6-Dichloro­methyl-3-propyl-1,2,4-triazolo[3,4-b][1,3,4]thia­diazole

In the title compound, C₇H₈Cl₂N₄S, the triazole ring and the thia­diazole ring are each planar and the C—N and N—N distances in the triazole ring indicate partial electron localization of the double bonds over the ring. π–π stacking inter­actions between the thiadiazole and triazole rings of neigboring molecules [centroid-to-centroid distance 3.8520 (15) Å] and close contacts between the N and S atoms of neighboring mol­ecules are observed in the crystal structure.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.039
• wR factor = 0.101
• Data-to-parameter ratio = 14.7

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT430_ALERT_2_B Short Inter D...A Contact  S1     ..  N3      ..       2.85 Ang.

Alert level C
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C1
PLAT322_ALERT_2_C Check Hybridisation of  S1     in Main Residue .          ?
PLAT431_ALERT_2_C Short Inter HL..A Contact  Cl1    ..  N1      ..       3.12 Ang.

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

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

1,2,4-Triazole and 1,3,4-thiadiazoles represent one of the most biologically active classes of compounds, possessing a wide spectrum of activities (Colanceska-Ragenovic et al., 2001; Labanauskas et al., 2004; Al-Soud et al., 2004; Foroumadi et al., 2001; Jain & Mishra, 2004). Various substituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues are associated with diverse pharmacological activities such as antimicrobial (Swamy et al., 2006), antibacterial (Wang et al., 1996), antitubercular (Udupi et al., 1999), anti-inflammatory (Gupta et al., 1984), and antifungal (Hirpara et al., 2003). If a dichloromethyl group is attached to the parent molecule, many new compounds can be obtained, such as aldehydes and their nucleophilic addition products. In view of these observations and our continued interest in the synthesis of biologically active heterocyclic compounds, we thought it worthwhile to synthesize new fused heterocyclic compounds which possess a dichloromethyl group as the biological activities may be improved many times over that of their parent compounds when incorporating biologically active groups that might interact with the microstructure of the cell.

In the molecule of (I) (Fig. 1), both the five-membered triazole ring as well as the thiadiazole ring are each planar, and the angle between both rings is bascically zero, thus indicating sp² hybridization for all carbon and nitrogen atoms of the heterocyclic rings. The short C—N bond lengths of 1.286 (3), 1.307 (3) and 1.299 (3) for N1—C2, C4—N4, and C3—N3, respectively, suggest partially localized double bonds localized as shown in scheme 1.

In the solid state each two molecules of (I) are arranged around an inversion center to form pairs of weakly π-π stacked dimers (symmetry operator 1/2 - x, 1/2 - y, -z), the centroid-to-centroid distances between the thiadiazole and triazole rings of neigboring molecules are 3.8520 (15) Å. Within the plane of the planar rings (I) forms another type of a loosly connected centrosymmetric dimers via close intermolecular contacts between the nitrogen atoms N3 and the sulfur atom S1 of neighboring molecules with N—S distances of 2.847 (2) Å (symmetry operator 1/2 - x, 3/2 - y, -z). This type of close contacts of chalcogens when with a more electronegative atom such as nitrogen or oxygen is not untypical and the interaction is usually interpreted as the donation of a nitrogen lone pair into the chalcogen-centered antibonding orbitals (Cozzolino et al., 2005).

Related literature

For related literature, see: Al-Soud et al. (2004); Colanceska-Ragenovic et al. (2001); Foroumadi et al. (2001); Gupta et al. (1984); Hirpara et al. (2003); Jain & Mishra (2004); Labanauskas et al. (2004); Lei, Huang et al. (2006); Lei, Zhang et al. (2006); Swamy et al. (2006); Udupi et al. (1999); Wang et al. (1996); Zhang et al. (1996).

For related literature, see: Cozzolino et al. (2005).

