Crystal structure and Hirshfeld surface analysis of 1-carb­oxy-2-(3,4-di­hydroxy­phen­yl)ethan-1-aminium chloride 2-ammonio-3-(3,4-di­hydroxy­phen­yl)propano­ate: a new polymorph of l-dopa HCl and isotypic with its bromide counterpart

The crystal structure of new monoclininc polymorph of l-dopa HCl is reported, and hydrogen-bonding inter­actions are discussed.

Abstract

The title mol­ecular salt, C₉H₁₂NO₄ ⁺·Cl⁻·C₉H₁₁NO₄, is isotypic with that of the bromide counterpart [Kathiravan et al. (2016 ▸). Acta Cryst. E72, 1544–1548]. The title salt is a second monoclinic polymorph of the l-dopa HCl structure reported earlier in the monoclinic space group P2₁ [Jandacek & Earle (1971 ▸). Acta Cryst. B27, 841–845; Mostad & Rømming (1974 ▸). Acta Chemica Scand. B28, 1161–1168]. In the title compound, monoclinic space group I2, one of the dopa mol­ecules has a positive charge with a protonated α-amino group and the α-carb­oxy­lic acid group uncharged, while the second dopa mol­ecule has a neutral charge, the α-amino group is protonated and the α-carb­oxy­lic acid is deprotonated. In the previously reported form, a single dopa mol­ecule is observed in which the α-amino group is protonated and the α-carb­oxy­lic acid group is uncharged. The invariant and variations of various types of inter­molecular inter­actions present in these two forms of dopa HCl structures are discussed with the aid of two-dimensional fingerprint plots.

Chemical context  

The aromatic amino acid enzyme, tyrosine-3-hy­droxy­lase, catalyses the conversion of the amino acid l-tyrosine to l-dopa (l-3,4-di­hydroxy­phenyl­alanine). After successful conversion, the l-dopa mol­ecule acts as a precursor for neurotransmitter mol­ecules, such as dopamine, nor­epin­ephrine and epinephrine. The l-dopa mol­ecule is found to be an effective drug in the symptomatic treatment of Parkinson’s disease (Chan et al., 2012 ▸). Polymorphism is very common amongst pharamaceutically important mol­ecules and is responsible for differences in many properties (Bernstein, 2002 ▸, 2011 ▸; Nangia, 2008 ▸; Guranda & Deeva, 2010 ▸). The first monoclinic form (I) [space group P2₁ and z′ = 1] of l-dopa HCl was reported in the 1970s (Jandacek & Earle, 1971 ▸; Mostad & Rømming, 1974 ▸). Herein, we report on the crystal and mol­ecular structure of a second monoclinic polymorph, form (II) (space group I2) of l-dopa HCl. The hydrogen-bonding patterns and the relative contributions of various inter­molecular inter­actions present in forms (I) and (II) are compared.

Structural commentary  

The asymmetric unit of the title compound, (II), is illustrated in Fig. 1 ▸. It consists of two dopa mol­ecules, and a Cl⁻ anion located on a twofold rotation axis. As observed in the isotypic l-dopa HBr mol­ecular salt (III) (Kathiravan et al., 2016 ▸), one of the dopa mol­ecules is in the zwitterionic form and the other in the cationic form. In the cationic dopa mol­ecule, the α-amino group is protonated and carries a positive charge and the hydrogen atom (H4O) of the α-carb­oxy­lic acid group is located in a general position and was refined with 50% occupancy.

Figure 1.

The mol­ecular structure of the title mol­ecular salt, (II), showing the atom labelling scheme [symmetry code: ($) −x + 3, y, −z + 1]. Displacement ellipsoids are drawn at the 50% probability level.

