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Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.25 no.9 São Paulo Sept. 2014

https://doi.org/10.5935/0103-5053.20140163 

ARTICLE

 

Synthesis of unsymmetrical aryl-ethynylated benzenes via regiocontrolled Sonogashira reaction of 1,3,5-tribromobenzene

 

 

Kamal M. Dawood*; Hamdi M. Hassaneen; Hyam A. Abdelhadi; Mohamed S. M. Ahmed; Mohamed A.-M. Mohamed

Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt

 

 


ABSTRACT

Sonogashira coupling of trimethylsilylacetylene with 4-alkyloxy-1-iodobenzenes gave 2-(4-(alkyloxy)phenyl)ethynyltrimethylsilanes which undergo deprotection via removal of TMS-group using tetrabutylammonium fluoride (TBAF) in THF at room temperature to afford the corresponding terminal 2-(4-(alkyloxy)phenyl)acetylenes. Regiocontrolled Sonogashira cross-coupling of 1,3,5-tribromobenzene with the terminal arylacetylenes in aqueous medium resulted in the formation of mono-, di- and tri-alkynylated benzene derivatives in moderate to good yields. Factors affecting the regioselective alkynylation were also examined.

Keywords: arylacetylenes, cross-coupling, catalysis, palladium, aqueous media


RESUMO

O acoplamento de Sonogashira do trimetilsililacetileno com 4-alcóxi-1-iodobenzenos resultou em 2-(4-(alquilóxi)fenil)etiniltrimetilsilanos, que sofrem desproteção pela retirada do grupo TMS usando fluoreto de tetrabutilamônio (TBAF) em THF à temperatura ambiente, resultando nos 2-(4-(alquilóxi)fenil)acetilenos terminais correspondentes. O acoplamento cruzado de Sonogashira do 1,3,5-tribromobenzeno com os arilacetilenos terminais em meio aquoso resultou na formação de derivados de benzeno mono-, di- e tri-alquinilados com rendimentos de moderados a bons. Os fatores que afetam a regiosseletividade da alquinilação também foram examinados.


 

 

Introduction

Sonogashira cross-coupling, reaction of terminal alkynes with aryl halides in the presence of palladium(0)/copper(I) catalyst under basic conditions, has been established as one of the most convenient routes to symmetrical and unsymmetrical diarylethynes of potential biological and non-biological applications.1-8 Synthesis of terminal arylacetylenes can be achieved through palladium-catalyzed Sonogashira coupling of aryl halides with mono-protected acetylenes followed by removal of the protecting group.9,10 Furthermore, terminal arylacetylenes are involved in the construction of conjugated oligo- and polyarylacetylenes of wide range of industrial applications.11-14 Polyhalogenated arenes were employed in Sonogashira coupling reactions with terminal alkynes.15-24 In addition, aqueous organic solvents have been used for promotion of Sonogashira cross-coupling reactions in the presence of PdCl2(PPh3)2.25-29 In continuation of our research work on Sonogashira coupling reaction27,30 we report in this work a regiocontrolled Sonogashira cross-coupling on 1,3,5-tribromobenzene as attractive strategy for synthesis of unsymmetrical ethynylated benzene derivatives. The effect of solvent/base ratios on the optimization of the regiocontrolled cross-coupling is evaluated.

 

Results and Discussion

At first, three different 4-alkyloxy-1-iodobenzene derivatives 1a-c were easily synthesized by reaction of 4-iodophenol with the appropriate alkyl bromides in dimethylsulfoxide (DMSO) in the presence of KOH at room temperature according to the reported Williamson method.31 Then, Sonogashira coupling of trimethylsilylacetylene with 4-alkyloxy-1-iodobenzene derivatives 1a-c using PdCl2(PPh3)2 (1 mol%) and CuI (2 mol%) in water/toluene (2 mL, 1:1) in the presence of 2 equivalents of triethylamine (Et3N) at room temperature for 24 h afforded 2-(4-(alkyloxy)phenyl)ethynyl-trimethylsilane 2a-c in 74, 86 and 96% yields, respectively (Scheme 1).

