N-(5-Benzyl­sulfanyl-1,3,4-thia­diazol-2-yl)-2-(piperidin-1-yl)acetamide

Ismailova, D.S.; Okmanov, R.Y.; Ziyaev, A.A.; Shakhidoyatov, K.M.; Tashkhodjaev, B.

doi:10.1107/S160053681400213X

N-(5-Benzylsulfanyl-1,3,4-thiadiazol-2-yl)-2-(piperidin-1-yl)acetamide

D. S. Ismailova, R. Y. Okmanov, A. A. Ziyaev, K. M. Shakhidoyatov and B. Tashkhodjaev

The title compound, C₁₆H₂₀N₄OS₂, was synthesized by the reaction of 2-benzylsulfanyl-5-chloroacetamido-1,3,4-thiadiazole and piperidine in a 1:2 ratio. The planes of the acetamide and 1,3,4-thiadiazole units are twisted by 10.8 (4)°. The thiadiazole S atom and the acetamide O atom are syn-oriented due to a hypervalent S

O interaction of 2.628 (4) Å. In the crystal, molecules form centrosymmetric dimers via N—H

N hydrogen bonds. These dimers are further connected by C—H

O interactions into (100) layers.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S160053681400213X/gk2599sup1.cif Contains datablocks I, Global
	Structure factor file (CIF format) https://doi.org/10.1107/S160053681400213X/gk2599Isup2.hkl Contains datablock I
	Chemical Markup Language (CML) file https://doi.org/10.1107/S160053681400213X/gk2599Isup3.cml Supplementary material

CCDC reference: 984204

checkCIF report

Key indicators

Single-crystal X-ray study
T = 290 K
Mean (C-C) = 0.009 Å
R factor = 0.069
wR factor = 0.217
Data-to-parameter ratio = 14.3

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0088 Ang.
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......      4.069 Check
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.595         13
PLAT934_ALERT_3_C Number of (Iobs-Icalc)/SigmaW > 10 Outliers ....          1 Check

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          1 Why ?
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT Unusually Large.       0.11
PLAT910_ALERT_3_G Missing # of FCF Reflections Below Th(Min) .....          1 Why ?

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   4 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   4 ALERT level G = General information/check it is not something unexpected

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

Comment top

1,3,4-Thiadiazoless are a very important class of compounds because of their interesting physiological properties. Derivatives of 1,3,4– thiadiazoles show different biological activities such as antihypertensive (Turner et al., 1988), anticonvulsant (Chapleo et al., 1987), anti-depressant (Cleici et al., 2001), and diuretic (Jain & Mishra, 2004). Acetazolamide, having a 1,3,4-thiadiazole moiety, is known in medicine as narcotic drug.

The title compound was obtained in the reaction of 2-benzylsulfanyl-5-chloroacetamido-1,3,4-thiadiazole and piperidine in a 1:2 ratio in the presence of benzene. The structure of the obtained product was confirmed by single-crystal X-ray analysis and ¹H NMR spectroscopy.

Molecular structure of title compound is shown in Figure 1. The acetamido-1,3,4-thiadiazole (S1/C1/N1/N2/C2/N3/C10/O1/C11) unit is essentially planar [r.m.s. deviation 0.082 Å]. The thiadiazole sulfur and the acetamido oxygen atoms are syn oriented due to a hypervalent interaction with the S···O distance of 2.628 (4) Å. In crystal, the molecules form centrosymmetric dimers through N-H···N hydrogen bonds (Table 1, Fig. 2). These dimers are further connected by C11—H···O1 interactions into (100) layers. As well as an intramolecular S···O hypervalent interaction [S1···O1 ═ 2.625 (5) Å] was observed.

Related literature top

For physiological properties and syntheses of 1,3,4-thiadiazole derivatives, see: Turner et al. (1988); Chapleo et al. (1987); Cleici et al. (2001); Jain & Mishra (2004). For the structures of related 1,3,4-thiadiazole derivatives, see: Leung et al. (1992); Zhang (2009).

