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Acta Crystallogr Sect E Struct Rep Online. 2009 September 1; 65(Pt 9): o2191.
Published online 2009 August 19. doi:  10.1107/S1600536809031791
PMCID: PMC2970061

Memanti­nium chloride 0.1-hydrate

Abstract

The crystal structure of the title compound, C12H22N+·Cl·0.1H2O, consists of (3,5-dimethyl-1-adamantyl)ammonium chloride (memanti­nium chloride) and uncoordinated water mol­ecules. The four six-membered rings of the memanti­nium cation assume typical chair conformations. The Cl counter-anion links with the memanti­nium cation via N—H(...)Cl hydrogen bonding, forming channels where the disordered crystal water molecules are located. The O atom of the water mol­ecule is located on a threefold rotation axis, its two H atoms symmetrically distributed over six sites; the water mol­ecule links with the Cl anions via O—H(...)Cl hydrogen bonding.

Related literature

For applications of memantine in medicine, see: Parsons et al. (1999 [triangle]); Tariot et al. (2004 [triangle]). For a related structure, see: Zahid et al. (2009 [triangle]). The H atoms of the ncoordinated water mol­ecule were placed at calculated positions, see: Nardelli (1999 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2191-scheme1.jpg

Experimental

Crystal data

  • C12H22N+·Cl·0.1H2O
  • M r = 217.56
  • Trigonal, An external file that holds a picture, illustration, etc.
Object name is e-65-o2191-efi1.jpg
  • a = 28.3787 (11) Å
  • c = 8.5236 (4) Å
  • V = 5944.8 (4) Å3
  • Z = 18
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 294 K
  • 0.41 × 0.18 × 0.16 mm

Data collection

  • Rigaku R-AXIS RAPID diffractometer
  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995 [triangle]) T min = 0.888, T max = 0.959
  • 18491 measured reflections
  • 2845 independent reflections
  • 1671 reflections with I > 2σ(I)
  • R int = 0.043

Refinement

  • R[F 2 > 2σ(F 2)] = 0.034
  • wR(F 2) = 0.104
  • S = 1.09
  • 2845 reflections
  • 132 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.31 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1329 Friedel pairs
  • Flack parameter: 0.06 (9)

Data collection: PROCESS-AUTO (Rigaku, 2006 [triangle]); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809031791/xu2585sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809031791/xu2585Isup2.hkl

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

Acknowledgments

The project was supported by the Zhejiang Provincial Natural Science Foundation of China.

supplementary crystallographic information

Comment

The title compound is one of a small group of tricycle antiviral drugs (TVA). Memantine also provides good and persistent activation of central nervous N-methyl-D-aspartate (NMDA) receptors, and, thus can be used in the treatment of Parkinson's disease and Alzheimer's disease (Parsons et al., 1999; Tariot et al., 2004).

In the asymmetric unit of the crystal structure of the title compound, there are one mamentinium cation, one Cl- anion and 0.10 lattice water molecule. The expected proton transfer from hydrochloric acid to N1 atom of amino group occurs. The four six-membered rings of the memantinium cation assume typical chair conformations, which is comparable with that found in related structures (Zahid et al., 2009). The Cl- counter-anion links with the memantinium cation via N—H···Cl hydrogen bonding (Fig. 1). The lattice water molecules are located on the channels formed by memantininum cations and Cl- anions (Fig. 2). The O atom of lattice water molecule is located at the threefold rotation axis, and its two H atoms are symmetrically distributed over six sites and linked to Cl- anions via O—H···Cl hydrogen bonding (Table 1).

Experimental

The crude product is supplied by Zhejiang Apeloa Pharmaceutical Co.,LTD. It was recrystallized from ethanol solution, giving colorless crystals of (1) suitable for X-ray diffraction.

Refinement

Site occupancy factor of the water O1 atom was refined to 0.093 and fixed as 0.1 at the final cycles of refinement. The two H atoms of the water molecule were placed at calculated positions (Nardelli, 1999), and refined as riding in as-found relative positions with Uiso(H) = 1.5Ueq(O). Other H atoms were placed in calculated positions with C—H = 0.96–0.98 Å and N—H = 0.89 Å, and included in the refinement in riding model, with Uiso(H) = 1.2Ueq(C) and 1.5Ueq(N).