Next, removal of the trimethylsilyl (TMS) group from 2-(4-(alkyloxy)phenyl)-ethynyltrimethylsilanes 2a-c is achieved under mild conditions using tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (THF) following a related literature methodology.32 The deprotection process is completed within one hour at room temperature to afford the corresponding terminal arylacetylene products 3a-c in 74-85% yields. Further deprotection methods were reported using strong bases (such as NaH, NaOH, KOH, K2CO3 or t-BuOK) at high temperature.33-38

Regio-controlled Sonogashira cross-coupling of 1,3,5-tribromobenzene 4 with 1-ethynyl-4-(alkyloxy)benzenes 3a-c

In the next part, the scope and limitations of the palladium-catalyzed regio-controlled Sonogashira cross-coupling reactions of 1,3,5-tribromobenzene 4 were investigated. Optimization of the reaction conditions for the regio-selective synthesis of mono-ethynylated dibromobenzene 5c from 1,3,5-tribromobenzene 4 was performed and the results are outlined in Table 1. Thus, firstly the cross-coupling reaction of 1,3,5-tribromobenzene 4 with 1-ethynyl-4-(octyloxy)benzene 3c in 1:1 molar ratio using PdCl2(PPh3)2 (1 mol%) in the presence of CuI (2 mol%) using triethylamine (4 equiv.) was carried out in water/toluene (1:1, v/v) under argon atmosphere at 60 °C for 24 h till full conversion of 4 as examined by thin layer chromatography (TLC). After column chromatography, two products were isolated. The major product was obtained in 74% yield (Table 1, entry 1) and its structure was established as 1,3-dibromo-5-(2-(4-(octyloxy)phenyl)-ethynyl)-benzene 5c on the basis of its spectral analyses. The mass spectrum of 5c exhibited a peak at m/z 464 corresponding to its molecular ion and its 1H and 13C nuclear magnetic resonance (NMR) spectra were in accordance with the assigned structure. The minor product was isolated in 20% and was confirmed as 1-bromo-3,5-di-(2-(4-(octyloxy)phenyl)-ethynyl)benzene 6c on the basis of its spectral analyses. Repeating the same reaction under similar conditions using three equiv. of Et3N led to the formation of mono- and di-ethynylated bromobenzenes 5c and 6c in 80 and 12% isolated yields, respectively (Table 1, entry 2). Using two equiv. of Et3N gave the desired products 5c and 6c in 90 and 8% isolated yields, respectively (Table 1, entry 3). The use of neat toluene as solvent under the optimized coupling conditions above employing 2 equiv. of Et3N gave the products 5c and 6c in lower yields, 62 and 3% isolated yields, respectively (Table 1, entry 4). Similarly, performing the coupling reaction in degassed neat water under argon in the presence of 2 equiv. of Et3N gave the products 5c and 6c in 70 and 5% isolated yields, respectively (Table 1, entry 5). Furthermore, the use of one equivalent of Et3N in water/toluene (1:1, v/v) resulted in the formation 5c and 6c in 78 and 18%, respectively (Table 1, entry 6). Under the latter condition, coupling of 4 with 3c in toluene only afforded 5c and 6c in 45 and 9%, respectively (Table 1, entry 7). These results of entries 1-3 and 6, Table 1, are consistent with the reported ones declaring that aqueous organic solvents enhance Sonogashira cross-coupling reactions in the presence of PdCl2(PPh3)2.25-29 Accordingly, the selectivity towards mono-ethynylated dibromobenzene 5c reached its maximum when 2 equiv. of Et3N and 1 equiv. of alkyne 3c were employed using a mixed reaction solvent; water/toluene (1:1, v/v).