The crystal structures of l-dopa (Mostad et al., 1971 ▸), its hydro­chloride form (I) (Jandacek & Earle, 1971 ▸; Mostad & Rømming, 1974), the hydro­bromide form (III) (Kathiravan et al., 2016 ▸) and the dihydrate form (André & Duarte, 2014 ▸), have been reported. The dihydrate form of dopa crystallizes in the ortho­rhom­bic space group P2₁2₁2₁ with a single dopa mol­ecule in its zwitterionic form. The free dopa mol­ecule and its hydro­chloride form (I) crystallized in the monoclinic space group P2₁. In the l-dopa structure, the dopa mol­ecule is in the zwitterionic form, while in the latter the α-amino group is proton­ated and the α-carb­oxy­lic acid is neutral. As mentioned earlier (Kathiravan et al., 2016 ▸), the deposited coordinates of the l-dopa HCl structure belong to the R configuration. Therefore, the l-dopa HCl structure was inverted and the inverted model used for superposition. As shown in Fig. 2 ▸, one of the dopa mol­ecules of the title mol­ecular salt (II) is superimposed with the inverted model of l-dopa HCl (I) and one of the dopa mol­ecules of the isotypic Br compound (III). The r.m.s. deviation of the former pair is 0.105 Å while for the latter pair it is calculated to be 0.094 Å.

Figure 2.

Structural superimposition of cationic dopa mol­ecules in (II) (red), bromide counterpart (green) and form (I) l-dopa HCl (blue).

Supra­molecular features  

The crystal structure of the title mol­ecular salt (II) displays a network of inter­molecular N—H⋯Cl, N—H⋯O and O—H⋯O hydrogen bonds (Table 1 ▸), producing a three-dimensional framework (Fig. 3 ▸). It is of inter­est to note that the N—H⋯O and O—H⋯O hydrogen-bonding geometries in the title compound are slightly different when compared to its isotypic bromide counterpart (III) (Kathiravan et al., 2016 ▸). A short inter­molecular O—H⋯O hydrogen bond links the carb­oxy­lic acid group of a dopa mol­ecule with the carboxyl­ate group of an adjacent dopa mol­ecule. This inter­action produces dopa dimers that are arranged as ribbons propagating along the b axis (Fig. 3 ▸). As observed in the bromide counterpart (III), the protonated amino group acts as a threefold donor for three inter­molecular hydrogen bonds, two of them with Cl⁻ anions and one with the carbonyl oxygen atom, O3, of the dopa acid group. One of the characteristic features observed in many amino acid–carb­oxy­lic acid/metal complexes (Sharma et al., 2006 ▸; Selvaraj et al., 2007 ▸; Balakrishnan, Ramamurthi & Thamotharan et al., 2013 ▸; Balakrishnan, Ramamurthi, Jeyakanthan et al., 2013 ▸; Sathiskumar et al., 2015a ▸,b ▸,c ▸; Revathi et al., 2015 ▸) is that the amino acid mol­ecules aggregate in head-to-tail sequences of the type ⋯NH₃ ⁺—CHR—COO⁻⋯NH₃ ⁺—CHR—COO⁻⋯ in which α-amino and α-carboxyl­ate groups are brought into periodic hydrogen-bonded proximity in a peptide-like arrangements. Similar arrangements (as layers) are observed in the title compound, in which α-amino (atom N1) and α-carboxyl­ate (atom O3) groups inter­act via an N—H⋯O hydrogen bond. Adjacent layers are inter­connected by strong O—H⋯O hydrogen bonds. The former N—H⋯O and the latter O—H⋯O inter­actions collectively form an (18) ring motif (Fig. 4 ▸). Similar inter­actions are presented in dopa and the HCl form (I).

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O3i	0.82	1.98	2.746 (2)	155
O2—H2O⋯O1ii	0.82	2.33	2.999 (2)	140
O2—H2O⋯O2ii	0.82	2.16	2.8730 (8)	146
O4—H4O⋯O4iii	0.90 (3)	1.50 (3)	2.373 (2)	161 (8)
N1—H1A⋯Cl1iv	0.91 (3)	2.35 (4)	3.249 (2)	167 (3)
N1—H1B⋯Cl1	0.89 (3)	2.31 (3)	3.178 (2)	166 (2)
N1—H1C⋯O3v	0.90 (3)	1.93 (3)	2.7901 (19)	160 (3)

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

Figure 3.

Crystal packing of the title mol­ecular salt, (II), viewed along the b axis. The hydrogen bonds are shown as dashed lines (see Table 1 ▸), and C-bound H atoms have been omitted for clarity.

