Palladium- and copper-catalyzed highly selective mono-coupling between 2,6-diiodoanisoles and terminal alkynes in the production of alkynylated anisoles as potential precursors of benzo[b]furans

SHORT REPORTS

Palladium- and copper-catalyzed highly selective mono-coupling between 2,6-diiodoanisoles and terminal alkynes in the production of alkynylated anisoles as potential precursors of benzo[b]furans

Allan F. C. Rossini^I; Carlise Frota^II; Gleison A. Casagrande^II; Lucas Pizzuti^II; Cristiano Raminelli^{*, I}

^IDepartamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, 09972-270 Diadema-SP, Brazil

^IIFaculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, km 12, 79804-970 Dourados-MS, Brazil

ABSTRACT

The coupling reaction between 2,6-diiodoanisoles and terminal alkynes using Pd(PPh₃)₂Cl₂ and CuI as catalysts and diisopropylamine as base in toluene at room temperature for 12 h produced selectively alkynylated 2-iodoanisoles, in good to excellent yields (52-95%), which are useful building blocks with potential application in the synthesis of functionalized benzo[b]furans.

Keywords: Sonogashira reaction, selective mono-coupling, alkynylated anisoles, diiodinated benzo[b]furans, palladium and copper catalysis

RESUMO

A reação de acoplamento entre 2,6-diiodoanisóis e alcinos terminais usando Pd(PPh₃)₂Cl₂ e CuI como catalisadores e diisopropilamina como base em tolueno a temperatura ambiente por 12 h produziu seletivamente 2-iodoanisóis aquinilados, em rendimentos de bons a excelentes (52-95%), os quais são blocos de construção úteis com potencial aplicação na síntese de benzo[b]furanos funcionalizados.

Introduction

Palladium-catalyzed cross-coupling reactions can be considered powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds,^1-4 including, for example, Sonogashira,¹ Stille,² Suzuki³ and Buchwald-Hartwig⁴ reactions. The mentioned transformations have been often employed in total syntheses of complex molecules,⁵ in the preparation of functional materials⁶ and for the production of polymers of importance in materials science.⁷ Furthermore, palladium-catalyzed reactions are in agreement with some principles of green chemistry.⁸ In this sense, a significant number of high-quality articles involving palladium-catalyzed cross-coupling reactions have been reported in the literature.^1-7 However, a critical evaluation of this active area of the organic chemistry indicates that methodologies for site-selective couplings,⁹ involving selective mono-couplings,¹⁰ are still required in organic synthesis, constituting a vast field for investigation. Nevertheless, significant advances for palladium-catalyzed selective couplings between organic halides and organometallic reagents have been reported in the literature.^9-11 Among them, we can mention advances achieved for selective Sonogashira mono-couplings.¹¹ Despite the advances mentioned, to the best of our knowledge, there is no methodology employing palladium as a catalyst for the selective mono-coupling between 2,6-diiodoanisoles and terminal alkynes, in order to produce alkynylated 2-iodoanisoles, which are useful intermediates in organic synthesis. Accordingly, aiming to enrich the literature, we wish to present in this manuscript results which conducted to the development of a selective mono-coupling between 2,6-diiodoanisoles (1) and terminal alkynes (2) using palladium and copper as catalysts in the presence of a nitrogen-containing base, in order to produce exclusively alkynylated 2-iodoanisoles (3) in good to excellent yields, which are useful building blocks with potential application in the synthesis of functionalized benzo[b]furans, that compose a class of aromatic heterocyclic compounds with an extensive number of pronounced biological activities, comprising, for example, anticancer,¹² antiviral¹³ and anti-inflammatory¹⁴ activities.

