1-{5-[2-(Tri­fluoro­methyl)­phenyl]-1,3,4-thia­diazol-2-yl}guanidinium chloride

In the title compound, C₁₀H₉F₃N₅S⁺·Cl^-, which was developed as a potential anticonvulsant, the phenyl ring, the thia­diazo­le ring and the guanidinium moiety are all planar. There is a dihedral angle of 48.9 (1)° between the thia­diazole and phenyl rings which prevents steric hindrance arising from the [pi] bonds within the former, and the tri­fluoro­phenyl moiety attached to the latter. The thia­diazole and guanidinium moieties are twisted by 12.7 (2)° with respect to each other. An extensive network of hydrogen bonds, predominantly involving the chloride ion, maintains the crystal structure.

S1. Comment

The title compound, (I), was synthesized and supplied by Reckett and Coleman Ltd (Chapleo et al., 1986), and was made as one of a series of substituted 1,3,4-thiadiazole-containing molecules being investigated as potential anticonvulsants (Stillings et al., 1986; Chapleo et al., 1987; Chapleo et al., 1988). A number of diverse 1,3,4-thiadiazole-containing compounds are currently being investigated by other groups for their anticonvulsant properties (Varvaresou et al. 1998; Srivastava et al., 1999; Srivastava & Rawat, 1999), although the title compound proved to be less efficacious than related compounds studied (Chapleo et al. 1986). Of interest, the title compound was also shown to possess vasodilatory properties (Turner et al., 1988). \sch

Selected geometric parameters are given in Table 1. Figure 1 shows a labelled displacement ellipsoid plot of the asymmetric unit at 50% probability, while Fig. 2 shows the packing and hydrogen bonding within the crystal, and the hydrogen-bonding geometry is given in Table 2. The phenyl and thiadiazole rings are both planar, with root mean square deviations (rmsd) for their ring atoms of 0.0193 and 0.0064 Å respectively. The two rings are not coplanar having a dihedral angle of 48.9 (1)° between them, and S1 is -0.729 (6) Å, and the two N atoms N3 and N4 are 1.127 (8) and 1.111 (6) Å, respectively, from the phenyl ring plane. The angle between the rings prevents steric hindrance between the thiadiazole ring and the trifluoromethyl substituent on the phenyl ring. The guanidinium group, principally the non-hydrogen atoms, N8, C9, N10, and N11 is also highly planar, with an rmsd of 0.0009 Å, indicative of this being a planar carbenium ion. This group has a dihedral angle of 12.7 (2)° to the thiadiazole ring.

As a result of the moieties attached to the phenyl group, the ring bonds display significant differences between their lengths. Notably, C1'—C2' at 1.399 (4) Å is significantly longer than both C3'—C4' [1.364 (6) Å] and C4'—C5' [1.373 (5) Å], and C2'—C3' at 1.392 (5) Å is also longer than C3'—C4'. The substituents on the phenyl also cause significant differences in the ring internal angles (Table 1). The thiadiazole moiety does not display differences in the symmetric pairs of bonds, (S1—C2, S1—C5, and C2—N3, C5—N4), despite there being two different groups attached to either side of the ring. However, with the sulfur atom in the ring the carbon-nitrogen bonds are significantly shortened (Table 1) in comparison to those found in a comparable imidazole-like ring, being more like the mean length for such bonds as found in a furazan ring, 1.298 Å (Allen et al., 1987).

The bond lengths for the N atoms and the carbon atom of the guanidinium moiety show significant differences between them. While the bonds C9—N10 and C9—N11 are marginally different in length (Table 1), but the bond N8—C9 is significantly longer than C9—N11. This difference indicates that the stabilization of the carbenium ion centred at C9 is mainly from the N10 and N11 amino groups rather than from the N8 atom.

There are a number of hydrogen bonds that stabilize the crystal packing (Fig. 2 and Table 2). Four of the six hydrogen bonds are to the chloride ion as the acceptor. One of these four hydrogen bonds, from N11—H111 is bifurcated to the sulfur atom of the thiadiazole ring. There is also an intramolecular hydrogen bond between N11—H112 and N3 of the thiadiazole ring. No π–π ring stacking is observed within the crystals probably as a result of the practical difficulties that would arise caused by the steric bulk of the trifluoromethyl group attached to the phenyl ring.

S2. Experimental

The crystals were grown by slow evaporation from a 50:50 water/propan-2-ol mixture. The R_int values, 0.0496 for Laue class 2/m and 0.516 for mmm, clearly show that the crystal system is monoclinic.

S3. Refinement

All H atoms were initially located in differences maps, but were then placed geometrically in riding positions and refined isotropically with U_iso set to 1.2U_eq of the associated atom.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: CAD77, CADRAL (Korber, 1999) and CADSHEL (Cooper, 1999); program(s) used to solve structure: SHELX76 (Sheldrick, 1976); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SNOOPI (Davies, 1983).

