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Acta Cryst. (2009). E65, 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

N. Mazoir, L. El Ammari, N. Bouhmaida, S. Dahaoui, A. Benharref and M. Berraho

Abstract top

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.

Comment top

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.

Related literature top

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 top

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.

Refinement top

Atoms H2 and H9 were located in a difference map and refined freely. The remaining H atoms were positioned geometrically and refined as riding, with C—H = 0.93 Å (aromatic), 0.96 Å (methyl), 0.97 Å (methylene), 0.98 Å (methine), and with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2005); data reduction: SAINT-Plus (Bruker, 2005); 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).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound, with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii.
[Figure 2] Fig. 2. Partial packing view showing the N—H···O hydrogen bonds (dashed lines) and the formation of a chain along the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity.
N-[4-Acetyl-5-(2-methylprop-1-enyl)-5-(2-p-tolylpropyl)-\ 4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide top
Crystal data top
C20H27N3O2SF000 = 800
Mr = 373.51Dx = 1.253 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 8068 reflections
a = 10.855 (2) Åθ = 2.8–26.4º
b = 14.193 (2) ŵ = 0.18 mm−1
c = 12.854 (4) ÅT = 100 K
β = 90.955 (11)ºPrism, colourless
V = 1980.1 (8) Å30.28 × 0.17 × 0.12 mm
Z = 4
Data collection top
Bruker X8 APEX CCD area-detector
diffractometer		3365 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.032
Monochromator: graphiteθmax = 26.4º
T = 100 Kθmin = 2.8º
φ and ω scansh = 0→13
Absorption correction: nonek = −17→17
7884 measured reflectionsl = −16→16
4030 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.094  w = 1/[σ2(Fo2) + (0.0257P)2 + 1.5568P]
where P = (Fo2 + 2Fc2)/3
S = 1.10(Δ/σ)max = 0.001
4030 reflectionsΔρmax = 0.24 e Å−3
249 parametersΔρmin = −0.20 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C20H27N3O2SV = 1980.1 (8) Å3
Mr = 373.51Z = 4
Monoclinic, P21/cMo Kα
a = 10.855 (2) ŵ = 0.18 mm−1
b = 14.193 (2) ÅT = 100 K
c = 12.854 (4) Å0.28 × 0.17 × 0.12 mm
β = 90.955 (11)º
Data collection top
Bruker X8 APEX CCD area-detector
diffractometer		4030 independent reflections
Absorption correction: none3365 reflections with I > 2σ(I)
7884 measured reflectionsRint = 0.032
Refinement top
R[F2 > 2σ(F2)] = 0.044249 parameters
wR(F2) = 0.094H atoms treated by a mixture of
independent and constrained refinement