Experimental top

To a solution of 2.99 g (10 mmol) of 2–benzylsulfanyl–5–chloroacetamido–1,3,4–thiadiazole in 15 ml benzene was added dropwise 1.7 g (20 mmol) of piperidine at room temperature. The reaction mixture was refluxed for 8 h. Benzene was distilled off, the residue was washed with water, 2% solution of NaOH, again with water and re-crystallized from hexane [yield 3.02 g (87%); m.p. 376–377 K]. Colourless crystals suitable for X–ray analysis were grown from hexane at room temperature.

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2009); cell refinement: CrysAlis PRO (Oxford Diffraction, 2009); data reduction: CrysAlis PRO (Oxford Diffraction, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures top

	Fig. 1. The molecular structure of the title compound. The displacement ellipsoid are drawn at the 30% probability level.
	Fig. 2. Crystal packing viewed down the c axis with hydrogen bonds shown as dashed lines.

N-(5-Benzylsulfanyl-1,3,4-thiadiazol-2-yl)-2-(piperidin-1-yl)acetamide top

Crystal data top

C₁₆H₂₀N₄OS₂	F(000) = 736
M_r = 348.48	D_x = 1.364 Mg m⁻³
Monoclinic, P2₁/c	Melting point < 376(1) K
Hall symbol: -P 2ybc	Cu Kα radiation, λ = 1.54184 Å
a = 17.429 (4) Å	Cell parameters from 124 reflections
b = 16.748 (3) Å	θ = 5.9–35.8°
c = 5.8390 (12) Å	µ = 2.92 mm⁻¹
β = 95.48 (3)°	T = 290 K
V = 1696.6 (6) Å³	Prizmatic, colourless
Z = 4	0.35 × 0.28 × 0.20 mm

Data collection top

Oxford Diffraction Xcalibur Ruby diffractometer	2970 independent reflections
Radiation source: Enhance (Cu) X-ray Source	1521 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.117
Detector resolution: 10.2576 pixels mm^-1	θ_max = 66.6°, θ_min = 3.7°
ω scans	h = −20→20
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)	k = 0→19
T_min = 0.431, T_max = 0.558	l = 0→6
7003 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.069	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.217	H-atom parameters constrained
S = 0.98	w = 1/[σ²(F_o²) + (0.1068P)²] where P = (F_o² + 2F_c²)/3
2970 reflections	(Δ/σ)_max < 0.001
208 parameters	Δρ_max = 0.41 e Å⁻³
0 restraints	Δρ_min = −0.39 e Å⁻³

Crystal data top

C₁₆H₂₀N₄OS₂	V = 1696.6 (6) Å³
M_r = 348.48	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 17.429 (4) Å	µ = 2.92 mm⁻¹
b = 16.748 (3) Å	T = 290 K
c = 5.8390 (12) Å	0.35 × 0.28 × 0.20 mm
β = 95.48 (3)°

Data collection top

Oxford Diffraction Xcalibur Ruby diffractometer	2970 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)	1521 reflections with I > 2σ(I)
T_min = 0.431, T_max = 0.558	R_int = 0.117
7003 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.069	0 restraints
wR(F²) = 0.217	H-atom parameters constrained
S = 0.98	Δρ_max = 0.41 e Å⁻³
2970 reflections	Δρ_min = −0.39 e Å⁻³
208 parameters

Special details top

Experimental. ¹H NMR (400 MHz, CDCl₃, DMSO): 7.30 (5H, m, H–5,6,7,8,9), 6.36 (1H, s, N–H), 4.39 (2H, s, CH₂–11), 3.17 (2H, s CH₂–3), 2.47 (4H, t, J═5.0 Hz, CH₂–12,16), 1.57 (4H, m, CH₂–13,15), 1.42 (2H, t, J═5.1 Hz, CH₂–14).