Results and Discussion

Initially, the reaction between 2,6-diiodoanisole (1a) and 2 equiv. of phenylacetylene (2a) using 10 mol% of Pd(PPh₃)₂Cl₂ and 10 mol% of CuI in the presence of 2 equiv. of triethylamine (Et₃N) as base and MeCN as solvent at 50 ºC for 24 h gave 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) in a 41% yield (Table 1, entry 1).¹⁵ In an attempt to produce compound 3a in a higher yield, we allowed 2,6-diiodoanisole (1a) to react with 1.5 equiv. of phenylacetylene (2a) using 5 mol% of Pd(OAc)₂, 10 mol% of triphenylphosphine (PPh₃) and 5 mol% of CuI in the presence of 2 equiv. of Et₃N as base and MeCN as solvent at 50 ºC for 24 h and obtained the alkynylated 2-iodoanisole 3a in a moderate yield of 43% (entry 2).¹⁶ Thereafter, we carried out the reaction employing 2,6-diiodoanisole (1a), 1.5 equiv. of compound 2a, 10 mol% of Pd(PPh₃)₄, 10 mol% of CuI and 2 equiv. of Et₃N in tetrahydrofuran (THF) at 60 ºC. After 24 h, compound 3a was obtained in only 37% yield (entry 3).¹⁷ Ultimately, by the reaction between 2,6-diiodoanisole (1a) and 2 equiv. of phenylacetylene (2a) using 5 mol% of Pd(PPh₃)₂Cl₂ and 15 mol% of CuI in the presence of 1 equiv. of diisopropylamine (DIPA) as base and toluene as solvent at room temperature for 12 h, we produced 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) in a 68% yield (entry 4).¹⁸ We did not observe the formation of the di-alkynylated product in the transformations outlined in Table 1, although for most cases (entries 1-3) the desired product 3a was obtained in low yields (< 43%). Besides, in all entries in Table 1 we observed by gas chromatography/mass spectrometry (GC/MS) the formation of the alkyne-alkyne homo-coupling as a byproduct.

Afterwards, we focused on the optimization of the conditions for the reaction shown in entry 4 of Table 1, performing variations in the stoichiometry of reagents, temperature and time of reaction, envisioning the production of 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) in a higher yield. Thus, as can be seen in Table 2, the best result was achieved when we carried out the reaction between 2,6-diiodoanisole (1a) and 2 equiv. of phenylacetylene (2a) in the presence of 5 mol% of Pd(PPh₃)₂Cl₂ and 15 mol% of CuI using 2 equiv. of DIPA as base and toluene as solvent at room temperature for 12 h, producing the alkynylated 2-iodoanisole 3a in a very good yield of 82% (Table 2, entry 4). In this case, we did not observe the formation of the di-alkynylated product. However, we observed by GC/MS the formation of the alkyne-alkyne homo-coupling as a byproduct.

Employing the optimal conditions shown in Table 2, entry 4, we examined the scope of the selective mono-coupling reaction using for some entries 2,6-diiodoanisoles containing electron-withdrawing and electron-donating groups (1b-c) and functionalized terminal alkynes (2c-f) (Table 3). The coupling between 2,6-diiodoanisole (1a) and 2 equiv. of 1-hexyne (2b) in the presence of 5 mol% of Pd(PPh₃)₂Cl₂ and 15 mol% of CuI using 2 equiv. of DIPA as base and toluene as solvent at room temperature for 12 h gave exclusively the compound 3b in an 82% yield (entry 2). By using 4-choro-2,6-diiodoanisole (1b), which contains an electron-withdrawing group, reactions with the alkynes 2a and 2b led to the alkynylated 2-iodoanisoles 3c and 3d, respectively, in excellent yields (> 93%) (entries 3 and 4). For entries 3 and 4 we observed by GC/MS the formation of di-alkynylated products in trace amounts. On the other hand, employing 4-methyl-2,6-diiodoanisole (1c), which contains an electron-donating group, reactions with the alkynes 2a and 2b were relatively sluggish leading to the alkynylated 2-iodoanisoles 3e and 3f, respectively, in yields around 70% (entries 5 and 6). For entries 5 and 6 we did not observe the formation of di-alkynylated products. In addition, transformations carried out with functionalized terminal alkynes 2c-f produced the mono-coupling products 3g-k in good yields (52-85%) (entries 7-11). Allowing the reaction between 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) and 2 equiv. of 1-hexyne (2b) in the presence of 5 mol% of Pd(PPh₃)₂Cl₂ and 15 mol% of CuI using 2 equiv. of DIPA as base and toluene as solvent at room temperature for 12 h, we obtained the unsymmetrical dialkyne 3l in a good yield of 78% (entry 12). It is noteworthy that when we carried out the coupling reaction between 1,4-diiodobenzene and phenylacetylene (2a), employing the optimal conditions shown in Table 2, entry 4, by the addition of DIPA all at once, we observed the prompt formation of a viscous mixture and the exclusive production of the di-coupled product after 12 h, according to GC/MS analysis. Performing the same transformation, however, by the addition of DIPA in portions, we did not notice the formation of a viscous mixture and we observed the production of the mono-coupled product along with the di-coupled product in a ratio of 1 to 1.25 after 12 h, according to GC/MS analysis.

