Dimethyl 3-acetyl-3-(1,3-benzothia­zol-2-yl)penta­nedioate

Yamna Baryala; Moussa Salem; El Mokhtar Essassi; Hans Reuter; Maher Izaaryene

doi:10.1107/S1600536808035782

. 2008 Nov 8;64(Pt 12):o2290. doi: 10.1107/S1600536808035782

Dimethyl 3-acetyl-3-(1,3-benzothiazol-2-yl)pentanedioate

Yamna Baryala ^a, Moussa Salem ^a, El Mokhtar Essassi ^b, Hans Reuter ^c,^*, Maher Izaaryene ^c

PMCID: PMC2959939 PMID: 21581268

Abstract

The title compound, C₁₆H₁₇NO₅S, was one of two condensation products from the reaction of 1-(1,3-benzothiazol-2-yl)propan-2-one with methyl chloroacetate. The non-H atoms in each of the four substituent groups on the central quaternary C atom are virtually coplanar. The maximum deviations from the least-squares planes are 0.015 (2) and 0.020 (2) Å for the methyl C atoms in the methyl acetate substituents and 0.033 (1) Å for the linked C atom of the benzothiazole substituent. The S, C and N atoms in the thiazole ring of the benzothiazole substituent lie −0.037 (2), 0.046 (2) and −0.028 (2) Å, respectively, from the mean plane defined by the benzene ring atoms.

Related literature

For general background, see: Palmer et al. (1971 ▶); Bénéteau et al., 1999 ▶; El-Sherbeny (2000 ▶); Abayeh et al. (1994 ▶); Ivanov & Yuritsyn (1971 ▶); Monsanto (1968 ▶); Lee et al. (2001 ▶). For related structures, see: Chen (1994 ▶); Chu et al. (2003 ▶). graphic file with name e-64-o2290-scheme1.jpg

Experimental

Crystal data

C₁₆H₁₇NO₅S
M _r = 335.37
Monoclinic,
a = 14.4075 (3) Å
b = 8.8089 (2) Å
c = 13.8968 (3) Å
β = 118.011 (1)°
V = 1557.10 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 100 (2) K
0.54 × 0.47 × 0.25 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.883, T _max = 0.945
94263 measured reflections
3766 independent reflections
3396 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.083
S = 1.02
3766 reflections
211 parameters
H-atom parameters constrained
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: SMART (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 1999 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808035782/fj2155sup1.cif

e-64-o2290-sup1.cif^{(19.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808035782/fj2155Isup2.hkl

e-64-o2290-Isup2.hkl^{(184.6KB, hkl)}

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

supplementary crystallographic information

Comment

Benzothiazole compounds show interesting biological and pharmacological properties (see, e.g., Palmer et al., 1971; Bénéteau et al., 1999; El-Sherbeny, 2000; Abayeh et al., 1994). Besides some few papers with industrial background (see, e.g., Ivanov & Yuritsyn, 1971; Monsanto, 1968) many papers discuss the synthesis, structure-property relationship and complexation behaviour of these compounds. An important group among the different derivatives of benzothiazole are those substituted at C2 (see, e.g., Lee et al., 2001).

In the following we describe the synthesis and structural characterization of such a kind of benzothiazole derivative. This compound, dimethyl 3-acetyl-3-(1,3-benzothiazol-2-yl)pentanedioate, 3, was synthesized according to reaction scheme 1 through alkylation of 1-(1,3-benzothiazol-2-yl)propan-2-one, 1, with methyl chloroacetate under classical condensation conditions, giving methyl 2-(2-(2-oxopropylidene)1,3-benzothiazol-3(2H)-yl)acetate, 2, as second reaction product. The starting material 1 was obtained by condensing 2-aminothiophenol with ethyl acetoacetate in xylene at 160° C for 1 h 30 min.