Under the optimized conditions, regio-controlled Sonogashira cross-coupling reactions of further arylacetylenes 3a-b with 1,3,5-tribromobenzene 4 was achieved as depicted in Table 2. Thus, cross-coupling of 1,3,5-tribromobenzene 4 with 1-ethynyl-4-(hexyloxy)benzene 3a and with 1-ethynyl-4-(heptyloxy)benzene 3b were carried out in 1:1 molar ratio using PdCl2(PPh3)2 in the presence of CuI in toluene/water mixed solvent and triethylamine as a base under argon atmosphere at 60 °C for 24 h resulted, in both cases, in full conversion into two products (major and minor) as depicted in Table 2. The reaction molar ratios were typically: 1 mmol arylacetylenes 3a-b, 1 mmol 1,3,5-tribromobenzene 4, 2 mmol Et3N, 1 mol% PdCl2(PPh3)2 and 2 mol% CuI in water/toluene (2 mL, 1:1 v/v). The major products were obtained in 94 and 93% yields, respectively (Table 2, entries 1 and 2) and their structures were established as 1-(3,5-dibromophenyl)-2-(4-hexyloxyphenyl)acetylene 5a and 1-(3,5-dibromophenyl)-2-(4-heptyloxyphenyl)acetylene 5b on the basis of their elemental and spectral analyses. The minor products were isolated in 2 and 4%, respectively (Table 2, entries 1 and 2), and were confirmed as 1-bromo-3,5-di-(2-(4-hexyloxyphenyl)-ethynyl)benzene 6a and 1-bromo-3,5-di-(2-(4-heptyloxyphenyl)ethynyl)benzene 6b on the basis of their spectral analyses (1H, 13C NMR and mass spectra) as mentioned in the experimental section.

Synthesis of unsymmetrical di- and tri-ethynylated benzenes

Next, cross-coupling of the mono-ethynylated dibromobenzene 5c with other terminal alkynes aiming to prepare unsymmetrical di- and tri-ethynylated benzenes via two successive Sonogashira reactions is evaluated as shown in Scheme 2. Thus, Sonogashira cross-coupling reaction of 1,3-dibromo-5-(2-(4-(octyloxy)phenyl)ethynyl)-benzene 5c with 1-ethynyl-4-(heptyloxy)benzene 3b was performed applying the following reaction condition: 5c (1 mmol), 3b (1 mmol), PdCl2(PPh3)2 (1 mol%), CuI (2 mol%) in toluene/water (2 mL, 1:1) using triethylamine (2 mmol) under argon atmosphere at 60 °C for 24 h to furnish two isolable products. After column chromatography, the obtained products were identified as 1-bromo-3-(2-(4-heptyloxyphenyl)ethynyl)-5-(2-(4-octyloxyphenyl)ethynyl)benzene (7) (40% yield) in addition to 1,3-di-(2-(4-heptyloxyphenyl)ethynyl)-5-(2-(4-octyloxyphenyl)ethynyl)-benzene (8) (4% yield), as shown in Scheme 2. Afterwards, the third regiocontrolled cross-coupling process for 1-bromo-3-(2-(4-heptyloxyphenyl)ethynyl)-5-(2-(4-octyloxyphenyl)ethynyl)benzene 7 was conducted via its reaction with 1-ethynylbenzene 9 in 1:1 molar ratio in the presence of PdCl2(PPh3)2 (1 mol%), CuI (2 mol%) in toluene/water (2 mL, 1:1) using triethylamine (2 mmol) under argon at 60 °C for 24 h. This sequenced cross-coupling furnished the desired unsymmetrical tri-ethynylated benzene derivative; 1-(2-(4-(heptyloxy)phenyl)ethynyl)-3-(2-(4-(octyloxy)-phenyl)ethynyl)-5-(2-phenyl-ethynyl)-benzene (10) in 60% yield as outlined in Scheme 2. The tri-ethynylated benzene product 10 was confirmed on the basis of its nuclear magnetic resonance (1H and 13C NMR) and mass spectra (MS) (see experimental section).

 

Conclusions

Three different 1-ethynyl-4-(alkyloxy)benzene candidates were prepared in three steps from 4-iodophenol. Then, these terminal acetylene candidates were employed in an efficient regiocontrolled Sonogashira cross-coupling with 1,3,5-tribromobenzene 4 for the preparation of unsymmetrical mono-, di- and tri-alkynylated benzene derivatives in moderate to good yields. Water/toluene mixed solvent was found to greatly enhance the cross-coupling reaction of 4-alkyloxyphenylacetylene with 1,3,5-tribromobenzene. These results encouraged us to conduct sequential Sonogashira followed by Susuki cross-coupling reactions on analogous candidates and the results are under progress.

