−0.0984 (5)	0.78125 (11)	0.0217 (9)
H11A	0.4582	−0.0942	0.7813	0.026*
H11B	0.2890	−0.1909	0.7981	0.026*
C12	0.3360 (5)	−0.0161 (5)	0.70943 (11)	0.0200 (8)
H12A	0.4675	−0.0160	0.7110	0.024*
H12B	0.2934	0.0975	0.7135	0.024*
C13	0.2764 (5)	−0.0781 (5)	0.66940 (12)	0.0195 (8)
H13	0.1450	−0.0604	0.6676	0.023*
C14	0.3619 (5)	0.0185 (5)	0.63636 (11)	0.0190 (7)
H14	0.3190	0.1345	0.6377	0.023*
C15	0.3219 (5)	−0.0488 (4)	0.59603 (11)	0.0202 (8)
H15A	0.1915	−0.0528	0.5920	0.024*
H15B	0.3688	−0.1619	0.5938	0.024*
C16	0.4070 (5)	0.0597 (5)	0.56468 (12)	0.0219 (9)
H16A	0.4128	−0.0016	0.5397	0.026*
H16B	0.3319	0.1580	0.5605	0.026*
C17	0.5927 (5)	0.1131 (5)	0.57633 (12)	0.0194 (8)
C18	0.7062 (6)	0.1889 (5)	0.54997 (12)	0.0224 (9)
H18	0.6683	0.2080	0.5238	0.027*
C19	0.8729 (6)	0.2363 (5)	0.56154 (12)	0.0253 (9)
C20	0.9358 (5)	0.2098 (5)	0.59908 (12)	0.0213 (8)
H20	1.0528	0.2418	0.6063	0.026*
C21	0.8238 (5)	0.1355 (5)	0.62564 (12)	0.0192 (8)
H21	0.8637	0.1160	0.6516	0.023*
C22	0.6531 (5)	0.0890 (4)	0.61476 (11)	0.0192 (8)
N1	0.2609 (5)	−0.1263 (4)	0.74016 (10)	0.0207 (7)
H1N	0.279 (6)	−0.221 (6)	0.7347 (13)	0.025*
H2N	0.130 (6)	−0.109 (5)	0.7406 (13)	0.025*
O1	0.4083 (3)	0.0325 (3)	0.85757 (8)	0.0220 (6)
O2	0.3686 (4)	0.1925 (3)	0.78601 (8)	0.0220 (6)
H2A	0.3087	0.2783	0.7825	0.033*
O3	0.3073 (4)	−0.2506 (3)	0.66653 (9)	0.0226 (6)
H3	0.4166	−0.2696	0.6690	0.034*
O4	0.5511 (3)	0.0167 (4)	0.64353 (7)	0.0209 (6)
O5	0.8099 (7)	0.8960 (7)	0.82485 (16)	0.0209 (12)*	0.50
H1O	0.760 (10)	0.996 (5)	0.8325 (18)	0.025*	0.50
H2O	0.824 (11)	0.901 (9)	0.7977 (7)	0.025*	0.50
F1	0.5065 (4)	0.0952 (3)	1.01561 (7)	0.0378 (7)
F2	0.9814 (3)	0.3121 (3)	0.53516 (7)	0.0337 (6)
Cl1	0.85980 (12)	0.99394 (12)	0.73521 (3)	0.0246 (2)

	U11	U22	U33	U12	U13	U23
C1	0.033 (2)	0.021 (2)	0.019 (2)	−0.0051 (18)	−0.0096 (17)	0.0018 (16)
C2	0.036 (2)	0.0172 (19)	0.020 (2)	−0.0008 (17)	0.0037 (18)	−0.0013 (15)
C3	0.025 (2)	0.0158 (18)	0.023 (2)	−0.0002 (16)	−0.0034 (16)	0.0046 (16)
C4	0.024 (2)	0.0164 (18)	0.0198 (19)	−0.0042 (15)	−0.0027 (15)	0.0023 (15)
C5	0.0254 (19)	0.0154 (17)	0.028 (2)	0.0006 (18)	−0.0029 (15)	0.0023 (18)
C6	0.024 (2)	0.024 (2)	0.031 (2)	−0.0009 (19)	−0.0112 (17)	0.0044 (18)
C7	0.018 (2)	0.024 (2)	0.029 (2)	0.0042 (17)	0.0013 (17)	−0.0008 (17)
