Methyl trans-()-1-oxo-2-phenethyl-3- (thiophen-2-yl)-1,2,3,4-tetrahydro- isoquinoline-4-carboxylate Mehmet Akkurt, a * Selvi Karaca, a Milen G. Bogdanov, b Meglena I. Kandinska b and Orhan Bu ¨yu ¨kgu ¨ngo ¨r c a Department of Physics, Faculty of Arts and Sciences, Erciyes University, 38039 Kayseri, Turkey, b Faculty of Chemistry, University of Sofia, 1 James Bourchier Boulevard, 1164 Sofia, Bulgaria, and c Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Samsun, Turkey Correspondence e-mail: [email protected]Received 28 April 2009; accepted 8 May 2009 Key indicators: single-crystal X-ray study; T = 296 K; mean (C–C) = 0.003 A ˚ ; disorder in main residue; R factor = 0.048; wR factor = 0.137; data-to-parameter ratio = 14.6. In the title compound, C 23 H 21 NO 3 S, the piperidine ring of the tetrahydroisoquinolinone unit adopts a screw-boat conforma- tion. The thiophene ring is disordered in a 0.700 (3):0.300 (3) ratio by an approximate 180 rotation of the ring around the C—C bond linking the ring to the tetrahydroisoquinolinone unit. The benzene ring of the tetrahydroisoquinolinone unit makes dihedral angles of 83.1 (2) and 62.38 (11) with the major occupancy thiophene ring and the phenyl ring, respectively. The dihedral angle between the phenyl ring and the thiophene ring is 71.0 (2) . In the crystal structure, molecules are linked together by intermolecular C—HO and C—Hinteractions. Related literature For background to the biological and pharmacological appli- cations of compounds containing a tetrahydroisoquinoline fragment, see: Bogdanov et al. (2007); Burdzhiev & Stanoeva (2006); Gitto et al. (2008); Humphries et al. (2009); Kandinska et al. (2006); Rothweiler et al. (2008). For reference structural data, see: Allen et al. (1987); Akkurt et al. (2008). For ring conformations, see: Cremer & Pople (1975). Experimental Crystal data C 23 H 21 NO 3 S M r = 391.48 Monoclinic, P2 1 =c a = 8.8841 (3) A ˚ b = 30.7095 (13) A ˚ c = 7.5757 (3) A ˚ = 105.472 (3) V = 1991.95 (14) A ˚ 3 Z =4 Mo Kradiation = 0.19 mm 1 T = 296 K 0.65 0.47 0.22 mm Data collection Stoe IPDS 2 diffractometer Absorption correction: integration (X-RED32; Stoe & Cie, 2002) T min = 0.889, T max = 0.960 13399 measured reflections 3986 independent reflections 3154 reflections with I >2(I) R int = 0.036 Refinement R[F 2 >2(F 2 )] = 0.048 wR(F 2 ) = 0.137 S = 1.04 3986 reflections 273 parameters 36 restraints H-atom parameters constrained Ámax = 0.32 e A ˚ 3 Ámin = 0.23 e A ˚ 3 Table 1 Hydrogen-bond geometry (A ˚ , ). D—HA D—H HA DA D—HA C2—H2O1 i 0.93 2.57 3.401 (3) 149 C15—H15O1 ii 0.93 2.55 3.420 (3) 155 C3—H3Cg1 iii 0.93 2.78 3.688 (3) 165 C3—H3Cg2 iii 0.93 2.77 3.688 (4) 167 C19—H19Cg3 iv 0.93 2.89 3.692 (3) 145 Symmetry codes: (i) x; y; z þ 1; (ii) x þ 2; y; z þ 1; (iii) x 1; y; z; (iv) x þ 1; y; z. Cg1, Cg2 and Cg3 are centroids of the S1A/C12/C13A/C14/C15, S1B/C12/C13B/C14/C15 and C1–C6 rings, respectively. 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 data and figures for this paper are available from the IUCr electronic archives (Reference: IS2413). References Akkurt, M., O ¨ ztu ¨rk Yıldırım, S., Bogdanov, M. G., Kandinska, M. I. & Bu ¨ yu ¨ kgu ¨ ngo ¨r, O. (2008). Acta Cryst. E64, o1955–o1956. Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119. Bogdanov, M. G., Gocheva, B. T., Dimitrova, D. B. & Palamreva, M. D. (2007). J. Heterocycl. Chem. 44, 673–677. Burdzhiev, N. T. & Stanoeva, E. R. (2006). Tetrahedron, 62, 8318–8326. Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. Gitto, R., Francica, E., De Sarro, G., Scicchitano, F. & Chimirri, A. (2008). Chem. Pharm. Bull. 56, 181–184. Humphries, P. S., Benbow, J. W., Bonin, P. D., Boyer, D., Doran, S. D., Frisbie, R. K., Piotrowski, D. W., Balan, G., Bechle, B. M., Conn, E. L., Dirico, K. J., Oliver, R. M., Soeller, W. C., Southers, J. A. & Yang, X. (2009). Bioorg. Med. Chem. Lett. 19, 2400–2403. organic compounds Acta Cryst. (2009). E65, o1287–o1288 doi:10.1107/S1600536809017383 Akkurt et al. o1287 Acta Crystallographica Section E Structure Reports Online ISSN 1600-5368
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Symmetry codes: (i) x; y; zþ 1; (ii) �xþ 2;�y;�zþ 1; (iii) x� 1; y; z; (iv) xþ 1; y; z.Cg1, Cg2 and Cg3 are centroids of the S1A/C12/C13A/C14/C15, S1B/C12/C13B/C14/C15and C1–C6 rings, respectively.
