supplementary materials


Acta Cryst. (2009). E65, o4    [ doi:10.1107/S1600536808039998 ]

N-[4-Acetyl-5-isobutyl-5-(2-p-tolylpropyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide ethyl acetate hemisolvate

M. Loughzail, N. Mazoir, C. M. Maya, M. Berraho, A. Benharref and N. Bouhmaida

Abstract top

The racemic title compound, a new terpenoid, C20H29N3O2S·0.5C4H8O2, was synthesized from Cedrus Atlantica essential oil. The compound crystallizes with a disordered ethyl acetate solvent molecule. The thiadiazole ring is almost planar, with a maximum deviation from the mean plane of 0.015 (2) Å for the C atom connected to the isobutyl group and has a puckering amplitude of 0.026 (2) Å. The dihedral angle between the benzene and thiadiazole rings is 18.32 (8)°. The crystal packing involves intermolecular N-H...O hydrogen bonds.

Comment top

1,3,4-Thiadiazole derivatives (Sakthivel et al., 2008) are associated with diverse activities: fungicidal (Abdou et al., 1991), pesticidal (Wang et al., 1999, 2004) and bactericidal (Tehranchian et al., 2005) properties.

As part of our ongoing valorization of Cedrus species native to the Medium-Atlas Mountains of Morocco, we have investigated the crystal structure of semi-synthetic terpenoid derivatives obtained through chemical modifications of 1-(4-methylcyclohex-3-enyl) ethanone (I). The latter is isolated from Cedrus Atlantica essential oil. The aromatization of (I) followed by condensation with thiosemicarbazide (Beatriz et al., 2002; Mohammed et al., 2008) ending with treatment by acetic anhydride in the presence of pyridine yielded the compound diastereoisomers in high stereoselectivity.

The title compound molecular structure is shown in figure 1. The solvant molecule is located on the inversion site and disordered. The thiadiazole ring is almost planar with a maximum deviation from the mean plane of 0.015 (2)Å for the C atoms connected to the isobutyl group and a puckering amplitude of 0.026 (2)Å (Cremer & Pople, 1975). Hydrogen bonds are listed in table 1. Investigation of the crystal packing reveals an intermolecular N1—H1···O2 hydrogen bonding generating parallel chains to b axis as shown in figure 2.

Related literature top

For 1,3,4-thiadiazole derivatives and their biological activity, see: Abdou et al. (1991); Sakthivel et al. (2008); Tehranchian et al. (2005); Wang et al. (1999,2004). For preparative methods, see: Beatriz et al., 2002; Mohammed et al. (2008); For puckering parameters, see: Cremer & Pople (1975).

Experimental top

A solution of 1-(4-methylcyclohex-3-enyl) ethanone (1 g, 4.5 mmol) and Pd/C (10%) were heated at 150°C during 12 h. The product obtained was treated with equimolecular quantity of thiosemicarbazide and several drops of HCl (cc) 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 (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 on a water bath during 1 h. The resulting residue was concentrated in vacuo and chromatographied on silica gel column with hexane-ethyl acetate (90:10) as an eluent. Suitable crystals were obtained by evaporation of ethyl acetate solution at 277 K.