S2. Experimental

A mixture of thiocarbohydrazide (0.03 mol) and butyric acid (0.03 mol) was refluxed for 4 h. Then the solution was cooled, and unreacted butyric acid was completely removed in vacuo. The resulting 3-propyl-4-amino-5-mercapto-1,2,4-triazole was first purified by reprecipitation using ethanol. Then, a mixture of 3-propyl-4-amino-5-mercapto-1,2,4-triazole (5.0 mmol) and dichloroacetic acid (5.5 mmol) in phosphorous oxychloride (20 ml) was heated to reflux for 7 h. The reaction mixture was poured gradually onto crushed ice with stirring. Some solid potassium carbonate was added to the mixture with stirring, then a appropriate amount of solid potassium hydroxide was added till the pH value was 8. The separated solid after standing overnight was filtered, washed with cold water, dried, and recrystallized from absolute alcohol to afford the title compounds 3-propyl-6-dichloromethyl-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazole [m.p. 340–341 K] in about 58.9% yield. IR (KBr): 2973, 2920 (RH), 1628 (C=N), 1513, 1464 (aromatic ring skeleton vibration), 1258 (N—N=C), 812, 739 (C—Cl), 695 (C—S—C) cm^{-1. 1}H NMR (DMSO-d₆): 0.96 (t, 3H, –CH₂), 1.76–1.84 (m, 2H, –CH₂–), 2.97–3.02 (m, 2H, –CH₂–), 5.22, 8.03 (s, H, –CHCl₂) p.p.m.. ¹³C NMR (DMSO-d₆): 13.56 (–CH₃), 19.67, 26.18, 39.42 (–CH₂–), 64.46 (–CHCl₂), 147.93, 152.70, 167.04 (fused heterocycle carbon) p.p.m..

S3. Refinement

All H atoms were positioned geometrically and allowed to ride on their parent atoms at distances of Csp²—H = 0.93 Å with U_iso=1.2U_eq(parent atom), and Csp³—H = 0.96 or 0.97 Å with U_iso=1.5U_eq(parent atom).

Computing details

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2002); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (I) with the atom numbering scheme, showing displacement ellipsoids at the 30% probability level.
	Fig. 2. Packing diagram for (I), showing the short contacts between N3 and S1 (blue dashed lines) and the π-π stacking interactions (green dotted lines).

6-Dichloromethyl-3-propyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

Crystal data

C7H8Cl2N4S	F(000) = 1024
Mr = 251.13	Dx = 1.584 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 2080 reflections
a = 21.116 (4) Å	θ = 2.5–25.0°
b = 5.1836 (9) Å	µ = 0.78 mm^−1
c = 19.781 (3) Å	T = 298 K
β = 103.440 (3)°	Rod, colorless
V = 2105.8 (6) Å^3	0.35 × 0.19 × 0.18 mm
Z = 8

Data collection

Bruker APEX area-detector diffractometer	1880 independent reflections
Radiation source: fine-focus sealed tube	1678 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.020
φ and ω scans	θmax = 25.2°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −20→24
Tmin = 0.772, Tmax = 0.872	k = −6→6
5254 measured reflections	l = −23→21