Figures

	Fig. 1. The asymmetric unit at 50% probability, showing the numbering scheme used in the text, produced using SNOOPI (Davies, E·K. 1983).
	Fig. 2. The packing of the unit cell viewed along the a axis, showing the hydrogen bonding, modified from SNOOPI.

2-guanidinium-5-[2-(fluoromethyl)phenyl]-1,3,4-thiadiazole chloride

Crystal data

C10H9F3N5S^+·Cl^−	F(000) = 656
Mr = 323.73	Dx = 1.614 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
a = 5.0864 (8) Å	Cell parameters from 25 reflections
b = 7.315 (3) Å	θ = 4.9–24.9°
c = 35.812 (9) Å	µ = 4.35 mm^−1
β = 90.00 (2)°	T = 296 K
V = 1332.4 (7) Å^3	Block, colourless
Z = 4	0.2 × 0.15 × 0.15 mm

Data collection

Enraf-Nonius CAD4 diffractometer	Rint = 0.050
Radiation source: fine-focus sealed tube	θmax = 70.0°, θmin = 2.5°
Graphite monochromator	h = −6→6
ω–2θ scans	k = −8→8
4900 measured reflections	l = −17→43
2519 independent reflections	3 standard reflections every 200 reflections
1956 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.051	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.149	Calculated w = 1/[σ^2(Fo^2) + (0.1023P)^2 + 0.0307P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
2519 reflections	Δρmax = 0.47 e Å^−3
182 parameters	Δρmin = −0.33 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0030 (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
S1	0.32878 (13)	0.36837 (10)	0.39726 (2)	0.0564 (3)
C2	0.3210 (5)	0.5843 (4)	0.41590 (7)	0.0500 (6)
N3	0.1331 (5)	0.6876 (3)	0.40333 (7)	0.0608 (6)
N4	−0.0251 (5)	0.5958 (3)	0.37800 (7)	0.0598 (6)
C5	0.0528 (5)	0.4302 (4)	0.37220 (8)	0.0522 (6)
C1'	−0.0890 (5)	0.2956 (4)	0.34905 (8)	0.0535 (6)
C2'	−0.1828 (6)	0.3327 (5)	0.31313 (8)	0.0601 (7)
C3'	−0.3474 (9)	0.2062 (5)	0.29589 (11)	0.0802 (10)
H3'	−0.4174	0.2326	0.2725	0.096*
C4'	−0.4078 (9)	0.0443 (6)	0.31271 (12)	0.0848 (11)
H4'	−0.5210	−0.0373	0.3010	0.102*
C5'	−0.3024 (8)	0.0009 (5)	0.34688 (11)	0.0755 (9)
H5'	−0.3358	−0.1123	0.3577	0.091*
C6'	−0.1455 (6)	0.1279 (4)	0.36495 (9)	0.0621 (7)
H6'	−0.0768	0.0998	0.3883	0.075*
C7'	−0.1128 (9)	0.5008 (6)	0.29185 (10)	0.0799 (10)
F1'	0.1263 (6)	0.5607 (4)	0.29877 (7)	0.1114 (9)
F2'	−0.2722 (7)	0.6400 (4)	0.29897 (9)	0.1189 (10)
F3'	−0.1286 (8)	0.4751 (4)	0.25532 (7)	0.1306 (11)
N8	0.5069 (5)	0.6379 (3)	0.44182 (7)	0.0545 (6)
H8	0.5985	0.5533	0.4522	0.065*
C9	0.5563 (6)	0.8109 (4)	0.45206 (8)	0.0538 (6)
N10	0.7560 (5)	0.8430 (4)	0.47494 (8)	0.0651 (7)
H101	0.7912	0.9531	0.4817	0.078*
H102	0.8504	0.7538	0.4830	0.078*
N11	0.4132 (5)	0.9472 (4)	0.43987 (7)	0.0658 (7)
H111	0.4488	1.0571	0.4467	0.079*
H112	0.2836	0.9267	0.4250	0.079*
Cl1	0.79798 (15)	0.28895 (10)	0.46763 (2)	0.0641 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0516 (4)	0.0495 (4)	0.0683 (5)	0.0068 (3)	−0.0119 (3)	−0.0083 (3)
C2	0.0504 (13)	0.0476 (15)	0.0519 (14)	0.0002 (11)	−0.0047 (10)	−0.0032 (11)
N3	0.0630 (14)	0.0500 (14)	0.0694 (15)	0.0060 (11)	−0.0199 (12)	−0.0097 (11)
N4	0.0639 (14)	0.0502 (14)	0.0654 (14)	0.0090 (11)	−0.0201 (11)	−0.0092 (11)
C5	0.0497 (13)	0.0525 (15)	0.0545 (14)	0.0036 (12)	−0.0052 (11)	−0.0042 (12)
C1'	0.0533 (14)	0.0494 (16)	0.0577 (15)	0.0071 (11)	−0.0046 (11)	−0.0096 (12)
C2'	0.0678 (17)	0.0552 (17)	0.0573 (15)	0.0094 (14)	−0.0115 (13)	−0.0098 (13)
C3'	0.100 (3)	0.068 (2)	0.072 (2)	0.0094 (19)	−0.0298 (19)	−0.0127 (17)
C4'	0.099 (3)	0.063 (2)	0.093 (3)	0.0011 (19)	−0.031 (2)	−0.0221 (19)
C5'	0.091 (2)	0.0529 (18)	0.082 (2)	−0.0030 (17)	−0.0145 (18)	−0.0118 (16)
C6'	0.0701 (17)	0.0519 (17)	0.0643 (18)	0.0053 (14)	−0.0098 (14)	−0.0075 (13)
C7'	0.102 (3)	0.076 (2)	0.0614 (19)	−0.001 (2)	−0.0210 (18)	−0.0019 (16)
F1'	0.1111 (18)	0.130 (2)	0.0935 (16)	−0.0362 (18)	−0.0134 (14)	0.0297 (16)
F2'	0.148 (2)	0.0668 (15)	0.142 (2)	0.0207 (16)	−0.028 (2)	0.0113 (15)
F3'	0.203 (3)	0.127 (2)	0.0620 (13)	−0.028 (2)	−0.0215 (16)	0.0104 (14)
N8	0.0561 (12)	0.0488 (13)	0.0586 (13)	0.0031 (10)	−0.0123 (10)	−0.0002 (10)
C9	0.0563 (14)	0.0541 (15)	0.0509 (14)	−0.0066 (12)	−0.0048 (11)	−0.0007 (11)
N10	0.0635 (14)	0.0626 (16)	0.0693 (15)	−0.0049 (12)	−0.0174 (12)	−0.0062 (13)
N11	0.0782 (16)	0.0486 (14)	0.0707 (15)	−0.0037 (12)	−0.0224 (13)	0.0005 (12)
Cl1	0.0691 (5)	0.0556 (5)	0.0675 (5)	−0.0055 (3)	−0.0185 (3)	0.0058 (3)

