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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 62| Part 9| September 2006| Pages o4196-o4199
https://doi.org/10.1107/S1600536806033691

Amodiaquinium dichloride dihydrate from laboratory powder diffraction data

CROSSMARK_Color_square_no_text.svg
Antonio Llinàs,a László Fábián,b Jonathan C. Burley,c Jacco van de Streekd and Jonathan M. Goodmana*

aUnilever Centre for Molecular Informatics, Pfizer Institute for Pharmaceutical Materials Science, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, England, bPfizer Institute for Pharmaceutical Materials Science, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England, cUniversity Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, England, and dCambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England
*Correspondence e-mail: fabian@ccdc.cam.ac.uk

(Received 17 July 2006; accepted 22 August 2006; online 31 August 2006)

The title compound (systematic name: {5-[(7-chloroquinolinium-4-yl)amino]-2-hydroxy­benzyl}dimethylammonium dichloride dihydrate), C20H24ClN3O2+·2Cl−·2H2O, has one amodiaquinium dication, two Cl− anions and two water mol­ecules in the asymmetric unit. The crystal structure was solved by simulated annealing from laboratory X-ray powder diffraction data, with data collected at room temperature. Rietveld refinement of this model led to a final Rwp of 0.047 to 1.79 Å resolution. A three-dimensional network of hydrogen bonding links the amodiaquinium cations via water mol­ecules and Cl− ions.

Comment

Amodiaquine, 4-[(7-chloro-4-quinolin­yl)amino]-2-[(diethyl­amino)meth­yl]phenol, is an anti­malarial drug (Olliaro & Mussano, 2003[Olliaro, P. & Mussano, P. (2003). Amodiaquine for Treating Malaria in The Cochrane Database of Systematic Reviews. (https://www.cochrane.org/reviews/index.htm)]), often formulated as a dihydro­chloride salt. This salt is known to exist in anhydrous, monohydrate and dihydrate forms. The crystal structure of the monohydrate form has been reported by Yennawar & Viswamitra (1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]). Here, the crystal structure of the dihydrate form, (I), is reported and compared with that of the monohydrate.

[Scheme 1]

The asymmetric unit of the dihydrate structure is shown in Fig. 1[link]. It was assumed that the same N atoms were protonated on hydro­chloride salt formation as in the monohydrate form (see Experimental). Yennawar & Viswamitra (1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]) found that the bonds that link the benzene and quinoline units through an N atom show strong double-bond character, as indicated by short C—N bond lengths and close-to-planar C—C—N—C torsion angles (Table 2[link]). A search of the Cambridge Structural Database (CSD, Version 5.27; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]) was performed in order to determine typical values for these parameters. The average Car—NH bond length was found to be ca 1.39 (3) Å and the distribution of the C—C—N—C torsion angles showed sharp maxima at 0° and 180°.

In the dihydrate form, the C8—C9—N2—C10 torsion angle is closer to the ideal value of 0° than in the monohydrate form, which suggests an increased C—N double-bond character (Table 1[link]). Even though the resolution of our data does not permit the determination of H-atom positions, the coordinates of both H2 and H2N can reasonably be estimated using idealized bond geometry and normalized bond lengths. The distance between the calculated H2 and H2N positions is 1.85 Å in the dihydrate, while 2.08 Å was reported for the monohydrate. Thus, the C8—C9—N2—C10 torsion angle in the dihydrate form approaches planarity despite considerable steric congestion. This behaviour is indicative of strong C9—N2 double-bond character.

The C9—N2—C10—C11 torsion angles are far from planar in both forms (Table 1[link]). The coplanarity of the quinoline and benzene rings is sterically hindered by the close approach of the C8—H8 and the C11—H11 H atoms (Fig. 1[link]).

The most apparent difference between the conformations of amodiaquine in the two structures is a rotation around the C12—C16 bond (Table 1[link]), which moves the diethyl­amino group to opposite sides (above/below; see Fig. 1[link]) of the benzene ring. In the dihydrate structure, one of the H atoms attached to atom C16 is involved in a close intra­molecular contact of 2.41 Å with atom O1.

