Protopine hydro­chloride

Protopine hydro­chloride (5,6,14,14a-tetra­hydro-14a-hydroxy-7-methyl-8H­-bis­[1,3]benzodioxolo­[5,6-a:4,5-g]­quinolizinium chloride, C₂₀H₂₀NO₅⁺·Cl^-) is the salt of the iso­quinoline alkaloid protopine. It is formed by the action of dilute hydro­chloric acid on the protopine free base. The N-methyl and hydroxyl groups are in a trans configuration in the quinolizine ring and the central quinolizine N-C bond is unusually long [1.579 (2) Å]. The crystal is a racemate.

S1. Comment

Protopine is an isoquinoline alkaloid of the protopine group which is common in the plants of the Papaveraceae, Fumariaceae, and other families (Guinaudeau & Shamma, 1982). The free base of protopine (I) with a ten-membered nitrogen heterocycle has already been investigated by X-ray analysis (Hall & Ahmed, 1968a) as well as the free bases of the related alkaloids cryptopine (Hall & Ahmed, 1968b), allocryptopine (Sakai et al., 1988; Marek et al., 1998), and corycavine (Kamigauchi et al., 1987). All the cited papers reported a strong electrostatic interaction between the nitrogen and the carbonyl carbon across the ten-membered ring. In an acidic environment, a fundamental alteration of the skeleton occurs and protopines take the forms of tetracyclic structures corresponding to the tetrahydroprotoberberines. Compound (II) has already been described using spectral data (UV, IR, NMR) and investigated by diffraction analysis (Luo et al., 1985). However, that report afforded neither complete geometric and crystal data parameters nor packing data. The detailed molecular study of protopine hydrochloride may be of interest in biosynthetic considerations and especially in pharmacological studies. Protopine has been shown to have multiple actions on cardiovascular system including anti-arrhythmic effects (Song et al., 2000) as well as anti-thrombotic activities (Saeed et al., 1997). Generally, it is known that the medically active forms of alkaloids are as salts rather than their free bases (Dostál, 2000). \sch

The title compound, protopine hydrochloride, (II), is the salt of protopine. NMR studies of protopine salts indicated the presence of two (cis, trans) isomers in solutions (Iwasa et al., 1982; Hussain et al., 1983). The crystal of (II), examined in the present paper, is a trans-isomer with respect to the position of the N-methyl and the hydroxyl group (Fig. 1). The dihedral angle along the C16—N7—C14—O22 junction is -166.31 (15)°. In the tetrahydroprotoberberine alkaloids canadinium camphorsulfonate (Sakai et al., 1987) and tetrahydropalmatine (Ribár et al., 1993), both the central rings also were found to be trans-fused. On the other hand, corycavinium camphorsulfonate, structurally close to protopine hydrochloride, is cis-configurated (Kamigauchi et al., 1994). The six-membered nitrogen heterocycles in (II) adopt distorted half-chair conformations. The angle between the mean planes of both aromatic rings is 17.10 (5)°.

Selected geometric parameters are given in Table 1. The central N7—C14 bond in the quinolizine ring is unusually long [1.579 (2) Å] and similar to coulteropine hydrobromide where the length of central bond was 1.58 Å (Stermitz et al., 1968). This finding implies that this particular bond easily breaks under the action of hydroxide ion to provide a ten-membered ring of the free base (I). The mean of the bond angles around the nitrogen is 109.5° (sp³ hybridization). The molecule bears two chiral centers (C14, N7) and from the centrosymmetric space group it follows that the crystal is a racemate. From plant extracts, protopines are usually obtained in the form of optically inactive free bases (type I) because they are stable and easy to crystallize. However, in plant tissues, protopine alkaloids occur as salts of type II (Kamigauchi et al., 1994). To the best of our knowledge, a natural salt of protopine has probably not yet been isolated from plant material directly without being alkalized. Thus, the in vitro prepared protopine hydrochloride (I) is obviously racemic whereas the configuration of the protopine salt generated in vivo still remains an open question. There are numerous contacts between the chloride ion and H atoms in the range of 2.78–2.87 Å, the shortest one being O22—H22···Cl (2.06 Å). The molecules are packed in a chain-like arrangement with chloride ions in between.

