Crystal structure of a methimazole-based ionic liquid

Abstract

The structure of 1-methyl-2-(prop-2-en-1-ylsulfan­yl)-1H-imidazol-3-ium bromide, C₇H₁₁N₂S⁺·Br⁻, has monoclinic (P2₁/c) symmetry. In the crystal, the components are linked by N—H⋯Br and C—H⋯Br hydrogen bonds. The crystal structure of the title compound undeniably proves that methimazole reacts through the thione tautomer, rather than the thiol tautomer in this system.

Related literature  

For the biological activity of methimazole, see: Rong et al. (2013 ▸). For its use as a ligand, see: Crossley et al. (2006 ▸). For a discussion of methimazole-based ionic liquids, see: Siriwardana et al. (2008 ▸). For reaction chemistry of methimazole, see: Roy & Mugesh (2005 ▸).

Experimental  

Crystal data  

• C₇H₁₁N₂S⁺·Br⁻

• M _r = 235.15

• Monoclinic,

• a = 10.8692 (7) Å

• b = 7.4103 (5) Å

• c = 12.8551 (9) Å

• β = 104.006 (7)°

• V = 1004.62 (11) ų

• Z = 4

• Mo Kα radiation

• μ = 4.24 mm⁻¹

• T = 180 K

• 0.6 × 0.32 × 0.25 mm

Data collection  

• Agilent Xcalibur, Eos diffractometer

• Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014 ▸) T _min = 0.321, T _max = 1.000

• 7388 measured reflections

• 1829 independent reflections

• 1558 reflections with I > 2σ(I)

• R _int = 0.042

Refinement  

• R[F ² > 2σ(F ²)] = 0.030

• wR(F ²) = 0.065

• S = 1.03

• 1829 reflections

• 105 parameters

• 1 restraint

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

• Δρ_max = 0.34 e Å⁻³

• Δρ_min = −0.38 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2014 ▸); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▸); software used to prepare material for publication: OLEX2 and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 1437865

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯Br1i	0.84 (3)	2.46 (3)	3.246 (2)	158 (3)
C2—H2A⋯Br1ii	0.93	2.84	3.723 (4)	159
C3—H3⋯Br1iii	0.93	2.91	3.757 (3)	152
C4—H4B⋯Br1	0.96	2.87	3.737 (3)	151
C5—H5B⋯Br1iv	0.97	2.89	3.814 (3)	161

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

supplementary crystallographic information

S1. Comment

2-Mercapto-1-methyl­imidazole or methimazole 1 belongs to a class of five-membered heterocyclic nitro­gen compounds, which possess various biological activities (e.g. it is a widely used anti-thyroid drug under the name Tapazole), see: Rong et al. (2013). Additionally, it has found use as a multidentate ligand in the fields of inorganic and organometallic chemistry, in which the sulfur atom can serve as a soft donor towards a wide variety of transition metals, see: Crossley et al. (2006). The alkyl­ation of methimazole with alkyl halides (e.g. iodo­ethane and chloro­butane) lead to the formation of methimazole-based ionic liquids in high yields, see Siriwardana et al. (2008). To date, no methimazole-based ionic liquids have been structurally characterized by X-ray diffraction.

Methimazole exists in two tautomeric forms, equilibrating between the 2-thiol 1a and 2-thione 1b, and both N-alkyl­ation and S-alkyl­ation reactions are possible, depending upon the reaction conditions and types of substrates employed, see Roy & Mugesh (2005). They reported that only S-alkyl­ated methimazoles were formed. The product structures were established by NMR spectroscopy, which is elusive in terms of proving the exclusive formation of S-alkyl­ated products over N-alkyl­ated products. Herein, we report the crystal structure of S-allyl­ated methimazolium bromide 2, which was prepared in qu­anti­tative yield (96%) via the reaction of methimazole with allyl bromide in refluxing aceto­nitrile (Scheme S1). The crystal structure of 2 undeniably proves that methimazole reacts through the 2-thione tautomer 1b.