 

Experimental

Melting points were determined in open glass capillaries with a Gallenkamp apparatus. The infrared (IR) spectra were recorded in potassium bromide disks on a Pye Unicam SP 3-300 and Shimaduz FTIR 8101 PC infrared spectrophotometer. NMR spectra were recorded with a Varian Mercury VXR-300 NMR spectrometer at 300 MHz (1H NMR) and at 75 MHz (13C NMR) using CDCl3 as solvent and internal standard (δ 7.27 and 77.36 ppm, for 1H NMR and 13C NMR, respectively). Chemical shifts (δ) and J values are reported in ppm and Hz, respectively. Multiplicities are shown as the abbreviations: s (singlet), d (doublet), t (triplet), m (multiplet). Electrospray ionization mass spectrometry (EI-MS) analyses were obtained at 70 eV with a Shimadzu GCMQP 1000 EX spectrometer. Analytical thin-layer chromatography (TLC) was performed using pre-coated silica gel 60778 plates (Fluka), and the spots were visualized with UV light at 254 nm. Fluka silica gel 60741 (70-230 mesh) was used for flash column chromatography. For the exclusion of atmospheric oxygen from the reaction medium, the aqueous solvent was firstly deoxygenated with a stream of argon for 30 min before use. 1-Hexyloxy-4-iodobenzene (1a),39,40 1-heptyloxy-4-iodobenzene (1b),39 and 1-octyloxy-4-iodobenzene (1c)41 were prepared following literature procedures.

Synthesis of 4-(alkyloxy)phenylethynyltrimethylsilanes 2a-c

To a mixture of PdCl2(PPh3)2 (14 mg, 0.02 mmol), CuI (7.6 mg, 0.04 mmol), and 1-alkyloxy-4-iodobenzenes 1a-c (2 mmol) in toluene (2 mL) was added trimethylsilylacetylene (0.34 mL, 2.4 mmol) at room temperature under an argon atmosphere. Triethylamine (0.28 mL, 4 mmol) in water (2 mL) was then added drop-wise and stirring was continued for 24 h at room temperature. The resulting two-phase mixture was separated and the aqueous layer was extracted with diethyl ether (3 × 30 mL). The combined organic layer was concentrated under reduced pressure to leave a crude solid, which was purified by chromatography on silica gel (hexane-ethyl acetate) to furnish the corresponding cross-coupled products 2a-c.

4-(Hexyloxy)phenylethynyltrimethylsilane (2a):42 this compound was purified by ethyl acetate-hexane (1:30) to yield 0.406 g of 2a (74%); 1H NMR (300 MHz, CDCl3) δ 0.24 (s, 9H) 0.91 (t, 3H, J 6.6 Hz), 1.26-1.45 (m, 6H), 1.74-1.80 (m, 2H), 3.95 (t, 2H, J 6.6 Hz), 6.81 (d, 2H, J 9.0 Hz), 7.39 (d, 2H, J 9.0 Hz).

4-(Heptyloxy)phenylethynyltrimethylsilane (2b):43 this compound was purified by ethyl acetate-hexane (1:50) to yield 0.496 g of 2b (86%); 1H NMR (300 MHz, CDCl3) δ 0.24 (s, 9H), 0.91 (m, 3H), 1.28-1.46 (m, 8H), 1.76-1.81 (m, 2H), 3.95 (t, 2H, J 6.6 Hz), 6.81 (d, J 8.1 Hz, 2H), 7.39 (d, J 7.8 Hz, 2H).

