Structures of 2,5-Diaryl- and 2,3,5,6-tetra[3,2-b]thiophene synthesized by the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction

Vietnam Journal of Chemistry, International Edition, 54(6): 672-677, 2016 DOI: 10.15625/0866-7144.2016-00385 672 Structures of 2,5-diaryl- and 2,3,5,6-tetra[3,2-b]thiophene synthesized by the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction Nguyen Hien 1* , Nguyen Bich Ngan 1 , Nguyen Dang Dat 1 , Luc van Meervelt 2 1 Faculty of Chemistry, Hanoi National University of Education 2 Department of Chemistry, KU Leuven Received 10 August 2016; Accepted for publication 19 December 2016 Abstract The crystal structures of 2,5-di(ethoxyphenyl)-3,6-dibromothieno[3,2-b]thiophene (I) and 2,5-di(ethoxyphenyl)- 3,6-diphenylthieno[3,2-b]thiophene (II) have been studied in order to evaluate the planarity of these molecules. The aromatic systems introduced to the thieno[3,2-b]thiophene core structure show a degree of rotation from 30.94 to 66.56 . The crystal packing of (I) are characterized by π π stacking, while in (II), C-H and C-H O interactions are observed. Keywords. thieno[3,2-b]thiophene, palladium-catalyzed, Suzuki-Miyaura, cross-coupling. 1. INTRODUCTION Thieno[3,2-b]thiophene possesses a rigid structure and an extended π-conjugation. This electron-rich two annulated thiophene structure enable it to construct conjugated and low band gap organic semiconductors. Functionalized thieno[3,2- b]thiophene units have been incorporated into, or designed as a part of the skeleton of conjugated oligomers and polymers to improve the electronic properties of the materials [1]. These kinds of materials were applied to produce high-performance organic field-effect transistors (OFETs) [2], organic light-emitting diodes (OLEDs) [3], and photovoltaics devices [4]. In fact, the performance of a functionalized material depends heavily on its molecular structure and the stacking motif. Therefore, design of functional molecular solid-state structures, or arrangements, through tuning of the intermolecular interactions is essential. One of the convenient methods for fine-tuning band gaps involves the arylation which promotes a greater conjugation in the ground state. This method is also employed for adjusting the band gap of organic materials and increasing intermolecular interactions in the solid state. The objective of this work was the partial and full functionalization of the thieno[3,2-b]thiophene ring starting from 2,3,5,6- tetrabromothieno[3,2-b]thiophene [5] using the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction [6]. Herein, the synthesis, the molecular and the crystal structures of the synthesized 2,5- di(ethoxyphenyl)-3,6-dibromothieno[3,2- b]thiophene (I) and 2,5-di(ethoxyphenyl)-3,6- diphenylthieno[3,2-b]thiophene (II) will be discussed. 2. EXPERIMENTAL 2.1. Chemicals Catalysts, solvents and other chemicals were purchased from Sigma-Aldrich or Merck and were used as received unless otherwise indicated. THF VJC, 54(6) 2016 Nguyen Hien, et al. 673 were refluxed over sodium wire in the presence of benzophenone as indicator and redistilled just before used. The Suzuki-Miyaura cross-coupling reactions were conducted under deaerated conditions. 2.2. Instrumentation The 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance 500 NMR spectrometer in CDCl3. Chemical shift was reported in ppm units with tetramethylsilane (TMS) as internal reference. Splitting patterns are designated as s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet). X-ray measurements were performed on an Agilent SuperNova (single source at offset, Eos detector) diffractometer at the Department of Chemistry, KU Leuven, Belgium. 2.3. Synthesis and crystallization 2.3.1. Synthesis of 2,5-di(ethoxyphenyl)-3,6- dibromothieno[3,2-b]thiophene (I) Toluene (4 ml) was deoxygenated and saturated with argon by exchanging between vacuum and a stream of argon (3 times). 