The amodiaquinium cations donate hydrogen bonds to two Cl− ions and a water mol­ecule in both forms (Table 2[link]; Yennawar & Viswamitra, 1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]). The roles of the donor groups, however, differ in the two forms. In the dihydrate, N2—H2N⋯OH2 and O1—H1O⋯Cl− hydrogen bonds are formed, while in the monohydrate there are N—H⋯Cl− and O—H⋯OH2 bonds.

Stacking inter­actions between the phenol and quinoline rings of screw-related mol­ecules were found in the monohydrate structure (Yennawar & Viswamitra, 1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]). No such inter­actions are present in the crystal structure of the di­hydrate form (Fig. 2[link]). The monohydrate structure appears to be deficient in hydrogen-bond donors, since one of the Cl− ions accepts only one hydrogen bond instead of the usual two or three (Infantes & Motherwell, 2004[Infantes, L. & Motherwell, W. D. S. (2004). Chem. Commun. pp. 1166-1167.]). The additional donating ability of the extra water mol­ecule in the dihydrate form permits a more optimal hydrogen-bonding scheme, and the stacking inter­actions between amodiaquinium cations are replaced by indirect hydrogen-bonded links through the solvent mol­ecules and the counterions.

[Figure 1]
Figure 1
A view of (I), with the atom-numbering scheme.
[Figure 2]
Figure 2
The crystal packing of (I), viewed along the a axis. Hydrogen bonds are indicated by dashed lines.
[Figure 3]
Figure 3
Final observed (points), calculated (line), difference [(yobs − ycalc)] and weighted difference [(yobs − ycalc)/σ] profiles for the Rietveld refinement of the title compound. Change of scale at 40° is a factor of 10 and the increment in 2θ is 0.01°.

Experimental

Amodiaquinium dihydro­chloride dihydrate was obtained from Sigma and used without further purification. No impurities were detected by X-ray powder diffraction. The sample was ground lightly and loaded into a 0.7 mm-diameter Lindemann glass capillary. Data were collected at room temperature and pressure in Debye–Scherrer geometry employing Co Kα1 radiation.

Crystal data

  • C20H24ClN3O2+·2Cl−·2H2O

  • Mr = 464.8

  • Monoclinic, P 21 /c

  • a = 7.83868 (10) Å

  • b = 26.9917 (5) Å

  • c = 10.80804 (18) Å

  • β = 92.9632 (13)°

  • V = 2283.6 (2) Å3

  • Z = 4

  • Dx = 1.352 Mg m−3

  • Co Kα1 radiation

  • μ = 0 mm−1

  • T = 298 K

  • Specimen shape: cylinder

  • 12 × 0.7 × 0.7 mm

  • Specimen prepared at 100 kPa

  • Specimen prepared at 298 K

  • Particle morphology: fine powder, yellow
Data collection

  • Stoe linear PSD diffractometer

  • Specimen mounting: 0.7 mm Lindemann glass capillary

  • Specimen mounted in transmission mode

  • Scan method: step

  • Absorption correction: none

  • 2θmin = 2.0, 2θmax = 60.0°

  • Increment in 2θ = 0.01°
Refinement

  • Refinement on Inet

  • Rp = 0.037

  • Rwp = 0.047

  • Rexp = 0.038

  • RB = 0.0622

  • S = 1.29

  • Wavelength of incident radiation: 1.78892 Å

  • Excluded region(s): none

  • Profile function: pseudo-Voigt (Thompson et al., 1987[Thompson, P., Cox, D. E. & Hastings, J. B. (1987). J. Appl. Cryst. 20, 79-83.]) with asymmetry correction (Finger et al., 1994[Finger, L. W., Cox, D. E. & Jephcoat, A. P. (1994). J. Appl. Cryst. 27, 892-900.])

  • 392 reflections

  • 181 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Weighting scheme based on measured s.u.'s, 1/σ(yobs)2

  • (Δ/σ)max = 0.14

  • Preferred orientation correction: March–Dollase, as implemented and documented in GSAS (Larson & Von Dreele, 2000[Larson, A. C. & Von Dreele, R. B. (2000). GSAS. Report LAUR 86-748. Los Alamos National Laboratory, New Mexico, USA.]), along the (100 axis), ratio = 1.066 (2), range: min = 0.82398, max = 1.10164