4-(Octyloxy)phenylethynyltrimethylsilane (2c):44,45 this compound was purified by ethyl acetate-hexane (1:70) to yield 0.58 g of 2c (96%); 1H NMR (300 MHz, CDCl3) δ 0.25 (s, 9H) 0.90 (m, 3H), 1.27-1.44 (m, 10H), 1.75-1.80 (m, 2H), 3.94 (t, 2H, J 6.6 Hz), 6.80 (d, 2H, J 8.7 Hz), 7.39 (d, 2H, J 9.0 Hz).

Synthesis of 1-ethynyl-4-(alkyloxy)benzenes 3a-c

To 2-(4-(alkyloxy)phenyl)ethynyltrimethylsilane 2a-c (0.5 mmol) in THF (3 mL), was added tetrabutylammonium fluoride (TBAF) (0.66 mL, 1 mmol) at room temperature. The resulting mixture was stirred for one hour at room temperature. The mixture was then filtered and the solvent was evaporated under reduced pressure to leave a crude oily product, which was purified by flash column chromatography using ethyl acetate-hexane (1:80) to furnish the corresponding desilylated products 3a-c in very good yields.

1-Ethynyl-4-(hexyloxy)benzene (3a):46 this compound was purified by ethyl acetate-hexane (1:80) to yield 155.5 mg (77%) as yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 3H, J 7.2 Hz), 1.23-1.49 (m, 6H), 1.71-1.81 (m, 2H), 2.97 (s, 1H), 3.93 (t, 2H, J 6.6 Hz), 6.82 (d, 2H, J 9.0 Hz), 7.39 (d, 2H, J 9.0 Hz).

1-Ethynyl-4-(heptyloxy)benzene (3b):47 this compound was purified by ethyl acetate-hexane (1:80) to furnish (162 mg, 75% yield), as yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.89 (t, 3H, J 7.2 Hz), 1.26-1.45 (m, 8H), 1.73-1.80 (m, 2H), 2.94 (s, 1H), 3.91 (t, 2H, J 6.6 Hz), 6.83 (d, 2H, J 9.0 Hz), 7.38 (d, 2H, J 9.0 Hz).

1-Ethynyl-4-(octyloxy)benzene (3c):41,45,48 this compound was purified by ethyl acetate-hexane (1:80) to give 184 mg (80% yield) as orange oil; 1H NMR (300 MHz, CDCl3) δ 0.88 (t, 3H, J 7.2 Hz), 1.26-1.45 (m, 10H), 1.71-1.80 (m, 2H), 2.96 (s, 1H), 3.91 (t, 2H, J 6.6 Hz), 6.81 (d, 2H, J 9.0 Hz), 7.38 (d, 2H, J 9.0 Hz).

Synthesis of mono- and dialkynylated benzene derivatives

To PdCl2(PPh3)2 (7 mg, 0.01 mmol), CuI (3.8 mg, 0.02 mmol) in toluene (1 mL) and Et3N (140 µL, 2 mmol) in water (1 mL) were added 1,3,5-tribromobenzene 4 (315 mg, 1 mmol) and 4-alkoxyphenylethyne 3a-c (1 mmol) under an argon atmosphere. Stirring was continued for 24 h at 60 °C. Two phases of the resulting mixture were separated and the aqueous layer was extracted three times with diethyl ether (3 × 30 mL). The combined organic layer was concentrated under reduced pressure to leave a crude solid, which was purified by flash column chromatography using hexane/ethyl acetate (20:1) to give the corresponding mono and dialkynylated products 5a-c and 6a-c.

1,3-Dibromo-5-(2-(4-(hexyloxy)phenyl)ethynyl)benzene (5a): yield: 409.5 mg (94%) as white powder; m.p. 54-55 ºC; IR (KBr) υmax/cm-1 3065, 2926, 2210, 1550, 1464, 1243; 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 3H, J 5.6 Hz), 1.28-1.85 (m, 8H), 3.99 (t, 2H, J 6.6 Hz), 6.89-7.03 (m, 2H), 7.43-7.49 (m, 2H), 7.58 (s, 2H), 7.61 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.8, 26.1, 29.0, 31.8, 68.2, 85.3, 92.5, 114.1, 114.5, 122.7, 127.4, 132.9, 133.5, 133.8, 160.1; MS (EI, 70 eV) m/z 436 (M+, 37.6%), 352 (100%), 271 (3.44%), 192 (20.8%), 163 (32.7%), 87 (7.9%), 55 (15.5%); anal. calcd. for C20H20Br2O: C, 55.07; H, 4.62%; found: C, 55.35; H, 4.79%.

