2-(Methoxy­carbon­yl)-4-methyl­thio­phen-3-aminium chloride monohydrate: the first crystal structure of a 3-amino­thio­phene-2-carboxylic acid ester

In the crystal structure of the title compound, C₇H₁₀NO₂S⁺·Cl⁻·H₂O, a weak N—H...O intra­molecular hydrogen bond is observed without the formation of a conjugated π-electron system. The three-dimensional network is sustained via extensive hydrogen bonding involving the ions and the water mol­ecule.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.040
• wR factor = 0.114
• Data-to-parameter ratio = 18.5

checkCIF/PLATON results

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Alert level C
PLAT042_ALERT_1_C Calc. and Rep. MoietyFormula Strings Differ ....          ?
PLAT199_ALERT_1_C Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_C Check the Reported _diffrn_ambient_temperature .        293 K
PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....       2.15
PLAT391_ALERT_3_C Deviating Methyl C11     H-C-H Bond Angle ......     100.00 Deg.

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

3-Aminothiophene-2-carboxylic acid derivatives, bioisosters of anthranilic acid ones, are very important building blocks in medicinal chemistry. They are extensively used as starting material to synthesize various thiophene-containing structures with potential activities in the fields of cancerology (Wyne et al., 2004; Andersen et al., 2002; Benish et al., 2002; Levin et al., 2000), neurosciences (Rault et al., 1996) or cardiovascular diseases (Eto et al., 2004; Inoue et al., 2004; Larsen et al., 2003; Weinstock & Franz, 2002; Nakashima et al., 1999). The chemical stability of many compounds of this family is limited. It must be pointed out that orthoaminothiophene carboxylic acids are not stable because of spontaneous decarboxylation. Among 3-aminothiophene-2-carboxylates, the title compound is the most important because it serves as starting material to produce carticaine (Malamed et al., 2000; Donaldson et al., 1987; Vree & Gielen, 2005), the local anaesthetic of choice in dentistry. Currently, the industrial synthesis of the title compound remains a subject of research because of the difficulties encountered in isolating the base or one of its salts with high yield and purity (Kadushkin et al., 2002). In the course of our studies aimed at the synthesis of new thiophenic compounds with potential biological activity, the title compound was needed but was hygroscopic when prepared according to the literature method (Barker et al., 2002). Its degree of hydratation could not be determined. In order to overcome theses difficulties, a new process in water was developed, leading to a stable monohydrate salt.

Fig. 1 shows a view of the asymmetric unit, which consists of one cation, one chloride ion and one water molecule. In the cation, the carboxyl group is coplanar with the thiophene ring [dihedral angle 2.75 (6)°]; thus one O atom of the carboxyl group (O7) lies in the proximity of one H atom (H10A) of the protonated amino group (N10). The intramolecular contact distance between O7 and H10A is 2.165 (2) Å, indicating the formation of a weak intramolecular hydrogen bond. With this hydrogen bond, the six atoms O7, C6, C2, C3, N10 and H10A form a six-membered pseudo-ring. Since the hydrogen bond closing the ring is a weak one, the observed length of the single and double bonds in the pseudo-ring (Table 1) are close to the typical values (Glusker et al., 1994), which excludes the formation of a weak conjugated π-electron system inside this pseudo-ring.

In the crystal packing, the three-dimensional network is sustained via extensive hydrogen bonding involving the ions and the water molecule (Table 2). The cations are linked into centrosymmetric dimers by a pair of intermolecular N—H···O hydrogen interactions (Fig. 2). The dimers are stacked in columns along the a axis through N—H···O and N—H···Cl hydrogen interactions (Fig. 3). Both H atoms of the water molecule are engaged in hydrogen bonds with adjacent chloride anions.

S2. Experimental

Methyl-3-amino-4-methylthiophene-2-carboxylate (10 g) was added to hydrochloric acid (100 ml, 6 N) and the mixture was refluxed. After 1 h, all the starting material was dissolved and the reflux was kept on for 3 h. The reactant mixture was left to cool; crystals suitable for X-ray analysis appeared after 10 h at room temperature.

S3. Refinement

All H atoms were located in a difference Fourier map and refined freely. A remarkable intensity decay was observed during the data collection (33%).

Computing details

Data collection: CAD-4-PC Software (Enraf–Nonius, 1996); cell refinement: CAD-4-PC Software; data reduction: JANA98 (Petříček & Dušek, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. View of the title compound, showing the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level. H atoms are drawn as small circles of arbitrary radii. Dashed lines indicate hydrogen bonds.
	Fig. 2. View of the dimer, showing the N—H···O hydrogen bonds (dashed lines).
	Fig. 3. Packing diagram of the title compound showing the stacking of the dimers along the a axis. N—H···O, N—H···Cl and O—H···Cl hydrogen bonds are shown as dashed lines. H atoms have been omitted for clarity.