2,3,5,6- Tetrabromothieno[3,2-b]thiophene (230 mg, 0.5 mmol, 1.0 equiv) and Pd(Ph3P)4 (57.7 mg, 0.05 mmol, 0.10 equiv) were dissolved in this solvent at 60-70 o C. To the obtained solution was added H2O (1 ml), K3PO4 (212 mg, 1.0 mmol, 2.0 equiv), and 4- ethoxyphenylboronic acid (182.6 mg, 2.2 equiv). The reaction was vigorously stirred under argon atmosphere at 110 o C until TLC (100 % n-hexane) showed the complete consumption of the starting material (about 8 hours). The reaction mixture was cooled by ice water. The white solid separated was filtered, washed several times with toluene and recrystallized from hot n-hexane:ethyl acetate (1:1, v/v) to give (I) (155.5 mg, yield 58 %) as white needles; mp 230-231 o C. 1 H NMR (CDCl3, 500 MHz): δ (ppm) 7.36 (t, J = 8.0 Hz, 1 H, aromatic), 7.27 (m, 2 H, aromatic), 6.95 (m, 1 H, aromatic), 4.10 (q, J = 7.0 Hz, 2 H, CH2), 1.45 (t, J = 7.0 Hz, 3 H, CH3); 13 C NMR (CDCl3, 125 MHz): δ (ppm) 159.1 (C-O), 139.4, 138.8, 134.0, 129.8, 121.3, 115.2, 114.9, 100.1, 63.6 (O-CH2), 14.8 (CH3). 2.3.2. Synthesis of 2,5-di(ethoxyphenyl)-3,6- diphenylthieno[3,2-b]thiophene (II) (I) (108 mg, 0.2 mmol) and Pd(Ph3P)4 (24 mg, 0.02 mmol, 0.10 equiv) were dissolved in toluene (4 ml) that was degassed and saturated with argon. To the mixture were added phenylboronic acid (47 mg, 0.44 mmol), K3PO4 (170 mg, 4.0 equiv) and distilled water (1 ml). The resulting mixture was refluxed at 110 o C, during which the progress of the reaction was monitored by TLC (100 % n-hexane). After 8 h, phenylboronic acid (21 mg, 0.2 mmol) and Pd(Ph3P)4 (12 mg, 0.01 mmol, 0.05 equiv) were added; the mixture was further refluxed for 12 h. After the reaction was completed, the reaction mixture was diluted with 20 ml toluene, washed with water (3 times) and dried over anhydrous Na2SO4. (II) was isolated by column chromatography (n- hexane:ethyl acetate 95:5, v/v) as a white solid (64 mg, yield 60 %); mp 231-233 o C. (II) was further purified by recrystallized from n-hexane:ethyl acetate (3:1, v/v) solution. 1 H NMR (CDCl3, 500 MHz): δ (ppm) 7.48 (dd, J = 8.0 Hz and 1.0 Hz, 2 H, aromatic), 7.37 (dt, J = 8.0 Hz and 1.0 Hz, 2 H, aromatic), 7.33 (d, J = 8.5 Hz, 1 H, aromatic), 7.16 (t, J = 8.0 Hz, 1 H, aromatic), 6.92 (td, J = 7.5 Hz and 0.5 Hz, 1 H, aromatic), 6.86 (m, 1 H, aromatic), 6.79 (m, 1 H, aromatic), 3.86 (q, J = 7.0 Hz, 2 H, CH2), 1.13 (t, J = 7.0 Hz, 3 H, CH3). 13 C NMR (CDCl3, 125 MHz): δ (ppm) 158.9 (C-O), 139.0, 138.9, 135.7, 135.2, 130.8, 129.5, 129.1, 128.8, 127.7, 121.6, 114.8, 114.6, 63.3 (O-CH2), 14.7 (CH3). 2.4. Structure solution and refinement The X-ray diffraction data were collected on an Agilent SuperNova diffractometer using mirror- monochromated MoK radiation ( = 0.71073 Å). Using Olex2 [7]. The structure was solved with the SHELXS [8] structure solution program using Direct Methods and refined by full-matrix least-squares methods based on F 2 using SHELXL [9]. All non- hydrogen atom parameters were refined anisotropically. All hydrogen atoms were placed in idealized positions and refined in riding mode with Uiso values assigned as 1.2 times those of the parent atoms (1.5 times for methyl groups), with a C–H distance of 0.95 (aromatic), 0.98 (methyl) or 0.99 Å (methylene). The crystal data, the data collection, and the structure refinement details are summarized in table 1. 3. RESULTS AND DISCUSSION The molecular structures of the diaryl (I) and tetraaryl (II) derivatives of thieno[3,2-b]thiophene are shown in Fig. 1. The bond lengths and angles are in good agreement with the average values in the Cambridge Structure Database (CSD, version 5.37, November 2015) [10]. In order to enlarge the -conjugated system of VJC, 54(6) 2016 Structures of 2,5-diaryl- and 2,3,5,6-tetra 674 the thieno[3,2-b]thiophene, aromatic rings were introduced into the thieno[3,2-b]thiophene skeleton by Suzuki-Miyaura cross-coupling reactions. In these reactions, the site-selectivity at the C2 and C5 positions was observed due to the effect of the sulphur heteroatom [10]. Table 1: Crystal data, data collection