N-[4-Acetyl-5-(2-methylprop-1-enyl)-5-(2-p-tolyl­prop­yl)-4,5-dihydro-1,3,4-thia­diazol-2-yl]acetamide

Noureddine Mazoir; Lahcen El Ammari; Nouzha Bouhmaida; Slimane Dahaoui; Ahmed Benharref; Moha Berraho

doi:10.1107/S1600536809017127

. 2009 May 14;65(Pt 6):o1269–o1270. doi: 10.1107/S1600536809017127

N-[4-Acetyl-5-(2-methylprop-1-enyl)-5-(2-p-tolylpropyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

Noureddine Mazoir ^a, Lahcen El Ammari ^b, Nouzha Bouhmaida ^c, Slimane Dahaoui ^d, Ahmed Benharref ^a, Moha Berraho ^a,^*

PMCID: PMC2969617 PMID: 21583133

Abstract

The title heterocyclic compound, C₂₀H₂₇N₃O₂S, was synthesized from 2-(4-methylcyclohex-3-enyl)-6-methylhepta-2,5-dien-4-one, which was isolated from the essential oil Cedrus atlantica. The thiadiazole ring is essentially planar [maximum deviation 0.006 (2) Å] and it forms a dihedral angle of 18.08 (9)° with the benzene ring. The dihedral angle between the thiadiazole ring and the acetamide plane is 7.62 (10)°. In the crystal, molecules are linked into chains running along the c axis by intermolecular N—H⋯O hydrogen bonds.

Related literature

For the biological activity of 1,3,4-thiadiazole derivatives, see: Demirbas et al. (2005 ▶); Holla et al. (2002 ▶); Kritsanida et al. (2002 ▶); Nizamuddin et al. (1999 ▶); Sun et al. (1999 ▶); Udupi et al. (2000 ▶). For the synthesis, see: Beatriz et al. (2002 ▶); Sakthivel et al. (2008 ▶). For related structures, see: Loughzail et al. (2009 ▶); Tebaa et al. (2009 ▶).

Experimental

Crystal data

C₂₀H₂₇N₃O₂S
M _r = 373.51
Monoclinic,
a = 10.855 (2) Å
b = 14.193 (2) Å
c = 12.854 (4) Å
β = 90.955 (11)°
V = 1980.1 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 100 K
0.28 × 0.17 × 0.12 mm

Data collection

Bruker X8 APEX CCD area-detector diffractometer
Absorption correction: none
7884 measured reflections
4030 independent reflections
3365 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.094
S = 1.10
4030 reflections
249 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT-Plus (Bruker, 2005 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809017127/ci2797sup1.cif

e-65-o1269-sup1.cif^{(21.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809017127/ci2797Isup2.hkl

e-65-o1269-Isup2.hkl^{(197.5KB, 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
N1—H2⋯O2ⁱ	0.87 (2)	1.96 (2)	2.811 (2)	167 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Professor J. C. Daran for fruitful discussions.

supplementary crystallographic information

Comment

1,3,4-Thiadiazole derivatives possess antimicrobial (Demirbas et al., 2005) and antiviral (Kritsanida et al., 2002) activities. They are also known for their broad-spectrum of biological activities such as antibacterial (Sun et al., 1999), anti-inflammatory (Udupi et al., 2000) and herbicidal (Nizamuddin et al., 1999). In addition, [1,3,4]thiadiazoles exhibit various biological activities possibly due to the presence of the ═ N—C—S moiety (Holla et al., 2002). In view of these findings and in continuation to our previous work on the synthesis of [1,3,4]thiadiazoles, we report herein the hemisynthesis of N-[4-acetyl-5-isobutenyl-5-(2-p-tolylpropyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide, (I), through chemical modification of 2-(4-methylcyclohex-3-enyl)-6-methylhepta-2,5-dien-4-one, which is isolated from Cedrus Atlantica essential oil. Thus, aromatization of this later, followed by condensation with thiosemicarbazide (Beatriz et al., 2002; Sakthivel et al., 2008) ending with treatment of acetic anhydride in the presence of pyridine yielded the diasterioisomers in high stereoselectivity.

The molecular structure of (I) is shown in Fig. 1. The geometric parameters (bond lengths and angles) are very similar to those observed in previously reported structures (Loughzail et al.,2009; Tebaa et al.,2009). The thiadiazole ring system is essentially planar and it forms a dihedral angle of 18.08 (9)° with the benzene ring.

In the crystal structure, molecules are linked into chains (Fig. 2) running along the c axis by intermolecular N—H···O hydrogen bonds (Table 1) involving the carbonyl and the acetamide groups.

Experimental

A mixture of 2-(4-methylcyclohex-3-enyl)-6-methylhepta-2,5-dien-4-one (0.5 g, 2.3 mmol) and Pd/C (10%) was heated at 423 K for 12 h. The product obtained was treated with equimolecular quantity of thiosemicarbazide and several drops of HCl were added. The reactional mixture was heated at reflux in ethanol for 5 h and then evaporated under reduced pressure and the residue obtained was purified on silica gel column using hexane–ethyl acetate (96:4) as an eluent. 0.25 mmol of the thiosemicarbazone obtained was dissolved in 2.5 ml of pyridine and 2.5 ml of acetic anhydride. The mixture was heated on a water bath for 1.5 h. The resulting residue was concentrated in vacuo and chromatographied on silica gel column with hexane–ethyl acetate (92:8) as an eluent. Suitable crystals were obtained by evaporation of an ethyl acetate solution at 277 K.