1,3-Benzothia­zole-6-carboxamidinium chloride dihydrate

The title compound, C₈H₈N₃S⁺·Cl^-·2H₂O, has been synthesized and characterized both spectroscopically and structurally. The structure consists of 1,3-benzothia­zole-6-carboxamidinium cations, chloride anions and water mol­ecules, all interconnected by hydrogen bonds into a three-dimensional network. The 1,3-benzo­thia­zole moiety is inclined to the 6-­amidine group by 36.71 (9)°.

S1. Comment

Small and simple heterocyclic structures often exhibit complex biological properties. Substituted benzothiazoles show biological activities including anti-tumor activity (Goldfarb et al., 1999), anti-infective and anti-fungal activity (Sener et al., 2000), and anti-helmintic activity (Nadkarn et al., 2000). In order to find new potent anti-tumor benzothiazole compounds (Racanè et al., 2001), we have introduced an amidino group into the benzothiazole moiety. This report describes the synthesis and crystal structure of a new cationic compound, benzo-1,3-thiazole-6-carboxamidinium chloride dihydrate, (I). Substituted benzothiazoles that are not bound to a metal are rare.

As depicted in the reaction Scheme, the starting compound was 6-cyanobenzothiazole (Boggust & Cocker, 1949). The conversion of the cyano function into the amidino function was achieved using the Pinner method (Boyd, 1991). The imidoyl ether hydrochloride that was generated as an intermediate product was converted into the free base with potassium carbonate and was then converted with ammonium chloride into the desired 6-amidinobenzothiazole hydrochloride (I).

The structure comprises benzo-1,3-thiazole-6-carboxamidinium cations, chloride anions and water molecules (Fig 1); pertinent bond lengths and angles are given in Table 1. The plane calculated through the atoms of the 1,3-benzothiazole moiety shows that it is planar, with the largest deviation from the plane being that of atom C6 [0.023 (2) Å.] However, the entire benzo-1,3-thiazole-6-carboxamidinium cation is not planar, since the plane through the 6-amidino group is inclined to that through the 1,3-benzothiazole moiety by 36.71 (9)°. The C—C differences within the benzene ring are usual for such fused rings. The bond angle around the S atom is within the range found in five-membered rings of other substituted benzothiazole derivatives (Davidović et al., 1999; Popović et al., 2001, Popović et al., 2002). The hydrogen-bond pattern is very interesting, since all N/H and O/H donor atoms are involved in the hydrogen bonding to the acceptor atoms: endocyclic N atoms, the Cl ion and water O atoms. Water molecules have an important role since they form six out of the eight hydrogen bonds that interconnect the ions and molecules into a three-dimensional network (Table 2).

S2. Experimental

A solution of 6-cyanobenzothiazole (4 g, 25 mmol) in dry 2-(2-ethoxyethoxy)ethanol (60 ml) was cooled to 278 K and saturated with HCl. The flask was then stoppered and the contents stirred at room temperature for 2 d (until IR spectra indicated the disappearance of the nitrile peak). Excess HCl was removed from the suspension by a stream of N₂. The reaction mixture was poured into 400 ml of dry ether, and crystals of imidoyl ether hydrochloride were filtered off, washed with dry ether and dried under reduced pressure over KOH. Imidoyl ether hydrochloride was poured into 150 ml of cold water with 20 ml of 20% K₂CO₃, and the free base was extracted with CHCl₃. The solvent was evaporated, and the oil residue was dissolved in 100 ml of ethanol. The solution of NH₄Cl (1.4 g, 26 mmol) in 25 ml of water was added to the ethanolic solution, and the mixture was heated under reflux for 5 h. After filtration (charcoal), the hot reaction mixture was left to stand at room temperature for 4 d. The title compound separated in colourless crystals [m.p. = 275°C, yield 3.94 g (68%)]. Spectroscopic analysis: IR (KBr, cm⁻¹): 3265, 3080 (NH), 1679 (C═N); ¹H NMR (300 MHz, DMSO-d₆) δ: 9.67 (s, 1H, H-2), 9.41 (br s, 4H, H—NH, disappeared with D₂O), 8.74 (d, 1H, J_7,5 = 1.7 Hz, H-7), 8.31 (d, 1H, J_4,5 = 8.6 Hz, H-4), 7.95 (dd, 1H, J_5,4 = 8.6 Hz, J_5,4 = 1.8 Hz, H-5). ¹³C NMR (75 MHz, DMSO-d₆) δ: 166.2 (s), 161.3 (d), 156.5 (s), 134.5 (s), 126.4 (d), 125.7 (s), 124.2 (d), 123.8 (d). Analysis: calculated for C₈H₈ClN₃S·2H₂O C 38.48, H 4.84, N 16.83, Cl 14.20%; found C 38.67, H 4.48, N 17.03, Cl 14.64%.