Table 1
Selected geometric parameters (°) of amodiaquine in the crystal structures of amodiaquinium dihydrochloride monohydrate (CSD refcode VOTFIT; Yennawar & Viswamitra, 1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]) and amodiaquinium dihydrochloride dihydrate, (I). Atom labels are given in Fig. 1

Parameter Monohydrate Dihydrate
C8—C9—N2—C10 17.2 (7) 5.0 (12)
C9—N2—C10—C11 34.7 (7) 46.9 (12)
Quinoline–phenyl interplanar angle 48 54.6 (4)
C11—C12—C16—N3 −91.4 77.4 (8)

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1N⋯Cl2i 0.93 (1) 2.26 (1) 3.160 (6) 162 (1)
N2—H2N⋯O2Wii 0.93 (2) 2.07 (2) 2.902 (12) 148 (1)
N3—H3N⋯Cl3 0.93 (1) 2.15 (1) 3.016 (7) 155 (1)
O1—H1O⋯Cl2iii 0.98 2.06 3.037 (7) 177
O1W—H1WA⋯Cl3 0.97 2.16 3.127 (11) 175
O1W—H1WB⋯Cl3iv 1.02 2.28 3.297 (11) 177
O2W—H2WA⋯O1W 0.98 1.84 2.816 (14) 171
O2W—H2WB⋯Cl2iv 1.06 2.13 3.188 (12) 177
Symmetry codes: (i) -x+2, -y+1, -z+1; (ii) -x+1, -y+1, -z+2; (iii) [x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]; (iv) -x+1, -y+1, -z+1.

The program DASH (David et al., 2004[David, W. I. F., Shankland, K., van de Streek, J., Pidcock, E. & Motherwell, S. (2004). DASH. Version 3.0. Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, England.]) was employed for structure solution. The powder pattern was truncated to 48.35° in 2θ (Co Kα), corresponding to a real-space resolution of 2.2 Å. The background was subtracted with a Bayesian high-pass filter (David & Sivia, 2001[David, W. I. F. & Sivia, D. S. (2001). J. Appl. Cryst. 34, 318-324.]). Peak positions for indexing were obtained by fitting with an asymmetry-corrected Voigt function (Thompson et al., 1987[Thompson, P., Cox, D. E. & Hastings, J. B. (1987). J. Appl. Cryst. 20, 79-83.]; Finger et al., 1994[Finger, L. W., Cox, D. E. & Jephcoat, A. P. (1994). J. Appl. Cryst. 27, 892-900.]). Indexing with the program DICVOL91 (Boultif & Louër, 1991[Boultif, A. & Louër, D. (1991). J. Appl. Cryst. 24, 987-993.]) failed, but the same 24 peak positions could be indexed with the program DICVOL04 (Boultif & Louër, 2004[Boultif, A. & Louër, D. (2004). J. Appl. Cryst. 37, 724-731.]) without allowing for impurity peaks. Pawley refinement was used to extract integrated intensities and their correlations, from which the space group was determined using Bayesian statistical analysis (Markvardsen et al., 2001[Markvardsen, A. J., David, W. I. F., Johnson, J. C. & Shankland, K. (2001). Acta Cryst. A57, 47-54.]). P21/c was returned as the only possible space group, which resulted in a Pawley χ2 of 0.70. Simulated annealing was used to solve the crystal structure of compound (I) from the powder pattern in direct space. The starting mol­ecular geometry was taken from the crystal structure of amodiaquinium dihydro­chloride monohydrate (Yennawar & Viswamitra, 1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]) from the CSD (refcode VOTFIT). The mol­ecule was assumed to be a salt in the solid state, based on the single-crystal structure of the monohydrate, where the two H atoms on the two positively charged N atoms had been located from the difference Fourier map. We note, however, that the three H atoms that were located only render two of the N atoms positive; charge balance therefore requires the hydroxide counterion that is stated to be present to be a water mol­ecule. The structure of VOTFIT is therefore the monohydrate, and this has now been corrected in the CSD.