Figures

Fig. 1.
Molecular structure of the title compound showing atom-labelling scheme and displacement ellipsoids at 30% probability level. H atoms are shown as small circles of arbitary radii. Dashed lines indicate the hydrogen bonding.
Fig. 2.
The unit cell packing diagram of the title compound.

Crystal data

C12H22N·Cl·0.1(H2O)Dx = 1.094 Mg m3
Mr = 217.56Mo Kα radiation, λ = 0.71073 Å
Trigonal, R3cCell parameters from 10816 reflections
Hall symbol: R 3 -2"cθ = 3.2–27.4°
a = 28.3787 (11) ŵ = 0.26 mm1
c = 8.5236 (4) ÅT = 294 K
V = 5944.8 (4) Å3Block, colorless
Z = 180.41 × 0.18 × 0.16 mm
F(000) = 2142

Data collection

Rigaku R-AXIS RAPID diffractometer2845 independent reflections
Radiation source: rolling anode1671 reflections with I > 2σ(I)
graphiteRint = 0.043
Detector resolution: 10.00 pixels mm-1θmax = 27.4°, θmin = 3.2°
ω scansh = −36→36
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)k = −36→36
Tmin = 0.888, Tmax = 0.959l = −11→9
18491 measured reflections

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.034w = 1/[σ2(Fo2) + (0.0331P)2 + 3.5112P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.104(Δ/σ)max = 0.001
S = 1.09Δρmax = 0.28 e Å3
2845 reflectionsΔρmin = −0.31 e Å3
132 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.00185 (17)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 1329 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.06 (9)

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. 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 (Å2)

xyzUiso*/UeqOcc. (<1)
N10.33309 (10)0.56273 (9)0.6470 (3)0.0597 (6)
H1A0.36320.59110.60980.090*
H1B0.33200.56560.75080.090*
H1C0.30410.56200.60460.090*
C10.33298 (13)0.51132 (11)0.6066 (3)0.0552 (7)
C70.28247 (16)0.41097 (14)0.6378 (5)0.0840 (10)
H70.24980.37980.68130.101*
C50.38468 (14)0.46190 (13)0.6423 (4)0.0727 (9)
C40.38361 (11)0.51418 (10)0.6791 (3)0.0621 (7)
H4A0.38330.51870.79180.074*
H4B0.41600.54530.63700.074*
C120.43554 (15)0.46469 (17)0.7130 (5)0.1084 (13)
H12A0.46740.49500.66890.130*
H12B0.43570.43170.68980.130*
H12C0.43550.46910.82460.130*
C20.28213 (12)0.46352 (12)0.6771 (4)0.0720 (8)
H2A0.24980.46210.63390.086*
H2B0.28190.46780.78990.086*
C100.38348 (15)0.45520 (14)0.4635 (4)0.0764 (9)
H10A0.41590.48560.41900.092*
H10B0.38410.42220.43880.092*
C30.33333 (14)0.50494 (13)0.4295 (3)0.0647 (9)
H3A0.36530.53600.38530.078*
H3B0.30140.50370.38440.078*
C60.33304 (14)0.41367 (13)0.7103 (5)0.0874 (10)
H6A0.33310.38010.68880.105*
H6B0.33240.41770.82320.105*
C90.33374 (13)0.45250 (12)0.3886 (4)0.0732 (8)
C110.33487 (18)0.44638 (16)0.2099 (4)0.1064 (14)
H11A0.36700.47690.16780.128*
H11B0.30320.44500.16440.128*
H11C0.33510.41340.18580.128*
C80.28330 (16)0.40466 (14)0.4610 (5)0.0876 (11)
H8A0.25090.40250.41570.105*
H8B0.28290.37110.43690.105*
Cl10.22918 (3)0.56280 (3)0.51793 (11)0.0756 (2)
O10.33330.66670.800 (4)0.181 (9)0.30
H1E0.33300.64100.85570.272*0.10
H1F0.30700.64800.72750.272*0.10