Refinement top

The H atoms linked to the C and N atoms were fixed geometrically and treated as riding with C—H = 0.93 Å (aromatic), 0.96Å (methyl), 0.97 Å (methylene), 0.98Å (methine) and N—H= 0.86 Å with Uiso(H) =1.2Ueq (aromatic, methylene, methine and NH) or Uiso(H) = 1.5Ueq(methyl).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia,1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. : Molecular structure shown with the atom-labelling scheme. Thermal ellipsoids are drawn at the 30% probability displacement. H atoms are represented as small spheres of arbitrary radius.
[Figure 2] Fig. 2. : The crystal packing showing the molecules connected by N–H···O hydrogen bondings (dashed lines). H atoms not involved in hydrogen bonding have been omitted.
N-[4-Acetyl-5-isobutyl-5-(2-p-tolylpropyl)-4,5-dihydro-1,3,4-thiadiazol- 2-yl]acetamide ethyl acetate hemisolvate top
Crystal data top
C20H29N3O2S·0.5C4H8O2F(000) = 904
Mr = 419.57Dx = 1.208 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 13322 reflections
a = 7.8713 (3) Åθ = 2.6–31.5°
b = 12.7587 (5) ŵ = 0.17 mm1
c = 22.9688 (9) ÅT = 295 K
β = 90.937 (2)°Prism, colourless
V = 2306.39 (16) Å30.5 × 0.4 × 0.3 mm
Z = 4
Data collection top
Bruker X8 APEX CCD area-detector
diffractometer
6688 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.037
graphiteθmax = 32.0°, θmin = 1.8°
φ and ω scansh = 1111
27541 measured reflectionsk = 1618
7243 independent reflectionsl = 3330
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.065Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.143H-atom parameters constrained
S = 1.23 w = 1/[σ2(Fo2) + (0.0435P)2 + 1.5861P]
where P = (Fo2 + 2Fc2)/3
7243 reflections(Δ/σ)max = 0.006
298 parametersΔρmax = 0.48 e Å3
0 restraintsΔρmin = 0.35 e Å3
Crystal data top
C20H29N3O2S·0.5C4H8O2V = 2306.39 (16) Å3
Mr = 419.57Z = 4
Monoclinic, P21/nMo Kα radiation
a = 7.8713 (3) ŵ = 0.17 mm1
b = 12.7587 (5) ÅT = 295 K
c = 22.9688 (9) Å0.5 × 0.4 × 0.3 mm
β = 90.937 (2)°
Data collection top
Bruker X8 APEX CCD area-detector
diffractometer
6688 reflections with I > 2σ(I)
27541 measured reflectionsRint = 0.037
7243 independent reflectionsθmax = 32.0°
Refinement top
R[F2 > 2σ(F2)] = 0.065H-atom parameters constrained
wR(F2) = 0.143Δρmax = 0.48 e Å3
S = 1.23Δρmin = 0.35 e Å3
7243 reflectionsAbsolute structure: ?
298 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
C1'0.5624 (2)0.56734 (16)0.09954 (8)0.0284 (4)
H1'0.61300.52140.07360.034*
C20.6060 (2)0.80786 (11)0.33245 (7)0.0160 (3)
C2'0.5345 (2)0.53523 (13)0.15666 (8)0.0231 (3)
H2'0.56710.46810.16800.028*
C30.4619 (2)0.92243 (12)0.40282 (7)0.0189 (3)