C8	0.0175 (18)	0.0185 (18)	0.027 (2)	0.0024 (17)	−0.0047 (17)	−0.0017 (16)
C9	0.023 (2)	0.0177 (19)	0.022 (2)	−0.0029 (16)	−0.0046 (17)	0.0019 (16)
C10	0.022 (2)	0.0140 (18)	0.025 (2)	−0.0036 (16)	−0.0039 (16)	0.0000 (16)
C11	0.032 (2)	0.0145 (18)	0.0186 (19)	−0.0021 (17)	−0.0033 (17)	−0.0001 (15)
C12	0.0174 (18)	0.0167 (18)	0.0258 (19)	−0.0008 (17)	−0.0019 (15)	0.0033 (16)
C13	0.0170 (19)	0.0147 (19)	0.027 (2)	0.0007 (15)	0.0007 (16)	−0.0004 (16)
C14	0.0148 (16)	0.0154 (17)	0.0267 (18)	0.0022 (16)	−0.0023 (15)	0.0022 (16)
C15	0.0172 (19)	0.0176 (18)	0.026 (2)	0.0001 (15)	−0.0010 (16)	−0.0018 (16)
C16	0.022 (2)	0.022 (2)	0.0214 (19)	0.0020 (16)	−0.0040 (16)	−0.0003 (16)
C17	0.021 (2)	0.0139 (17)	0.0232 (19)	0.0040 (15)	0.0006 (16)	−0.0033 (15)
C18	0.026 (2)	0.0177 (19)	0.023 (2)	0.0032 (17)	0.0046 (17)	0.0000 (16)
C19	0.024 (2)	0.023 (2)	0.028 (2)	0.0026 (19)	0.0091 (19)	0.0013 (18)
C20	0.0179 (19)	0.0192 (19)	0.027 (2)	−0.0015 (16)	−0.0005 (16)	−0.0034 (17)
C21	0.0170 (19)	0.0158 (18)	0.025 (2)	0.0044 (15)	0.0020 (16)	−0.0004 (15)
C22	0.0209 (19)	0.0123 (17)	0.0243 (19)	0.0022 (16)	0.0019 (17)	−0.0018 (15)
N1	0.0265 (18)	0.0151 (16)	0.0207 (18)	−0.0058 (15)	−0.0025 (15)	−0.0021 (14)
O1	0.0213 (14)	0.0252 (15)	0.0193 (13)	0.0044 (12)	−0.0030 (11)	0.0007 (12)
O2	0.0263 (15)	0.0118 (12)	0.0280 (15)	−0.0005 (12)	−0.0028 (13)	0.0022 (11)
O3	0.0255 (15)	0.0145 (13)	0.0279 (15)	0.0006 (11)	0.0013 (13)	−0.0016 (12)
O4	0.0178 (13)	0.0246 (14)	0.0204 (13)	−0.0001 (12)	−0.0017 (10)	0.0044 (12)
F1	0.0514 (18)	0.0392 (15)	0.0229 (13)	0.0007 (14)	−0.0093 (13)	−0.0011 (12)
F2	0.0313 (14)	0.0413 (15)	0.0285 (14)	−0.0062 (12)	0.0108 (12)	0.0057 (12)
Cl1	0.0251 (4)	0.0197 (4)	0.0289 (5)	0.0010 (4)	−0.0055 (4)	−0.0040 (4)

C1—C2	1.362 (6)	C12—H12B	0.9900
C1—F1	1.365 (5)	C13—O3	1.429 (5)
C1—C6	1.377 (6)	C13—C14	1.519 (5)
C2—C3	1.403 (6)	C13—H13	1.0000
C2—H2	0.9500	C14—O4	1.443 (4)
C3—C4	1.387 (6)	C14—C15	1.513 (5)
C3—C7	1.507 (6)	C14—H14	1.0000
C4—O1	1.379 (5)	C15—C16	1.529 (5)
C4—C5	1.386 (5)	C15—H15A	0.9900
C5—C6	1.382 (5)	C15—H15B	0.9900
C5—H5	0.9500	C16—C17	1.516 (5)
C6—H6	0.9500	C16—H16A	0.9900
C7—C8	1.525 (5)	C16—H16B	0.9900
C7—H7A	0.9900	C17—C18	1.386 (6)
C7—H7B	0.9900	C17—C22	1.403 (5)
C8—C9	1.506 (5)	C18—C19	1.370 (6)
C8—H8A	0.9900	C18—H18	0.9500