2-(Methoxycarbonyl)-4-methylthiophen-3-aminium chloride monohydrate

Crystal data

C7H10NO2S^+·Cl^−·H2O	Z = 2
Mr = 225.69	F(000) = 236
Triclinic, P1	Dx = 1.424 Mg m^−3
Hall symbol: -P 1	Melting point: 361 K
a = 7.1872 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.562 (1) Å	Cell parameters from 25 reflections
c = 10.9203 (13) Å	θ = 18–25°
α = 107.887 (10)°	µ = 0.54 mm^−1
β = 97.596 (10)°	T = 293 K
γ = 106.276 (9)°	Prism, colourless
V = 526.49 (11) Å^3	0.57 × 0.45 × 0.18 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	2509 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.014
Graphite monochromator	θmax = 30.0°, θmin = 2.0°
θ/2θ scans	h = −10→10
Absorption correction: GAUSSIAN (Gaussian et al., 1998) [please provide correct reference]	k = −10→10
Tmin = 0.585, Tmax = 0.803	l = 0→15
3215 measured reflections	3 standard reflections every 60 min
3065 independent reflections	intensity decay: 33%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.114	All H-atom parameters refined
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0708P)^2 + 0.0703P] where P = (Fo^2 + 2Fc^2)/3
3065 reflections	(Δ/σ)max < 0.001
166 parameters	Δρmax = 0.48 e Å^−3
0 restraints	Δρmin = −0.33 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.20700 (6)	0.59377 (6)	0.85666 (4)	0.04889 (13)
S1	0.16594 (6)	−0.19815 (6)	0.45578 (4)	0.04531 (13)
C2	0.2720 (2)	0.0498 (2)	0.48833 (14)	0.0366 (3)
C3	0.3268 (2)	0.1536 (2)	0.62230 (13)	0.0352 (3)
C4	0.2808 (2)	0.0361 (2)	0.70059 (15)	0.0410 (3)
C5	0.1947 (3)	−0.1582 (3)	0.62092 (17)	0.0468 (3)
H5	0.149 (3)	−0.264 (3)	0.655 (2)	0.063 (6)*
C6	0.2930 (2)	0.1324 (2)	0.38399 (14)	0.0394 (3)
O7	0.3611 (2)	0.30737 (18)	0.40581 (12)	0.0545 (3)
O8	0.2272 (2)	−0.00655 (18)	0.26428 (11)	0.0523 (3)
C9	0.2405 (4)	0.0607 (4)	0.15389 (18)	0.0664 (6)
H9A	0.190 (4)	−0.056 (4)	0.079 (3)	0.093 (9)*
H9B	0.166 (4)	0.146 (4)	0.157 (2)	0.067 (7)*
H9C	0.384 (4)	0.139 (4)	0.165 (3)	0.093 (9)*
N10	0.4247 (2)	0.36621 (19)	0.68062 (13)	0.0395 (3)
H10A	0.456 (3)	0.421 (3)	0.621 (2)	0.064 (6)*
H10B	0.546 (3)	0.398 (3)	0.741 (2)	0.047 (5)*
H10C	0.342 (3)	0.421 (3)	0.727 (2)	0.055 (5)*
C11	0.3173 (4)	0.1150 (3)	0.84851 (17)	0.0579 (5)
H11A	0.297 (4)	0.017 (5)	0.877 (3)	0.093 (9)*
H11B	0.456 (4)	0.191 (4)	0.895 (3)	0.090 (8)*
H11C	0.250 (4)	0.211 (4)	0.882 (3)	0.088 (8)*
O12	0.7603 (2)	0.4838 (3)	0.87035 (15)	0.0637 (4)
H12A	0.762 (5)	0.446 (4)	0.935 (4)	0.098 (10)*
H12B	0.871 (5)	0.490 (5)	0.859 (3)	0.103 (10)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0535 (2)	0.0559 (2)	0.0368 (2)	0.01748 (17)	0.01544 (16)	0.01530 (16)
S1	0.0498 (2)	0.0446 (2)	0.0349 (2)	0.01194 (16)	0.00615 (15)	0.01067 (15)
C2	0.0371 (6)	0.0447 (7)	0.0287 (6)	0.0146 (5)	0.0083 (5)	0.0133 (5)
C3	0.0360 (6)	0.0443 (7)	0.0271 (6)	0.0151 (5)	0.0080 (5)	0.0138 (5)
C4	0.0435 (7)	0.0511 (8)	0.0310 (7)	0.0147 (6)	0.0092 (5)	0.0194 (6)
C5	0.0512 (8)	0.0500 (8)	0.0403 (8)	0.0146 (7)	0.0094 (7)	0.0208 (7)
C6	0.0408 (7)	0.0509 (8)	0.0251 (6)	0.0149 (6)	0.0081 (5)	0.0123 (6)
O7	0.0730 (8)	0.0503 (6)	0.0311 (5)	0.0084 (6)	0.0094 (5)	0.0153 (5)
O8	0.0727 (8)	0.0532 (6)	0.0243 (5)	0.0155 (6)	0.0101 (5)	0.0110 (5)
C9	0.0945 (16)	0.0714 (13)	0.0262 (8)	0.0192 (12)	0.0135 (9)	0.0167 (8)
N10	0.0457 (7)	0.0447 (6)	0.0268 (6)	0.0134 (5)	0.0095 (5)	0.0126 (5)
C11	0.0790 (13)	0.0610 (11)	0.0304 (8)	0.0139 (10)	0.0128 (8)	0.0215 (7)
O12	0.0488 (7)	0.0979 (11)	0.0465 (7)	0.0209 (7)	0.0083 (6)	0.0340 (8)