C3'0.4581 (2)0.60205 (12)0.19769 (7)0.0198 (3)
C4'0.4129 (2)0.70239 (13)0.17921 (8)0.0261 (4)
H4'0.36360.74880.20520.031*
C40.4186 (2)1.03550 (13)0.41486 (8)0.0247 (3)
H410.39531.07100.37880.037*
H420.51271.06870.43450.037*
H430.32021.03870.43890.037*
C50.6899 (2)0.61643 (11)0.31921 (7)0.0163 (3)
C5'0.4414 (3)0.73375 (16)0.12186 (9)0.0334 (4)
H5'0.41000.80110.11050.040*
C6'0.5158 (3)0.66697 (17)0.08093 (9)0.0316 (4)
C60.5755 (2)0.53023 (11)0.29360 (7)0.0168 (3)
H610.64390.48690.26840.020*
H620.53820.48620.32540.020*
C7'0.5422 (3)0.6998 (2)0.01806 (10)0.0496 (6)
H71'0.44990.67410.00580.074*
H72'0.64720.67110.00460.074*
H73'0.54610.77490.01570.074*
C70.4196 (2)0.56528 (12)0.25922 (7)0.0199 (3)
H70.36860.62410.28010.024*
C80.2898 (2)0.47506 (15)0.25783 (9)0.0280 (4)
H810.26460.45440.29690.042*
H820.33630.41650.23720.042*
H830.18740.49800.23840.042*
C90.8420 (2)0.56432 (12)0.34917 (7)0.0203 (3)
H910.79950.50740.37280.024*
H920.91130.53320.31920.024*
C100.9575 (2)0.63119 (15)0.38756 (8)0.0260 (4)
H100.88830.66400.41760.031*
C111.0522 (2)0.71819 (16)0.35485 (11)0.0358 (5)
H1110.97210.76950.34100.054*
H1121.11050.68830.32240.054*
H1131.13300.75100.38070.054*
C121.0842 (3)0.55835 (18)0.41726 (9)0.0389 (5)
H1231.02430.50620.43900.058*
H1211.15630.59800.44320.058*
H1221.15220.52470.38840.058*
C410.8340 (2)0.67172 (12)0.22639 (7)0.0182 (3)
C420.8709 (3)0.75771 (13)0.18334 (8)0.0259 (4)
H4230.77610.80500.18110.039*
H4210.88940.72760.14570.039*
H4220.97070.79530.19580.039*
O10.42441 (18)0.85144 (10)0.43626 (6)0.0281 (3)
O20.88630 (16)0.58120 (9)0.21879 (5)0.0211 (2)
N10.54896 (18)0.90516 (10)0.35115 (6)0.0174 (3)
H10.56860.95850.32940.021*
N30.69220 (17)0.80070 (9)0.28451 (6)0.0169 (3)
N40.74060 (18)0.69617 (9)0.27477 (6)0.0167 (3)
S10.56524 (5)0.69427 (3)0.372883 (17)0.01838 (10)
C1"0.4182 (8)0.3287 (4)0.4750 (2)0.0377 (11)0.50
H13"0.40990.30380.43570.057*0.50
H12"0.31150.31840.49390.057*0.50
H11"0.50550.29060.49560.057*0.50
C2"0.4610 (5)0.4425 (3)0.47503 (16)0.0282 (7)0.50
C3"0.4243 (5)0.6083 (3)0.52319 (18)0.0325 (8)0.50
H32"0.34040.63960.54830.039*0.50
H31"0.40710.63670.48440.039*0.50
C4"0.5952 (7)0.6366 (4)0.5446 (3)0.0398 (11)0.50
H42"0.61420.60660.58250.060*0.50
H43"0.60460.71150.54700.060*0.50
H41"0.67840.61010.51820.060*0.50
O1'0.5439 (5)0.4867 (3)0.43748 (15)0.0456 (8)0.50
O2'0.3987 (4)0.4949 (2)0.52147 (12)0.0326 (6)0.50
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C1'0.0218 (9)0.0388 (10)0.0247 (9)0.0006 (7)0.0002 (7)0.0008 (7)
C20.0157 (7)0.0133 (6)0.0190 (7)0.0004 (5)0.0000 (5)0.0009 (5)
C2'0.0214 (8)0.0239 (7)0.0239 (8)0.0030 (6)0.0013 (6)0.0002 (6)
C30.0168 (7)0.0191 (7)0.0209 (7)0.0015 (5)0.0023 (6)0.0008 (5)