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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	U_iso*/U_eq
S1	0.52312 (7)	0.33111 (9)	0.9429 (2)	0.0528 (4)
S2	0.39119 (9)	0.32063 (11)	1.2305 (3)	0.0642 (5)
O1	0.6512 (2)	0.3164 (3)	0.7429 (8)	0.0675 (12)
N1	0.4609 (3)	0.4532 (3)	0.7342 (8)	0.0545 (12)
N2	0.4113 (3)	0.4313 (3)	0.8972 (8)	0.0536 (12)
N3	0.5742 (3)	0.4130 (3)	0.5819 (8)	0.0549 (12)
H3	0.5681	0.4490	0.4769	0.066*
N4	0.7677 (3)	0.3620 (3)	0.4568 (7)	0.0499 (11)
C1	0.5195 (3)	0.4055 (4)	0.7371 (9)	0.0496 (14)
C2	0.4357 (3)	0.3686 (4)	1.0141 (9)	0.0524 (15)
C3	0.3196 (3)	0.3937 (4)	1.3030 (10)	0.0637 (17)
H3B	0.3186	0.3945	1.4688	0.076*
H3C	0.3357	0.4461	1.2561	0.076*
C4	0.2399 (3)	0.3782 (4)	1.1947 (9)	0.0526 (14)
C5	0.2152 (3)	0.4084 (4)	0.9797 (10)	0.0641 (17)
H5A	0.2496	0.4359	0.8964	0.077*
C6	0.1403 (4)	0.3980 (5)	0.8881 (11)	0.074 (2)
H6A	0.1248	0.4181	0.7426	0.089*
C7	0.0882 (4)	0.3586 (4)	1.0077 (12)	0.0730 (19)
H7A	0.0371	0.3534	0.9472	0.088*
C8	0.1127 (4)	0.3267 (5)	1.2187 (12)	0.077 (2)
H8A	0.0782	0.2981	1.2991	0.093*
C9	0.1871 (3)	0.3364 (4)	1.3124 (11)	0.0677 (18)
H9A	0.2025	0.3147	1.4562	0.081*
C10	0.6380 (3)	0.3646 (4)	0.5903 (10)	0.0500 (14)
C11	0.6864 (3)	0.3734 (4)	0.3892 (9)	0.0550 (15)
H11A	0.6694	0.3347	0.2717	0.066*
H11B	0.6784	0.4263	0.3231	0.066*
C12	0.8104 (3)	0.3476 (4)	0.2561 (10)	0.0606 (16)
H12A	0.8052	0.3935	0.1545	0.073*
H12B	0.7888	0.3016	0.1719	0.073*
C13	0.8937 (3)	0.3331 (4)	0.3287 (11)	0.0691 (18)
H13A	0.9210	0.3260	0.1930	0.083*
H13B	0.8988	0.2841	0.4176	0.083*
C14	0.9299 (3)	0.4006 (5)	0.4705 (11)	0.074 (2)
H14A	0.9324	0.4477	0.3750	0.089*
H14B	0.9821	0.3862	0.5281	0.089*
C15	0.8832 (4)	0.4190 (5)	0.6722 (11)	0.075 (2)
H15A	0.8879	0.3751	0.7811	0.090*
H15B	0.9032	0.4667	0.7506	0.090*
C16	0.7994 (3)	0.4313 (4)	0.5881 (10)	0.0592 (16)
H16A	0.7701	0.4401	0.7188	0.071*
H16B	0.7944	0.4784	0.4914	0.071*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0408 (7)	0.0584 (9)	0.0596 (9)	0.0043 (7)	0.0063 (6)	0.0094 (8)
S2	0.0531 (8)	0.0744 (11)	0.0673 (10)	0.0131 (8)	0.0177 (7)	0.0167 (9)
O1	0.053 (2)	0.074 (3)	0.077 (3)	0.014 (2)	0.017 (2)	0.030 (3)
N1	0.051 (3)	0.053 (3)	0.059 (3)	0.008 (2)	0.006 (2)	0.007 (2)
N2	0.045 (3)	0.055 (3)	0.062 (3)	0.004 (2)	0.011 (2)	0.008 (3)
N3	0.045 (2)	0.064 (3)	0.055 (3)	0.001 (2)	0.005 (2)	0.014 (3)
N4	0.045 (2)	0.058 (3)	0.047 (3)	0.002 (2)	0.0067 (19)	−0.003 (2)
C1	0.036 (3)	0.058 (4)	0.054 (3)	−0.001 (2)	0.000 (2)	0.003 (3)
C2	0.042 (3)	0.063 (4)	0.052 (3)	−0.001 (3)	0.004 (2)	−0.003 (3)
C3	0.053 (3)	0.085 (5)	0.054 (4)	0.005 (3)	0.008 (3)	−0.007 (3)
C4	0.050 (3)	0.059 (4)	0.050 (3)	0.004 (3)	0.011 (2)	−0.001 (3)
C5	0.057 (4)	0.079 (5)	0.057 (4)	0.000 (3)	0.012 (3)	0.012 (3)
C6	0.065 (4)	0.092 (6)	0.063 (4)	0.006 (4)	−0.001 (3)	0.009 (4)
C7	0.047 (3)	0.085 (5)	0.086 (5)	0.000 (3)	0.003 (3)	−0.002 (4)
C8	0.056 (4)	0.090 (5)	0.089 (5)	−0.006 (4)	0.025 (3)	0.016 (4)
C9	0.059 (4)	0.088 (5)	0.058 (4)	0.007 (3)	0.015 (3)	0.018 (4)
C10	0.040 (3)	0.050 (3)	0.060 (4)	−0.002 (2)	0.005 (2)	−0.002 (3)
C11	0.050 (3)	0.060 (4)	0.055 (3)	0.002 (3)	0.007 (3)	0.003 (3)
C12	0.061 (4)	0.070 (4)	0.052 (3)	−0.002 (3)	0.012 (3)	−0.012 (3)
C13	0.056 (3)	0.084 (5)	0.070 (4)	0.008 (4)	0.022 (3)	−0.011 (4)
C14	0.044 (3)	0.099 (6)	0.078 (5)	−0.003 (3)	0.004 (3)	−0.005 (4)
C15	0.054 (4)	0.102 (6)	0.071 (4)	−0.006 (4)	0.007 (3)	−0.027 (4)
C16	0.054 (3)	0.066 (4)	0.058 (4)	0.001 (3)	0.013 (3)	−0.014 (3)