S = 1.10Δρmax = 0.24 e Å−3
4030 reflectionsΔρmin = −0.20 e Å−3
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
H20.357 (2)0.0915 (17)0.0811 (19)0.039 (7)*
H90.5323 (18)0.1563 (13)0.5491 (16)0.018 (5)*
C1'0.04998 (19)0.36320 (14)0.44410 (16)0.0263 (4)
H1'0.04730.41820.48330.032*
C2'0.10902 (18)0.28480 (14)0.48503 (15)0.0231 (4)
H2'0.14420.28790.55140.028*
C20.37116 (16)0.09545 (13)0.23153 (13)0.0180 (4)
C3'0.11662 (17)0.20141 (13)0.42843 (14)0.0188 (4)
C30.35748 (17)−0.04166 (13)0.11768 (14)0.0204 (4)
C40.33879 (19)−0.07060 (14)0.00610 (14)0.0252 (4)
H400.3814−0.1287−0.00610.038*
H410.3706−0.0225−0.03860.038*
H420.2524−0.0790−0.00830.038*
C4'0.05884 (17)0.19924 (14)0.33050 (14)0.0216 (4)
H4'0.06110.14420.29130.026*
C50.41102 (17)0.13772 (12)0.42180 (14)0.0178 (4)
C5'−0.00180 (17)0.27755 (14)0.29079 (15)0.0234 (4)
H5'−0.04080.27370.22600.028*
C60.31344 (17)0.12846 (13)0.50691 (13)0.0185 (4)
H600.33700.07590.55120.022*
H610.31760.18480.54950.022*
C6'−0.00551 (18)0.36170 (14)0.34573 (16)0.0247 (4)
C70.17835 (17)0.11399 (13)0.47324 (14)0.0191 (4)
H70.17520.06440.42030.023*
C7'−0.0625 (2)0.44905 (15)0.29915 (17)0.0326 (5)
H70'−0.00040.48480.26440.049*
H71'−0.09740.48660.35330.049*
H72'−0.12600.43150.25000.049*
C80.10620 (18)0.07994 (13)0.56829 (14)0.0227 (4)
H800.14030.02150.59280.034*
H810.02130.07080.54870.034*
H820.11200.12630.62260.034*
C90.53585 (18)0.15303 (13)0.47409 (14)0.0200 (4)
C100.64558 (18)0.16273 (13)0.43130 (15)0.0226 (4)
C110.67035 (19)0.16274 (15)0.31623 (16)0.0286 (5)
H1110.73020.11510.30090.043*
H1120.70130.22330.29610.043*
H1130.59530.14980.27840.043*
C120.75806 (19)0.17719 (15)0.49976 (17)0.0304 (5)
H1210.79820.23480.48070.046*
H1220.81380.12540.49110.046*
H1230.73390.18070.57120.046*
C410.37297 (17)0.30457 (13)0.37021 (13)0.0177 (4)
C420.33714 (19)0.37167 (13)0.28539 (14)0.0231 (4)
H4200.39910.37150.23300.035*
H4210.32960.43400.31370.035*
H4220.25970.35270.25500.035*
N10.35903 (15)0.05391 (11)0.13421 (12)0.0192 (3)
N30.35840 (14)0.18471 (10)0.24065 (11)0.0183 (3)
N40.38013 (14)0.21218 (10)0.34384 (11)0.0174 (3)
O10.36850 (13)−0.09778 (9)0.18908 (10)0.0256 (3)
O20.39419 (12)0.32905 (9)0.46085 (9)0.0213 (3)
S10.40785 (4)0.02872 (3)0.34223 (3)0.01914 (12)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C1'0.0305 (11)0.0224 (10)0.0261 (10)0.0034 (8)0.0050 (8)−0.0035 (8)
C2'0.0251 (10)0.0248 (10)0.0195 (9)0.0012 (8)0.0007 (8)−0.0015 (8)
C20.0184 (9)0.0205 (9)0.0153 (9)0.0010 (7)0.0019 (7)0.0011 (7)
C3'0.0175 (9)0.0199 (9)0.0192 (9)−0.0004 (7)0.0020 (7)0.0011 (7)
C30.0198 (9)0.0198 (9)0.0215 (10)0.0000 (8)0.0010 (7)−0.0005 (7)
C40.0334 (11)0.0220 (10)0.0201 (10)0.0008 (8)−0.0041 (8)−0.0041 (8)
C4'0.0212 (10)0.0228 (9)0.0207 (9)−0.0018 (8)0.0007 (7)−0.0010 (8)