The highly selective formation of alkynylated 2-iodoanisoles (3a-k) was not completely rationalized until this moment, however, having in mind that iodinated aromatic compounds were employed, the transmetalation reaction can be considered the rate-determining step for the Sonogashira coupling.¹ In this sense, the transition states for the transmetalation step when we consider the catalytic cycle with alkynylated 2-iodoanisoles (3a-k) are substantially more sterically crowded and presumably present higher energies than the transition states for the transmetalation step when we consider the catalytic cycle involving 2,6-diiodoanisoles (1a-c). All these assumptions can be supported by the almost exclusive formation of alkynylated 2-iodoanisoles (3a-k) in good to excellent yields (52-95%).

The alkynylated anisoles 3a-l are versatile building blocks in organic synthesis, which can find application in electrophilic cyclization reactions. Accordingly, we subjected 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) to the reaction with iodine and obtained the diiodinated benzo[b]furan 4 in an isolated yield of 44%¹⁹ (Scheme 1).

The structures of the compounds 3a-l and 4 have been assigned on the basis of a variety of spectroscopic techniques, namely, according to their mass spectra (MS), infrared (IR), ¹H and ¹³C nuclear magnetic resonance (NMR) spectra. All compounds (3a-l and 4) provided high-resolution mass spectra (HRMS) that are in agreement with the proposed structures.

Conclusions

In summary, we developed a highly selective reaction for the mono-coupling between 2,6-diodoanisoles (1) and terminal alkynes (2) using Pd(PPh₃)₂Cl₂ and CuI as catalysts and DIPA as base, in order to produce alkynylated 2-iodoanisoles (3) in good to excellent yields (52-95%). Employing the same reaction conditions, the coupling between alkynylated 2-iodoanisole 3a and 1-hexyne (2b) led to the formation of the unsymmetrical dialkyne 3l in a good yield of 78%. Besides, 1-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) has found application in the preparation of the diiodinated benzo[b]furan 4 in a moderate yield of 44%.

Experimental

General methods

¹H and ¹³C NMR spectra were recorded on spectrometers operating at 300 or 200 MHz and 75 or 50 MHz, respectively. ¹H NMR spectra were taken in CDCl₃ and the chemical shifts of the signals are given in ppm with respect to tetramethylsilane (TMS) used as an internal standard. ¹³C NMR spectra were taken in CDCl₃ and the chemical shifts of the signals are given in ppm with respect to the central peak of the deuterated solvent adjusted to 77.00 ppm and used as a reference. Infrared spectra were obtained using attenuated total reflectance (ATR) or KBr pellets in the 4000-400 cm^-1 region. Mass spectra were registered on a mass spectrometer connected to a gas chromatograph using electron impact ionization at 70 eV. High-resolution mass spectra were performed on a time-of-flight mass spectrometer. All melting point values are uncorrected. Column chromatography separations were carried out using 70-230 mesh silica gel. Catalysts, reagents and solvents were used as obtained commercially. 2,6-Diiodoanisoles (1a-c) were prepared according to literature procedures.²⁰

General procedure for preparation of mono-coupling products (3a-k) and unsymmetrical dialkyne 3l