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0637 (13)0.0571 (13)0.0653 (14)0.0355 (12)−0.0009 (11)0.0000 (11)
C10.0562 (17)0.0471 (16)0.065 (2)0.0274 (14)0.0031 (14)0.0011 (13)
C70.077 (2)0.0513 (19)0.112 (3)0.0234 (17)0.011 (2)0.0112 (17)
C50.074 (2)0.0604 (19)0.094 (3)0.0408 (18)−0.0034 (17)0.0013 (17)
C40.0613 (16)0.0568 (16)0.0704 (18)0.0312 (13)−0.0010 (14)0.0009 (14)
C120.110 (3)0.110 (3)0.137 (4)0.079 (3)−0.029 (3)−0.011 (2)
C20.0639 (18)0.0590 (17)0.088 (2)0.0269 (15)0.0116 (15)0.0076 (15)
C100.083 (2)0.066 (2)0.091 (2)0.0453 (18)0.0076 (18)−0.0068 (18)
C30.074 (2)0.0591 (18)0.066 (2)0.0364 (17)−0.0033 (17)−0.0064 (14)
C60.102 (3)0.064 (2)0.101 (3)0.0448 (19)0.009 (2)0.0171 (18)
C90.088 (2)0.0599 (17)0.077 (2)0.0406 (17)−0.0032 (17)−0.0150 (15)
C110.150 (4)0.094 (3)0.085 (3)0.069 (3)−0.009 (2)−0.028 (2)
C80.086 (3)0.0538 (19)0.115 (3)0.0293 (19)−0.011 (2)−0.016 (2)
Cl10.0867 (6)0.0914 (6)0.0679 (4)0.0589 (4)−0.0076 (5)−0.0064 (5)
O10.145 (9)0.145 (9)0.25 (3)0.073 (4)0.0000.000

Geometric parameters (Å, °)