Because H atoms do not contribute significantly to the powder diffraction pattern, due to their low X-ray scattering power, they can be ignored during the structure solution process. Hence, a water mol­ecule can be reduced to an O atom, which reduces its number of degrees of freedom from six to three. The amodiaquine mol­ecule has six flexible torsion angles, which, combined with the two water mol­ecules and the two Cl− ions, give a total of 24 degrees of freedom. Because of the large number of degrees of freedom, it cannot be expected that the default settings for simulated annealing in DASH (ten simulated annealing runs of 10 000 000 moves each) would be sufficient. Instead, 50 simulated annealing runs of 100 000 000 moves each were performed. In 50 simulated annealing runs, the correct crystal structure was found ten times, with a profile χ2 of 1.60, 2.3 times the Pawley χ2. The next best solution had a significantly higher profile χ2 of 7.66.

The background subtraction, peak fitting, Pawley refinement, space-group determination and simulated-annealing algorithms were used as implemented in the program DASH.

Rietveld refinement was carried out on the solution with the lowest profile χ2, with H atoms added in calculated positions. Bond lengths and angles involving heavy atoms were restrained to values taken from CSD entry VOTFIT (Yennawar & Viswamitra, 1991[Yennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39-43.]). Planar group restraints were applied for aromatic rings. The CH, CH2 and CH3 distances were restrained to be 0.93 (1), 0.97 (1) and 0.96 (1) Å respectively, with idealized bond angles. The refinement (Fig. 3[link]), using the GSAS software suite (Larson & Von Dreele, 2000[Larson, A. C. & Von Dreele, R. B. (2000). GSAS. Report LAUR 86-748. Los Alamos National Laboratory, New Mexico, USA.]), converged readily to yield acceptable figures of merit (χ2 = 1.655, Rp = 0.0366, Rwp = 0.0465) and a chemically reasonable structural model. A single overall isotropic displacement parameter was employed. The orientations of the water mol­ecules were kept fixed to enforce a chemically reasonable hydrogen-bonding geometry. Reported standard deviations are taken from the program employed and represent statistical uncertainties rather than estimates of the absolute error, which are likely to be considerably greater.

Data collection: WinXPow (Stoe, 1999[Stoe (1999). WinXPow. Stoe & Cie, Darmstadt, Germany.]); cell refinement: GSAS (Larson & Von Dreele, 2000[Larson, A. C. & Von Dreele, R. B. (2000). GSAS. Report LAUR 86-748. Los Alamos National Laboratory, New Mexico, USA.]); data reduction: WinXPow; program(s) used to solve structure: DASH (David et al., 2004[David, W. I. F., Shankland, K., van de Streek, J., Pidcock, E. & Motherwell, S. (2004). DASH. Version 3.0. Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, England.]); program(s) used to refine structure: GSAS; molecular graphics: MERCURY (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]); software used to prepare material for publication: vi (https://www.vim.org/).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536806033691/ci2110sup1.cif

Rietveld powder data: contains datablock I. DOI: https://doi.org/10.1107/S1600536806033691/ci2110Isup2.rtv


Computing details top

Data collection: Stoe software [Please specify]; cell refinement: GSAS (Larson & Von Dreele, 2000); program(s) used to solve structure: DASH (David et al., 2004); program(s) used to refine structure: GSAS; molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: vi (https://www.vim.org/).

5-[(7-chloroquinolinium-4-yl)amino]-2-hydroxybenzyl}dimethylammonium dichloride dihydrate top
Crystal data top
C20H24ClN3O2+·2Cl−·2H2OF(000) = 976
Mr = 464.8Dx = 1.352 Mg m−3
Monoclinic, P21/cCo Kα1 radiation, λ = 1.78892 Å
Hall symbol: -P 2ybcµ = 0 mm−1
a = 7.83868 (10) ÅT = 298 K
b = 26.9917 (5) ÅParticle morphology: Please complete
c = 10.80804 (18) Åyellow
β = 92.9632 (13)°cylinder, 12 × 0.7 mm
V = 2283.6 (2) Å3Specimen preparation: Prepared at 298 K
Z = 4
Data collection top
Stoe linear PSD
diffractometer		Data collection mode: transmission
Radiation source: sealed X-ray tube, Stoe STADI-PScan method: step
Primary focusing, Ge 111 monochromator2θmin = 2.0°, 2θmax = 79.99°, 2θstep = 0.01°
Specimen mounting: 0.7 mm Lindemann glass capillary
Refinement top
Refinement on Inet181 parameters
Least-squares matrix: selected elements only164 restraints
Rp = 0.037H atoms treated by a mixture of independent and constrained refinement
Rwp = 0.047Weighting scheme based on measured s.u.'s 1/σ(Yobs)2
Rexp = 0.038(Δ/σ)max = 0.14
R(F2) = 0.05179Background function: Shifted Chebyshev polynomial of the first type, 15 terms, GSAS ((Larson & Von Dreele, 2000).
7199 data pointsPreferred orientation correction: March–Dollase, as implemented and documented in GSAS (Larson & Von Dreele, 2000), along the (100 axis), ratio = 1.066(2), Prefered orientation correction range: min = 0.82398, max = 1.10164
Profile function: pseudo-Voigt (Thompson et al., 1987) with asymmetry correction (Finger et al., 1994)
Special details top