C8—H8B	0.9900	C19—F2	1.364 (5)
C9—O1	1.446 (5)	C19—C20	1.384 (6)
C9—C10	1.516 (5)	C20—C21	1.378 (6)
C9—H9	1.0000	C20—H20	0.9500
C10—O2	1.433 (5)	C21—C22	1.389 (5)
C10—C11	1.523 (5)	C21—H21	0.9500
C10—H10	1.0000	C22—O4	1.379 (5)
C11—N1	1.505 (5)	N1—H1N	0.80 (5)
C11—H11A	0.9900	N1—H2N	1.00 (5)
C11—H11B	0.9900	O2—H2A	0.8400
C12—N1	1.492 (5)	O3—H3	0.8400
C12—C13	1.525 (5)	O5—H1O	0.94 (2)
C12—H12A	0.9900	O5—H2O	0.93 (2)
C2—C1—F1	118.5 (4)	O3—C13—C14	113.0 (3)
C2—C1—C6	122.5 (4)	O3—C13—C12	109.9 (3)
F1—C1—C6	118.9 (4)	C14—C13—C12	111.8 (3)
C1—C2—C3	120.0 (4)	O3—C13—H13	107.3
C1—C2—H2	120.0	C14—C13—H13	107.3
C3—C2—H2	120.0	C12—C13—H13	107.3
C4—C3—C2	117.9 (4)	O4—C14—C15	110.3 (3)
C4—C3—C7	121.4 (4)	O4—C14—C13	106.6 (3)
C2—C3—C7	120.7 (4)	C15—C14—C13	113.9 (3)
O1—C4—C5	116.2 (4)	O4—C14—H14	108.6
O1—C4—C3	122.6 (4)	C15—C14—H14	108.6
C5—C4—C3	121.1 (4)	C13—C14—H14	108.6
C6—C5—C4	120.6 (4)	C14—C15—C16	110.2 (3)
C6—C5—H5	119.7	C14—C15—H15A	109.6
C4—C5—H5	119.7	C16—C15—H15A	109.6
C1—C6—C5	117.9 (4)	C14—C15—H15B	109.6
C1—C6—H6	121.0	C16—C15—H15B	109.6
C5—C6—H6	121.0	H15A—C15—H15B	108.1
C3—C7—C8	110.5 (3)	C17—C16—C15	111.5 (3)
C3—C7—H7A	109.5	C17—C16—H16A	109.3
C8—C7—H7A	109.5	C15—C16—H16A	109.3
C3—C7—H7B	109.5	C17—C16—H16B	109.3
C8—C7—H7B	109.5	C15—C16—H16B	109.3
H7A—C7—H7B	108.1	H16A—C16—H16B	108.0
C9—C8—C7	109.8 (3)	C18—C17—C22	118.1 (4)
C9—C8—H8A	109.7	C18—C17—C16	121.6 (4)
C7—C8—H8A	109.7	C22—C17—C16	120.2 (4)
C9—C8—H8B	109.7	C19—C18—C17	120.1 (4)
C7—C8—H8B	109.7	C19—C18—H18	120.0
H8A—C8—H8B	108.2	C17—C18—H18	120.0
O1—C9—C8	111.3 (3)	F2—C19—C18	119.0 (4)
O1—C9—C10	106.3 (3)	F2—C19—C20	118.6 (4)
C8—C9—C10	112.9 (3)	C18—C19—C20	122.4 (4)
O1—C9—H9	108.8	C21—C20—C19	118.0 (4)
C8—C9—H9	108.8	C21—C20—H20	121.0
C10—C9—H9	108.8	C19—C20—H20	121.0
O2—C10—C9	112.0 (3)	C20—C21—C22	120.6 (4)
O2—C10—C11	108.3 (3)	C20—C21—H21	119.7
C9—C10—C11	111.2 (3)	C22—C21—H21	119.7
O2—C10—H10	108.4	O4—C22—C21	116.1 (3)
C9—C10—H10	108.4	O4—C22—C17	123.2 (4)
C11—C10—H10	108.4	C21—C22—C17	120.7 (4)
N1—C11—C10	110.6 (3)	C12—N1—C11	116.2 (3)
N1—C11—H11A	109.5	C12—N1—H1N	110 (3)
C10—C11—H11A	109.5	C11—N1—H1N	108 (3)
N1—C11—H11B	109.5	C12—N1—H2N	107 (3)
C10—C11—H11B	109.5	C11—N1—H2N	107 (3)
H11A—C11—H11B	108.1	H1N—N1—H2N	108 (4)
N1—C12—C13	108.7 (3)	C4—O1—C9	116.2 (3)
N1—C12—H12A	109.9	C10—O2—H2A	109.5