S3. Refinement

Intensities were corrected for Lorentz and polarization and absorption effects (Stoe & Cie, 1995). The structure was solved by direct methods. H atoms were found in the difference Fourier map and were refined isotropically, giving C—H distances in the range 0.91 (3)–0.96 (2) Å, O—H distances in the range 0.73 (5)–0.91 (4) Å and N—H distances in the range 0.81 (3)–0.85 (2) Å.

Computing details

Data collection: STADI4 (Stoe & Cie, 1995); cell refinement: X-RED (Stoe & Cie, 1995); data reduction: X-RED (Stoe & Cie, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON98 (Spek, 1990); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures

	Fig. 1. View of (I) with the atom labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Packing of the ions and molecules in the unit cell. Hydrogen bonds are indicated by dashed lines.

Benzo-1,3-thiazole-6-carboxamidinium chloride dihydrate

Crystal data

C8H8N3S^+·Cl^−·2H2O	Dx = 1.429 Mg m^−3
Mr = 249.72	Melting point: 548 K
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 60 reflections
a = 16.9296 (9) Å	θ = 12.5–17.8°
b = 9.3433 (5) Å	µ = 0.49 mm^−1
c = 7.3389 (15) Å	T = 293 K
V = 1160.9 (3) Å^3	Block, colourless
Z = 4	0.47 × 0.42 × 0.22 mm
F(000) = 520

Data collection

Philips PW1100 (updated by STOE) diffractometer	2945 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.034
Planar Graphite monochromator	θmax = 30.0°, θmin = 3.3°
ω scans	h = −23→23
Absorption correction: Ψ scan X-RED (Stoe & Cie, 1995)	k = −13→13
Tmin = 0.792, Tmax = 0.893	l = −10→10
4203 measured reflections	4 standard reflections every 90 min
3377 independent reflections	intensity decay: 4%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.032	w = 1/[σ^2(Fo^2) + (0.0471P)^2 + 0.0723P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.081	(Δ/σ)max < 0.001
S = 1.06	Δρmax = 0.25 e Å^−3
3377 reflections	Δρmin = −0.20 e Å^−3
185 parameters	Extinction correction: SHELXL97, Fc^* = kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.083 (4)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.02 (6)

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
Cl	0.51091 (2)	0.31217 (5)	0.39859 (8)	0.04496 (12)
N1	0.79005 (10)	0.30764 (15)	0.1236 (2)	0.0438 (3)
C1	0.86375 (13)	0.30760 (18)	0.0754 (3)	0.0455 (4)
S	0.90695 (2)	0.47046 (5)	0.02443 (7)	0.04415 (12)
C2	0.81749 (9)	0.55165 (16)	0.0712 (2)	0.0335 (3)
C3	0.79721 (9)	0.69579 (15)	0.0596 (2)	0.0337 (3)
C4	0.72051 (9)	0.73514 (16)	0.1035 (2)	0.0317 (3)
C5	0.66498 (9)	0.63239 (18)	0.1604 (2)	0.0367 (3)
C6	0.68528 (11)	0.48995 (19)	0.1721 (3)	0.0394 (3)
C7	0.76184 (10)	0.44770 (16)	0.1244 (2)	0.0349 (3)
C8	0.69649 (9)	0.88729 (17)	0.0880 (2)	0.0347 (3)
N2	0.74765 (11)	0.98737 (16)	0.1322 (2)	0.0424 (3)
N3	0.62544 (9)	0.91850 (17)	0.0301 (3)	0.0434 (3)
O1	0.90985 (10)	0.92882 (19)	0.2589 (3)	0.0576 (4)
O2	0.57384 (14)	0.20048 (17)	0.0155 (4)	0.0705 (5)
H1	0.8971 (13)	0.227 (3)	0.068 (3)	0.048 (6)*
H3	0.8363 (12)	0.758 (3)	0.017 (3)	0.047 (5)*
H5	0.6120 (14)	0.660 (2)	0.192 (3)	0.042 (5)*
H6	0.6527 (13)	0.420 (3)	0.215 (3)	0.046 (6)*
H21	0.7921 (13)	0.964 (2)	0.177 (3)	0.037 (5)*
H22	0.7352 (15)	1.074 (3)	0.120 (3)	0.051 (6)*
H31	0.5958 (16)	0.855 (3)	−0.003 (4)	0.061 (8)*
H32	0.6107 (15)	1.002 (3)	0.027 (5)	0.052 (6)*
H101	0.938 (2)	0.910 (4)	0.156 (5)	0.078 (9)*
H102	0.929 (2)	0.991 (5)	0.300 (6)	0.093 (12)*
H201	0.558 (2)	0.225 (4)	0.109 (5)	0.067 (9)*
H202	0.5813 (16)	0.264 (4)	−0.053 (4)	0.068 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl	0.03552 (17)	0.0478 (2)	0.0516 (2)	0.00226 (15)	0.00166 (18)	0.0037 (2)
N1	0.0542 (9)	0.0260 (6)	0.0511 (9)	−0.0016 (6)	−0.0122 (7)	0.0014 (5)
C1	0.0574 (10)	0.0296 (7)	0.0493 (10)	0.0069 (7)	−0.0104 (8)	−0.0015 (6)
S	0.04013 (19)	0.03467 (18)	0.0576 (3)	0.00547 (15)	0.00139 (19)	−0.00148 (19)
C2	0.0350 (6)	0.0282 (6)	0.0373 (8)	−0.0025 (5)	−0.0036 (5)	−0.0012 (5)
C3	0.0331 (6)	0.0262 (6)	0.0417 (9)	−0.0038 (5)	0.0019 (6)	−0.0003 (5)
C4	0.0342 (6)	0.0256 (6)	0.0351 (7)	−0.0026 (5)	−0.0029 (6)	−0.0008 (5)
C5	0.0315 (7)	0.0359 (7)	0.0428 (8)	−0.0054 (6)	−0.0010 (6)	0.0021 (6)
C6	0.0386 (7)	0.0330 (7)	0.0466 (9)	−0.0115 (6)	−0.0049 (7)	0.0055 (7)
C7	0.0417 (7)	0.0266 (6)	0.0363 (8)	−0.0055 (6)	−0.0077 (6)	0.0018 (5)
C8	0.0387 (7)	0.0299 (6)	0.0356 (7)	0.0018 (6)	0.0044 (6)	−0.0014 (6)
N2	0.0472 (8)	0.0252 (6)	0.0547 (9)	−0.0017 (6)	−0.0005 (7)	−0.0020 (6)
N3	0.0415 (6)	0.0349 (6)	0.0540 (8)	0.0069 (6)	−0.0027 (7)	−0.0026 (7)
O1	0.0595 (9)	0.0531 (9)	0.0603 (10)	−0.0125 (7)	−0.0017 (7)	−0.0139 (7)
O2	0.1033 (15)	0.0359 (7)	0.0724 (12)	−0.0017 (7)	0.0238 (11)	−0.0056 (9)