Refinement. CW Profile function number 3 with 19 terms Pseudo-Voigt profile coefficients as parameterized in P. Thompson, D·E. Cox & J·B. Hastings (1987). J. Appl. Cryst.,20,79–83. Asymmetry correction of L·W. Finger, D·E. Cox & A. P. Jephcoat (1994). J. Appl. Cryst.,27,892–900. #1(GU) = 133.258 #2(GV) = 0.000 #3(GW) = 4.899 #4(GP) = 0.000 #5(LX) = 4.575 #6(LY) = 0.000 #7(S/L) = 0.0130 #8(H/L) = 0.0350 #9(trns) = 0.00 #10(shft)= 0.0000 #11(stec)= 0.00 #12(ptec)= 0.00 #13(sfec)= 0.00 #14(L11) = 0.000 #15(L22) = 0.000 #16(L33) = 0.000 #17(L12) = 0.000 #18(L13) = 0.000 #19(L23) = 0.000 Peak tails are ignored where the intensity is below 0.0010 times the peak

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.7990 (14)0.48320 (19)0.9281 (7)0.1333 (14)*
C20.7130 (15)0.48123 (2)1.0395 (8)0.1333 (14)*
H20.6666 (3)0.50990 (2)1.0716 (14)0.1333 (14)*
C30.6969 (13)0.43719 (18)1.0998 (7)0.1333 (14)*
H30.6373 (2)0.43588 (2)1.1719 (11)0.1333 (14)*
C40.7618 (13)0.39305 (17)1.0494 (7)0.1333 (14)*
Cl10.7399 (6)0.33753 (16)1.1292 (4)0.1333 (14)*
C50.8521 (12)0.39204 (18)0.9475 (7)0.1333 (14)*
H50.9022 (16)0.36312 (2)0.9200 (9)0.1333 (14)*
C60.8712 (11)0.43766 (19)0.8871 (7)0.1333 (14)*
N10.9654 (10)0.43801 (2)0.7841 (6)0.1333 (14)*
H1N1.0109 (17)0.40865 (3)0.7551 (10)0.1333 (14)*
C70.9826 (12)0.47951 (3)0.7216 (7)0.1333 (14)*
H71.0455 (2)0.47865 (3)0.6511 (12)0.1333 (14)*
C80.9044 (10)0.52451 (3)0.7524 (6)0.1333 (14)*
H80.9262 (19)0.55311 (3)0.7079 (10)0.1333 (14)*
C90.8183 (11)0.52747 (2)0.8605 (7)0.1333 (14)*
N20.7370 (10)0.56989 (2)0.8933 (5)0.1333 (14)*
H2N0.6669 (3)0.5666 (4)0.9597 (16)0.1333 (14)*
C100.7152 (9)0.61374 (18)0.8255 (5)0.1333 (14)*
C110.6597 (14)0.61408 (15)0.6994 (5)0.1333 (14)*
H110.6230 (3)0.58484 (2)0.6610 (7)0.1333 (14)*
C120.6600 (10)0.65765 (13)0.6326 (4)0.1333 (14)*
C130.7070 (13)0.70191 (15)0.6884 (4)0.1333 (14)*
O10.7076 (11)0.74355 (15)0.6207 (5)0.1333 (14)*
H1O0.757050.772440.664460.1333 (14)*
C140.7715 (15)0.70075 (2)0.8127 (5)0.1333 (14)*
H140.8095 (3)0.72981 (3)0.8512 (8)0.1333 (14)*
C150.7790 (12)0.65725 (2)0.8762 (5)0.1333 (14)*
H150.8188 (2)0.65746 (3)0.9588 (7)0.1333 (14)*
C160.5877 (8)0.65740 (19)0.4983 (4)0.1333 (14)*
H16A0.6280 (10)0.62802 (3)0.4572 (6)0.1333 (14)*
H16B0.6284 (9)0.68653 (3)0.4564 (6)0.1333 (14)*
N30.3910 (8)0.65751 (16)0.4907 (6)0.1333 (14)*
H3N0.3550 (10)0.62970 (2)0.5329 (8)0.1333 (14)*
C170.3268 (10)0.65258 (3)0.3591 (7)0.1333 (14)*
H17A0.2042 (12)0.6474 (6)0.3567 (10)0.1333 (14)*
H17B0.3807 (2)0.6241 (4)0.3227 (9)0.1333 (14)*
C180.3649 (15)0.6987 (4)0.2829 (6)0.1333 (14)*
H18A0.478 (6)0.7101 (3)0.305 (8)0.1333 (14)*
H18B0.356 (15)0.6905 (13)0.1963 (7)0.1333 (14)*
