(±)-N-[4-Acetyl-5-methyl-5-(4-methyl­cyclo­hex-3-en­yl)-4,5-dihydro-1,3,4-thia­diazol-2-yl]acetamide

Tebbaa Mohammed; Noureddine Mazoir; Jean-Claude Daran; Moha Berraho; Ahmed Benharref

doi:10.1107/S1600536808004728

. 2008 Feb 20;64(Pt 3):o610–o611. doi: 10.1107/S1600536808004728

(±)-N-[4-Acetyl-5-methyl-5-(4-methylcyclohex-3-enyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

Tebbaa Mohammed ^a, Noureddine Mazoir ^a, Jean-Claude Daran ^b,^*, Moha Berraho ^a, Ahmed Benharref ^a

PMCID: PMC2960842 PMID: 21201946

Abstract

The new title thiadiazole compound, C₁₄H₂₁N₃O₂S, was semi-synthesized starting from 1-(4-methylcyclohex-3-enyl)ethanone, a natural product isolated from Cedrus atlantica essential oil. The stereochemistry has been confirmed by single-crystal X-ray diffraction. The thiadiazoline ring is roughly planar, although it may be regarded as having a half-chair conformation. The cyclohexenyl ring has a half-chair conformation. The most interesting feature is the formation of a pseudo-ring formed by four molecules associated through N—H⋯O hydrogen bonds around a fourfold inversion axis, forming an R ₄ ⁴(28) motif.

Related literature

For related literature, see: Aly et al. (2007 ▶); Beatriz et al. (2002 ▶); Bernstein et al. (1995 ▶); Cremer & Pople (1975 ▶); Demirbas et al. (2005 ▶); Etter et al. (1990 ▶); Farghaly et al. (2006 ▶); Invidiata et al. (1996 ▶); Kubota et al. (1982 ▶); Nizamuddin et al. (1999 ▶); Ourhriss et al. (2005 ▶); Paolo et al. (2005 ▶); Radul et al. (2005 ▶); Sun et al. (1999 ▶); Udupi et al. (2000 ▶).

Experimental

Crystal data

C₁₄H₂₁N₃O₂S
M _r = 295.40
Tetragonal,
a = 16.6855 (3) Å
c = 21.8961 (8) Å
V = 6096.0 (3) Å³
Z = 16
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 180 (2) K
0.29 × 0.24 × 0.08 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: none
87517 measured reflections
4637 independent reflections
3849 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.113
S = 1.11
4637 reflections
185 parameters
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶), ORTEP-3 for Windows (Farrugia, 1997 ▶) and CAMERON (Watkin et al., 1993 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808004728/bg2164sup1.cif

e-64-0o610-sup1.cif^{(17.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808004728/bg2164Isup2.hkl

e-64-0o610-Isup2.hkl^{(222.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O1ⁱ	0.88	1.95	2.8223 (14)	171

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Professor Abdelkader Mokhlisse for fruitful discussions.

supplementary crystallographic information

Comment

Thiadiazolic compounds have beenreported in a large number of papers (Beatriz et al., 2002, Farghaly et al., 2006). These compounds are associated with diverse biological activities. Likewise, the 1,3,4-thiadiazoles nuclei which incorporate toxiphoric –N=C—S– linkage possess anti-inflammatory (Udupi et al., 2000), herbicidal (Nizamuddin et al., 1999), antimicrobial (Demirbas et al., 2005) bactericidal (Sun et al., 1999) and anti-HIV-1 properties(Invidiata et al., 1996).

In this connection, the chemical modification of a natural product isolated from Cedrus atlantica essential oil, 1-(4-methylcyclohex-3-enyl) ethanone, using thiosemicarbazide (Paolo et al., 2005; Ourhriss et al., 2005; Aly et al., 2007) followed by treatment of acetic anhydride and pyridine yielded the 1,3,4-thiadiazolic compound (II) with a good yield and high chimiospecifity.

The structure of (II) was established by ¹H and ¹³CNMR and confirmed by its single-Crystal X-ray structure (Fig. 1).

The thiadiazoline ring may be regarded as having a half-chair conformation with puckering parameters Q= 0.184 (1) Å and φ= 34.1 (4)° (Cremer & Pople, 1975); however it could be also considered as roughly planar with the largest deviation from the mean plane being -0.1069 (8) Å at N1. Such conformation is usual for thiadiazoline rings (Kubota et al., 1982; Radul et al., 2005). The cyclohexenyl ring has a half-chair conformation with puckering parameters Q=0.489 (2) Å, θ= 49.5 (2)° and φ= 344.8 (3)°.

The most interesting feature is the formation of a pseudo ring formed by four molecules associated through N—H···O hydrogen bonds around a fourfold screw axis (Fig. 2, Table 1) so completing a R₄⁴(28) motif (Etter et al., 1990; Bernstein et al., 1995).

Experimental

To a solution of an equimolecular quantity of compound (I) and thiosemicarbazide dissolved in ethanol, several drops of HCl (c) were added. The reactional mixture was heated at reflux during 5 h and then evaporated under reduced pressure. The residue obtained was analysed on silica gel column with hexane: ethyl acetate (95:5) as an eluent. 0.25 mmol of the thiosemicarbazone obtained was dissolved in 2 ml of pyridine and 2 ml of acetic anhydride. The mixture was heated at reflux during 1 h with magnetic stirring, and then evaporated under reduced pressure. The residue obtained was purified on a silicagel column using hexane-ethyl acetate (90:10) as an eluent yielded compound (II) in 60% yield. Suitable crystals were obtained by evaporation of a dichloromethane solution at 277 K. m.p.= 483–484 K (dichloromethane); Spectroscopic analysis: ¹H NMR (300 MHz, CDCl₃) δ (p.p.m.): 9.49 (NH, s), 1.80 (3H2, s), 2.07 (1H1', m), 5.57 (1H3', dd, J₁ = 10 Hz, J₂ = 6 Hz), 1.58 (3H-7', s), 2.13, 2.27 (CH₃CO, 2 s); ¹³C NMR (75 MHz, CDCl₃) δ (p.p.m.): 85.4 (C-1), 19.2 (C-2), 36.7 (C-1'), 26.2 (C-2'), 118.1 (C-3'), 132.7 (C-4'), 28.2 (C-5'), 23.0 (C-6'), 22.2 (C-7'), 158.1 (C=N), 169.5, 170.4 (COCH₃), 22.6, 24.5 (COCH₃).