organic compounds
of bis{2-[amino(iminiumyl)methyl]-1,1-dimethylguanidine} carbonate methanol disolvate
aInstitute of Molecular Science, Key Laboratory of Chemical Biology of Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, People's Republic of China
*Correspondence e-mail: dongjinlong20123@163.com
In the title solvated molecular salt, 2C4H12N5+·CO32−·2CH3OH, the complete carbonate ion is generated by crystallographic twofold symmetry, with the C atom and one O atom lying on the rotation axis. The cation is twisted about the central C—N bond [C—N—C—N = −137.7 (6)°]. In the crystal, the components are linked by N—H⋯O, N—H⋯N and O—H⋯O hydrogen bonds, generating a three-dimensional supramolecular network.
Keywords: crystal structure; metformin; sodium carbonate; hydrogen bonding.
CCDC reference: 1422939
1. Related literature
For background to and medical applications of metformin (systematic name: N,N-dimethylimidodicarbonimidic diamide), see: Castagnolo et al. (2011); De Jager et al. (2005); Pérez-Fernández et al. (2013); Yardımcı & Özaltın (2005); Xi et al. (2008); Li et al. (2005). For a related structure, see: Huang et al. (2008).
2. Experimental
2.1. Crystal data
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2.3. Refinement
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Data collection: APEX2 (Bruker, 2000); cell SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.
Supporting information
CCDC reference: 1422939
10.1107/S2056989015016771/hb7495sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2056989015016771/hb7495Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989015016771/hb7495Isup3.cml
Metformin, an oral antidiabetic drug, has been extensively used throughout the world over the last five decades to treat type-2 diabetes mellitus[Castagnolo et al. , 2011; De Jager et al. , 2005; Pérez-Fernández et al. , 2013 ], in particular, in overweight and obese people. Metformin has a distinct advantage of lowering serum glucose levels without causing hyper-insulinemia and subsequent risk of hypoglycemia [Yardimci et al. , 2005; Xi et al. , 2008; Liu et al. , 2005]. In order to find a substance that enhances the therapeutic effects of metformin, and exhibits additional pancreas-protecting effects, we synthesized the title compound (Fig. 1). Some examples of related structures already appear in the literature[Pérez-Fernández et al. , 2013; Huamg et al. , 2008]. The structure of the title compound contains two metformin molecules, one methanol molecule and carbonate ion (Fig. 1). In the crystal, N—H···O, N—H···N and O—H···O hydrogen bonds connect molecules to form a two-dimensional network parallel to (001) (Fig. 2).
Crystal data, data collection and structure
details are summarized in Table 1.The N—H hydrogen atom was located in a difference Fourier map and freely refined: N—H = 0.86 Å. The C-bound H-atoms were included in calculated positions and treated as riding atoms: C—H = 0.96 Å with Uiso (H) = 1.2 or 1.5Ueq (C).A methanol solution (20 ml) of sodium carbonate (485 mg, 3.03 mmol) and metformin hydrochloride (500 mg, 3.03 mmol) was stirred for 12 h at room temperature. The solid part (sodium chloride) was filtered off. The rest of the solution was slowly evaporated at room temperature, yielding colourless blocks of the title compound.
Data collection: APEX2 (Bruker, 2000); cell
SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level. | |
Fig. 2. Part of the crystal structure with the hydrogen bonds drawn as dashed lines. |
2C4H12N5+·CO32−·2CH4O | F(000) = 832 |
Mr = 384.46 | Dx = 1.274 Mg m−3 |
Monoclinic, C2/c | Mo Kα radiation, λ = 0.71073 Å |
a = 13.5726 (12) Å | Cell parameters from 1052 reflections |
b = 10.5634 (8) Å | θ = 2.8–22.8° |
c = 13.9825 (13) Å | µ = 0.10 mm−1 |
β = 90.386 (1)° | T = 298 K |
V = 2004.7 (3) Å3 | Block, colourless |
Z = 4 | 0.40 × 0.32 × 0.29 mm |
Bruker APEXII CCD diffractometer | 947 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.065 |
φ and ω scans | θmax = 25.1°, θmin = 2.8° |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | h = −16→15 |
Tmin = 0.961, Tmax = 0.971 | k = −12→11 |
4837 measured reflections | l = −16→16 |
1749 independent reflections |
Refinement on F2 | 6 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.083 | H-atom parameters constrained |
wR(F2) = 0.280 | w = 1/[σ2(Fo2) + (0.1395P)2 + 3.7847P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
1749 reflections | Δρmax = 0.64 e Å−3 |
123 parameters | Δρmin = −0.29 e Å−3 |
2C4H12N5+·CO32−·2CH4O | V = 2004.7 (3) Å3 |
Mr = 384.46 | Z = 4 |
Monoclinic, C2/c | Mo Kα radiation |
a = 13.5726 (12) Å | µ = 0.10 mm−1 |
b = 10.5634 (8) Å | T = 298 K |
c = 13.9825 (13) Å | 0.40 × 0.32 × 0.29 mm |
β = 90.386 (1)° |
Bruker APEXII CCD diffractometer | 1749 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | 947 reflections with I > 2σ(I) |
Tmin = 0.961, Tmax = 0.971 | Rint = 0.065 |
4837 measured reflections |
R[F2 > 2σ(F2)] = 0.083 | 6 restraints |
wR(F2) = 0.280 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.64 e Å−3 |
1749 reflections | Δρmin = −0.29 e Å−3 |
123 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.9937 (3) | 0.6120 (4) | 0.3964 (3) | 0.0764 (14) | |
H1A | 1.0180 | 0.6664 | 0.3574 | 0.092* | |
H1B | 1.0312 | 0.5752 | 0.4377 | 0.092* | |
N2 | 0.8445 (3) | 0.6436 (4) | 0.3289 (3) | 0.0651 (12) | |
H2A | 0.8709 | 0.6975 | 0.2908 | 0.078* | |
H2B | 0.7824 | 0.6279 | 0.3250 | 0.078* | |
N3 | 0.8641 (3) | 0.5040 (4) | 0.4562 (3) | 0.0753 (14) | |
N4 | 0.7163 (3) | 0.4414 (5) | 0.5183 (3) | 0.0787 (14) | |
N5 | 0.7482 (3) | 0.3984 (4) | 0.3619 (3) | 0.0663 (12) | |
H5A | 0.6934 | 0.3578 | 0.3579 | 0.080* | |
H5B | 0.7857 | 0.4044 | 0.3128 | 0.080* | |
O1 | 0.43093 (19) | 0.6744 (3) | 0.7084 (2) | 0.0513 (9) | |
O2 | 0.5000 | 0.4941 (4) | 0.7500 | 0.0802 (17) | |
O3 | 0.3680 (3) | 0.3385 (6) | 0.6850 (5) | 0.143 (2) | |
H3 | 0.4110 | 0.3854 | 0.7063 | 0.214* | |
C1 | 0.8990 (3) | 0.5850 (5) | 0.3931 (3) | 0.0584 (12) | |
C2 | 0.7748 (3) | 0.4516 (5) | 0.4435 (3) | 0.0627 (14) | |
C3 | 0.6269 (4) | 0.3681 (7) | 0.5153 (4) | 0.095 (2) | |
H3A | 0.5800 | 0.4085 | 0.4737 | 0.143* | |
H3B | 0.6001 | 0.3621 | 0.5785 | 0.143* | |
H3C | 0.6410 | 0.2847 | 0.4917 | 0.143* | |
C4 | 0.7393 (6) | 0.5018 (9) | 0.6077 (5) | 0.127 (3) | |
H4A | 0.8000 | 0.5476 | 0.6020 | 0.191* | |
H4B | 0.7458 | 0.4389 | 0.6568 | 0.191* | |
H4C | 0.6873 | 0.5594 | 0.6240 | 0.191* | |
C5 | 0.3996 (9) | 0.2845 (15) | 0.6049 (14) | 0.279 (10) | |
H5D | 0.3442 | 0.2644 | 0.5646 | 0.419* | |
H5E | 0.4349 | 0.2084 | 0.6203 | 0.419* | |
H5F | 0.4424 | 0.3419 | 0.5719 | 0.419* | |
C6 | 0.5000 | 0.6130 (5) | 0.7500 | 0.0422 (13) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.055 (2) | 0.092 (3) | 0.082 (3) | −0.035 (2) | −0.022 (2) | 0.034 (2) |
N2 | 0.050 (2) | 0.079 (3) | 0.067 (3) | −0.0205 (19) | −0.0089 (19) | 0.017 (2) |
N3 | 0.065 (3) | 0.104 (3) | 0.056 (2) | −0.049 (2) | −0.0220 (19) | 0.023 (2) |
N4 | 0.076 (3) | 0.108 (4) | 0.051 (3) | −0.041 (3) | 0.000 (2) | −0.003 (2) |
N5 | 0.058 (2) | 0.093 (3) | 0.047 (2) | −0.034 (2) | −0.0063 (17) | 0.000 (2) |
O1 | 0.0389 (15) | 0.0469 (17) | 0.068 (2) | −0.0007 (12) | −0.0176 (13) | −0.0020 (14) |
O2 | 0.060 (3) | 0.037 (3) | 0.144 (5) | 0.000 | −0.032 (3) | 0.000 |
O3 | 0.063 (3) | 0.135 (4) | 0.230 (7) | −0.016 (3) | 0.011 (3) | −0.097 (4) |
C1 | 0.051 (3) | 0.076 (3) | 0.048 (2) | −0.024 (2) | −0.009 (2) | 0.006 (2) |
C2 | 0.059 (3) | 0.079 (3) | 0.050 (3) | −0.032 (2) | −0.012 (2) | 0.015 (2) |
C3 | 0.076 (4) | 0.133 (5) | 0.077 (4) | −0.048 (4) | 0.007 (3) | 0.010 (4) |
C4 | 0.140 (6) | 0.180 (8) | 0.062 (4) | −0.046 (6) | 0.006 (4) | −0.028 (5) |
C5 | 0.153 (9) | 0.254 (15) | 0.43 (2) | −0.090 (10) | 0.122 (12) | −0.223 (16) |
C6 | 0.029 (3) | 0.039 (3) | 0.059 (4) | 0.000 | −0.007 (2) | 0.000 |
N1—C1 | 1.317 (6) | C6—O1 | 1.276 (4) |
N1—H1A | 0.8600 | C6—O2 | 1.257 (7) |
N1—H1B | 0.8600 | O3—C5 | 1.330 (13) |
N2—C1 | 1.314 (6) | O3—H3 | 0.8200 |
N2—H2A | 0.8600 | C3—H3A | 0.9600 |
N2—H2B | 0.8600 | C3—H3B | 0.9600 |
N3—C1 | 1.319 (6) | C3—H3C | 0.9600 |
N3—C2 | 1.344 (5) | C4—H4A | 0.9600 |
N4—C2 | 1.321 (6) | C4—H4B | 0.9600 |
N4—C4 | 1.436 (8) | C4—H4C | 0.9600 |
N4—C3 | 1.440 (6) | C5—H5D | 0.9600 |
N5—C2 | 1.320 (6) | C5—H5E | 0.9600 |
N5—H5A | 0.8600 | C5—H5F | 0.9600 |
N5—H5B | 0.8600 | C6—O1i | 1.276 (4) |
C1—N1—H1A | 120.0 | N4—C3—H3B | 109.5 |
C1—N1—H1B | 120.0 | H3A—C3—H3B | 109.5 |
H1A—N1—H1B | 120.0 | N4—C3—H3C | 109.5 |
C1—N2—H2A | 120.0 | H3A—C3—H3C | 109.5 |
C1—N2—H2B | 120.0 | H3B—C3—H3C | 109.5 |
H2A—N2—H2B | 120.0 | N4—C4—H4A | 109.5 |
C1—N3—C2 | 120.4 (4) | N4—C4—H4B | 109.5 |
C2—N4—C4 | 121.7 (5) | H4A—C4—H4B | 109.5 |
C2—N4—C3 | 122.1 (4) | N4—C4—H4C | 109.5 |
C4—N4—C3 | 116.2 (5) | H4A—C4—H4C | 109.5 |
C2—N5—H5A | 120.0 | H4B—C4—H4C | 109.5 |
C2—N5—H5B | 120.0 | O3—C5—H5D | 109.5 |
H5A—N5—H5B | 120.0 | O3—C5—H5E | 109.5 |
C5—O3—H3 | 109.5 | H5D—C5—H5E | 109.5 |
N2—C1—N1 | 117.9 (4) | O3—C5—H5F | 109.5 |
N2—C1—N3 | 124.0 (4) | H5D—C5—H5F | 109.5 |
N1—C1—N3 | 118.1 (4) | H5E—C5—H5F | 109.5 |
N5—C2—N4 | 119.2 (4) | O2—C6—O1i | 120.5 (2) |
N5—C2—N3 | 122.0 (4) | O2—C6—O1 | 120.5 (2) |
N4—C2—N3 | 118.4 (4) | O1i—C6—O1 | 119.0 (5) |
N4—C3—H3A | 109.5 | ||
C2—N3—C1—N2 | 17.2 (8) | C4—N4—C2—N3 | 9.8 (9) |
C2—N3—C1—N1 | −165.0 (5) | C3—N4—C2—N3 | −169.3 (6) |
C4—N4—C2—N5 | −177.3 (7) | C1—N3—C2—N5 | 49.6 (8) |
C3—N4—C2—N5 | 3.6 (9) | C1—N3—C2—N4 | −137.7 (6) |
Symmetry code: (i) −x+1, y, −z+3/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1ii | 0.86 | 2.04 | 2.883 (5) | 166 |
N1—H1B···N3iii | 0.86 | 2.21 | 3.069 (6) | 175 |
N2—H2A···O1iv | 0.86 | 1.96 | 2.818 (5) | 178 |
N2—H2B···O3v | 0.86 | 2.08 | 2.896 (6) | 159 |
N5—H5A···O1v | 0.86 | 1.95 | 2.728 (4) | 150 |
O3—H3···O2 | 0.82 | 1.77 | 2.591 (5) | 177 |
Symmetry codes: (ii) −x+3/2, −y+3/2, −z+1; (iii) −x+2, −y+1, −z+1; (iv) x+1/2, −y+3/2, z−1/2; (v) −x+1, −y+1, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1i | 0.86 | 2.04 | 2.883 (5) | 166 |
N1—H1B···N3ii | 0.86 | 2.21 | 3.069 (6) | 175 |
N2—H2A···O1iii | 0.86 | 1.96 | 2.818 (5) | 178 |
N2—H2B···O3iv | 0.86 | 2.08 | 2.896 (6) | 159 |
N5—H5A···O1iv | 0.86 | 1.95 | 2.728 (4) | 150 |
O3—H3···O2 | 0.82 | 1.77 | 2.591 (5) | 177 |
Symmetry codes: (i) −x+3/2, −y+3/2, −z+1; (ii) −x+2, −y+1, −z+1; (iii) x+1/2, −y+3/2, z−1/2; (iv) −x+1, −y+1, −z+1. |
Acknowledgements
We are very grateful for financial support from the National Natural Science Foundation of PR China (Nos. 21271122 and 21571117) and a Research Project Supported by Shanxi Scholarship Council of China (2013–018).
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