Related literature

For related literature, see: Dostál (2000); Guinaudeau & Shamma (1982); Hall & Ahmed (1968a, 1968b); Hussain et al. (1983); Iwasa et al. (1982); Kamigauchi et al. (1987, 1994); Luo et al. (1985); Marek et al. (1998); Ribár et al. (1993); Saeed et al. (1997); Sakai et al. (1987, 1988); Slavík et al. (1965); Song et al. (2000); Stermitz et al. (1968).

S2. Experimental

Protopine, (I), isolated from Chelidonium majus L. (Slavík et al., 1965), was dissolved in hot 3% hydrochloric acid and the solution allowed to stand at ambient temperature. After three weeks colourless crystals of protopine hydrochloride, (II), were collected, washed and dried, m.p. 534–537 K (decomposition).

Computing details

Data collection: KUMA KM-4 Software (Kuma, 1992); cell refinement: KUMA KM-4 Software; data reduction: KUMA KM-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Johnson & Burnett, 1996); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. A perspective view of compound (II). Displacement ellipsoids are drawn with 50% probability.

5,6,8,14-tetrahydro-14a-hydroxy-7-methyl-1,3-benzodioxolo[5,6-a] -1,3-benzodioxolo[4,5-g]quinolizinium chloride

Crystal data

C20H20NO5^+·Cl^−	F(000) = 816
Mr = 389.82	Dx = 1.567 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 6.940 (1) Å	Cell parameters from 1967 reflections
b = 17.755 (1) Å	θ = 3.3–23.0°
c = 13.829 (2) Å	µ = 0.27 mm^−1
β = 104.18 (1)°	T = 150 K
V = 1652.1 (3) Å^3	Prism, colourless
Z = 4	0.50 × 0.40 × 0.35 mm

Data collection

KUMA KM-4 with CCD diffractometer	2546 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.020
Graphite monochromator	θmax = 25.0°, θmin = 1.9°
Detector resolution: 0.06 mm pixels mm^-1	h = −8→8
ω scans	k = −21→10
11498 measured reflections	l = −16→16
2900 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.039	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.102	w = 1/[σ^2(Fo^2) + (0.0382P)^2 + 1.9P] where P = (Fo^2 + 2Fc^2)/3
S = 1.16	(Δ/σ)max = 0.001
2900 reflections	Δρmax = 0.29 e Å^−3
246 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: 0.0064 (9)

Special details

Experimental. All H atoms except the oxygen bonded one were added according to geometry and refined using riding model. The oxygen bound hydrogen was found from difference Fourier map, and treated using riding model subsequently.

