In the title compound, C
10H
9F
3N
5S
+·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
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.
Supporting information
CCDC reference: 144661
The crystals were grown by slow evaporation from a 50:50 water/propan-2-ol
mixture. The Rint values, 0.0496 for Laue class 2/m and 0.516 for
mmm, clearly show that the crystal system is monoclinic.
All H atoms were initially located in differences maps, but were then placed
geometrically in riding positions and refined isotropically with Uiso
set to 1.2Ueq of the associated atom.
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).
2-guanidinium-5-[2-(fluoromethyl)phenyl]-1,3,4-thiadiazole chloride
top
Crystal data top
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) Å3 | Block, colourless |
Z = 4 | 0.2 × 0.15 × 0.15 mm |
Data collection top
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 top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.051 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.149 | Calculated w = 1/[σ2(Fo2) + (0.1023P)2 + 0.0307P] where P = (Fo2 + 2Fc2)/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+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0030 (6) |
Crystal data top
C10H9F3N5S+·Cl− | V = 1332.4 (7) Å3 |
Mr = 323.73 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 5.0864 (8) Å | µ = 4.35 mm−1 |
b = 7.315 (3) Å | T = 296 K |
c = 35.812 (9) Å | 0.2 × 0.15 × 0.15 mm |
β = 90.00 (2)° | |
Data collection top
Enraf-Nonius CAD4 diffractometer | Rint = 0.050 |
4900 measured reflections | 3 standard reflections every 200 reflections |
2519 independent reflections | intensity decay: none |
1956 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | 0 restraints |
wR(F2) = 0.149 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.47 e Å−3 |
2519 reflections | Δρmin = −0.33 e Å−3 |
182 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 | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
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···Cl1i | 0.86 | 2.51 | 3.279 (3) | 150 |
N10—H102···Cl1ii | 0.86 | 2.53 | 3.211 (3) | 136 |
N11—H111···Cl1i | 0.86 | 2.57 | 3.327 (3) | 148 |
N11—H111···S1i | 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. |
Experimental details
Crystal data |
Chemical formula | C10H9F3N5S+·Cl− |
Mr | 323.73 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 296 |
a, b, c (Å) | 5.0864 (8), 7.315 (3), 35.812 (9) |
β (°) | 90, 90.00 (2), 90 |
V (Å3) | 1332.4 (7) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 4.35 |
Crystal size (mm) | 0.2 × 0.15 × 0.15 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4900, 2519, 1956 |
Rint | 0.050 |
(sin θ/λ)max (Å−1) | 0.610 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.149, 1.04 |
No. of reflections | 2519 |
No. of parameters | 182 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.47, −0.33 |
Selected geometric parameters (Å, º) topS1—C2 | 1.715 (3) | N4—C5 | 1.291 (4) |
S1—C5 | 1.726 (3) | N8—C9 | 1.342 (4) |
C2—N3 | 1.299 (4) | C9—N11 | 1.309 (4) |
C2—N8 | 1.382 (3) | C9—N10 | 1.326 (4) |
N3—N4 | 1.386 (3) | | |
| | | |
C2—S1—C5 | 86.7 (1) | C4'—C3'—C2' | 121.1 (3) |
N3—C2—S1 | 114.7 (2) | C3'—C4'—C5' | 120.4 (4) |
C2—N3—N4 | 111.8 (2) | C4'—C5'—C6' | 119.1 (4) |
C5—N4—N3 | 112.4 (2) | C1'—C6'—C5' | 121.5 (3) |
N4—C5—S1 | 114.3 (2) | N11—C9—N10 | 119.8 (3) |
C6'—C1'—C2' | 118.7 (3) | N11—C9—N8 | 121.5 (3) |
C3'—C2'—C1' | 118.9 (3) | N10—C9—N8 | 118.6 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···Cl1 | 0.86 | 2.25 | 3.092 (3) | 165.5 |
N10—H101···Cl1i | 0.86 | 2.51 | 3.279 (3) | 149.6 |
N10—H102···Cl1ii | 0.86 | 2.53 | 3.211 (3) | 136.1 |
N11—H111···Cl1i | 0.86 | 2.57 | 3.327 (3) | 147.8 |
N11—H111···S1i | 0.86 | 2.95 | 3.465 (3) | 120.5 |
N11—H112···N3 | 0.86 | 2.06 | 2.711 (4) | 131.7 |
Symmetry codes: (i) x, y+1, z; (ii) −x+2, −y+1, −z+1. |
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.