Geometric parameters (Å, º)

S1—C2	1.715 (3)	C2'—C7'	1.490 (5)
S1—C5	1.726 (3)	C3'—C4'	1.364 (6)
C2—N3	1.299 (4)	C4'—C5'	1.373 (5)
C2—N8	1.382 (3)	C5'—C6'	1.385 (4)
N3—N4	1.386 (3)	C7'—F1'	1.317 (5)
N4—C5	1.291 (4)	C7'—F3'	1.324 (4)
C5—C1'	1.475 (4)	C7'—F2'	1.327 (5)
C1'—C6'	1.382 (4)	N8—C9	1.342 (4)
C1'—C2'	1.399 (4)	C9—N11	1.309 (4)
C2'—C3'	1.392 (5)	C9—N10	1.326 (4)
C2—S1—C5	86.7 (1)	C4'—C3'—C2'	121.1 (3)
N3—C2—N8	124.9 (3)	C3'—C4'—C5'	120.4 (4)
N3—C2—S1	114.7 (2)	C4'—C5'—C6'	119.1 (4)
N8—C2—S1	120.4 (2)	C1'—C6'—C5'	121.5 (3)
C2—N3—N4	111.8 (2)	F1'—C7'—F3'	106.8 (4)
C5—N4—N3	112.4 (2)	F1'—C7'—F2'	105.8 (4)
N4—C5—C1'	124.5 (2)	F3'—C7'—F2'	105.2 (3)
N4—C5—S1	114.3 (2)	F1'—C7'—C2'	113.5 (3)
C1'—C5—S1	121.0 (2)	F3'—C7'—C2'	111.9 (3)
C6'—C1'—C2'	118.7 (3)	F2'—C7'—C2'	112.9 (4)
C6'—C1'—C5	117.5 (3)	C9—N8—C2	125.4 (2)
C2'—C1'—C5	123.6 (3)	N11—C9—N10	119.8 (3)
C3'—C2'—C1'	118.9 (3)	N11—C9—N8	121.5 (3)
C3'—C2'—C7'	117.7 (3)	N10—C9—N8	118.6 (3)
C1'—C2'—C7'	123.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N8—H8···Cl1	0.86	2.25	3.092 (3)	166
N10—H101···Cl1^i	0.86	2.51	3.279 (3)	150
N10—H102···Cl1^ii	0.86	2.53	3.211 (3)	136
N11—H111···Cl1^i	0.86	2.57	3.327 (3)	148
N11—H111···S1^i	0.86	2.95	3.465 (3)	121
N11—H112···N3	0.86	2.06	2.711 (4)	132

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