Figure 4.

Part of the crystal structure of (II) showing the (18) motifs formed through N—H⋯O and O—H⋯O hydrogen bonds (see Table 1 ▸).

As shown in Table 1 ▸, the amino group (via H1A and H1B) of the dopa mol­ecule participates in N—H⋯Cl inter­actions with two different Cl⁻ anions. As observed in the bromide counterpart (III), these inter­actions inter­connect the cations and anions into a chain of cyclic motifs that enclose (8) rings and runs parallel to the b axis (Fig. 5 ▸ a). Forms (I) and (II) of the dopa HCl structures differ in the formation of cyclic motifs. In form (I), two N—H⋯Cl hydrogen bonds link the cations and anions into a chain. Adjacent chains are inter­connected through O—H⋯Cl inter­actions (carb­oxy­lic acid⋯Cl). Collectively, these inter­actions generate cyclic motifs (Fig. 5 ▸ b).

Figure 5.

(a) Part of the crystal structure of (II) showing the (8) motif formed by inter­molecular N—H⋯Cl hydrogen bonds (see Table 1 ▸), and (b) part of the crystal structure of form (I) dopa HCl showing the cyclic motif formed by N—H⋯Cl and O—H⋯Cl hydrogen bonds.

The side-chain hy­droxy groups (O1—H1O and O2—H2O) of the dopa mol­ecules are involved in O—H⋯O hydrogen-bonding inter­actions, the former with the carbonyl oxygen atom (O3) and the latter in a bifurcated mode with two different hy­droxy (O1 and O2) oxygen atoms of adjacent dopa layers (Fig. 6 ▸). These inter­actions are invariant in the dopa structures reported earlier.

Figure 6.

Adjacent dopa layers are inter­linked by side chain–side chain inter­actions in (II) through inter­molecular O—H⋯O hydrogen bonds (see Table 1 ▸).

Hirshfeld surface analysis  

The Hirshfeld surfaces (HS) and the decomposed two-dimensional fingerprint plots have been generated, using the program CrystalExplorer (Wolff et al., 2012 ▸), to investigate the similarities and differences in the crystal packing amongst polymorphs. The two different views of the HS diagram for the complete unit of dopa mol­ecules along with the Cl⁻ anion and the two-dimensional fingerprint plots are shown in Fig. 7 ▸.

Figure 7.

(a) Two different views of Hirshfeld surfaces of dimeric dopa mol­ecules along with a Cl⁻ anion, (b) two-dimensional fingerprint plots for complete unit of dopa and (c) anionic Cl⁻. Various types of contacts are indicated.

The analysis suggests that the O⋯H contacts contribute more (41.6%) to the crystal packing when compared to other contacts with respect to the dopa mol­ecules in the title compound. The relative contributions of H⋯H, C⋯H and H⋯Cl contacts are 29, 18.6 and 6.2%, respectively, with respect to the complete unit of dopa mol­ecule. These contacts are nearly identical in the case of the bromide counterpart. The H⋯Cl and O⋯Cl contacts contributions to the Hirshfeld surface area for the Cl ion are 71.9 and 13.7%, respectively. In the bromide counterpart (III), the corres­ponding contacts are found to be 64.1 (H⋯Br) and 10.2% (O⋯Br). It is clearly seen that these contacts are lower in the bromide counterpart (III) when compared to the title salt (II).

In form (I) of the dopa HCl structure, the relative contributions of O⋯H, H⋯H, C⋯H and H⋯Cl contacts are 40.5, 25.2, 17.1 and 14.1%, respectively, with respect to the cationic dopa mol­ecule. It is worthy to note that O⋯H and H⋯H contacts are reduced by 1.1–3.8% when compared to form (II). The H⋯Cl contact is increased by 7.9% in (I) when compared to (II) of the dopa HCl structure. In (I) anionic Cl⁻, the relative contribution of H⋯Cl contacts is found be 90.4%. This is approximately 18.5 and 26% higher when compared to (II) and its bromide counterpart (III). These contacts are used to discriminate between forms (I) and (II).