Geometric parameters (Å, º) top

S1—C1	1.728 (6)	C7—C8	1.373 (9)
S1—C2	1.736 (5)	C7—H7A	0.9300
S2—C2	1.741 (6)	C8—C9	1.368 (9)
S2—C3	1.825 (6)	C8—H8A	0.9300
O1—C10	1.208 (7)	C9—H9A	0.9300
N1—C1	1.295 (7)	C10—C11	1.517 (7)
N1—N2	1.394 (6)	C11—H11A	0.9700
N2—C2	1.301 (8)	C11—H11B	0.9700
N3—C10	1.372 (7)	C12—C13	1.492 (8)
N3—C1	1.383 (7)	C12—H12A	0.9700
N3—H3	0.8600	C12—H12B	0.9700
N4—C11	1.448 (7)	C13—C14	1.504 (9)
N4—C12	1.467 (7)	C13—H13A	0.9700
N4—C16	1.469 (7)	C13—H13B	0.9700
C3—C4	1.493 (8)	C14—C15	1.527 (8)
C3—H3B	0.9700	C14—H14A	0.9700
C3—H3C	0.9700	C14—H14B	0.9700
C4—C5	1.383 (8)	C15—C16	1.509 (8)
C4—C9	1.390 (8)	C15—H15A	0.9700
C5—C6	1.373 (8)	C15—H15B	0.9700
C5—H5A	0.9300	C16—H16A	0.9700
C6—C7	1.368 (9)	C16—H16B	0.9700
C6—H6A	0.9300

