HETEROCYCLES

Short Paper | Regular issue | Vol. 87, No. 6, 2013, pp. 1319-1326
Received, 25th March, 2013, Accepted, 25th April, 2013, Published online, 30th April, 2013.
DOI: 10.3987/COM-13-12718

■ Intramolecular [2π+2π]-Photocyclization and Conformational Preference of 5-(2-Benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a,d]cycloheptene

Motoko Akita, Sin-ya Mohri, Mai Takahashi, and Keiji Kobayashi*

Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

The photoirradiation of 5-(2-benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a.d]cycloheptene (2) in acetonitrile afforded a cagelike tetracyclic compound (1) via intramolecular [2π+2π]-photocycloaddition. The molecular and crystal structures of 1 and 2 were characterized by a single-crystal X-ray diffraction study. The formation of the cycloadduct is discussed in relation to the preferable conformation of the central C-C bond in 2, which was revealed to be in restricted rotation on the basis of the temperature-dependent 1H NMR spectra.

Thiophene derivatives show versatile photoreactivity and wide mechanistic perspectives.1 An unsaturated bond of the thiophene ring frequently exhibits photoreactivity as a 2π-electron component. A relevant example is the photoinduced electrocyclization of 1,2-di(2-thienyl)ethylenes to give a cyclohexadiene framework, which has been attracting considerable attention in relation to photochromic functions.2 The thiophene ring of benzo[b]thiophenes also participates in inter- and intramolecular [2π+2π]-cycloadditions.3 We previously reported the novel intramolecular photocyclization and di-π-methane rearrangement of tris(2-benzo[b]thienyl)methane derivatives.4,5 In the course of our continuous study, we have now found an unexpected intramolecular [2π+2π]-photocyclization of 5-(2-benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a,d]cycloheptene (2). Herein, we demonstrate the formation of 1, a novel cagelike tetracyclic compound, from participation of the spatially remote olefinic bond in intramolecular [2π+2π]-photocyclization,6 in which the conformation of the starting compound is preferable for the reaction to be induced.
An acetonitrile solution of 2 (ca 0.5 mM) was irradiated with a high-pressure Hg lamp through a Pyrex filter under nitrogen at 0 °C for 1 h. The chromatography of the resulting mixture on a silica gel gave 1 in 54% yield (Scheme 1). The photoreaction proceeds rather cleanly without the formation of byproducts as indicated by the 1H NMR spectrum of the photoreaction mixture.

Single crystals of 1 suited for single-crystal structural analysis were isolated by recrystallization from ethanol. The crystal structure analysis of 1 confirms the formation of the cyclobutane ring, which arises from the intramolecular [2π+2π]-cyclization of the C2=C3 double bond of the benzo[b]thiophene ring and the C10=C11 double bond of the dibenzocycloheptene ring　(Scheme 1). The involvement of the double bond of the dibenzocycloheptene framework in intramolecular [2π+2π]-photocycloaddition has been reported for photoreaction of tetrabenzoheptafulvalene,7 but such examples are rather rarely encountered. The cyclobutane ring of 1 is not planar but bent, and its four internal angles are all less than 90°. Although the results of the X-ray analysis are not good enough to estimate accurate structural parameters because of the poor crystallinity of the single crystal employed for data collection, they are still satisfactory for revealing the gross dihedral angles of H58-C6-C13-H53 and H53-C13-C2-H52 to be 93° and 33°, respectively (Figure 1).8 Thus, on the basis of the Karplus correlation, these geometries of hydrogen atoms provide a rational reason for their observed vicinal spin coupling constants in the 1H NMR spectrum: JH53-H58 = 0 and JH52-H53 = 5.6 Hz.

Intramolecular cyclization could be induced in the syn form with respect to the central C-C bond (Figure 2). Otherwise, the two 2π moieties are far apart to enter into the mutual reaction. The preference of an sc conformation was actually revealed by the X-ray crystallographic analysis of 2 (Figure 3).

Thus, judging from the molecular structure in the crystalline state, the intramolecular C---C distances associated with new bond formation (C8-C16 and C9-C17 of 2 in Figure 3) are 2.992 and 3.002 Å.9,10 The preference of the conformation, in which the C-S and C-O bonds are close to each other, is reasonable because of existence of attractive interactions between these two bonds.11,12 As seen in the side view of the molecular structure (Figure 3-a), the rotation of the planar thieno[b]thiophene ring about the central C-C bond suffers steric hindrance by both the C10H=C11H and C2H5O- moieties, resulting in restriction of the internal conversion between +sc and –sc forms (Figure 2). Such conformational restriction is advantageous for the intramolecular [2π+2π]-cycloaddition. Furthermore, the conformational fixation of the central bond of 2 at room temperature in the NMR time-scale was revealed by the temperature-dependent 1H NMR spectra.
The 1H NMR of 2 at room temperature displays distinct chemical shifts for H10 and H11 as well as for H4 and H6 (Scheme 1). As shown in Figure 4-a, when temperature was increased, the AB quartet signals at approximately 6.8 ppm due to H10 and H11 broadened and eventually coalesced at 60°. A similar behavior was also observed in the two doublet signals of H4 and H5 as shown in Figure 4-a. Thus, the single bond connecting the thieno[b]thiophene and dibenzocycloheptene rings of 2 has a high-energy barrier to rotation, which is attributed to the steric hindrance and the ground state stabilization of the sc form. A free-energy barrier (Δ G‡) for the rotation was estimated by the coalescence method to be 70 kJmol-1 at 60 °C, the coalescence temperature of the H10 and H11 signals.13,14