Synthesis and crystallization  

l-dopa and HCl (1:1 molar ratio) were dissolved in double-distilled water and stirred well for 6 h. The mixture was filtered and the filtrate left to evaporate slowly. Colourless block-shaped crystals of the title mol­ecular salt (II) were obtained after a growth period of 15 days.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. Since the title mol­ecular salt (I) is isotypic with its bromide counterpart (III) (Kathiravan et al., 2016 ▸), it was refined with the coordinates of the dopa mol­ecule of the latter as a starting model. The Cl⁻ anion was located from a difference Fourier map. The amino and carb­oxy­lic acid H atoms were located from a difference Fourier map and freely refined. The OH groups of the dopa side chain and C-bound H atoms were treated as riding atoms and included in geometrically calculated positions: C—H = 0.93–0.98 and O—H = 0.82 Å, with U _iso(H) = 1.2U _eq(C) and 1.5U _eq(O). The carb­oxy­lic acid O—H bond length was restrained to 0.90 (2) Å, using a DFIX option.

Table 2. Experimental details.

Crystal data
Chemical formula	C9H12NO4 +·Cl−·C9H11NO4
M r	430.83
Crystal system, space group	Monoclinic, I2
Temperature (K)	293
a, b, c (Å)	6.1768 (3), 5.4349 (3), 28.7651 (16)
β (°)	98.140 (4)
V (Å3)	955.92 (9)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.25
Crystal size (mm)	0.30 × 0.25 × 0.20
Data collection
Diffractometer	Bruker Kappa APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2004 ▸)
T min, T max	0.927, 0.959
No. of measured, independent and observed [I > 2σ(I)] reflections	14303, 2982, 2623
R int	0.024
(sin θ/λ)max (Å−1)	0.777
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.035, 0.094, 1.05
No. of reflections	2982
No. of parameters	151
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.57, −0.21
Absolute structure	Flack x determined using 1021 quotients [(I +) − (I −)]/[(I +) + (I −)] (Parsons et al., 2013 ▸)
Absolute structure parameter	0.033 (17)

Computer programs: APEX2, SAINT and XPREP (Bruker, 2004 ▸), Mercury (Macrae et al., 2006 ▸), SHELXL2014/7 (Sheldrick, 2015 ▸) and publCIF (Westrip, 2010 ▸). Structure solution – isomorphous replacement.

Supplementary Material

CCDC reference: 1511067

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Crystal data

C9H12NO4+·Cl−·C9H11NO4	F(000) = 452
Mr = 430.83	Dx = 1.497 Mg m−3
Monoclinic, I2	Mo Kα radiation, λ = 0.71073 Å
a = 6.1768 (3) Å	Cell parameters from 7161 reflections
b = 5.4349 (3) Å	θ = 3.8–31.1°
c = 28.7651 (16) Å	µ = 0.25 mm−1
β = 98.140 (4)°	T = 293 K
V = 955.92 (9) Å3	Block, colourless
Z = 2	0.30 × 0.25 × 0.20 mm

Data collection

Bruker Kappa APEXII CCD diffractometer	2623 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.024
ω and φ scan	θmax = 33.5°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −8→9
Tmin = 0.927, Tmax = 0.959	k = −7→7
14303 measured reflections	l = −39→40
2982 independent reflections

Refinement

Refinement on F2	2 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.094	w = 1/[σ2(Fo2) + (0.0541P)2 + 0.236P] where P = (Fo2 + 2Fc2)/3
S = 1.05	(Δ/σ)max < 0.001
2982 reflections	Δρmax = 0.57 e Å−3
151 parameters	Δρmin = −0.21 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.

