3-(4-Fluoro­benz­yl)-4-(2-methoxy­phen­yl)-1H-1,2,4-triazole-5(4H)-thione

The title compound, C₁₆H₁₄FN₃OS, is an important biologically active heterocyclic compound, containing one planar five-membered and two planar six-membered rings. The five-membered ring is oriented with respect to the six-membered rings at dihedral angles of 86.96 (3) and 74.42 (3)°. In the crystal structure, inter­molecular N—H...S and C—H...F hydrogen bonds link the mol­ecules into infinite chains.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.033
• wR factor = 0.091
• Data-to-parameter ratio = 13.5

checkCIF/PLATON results

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Alert level C
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C14

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   0 ALERT level B = Potentially serious problem
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   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
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S1. Comment

Substituted triazole derivatives display significant biological activity including antimicrobial (Holla et al., 1998), analgesic (Turan-Zitouni et al., 1999), antitumor (Demirbas et al., 2002), antihypertensive (Paulvannan et al., 2000) and antiviral activities (Kritsanida et al., 2002). The biological activity is closely related to the structure, possibly being due to the presence of the —N—C ═S unit (Omar et al., 1986). We are interested in the synthesis and biological activity of aryloxyacetyl hydrazide derivatives and report herein the synthesis and crystal structure of the title compound, (I).

In the molecule of (I) (Fig. 1), the ligand bond lengths and angles are within normal ranges (Allen et al., 1987), and are comparable with those observed in related structures (Ozturk et al., 2004a,b).

The C8═S1 [1.6738 (17) Å] bond is in accordance with the corresponding values of 1.6773 (19) Å in 4-(4-chlorophenyl)-3-(furan-2-yl)-1H-1,2,4- triazole-5(4H)-thione (Ozturk et al., 2004a) and 1.668 (5) Å in 4-amino-3-(1,2,3,4,5-pentahydroxypentyl)-1H-1,2,4-triazole-5(4H)-thione (Zhang et al., 2004). In the triazole ring, the N3 ═C9 [1.300 (2) Å] bond shows double-bond character.

The rings A (N1—N3/C8/C9), B (C2—C7) and C (C11—C16) are, of course, planar and dihedral angles between them are A/B = 89.96 (3)°, A/C = 74.42 (3)° and B/C = 19.58 (3)°.

In the crystal structure, intermolecular N—H···S and C—H···F hydrogen bonds (Table 1) link the molecules into infinite chains (Fig. 2), in which they may be effective in the stabilization of the structure.

Related literature

For bond-length data, see: Allen et al. (1987). For general background, see: Holla et al. (1998); Turan-Zitouni et al. (1999); Demirbas et al. (2002); Paulvannan et al. (2000); Kritsanida et al. (2002); Omar et al. (1986). For related structures, see: Öztürk et al. (2004a,b); Zhang et al. (2004).

S2. Experimental

The synthesis of the title compound was carried out by refluxing a solution of 1-(2-(4-fluorophenyl)acetyl)-4-(2-methoxy phenyl)thiosemicarbazide (3.33 g, 10 mmol) in 2 M NaOH for 5 h. Single crystals suitable for X-ray analysis were obtained by recrystallization from an aqeous ethanol solution at room temperature (yield; 78%; m.p. 464–465 K).

S3. Refinement

H1 (for NH) was located in difference syntheses and refined isotropically [N2—H1 = 0.824 (19) Å and U_iso(H) = 0.069 (5) Ų]. The remaining H atoms were positioned geometrically, with C—H = 0.93, 0.97 and 0.96 Å for aromatic, methylene and methyl H atoms, and constrained to ride on their parent atoms, with U_iso(H) = xU_eq(C), where x = 1.5 for methyl H, and x = 1.2 for all other H atoms.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1999); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A packing diagram for (I). Hydrogen bonds are shown as dashed lines.
	Fig. 3. Preparation of the title compound.

3-(4-Fluorobenzyl)-4-(2-methoxyphenyl)-1H-1,2,4-triazole-5(4H)-thione

Crystal data

C16H14FN3OS	F(000) = 656
Mr = 315.36	Dx = 1.340 Mg m^−3
Monoclinic, P21/n	Melting point: 464(1) K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 7.4910 (7) Å	Cell parameters from 5348 reflections
b = 16.1656 (15) Å	θ = 2.4–26.4°
c = 12.9147 (12) Å	µ = 0.22 mm^−1
β = 91.956 (2)°	T = 298 K
V = 1563.0 (3) Å^3	Block, colourless
Z = 4	0.30 × 0.24 × 0.22 mm

Data collection

Bruker SMART CCD area-dedector diffractometer	2735 independent reflections
Radiation source: fine-focus sealed tube	2209 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.016
ω and φ scans	θmax = 25.0°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −8→8
Tmin = 0.873, Tmax = 0.950	k = −19→9
7491 measured reflections	l = −15→15