and structure refinement parameters for (I) and (II) (I) (II) CSD code CSD 1497991 CSD 1497992 Chemical formula C22H18Br2O2S2 C34H28O2S2 Mr 538.30 532.68 Crystal system, space group Monoclinic, P21/n Triclinic, P-1 Temperature (K) 100 100 a, b, c (Å) 3.9155(3), 14.7861(11), 17.4836(14) 5.7894(5), 9.3851(11), 13.4001(14) , , (°) 90, 91.395(7), 90 82.144(9), 84.093(8), 75.788(9) V (Å 3 ) 1011.92(13) 697.35(13) Z 2 1 Radiation type MoK MoK (mm -1 ) 4.23 0.22 Crystal size (mm 3 ) 0.3 × 0.1 × 0.1 0.45 × 0.12 × 0.08 Data collection Tmin, Tmax 0.679, 1.000 0.638, 1.000 No. of measured, independent and observed [I> 2 (I)] reflections 10583, 2054, 1917 14116, 2842, 2541 Rint 0.033 0.047 (sin / )max (Å -1 ) 0.625 0.625 Refinement R[F 2 > 2 (F 2 )], wR(F 2 ), S 0.020, 0.048, 1.07 0.040, 0.104, 1.07 No. of reflections 2054 2842 No. of parameters 128 173 max, min (e Å -3 ) 0.36, -0.25 0.47, -0.27 Compound (I) crystallizes in space group P21/n, while (II) crystallizes in space group P-1. Both compounds have an inversion centre located in the middle of the C1-C1 i bond in (I) and C2-C2 ii bond in (II) (Symmetry codes: (i) -x, -y + 1, -z + 1; (ii) -x + 1, -y + 1, -z; Fig. 1). As a result, the asymmetric unit consists of one half of the molecule, the second half being generated by an inversion centre. The fused thiophene rings in both structures are planar (r.m.s. deviation = 0.002 Å for (I) and 0.001 Å for (II)). The introduced phenyl rings are non-planar with the core structure. In (I), the dihedral angle between the thieno[3,2-b]thiophene ring and the ethoxyphenyl ring is 46.93(8) . The rotation is to reduce the repulsion between Br1 H5 and S1 H9, that is in good agreement with the case of 3,6-dibromo-2(4- tert-butylphenyl)-5-(4-methylstyryl)thieno[3,2- b]thiophene [12]. In (II), the dihedral angles between the thieno[3,2-b]thiophene ring and the two phenyl rings are 31.24(6) and 66.61(7) , respectively. In addition, in this compound, the ethoxyphenyl ring is almost perpendicular to the phenyl ring (the dihedral angle between both rings is 64.09(8) ). Only one tetra-substituted thieno[3,2- b]thiophene structure similar to (II) is present in the CSD: 2,3,5,6-tetraphenylthieno[3,2-b]thiophene (refcode WEXBOS, [12]). In that case, the 2,5- phenyl rings and the 3,6-phenyl rings are rotated out of the plane of the thieno[3,2-b]thiophene ring by dihedral angles of 35.31(7) and 59.38(6) , respectively. Possibly, the ethoxy-substituted phenyl groups force the un-substituted ones to rotate less from the core structure, while they themselves are twisted more The packing of (I) shows - stacking between the 4-ethoxyphenyl rings [Cg1 Cg1 i = 3.9155(3) Å; Cg1 is the centroid of the C4-C9 ring; symmetry code: (i) x + 1, y, z; Fig. 2a]. A weak C- Br interaction is observed [C2-Br1 Cg1 ii ; VJC, 54(6) 2016 Nguyen Hien, et al. 675 Br1 Cg1 ii = 3.9290(9) Å; symmetry code: (ii) -x + 1, -y + 1, -z + 1]. (I) (II) Figure 1: Molecular structures of (I) and (II), showing the atom-labelling schemes. Displacement ellipsoids are drawn at the 50% probability level. [Symmetry codes: (i) -x, -y + 1, -z + 1; (ii) -x + 1, -y + 1, -z] Due to the presence of the four bulky substituents, the packing of (II) shows no - stacking (Fig. 2b), which is in agreement with the analogous structure 2,3,5,6-tetraphenylthieno[3,2- b]thiophene [12]. C-H O interactions are present in the crystal packing resulting in a chain of molecules in the (204) plane. Parallel chains of the molecules are linked by C-H interactions with the ethoxy- substituted phenyl groups (table 2, Fig. 2b). Possible intermolecular S S interactions which could increase the electronic transport between neighboring molecules are not observed in the crystal packing of both (I) and (II). Table 2: Hydrogen bond geometry (Å, °) for (II) D-H A D-H H A D A D-H A C14-H14 O17 i 0.95 2.54 3.476(2) 168 C6-H6 Cg1 ii 0.95 2.67 3.515(2) 148 C19-H19C Cg2 iii 0.98 2.87 3.697(2) 143 Symmetry codes: (i) -x - 1, -y - 1, -z - 1; (ii) x + 1, y, z; (iii) -x, -y + 1, -z + 1. 