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.101	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0462P)^2 + 2.565P] where P = (Fo^2 + 2Fc^2)/3
1880 reflections	(Δ/σ)max = 0.001
128 parameters	Δρmax = 0.40 e Å^−3
0 restraints	Δρmin = −0.30 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	0.19565 (3)	0.03777 (12)	0.90696 (3)	0.0436 (2)
Cl1	0.17703 (4)	0.25892 (16)	0.72291 (3)	0.0635 (3)
Cl2	0.09661 (4)	0.4437 (2)	0.81287 (4)	0.0754 (3)
N1	0.28183 (9)	0.3513 (4)	0.87479 (10)	0.0403 (5)
N2	0.31298 (9)	0.1848 (4)	0.92536 (10)	0.0388 (5)
N3	0.31385 (10)	−0.1427 (4)	0.99590 (11)	0.0511 (6)
N4	0.37773 (11)	−0.0510 (4)	1.00200 (12)	0.0519 (6)
C1	0.17588 (12)	0.4254 (5)	0.80105 (13)	0.0427 (6)
H1	0.1920	0.6011	0.7976	0.051*
C2	0.22106 (11)	0.2914 (4)	0.86033 (12)	0.0373 (5)
C3	0.27697 (12)	0.0023 (5)	0.94926 (12)	0.0408 (6)
C4	0.37629 (12)	0.1447 (5)	0.96000 (12)	0.0442 (6)
C5	0.43185 (12)	0.2989 (5)	0.94811 (13)	0.0486 (6)
H5A	0.4706	0.2527	0.9830	0.058*
H5B	0.4231	0.4801	0.9542	0.058*
C6	0.44528 (14)	0.2615 (6)	0.87671 (16)	0.0564 (7)
H6A	0.4586	0.0845	0.8722	0.068*
H6B	0.4055	0.2914	0.8416	0.068*
C7	0.49772 (15)	0.4413 (7)	0.86391 (18)	0.0708 (9)
H7A	0.4853	0.6167	0.8696	0.106*
H7B	0.5031	0.4170	0.8175	0.106*
H7C	0.5380	0.4044	0.8965	0.106*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0417 (4)	0.0432 (4)	0.0470 (4)	−0.0081 (3)	0.0126 (3)	0.0023 (3)
Cl1	0.0646 (5)	0.0792 (5)	0.0429 (4)	0.0160 (4)	0.0047 (3)	−0.0107 (3)
Cl2	0.0481 (4)	0.1088 (7)	0.0736 (5)	0.0196 (4)	0.0228 (4)	0.0109 (5)
N1	0.0439 (11)	0.0403 (11)	0.0374 (11)	−0.0030 (9)	0.0109 (8)	0.0041 (9)
N2	0.0417 (11)	0.0381 (11)	0.0362 (10)	−0.0054 (9)	0.0085 (8)	0.0031 (8)
N3	0.0512 (13)	0.0497 (13)	0.0510 (13)	−0.0063 (10)	0.0091 (10)	0.0119 (11)
N4	0.0496 (13)	0.0537 (13)	0.0497 (13)	−0.0028 (10)	0.0065 (10)	0.0080 (11)
C1	0.0424 (13)	0.0409 (13)	0.0459 (14)	0.0030 (11)	0.0122 (11)	−0.0030 (11)
C2	0.0413 (13)	0.0366 (12)	0.0360 (12)	−0.0032 (10)	0.0131 (10)	−0.0025 (10)
C3	0.0432 (13)	0.0405 (13)	0.0403 (13)	−0.0069 (11)	0.0128 (10)	−0.0008 (10)
C4	0.0413 (13)	0.0499 (15)	0.0399 (13)	−0.0033 (11)	0.0063 (10)	−0.0004 (11)
C5	0.0397 (13)	0.0518 (15)	0.0524 (15)	−0.0084 (11)	0.0072 (11)	−0.0021 (12)
C6	0.0539 (16)	0.0562 (17)	0.0619 (18)	−0.0044 (13)	0.0192 (13)	−0.0025 (13)
C7	0.0619 (19)	0.077 (2)	0.083 (2)	−0.0040 (16)	0.0351 (17)	0.0057 (18)

Geometric parameters (Å, º)

S1—C3	1.736 (3)	C1—H1	0.9800
S1—C2	1.760 (2)	C4—C5	1.483 (3)
Cl1—C1	1.775 (2)	C5—C6	1.516 (4)
Cl2—C1	1.746 (2)	C5—H5A	0.9700
N1—C2	1.286 (3)	C5—H5B	0.9700
N1—N2	1.368 (3)	C6—C7	1.513 (4)
N2—C3	1.365 (3)	C6—H6A	0.9700
N2—C4	1.369 (3)	C6—H6B	0.9700
N3—C3	1.299 (3)	C7—H7A	0.9600
N3—N4	1.409 (3)	C7—H7B	0.9600
N4—C4	1.307 (3)	C7—H7C	0.9600
C1—C2	1.499 (3)
C3—S1—C2	86.78 (11)	N4—C4—C5	128.1 (2)
C2—N1—N2	107.21 (18)	N2—C4—C5	123.7 (2)
C3—N2—N1	118.59 (19)	C4—C5—C6	113.9 (2)
C3—N2—C4	106.2 (2)	C4—C5—H5A	108.8
N1—N2—C4	135.2 (2)	C6—C5—H5A	108.8
C3—N3—N4	105.6 (2)	C4—C5—H5B	108.8
C4—N4—N3	109.1 (2)	C6—C5—H5B	108.8
C2—C1—Cl2	112.10 (17)	H5A—C5—H5B	107.7
C2—C1—Cl1	108.72 (17)	C7—C6—C5	112.3 (2)
Cl2—C1—Cl1	110.52 (14)	C7—C6—H6A	109.1
C2—C1—H1	108.5	C5—C6—H6A	109.1
Cl2—C1—H1	108.5	C7—C6—H6B	109.1
Cl1—C1—H1	108.5	C5—C6—H6B	109.1
N1—C2—C1	118.9 (2)	H6A—C6—H6B	107.9
N1—C2—S1	118.26 (18)	C6—C7—H7A	109.5
C1—C2—S1	122.67 (17)	C6—C7—H7B	109.5
N3—C3—N2	110.9 (2)	H7A—C7—H7B	109.5
N3—C3—S1	140.0 (2)	C6—C7—H7C	109.5
N2—C3—S1	109.12 (17)	H7A—C7—H7C	109.5
N4—C4—N2	108.2 (2)	H7B—C7—H7C	109.5