1-Bromo-3,5-bis(2-(4-(hexyloxy)phenyl)ethynyl)benzene (6a): yield: 11 mg (2%) as white crystals; m.p. 108 ºC; IR (KBr) υmax/cm-1 3068, 2929, 2206, 1592, 1463, 1245; 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 6H, J 6.7 Hz), 1.28-1.83 (m, 16H), 3.99 (t, 4H, J 6.4 Hz), 6.87-6.95 (m, 4H), 7.44 (d, 4H, J 7.7 Hz), 7.47-7.58 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 14.0, 23.1, 26.5, 28.5, 31.8, 68.4, 86.3, 91.7, 114.3, 114.8, 122.1, 132.4, 133.1, 133.6, 134.7, 159.7; MS (EI, 70 eV) m/z 557 (M+, 35.0%), 258 (4.0%), 250 (27.6%), 235 (59.4%), 205 (53.7%), 189 (95.1%), 179 (55.6%), 124 (59.1%), 93 (31.0%), 75 (27.7%), 53 (100%); anal. calcd. for C34H37BrO2: C, 73.24; H, 6.69%; found: C, 73.13; H, 6.71%.

1,3-Dibromo-5-(2-(4-(heptyloxy)phenyl)ethynyl)benzene (5b): yield: 418.5 mg (93%) as white crystals; m.p. 96 ºC; IR (KBr) υmax/cm-1 3046, 2927, 2131, 1596, 1464, 1243; 1H NMR (300 MHz, CDCl3) δ 0.93 (t, 3H, J 5.5 Hz), 1.28-1.84 (m, 10H), 3.97 (t, 2H, J 8.52 Hz), 6.90-7.15 (m, 2H), 7.43-7.47 (m, 2H), 7.58 (s, 2H), 7.61 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.5, 26.2, 28.7, 29.1, 31.9, 68.1, 85.2, 92.3, 114.0, 114.5, 122.5, 127.2, 132.8, 133.2, 133.6, 159.8; MS (EI, 70 eV) m/z 450 (M+, 3.8%), 433 (74.8%), 332 (29.6%), 234 (97.9%), 121 (100%), 93 (25.0%), 64 (47.2%), 56 (26.8%); anal. calcd. for C21H22Br2O: C, 56.02; H, 4.93%; found: C, 56.29; H, 4.78%.

1-Bromo-3,5-bis(2-(4-(heptyloxy)phenyl)ethynyl)benzene (6b): yield: 23.4 mg (4%) as white powder; m.p. 55-56 ºC; IR (KBr) υmax/cm-1 3042, 2923, 2219, 1550, 1463, 1249; 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 6H, J 6.8 Hz), 1.28-1.83 (m, 20H), 3.99 (t, 4H, J 6.9 Hz), 6.88-6.97 (m, 4H), 7.44 (d, 4H, J 7.7 Hz), 7.47-7.54 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 14.2, 22.8, 26.2, 29.1, 29.6, 31.8, 68.1, 86.1, 91.2, 114.1, 114.4, 121.8, 132.4, 133.0, 133.3, 134.2, 159.4; MS (EI, 70 eV) m/z 585 (M+, 6.6%), 519 (6.9%), 457 (7.8%), 254 (9.0%), 80 (52.9%), 64 (73.7%), 57 (100%), 50 (18.8%); anal. calcd. for C36H14BrO2: C, 73.83; H, 7.06%; found: C, 73.59; H, 7.15%.