4. CONCLUSION In conclusion, the crystal structures of a 2,5- diaryl- and a 2,3,5,6-tetraayl derivatives of thieno[3,2-b]thiophene were recorded and analyzed. The results showed that the phenyl rings introduced into the thieno[3,2-b]thiophene core structure undergo a degree of rotation from 30.94 to 66.56 . In addition, π π stacking is the dominant arrangement in the crystal packing of (I). On the other hand, C-H and C-H O interactions are observed in the crystal structure of (II). Intermolecular S S interactions which could increase the electronic transport between neighboring molecules are not found in the crystal packing of both (I) and (II). Attempts to planarize the introduced aromatic rings with the thieno[3,2- b]thiophene by the FeCl3-oxidation reaction are in progress in our laboratory and will be reported in near future. Acknowledgements. This research is funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grand number 104.01-2012.26. The authors thank VLIR-UOS (project ZEIN2014Z182) for financial support and the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035. REFERENCES 1. Cinar M. E., Ozturk T., Thienothiophenes, dithienothiophenes, and thienoacenes: syntheses, oligomers, polymers, and properties, Chem. Rev., 115, 3036 (2015). VJC, 54(6) 2016 Structures of 2,5-diaryl- and 2,3,5,6-tetra 676 (a) (b) Figure 2: (a) - stacking in (I); (b) partial crystal packing of (II) showing C-H (grey) and C-H O (red) interactions 2. Chen Z., Lee M. J., Ashraf R. S., Gu Y., Albert- Seifried S., Nielsen M. M., Schroeder B., Anthopoulos T. D., Heeney M., McCulloch I., Sirringhaus H. High-performance ambipolar diketopyrrolopyrrolethieno[3,2-b]thiophene copolymer field-effect transistors with balanced hole and electron mobilities, Adv. Mater., 24, 647 (2012). 3. Tang W., Ke L., Tan L., Lin T., Kietzke T., Chen Z.- K. Conjugated copolymers based on fluorene- thieno[3,2-b]thiophene for light-emitting diodes and photovoltaic cells, Macromolecules, 40, 6164 (2007). 4. Chen Z., Lee M. J., Ashraf R. S., Gu Y., Albert- Seifried S., Nielsen M. M., Schroeder B., Anthopoulos T. D., Heeney M., McCulloch I., Sirringhaus H. High-performance ambipolar diketopyrrolopyrrolethieno[3,2-b]thiophene copolymer field-effect transistors with balanced hole and electron mobilities, Adv. Mater., 24, 647 (2012). 5. Fuller L. S., Iddon B., Smith K. A. Synthesis, metallation and bromine → lithium exchange reactions of thieno[3,2-b]thiophene and its polybromo derivatives, J. Chem. Soc., Perkin Trans., 1, 3465 (1997). 6. Maluenda I., Navarro O. Recent Developments in the Suzuki-Miyaura Reaction: 2010-2014, Molecules, 20, 7528 (2015). 7. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program, J. Appl. Cryst., 42, 339 (2009). 8. Sheldrick, G.M., A short history of SHELX, Acta Cryst., A64, 112 (2008). 9. Sheldrick, G.M.,Crystal structure refinement with SHELXL, Acta Cryst., C71, 3 (2015). 10. Groom, C. R., Bruno, I. J., Lightfoot, M. P., Ward, S. C. The Cambridge structural database, Acta Cryst., B72, 171 (2016). 11. Dang T. T., Dang T. T., N. Rasool, A. Villinger, H. Reinke, C. Fischer, P. Langer. Regioselective palladium(0)-catalyzed cross-coupling reactions and metal-halide exchange reactions of tetrabromothiophene: optimization, scope and limitations, Adv. Synth. Catal., 351, 1595 (2009). 12. Nguyen H., Nguyen B. N., Dang T. T., Meervelt L. V. Stacking patterns of thieno[3,2-b ]thiophenes VJC, 54(6) 2016 Nguyen Hien, et al. 677 functionalized by sequential palladium-catalyzed Suzuki and Heck cross-coupling reactions, Acta Cryst., C70, 895 (2014). 13. Liu Y., Liu Q., Zhang X., Ai L., Wang Y., Peng R., Ge Z. Synthesis, crystal structure, and polymerization of butterfly-shaped thieno[3,2- b]thiophene oligomers, New J. Chem., 37, 1189 (2013). Corresponding author: Nguyen Hien Faculty of Chemistry Hanoi National University of Education 136, Xuan Thuy, Cau Giay, Hanoi E-mail: hiennguyendhsphn@gmail.com; Telephone: 0983825316.