C3'0.0163 (7)0.0189 (7)0.0241 (8)0.0009 (5)0.0036 (6)0.0012 (6)
C4'0.0244 (9)0.0213 (7)0.0324 (9)0.0032 (6)0.0063 (7)0.0017 (6)
C40.0287 (9)0.0182 (7)0.0274 (9)0.0056 (6)0.0075 (7)0.0016 (6)
C50.0182 (7)0.0141 (6)0.0167 (7)0.0015 (5)0.0033 (5)0.0001 (5)
C5'0.0314 (10)0.0288 (9)0.0396 (11)0.0015 (7)0.0097 (8)0.0128 (8)
C6'0.0237 (9)0.0410 (10)0.0300 (10)0.0049 (8)0.0027 (7)0.0118 (8)
C60.0168 (7)0.0140 (6)0.0197 (7)0.0003 (5)0.0030 (6)0.0012 (5)
C7'0.0455 (14)0.0672 (17)0.0360 (12)0.0024 (12)0.0003 (10)0.0221 (11)
C70.0163 (7)0.0200 (7)0.0236 (8)0.0021 (6)0.0019 (6)0.0017 (6)
C80.0194 (8)0.0341 (9)0.0304 (9)0.0049 (7)0.0026 (7)0.0002 (7)
C90.0213 (8)0.0194 (7)0.0201 (7)0.0027 (6)0.0006 (6)0.0008 (5)
C100.0198 (8)0.0319 (9)0.0263 (9)0.0054 (7)0.0023 (7)0.0096 (7)
C110.0186 (9)0.0334 (9)0.0552 (13)0.0012 (7)0.0059 (9)0.0046 (9)
C120.0381 (12)0.0469 (12)0.0312 (10)0.0131 (9)0.0140 (9)0.0090 (9)
C410.0189 (7)0.0165 (6)0.0192 (7)0.0032 (5)0.0020 (6)0.0025 (5)
C420.0341 (10)0.0189 (7)0.0252 (8)0.0031 (6)0.0116 (7)0.0002 (6)
O10.0367 (8)0.0199 (5)0.0280 (7)0.0030 (5)0.0130 (6)0.0025 (5)
O20.0224 (6)0.0179 (5)0.0231 (6)0.0007 (4)0.0039 (5)0.0040 (4)
N10.0207 (7)0.0137 (5)0.0179 (6)0.0020 (5)0.0031 (5)0.0003 (4)
N30.0182 (6)0.0126 (5)0.0200 (6)0.0002 (5)0.0020 (5)0.0003 (4)
N40.0202 (6)0.0126 (5)0.0175 (6)0.0004 (5)0.0037 (5)0.0007 (4)
S10.0229 (2)0.01389 (16)0.01860 (18)0.00144 (13)0.00611 (14)0.00131 (12)
C1"0.057 (3)0.029 (2)0.027 (2)0.001 (2)0.001 (2)0.0012 (17)
C2"0.0284 (19)0.0352 (18)0.0210 (17)0.0066 (15)0.0007 (14)0.0079 (14)
C3"0.033 (2)0.0322 (18)0.032 (2)0.0021 (16)0.0019 (16)0.0023 (15)
C4"0.031 (2)0.039 (3)0.048 (3)0.002 (2)0.006 (2)0.000 (2)
O1'0.063 (2)0.0384 (16)0.0367 (18)0.0035 (15)0.0194 (16)0.0102 (13)
O2'0.0443 (17)0.0310 (13)0.0225 (13)0.0037 (12)0.0010 (12)0.0033 (10)
Geometric parameters (Å, °) top
C1'—C6'1.389 (3)C8—H830.9600
C1'—C2'1.395 (3)C9—C101.519 (2)
C1'—H1'0.9300C9—H910.9700
C2—N31.306 (2)C9—H920.9700
C2—N11.3904 (19)C10—C121.517 (3)
C2—S11.7537 (15)C10—C111.540 (3)
C2'—C3'1.413 (2)C10—H100.9800
C2'—H2'0.9300C11—H1110.9600
C3—O11.227 (2)C11—H1120.9600
C3—N11.398 (2)C11—H1130.9600
C3—C41.509 (2)C12—H1230.9600
C3'—C4'1.393 (2)C12—H1210.9600
C3'—C71.524 (2)C12—H1220.9600
C4'—C5'1.398 (3)C41—O21.2394 (18)
C4'—H4'0.9300C41—N41.378 (2)
C4—H410.9600C41—C421.508 (2)
C4—H420.9600C42—H4230.9600
C4—H430.9600C42—H4210.9600
C5—N41.4998 (19)C42—H4220.9600
C5—C91.524 (2)N1—H10.8600
C5—C61.533 (2)N3—N41.4058 (17)
C5—S11.8732 (15)C1"—C2"1.490 (6)
C5'—C6'1.404 (3)C1"—H13"0.9600
C5'—H5'0.9300C1"—H12"0.9600
C6'—C7'1.521 (3)C1"—H11"0.9600
C6—C71.516 (2)C2"—O1'1.227 (5)
C6—H610.9700C2"—O2'1.358 (5)