Refinement. Refined as a two-component inversion twin

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.3951 (2)	1.2691 (3)	0.33134 (6)	0.0290 (3)
H1O	0.4509	1.3678	0.3510	0.044*
O2	0.3026 (2)	0.9556 (3)	0.26334 (5)	0.0299 (3)
H2O	0.2767	0.8411	0.2448	0.045*
O3	1.4771 (2)	0.5509 (3)	0.41112 (5)	0.0329 (4)
O4	1.32315 (19)	0.6323 (4)	0.47766 (4)	0.0276 (3)
H4O	1.467 (5)	0.623 (16)	0.489 (3)	0.07 (2)*	0.5
N1	0.9230 (2)	0.6219 (4)	0.44032 (5)	0.0192 (3)
H1A	0.937 (4)	0.751 (7)	0.4608 (11)	0.038 (8)*
H1B	0.933 (3)	0.498 (5)	0.4608 (8)	0.013 (5)*
H1C	0.784 (5)	0.629 (7)	0.4261 (10)	0.043 (7)*
C1	0.8763 (3)	0.8689 (4)	0.34670 (6)	0.0203 (4)
C2	0.7324 (3)	1.0590 (4)	0.35439 (7)	0.0216 (4)
H2	0.7691	1.1672	0.3793	0.026*
C3	0.5418 (3)	1.0860 (3)	0.32596 (6)	0.0202 (4)
C4	0.4932 (3)	0.9175 (4)	0.29009 (6)	0.0207 (4)
C5	0.6340 (3)	0.7289 (4)	0.28237 (7)	0.0237 (4)
H5	0.5961	0.6194	0.2577	0.028*
C6	0.8254 (3)	0.7042 (4)	0.31046 (7)	0.0238 (4)
H6	0.9217	0.5784	0.3056	0.029*
C7	1.0881 (3)	0.8448 (4)	0.37635 (7)	0.0231 (4)
H7A	1.1137	0.9888	0.3963	0.028*
H7B	1.2030	0.8373	0.3566	0.028*
C8	1.0974 (2)	0.6136 (4)	0.40704 (6)	0.0170 (3)
H8	1.0707	0.4692	0.3866	0.020*
C9	1.3196 (3)	0.5949 (4)	0.43384 (6)	0.0193 (4)
Cl1	1.0000	0.12970 (14)	0.5000	0.0428 (2)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0242 (7)	0.0254 (7)	0.0347 (8)	0.0052 (6)	−0.0053 (6)	−0.0063 (6)
O2	0.0210 (6)	0.0325 (8)	0.0314 (8)	0.0000 (6)	−0.0127 (5)	−0.0043 (6)
O3	0.0148 (5)	0.0560 (11)	0.0263 (7)	0.0060 (6)	−0.0025 (5)	−0.0092 (7)
O4	0.0137 (5)	0.0486 (9)	0.0186 (6)	0.0019 (7)	−0.0049 (4)	−0.0034 (7)
N1	0.0122 (6)	0.0258 (8)	0.0185 (7)	−0.0008 (6)	−0.0015 (5)	0.0018 (8)
C1	0.0176 (7)	0.0246 (9)	0.0175 (8)	−0.0016 (7)	−0.0022 (6)	0.0054 (7)
C2	0.0201 (7)	0.0237 (9)	0.0192 (8)	−0.0031 (7)	−0.0028 (6)	−0.0007 (7)
C3	0.0180 (7)	0.0205 (10)	0.0210 (8)	−0.0009 (7)	−0.0007 (6)	0.0025 (7)
C4	0.0178 (7)	0.0240 (9)	0.0188 (8)	−0.0028 (7)	−0.0029 (6)	0.0025 (7)
C5	0.0240 (9)	0.0258 (10)	0.0197 (9)	−0.0012 (8)	−0.0021 (7)	−0.0029 (7)
C6	0.0216 (8)	0.0265 (10)	0.0224 (9)	0.0041 (7)	0.0003 (7)	0.0007 (7)
C7	0.0151 (7)	0.0291 (10)	0.0233 (9)	−0.0042 (7)	−0.0038 (6)	0.0065 (8)
C8	0.0122 (6)	0.0215 (8)	0.0161 (7)	−0.0002 (7)	−0.0022 (5)	−0.0005 (7)
C9	0.0130 (6)	0.0237 (10)	0.0197 (8)	0.0003 (7)	−0.0033 (5)	−0.0012 (7)
Cl1	0.0677 (5)	0.0189 (3)	0.0390 (4)	0.000	−0.0016 (4)	0.000

Geometric parameters (Å, º)