To a solution of the appropriate 2,6-diiodoanisole (1a-c) or compound 3a (1 mmol), Pd(PPh₃)₂Cl₂ (0.0351 g, 0.05 mmol) and CuI (0.0285, 0.15 mmol) in toluene (5 mL) under nitrogen atmosphere were added the appropriate terminal alkyne (2a-f) (2 mmol) and diisopropylamine (0.2020 g, 2 mmol). After that, the mixture was stirred at room temperature for 12 h. Then, brine (20 mL) was added to the reaction, which was extracted with ethyl acetate (3 × 20 mL). The organic phase was dried over MgSO₄. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using hexane as eluent, unless otherwise indicated, affording mono-coupling products (3a-k) and the unsymmetrical dialkyne 3l.

Procedure for preparation of benzo[b]furan 4

To a vial (20 mL) were added 2-iodo-2-methoxy-3-(phenylethynyl)benzene (3a) (0.0835 g, 0.25 mmol) and a solution of iodine (0.1270 g, 0.5 mmol) in CH₂Cl₂ (5 mL). The vial was sealed using a cap, and the mixture was stirred at 40 ºC for 12 h. Afterwards, a saturated solution of sodium thiosulfate (10 mL) was added to the reaction, which was extracted with ethyl acetate (3 × 10 mL). The organic phase was dried over MgSO₄. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using hexane as eluent, affording 3,7-diiodo-2-phenylbenzo[b]furan (4).

Characterization data for compounds 3a-l and 4

1-Iodo-2-methoxy-3-(phenylethynyl)benzene (3a): Rf = 0.33 (obtained after three runs in hexane); yield 0.2739 g (82%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) δ 7.75 (dd, 1H, J 7.9, 1.6 Hz), 7.57-7.52 (m, 2H), 7.74 (dd, 1H, J 7.7, 1.6 Hz), 7.39-7.34 (m, 3H), 6.82 (t, 1H, J 7.8 Hz), 4.03 (s, 3H); ¹³C NMR (50 MHz, CDCl₃) δ 160.3, 139.4, 133.7, 131.5, 128.6, 128.4, 125.4, 122.9, 117.6, 94.5, 91.8, 85.0, 61.0; IR (ATR) ν_max/cm^-1 1653, 1238, 1026, 522; LRMS m/z (%) 334 (100.0), 257 (5.1), 178 (6.4), 164 (2.8); HRMS [M + Na]⁺ found: 356.9746, calcd.: 356.9752.

1-(Hex-1-ynyl)-3-iodo-2-methoxybenzene (3b): Rf = 0.63 (obtained after three runs in hexane); yield 0.2575 g (82%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) d 7.68 (dd, 1H, J 7.9, 1.6 Hz), 7.34 (dd, 1H, J 7.7, 1.6 Hz), 6.75 (t, 1H, J 7.8 Hz), 3.93 (s, 3H), 2.45 (t, 2H, J 6.8 Hz), 1.61-1.45 (m, 4H), 0.93 (t, 3H, J 7.3 Hz); ¹³C NMR (50 MHz, CDCl₃) δ 160.3, 138.6, 133.8, 125.3, 118.4, 96.0, 91.7, 76.1, 60.7, 30.6, 22.0, 19.3, 13.6; IR (ATR) ν_max/cm^-1 1647, 1239, 1071, 716, 500; LRMS m/z (%) 314 (100.0), 299 (37.7), 257 (33.4), 144 (35.9); HRMS [M + Na]⁺ found: 337.0050, calcd.: 337.0065.

5-Chloro-1-iodo-2-methoxy-3-(phenylethynyl)benzene (3c): Rf = 0.67 (obtained after three runs in hexane); yield 0.3495 g (95%); off-white solid; m.p. 68-69 ºC; ¹H NMR (200 MHz, CDCl₃) δ 7.71 (d, 1H, J 2.5 Hz), 7.56-7.50 (m, 2H), 7.46 (d, 1H, J 2.5 Hz), 7.41-7.33 (m, 3H), 4.00 (s, 3H); ¹³C NMR (50 MHz, CDCl₃) δ 159.1, 138.4, 133.1, 131.6, 129.5, 129.0, 128.5, 122.4, 118.2, 95.5, 92.0, 83.8, 61.1; IR (KBr) ν_max/cm^-1 1653, 1240, 1025, 754, 511; LRMS m/z (%) 368 (100.0), 206 (3.2), 291 (4.3), 178 (5.6); HRMS [M + Na]⁺ found: 390.9352, calcd.: 390.9363.