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
C1	0.5681 (3)	−0.16359 (11)	0.93414 (14)	0.0159 (4)
H1	0.6691	−0.1979	0.9656	0.019*
C2	0.6081 (3)	−0.08890 (11)	0.92558 (15)	0.0170 (4)
C3	0.4618 (3)	−0.03741 (11)	0.88243 (14)	0.0164 (4)
C4	0.2672 (3)	−0.05854 (11)	0.84939 (14)	0.0170 (4)
H4	0.1663	−0.0225	0.8243	0.020*
C4A	0.2212 (3)	−0.13571 (11)	0.85385 (14)	0.0159 (4)
C5	0.0087 (3)	−0.15928 (11)	0.81031 (16)	0.0190 (4)
H5A	−0.0810	−0.1236	0.8327	0.023*
H5B	−0.0199	−0.1563	0.7367	0.023*
C6	−0.0342 (3)	−0.23803 (11)	0.84002 (15)	0.0164 (4)
H6A	−0.1654	−0.2545	0.7992	0.020*
H6B	−0.0395	−0.2384	0.9109	0.020*
N7	0.1245 (2)	−0.29212 (9)	0.82523 (12)	0.0140 (4)
C8	0.0608 (3)	−0.36941 (11)	0.84789 (15)	0.0162 (4)
H8A	0.0144	−0.3676	0.9101	0.019*
H8B	−0.0523	−0.3857	0.7933	0.019*
C8A	0.2249 (3)	−0.42593 (11)	0.85970 (14)	0.0154 (4)
C9	0.1845 (3)	−0.50161 (11)	0.86441 (14)	0.0165 (4)
C10	0.3302 (3)	−0.55618 (11)	0.88120 (14)	0.0166 (4)
C11	0.5266 (3)	−0.53805 (11)	0.89188 (15)	0.0182 (4)
H11	0.6272	−0.5755	0.9026	0.022*
C12	0.5712 (3)	−0.46139 (11)	0.88623 (15)	0.0177 (4)
H12	0.7053	−0.4469	0.8919	0.021*
C12A	0.4253 (3)	−0.40573 (11)	0.87259 (14)	0.0153 (4)
C13	0.4833 (3)	−0.32315 (11)	0.87550 (14)	0.0152 (4)
H13A	0.5030	−0.3084	0.8096	0.018*
H13B	0.6112	−0.3161	0.9254	0.018*
C14	0.3270 (3)	−0.27198 (11)	0.90168 (14)	0.0143 (4)
C14A	0.3697 (3)	−0.18793 (11)	0.89415 (14)	0.0156 (4)
C15	0.7536 (3)	0.02127 (12)	0.91057 (17)	0.0227 (5)
H15A	0.8071	0.0225	0.8505	0.027*
H15B	0.8204	0.0609	0.9572	0.027*
C16	0.1405 (3)	−0.28998 (11)	0.71829 (14)	0.0179 (4)
H16A	0.2170	−0.3336	0.7053	0.027*
H16B	0.2078	−0.2435	0.7067	0.027*
H16C	0.0071	−0.2914	0.6735	0.027*
C17	0.0363 (3)	−0.61402 (11)	0.85651 (16)	0.0212 (5)
H17A	−0.0304	−0.6401	0.9026	0.025*
H17B	−0.0171	−0.6343	0.7885	0.025*
O18	0.7867 (2)	−0.05142 (8)	0.95742 (11)	0.0215 (3)
O19	0.5418 (2)	0.03335 (8)	0.88356 (11)	0.0203 (3)
O20	0.0008 (2)	−0.53373 (8)	0.85779 (12)	0.0224 (3)
O21	0.2464 (2)	−0.62578 (8)	0.88711 (11)	0.0219 (3)
O22	0.3069 (2)	−0.29289 (7)	0.99584 (10)	0.0167 (3)