O1—C3	1.369 (2)	C1—C7	1.463 (2)
O1—H1O	0.8200	C2—C3	1.343 (2)
O2—C4	1.329 (2)	C2—H2	0.9300
O2—H2O	0.8200	C3—C4	1.380 (3)
O3—C9	1.269 (2)	C4—C5	1.382 (3)
O4—C9	1.274 (2)	C5—C6	1.341 (3)
O4—H4O	0.90 (3)	C5—H5	0.9300
N1—C8	1.540 (2)	C6—H6	0.9300
N1—H1A	0.91 (3)	C7—C8	1.532 (3)
N1—H1B	0.89 (3)	C7—H7A	0.9700
N1—H1C	0.90 (3)	C7—H7B	0.9700
C1—C6	1.376 (3)	C8—C9	1.479 (2)
C1—C2	1.401 (3)	C8—H8	0.9800
C3—O1—H1O	109.5	C6—C5—C4	119.90 (18)
C4—O2—H2O	109.5	C6—C5—H5	120.0
C9—O4—H4O	103 (5)	C4—C5—H5	120.0
C8—N1—H1A	114.6 (18)	C5—C6—C1	118.60 (18)
C8—N1—H1B	113.7 (14)	C5—C6—H6	120.7
H1A—N1—H1B	99 (2)	C1—C6—H6	120.7
C8—N1—H1C	115.1 (18)	C1—C7—C8	111.52 (15)
H1A—N1—H1C	105 (3)	C1—C7—H7A	109.3
H1B—N1—H1C	108 (3)	C8—C7—H7A	109.3
C6—C1—C2	121.15 (15)	C1—C7—H7B	109.3
C6—C1—C7	118.24 (18)	C8—C7—H7B	109.3
C2—C1—C7	120.58 (17)	H7A—C7—H7B	108.0
C3—C2—C1	120.37 (17)	C9—C8—C7	108.25 (15)
C3—C2—H2	119.8	C9—C8—N1	110.92 (13)
C1—C2—H2	119.8	C7—C8—N1	111.19 (16)
C2—C3—O1	123.21 (17)	C9—C8—H8	108.8
C2—C3—C4	117.50 (17)	C7—C8—H8	108.8
O1—C3—C4	119.29 (15)	N1—C8—H8	108.8
O2—C4—C3	114.24 (17)	O3—C9—O4	129.22 (14)
O2—C4—C5	123.27 (17)	O3—C9—C8	117.83 (15)
C3—C4—C5	122.47 (16)	O4—C9—C8	112.93 (14)
C6—C1—C2—C3	−0.8 (3)	C2—C1—C6—C5	0.0 (3)
C7—C1—C2—C3	177.45 (18)	C7—C1—C6—C5	−178.29 (19)
C1—C2—C3—O1	−179.42 (18)	C6—C1—C7—C8	−69.7 (2)
C1—C2—C3—C4	1.3 (3)	C2—C1—C7—C8	112.0 (2)
C2—C3—C4—O2	−179.88 (17)	C1—C7—C8—C9	176.83 (16)
O1—C3—C4—O2	0.8 (3)	C1—C7—C8—N1	−61.1 (2)
C2—C3—C4—C5	−1.1 (3)	C7—C8—C9—O3	−67.7 (2)
O1—C3—C4—C5	179.57 (18)	N1—C8—C9—O3	170.10 (19)
O2—C4—C5—C6	179.00 (19)	C7—C8—C9—O4	110.8 (2)
C3—C4—C5—C6	0.4 (3)	N1—C8—C9—O4	−11.4 (3)
C4—C5—C6—C1	0.2 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O3i	0.82	1.98	2.746 (2)	155
O2—H2O···O1ii	0.82	2.33	2.999 (2)	140
O2—H2O···O2ii	0.82	2.16	2.8730 (8)	146
O4—H4O···O4iii	0.90 (3)	1.50 (3)	2.373 (2)	161 (8)
N1—H1A···Cl1iv	0.91 (3)	2.35 (4)	3.249 (2)	167 (3)
N1—H1B···Cl1	0.89 (3)	2.31 (3)	3.178 (2)	166 (2)
N1—H1C···O3v	0.90 (3)	1.93 (3)	2.7901 (19)	160 (3)

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