5-Chloro-1-(hex-1-ynyl)-3-iodo-2-methoxybenzene (3d): Rf = 0.51 (obtained after three runs in hexane); yield 0.3236 g (93%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) δ 7.65 (d, 1H, J 2.5 Hz), 7.32 (d, 1H, J 2.5 Hz), 3.91 (s, 3H), 2.44 (t, 2H, J 6.8 Hz), 1.61-1.46 (m, 4H), 0.95 (t, 3H, J 7.2 Hz); ¹³C NMR (50 MHz, CDCl₃) δ 159.2, 137.7, 133.3, 129.3, 119.1, 97.3, 91.8, 75.1, 60.8, 30.5, 22.0, 19.3, 13.6; IR (ATR) ν_max/cm^-1 2228, 1232, 1099, 723, 509; LRMS m/z (%) 349 (100.0), 291 (10.9), 178 (6.6); HRMS [M + Na]⁺ found: 370.9673, calcd.: 370.9676.

1-Iodo-2-methoxy-5-methyl-3-(phenylethynyl)benzene (3e): Rf = 0.47 (obtained after three runs in hexane); yield 0.2436 g (70%); orange oil; ¹H NMR (200 MHz, CDCl₃) d 7.56-7.48 (m, 3H), 7.36-7.31 (m, 3H), 7.26 (d, 1H, J 2.1 Hz), 3.97 (s, 3H), 2.23 (s, 3H); ¹³C NMR (50 MHz, CDCl₃) δ 158.1, 139.8, 135.1, 134.0, 131.4, 128.4, 128.3, 122.9, 116.8, 94.0, 91.5, 85.1, 60.9, 20.0; IR (ATR) ν_max/cm^-1 1003, 1242, 756; LRMS m/z (%) 348 (100.0), 347 (26.2), 178 (7.5); HRMS [M + H]⁺ found: 349.0072, calcd.: 349.0089.

1-(Hex-1-ynyl)-3-iodo-2-methoxy-5-methylbenzene (3f): Rf = 0.31 (obtained after three runs in hexane); yield 0.2231 g (68%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) δ 7.49 (dd, 1H, J 2.2, 0.6 Hz), 7.14 (dd, 1H, J 2.0, 0.6 Hz), 3.89 (s, 3H), 2.45 (t, 2H, J 6.8 Hz), 2.21 (s, 3H), 1.61-1.46 (m, 4H), 0.95 (t, 3H, J 7.1 Hz); ¹³C NMR (50 MHz, CDCl₃) δ 158.1, 139.0, 135.0, 134.2, 117.7, 95.4, 91.3, 60.6, 30.6, 29.6, 21.9, 19.9, 19.2, 13.6; IR (ATR) ν_max/cm^-1 2230, 1240, 1005, 725, 581; LRMS m/z (%) 328 (100.0), 313 (13.5), 271 (16.8), 171 (9.5); HRMS [M + Na]⁺ found: 351.0210; calcd.: 351.0222.