The restricted rotation around the central bond was also indicated in the methylene protons of the ethoxy group, which occur at 3.12 and 3.45 ppm as double triplet signals, respectively (Figure 4-b). These signals showed averaging to coalesce at about 80 °C. The conformational rigidity is also shown by 13C NMR spectra of 2, in which twenty five signals are observed because of the nonequivalency of the dibenzo moiety.
Upon irradiation for 4 hours under nitrogen, no photoreaction was induced in 3, a compound analogous to 1 but bearing no ethoxy substituent. Furthermore, 3 indicated no restricted rotation in its 1H NMR spectra. Thus, the photoreactivity of 2 could be partially attributed to the preferable conformation, the sc form, which is considered to be persistent enough to undergo the photocyclization.

In summary, we described a novel photochemical reaction, i.e., the intramolecular [2π+2π]-cycloaddition between the unsaturated bond of the thieno[b]thiophene ring and the C=C double bond of the dibenzocycloheptene moiety. The fascinating cagelike structure of the intramolecular cycloadduct was elucidated by X-ray crystallographic structural analysis. The conformational preference and rigidity of the starting compound, revealed by X-ray analysis and dynamic 1H NMR spectroscopy, respectively, are suggested to have effect on the intramolecular photocycloaddition.

EXPERIMENTAL
All the melting points were determined using a Yanaco MS-500V apparatus and are uncorrected. The 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded using a Varian 400-MR spectrometer. Chemical shifts are given in δ values (ppm) using TMS as the internal standard. Mass spectra were taken on a Shimadzu GCMS-QP5050A mass spectrometer. Elementary combustion analyses were recorded using a Yanaco CHN CORDER MT-6 analyzer. All reactions were monitored by TCL employing a 0.25 mm silica gel plate (Merck 60F 254). Column chromatography was carried out on silica gel (Merck 60N spherical).
Photoreaction: A solution of 2 (0.035 g, 0.095 mmol) in acetonitrile (200 mL) was degassed with nitrogen for 20 min prior to irradiation with 100W Hg vapor lamp. Photoirradiation was carried out through Pyrex filter for 20 min under nitrogen. After evaporation to dryness the residue was purified by silica gel chromatography to afford 1 (0.019 g, 54%) as colorless prisms.
[2π+2π]-Photocycloadduct (1): colorless solids; mp 163 °C; MS m/z = 368; IR (KBr) 1445, 1223, 1196 cm-1; 1H NMR (CDCl3) δ 1.39 (3H, t, J = 6.7 Hz), 3.62 (1H, s), 3.83 (1H, quint, J = 6.9 Hz), 4.05 (1H, d, J = 5.6 Hz), 4.10 (1H, quint, J = 6.9 Hz), 4.44 (1H, d, J = 5.6 Hz), 6.99 (1H, d, J = 7.3 Hz), 7.02 (1H, d, J = 7.3 Hz), 7.04 (1H, t, J = 7.3 Hz), 7.10 (1H, t, J = 7.3 Hz), 7.12 (1H, t, J = 6.8 Hz), 7.15 (1H, t, J = 6.8 Hz), 7.18 (1H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.3 Hz), 7.26 (1H, d, J = 7.6 Hz), 7.38 (1H, d, J = 7.3 Hz), 7.42 (1H, d, J = 7.3 Hz), 7.48 (1H, d, J = 7.6 Hz); 13C NMR (CDCl3) δ 15.50, 49.51, 58.06, 58.50, 61.54, 88.52, 119.98, 122.32, 124.22, 124.81, 125.64, 125.87, 126.87, 126.93, 127.47, 127.54, 127.66, 128.36, 135.42, 138.90, 139.56, 141.60, 144.07, 154.72. Anal. Calcd for C25H20OS: C; 81.48, H; 5.47. Found: C; 81.58, H; 5.53.
X-ray data for 1: 223 K: C25H20OS, M = 368.49, monoclinic, P21/n (#14), a = 10.396(3) Å, b = 30.936(5) Å, c = 17.575(4), Å, β = 91.323(10)°, Z = 12, V = 5651(2) A3. Dcalcd = 1.299 g/cm3. R1(I>2.00σ(I)) = 0.0614, wR2(I>3.00σ(I)) = 0.1241.
Preparation of 2: 5-(2-Benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a,d]cycloheptene (2) was prepared by ethanolysis of 5-(2-benzo[b]thienyl)-5-hydroxy-5H-dibenzo[a,d]cycloheptene (4).