H18C0.284 (9)0.7242 (14)0.300 (9)0.1333 (14)*
C190.3271 (9)0.70192 (3)0.5556 (8)0.1333 (14)*
H19A0.3609 (17)0.73147 (2)0.5120 (16)0.1333 (14)*
H19B0.3778 (14)0.7027 (6)0.6394 (10)0.1333 (14)*
C200.1324 (9)0.7013 (4)0.5611 (12)0.1333 (14)*
H20A0.0973 (16)0.6709 (18)0.598 (10)0.1333 (14)*
H20B0.0966 (13)0.7289 (2)0.610 (9)0.1333 (14)*
H20C0.0812 (14)0.704 (4)0.4786 (17)0.1333 (14)*
Cl20.8709 (6)0.66762 (18)0.2523 (4)0.1333 (14)*
Cl30.2586 (6)0.55560 (17)0.5482 (4)0.1333 (14)*
O1W0.4815 (12)0.4714 (4)0.6724 (9)0.1333 (14)*
H1WA0.410750.496190.629920.1333 (14)*
H1WB0.558140.462340.602820.1333 (14)*
O2W0.4008 (14)0.4084 (4)0.8686 (9)0.1333 (14)*
H2WA0.420480.428660.795130.1333 (14)*
H2WB0.309320.384090.826290.1333 (14)*
Geometric parameters (Å, º) top
C1—C21.4108 (17)C14—H140.9299 (18)
C1—C61.4329 (16)C14—C151.3597 (17)
C1—C91.4129 (17)H14—C140.9299 (18)
C2—H20.9299 (18)C15—C101.3792 (17)
C2—C31.3645 (17)C15—C141.3597 (17)
H2—C20.9299 (18)C15—H150.9301 (18)
C3—H30.9300 (18)H15—C150.9301 (18)
C3—C41.4153 (17)C16—C121.5300 (18)
H3—C30.9300 (18)C16—H16A0.9700 (18)
C4—C51.3397 (17)C16—H16B0.9699 (18)
C5—C41.3397 (17)C16—N31.5398 (18)
C5—H50.9299 (18)H16A—C160.9700 (18)
C5—C61.4055 (17)H16B—C160.9699 (18)
H5—C50.9299 (18)N3—C161.5398 (18)
C6—C51.4055 (17)N3—H3N0.9300 (18)
N1—C61.3678 (17)N3—C171.4897 (18)
N1—H1N0.9298 (18)N3—C191.4891 (18)
N1—C71.3182 (17)H3N—N30.9300 (18)
H1N—N10.9298 (18)C17—N31.4897 (18)
C7—N11.3182 (17)C17—H17A0.9701 (18)
C7—H70.9301 (18)C17—H17B0.9700 (18)
C7—C81.4080 (17)C17—C181.5297 (18)
H7—C70.9301 (18)H17A—C170.9701 (18)
C8—C71.4080 (17)H17B—C170.9700 (18)
C8—H80.9300 (18)C18—C171.5297 (18)
C8—C91.3811 (17)C18—H18A0.9600 (18)
H8—C80.9300 (18)C18—H18B0.9603 (18)
C9—N21.3664 (18)C18—H18C0.9600 (18)
N2—C91.3664 (18)H18A—C180.9600 (18)
N2—H2N0.9298 (18)H18B—C180.9603 (18)
N2—C101.3981 (18)H18C—C180.9600 (18)
H2N—N20.9298 (18)C19—N31.4891 (18)
C10—N21.3981 (18)C19—H19A0.9701 (18)
C10—C111.4092 (17)C19—H19B0.9702 (18)
C10—C151.3792 (17)C19—C201.5302 (18)
C11—H110.9301 (18)H19A—C190.9701 (18)
C11—C121.3800 (17)H19B—C190.9702 (18)
H11—C110.9301 (18)C20—H20A0.9604 (18)
C12—C131.3798 (17)C20—H20B0.9601 (18)
C12—C161.5300 (18)C20—H20C0.9603 (18)
C13—C141.4110 (17)O1W—H1WA0.969 (10)
O1—C131.3412 (18)O1W—H1WB1.017 (10)
O1—H1O0.9811 (18)O2W—H2WA0.983 (9)
H1O—O10.9811 (18)O2W—H2WB1.059 (11)
C14—C131.4110 (17)
C2—C1—C6116.43 (13)C13—C14—H14119.88 (17)
C2—C1—C9122.84 (13)C13—C14—C15120.26 (12)
C6—C1—C9120.71 (13)H14—C14—C15119.86 (19)
C1—C2—H2120.01 (18)C10—C15—C14121.96 (16)
C1—C2—C3120.03 (12)C10—C15—H15118.90 (15)
H2—C2—C3119.96 (19)C14—C15—H15118.88 (15)
C2—C3—H3119.75 (15)C12—C16—H16A109.00 (16)