1-Iodo-2-methoxy-3-(3-methylbut-3-en-1-ynyl)benzene (3g): Rf = 0.58 (obtained after three runs in hexane); yield 0.1937 g (65%); colorless oil; ¹H NMR (200 MHz, CDCl₃) δ 7.72 (dd, 1H, J 7.9, 1.6 Hz), 7.38 (dd, 1H, J 7.7, 1.6 Hz), 6.78 (t, 1H, J 7.8 Hz), 5.43-5.41 (m, 1H), 5.35-5.32 (m, 1H), 3.97 (s, 3H), 2.00 (dd, 3H, J 1.5, 1.1 Hz); ¹³C NMR (50 MHz, CDCl₃) d 160.2, 139.3, 133.6, 126.6, 125.3, 122.4, 117.5, 95.7, 91.7, 83.9, 60.8, 23.2; IR (ATR) ν_max/cm^-1 2936, 1238, 1032, 1003, 779; LRMS m/z (%) 298 (100.0), 283 (22.0), 271 (0.5), 257 (4.6), 244 (0.7), 141 (13.2), 128 (57.3); HRMS [M + Na]⁺ found: 320.9723, calcd.: 320.9752.

3-(3-Iodo-2-methoxyphenyl)-N,N-dimethylprop-2-yn-1-amine (3h): The eluents used were ethyl acetate and then methanol. Rf = 0.62 (ethyl acetate and then methanol); yield 0.1953 g (62%); brownish solid; m.p. 49-50 ºC; ¹H NMR (200 MHz, CDCl₃) δ 7.73 (dd, 1H, J 7.9, 1.6 Hz), 7.40 (dd, 1H, J 7.7, 1.6 Hz), 6.78 (t, 1H, J 7.8 Hz), 3.95 (s, 3H), 3.56 (s, 2H), 2.40 (s, 6H); ¹³C NMR (50 MHz, CDCl₃) d 160.3, 139.2, 133.9, 125.3, 117.5, 91.7, 89.6, 81.0, 60.9, 48.5, 44.0; IR (KBr) ν_max/cm^-1 2934, 2207, 1238, 777; LRMS m/z (%) 341 (25.1), 300 (10.1), 284 (15.7), 270 (100.0), 157 (8.4); HRMS [M + H]⁺ found: 316.0196, calcd.: 316.0198.

1-(3-Cyclopentylprop-1-ynyl)-3-iodo-2-methoxybenzene (3i): Rf = 0.41 (obtained after three runs in hexane); yield 0.2652 g (78%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) δ 7.68 (dd, 1H, J 7.9, 1.6 Hz), 7.34 (dd, 1H, J 7.7, 1.6 Hz), 6.75 (t, 1H, J 7.8 Hz), 3.94 (s, 3H), 2.47 (d, 2H, J 6.7 Hz), 2.16 (septet, 1H, J 7.3 Hz), 1.88-1.79 (m, 2H), 1.68-1.57 (m, 4H), 1.41-1.30 (m, 2H); ¹³C NMR (50 MHz, CDCl₃) δ 160.3, 138.6, 133.9, 125.3, 118.5, 95.5, 91.7, 60.7, 39.0, 32.0, 29.7, 25.4, 25.3; IR (ATR) ν_max/cm^-1 2949, 2227, 1238, 1003, 776; LRMS m/z (%) 340 (24.8), 325 (43.3), 297 (19.4), 257 (100.0), 146 (98.6); HRMS [M + Na]⁺ found: 363.0217, calcd.: 363.0222.

1-Iodo-2-methoxy-3-((4-methoxyphenyl)ethynyl)benzene (3j): Rf = 0.48 (obtained after three runs in hexane); yield 0.1893 g (52%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) d 7.73 (dd, 1H, J 7.9, 1.5 Hz), 7.9-7.43 (m, 3H), 6.92-6.87 (m, 2H), 6.81 (t, 1H, J 7.8 Hz), 4.02 (s, 3H), 3.84 (s, 3H); ¹³C NMR (50 MHz, CDCl₃) δ 160.1, 159.9, 139.1, 133.6, 133.0, 125.4, 118.0, 115.1, 114.1, 94.7, 91.8, 83.7, 60.9, 55.3; IR (ATR) ν_max/cm^-1 2915, 2210, 1241, 1000, 751; LRMS m/z (%) 364 (98.1), 363 (100.0), 349 (9.3), 333 (11.1), 257 (2.6), 165 (6.4); HRMS [M + Na]⁺ found: 386.9854, calcd.: 386.9858.