The structure of the title compound can be best described in relation to the central quaternary carbon atom [C1] surrounded by a benzothiazole moiety, two methyl acetate residues and an acetyl group (Fig. 1). The corresponding bond lengths at C1 of 1.537 (2) Å [C30], 1.538 (2) Å [C20], 1.561 (2) Å [C10] and 1.521 (2) Å are in good agreement with carbon-carbon single bonds, as well as are the angles of 110.9 (1)° - 108.5 (1)° in the range for a tetrahedral coordination. Within the benzothiazole rest bond lengths and angles are very similar to those in comparable compounds like the 2-methyl benzothiazole molecule (Chen, 1994; Chu et al., 2003), which was found as non complexing agent in some crystal structures. Especially the bond angle at the sulfur [88.99 (6)°] and nitrogen [110.5 (1)°] atoms as well as the lengths of the sulfur carbon bonds [1.734 (1)/1.755 (1) A] and the carbon nitrogen double bond between C2 and N3 [129.2 (2) A] are very similar. In relation to the benzenic part [C4 - C9] of the benzothiazole rest which is almost planar [maximal deviation from the least squares plain: -0.0031 (8) Å] the remaining atoms [S1, C2, N3] of the thiazole ring lie -0.037 (2), 0.046 (2) and -0.028 (2) Å above/below this point of reference. This conformation is somewhat different to the 2-methyl benzothiazole molecule where the corresponding values are -0.028 (1), -0.004 (5), 0.017 (4) Å (Chen, 1994) and -0.024 (1), -0.030 (3), -0.017 (3) Å (Chu et al., 2003), respectively, indicating a conformational flexibility of the thiazole moitie. Bond angles and lengths of the two methyl acetate rests as well as those of the acetyl moietie are in the expected ranges [f.e. d(C=O) = 1.201 (2) - 1.206 (2) Å, d(C_carbonyl—O_methoxy) = 1.341 (2)/1.332 (2) Å, d(C_methyl—O) = 1.450 (2)/1.450 (2) Å].

Intermolecular forces are restricted mainly to van der Waals ones. No π-π interactions as well as classical hydrogen bonds are found although there are two short intramolecular contacts between the oxygen atoms of two carbonyl groups and adjacent hydrogen atoms [d(O21 - H301) = 2.49 Å, d(O31—H202) = 2.54 Å] and one short intermolecular contact between the sulfur atom of the benzothiazole group and the hydrogen atom of a methylene group [d(Sn1—H301) = 2.86 Å] of a neigbhouring molecule.

Experimental

All solvents and reagents were used as received from Aldrich and Fluka. IR data were recorded using a Bruker VERTEX 70 FTIR spectrometer with ATR device. Wavelengths (ν) are reported in cm^{-1. 1}H and ¹³C NMR were obtained at ambient temperature using a Bruker AVANCE 300 A spectrometer. Chemical shifts (δ) are reported in parts per million (p.p.m.) relative to internal standards. Mass spectra were carried out using a LCQ Advantage MAX spectrometer employing Electro Spray Ionization (ESI).

2.84 g (2.61 mmol) methyl chloroacetate were added in one portion to a stirred solution of 100 ml acetone containing 1 g (5.23 mmol) 1-(benzothiazol-2-yl)propan-2-one, 1, and 7.22 g (52.3 mmol) K₂CO₃. The reaction mixture was refluxed for 12 h, filtered off and the solvent evaporated. After cooling a pale white precipitate of 2 appeared. These crystals were collected by filtration and recrystallized from ethanol (yield 0.5 g, 36.5%). The filtrate was leaved overnight at room temperature. Thereafter a second crystalline product was obtained which on recrystallization from ethanol gave white single crystals of 3 (yield 0.8 g, 45.6%).

Methyl 2-(2-(2-oxopropylidene)1,3-benzothiazol-3(2H)-yl)acetate, 2: mp. 208–210° C; IR (ATR), ν[cm^-1]): 1608; 1739; ¹H-NMR (300 MHz; CDCl₃), δ (p.p.m.): 3.78 (s, 2H), 5.75 (s,1H), 6.9–7.6 (m, 4H); ¹³C-NMR (75 MHZ; CDCl₃), δ (p.p.m.): 29.3; 46,9, 53,1; 90.9; 109.5; 122.7; 123.3; 127.2; 139.4; 160.5; 167.2, 191.5.

Dimethyl 3-acetyl-3-(1,3-benzothiazol-2-yl)pentandioate, 3: mp: 166–168° C; IR (ATR), ν[cm^-1): 1617; 1718; ¹H-NMR (30 MHz; CDCl₃), δ (p.p.m.): 2.24 (s, 3H), 3.54–371 (m, 10H) 7.4–8.0 (m, 4H);¹³C-NMR (75 MHz; CDCl₃), δ (p.p.m.): 25.7; 38.9; 51.9, 57.5, 121.6, 123.4, 125.5, 126.2, 135.4, 152.4, 152.6 169.8, 171.0, 203.6; MS(ESI): m/z 336 [M+1]⁺, 639 [2M+23]⁺.

A suitable single-crystal of 3 was selected under a polarization microsope and mounted on a 50 µm MicroMesh MiTeGen Micromount^TMusing FROMBLIN Y perfluoropolyether (LVAC 16/6, Aldrich).