(±)-trans-6,7-Dimeth­oxy-1-oxo-3-(2-thien­yl)isochroman-4-carboxylic acid

Mehmet Akkurt; Zeliha Baktır; Milen G Bogdanov; Ivan V Svinyarov; Orhan Büyükgüngör

doi:10.1107/S1600536809018844

. 2009 May 23;65(Pt 6):o1377. doi: 10.1107/S1600536809018844

(±)-trans-6,7-Dimethoxy-1-oxo-3-(2-thienyl)isochroman-4-carboxylic acid

Mehmet Akkurt ^a,^*, Zeliha Baktır ^a, Milen G Bogdanov ^b, Ivan V Svinyarov ^b, Orhan Büyükgüngör ^c

PMCID: PMC2969835 PMID: 21583225

Abstract

The title compound, C₁₆H₁₄O₆S, was synthesized by the reaction of 6,7-dimethoxyhomophthalic anhydride with thiophene-2-carbaldehyde in the presence of 4-(dimethylamino)pyridine (DMAP) as a basic catalyst. The thiophene ring of the title molecule is disordered over two sites with occupancies of 0.877 (3) and 0.123 (3). The disorder corresponds to an approximate 180° rotation of the thiophene ring with respect to the C—C bond linking it to the rest of the molecule. The six-membered ring of the 3,4-dihydroisochromanone ring system is not planar [puckering parameters Q _T = 0.571 (2) Å, θ = 115.2 (2)° and ϕ = 99.1 (2)°]. The benzene ring of the 3,4-dihydroisochromanone ring system makes dihedral angles of 75.0 (2) and 77.2 (5)° with the disordered thiophene rings. Intermolecular O—H⋯O and C—H⋯O hydrogen bonds, as well as C—H⋯π interactions, lead to the observed supramolecular structure.

Related literature

For details of the synthesis of the title compound, see: Bogdanov & Palamareva (2004 ▶). For the synthesis of new dihydroisocoumarins, see: Bogdanov et al. (2007a ▶,b ▶). For ring-puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₆H₁₄O₆S
M _r = 334.34
Triclinic,
a = 8.3369 (6) Å
b = 8.4587 (6) Å
c = 11.9143 (9) Å
α = 76.441 (6)°
β = 81.127 (6)°
γ = 72.958 (6)°
V = 777.6 (1) Å³
Z = 2
Mo Kα radiation
μ = 0.24 mm⁻¹
T = 296 K
0.53 × 0.41 × 0.21 mm

Data collection

Stoe IPDS II diffractometer
Absorption correction: integration (X-RED32; Stoe & Cie, 2002 ▶) T _min = 0.885, T _max = 0.952
8329 measured reflections
3229 independent reflections
2663 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.113
S = 1.07
3229 reflections
219 parameters
13 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.31 e Å⁻³

Data collection: X-AREA (Stoe & Cie, 2002 ▶); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); 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 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809018844/im2117sup1.cif

e-65-o1377-sup1.cif^{(24.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809018844/im2117Isup2.hkl

e-65-o1377-Isup2.hkl^{(155.1KB, 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
O6—H6⋯O3ⁱ	0.86 (3)	1.84 (2)	2.658 (2)	159 (3)
C2—H2⋯O5ⁱⁱ	0.93	2.54	3.465 (2)	172
C10—H10⋯O6ⁱⁱⁱ	0.98	2.54	3.475 (2)	159
C11—H11⋯Cg4^iv	0.98	2.61	3.525 (2)	156

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) . Cg4 is the centroid of the C1–C6 ring.

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS2 diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

Comment

The title compound (I) was obtained as a part of a research project aimed at the synthesis of new dihydroisocoumarins with potential pharmacological activities (Bogdanov et al., 2007a,b). (I) was synthesized by a one-pot reaction of 6,7-dimethoxyhomophthalic anhydride with thiophene-2-carboxaldehyde in the presence of DMAP as a basic catalyst (Bogdanov & Palamareva, 2004). The structure of (I) was determined by spectral methods (¹H NMR & IR) and microanalysis. In this paper, we report the X-ray crystallographic study of (I).

In the title molecule, (I), the thiophene ring is disordered over two sites and the major component of the disorder labelled with suffix A is shown in Fig. 1. The disorder corresponds to an approximate 180° rotation with respect to the C10—C13 bond. The six-membered ring (O4/C1/C6/C9–C11) of the 3,4-dihydroisochromanone ring system is not planar, showing the puckering parameters: Q_T = 0.571 (2) Å, θ = 115.2 (2)° and φ = 99.1 (2)° (Cremer & Pople, 1975). The benzene ring (C1–C6) of the 3,4-dihydroisochromanone ring system encloses dihedral angles of 75.0 (2)° and 77.2 (5)° with the thiophene rings A(C13/C14A/C15/C16/S1A) and B (C13/C14B/C15/C16/S1B), respectively.

The crystal structure is realized by intermolecular O—H···O and C—H···O hydrogen bonds and C—H···π interactions (Table 1, Fig. 2).

Experimental

Compound (I) was synthesized by the reaction of 6,7-dimethoxyhomophthalic anhydride (1) with thiophene-2-carbaldehyde (2) in the presence of DMAP as a basic catalyst (Bogdanov & Palamareva, 2004). To a mixture of 1 (0.33 g, 1.5 mmol) and 2 (0.15 ml, 1.65 mmol) in dry chloroform (5 ml) DMAP (0.18 g, 1.5 mmol) was added. The mixture was stirred at room temperature for 1 h. At the end of the reaction (monitored by TLC), the reaction mixture was extracted with 10% sodium hydrogen carbonate. The aqueous layer was further acidified (pH = 3) with 10% hydrochloric acid and extracted with ethyl acetate. The organic layer was dried (sodium sulfate), filtered and the solvent was then evaporated under reduced pressure giving (0.49 g, 98%) of a diastereomeric mixture of cis- and trans-(±)-6,7-dimethoxy-1-oxo-3-(thiophen-2-yl)isochroman-4-carboxylic acids, in a 30:70 ratio, favoring the trans diastereomer. Pure trans-diastereomer (I) was obtained by fractional crystallization of the residue from ethyl acetate. The product was characterized by ¹H NMR, IR spectra and elemental analysis. Single crystals were obtained by slow evaporation of a chloroform–ethyl acetate (3:1) solution of (I) at room temperature (m.p. 465–467 K). Analysis, calculated for C₁₆H₁₄O₆S (334.34): C 57.48, H 4.22, O 28.71, S 9.59 (%); found: C 57.74, H 3.97, O 28.71, S 9.91 (%). IR (KBr) 1693 cm^-1 (C═O), 1741 cm^-1 (C═O). The ¹H NMR spectrum of (I) was obtained on a Bruker DRX-250 spectrometer at 250.13 MHz. Chemical shifts (δ) are expressed in parts per million (p.p.m.). ¹H NMR (250 MHz, DMSO-d₆) δ = 3.82 (3H, s, –O—CH₃), 3.85 (3H, s, –O—CH₃), 4.43 (1H, d, J = 3 Hz, H-4), 6.29 (1H, d, J = 3 Hz, H-3), 6.96 (1H, dd, J = 3.6 and 5 Hz, Th—H), 7.08 (1H, s, Ph—H), 7.13 (1H, d, J = 3.5 Hz, Th—H), 7.37 (1H, s, Ph—H), 7.44 (1H, dd, J = 1 and 5 Hz, Th—H).