S2. Synthesis and crystallization

2-Mercapto-1-methyl­imidazole (0.57 g, 5 mmol) and allyl bromide (0.85 g, 7 mmol) were dissolved in aceto­nitrile (5.0 mL) and the mixture refluxed for 48 hours. The solvent and excess allyl bromide were removed under vacuum to afford an off-white solid. The solid was washed with toluene (3 x 10 mL) and then recrystallized in aceto­nitrile to yield pure product 2 as an off-white solid in 96% isolated yield.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. The H-atom (H2) located on N2 was allowed to freely refine (isotropically). The remaining H-atoms were placed in calculated positions and allowed to ride during subsequent refinement, with U_iso(H) = 1.5U_eq(C) and C—H distances of 0.96 Å for methyl hydrogens, with U_iso(H) = 1.2U_eq(C) and C—H distances of 0.97 Å for the secondary hydrogens, and with U_iso(H) = 1.2U_eq(C) and C—H distances of 0.93 Å for all remaining hydrogen atoms.

Figures

Fig. 1.

A thermal ellipsoid diagram of the structure of the title compound.

Fig. 2.

Reaction scheme.

Crystal data

C7H11N2S+·Br−	F(000) = 472
Mr = 235.15	Dx = 1.555 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.8692 (7) Å	Cell parameters from 2203 reflections
b = 7.4103 (5) Å	θ = 3.9–27.0°
c = 12.8551 (9) Å	µ = 4.24 mm−1
β = 104.006 (7)°	T = 180 K
V = 1004.62 (11) Å3	Prism, colourless
Z = 4	0.6 × 0.32 × 0.25 mm

Data collection

Agilent Xcalibur, Eos diffractometer	1829 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1558 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.042
Detector resolution: 16.0514 pixels mm-1	θmax = 25.3°, θmin = 3.2°
ω scans	h = −13→13
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −8→8
Tmin = 0.321, Tmax = 1.000	l = −15→15
7388 measured reflections

Refinement

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)] = 0.030	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.065	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ2(Fo2) + (0.027P)2] where P = (Fo2 + 2Fc2)/3
1829 reflections	(Δ/σ)max = 0.001
105 parameters	Δρmax = 0.34 e Å−3
1 restraint	Δρmin = −0.38 e Å−3

Special details

Experimental. CrysAlis Pro (Agilent, 2014) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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 > 2σ(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 (Ų)

	x	y	z	Uiso*/Ueq
Br1	0.70880 (3)	0.66161 (4)	0.53045 (2)	0.02621 (12)
N2	0.6562 (2)	0.0414 (3)	0.2392 (2)	0.0273 (6)
N1	0.6302 (2)	0.1226 (3)	0.39296 (18)	0.0233 (6)
C2	0.5297 (3)	0.0739 (4)	0.2258 (3)	0.0316 (8)
H2A	0.4669	0.0623	0.1625	0.038*
C3	0.5134 (3)	0.1262 (4)	0.3221 (3)	0.0285 (7)
H3	0.4371	0.1587	0.3376	0.034*
C1	0.7171 (3)	0.0704 (4)	0.3410 (2)	0.0234 (7)
S1	0.87834 (8)	0.04183 (11)	0.39532 (7)	0.0373 (2)
C4	0.6547 (4)	0.1637 (4)	0.5076 (2)	0.0370 (9)
H4A	0.5756	0.1749	0.5278	0.055*
H4B	0.7009	0.2750	0.5221	0.055*
H4C	0.7037	0.0681	0.5481	0.055*
C6	0.9092 (3)	0.3747 (4)	0.3027 (3)	0.0410 (9)
H6	0.9450	0.3274	0.2498	0.049*
C5	0.9322 (3)	0.2790 (4)	0.4066 (3)	0.0405 (9)
H5A	0.8889	0.3429	0.4532	0.049*
H5B	1.0223	0.2818	0.4401	0.049*
C7	0.8417 (3)	0.5215 (5)	0.2809 (3)	0.0436 (9)
H7A	0.8047	0.5719	0.3323	0.052*
H7B	0.8305	0.5758	0.2141	0.052*
H2	0.689 (3)	0.007 (4)	0.190 (2)	0.049 (11)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Br1	0.02573 (18)	0.0284 (2)	0.02529 (19)	−0.00350 (13)	0.00772 (13)	−0.00185 (13)
N2	0.0309 (15)	0.0295 (16)	0.0227 (15)	0.0016 (12)	0.0088 (13)	−0.0005 (12)
N1	0.0304 (15)	0.0165 (13)	0.0238 (14)	−0.0003 (11)	0.0081 (12)	0.0002 (10)
C2	0.0256 (17)	0.030 (2)	0.0354 (19)	−0.0008 (14)	−0.0003 (15)	0.0026 (15)
C3	0.0190 (16)	0.0255 (18)	0.041 (2)	0.0028 (13)	0.0064 (14)	0.0023 (15)
C1	0.0253 (17)	0.0180 (17)	0.0264 (17)	−0.0015 (13)	0.0057 (14)	0.0027 (13)
S1	0.0229 (4)	0.0335 (5)	0.0518 (6)	0.0031 (4)	0.0019 (4)	0.0112 (4)
C4	0.059 (2)	0.028 (2)	0.0254 (18)	−0.0016 (16)	0.0128 (17)	−0.0035 (14)
C6	0.039 (2)	0.045 (2)	0.044 (2)	−0.0026 (17)	0.0186 (18)	0.0108 (18)
C5	0.0249 (18)	0.040 (2)	0.051 (2)	−0.0105 (15)	−0.0023 (16)	0.0134 (17)
C7	0.049 (2)	0.042 (2)	0.037 (2)	0.0000 (18)	0.0056 (18)	0.0126 (17)