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.091	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0403P)^2 + 0.323P] where P = (Fo^2 + 2Fc^2)/3
2735 reflections	(Δ/σ)max < 0.001
203 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.18 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
S1	0.06617 (6)	0.05788 (3)	0.15775 (4)	0.07306 (18)
O1	0.30466 (16)	0.27259 (7)	0.13357 (9)	0.0683 (3)
N1	0.38497 (16)	0.11534 (7)	0.08812 (10)	0.0531 (3)
N2	0.2222 (2)	0.05914 (9)	−0.02932 (11)	0.0610 (4)
H1	0.141 (2)	0.0337 (11)	−0.0595 (15)	0.069 (5)*
N3	0.3773 (2)	0.07973 (9)	−0.07693 (11)	0.0644 (4)
F1	0.7511 (3)	0.48608 (9)	0.02635 (19)	0.1811 (9)
C1	0.2793 (3)	0.35942 (12)	0.14504 (18)	0.0876 (6)
H1A	0.2010	0.3793	0.0902	0.131*
H1B	0.3925	0.3870	0.1421	0.131*
H1C	0.2274	0.3704	0.2106	0.131*
C2	0.4123 (2)	0.23355 (10)	0.20422 (12)	0.0547 (4)
C3	0.4880 (2)	0.26997 (12)	0.29317 (13)	0.0662 (5)
H3A	0.4650	0.3252	0.3080	0.079*
C4	0.5963 (3)	0.22433 (15)	0.35849 (15)	0.0792 (6)
H4A	0.6462	0.2490	0.4178	0.095*
C5	0.6325 (3)	0.14310 (15)	0.33837 (16)	0.0866 (6)
H5A	0.7066	0.1131	0.3838	0.104*
C6	0.5588 (2)	0.10541 (12)	0.25025 (15)	0.0719 (5)
H6A	0.5821	0.0501	0.2363	0.086*
C7	0.4511 (2)	0.15124 (10)	0.18398 (12)	0.0532 (4)
C8	0.2221 (2)	0.07788 (9)	0.07140 (12)	0.0550 (4)
C9	0.4741 (2)	0.11411 (9)	−0.00335 (13)	0.0564 (4)
C10	0.6603 (2)	0.14446 (11)	−0.01445 (15)	0.0667 (5)
H10A	0.7006	0.1283	−0.0821	0.080*
H10B	0.7370	0.1172	0.0371	0.080*
C11	0.6828 (2)	0.23688 (10)	−0.00278 (13)	0.0563 (4)
C12	0.6120 (3)	0.29033 (13)	−0.07650 (15)	0.0731 (5)
H12A	0.5470	0.2694	−0.1332	0.088*
C13	0.6366 (3)	0.37436 (14)	−0.0671 (2)	0.0961 (7)
H13A	0.5907	0.4105	−0.1174	0.115*
C14	0.7288 (4)	0.40306 (13)	0.0170 (2)	0.1012 (7)
C15	0.7993 (3)	0.35367 (14)	0.0920 (2)	0.0924 (7)
H15A	0.8606	0.3758	0.1493	0.111*
C16	0.7777 (2)	0.26923 (11)	0.08116 (15)	0.0699 (5)
H16A	0.8277	0.2338	0.1310	0.084*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0624 (3)	0.0913 (4)	0.0649 (3)	−0.0217 (2)	−0.0057 (2)	−0.0104 (2)
O1	0.0728 (7)	0.0605 (7)	0.0703 (7)	0.0086 (6)	−0.0161 (6)	−0.0076 (6)
N1	0.0534 (7)	0.0482 (7)	0.0570 (8)	−0.0037 (6)	−0.0081 (6)	−0.0051 (6)
N2	0.0668 (9)	0.0547 (8)	0.0606 (9)	−0.0108 (7)	−0.0120 (7)	−0.0068 (6)
N3	0.0756 (9)	0.0557 (8)	0.0616 (8)	−0.0073 (7)	−0.0012 (7)	−0.0073 (7)
F1	0.223 (2)	0.0594 (9)	0.261 (2)	−0.0284 (10)	−0.0003 (18)	0.0010 (11)
C1	0.1005 (15)	0.0630 (12)	0.0987 (15)	0.0142 (10)	−0.0065 (12)	−0.0051 (11)
C2	0.0479 (8)	0.0622 (10)	0.0538 (9)	−0.0068 (7)	−0.0018 (7)	−0.0046 (7)
C3	0.0608 (10)	0.0775 (12)	0.0602 (10)	−0.0129 (9)	0.0007 (8)	−0.0153 (9)
C4	0.0718 (12)	0.1044 (16)	0.0603 (11)	−0.0187 (11)	−0.0144 (9)	−0.0084 (11)
C5	0.0796 (13)	0.1053 (17)	0.0727 (13)	−0.0062 (12)	−0.0295 (10)	0.0160 (12)
C6	0.0698 (11)	0.0690 (11)	0.0759 (12)	−0.0011 (9)	−0.0147 (9)	0.0092 (9)
C7	0.0483 (8)	0.0581 (9)	0.0527 (8)	−0.0081 (7)	−0.0053 (7)	−0.0016 (7)
C8	0.0573 (9)	0.0456 (8)	0.0612 (10)	−0.0029 (7)	−0.0124 (7)	−0.0031 (7)
C9	0.0632 (9)	0.0453 (8)	0.0605 (10)	0.0002 (7)	−0.0012 (8)	−0.0027 (7)
C10	0.0620 (10)	0.0619 (10)	0.0766 (12)	0.0005 (8)	0.0072 (8)	−0.0069 (9)
C11	0.0489 (8)	0.0581 (9)	0.0621 (10)	−0.0014 (7)	0.0063 (7)	0.0024 (8)
C12	0.0714 (11)	0.0802 (13)	0.0676 (11)	0.0055 (9)	0.0007 (9)	0.0058 (10)
C13	0.1059 (17)	0.0745 (15)	0.1082 (18)	0.0126 (12)	0.0100 (14)	0.0312 (13)
C14	0.1111 (18)	0.0557 (13)	0.137 (2)	−0.0129 (12)	0.0083 (17)	0.0055 (14)
C15	0.0853 (14)	0.0778 (14)	0.1133 (18)	−0.0219 (11)	−0.0074 (12)	−0.0179 (13)
C16	0.0611 (10)	0.0703 (11)	0.0776 (12)	−0.0053 (8)	−0.0070 (9)	0.0046 (9)