C50.0221 (9)0.0169 (9)0.0144 (8)0.0007 (7)0.0003 (7)0.0003 (7)
C5'0.0206 (10)0.0304 (10)0.0192 (9)−0.0002 (8)0.0002 (8)0.0043 (8)
C60.0239 (10)0.0187 (9)0.0128 (8)0.0013 (8)−0.0008 (7)0.0012 (7)
C6'0.0196 (10)0.0272 (10)0.0276 (10)0.0032 (8)0.0058 (8)0.0068 (8)
C70.0231 (10)0.0181 (9)0.0160 (9)−0.0001 (7)0.0011 (7)−0.0020 (7)
C7'0.0328 (12)0.0314 (11)0.0338 (12)0.0119 (9)0.0082 (9)0.0077 (9)
C80.0248 (10)0.0216 (9)0.0216 (10)−0.0014 (8)0.0009 (8)0.0000 (8)
C90.0245 (10)0.0197 (9)0.0157 (9)0.0011 (7)−0.0032 (7)0.0018 (7)
C100.0253 (10)0.0171 (9)0.0254 (10)0.0020 (8)−0.0015 (8)0.0013 (7)
C110.0258 (11)0.0285 (11)0.0316 (11)−0.0001 (9)0.0064 (9)−0.0002 (9)
C120.0229 (11)0.0271 (11)0.0410 (12)0.0019 (9)−0.0029 (9)−0.0013 (9)
C410.0193 (9)0.0187 (9)0.0153 (9)−0.0014 (7)0.0009 (7)−0.0003 (7)
C420.0332 (11)0.0183 (9)0.0176 (9)0.0004 (8)−0.0029 (8)−0.0003 (7)
N10.0274 (9)0.0185 (8)0.0117 (7)0.0001 (7)0.0000 (6)−0.0010 (6)
N30.0230 (8)0.0188 (8)0.0130 (7)0.0003 (6)−0.0009 (6)−0.0019 (6)
N40.0240 (8)0.0174 (7)0.0107 (7)0.0021 (6)−0.0006 (6)0.0014 (6)
O10.0358 (8)0.0201 (7)0.0208 (7)0.0013 (6)0.0010 (6)0.0016 (6)
O20.0277 (7)0.0211 (7)0.0149 (6)0.0000 (6)−0.0011 (5)−0.0019 (5)
S10.0254 (2)0.0175 (2)0.0145 (2)0.00277 (19)0.00084 (17)0.00137 (18)
Geometric parameters (Å, °) top
C1'—C2'1.384 (3)C6'—C7'1.505 (3)
C1'—C6'1.392 (3)C7—C81.540 (3)
C1'—H1'0.93C7—H70.98
C2'—C3'1.392 (3)C7'—H70'0.96
C2'—H2'0.93C7'—H71'0.96
C2—N31.280 (2)C7'—H72'0.96
C2—N11.387 (2)C8—H800.96
C2—S11.7497 (18)C8—H810.96
C3'—C4'1.397 (3)C8—H820.96
C3'—C71.519 (2)C9—C101.327 (3)
C3—O11.219 (2)C9—H90.97 (2)
C3—N11.373 (2)C10—C121.507 (3)
C3—C41.502 (3)C10—C111.508 (3)
C4—H400.96C11—H1110.96
C4—H410.96C11—H1120.96
C4—H420.96C11—H1130.96
C4'—C5'1.385 (3)C12—H1210.96
C4'—H4'0.93C12—H1220.96
C5—N41.491 (2)C12—H1230.96
C5—C91.518 (3)C41—O21.234 (2)
C5—C61.541 (2)C41—N41.357 (2)
C5—S11.8545 (18)C41—C421.494 (2)
C5'—C6'1.388 (3)C42—H4200.96
C5'—H5'0.93C42—H4210.96
C6—C71.536 (3)C42—H4220.96
C6—H600.97N1—H20.87 (2)
C6—H610.97N3—N41.399 (2)
C2'—C1'—C6'121.60 (18)C6'—C7'—H70'109.5
C2'—C1'—H1'119.2C6'—C7'—H71'109.5
C6'—C1'—H1'119.2H70'—C7'—H71'109.5
C1'—C2'—C3'121.06 (18)C6'—C7'—H72'109.5
C1'—C2'—H2'119.5H70'—C7'—H72'109.5
C3'—C2'—H2'119.5H71'—C7'—H72'109.5
N3—C2—N1119.63 (16)C7—C8—H80109.5
N3—C2—S1119.00 (14)C7—C8—H81109.5
N1—C2—S1121.35 (14)H80—C8—H81109.5
C2'—C3'—C4'117.38 (17)C7—C8—H82109.5
C2'—C3'—C7121.72 (16)H80—C8—H82109.5
C4'—C3'—C7120.80 (16)H81—C8—H82109.5
O1—C3—N1121.87 (17)C10—C9—C5129.19 (17)
O1—C3—C4123.36 (17)C10—C9—H9117.4 (12)
N1—C3—C4114.76 (16)C5—C9—H9113.5 (12)
C3—C4—H40109.5C9—C10—C12119.73 (18)
C3—C4—H41109.5C9—C10—C11125.62 (18)