Geometric parameters (Å, º)

N2—C2	1.366 (4)	C4—H4A	0.9600
N2—C1	1.334 (4)	C4—H4B	0.9600
N2—H2	0.836 (17)	C4—H4C	0.9600
N1—C3	1.373 (4)	C6—H6	0.9300
N1—C1	1.338 (3)	C6—C5	1.480 (4)
N1—C4	1.465 (4)	C6—C7	1.304 (4)
C2—H2A	0.9300	C5—H5A	0.9700
C2—C3	1.349 (4)	C5—H5B	0.9700
C3—H3	0.9300	C7—H7A	0.9300
C1—S1	1.736 (3)	C7—H7B	0.9300
S1—C5	1.847 (3)
C2—N2—H2	124 (2)	N1—C4—H4B	109.5
C1—N2—C2	109.9 (3)	N1—C4—H4C	109.5
C1—N2—H2	126 (2)	H4A—C4—H4B	109.5
C3—N1—C4	125.3 (3)	H4A—C4—H4C	109.5
C1—N1—C3	109.0 (2)	H4B—C4—H4C	109.5
C1—N1—C4	125.7 (3)	C5—C6—H6	118.1
N2—C2—H2A	126.7	C7—C6—H6	118.1
C3—C2—N2	106.7 (3)	C7—C6—C5	123.8 (3)
C3—C2—H2A	126.7	S1—C5—H5A	108.8
N1—C3—H3	126.3	S1—C5—H5B	108.8
C2—C3—N1	107.3 (3)	C6—C5—S1	113.8 (2)
C2—C3—H3	126.3	C6—C5—H5A	108.8
N2—C1—N1	107.1 (3)	C6—C5—H5B	108.8
N2—C1—S1	126.0 (2)	H5A—C5—H5B	107.7
N1—C1—S1	126.9 (2)	C6—C7—H7A	120.0
C1—S1—C5	100.68 (14)	C6—C7—H7B	120.0
N1—C4—H4A	109.5	H7A—C7—H7B	120.0
N2—C2—C3—N1	−0.7 (3)	C1—N2—C2—C3	0.7 (4)
N2—C1—S1—C5	104.2 (3)	C1—N1—C3—C2	0.5 (3)
N1—C1—S1—C5	−77.0 (3)	C1—S1—C5—C6	−61.4 (3)
C2—N2—C1—N1	−0.4 (3)	C4—N1—C3—C2	−177.7 (3)
C2—N2—C1—S1	178.7 (2)	C4—N1—C1—N2	178.1 (3)
C3—N1—C1—N2	−0.1 (3)	C4—N1—C1—S1	−0.9 (4)
C3—N1—C1—S1	−179.1 (2)	C7—C6—C5—S1	121.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···Br1i	0.84 (3)	2.46 (3)	3.246 (2)	158 (3)
C2—H2A···Br1ii	0.93	2.84	3.723 (4)	159
C3—H3···Br1iii	0.93	2.91	3.757 (3)	152
C4—H4B···Br1	0.96	2.87	3.737 (3)	151
C5—H5B···Br1iv	0.97	2.89	3.814 (3)	161

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