5-Chloro-1-(3-cyclopentylprop-1-ynyl)-3-iodo-2-methoxybenzene (3k): Rf = 0.62 (obtained after three runs in hexane); yield 0.3179 g (85%); yellowish oil; ¹H NMR (200 MHz, CDCl₃) δ 7.65 (d, 1H, J 2.5 Hz), 7.32 (d, 1H, J 2.5 Hz), 3.91 (s, 3H), 2.46 (d, 2H, J 6.7 Hz), 2.15 (septet, 1H, J 7.3 Hz), 1.92-1.79 (m, 2H), 1.67-1.55 (m, 4H), 1.39-1.27 (m, 2H); ¹³C NMR (50 MHz, CDCl₃) δ 159.2, 137.6, 133.3, 129.3, 119.1, 96.8, 91.8, 75.2, 60.8, 38.9, 32.0, 25.4, 25.2; IR (ATR) ν_max/cm^-1 2948, 1572, 1537, 1233, 999, 577; LRMS m/z (%) 374 (100.0), 345 (9.3), 339 (20.8), 291 (45.9), 212 (12.2); HRMS [M + Na]⁺ found: 396.9830, calcd.: 396.9832.

1-(Hex-1-ynyl)-2-methoxy-3-(phenylethynyl)benzene (3l): Rf = 0.29 (obtained after three runs in hexane); yield 0.2246 g (78%); yellowish oil; ¹H NMR (300 MHz, CDCl₃) δ 4.49-7.44 (m, 2H), 7.33 (dd, 1H, J 7.7, 1.7 Hz), 7.30-7.24 (m, 4H), 6.91 (t, 1H, J 7.7 Hz), 3.99 (s, 3H), 2.39 (t, 2H, J 6.9 Hz), 1.58-1.39 (m, 4H), 0.88 (t, 3H, J 7.2 Hz); ¹³C NMR (75 MHz, CDCl₃) δ 161.8, 133.6, 132.7, 131.5, 128.3, 123.4, 123.3, 118.3, 117.4, 95.2, 93.5, 76.2, 61.1, 30.7, 21.9, 19.3, 13.6; IR (ATR) ν_max/cm^-1 3057, 2955, 2932, 1597, 1412, 1236, 1005, 754; LRMS m/z (%) 288 (100.0), 273 (14.1), 245 (30.2), 231 (27.3), 207 (20.3), 152 (9.1), 77 (7.4); HRMS [M + NH₄]⁺ found: 306.1849, calcd.: 306.1858.

3,7-Diiodo-2-phenylbenzo[b]furan (4): Rf = 0.54 (hexane); yield 0.0490 g (44%); off-white solid; m.p. 110-112 ºC; ¹H NMR (200 MHz, CDCl₃) δ 8.23-8.17 (m, 2H), 7.70 (dd, 1H, J 7.7, 1.1 Hz), 7.55-7.43 (m, 3H), 7.39 (dd, 1H, J 7.8, 1.1 Hz), 7.06 (t, 1H, J 7.7 Hz); ¹³C NMR (50 MHz, CDCl₃) δ 153.9, 153.4, 134.4, 132.4, 129.5, 129.4, 128.5, 127.5, 125.0, 121.9, 75.6, 62.4; IR (KBr) ν_max/cm^-1 3055, 1905, 1485, 1482, 1060; LRMS m/z (%) 446 (100.0), 319 (8.7), 192 (10.0); HRMS [M + Na]⁺ found: 468.8548, calcd.: 468.8562.

Supplementary Information

Supplementary information (copies of ¹H and ¹³C NMR spectra) is available free of charge at http://jbcs.sbq.org.br as a PDF file.

Acknowledgements

We gratefully acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for financial support.

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Submitted: May 12, 2014

Published online: August 29, 2014

FAPESP has sponsored the publication of this article.

Supplementary Information

The supplementary material is available in pdf: [Supplementary material]

Publication Dates

• Publication in this collection
  13 Nov 2014
• Date of issue
  Nov 2014

History

• Accepted
  29 Aug 2014
• Received
  12 May 2014