H22	0.2445	−0.2546	1.0277	0.025*
Cl	0.08851 (7)	−0.20199 (3)	1.11743 (4)	0.02114 (16)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0149 (9)	0.0157 (10)	0.0169 (10)	0.0010 (8)	0.0035 (8)	0.0000 (8)
C2	0.0156 (9)	0.0175 (10)	0.0180 (10)	−0.0024 (8)	0.0045 (8)	−0.0040 (8)
C3	0.0225 (10)	0.0114 (9)	0.0163 (10)	−0.0025 (8)	0.0071 (8)	−0.0020 (7)
C4	0.0200 (10)	0.0131 (10)	0.0185 (10)	0.0025 (8)	0.0061 (8)	0.0001 (8)
C4A	0.0176 (10)	0.0164 (10)	0.0148 (9)	0.0001 (8)	0.0063 (8)	−0.0007 (8)
C5	0.0138 (9)	0.0144 (10)	0.0281 (11)	0.0020 (8)	0.0038 (8)	0.0025 (8)
C6	0.0128 (9)	0.0160 (10)	0.0208 (10)	0.0006 (8)	0.0048 (8)	0.0003 (8)
N7	0.0124 (8)	0.0136 (8)	0.0159 (8)	−0.0006 (6)	0.0030 (6)	0.0007 (6)
C8	0.0153 (9)	0.0118 (10)	0.0213 (10)	−0.0017 (8)	0.0044 (8)	0.0001 (8)
C8A	0.0174 (10)	0.0138 (10)	0.0155 (9)	0.0000 (8)	0.0047 (8)	−0.0012 (7)
C9	0.0194 (10)	0.0150 (10)	0.0157 (9)	−0.0015 (8)	0.0053 (8)	−0.0014 (8)
C10	0.0227 (10)	0.0101 (9)	0.0172 (10)	−0.0019 (8)	0.0053 (8)	−0.0021 (8)
C11	0.0217 (10)	0.0144 (10)	0.0189 (10)	0.0038 (8)	0.0056 (8)	−0.0014 (8)
C12	0.0157 (10)	0.0193 (11)	0.0190 (10)	0.0009 (8)	0.0056 (8)	−0.0014 (8)
C12A	0.0186 (10)	0.0135 (10)	0.0139 (9)	0.0003 (8)	0.0044 (8)	−0.0005 (7)
C13	0.0146 (9)	0.0124 (10)	0.0185 (10)	−0.0008 (8)	0.0039 (8)	0.0003 (7)
C14	0.0115 (9)	0.0157 (10)	0.0151 (9)	−0.0018 (7)	0.0020 (7)	0.0000 (7)
C14A	0.0184 (10)	0.0140 (10)	0.0153 (9)	0.0006 (8)	0.0060 (8)	0.0003 (7)
C15	0.0211 (10)	0.0160 (10)	0.0300 (12)	−0.0049 (8)	0.0044 (9)	0.0001 (9)
C16	0.0201 (10)	0.0209 (10)	0.0128 (9)	0.0002 (8)	0.0041 (8)	−0.0001 (8)
C17	0.0224 (11)	0.0133 (10)	0.0279 (11)	−0.0016 (8)	0.0063 (9)	−0.0005 (8)
O18	0.0189 (7)	0.0146 (7)	0.0287 (8)	−0.0040 (6)	0.0012 (6)	0.0003 (6)
O19	0.0207 (7)	0.0118 (7)	0.0268 (8)	−0.0021 (6)	0.0027 (6)	−0.0003 (6)
O20	0.0177 (7)	0.0133 (7)	0.0359 (9)	−0.0021 (6)	0.0064 (6)	0.0000 (6)
O21	0.0215 (8)	0.0115 (7)	0.0311 (8)	−0.0003 (6)	0.0034 (6)	0.0002 (6)
O22	0.0204 (7)	0.0154 (7)	0.0147 (7)	0.0019 (5)	0.0054 (6)	0.0031 (5)
Cl	0.0234 (3)	0.0192 (3)	0.0223 (3)	0.00144 (19)	0.0087 (2)	0.00052 (19)