Geometric parameters (Å, º)

C1—O1	1.425 (2)	C9—N3	1.300 (2)
C1—H1A	0.9600	C9—N1	1.377 (2)
C1—H1B	0.9600	C9—C10	1.490 (2)
C1—H1C	0.9600	C10—C11	1.510 (2)
C2—O1	1.3529 (19)	C10—H10A	0.9700
C2—C7	1.389 (2)	C10—H10B	0.9700
C2—C3	1.394 (2)	C11—C12	1.378 (2)
C3—C4	1.366 (3)	C11—C16	1.379 (2)
C3—H3A	0.9300	C12—C13	1.376 (3)
C4—C5	1.368 (3)	C12—H12A	0.9300
C4—H4A	0.9300	C13—C14	1.349 (3)
C5—C6	1.389 (3)	C13—H13A	0.9300
C5—H5A	0.9300	C14—C15	1.349 (3)
C6—C7	1.373 (2)	C14—F1	1.357 (3)
C6—H6A	0.9300	C15—C16	1.381 (3)
C7—N1	1.4397 (19)	C15—H15A	0.9300
C8—N2	1.336 (2)	C16—H16A	0.9300
C8—N1	1.3725 (19)	N2—N3	1.374 (2)
C8—S1	1.6738 (17)	N2—H1	0.824 (19)
O1—C1—H1A	109.5	C9—C10—H10A	108.6
O1—C1—H1B	109.5	C11—C10—H10A	108.6
H1A—C1—H1B	109.5	C9—C10—H10B	108.6
O1—C1—H1C	109.5	C11—C10—H10B	108.6
H1A—C1—H1C	109.5	H10A—C10—H10B	107.6
H1B—C1—H1C	109.5	C12—C11—C16	118.76 (17)
O1—C2—C7	116.35 (13)	C12—C11—C10	120.82 (16)
O1—C2—C3	125.11 (16)	C16—C11—C10	120.41 (16)
C7—C2—C3	118.54 (15)	C13—C12—C11	120.7 (2)
C4—C3—C2	119.80 (18)	C13—C12—H12A	119.6
C4—C3—H3A	120.1	C11—C12—H12A	119.6
C2—C3—H3A	120.1	C14—C13—C12	118.3 (2)
C3—C4—C5	121.25 (17)	C14—C13—H13A	120.9
C3—C4—H4A	119.4	C12—C13—H13A	120.9
C5—C4—H4A	119.4	C15—C14—C13	123.5 (2)
C4—C5—C6	120.07 (18)	C15—C14—F1	118.5 (3)
C4—C5—H5A	120.0	C13—C14—F1	118.0 (3)
C6—C5—H5A	120.0	C14—C15—C16	118.1 (2)
C7—C6—C5	118.86 (18)	C14—C15—H15A	120.9
C7—C6—H6A	120.6	C16—C15—H15A	120.9
C5—C6—H6A	120.6	C11—C16—C15	120.64 (19)
C6—C7—C2	121.47 (15)	C11—C16—H16A	119.7
C6—C7—N1	119.73 (15)	C15—C16—H16A	119.7
C2—C7—N1	118.69 (13)	C8—N1—C9	108.26 (13)
N2—C8—N1	102.91 (14)	C8—N1—C7	126.22 (13)
N2—C8—S1	128.94 (12)	C9—N1—C7	125.52 (13)
N1—C8—S1	128.12 (12)	C8—N2—N3	114.16 (14)
N3—C9—N1	111.00 (14)	C8—N2—H1	123.4 (13)
N3—C9—C10	124.82 (16)	N3—N2—H1	122.3 (13)
N1—C9—C10	124.11 (14)	C9—N3—N2	103.63 (14)
C9—C10—C11	114.68 (14)	C2—O1—C1	117.90 (14)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1···S1^i	0.824 (19)	2.465 (17)	3.2789 (16)	171.1 (16)
C5—H5A···F1^ii	0.93	2.37	3.186 (3)	146

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