1,3-Dibromo-5-(2-(4-(octyloxy)phenyl)ethynyl)benzene (5c): Yield: 417.5 mg (90%) as white powder; m.p. 58-59 ºC; IR (KBr) υmax/cm-1 3040, 2922, 2213, 1577, 1463, 1250; 1H NMR (300 MHz, CDCl3) δ 0.93 (t, 3H, J 5.4 Hz), 1.28-1.85 (m, 12H), 3.98 (t, 2H, J 6.5 Hz), 6.85-6.91 (m, 2H), 7.42-7.47 (m, 2H), 7.58 (s, 2H), 7.61 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.6, 26.0, 29.1, 29.2, 29.3, 31.8, 68.1, 85.2, 92.3, 113.9, 114.6, 122.6, 127.2, 132.7, 133.2, 133.4,159.8; MS (EI, 70 eV) m/z 464 (M+, 29.4%), 352 (100%), 350 (54.7%), 192 (23.3%), 163 (37.4%), 71 (13.9%), 57 (44.4%), 55 (28.9%); anal. calcd. for C22H24Br2O: C, 56.92; H, 5.21%; found: C, 56.85; H, 5.09%.

1-Bromo-3,5-bis(2-(4-(octyloxy)phenyl)ethynyl)benzene (6c): yield: 49 mg (8%) as white crystals; m.p. 63 ºC; IR (KBr) υmax/cm-1 3042, 2923, 2205, 1589, 1464, 1247; 1H NMR (300 MHz, CDCl3) δ 0.91 (t, 6H, J 6.6 Hz), 1.28-1.83 (m, 24H), 3.99 (t, 4H, J 6.5 Hz), 6.83-6.89 (m, 4H), 7.44 (d, 4H, J 7.8 Hz), 7.47-7.58 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.6, 26.0, 29.1, 29.2, 29.3, 31.8, 68.1, 86.0, 91.4, 114.3, 114.6, 121.8, 132.7, 133.1, 133.3, 133.9, 159.7; MS (EI, 70 eV) m/z 614 (M+, 39.2%), 502 (12.5%), 390 (67.7%), 250 (10.9%), 71 (56.7%), 57 (100%), 55 (57.1%); anal. calcd. for C38H45BrO2: C, 74.37; H, 7.39%; found: C, 74.05; H, 7.19%.

Synthesis of 1-(2-(3-bromo-5-(2-(4-(octyloxy)phenyl)ethynyl)phenyl)ethynyl)-4-(heptyloxy)-benzene (7)

To PdCl2(PPh3)2 (7 mg, 0.01 mmol), CuI (3.8 mg, 0.02 mmol) in toluene (1 mL) and Et3N (140 µL, 2 mmol) in water (1 mL) were added 1-(2-(3,5-dibromophenyl)ethynyl)-4-(octyloxy)benzene 5c (464.2 mg, 1 mmol) and 1-ethynyl-4-(heptyloxy)benzene 3b (216 mg, 1 mmol) under argon atmosphere. The reaction mixture was stirred for 24 h at 60 °C. Two phases of the resulting mixture were separated and the aqueous layer was extracted three times with diethyl ether (3 × 30 mL). The combined extracts were evaporated under reduced pressure to leave a crude solid, which was purified by flash column chromatography on silica gel using hexane/ethyl acetate (10:1) to furnish 7 (40% yield) and 8 (4% yield).

1-Bromo-3-(2-(4-(heptyloxy)phenyl)ethynyl)-5-(2-(4-(octyloxy)phenyl)ethynyl)benzene (7): yield: 239.5 mg (40%) as white powder; m.p. 56-57 ºC; IR (KBr) υmax/cm-1 3096, 2926, 2205, 1595, 1464, 1246; 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 6H, J 4.3 Hz), 1.28-1.82 (m, 22H), 3.95-4.00 (m, 4H), 6.83-6.89 (m, 4H), 7.42-7.44 (m, 4H), 7.45-7.46 (m, 2H), 7.58 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.6, 22.7, 25.9, 29.0, 29.15, 29.18, 29.2, 29.3, 29.7, 31.7, 68.1, 68.2, 81.9, 85.9, 87.9, 91.4, 114.5, 114.6, 121.8, 125.7, 125.8, 125.9, 132.7, 132.8, 133.9, 158.9, 159.7; MS (EI, 70 eV) m/z 599 (M+, 17.0%), 598 (40.9%), 586 (24.7%), 390 (100%), 250 (18.9%), 96 (11.9%), 71 (20.9%); anal. calcd. for C37H43BrO2: C, 74.11; H, 7.23%; found: C, 73.85; H, 7.09%.