To a solution of benzo[b]thiophene (1.34 g, 10.0 mmol) in 120 mL of dried THF (100 mL), was added 8.2 mL of a solution of n-butyllithium (1.6 M in hexane) under nitrogen at 0 °C. After addition, the mixture was stirred for 30 min at this temperature. To this solution a solution of dibenzosuberenone (2.06 g, 10 mmol) in 60 mL of THF was added dropwise at 0 °C. After being stirred for 1 h at room temperature the solution was refluxed for 4 h under nitrogen. The reaction mixture was then poured into water and treated with CH2Cl2 and the aqueous layer was extracted twice with 40 mL of CH2Cl2. The combined organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was chromatographed on silica using CH2Cl2 as eluent to give (4) (2.83 g, 83%) as colorless solids.
5-(2-Benzo[b]thienyl)-5-hydroxy-5H-dibenzo[a,d]cycloheptene (4): mp 150 °C; MS m/z = 340; IR (KBr) 3460, 1302, 1159 cm-1; 1H NMR (CDCl3) 2.62 (1H, s), 6.57 (1H, s), 6.80 (2H, s), 7.20-7.23 (2H, m), 7.34-7.40 (4H, m), 7.48-7.53 (3H, m), 7.59 (1H, d, J = 8.0 Hz), 8.20 (2H, d, J = 7.9 Hz); 13C NMR (CDCl3) δ 75.70, 122.15, 123.10, 123.50, 124.04, 124.19, 124.42, 127.27, 128.11, 128.73, 131.28, 133.54, 138.75, 139.18, 141.81, 151.84. Anal. Calcd for C23H16SO: C, 81.15; H, 4.74; S, 9.42. Found: C, 81.29; H, 4.77; S, 9.46.
A solution of 4 (0.68 g, 2.00 mmol) in 80 mL EtOH was refluxed with conc H2SO4 (ca. 0.2 mL) for 3 h. The reaction mixture was then poured into water, treated with 50 mL of brine and with 80 mL of CHCl3, and the aqueous layer was extracted twice with 40 mL of CHCl3. The combined organic layer was dried over anhydrous MgSO4 and concentrated. The residue was chromatographed on silica gel using CH2Cl2 as eluent to give 2 (0.57 g, 78%) as colorless solids.
5-(2-Benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a,d]cycloheptene (2): mp 96-97 °C; MS m/z = 368; 1H NMR (CDCl3) δ 1.39 (3H, t, J = 7.0 Hz), 3.17 (1H, m), 3.48 (1H, m), 6.61 (1H, s), 6.78 (2H, q, J = 9.4 Hz), 7.22 (2H, m), 7.33 (4H, m), 7.46-7.52 (3H, m), 7.60 (1H, d, J = 5.2 Hz), 7.90 (1H, d, J = 7.9 Hz), 8.17 (1H, d, J = 7.9 Hz); 13C NMR (CDCl3) δ 15.21, 60.50, 122.11, 123.45, 124.03, 124.15, 124.28, 124.53, 125.98, 126.70, 126.99, 127.85, 128.12, 128.70, 128.78, 128.88, 130.50, 131.82, 133.76, 133.90, 138.33, 139.53, 140.01, 142.40, 146.41. Anal. Calcd for C25H20SO: C, 81.48; H, 5.47. Found: C, 81.48; H, 5.47.
X-ray data for 2: 93 K: C25H20OS, M = 368.49, orthorhombic, P212121 (#19), a = 7.151(3) Å, b = 14.398(4) Å, c = 17.328(8) Å, Z = 4, V = 1784.2(11) A3. Dcalcd = 1.372 g/cm3. R1(I>2.00σ(I)) = 0.0813, wR2 (I>1.50σ(I)) = 0.2320.
Preparation of 3: A mixture of 4 (1.7 g, 5.0 mmol) and hydriodic acid (57%) (2.5 mL) in AcOH (100mL) was refluxed under nitrogen for 4 h at 110 °C. The reaction mixture was poured into a aqueous solution of Na2S2O3 and extracted twice with CH2Cl2. The combined organic layer was dried over anhydrous MgSO4 and concentrated. The residue was chromatographed on silica gel using benzene and hexane (1:1) as eluent to give 3 (1.39 g, 86%) as colorless crystals.
5-(2-Benzo[b]thienyl)-5H-dibenzo[a,d]cycloheptene (3): mp 168-169 °C; MS m/z = 324; 1H NMR (CDCl3) δ 5.55 (1H, s), 6.36 (1H, s), 6.78 (2H, s), 7.14 (1H, t, J = 7.5 Hz), 7.19 (1H, t, J = 7.5 Hz), 7.34-7.45 (7H, m), 7.50 (2H, d, J = 7.5 Hz), 7.57 (1H, d, J = 8.1 Hz). Anal. Calcd for C23H16S: C, 85.14; H, 4.97, S, 9.88. Found: C, 85.40; H. 5.02; S, 9.92.
Crystallographic data for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre. 1: CCDC 912714. 2: CCDC 928802.

References

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9. A flip-flop disorder is involved in the benzo[b]thiophene ring. The existence of this disorder gave rather poor results in the X-ray analysis.
10. Despite of these short distances, 2 showed no photoreactivity in the solid state.
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