C1—S1—C2	86.0 (3)	O1—C10—N3	121.2 (5)
C2—S2—C3	102.7 (3)	O1—C10—C11	123.7 (5)
C1—N1—N2	111.6 (5)	N3—C10—C11	115.0 (5)
C2—N2—N1	112.3 (4)	N4—C11—C10	112.2 (5)
C10—N3—C1	122.1 (5)	N4—C11—H11A	109.2
C10—N3—H3	119.0	C10—C11—H11A	109.2
C1—N3—H3	119.0	N4—C11—H11B	109.2
C11—N4—C12	111.3 (4)	C10—C11—H11B	109.2
C11—N4—C16	110.3 (5)	H11A—C11—H11B	107.9
C12—N4—C16	110.6 (5)	N4—C12—C13	110.7 (5)
N1—C1—N3	121.9 (5)	N4—C12—H12A	109.5
N1—C1—S1	115.5 (4)	C13—C12—H12A	109.5
N3—C1—S1	122.6 (4)	N4—C12—H12B	109.5
N2—C2—S1	114.6 (4)	C13—C12—H12B	109.5
N2—C2—S2	127.4 (4)	H12A—C12—H12B	108.1
S1—C2—S2	118.0 (4)	C12—C13—C14	112.3 (5)
C4—C3—S2	114.5 (5)	C12—C13—H13A	109.1
C4—C3—H3B	108.6	C14—C13—H13A	109.1
S2—C3—H3B	108.6	C12—C13—H13B	109.1
C4—C3—H3C	108.6	C14—C13—H13B	109.1
S2—C3—H3C	108.6	H13A—C13—H13B	107.9
H3B—C3—H3C	107.6	C13—C14—C15	110.4 (5)
C5—C4—C9	118.0 (6)	C13—C14—H14A	109.6
C5—C4—C3	121.2 (5)	C15—C14—H14A	109.6
C9—C4—C3	120.7 (6)	C13—C14—H14B	109.6
C6—C5—C4	120.6 (6)	C15—C14—H14B	109.6
C6—C5—H5A	119.7	H14A—C14—H14B	108.1
C4—C5—H5A	119.7	C16—C15—C14	110.3 (5)
C7—C6—C5	121.0 (7)	C16—C15—H15A	109.6
C7—C6—H6A	119.5	C14—C15—H15A	109.6
C5—C6—H6A	119.5	C16—C15—H15B	109.6
C6—C7—C8	118.7 (6)	C14—C15—H15B	109.6
C6—C7—H7A	120.6	H15A—C15—H15B	108.1
C8—C7—H7A	120.6	N4—C16—C15	111.5 (5)
C9—C8—C7	121.0 (6)	N4—C16—H16A	109.3
C9—C8—H8A	119.5	C15—C16—H16A	109.3
C7—C8—H8A	119.5	N4—C16—H16B	109.3
C8—C9—C4	120.6 (6)	C15—C16—H16B	109.3
C8—C9—H9A	119.7	H16A—C16—H16B	108.0
C4—C9—H9A	119.7

C1—N1—N2—C2	0.3 (7)	C5—C6—C7—C8	−2.4 (12)
N2—N1—C1—N3	176.5 (5)	C6—C7—C8—C9	2.3 (12)
N2—N1—C1—S1	−2.1 (7)	C7—C8—C9—C4	−0.6 (12)
C10—N3—C1—N1	177.3 (5)	C5—C4—C9—C8	−1.1 (10)
C10—N3—C1—S1	−4.2 (8)	C3—C4—C9—C8	175.8 (6)
C2—S1—C1—N1	2.5 (5)	C1—N3—C10—O1	−4.4 (9)
C2—S1—C1—N3	−176.1 (5)	C1—N3—C10—C11	172.2 (5)
N1—N2—C2—S1	1.7 (7)	C12—N4—C11—C10	163.5 (5)
N1—N2—C2—S2	−179.1 (4)	C16—N4—C11—C10	−73.3 (6)
C1—S1—C2—N2	−2.3 (5)	O1—C10—C11—N4	−37.3 (8)
C1—S1—C2—S2	178.4 (4)	N3—C10—C11—N4	146.2 (5)
C3—S2—C2—N2	−14.8 (6)	C11—N4—C12—C13	−178.0 (5)
C3—S2—C2—S1	164.4 (3)	C16—N4—C12—C13	58.9 (7)
C2—S2—C3—C4	99.2 (5)	N4—C12—C13—C14	−56.4 (7)
S2—C3—C4—C5	−88.5 (7)	C12—C13—C14—C15	52.9 (8)
S2—C3—C4—C9	94.7 (6)	C13—C14—C15—C16	−52.0 (8)
C9—C4—C5—C6	1.0 (10)	C11—N4—C16—C15	176.8 (5)
C3—C4—C5—C6	−175.9 (6)	C12—N4—C16—C15	−59.6 (7)
C4—C5—C6—C7	0.7 (12)	C14—C15—C16—N4	56.1 (8)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···N1ⁱ	0.86	2.08	2.930 (7)	169
C11—H11A···O1ⁱⁱ	0.97	2.55	3.334 (8)	138

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