Geometric parameters (Å, º)

S—C1	1.7292 (19)	C6—C7	1.399 (3)
S—C2	1.7283 (16)	C6—H6	0.91 (3)
N1—C1	1.297 (3)	C8—N3	1.309 (2)
N1—C7	1.393 (2)	C8—N2	1.315 (2)
C1—H1	0.95 (3)	N2—H21	0.85 (2)
C2—C3	1.392 (2)	N2—H22	0.84 (3)
C2—C7	1.408 (2)	N3—H31	0.82 (3)
C3—C4	1.388 (2)	N3—H32	0.82 (3)
C3—H3	0.93 (2)	O1—H101	0.91 (4)
C4—C5	1.407 (2)	O1—H102	0.73 (4)
C4—C8	1.483 (2)	O2—H201	0.77 (4)
C5—C6	1.377 (2)	O2—H202	0.79 (4)
C5—H5	0.96 (2)
C1—S—C2	88.43 (9)	C3—C4—C8	119.51 (13)
S—C2—C3	128.93 (12)	C5—C4—C8	119.59 (14)
S—C2—C7	109.79 (12)	C4—C5—C6	120.74 (15)
S—C1—N1	117.76 (13)	C6—C5—H5	118.3 (14)
C1—N1—C7	109.34 (14)	C4—C5—H5	120.9 (14)
N1—C7—C2	114.67 (15)	C5—C6—C7	119.22 (15)
N1—C7—C6	125.70 (15)	C5—C6—H6	124.2 (15)
N2—C8—N3	121.80 (16)	C7—C6—H6	116.5 (15)
N2—C8—C4	118.81 (15)	C2—C7—C6	119.63 (14)
N3—C8—C4	119.38 (15)	C8—N2—H21	119.5 (14)
N1—C1—H1	126.2 (15)	C8—N2—H22	119.6 (18)
S—C1—H1	116.0 (15)	H21—N2—H22	121 (2)
C3—C2—C7	121.27 (15)	C8—N3—H31	120 (2)
C2—C3—C4	118.21 (13)	C8—N3—H32	120.1 (18)
C4—C3—H3	125.3 (14)	H31—N3—H32	120 (3)
C2—C3—H3	116.4 (15)	H101—O1—H102	105 (4)
C3—C4—C5	120.90 (14)	H201—O2—H202	113 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H21···O1	0.85 (2)	2.11 (2)	2.950 (3)	171 (2)
N2—H22···N1^i	0.84 (3)	2.37 (3)	3.078 (2)	142 (2)
N3—H31···Cl^ii	0.81 (3)	2.49 (3)	3.3023 (18)	171 (3)
N3—H32···O2^i	0.82 (3)	1.96 (3)	2.778 (2)	179 (4)
O1—H101···Cl^iii	0.91 (4)	2.27 (3)	3.159 (2)	165 (3)
O1—H102···Cl^iv	0.73 (5)	2.41 (4)	3.136 (2)	170 (3)
O2—H201···Cl	0.77 (4)	2.41 (4)	3.183 (3)	177.4 (17)
O2—H202···O1^v	0.79 (3)	2.07 (3)	2.859 (3)	175 (3)

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