C6—H620.9700C3"—O2'1.461 (5)
C7'—H71'0.9600C3"—C4"1.470 (7)
C7'—H72'0.9600C3"—H32"0.9700
C7'—H73'0.9600C3"—H31"0.9700
C7—C81.539 (2)C4"—H42"0.9600
C7—H70.9800C4"—H43"0.9600
C8—H810.9600C4"—H41"0.9600
C8—H820.9600
C6'—C1'—C2'120.88 (18)H81—C8—H82109.5
C6'—C1'—H1'119.6C7—C8—H83109.5
C2'—C1'—H1'119.6H81—C8—H83109.5
N3—C2—N1119.84 (13)H82—C8—H83109.5
N3—C2—S1119.38 (11)C10—C9—C5118.40 (13)
N1—C2—S1120.77 (12)C10—C9—H91107.7
C1'—C2'—C3'121.70 (16)C5—C9—H91107.7
C1'—C2'—H2'119.2C10—C9—H92107.7
C3'—C2'—H2'119.2C5—C9—H92107.7
O1—C3—N1122.80 (14)H91—C9—H92107.1
O1—C3—C4122.25 (15)C12—C10—C9107.44 (15)
N1—C3—C4114.95 (14)C12—C10—C11109.96 (17)
C4'—C3'—C2'117.43 (16)C9—C10—C11114.31 (16)
C4'—C3'—C7120.79 (16)C12—C10—H10108.3
C2'—C3'—C7121.74 (14)C9—C10—H10108.3
C3'—C4'—C5'120.40 (18)C11—C10—H10108.3
C3'—C4'—H4'119.8C10—C11—H111109.5
C5'—C4'—H4'119.8C10—C11—H112109.5
C3—C4—H41109.5H111—C11—H112109.5
C3—C4—H42109.5C10—C11—H113109.5
H41—C4—H42109.5H111—C11—H113109.5
C3—C4—H43109.5H112—C11—H113109.5
H41—C4—H43109.5C10—C12—H123109.5
H42—C4—H43109.5C10—C12—H121109.5
N4—C5—C9112.80 (13)H123—C12—H121109.5
N4—C5—C6112.75 (12)C10—C12—H122109.5
C9—C5—C6108.21 (12)H123—C12—H122109.5
N4—C5—S1103.67 (9)H121—C12—H122109.5
C9—C5—S1110.51 (11)O2—C41—N4120.49 (14)
C6—C5—S1108.79 (11)O2—C41—C42121.15 (15)
C4'—C5'—C6'122.16 (17)N4—C41—C42118.36 (13)
C4'—C5'—H5'118.9C41—C42—H423109.5
C6'—C5'—H5'118.9C41—C42—H421109.5
C1'—C6'—C5'117.43 (18)H423—C42—H421109.5
C1'—C6'—C7'120.3 (2)C41—C42—H422109.5
C5'—C6'—C7'122.3 (2)H423—C42—H422109.5
C7—C6—C5116.99 (12)H421—C42—H422109.5
C7—C6—H61108.1C2—N1—C3124.63 (13)
C5—C6—H61108.1C2—N1—H1117.7
C7—C6—H62108.1C3—N1—H1117.7
C5—C6—H62108.1C2—N3—N4110.27 (12)
H61—C6—H62107.3C41—N4—N3119.50 (12)
C6'—C7'—H71'109.5C41—N4—C5123.13 (12)
C6'—C7'—H72'109.5N3—N4—C5117.36 (12)
H71'—C7'—H72'109.5C2—S1—C589.27 (7)
C6'—C7'—H73'109.5O1'—C2"—O2'121.9 (4)
H71'—C7'—H73'109.5O1'—C2"—C1"124.8 (4)
H72'—C7'—H73'109.5O2'—C2"—C1"113.3 (4)
C6—C7—C3'113.72 (14)O2'—C3"—C4"112.2 (4)
C6—C7—C8108.77 (13)O2'—C3"—H32"109.2
C3'—C7—C8110.65 (14)C4"—C3"—H32"109.2
C6—C7—H7107.8O2'—C3"—H31"109.2
C3'—C7—H7107.8C4"—C3"—H31"109.2
C8—C7—H7107.8H32"—C3"—H31"107.9
C7—C8—H81109.5C2"—O2'—C3"117.3 (3)
C7—C8—H82109.5
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.861.952.812 (2)179
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.861.952.812 (2)179
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2.
Acknowledgements top

We thank Professor Jean-Claude Daran, Laboratoire de Chimie de Coordination Toulouse, France, for his fruitful help.

references
References top

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