N1—C11.497 (3)C2—H2A0.9700
N1—H1A0.8900C2—H2B0.9700
N1—H1B0.8900C10—C91.516 (5)
N1—H1C0.8900C10—H10A0.9700
C1—C31.521 (3)C10—H10B0.9700
C1—C21.525 (4)C3—C91.534 (4)
C1—C41.529 (4)C3—H3A0.9700
C7—C81.519 (5)C3—H3B0.9700
C7—C61.529 (5)C6—H6A0.9700
C7—C21.533 (5)C6—H6B0.9700
C7—H70.9800C9—C81.526 (5)
C5—C121.529 (4)C9—C111.535 (5)
C5—C41.532 (4)C11—H11A0.9600
C5—C101.534 (4)C11—H11B0.9600
C5—C61.533 (5)C11—H11C0.9600
C4—H4A0.9700C8—H8A0.9700
C4—H4B0.9700C8—H8B0.9700
C12—H12A0.9600O1—H1E0.8634
C12—H12B0.9600O1—H1F0.9108
C12—H12C0.9600
C1—N1—H1A109.5C7—C2—H2B110.0
C1—N1—H1B109.5H2A—C2—H2B108.4
H1A—N1—H1B109.5C9—C10—C5112.8 (3)
C1—N1—H1C109.5C9—C10—H10A109.0
H1A—N1—H1C109.5C5—C10—H10A109.0
H1B—N1—H1C109.5C9—C10—H10B109.0
N1—C1—C3110.3 (3)C5—C10—H10B109.0
N1—C1—C2108.4 (2)H10A—C10—H10B107.8
C3—C1—C2110.2 (2)C1—C3—C9110.2 (3)
N1—C1—C4108.1 (2)C1—C3—H3A109.6
C3—C1—C4110.2 (2)C9—C3—H3A109.6
C2—C1—C4109.5 (2)C1—C3—H3B109.6
C8—C7—C6109.7 (3)C9—C3—H3B109.6
C8—C7—C2109.8 (3)H3A—C3—H3B108.1
C6—C7—C2109.0 (3)C7—C6—C5110.2 (3)
C8—C7—H7109.4C7—C6—H6A109.6
C6—C7—H7109.4C5—C6—H6A109.6
C2—C7—H7109.4C7—C6—H6B109.6
C12—C5—C4110.2 (3)C5—C6—H6B109.6
C12—C5—C10111.1 (3)H6A—C6—H6B108.1
C4—C5—C10108.2 (2)C10—C9—C8108.1 (3)
C12—C5—C6110.7 (3)C10—C9—C3108.3 (3)
C4—C5—C6108.3 (3)C8—C9—C3108.2 (3)
C10—C5—C6108.2 (3)C10—C9—C11110.6 (3)
C1—C4—C5109.8 (2)C8—C9—C11111.3 (3)
C1—C4—H4A109.7C3—C9—C11110.2 (3)
C5—C4—H4A109.7C9—C11—H11A109.5
C1—C4—H4B109.7C9—C11—H11B109.5
C5—C4—H4B109.7H11A—C11—H11B109.5
H4A—C4—H4B108.2C9—C11—H11C109.5
C5—C12—H12A109.5H11A—C11—H11C109.5
C5—C12—H12B109.5H11B—C11—H11C109.5
H12A—C12—H12B109.5C7—C8—C9111.0 (3)
C5—C12—H12C109.5C7—C8—H8A109.4
H12A—C12—H12C109.5C9—C8—H8A109.4
H12B—C12—H12C109.5C7—C8—H8B109.4
C1—C2—C7108.4 (3)C9—C8—H8B109.4
C1—C2—H2A110.0H8A—C8—H8B108.0
C7—C2—H2A110.0H1E—O1—H1F102.8
C1—C2—H2B110.0
N1—C1—C4—C5179.2 (2)C8—C7—C6—C559.3 (4)
C3—C1—C4—C5−60.1 (3)C2—C7—C6—C5−61.0 (4)
C2—C1—C4—C561.2 (3)C12—C5—C6—C7−179.5 (3)
C12—C5—C4—C1179.4 (3)C4—C5—C6—C759.6 (4)
C10—C5—C4—C157.8 (3)C10—C5—C6—C7−57.5 (4)
C6—C5—C4—C1−59.4 (3)C5—C10—C9—C8−58.5 (3)
N1—C1—C2—C7−179.1 (3)C5—C10—C9—C358.5 (3)
C3—C1—C2—C760.0 (3)C5—C10—C9—C11179.4 (3)
C4—C1—C2—C7−61.4 (3)C1—C3—C9—C10−58.1 (3)
C8—C7—C2—C1−59.2 (4)C1—C3—C9—C858.8 (3)
C6—C7—C2—C161.0 (4)C1—C3—C9—C11−179.2 (3)
C12—C5—C10—C9−179.7 (3)C6—C7—C8—C9−59.8 (4)
C4—C5—C10—C9−58.7 (3)C2—C7—C8—C960.0 (4)
C6—C5—C10—C958.5 (3)C10—C9—C8—C758.3 (4)
N1—C1—C3—C9179.5 (3)C3—C9—C8—C7−58.8 (4)
C2—C1—C3—C9−60.8 (3)C11—C9—C8—C7180.0 (3)
C4—C1—C3—C960.1 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1A···Cl1i0.892.263.147 (3)176
N1—H1B···Cl1ii0.892.283.161 (2)171
N1—H1C···Cl10.892.263.148 (3)175
O1—H1E···Cl1ii0.862.623.486 (17)179
O1—H1F···Cl10.912.933.81 (2)163

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: XU2585).

References

  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Higashi, T. (1995). ABSCOR Rigaku Corporation, Tokyo, Japan.
  • Nardelli, M. (1999). J. Appl. Cryst.32, 563–571.
  • Parsons, C. G., Danysz, W. & Quack, G. (1999). Neuropharmacology, 38, 735–767. [PubMed]
  • Rigaku (2006). PROCESS-AUTO Rigaku Corporation, Tokyo, Japan.
  • Rigaku (2007). CrystalStructure Rigaku Corporation, Tokyo, Japan.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Tariot, P. N., Farlow, M. R., Grossbeq, G. T., Graham, S. M., McDonald, S. & Gergel, I. (2004). J. Am. Med. Assoc.291, 317–324. [PubMed]
  • Zahid, M., Khawar Rauf, M., Bolte, M. & Hameed, S. (2009). Acta Cryst. E65, o1891. [PMC free article] [PubMed]

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