C13—C12—H12A	109.9	C13—O3—H3	109.5
N1—C12—H12B	109.9	C22—O4—C14	115.0 (3)
C13—C12—H12B	109.9	H1O—O5—H2O	107 (3)
H12A—C12—H12B	108.3
F1—C1—C2—C3	−178.7 (4)	C12—C13—C14—C15	174.2 (3)
C6—C1—C2—C3	2.2 (6)	O4—C14—C15—C16	−62.4 (4)
C1—C2—C3—C4	−0.1 (6)	C13—C14—C15—C16	177.8 (3)
C1—C2—C3—C7	−178.9 (4)	C14—C15—C16—C17	41.5 (4)
C2—C3—C4—O1	−179.2 (4)	C15—C16—C17—C18	169.2 (4)
C7—C3—C4—O1	−0.4 (6)	C15—C16—C17—C22	−11.9 (5)
C2—C3—C4—C5	−1.7 (6)	C22—C17—C18—C19	0.7 (6)
C7—C3—C4—C5	177.1 (4)	C16—C17—C18—C19	179.7 (4)
O1—C4—C5—C6	179.1 (4)	C17—C18—C19—F2	−179.3 (4)
C3—C4—C5—C6	1.5 (6)	C17—C18—C19—C20	0.8 (6)
C2—C1—C6—C5	−2.4 (6)	F2—C19—C20—C21	178.9 (3)
F1—C1—C6—C5	178.5 (4)	C18—C19—C20—C21	−1.2 (6)
C4—C5—C6—C1	0.5 (6)	C19—C20—C21—C22	0.1 (6)
C4—C3—C7—C8	−16.2 (5)	C20—C21—C22—O4	−179.6 (3)
C2—C3—C7—C8	162.5 (4)	C20—C21—C22—C17	1.5 (6)
C3—C7—C8—C9	45.4 (5)	C18—C17—C22—O4	179.2 (3)
C7—C8—C9—O1	−61.5 (4)	C16—C17—C22—O4	0.3 (6)
C7—C8—C9—C10	179.1 (3)	C18—C17—C22—C21	−1.8 (6)
O1—C9—C10—O2	−57.6 (4)	C16—C17—C22—C21	179.2 (3)
C8—C9—C10—O2	64.6 (4)	C13—C12—N1—C11	171.7 (3)
O1—C9—C10—C11	63.8 (4)	C10—C11—N1—C12	70.9 (4)
C8—C9—C10—C11	−174.0 (3)	C5—C4—O1—C9	168.0 (3)
O2—C10—C11—N1	−86.3 (4)	C3—C4—O1—C9	−14.4 (5)
C9—C10—C11—N1	150.1 (3)	C8—C9—O1—C4	45.4 (4)
N1—C12—C13—O3	−48.4 (4)	C10—C9—O1—C4	168.7 (3)
N1—C12—C13—C14	−174.6 (3)	C21—C22—O4—C14	160.5 (3)
O3—C13—C14—O4	−72.2 (4)	C17—C22—O4—C14	−20.5 (5)
C12—C13—C14—O4	52.3 (4)	C15—C14—O4—C22	51.4 (4)
O3—C13—C14—C15	49.7 (4)	C13—C14—O4—C22	175.5 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···Cl1i	0.80 (5)	2.75 (5)	3.333 (4)	131 (4)
N1—H2N···Cl1ii	1.00 (5)	2.20 (5)	3.175 (4)	165 (4)
O2—H2A···Cl1iii	0.84	2.25	3.084 (3)	172
O3—H3···O2iii	0.84	2.25	2.963 (4)	143
O3—H3···O1iii	0.84	2.27	2.893 (4)	131
O5—H1O···O3iv	0.94 (2)	2.12 (3)	3.026 (6)	161 (6)
O5—H2O···Cl1	0.93 (2)	2.28 (3)	3.187 (6)	163 (6)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯Cl1i	0.80 (5)	2.75 (5)	3.333 (4)	131 (4)
N1—H2N⋯Cl1ii	1.00 (5)	2.20 (5)	3.175 (4)	165 (4)
O2—H2A⋯Cl1iii	0.84	2.25	3.084 (3)	172
O3—H3⋯O2iii	0.84	2.25	2.963 (4)	143
O3—H3⋯O1iii	0.84	2.27	2.893 (4)	131
O5—H1O⋯O3iv	0.94 (2)	2.12 (3)	3.026 (6)	161 (6)
O5—H2O⋯Cl1	0.93 (2)	2.28 (3)	3.187 (6)	163 (6)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .