1-Carboxy­methyl-2-ethyl-4-methyl-1H-imidazol-3-ium chloride monohydrate

Chen, C.-Q.; Luo, S.-N.; Lin, J.-G.; Qiu, L.; Xia, Y.-M.

doi:10.1107/S1600536809013403

organic compounds

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ISSN: 2056-9890

Volume 65| Part 5| May 2009| Page o1081

doi:10.1107/S1600536809013403

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1-Carboxymethyl-2-ethyl-4-methyl-1H-imidazol-3-ium chloride monohydrate

Chuan-Qing Chen,^a Shi-Neng Luo,^b ^* Jian-Guo Lin,^b Ling Qiu ^b and Yong-Mei Xia ^a

^aSchool of Chemical and Materials Engineering, Jiangnan University, Wuxi 214122, People's Republic of China, and ^bThe Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, People's Republic of China
^*Correspondence e-mail: shineng914@yahoo.com.cn

(Received 27 March 2009; accepted 9 April 2009; online 22 April 2009)

In the title compound, C₈H₁₃N₂O₂⁺·Cl⁻·H₂O, the methyl C atom of the ethyl group is slightly out of the imidazole plane, with an N—C(ring)—C—C torsion angle of −15.1 (2)°. In the crystal structure, there are strong intermolecular hydrogen-bonding interactions between the solvent water molecule, the free chloride anion and the organic cation, resulting in a two-dimensional supramolecular network in the ab plane.

Related literature

The title compound is a vital intermediate in the synthesis of bisphosphonic acid, i.e. 2-(2-ethyl-4-methyl-1H-imidazol-1-yl)-1-hydroxyethane-1,1-diyldiphosphonic acid; for a general background on bisphosphonates, see: Dawson (2003 ); Vasireddy et al. (2003 ). For related structures, see: Gao et al. (2004 ); Barczynski et al. (2008 ). For the synthesis, see: Zederenko et al. (1994 ).

Experimental

Crystal data

C₈H₁₃N₂O₂⁺·Cl⁻·H₂O
M_r = 222.67
Monoclinic, P 2₁ /n
a = 11.077 (2) Å
b = 8.4542 (18) Å
c = 11.938 (3) Å
β = 90.265 (3)°
V = 1117.9 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.33 mm⁻¹
T = 93 K
0.40 × 0.40 × 0.35 mm

Data collection

Rigaku SPIDER diffractometer
Absorption correction: multi-scan (RAPID-AUTO; Rigaku, 2004 ) T_min = 0.880, T_max = 0.894
8869 measured reflections
2532 independent reflections
2203 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.036
wR(F²) = 0.099
S = 1.00
2532 reflections
145 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯Cl1	0.881 (17)	2.300 (18)	3.1635 (14)	166.6 (15)
O3—H3A⋯Cl1	0.91 (2)	2.20 (2)	3.1062 (14)	177 (2)
O1—H1O⋯O3ⁱ	0.96 (2)	1.60 (2)	2.5557 (16)	170 (2)
O3—H3B⋯Cl1ⁱⁱ	0.96 (2)	2.14 (2)	3.0860 (14)	168.2 (19)
Symmetry codes: (i) $[-x+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: RAPID-AUTO (Rigaku, 2004); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; 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

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809013403/fj2205sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809013403/fj2205Isup2.hkl

checkCIF report

Comment top

Bisphosphonates with an imidazole ring, namely zoledronate, are effective bone-specific palliative treatments that reduce tumor-induced skeletal complications. With this idea in mind, we intend to synthesis one of the third-generation bisphosphonate compound, 2-(2-ethyl-4-methyl-1H-imidazol-1-yl)-1–1-hydroxyethane-1,1- bisphosphonic acid, which is potentially used for treatment of patients. As a vital intermediate compound for the stepwise reactions of the bisphosphonic acid, the synthesis and crystal structure of the title compound has been reported herein.

In the title compound (I) (Fig. 1), C₈H₁₃N₂O₂⁺.Cl^-.H₂O, all the carbon atoms (C4, C5 and C7) linked to the imidazole ring are almost coplanar with the imidazole ring. The ethyl is slightly out of the imidazole plane with an N1—C3(ring)-C5—C6 torsion angle of -15.116 (211)°. While the 1-substituted acetic acid group is approximately perpendicular to the imidazole ring [dihedral angle = 77.438 (111)°]. There are strong intermolecular hydrogen interactions between the free water molecule (O3), the free chloride anion (Cl1), and the O1 and N1 from the organic cation (Table 1). And the crystal structure is stabilized by these strong hydrogen bond interactions to form two-dimensional supramolecular network along ab plane (Table 1 and Fig. 2).

Related literature top

For general background to bisphosphonates, see: Dawson (2003); Vasireddy et al. (2003). For related structures, see: Gao et al. (2004); Barczynski et al. (2008). For the synthesis, see: Zederenko et al. (1994).

Experimental top

The title compound (I) was synthesized according to previous literature (Zederenko et al., 1994). After reaction, a white powder was obtained (yield 65%). Mp 170–171 °C. Then, compound (I) was recrystallized from acetone solvent; colourless block-shaped crystals were formed after several days (yield 61%). Analysis calculated for C₈H₁₅ClN₂O₃: 43.15, H 6.79, N 12.58%; found: C 43.01, H 6.96, N 12.45%.

Computing details top

Data collection: RAPID-AUTO (Rigaku, 2004); cell refinement: RAPID-AUTO (Rigaku, 2004); data reduction: RAPID-AUTO (Rigaku, 2004); 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).

Figures top

	Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Perspective view of the supramolecular network built from strong intermolecular hydrogen bonds (dashed lines). H atoms not involved in hydrogen bonds have been omitted.

1-Carboxymethyl-2-ethyl-4-methyl-1H-imidazol-3-ium chloride monohydrate top

Crystal data top

C₈H₁₃N₂O₂⁺·Cl⁻·H₂O	F(000) = 472
M_r = 222.67	D_x = 1.323 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3544 reflections
a = 11.077 (2) Å	θ = 3.0–27.5°
b = 8.4542 (18) Å	µ = 0.33 mm⁻¹
c = 11.938 (3) Å	T = 93 K
β = 90.265 (3)°	Block, colorless
V = 1117.9 (4) Å³	0.40 × 0.40 × 0.35 mm
Z = 4

Data collection top

Rigaku SPIDER diffractometer	2532 independent reflections
Radiation source: Rotating Anode	2203 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.031
ω scans	θ_max = 27.5°, θ_min = 3.0°
Absorption correction: multi-scan (RAPID-AUTO; Rigaku, 2004)	h = −13→14
T_min = 0.880, T_max = 0.894	k = −10→10
8869 measured reflections	l = −15→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.099	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ²(F_o²) + (0.0582P)² + 0.06P] where P = (F_o² + 2F_c²)/3
2532 reflections	(Δ/σ)_max < 0.001
145 parameters	Δρ_max = 0.29 e Å⁻³
1 restraint	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₈H₁₃N₂O₂⁺·Cl⁻·H₂O	V = 1117.9 (4) Å³
M_r = 222.67	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 11.077 (2) Å	µ = 0.33 mm⁻¹
b = 8.4542 (18) Å	T = 93 K
c = 11.938 (3) Å	0.40 × 0.40 × 0.35 mm
β = 90.265 (3)°

Data collection top

Rigaku SPIDER diffractometer	2532 independent reflections
Absorption correction: multi-scan (RAPID-AUTO; Rigaku, 2004)	2203 reflections with I > 2σ(I)
T_min = 0.880, T_max = 0.894	R_int = 0.031
8869 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.036	1 restraint
wR(F²) = 0.099	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	Δρ_max = 0.29 e Å⁻³
2532 reflections	Δρ_min = −0.20 e Å⁻³
145 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.19761 (3)	0.57092 (4)	0.31835 (3)	0.02509 (14)
O1	0.88525 (10)	0.95264 (13)	0.14174 (10)	0.0295 (3)
O2	0.79630 (9)	0.72040 (13)	0.17923 (9)	0.0273 (3)
O3	0.40590 (10)	0.32662 (16)	0.33959 (12)	0.0382 (3)
N1	0.42391 (11)	0.70595 (14)	0.18900 (10)	0.0184 (3)
N2	0.57147 (10)	0.84373 (14)	0.12622 (10)	0.0184 (3)
C1	0.42085 (12)	0.68984 (18)	0.07348 (12)	0.0210 (3)
C2	0.51409 (12)	0.77535 (17)	0.03442 (12)	0.0211 (3)
H2	0.5366	0.7869	−0.0418	0.025*
C3	0.51465 (12)	0.79974 (16)	0.21927 (12)	0.0178 (3)
C4	0.32597 (14)	0.5958 (2)	0.01537 (14)	0.0292 (4)
H4A	0.3426	0.5934	−0.0652	0.035*
H4B	0.2469	0.6445	0.0281	0.035*
H4C	0.3258	0.4877	0.0449	0.035*
C5	0.54916 (13)	0.84647 (19)	0.33464 (12)	0.0234 (3)
H5A	0.5677	0.9610	0.3355	0.028*
H5B	0.6236	0.7891	0.3562	0.028*
C6	0.45261 (15)	0.8131 (2)	0.42068 (13)	0.0304 (4)
H6A	0.3789	0.8710	0.4008	0.037*
H6B	0.4809	0.8473	0.4947	0.037*
H6C	0.4355	0.6994	0.4222	0.037*
C7	0.67760 (12)	0.94450 (17)	0.12097 (12)	0.0202 (3)
H7A	0.6672	1.0345	0.1731	0.024*
H7B	0.6849	0.9879	0.0443	0.024*
C8	0.79233 (12)	0.85727 (18)	0.15091 (12)	0.0205 (3)
H1N	0.3693 (15)	0.667 (2)	0.2348 (14)	0.027 (4)*
H1O	0.961 (2)	0.900 (3)	0.1558 (18)	0.060 (7)*
H3A	0.344 (2)	0.397 (3)	0.336 (2)	0.077 (8)*
H3B	0.385 (2)	0.243 (3)	0.289 (2)	0.067 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0190 (2)	0.0276 (2)	0.0287 (2)	−0.00309 (14)	0.00545 (15)	−0.00028 (14)
O1	0.0168 (5)	0.0245 (6)	0.0472 (7)	−0.0020 (5)	0.0009 (5)	0.0008 (5)
O2	0.0199 (5)	0.0236 (6)	0.0384 (6)	0.0035 (4)	0.0019 (5)	0.0087 (5)
O3	0.0206 (6)	0.0333 (7)	0.0605 (9)	0.0012 (5)	−0.0053 (6)	−0.0059 (6)
N1	0.0141 (6)	0.0215 (6)	0.0196 (6)	−0.0007 (5)	0.0018 (5)	−0.0005 (5)
N2	0.0139 (6)	0.0212 (6)	0.0202 (6)	0.0015 (5)	0.0002 (5)	0.0007 (5)
C1	0.0162 (7)	0.0250 (8)	0.0220 (7)	0.0033 (6)	−0.0002 (6)	−0.0028 (6)
C2	0.0178 (7)	0.0276 (8)	0.0178 (7)	0.0040 (6)	0.0004 (5)	−0.0008 (6)
C3	0.0139 (6)	0.0179 (7)	0.0217 (7)	0.0029 (5)	0.0018 (5)	−0.0005 (5)
C4	0.0202 (8)	0.0392 (10)	0.0281 (8)	−0.0016 (7)	−0.0013 (6)	−0.0088 (7)
C5	0.0236 (8)	0.0269 (8)	0.0197 (7)	−0.0040 (6)	−0.0004 (6)	−0.0027 (6)
C6	0.0303 (9)	0.0381 (10)	0.0229 (8)	−0.0054 (7)	0.0031 (7)	−0.0040 (7)
C7	0.0165 (7)	0.0195 (7)	0.0247 (7)	−0.0007 (6)	0.0021 (6)	0.0018 (5)
C8	0.0173 (7)	0.0232 (8)	0.0211 (7)	−0.0001 (6)	0.0021 (6)	−0.0003 (6)

Geometric parameters (Å, º) top

O1—C8	1.3125 (18)	C3—C5	1.481 (2)
O1—H1O	0.96 (2)	C4—H4A	0.9800
O2—C8	1.2063 (18)	C4—H4B	0.9800
O3—H3A	0.91 (2)	C4—H4C	0.9800
O3—H3B	0.96 (2)	C5—C6	1.513 (2)
N1—C3	1.3290 (18)	C5—H5A	0.9900
N1—C1	1.3860 (18)	C5—H5B	0.9900
N1—H1N	0.881 (17)	C6—H6A	0.9800
N2—C3	1.3322 (18)	C6—H6B	0.9800
N2—C2	1.3903 (18)	C6—H6C	0.9800
N2—C7	1.4534 (18)	C7—C8	1.5109 (19)
C1—C2	1.346 (2)	C7—H7A	0.9900
C1—C4	1.487 (2)	C7—H7B	0.9900
C2—H2	0.9500