Geometric parameters (Å, º)

C1—C2	1.366 (3)	C10—C11	1.372 (3)
C1—C14A	1.419 (3)	C10—O21	1.377 (2)
C2—O18	1.381 (2)	C11—C12	1.402 (3)
C2—C3	1.388 (3)	C12—C12A	1.394 (3)
C3—C4	1.368 (3)	C12A—C13	1.518 (3)
C3—O19	1.372 (2)	C13—C14	1.525 (3)
C4—C4A	1.412 (3)	C14—O22	1.394 (2)
C4A—C5	1.509 (3)	C14—C14A	1.530 (3)
C4A—C14A	1.397 (3)	C15—O18	1.437 (3)
C5—C6	1.507 (3)	C15—O19	1.441 (3)
N7—C6	1.513 (2)	C17—O21	1.431 (3)
N7—C8	1.498 (2)	C17—O20	1.447 (2)
N7—C14	1.579 (2)	Cl—H22	2.0595
N7—C16	1.510 (2)	Cl—H6A^i	2.7807
C8—C8A	1.497 (3)	Cl—H16C^i	2.8197
C8A—C9	1.377 (3)	Cl—H17A^ii	2.8367
C8A—C12A	1.404 (3)	Cl—H15B^iii	2.8385
C9—C10	1.379 (3)	Cl—H6B	2.8497
C9—O20	1.379 (2)	Cl—H13A^iv	2.8667
C2—C1—C14A	117.39 (18)	O22—C14—C14A	112.88 (15)
C1—C2—O18	128.76 (18)	C13—C14—C14A	113.85 (16)
C1—C2—C3	122.28 (18)	O22—C14—N7	106.77 (14)
O18—C2—C3	108.94 (17)	C13—C14—N7	105.92 (15)
C4—C3—O19	128.21 (18)	C14A—C14—N7	109.31 (15)
C4—C3—C2	121.42 (18)	C4A—C14A—C1	120.25 (18)
O19—C3—C2	110.31 (17)	C4A—C14A—C14	122.58 (17)
C3—C4—C4A	117.84 (18)	C1—C14A—C14	117.12 (17)
C14A—C4A—C4	120.59 (18)	O18—C15—O19	106.89 (15)
C14A—C4A—C5	121.90 (18)	O21—C17—O20	107.70 (15)
C4—C4A—C5	117.47 (17)	C2—O18—C15	104.91 (15)
C6—C5—C4A	112.81 (16)	C3—O19—C15	104.52 (15)
C5—C6—N7	110.65 (15)	C9—O20—C17	104.54 (15)
C6—N7—C8	106.93 (14)	C10—O21—C17	105.46 (15)
C6—N7—C14	108.91 (14)	H22—Cl—H6A^i	97.0
C8—N7—C14	109.11 (14)	H22—Cl—H16C^i	59.3
C6—N7—C16	110.30 (15)	H6A^i—Cl—H16C^i	51.4
C8—N7—C16	108.90 (15)	H22—Cl—H17A^ii	64.9
C14—N7—C16	112.53 (14)	H6A^i—Cl—H17A^ii	81.6
C8A—C8—N7	112.41 (16)	H16C^i—Cl—H17A^ii	95.6
C9—C8A—C12A	116.73 (18)	H22—Cl—H15B^iii	89.1
C9—C8A—C8	120.06 (17)	H6A^i—Cl—H15B^iii	115.6
C12A—C8A—C8	123.09 (17)	H16C^i—Cl—H15B^iii	80.2
C8A—C9—C10	122.97 (19)	H17A^ii—Cl—H15B^iii	151.1
C8A—C9—O20	126.58 (18)	H22—Cl—H6B	51.2
C10—C9—O20	110.40 (17)	H6A^i—Cl—H6B	144.6
C11—C10—O21	128.85 (18)	H16C^i—Cl—H6B	108.3
C11—C10—C9	121.42 (18)	H17A^ii—Cl—H6B	71.1
O21—C10—C9	109.72 (17)	H15B^iii—Cl—H6B	83.0
C10—C11—C12	116.66 (18)	H22—Cl—H13A^iv	147.8
C12A—C12—C11	122.18 (19)	H6A^i—Cl—H13A^iv	53.2
C12—C12A—C8A	119.98 (18)	H16C^i—Cl—H13A^iv	100.4
C12—C12A—C13	120.11 (17)	H17A^ii—Cl—H13A^iv	95.6