H40—C4—H41109.5C12—C10—C11114.63 (17)
C3—C4—H42109.5C10—C11—H111109.5
H40—C4—H42109.5C10—C11—H112109.5
H41—C4—H42109.5H111—C11—H112109.5
C5'—C4'—C3'121.18 (18)C10—C11—H113109.5
C5'—C4'—H4'119.4H111—C11—H113109.5
C3'—C4'—H4'119.4H112—C11—H113109.5
N4—C5—C9112.66 (15)C10—C12—H121109.5
N4—C5—C6112.84 (14)C10—C12—H122109.5
C9—C5—C6108.48 (15)H121—C12—H122109.5
N4—C5—S1102.63 (11)C10—C12—H123109.5
C9—C5—S1111.83 (13)H121—C12—H123109.5
C6—C5—S1108.29 (12)H122—C12—H123109.5
C4'—C5'—C6'121.37 (18)O2—C41—N4119.83 (16)
C4'—C5'—H5'119.3O2—C41—C42123.49 (16)
C6'—C5'—H5'119.3N4—C41—C42116.67 (15)
C7—C6—C5118.41 (15)C41—C42—H420109.5
C7—C6—H60107.7C41—C42—H421109.5
C5—C6—H60107.7H420—C42—H421109.5
C7—C6—H61107.7C41—C42—H422109.5
C5—C6—H61107.7H420—C42—H422109.5
H60—C6—H61107.1H421—C42—H422109.5
C5'—C6'—C1'117.35 (18)C3—N1—C2124.06 (16)
C5'—C6'—C7'121.43 (18)C3—N1—H2119.1 (16)
C1'—C6'—C7'121.17 (19)C2—N1—H2116.7 (16)
C3'—C7—C6114.25 (15)C2—N3—N4110.24 (14)
C3'—C7—C8109.29 (15)C41—N4—N3119.79 (14)
C6—C7—C8108.32 (15)C41—N4—C5122.03 (14)
C3'—C7—H7108.3N3—N4—C5118.18 (14)
C6—C7—H7108.3C2—S1—C589.94 (8)
C8—C7—H7108.3
C6'—C1'—C2'—C3'0.9 (3)O1—C3—N1—C2−1.0 (3)
C1'—C2'—C3'—C4'−2.1 (3)C4—C3—N1—C2177.88 (17)
C1'—C2'—C3'—C7−178.47 (17)N3—C2—N1—C3−172.52 (18)
C2'—C3'—C4'—C5'1.0 (3)S1—C2—N1—C39.3 (3)
C7—C3'—C4'—C5'177.45 (17)N1—C2—N3—N4−177.12 (15)
C3'—C4'—C5'—C6'1.3 (3)S1—C2—N3—N41.1 (2)
N4—C5—C6—C753.5 (2)O2—C41—N4—N3−178.76 (15)
C9—C5—C6—C7179.04 (15)C42—C41—N4—N32.1 (2)
S1—C5—C6—C7−59.41 (18)O2—C41—N4—C51.1 (3)
C4'—C5'—C6'—C1'−2.5 (3)C42—C41—N4—C5−178.05 (16)
C4'—C5'—C6'—C7'175.03 (18)C2—N3—N4—C41179.12 (16)
C2'—C1'—C6'—C5'1.4 (3)C2—N3—N4—C5−0.7 (2)
C2'—C1'—C6'—C7'−176.10 (19)C9—C5—N4—C41−59.4 (2)
C2'—C3'—C7—C6−57.9 (2)C6—C5—N4—C4163.9 (2)
C4'—C3'—C7—C6125.84 (18)S1—C5—N4—C41−179.78 (14)
C2'—C3'—C7—C863.6 (2)C9—C5—N4—N3120.51 (17)
C4'—C3'—C7—C8−112.64 (19)C6—C5—N4—N3−116.23 (16)
C5—C6—C7—C3'−73.3 (2)S1—C5—N4—N30.08 (18)
C5—C6—C7—C8164.63 (15)N3—C2—S1—C5−0.96 (16)
N4—C5—C9—C10−55.8 (3)N1—C2—S1—C5177.27 (16)
C6—C5—C9—C10178.55 (19)N4—C5—S1—C20.41 (12)
S1—C5—C9—C1059.2 (2)C9—C5—S1—C2−120.59 (14)
C5—C9—C10—C12−179.85 (17)C6—C5—S1—C2119.95 (13)
C5—C9—C10—C111.5 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H2···O2i0.87 (2)1.96 (2)2.811 (2)167 (2)
Symmetry codes: (i) x, −y+1/2, z−1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H2···O2i0.87 (2)1.96 (2)2.811 (2)167 (2)
Symmetry codes: (i) x, −y+1/2, z−1/2.
Acknowledgements top

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

references
References top

Beatriz, N. B., Albertina, G. M., Miriam, M. A., Angel, A. L., Graciela, Y. M. & Norma, B. D. (2002). Arkivoc, x, 14–23.

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