C2—C3—C4120.39 (16)C12—C16—H16B109.00 (16)
H3—C3—C4119.76 (15)C12—C16—N3111.81 (16)
C3—C4—C5123.28 (12)H16A—C16—H16B108.98 (17)
C4—C5—H5121.99 (17)H16A—C16—N3109.00 (17)
C4—C5—C6115.96 (12)H16B—C16—N3109.00 (17)
H5—C5—C6122.01 (15)C16—N3—H3N107.47 (17)
C1—C6—C5123.68 (12)C16—N3—C17109.84 (16)
C1—C6—N1118.98 (11)C16—N3—C19109.68 (16)
C5—C6—N1117.34 (12)H3N—N3—C17107.49 (17)
C6—N1—H1N120.07 (14)H3N—N3—C19107.48 (16)
C6—N1—C7119.74 (12)C17—N3—C19114.59 (16)
H1N—N1—C7120.04 (19)N3—C17—H17A108.92 (17)
N1—C7—H7118.11 (15)N3—C17—H17B108.95 (17)
N1—C7—C8123.73 (12)N3—C17—C18112.07 (16)
H7—C7—C8118.10 (16)H17A—C17—H17B108.97 (17)
C7—C8—H8120.01 (15)H17A—C17—C18108.93 (17)
C7—C8—C9119.14 (15)H17B—C17—C18108.95 (16)
H8—C8—C9120.0 (2)C17—C18—H18A109.47 (2)
C1—C9—C8117.32 (14)C17—C18—H18B109.48 (2)
C1—C9—N2120.66 (13)C17—C18—H18C109.4 (4)
C8—C9—N2121.55 (16)H18A—C18—H18B109.47 (17)
C9—N2—H2N115.05 (19)H18A—C18—H18C109.48 (2)
C9—N2—C10128.25 (17)H18B—C18—H18C109.48 (2)
H2N—N2—C10115.04 (18)N3—C19—H19A109.02 (19)
N2—C10—C11122.43 (14)N3—C19—H19B109.00 (18)
N2—C10—C15118.71 (18)N3—C19—C20111.77 (18)
C11—C10—C15117.79 (12)H19A—C19—H19B109.0 (4)
C10—C11—H11119.89 (17)H19A—C19—C20109.01 (18)
C10—C11—C12120.19 (12)H19B—C19—C20109.01 (18)
H11—C11—C12119.92 (18)C19—C20—H20A109.46 (3)
C11—C12—C13121.11 (11)C19—C20—H20B109.49 (3)
C11—C12—C16118.80 (15)C19—C20—H20C109.46 (17)
C13—C12—C16119.73 (16)H20A—C20—H20B109.47 (18)
C12—C13—O1119.71 (14)H20A—C20—H20C109.47 (2)
C12—C13—C14118.13 (14)H20B—C20—H20C109.49 (2)
O1—C13—C14121.77 (17)H1WA—O1W—H1WB99.3 (9)
C13—O1—H1O114.6 (4)H2WA—O2W—H2WB97.3 (8)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···Cl2i0.93 (1)2.26 (1)3.160 (6)162 (1)
N2—H2N···O2Wii0.93 (2)2.07 (2)2.902 (12)148 (1)
N3—H3N···Cl30.93 (1)2.15 (1)3.016 (7)155 (1)
O1—H1O···Cl2iii0.982.063.037 (7)177
O1W—H1WA···Cl30.972.163.127 (11)175
O1W—H1WB···Cl3iv1.022.283.297 (11)177
O2W—H2WA···O1W0.981.842.816 (14)171
O2W—H2WB···Cl2iv1.062.133.188 (12)177
C2—H2···O2Wii0.93 (1)2.37 (1)3.279 (12)167 (1)
C5—H5···Cl2i0.93 (1)2.77 (1)3.529 (9)140 (1)
C16—H16B···O10.97 (1)2.41 (1)2.813 (7)105 (1)
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, −y+1, −z+2; (iii) x, −y+3/2, z+1/2; (iv) −x+1, −y+1, −z+1.
Selected geometric parameters (Å, °) of amodiaquine in the crystal structures of amodiaquinium dihydrochloride monohydrate (VOTFIT; Yennawar & Viswamitra, 1991) and amodiaquinium dihydrochloride dihydrate, (I). Atom labels are given in Fig. 1. top
Parametermonohydratedihydrate
C8—C9—N2—C1017.2 (7)5.0 (12)
C9—N2—C10—C1134.7 (7)46.9 (12)
Quinoline–phenyl interplanar angle4854.6 (4)
C11—C12—C16—N3-91.477.4 (8)
 