Geometric parameters (Å, º)

S1—C5	1.7082 (18)	C9—H9A	0.94 (3)
S1—C2	1.7151 (15)	C9—H9B	0.94 (2)
C2—C3	1.3713 (19)	C9—H9C	1.00 (3)
C2—C6	1.463 (2)	N10—H10A	0.89 (2)
C3—C4	1.416 (2)	N10—H10B	0.94 (2)
C3—N10	1.4506 (19)	N10—H10C	0.93 (2)
C4—C5	1.364 (2)	C11—H11A	0.88 (3)
C4—C11	1.498 (2)	C11—H11B	0.98 (3)
C5—H5	0.98 (2)	C11—H11C	0.99 (3)
C6—O7	1.2082 (19)	O12—H12A	0.84 (4)
C6—O8	1.3231 (18)	O12—H12B	0.81 (3)
O8—C9	1.449 (2)
C5—S1—C2	91.39 (8)	O8—C9—H9B	108.7 (15)
C3—C2—C6	126.58 (14)	H9A—C9—H9B	114 (2)
C3—C2—S1	110.48 (11)	O8—C9—H9C	108.4 (18)
C6—C2—S1	122.92 (11)	H9A—C9—H9C	114 (2)
C2—C3—C4	114.54 (13)	H9B—C9—H9C	108 (2)
C2—C3—N10	123.33 (13)	C3—N10—H10A	113.1 (14)
C4—C3—N10	122.13 (13)	C3—N10—H10B	110.5 (12)
C5—C4—C3	109.85 (14)	H10A—N10—H10B	105.4 (18)
C5—C4—C11	125.35 (15)	C3—N10—H10C	108.3 (13)
C3—C4—C11	124.78 (15)	H10A—N10—H10C	110.9 (19)
C4—C5—S1	113.72 (13)	H10B—N10—H10C	108.6 (18)
C4—C5—H5	123.3 (14)	C4—C11—H11A	110 (2)
S1—C5—H5	122.9 (14)	C4—C11—H11B	114.6 (18)
O7—C6—O8	124.52 (14)	H11A—C11—H11B	100 (3)
O7—C6—C2	123.40 (13)	C4—C11—H11C	113.2 (18)
O8—C6—C2	112.07 (13)	H11A—C11—H11C	116 (3)
C6—O8—C9	116.25 (15)	H11B—C11—H11C	102 (2)
O8—C9—H9A	104.2 (19)	H12A—O12—H12B	101 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N10—H10A···O7	0.89 (2)	2.18 (2)	2.8489 (18)	131.7 (19)
N10—H10A···O7^i	0.89 (2)	2.24 (2)	3.0064 (19)	145 (2)
N10—H10B···O12	0.94 (2)	1.76 (2)	2.692 (2)	171.0 (18)
N10—H10C···Cl1	0.93 (2)	2.15 (2)	3.0624 (15)	168.2 (19)
O12—H12B···Cl1^ii	0.81 (3)	2.33 (4)	3.1187 (17)	165 (3)
O12—H12A···Cl1^iii	0.84 (4)	2.38 (4)	3.202 (2)	169 (3)

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