C8—O1—H1O	112.3 (13)	H4B—C4—H4C	109.5
H3A—O3—H3B	106.1 (16)	C3—C5—C6	113.66 (12)
C3—N1—C1	110.13 (12)	C3—C5—H5A	108.8
C3—N1—H1N	125.1 (11)	C6—C5—H5A	108.8
C1—N1—H1N	124.5 (11)	C3—C5—H5B	108.8
C3—N2—C2	108.97 (12)	C6—C5—H5B	108.8
C3—N2—C7	125.80 (12)	H5A—C5—H5B	107.7
C2—N2—C7	125.22 (12)	C5—C6—H6A	109.5
C2—C1—N1	106.06 (12)	C5—C6—H6B	109.5
C2—C1—C4	131.87 (14)	H6A—C6—H6B	109.5
N1—C1—C4	122.06 (13)	C5—C6—H6C	109.5
C1—C2—N2	107.40 (13)	H6A—C6—H6C	109.5
C1—C2—H2	126.3	H6B—C6—H6C	109.5
N2—C2—H2	126.3	N2—C7—C8	112.54 (12)
N1—C3—N2	107.43 (12)	N2—C7—H7A	109.1
N1—C3—C5	127.13 (13)	C8—C7—H7A	109.1
N2—C3—C5	125.44 (13)	N2—C7—H7B	109.1
C1—C4—H4A	109.5	C8—C7—H7B	109.1
C1—C4—H4B	109.5	H7A—C7—H7B	107.8
H4A—C4—H4B	109.5	O2—C8—O1	125.81 (14)
C1—C4—H4C	109.5	O2—C8—C7	124.34 (13)
H4A—C4—H4C	109.5	O1—C8—C7	109.85 (13)

C3—N1—C1—C2	0.88 (16)	C7—N2—C3—N1	−178.83 (12)
C3—N1—C1—C4	−177.84 (13)	C2—N2—C3—C5	179.31 (13)
N1—C1—C2—N2	−0.76 (16)	C7—N2—C3—C5	0.3 (2)
C4—C1—C2—N2	177.78 (15)	N1—C3—C5—C6	−15.1 (2)
C3—N2—C2—C1	0.40 (16)	N2—C3—C5—C6	165.88 (14)
C7—N2—C2—C1	179.39 (13)	C3—N2—C7—C8	77.86 (17)
C1—N1—C3—N2	−0.63 (16)	C2—N2—C7—C8	−100.96 (15)
C1—N1—C3—C5	−179.78 (14)	N2—C7—C8—O2	−2.0 (2)
C2—N2—C3—N1	0.14 (15)	N2—C7—C8—O1	178.25 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···Cl1	0.881 (17)	2.300 (18)	3.1635 (14)	166.6 (15)
O3—H3A···Cl1	0.91 (2)	2.20 (2)	3.1062 (14)	177 (2)
O1—H1O···O3ⁱ	0.96 (2)	1.60 (2)	2.5557 (16)	170 (2)
O3—H3B···Cl1ⁱⁱ	0.96 (2)	2.14 (2)	3.0860 (14)	168 (2)

Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1/2, y−1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₈H₁₃N₂O₂⁺·Cl⁻·H₂O
M_r	222.67
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	93
a, b, c (Å)	11.077 (2), 8.4542 (18), 11.938 (3)
β (°)	90.265 (3)
V (Å³)	1117.9 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.33
Crystal size (mm)	0.40 × 0.40 × 0.35

Data collection
Diffractometer	Rigaku SPIDER diffractometer
Absorption correction	Multi-scan (RAPID-AUTO; Rigaku, 2004)
T_min, T_max	0.880, 0.894
No. of measured, independent and observed [I > 2σ(I)] reflections	8869, 2532, 2203
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.099, 1.00
No. of reflections	2532
No. of parameters	145
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.20

Computer programs: RAPID-AUTO (Rigaku, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···Cl1	0.881 (17)	2.300 (18)	3.1635 (14)	166.6 (15)
O3—H3A···Cl1	0.91 (2)	2.20 (2)	3.1062 (14)	177 (2)
O1—H1O···O3ⁱ	0.96 (2)	1.60 (2)	2.5557 (16)	170 (2)
O3—H3B···Cl1ⁱⁱ	0.96 (2)	2.14 (2)	3.0860 (14)	168.2 (19)

Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1/2, y−1/2, −z+1/2.

Acknowledgements

This work was supported by the Wu Jieping Medical Fund (32067500615) and the National Natural Science Foundation of China (No. 20801024).

References

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