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 data and figures for this paper are available from theIUCr electronic archives (Reference: IS2413).
References
Akkurt, M., Ozturk Yıldırım, S., Bogdanov, M. G., Kandinska, M. I. &Buyukgungor, O. (2008). Acta Cryst. E64, o1955–o1956.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C.,Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J.Appl. Cryst. 32, 115–119.
Bogdanov, M. G., Gocheva, B. T., Dimitrova, D. B. & Palamreva, M. D. (2007).J. Heterocycl. Chem. 44, 673–677.
Burdzhiev, N. T. & Stanoeva, E. R. (2006). Tetrahedron, 62, 8318–8326.Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.Gitto, R., Francica, E., De Sarro, G., Scicchitano, F. & Chimirri, A. (2008).
Chem. Pharm. Bull. 56, 181–184.Humphries, P. S., Benbow, J. W., Bonin, P. D., Boyer, D., Doran, S. D., Frisbie,
R. K., Piotrowski, D. W., Balan, G., Bechle, B. M., Conn, E. L., Dirico, K. J.,Oliver, R. M., Soeller, W. C., Southers, J. A. & Yang, X. (2009). Bioorg. Med.Chem. Lett. 19, 2400–2403.
organic compounds
Acta Cryst. (2009). E65, o1287–o1288 doi:10.1107/S1600536809017383 Akkurt et al. o1287
M. Akkurt, S. Karaca, M. G. Bogdanov, M. I. Kandinska and O. Büyükgüngör
Comment
Compounds containing tetrahydroisoquinoline fragment in their structure display a broad spectrum of biological activities.In particular, derivatives of this type have been recently recognized as being G-protein-coupled receptor 40 (GPR40) ant-agonists (Humphries et al.2009), inhibitors of the MDM2–p53 interaction (Rothweiler et al., 2008), potent anticonvulsantagents (Gitto et al., 2008), etc. Thus, the title compound (I) was synthesized as a part of our ongoing program related toanhydride-based synthesis of new heterocyclic compounds with potential pharmacological activities (Bogdanov et al., 2007;Burdzhiev & Stanoeva, 2006; Kandinska et al., 2006).
In the title molecule, (I), the thiophene ring is disordered over two sites and the major component of the disorder labelledwith suffix A is shown in Fig. 1. The disorder corresponds to a rotation of approximately 180° rotation about the single C—Cbond to which it is attached. All the bond lengths and angles of (I) are in normal ranges (Allen et al., 1987; Akkurt et al.,2008). The six-membered piperidine ring (N1/C1/C6–C9) of 3,4-dihydroisoquinolinone ring system adopts a screw-boatconformation, as shown with the Cremer–Pople puckering parameters [Cremer & Pople, 1975; QT = 0.4620 (18) Å, θ =
114.5 (2)° and φ = 90.8 (23)°]. The benzene ring (C1–C6) of 3,4-dihydroisoquinolinone ring system is essentially planar,with an r.m.s. deviation of 0.002 (2) Å for C2 and C5. This benzene ring makes dihedral angles of 83.1 (2), 83.1 (4) and62.38 (11)°, with the thiophene rings A (C12/C13A/C14/C15/S1A) and B (C12/C13B/C14/C15/S1B), and the phenyl ringC (C18–C23), respectively. The dihedral angles between the phenyl ring C and the thiophene rings A and B are C/A =71.0 (2) and C/B = 70.4 (4)°, respectively.
In the crystal structure, molecules are linked together by intermolecular C—H···O interactions (Table 1 and Fig. 2). Thecrystal structure is further stabilized by intermolecular C—H···π interactions (Table 1).
Experimental
The title compound (I) was synthesized by esterification reaction of trans-1-oxo-2-phenethyl-3-(thiophen-2-yl)-1,2,3,4- tet-rahydroisoquinoline-4-carboxylic acid (20 g, 0.053 mol) in the presence of H2SO4 (4.3 ml) in methanol. The reaction mix-
ture was refluxed for 3 h. and then left over night. The colourless crystals were filtered and washed with water/methanolmixture yielding 18.6 g (90%) of (I). Single crystals were obtained by slow evaporation of a chloroform–ethyl acetate (3:1)solution of (I) at room temperature (mp 401–402 K). Analysis, calculated for C23H21NO3S (391.48): C 70.56, H 5.41 (%);
found: C 70.24, H 5.38 (%). IR (CHCl3) 1650 cm-1 (C═O), 1740 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.) from
tetramethylsilane as an internal standard. 1H NMR (250 MHz, deuterochloroform) δ = 2.90–3.05 (2H, m, CH2-Phenyl),
H atoms bound to C atoms were in geometrically generated positions and constrained to ride on their parent atoms [C—H= 0.93–0.98 Å and Uiso(H) = 1.2 (1.5 for methyl groups) × Ueq(C)]. The ratio of the refined occupancies for the major
and minor components of the disordered thiophene ring is 0.700 (3):0.300 (3). Rigid-bond restrains were applied to thedisordered atoms.
Figures
Fig. 1. View of the title molecule, (I), with the atom-labelling scheme. Displacement ellips-oids are drawn at the 30% probability level. H atoms are shown as spheres of arbitrary radius.The minor component of the disorder groups has been omitted.
Fig. 2. Part of the crystal structure of (I), viewed along the a axis. Dashed lines show inter-molecular C—H···O interactions. H atoms not involved in hydrogen bonding and the minorcomponent of the disorder groups have been omitted for clarity.
36 restraints Extinction correction: nonePrimary atom site location: structure-invariant directmethods
Special details
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from thevariances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and tor-sion angles
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-
factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The
observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refine-
ment. 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 evenlarger.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)