C8A—C12A—C13	119.87 (17)	H15B^iii—Cl—H13A^iv	113.3
C12A—C13—C14	112.47 (16)	H6B—Cl—H13A^iv	149.2
O22—C14—C13	107.65 (15)
C14A—C1—C2—O18	−179.67 (18)	C12—C12A—C13—C14	−156.61 (17)
C14A—C1—C2—C3	1.9 (3)	C8A—C12A—C13—C14	21.1 (2)
C1—C2—C3—C4	2.5 (3)	C12A—C13—C14—O22	60.4 (2)
O18—C2—C3—C4	−176.22 (17)	C12A—C13—C14—C14A	−173.68 (15)
C1—C2—C3—O19	179.86 (18)	C12A—C13—C14—N7	−53.5 (2)
O18—C2—C3—O19	1.1 (2)	C8—N7—C14—O22	−45.32 (18)
O19—C3—C4—C4A	178.64 (18)	C16—N7—C14—O22	−166.31 (15)
C2—C3—C4—C4A	−4.5 (3)	C6—N7—C14—O22	71.07 (18)
C3—C4—C4A—C14A	2.2 (3)	C8—N7—C14—C13	69.22 (18)
C3—C4—C4A—C5	−175.60 (18)	C16—N7—C14—C13	−51.77 (19)
C14A—C4A—C5—C6	15.7 (3)	C6—N7—C14—C13	−174.40 (15)
C4—C4A—C5—C6	−166.49 (17)	C8—N7—C14—C14A	−167.73 (15)
C4A—C5—C6—N7	−47.8 (2)	C16—N7—C14—C14A	71.28 (19)
C5—C6—N7—C8	−175.16 (16)	C6—N7—C14—C14A	−51.34 (19)
C5—C6—N7—C16	−56.9 (2)	C4—C4A—C14A—C1	2.0 (3)
C5—C6—N7—C14	67.07 (19)	C5—C4A—C14A—C1	179.79 (18)
C16—N7—C8—C8A	74.33 (19)	C4—C4A—C14A—C14	179.32 (17)
C6—N7—C8—C8A	−166.49 (16)	C5—C4A—C14A—C14	−2.9 (3)
C14—N7—C8—C8A	−48.8 (2)	C2—C1—C14A—C4A	−4.1 (3)
N7—C8—C8A—C9	−169.35 (17)	C2—C1—C14A—C14	178.52 (17)
N7—C8—C8A—C12A	14.7 (3)	O22—C14—C14A—C4A	−97.9 (2)
C12A—C8A—C9—C10	0.2 (3)	C13—C14—C14A—C4A	138.95 (19)
C8—C8A—C9—C10	−176.00 (18)	N7—C14—C14A—C4A	20.7 (2)
C12A—C8A—C9—O20	177.29 (18)	O22—C14—C14A—C1	79.4 (2)
C8—C8A—C9—O20	1.1 (3)	C13—C14—C14A—C1	−43.7 (2)
C8A—C9—C10—C11	−1.7 (3)	N7—C14—C14A—C1	−161.89 (16)
O20—C9—C10—C11	−179.15 (18)	C1—C2—O18—C15	167.8 (2)
C8A—C9—C10—O21	176.87 (18)	C3—C2—O18—C15	−13.6 (2)
O20—C9—C10—O21	−0.6 (2)	O19—C15—O18—C2	20.7 (2)
O21—C10—C11—C12	−177.38 (19)	C4—C3—O19—C15	−171.1 (2)
C9—C10—C11—C12	0.9 (3)	C2—C3—O19—C15	11.8 (2)
C10—C11—C12—C12A	1.3 (3)	O18—C15—O19—C3	−20.0 (2)
C11—C12—C12A—C8A	−2.8 (3)	C8A—C9—O20—C17	174.2 (2)
C11—C12—C12A—C13	174.96 (18)	C10—C9—O20—C17	−8.4 (2)
C9—C8A—C12A—C12	1.9 (3)	O21—C17—O20—C9	14.1 (2)
C8—C8A—C12A—C12	178.02 (18)	C11—C10—O21—C17	−172.1 (2)
C9—C8A—C12A—C13	−175.82 (17)	C9—C10—O21—C17	9.5 (2)
C8—C8A—C12A—C13	0.3 (3)	O20—C17—O21—C10	−14.6 (2)

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

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O22—H22···Cl	0.97	2.06	2.9962 (15)	162