supplementary materials


HTML versionpdf versioncif file3d viewstructure factorssupplementary materialsCIF check reportsimilar papers Open access

Acta Cryst. (2009). E65, o2191    [ doi:10.1107/S1600536809031791 ]

Memantinium chloride 0.1-hydrate

W.-J. Lou, X.-R. Hu and J.-M. Gu

Abstract top

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.

Comment top

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).

Related literature top

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

Experimental top

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 top

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).

Computing details top

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

Figures top
[Figure 1] 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.
[Figure 2] Fig. 2. The unit cell packing diagram of the title compound.
(3,5-dimethyl-1-adamantyl)ammonium chloride 0.1-hydrate top
Crystal data top
C12H22N·Cl·0.1(H2O)Dx = 1.094 Mg m−3
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 mm−1
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 top
Rigaku R-AXIS RAPID
diffractometer		2845 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 top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.034 w = 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 Å−3
2845 reflectionsΔρmin = −0.31 e Å−3
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)
Crystal data top
C12H22N·Cl·0.1(H2O)Z = 18
Mr = 217.56Mo Kα radiation
Trigonal, R3cµ = 0.26 mm−1
a = 28.3787 (11) ÅT = 294 K
c = 8.5236 (4) Å0.41 × 0.18 × 0.16 mm
V = 5944.8 (4) Å3
Data collection top
Rigaku R-AXIS RAPID
diffractometer		2845 independent reflections
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)		1671 reflections with I > 2σ(I)
Tmin = 0.888, Tmax = 0.959Rint = 0.043
18491 measured reflectionsθmax = 27.4°
Refinement top
R[F2 > 2σ(F2)] = 0.034H-atom parameters constrained
wR(F2) = 0.104Δρmax = 0.28 e Å−3
S = 1.09Δρmin = −0.31 e Å−3
2845 reflectionsAbsolute structure: Flack (1983), 1329 Friedel pairs
132 parametersFlack parameter: 0.06 (9)
1 restraint
Special details top

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) top
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) top
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, °) top
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, °) top
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, x−y+1, z; (ii) −x+y, y, z+1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
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, x−y+1, z; (ii) −x+y, y, z+1/2.
Acknowledgements top

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

references
References top

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.

Rigaku (2006). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.

Rigaku (2007). CrystalStructure. Rigaku Corporation, Tokyo, Japan.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Tariot, P. N., Farlow, M. R., Grossbeq, G. T., Graham, S. M., McDonald, S. & Gergel, I. (2004). J. Am. Med. Assoc. 291, 317–324.

Zahid, M., Khawar Rauf, M., Bolte, M. & Hameed, S. (2009). Acta Cryst. E65, o1891.