Acknowledgements

AL, LF and JMG thank the Pfizer Institute for Pharmaceutical Materials Science for funding. JB thanks Jesus College, Cambridge, for the award of a Junior Research Fellowship.

References

First citationAllen, F. H. (2002). Acta Cryst. B58, 380–388.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
 First citationBoultif, A. & Louër, D. (1991). J. Appl. Cryst. 24, 987–993.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationBoultif, A. & Louër, D. (2004). J. Appl. Cryst. 37, 724–731.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationDavid, W. I. F., Shankland, K., van de Streek, J., Pidcock, E. & Motherwell, S. (2004). DASH. Version 3.0. Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, England.  Google Scholar
 First citationDavid, W. I. F. & Sivia, D. S. (2001). J. Appl. Cryst. 34, 318–324.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationFinger, L. W., Cox, D. E. & Jephcoat, A. P. (1994). J. Appl. Cryst. 27, 892–900.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationInfantes, L. & Motherwell, W. D. S. (2004). Chem. Commun. pp. 1166–1167.  Web of Science CrossRef Google Scholar
 First citationLarson, A. C. & Von Dreele, R. B. (2000). GSAS. Report LAUR 86-748. Los Alamos National Laboratory, New Mexico, USA.  Google Scholar
 First citationMacrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
 First citationMarkvardsen, A. J., David, W. I. F., Johnson, J. C. & Shankland, K. (2001). Acta Cryst. A57, 47–54.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationOlliaro, P. & Mussano, P. (2003). Amodiaquine for Treating Malaria in The Cochrane Database of Systematic Reviews. (https://www.cochrane.org/reviews/index.htm)  Google Scholar
 First citationStoe (1999). WinXPow. Stoe & Cie, Darmstadt, Germany.  Google Scholar
 First citationThompson, P., Cox, D. E. & Hastings, J. B. (1987). J. Appl. Cryst. 20, 79–83.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationYennawar, H. P. & Viswamitra, M. A. (1991). Curr. Sci. 61, 39–43.  CAS Google Scholar

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ISSN: 2056-9890
Volume 62| Part 9| September 2006| Pages o4196-o4199
https://doi.org/10.1107/S1600536806033691
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