1,3-Bis(2-(4-(heptyloxy)phenyl)ethynyl)-5-(2-(4-(octyloxy)phenyl)ethynyl)benzene (8): yield: 29 mg (4%) as yellow oil; IR (KBr) υmax/cm-1 3048, 2925, 2208, 1602, 1465, 1247; 1H NMR (300 MHz, CDCl3) δ 0.92 (m, 9H), 1.28-1.80 (m, 32H), 3.96-4.01 (m, 6H), 6.87-6.90 (m, 6H), 7.44-7.47 (m, 6H), 7.59 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 14.0, 22.6, 25.9, 29.0, 29.2, 29.7, 31.7, 68.2, 86.7, 90.5, 114.7, 124.3, 133.1, 133.4, 159.5; MS (EI, 70 eV) m/z 735 (M+, 17.0%), 718 (15.9%), 575 (19.5%), 486 (24.5%), 462 (36.7%), 410 (24.5%), 351 (23.6%), 220 (43.7%), 107 (74.5%), 82 (100%), 65 (34.7%), 50 (13.5%); anal. calcd. for C52H62O3: C, 84.97; H, 8.50%; found: C, 84.85; H, 8.48%.

Synthesis of 1-(2-(4-(heptyloxy)phenyl)ethynyl)-3-(2-(4-(octyloxy)-phenyl)ethynyl)-5-(2-phenylethynyl)benzene (10)

To a mixture of 1-(2-(3-bromo-5-(2-(4-(octyloxy)phenyl)-ethynyl)phenyl)ethynyl)-4-(heptyloxy)benzene (7) (599 mg, 1 mmol) and phenylethyne (9) (90 µL, 1 mmol), in toluene (1 mL) and water (1 mL), was added Et3N (140 µL, 2 mmol) followed by adding PdCl2(PPh3)2 (7 mg, 0.01 mmol) then CuI (3.8 mg, 0.02 mmol) under argon atmosphere. The reaction mixture was stirred for 24 h at 60 °C. Two phases of the resulting mixture were separated and the aqueous layer was extracted three times with diethyl ether (3 × 30 mL). The combined extracts were evaporated under reduced pressure to leave a crude solid, which was purified by flash column chromatography on silica gel using hexane/ethyl acetate (10:1) to give compound 10 in 372.5 mg (60% yield) as yellow oil. IR (KBr) υmax/cm-1 3046, 2922, 2205, 1573, 1464, 1246; 1H NMR (300 MHz, CDCl3) δ 0.91-0.94 (m, 6H), 1.30-1.84 (m, 22H), 3.99 (t, 4H, J 6.4 Hz), 6.90 (d, 4H, J 6.7 Hz), 7.37-7.39 (m, 3H), 7.49 (d, 4H, J 5.7 Hz), 7.56 (d, 2H, J 3.9 Hz), 7.63 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.6, 22.6, 25.9, 26.0, 29.0, 29.1, 29.2, 29.3, 29.6, 29.7, 31.7, 31.8, 68.1, 86.6, 88.0, 90.3, 90.7, 114.5, 114.6, 122.9, 123.9, 124.4, 128.3, 128.5, 131.7, 132.8, 133.1, 133.5, 133.7, 159.5; MS (EI, 70 eV) m/z 621 (M+, 22.5%), 598 (0.4%), 430 (29.9%), 406 (36.3%), 234 (51.2%), 210 (100%), 181 (18.2%), 57 (70.3%), 55 (20.6%); anal. calcd. for C45H48O2: C, 87.05; H, 7.79%; found: C, 86.87; H, 7.68%.

 

Supplementary Information

Supplementary data are available free of charge at http://jbcs.sbq.org.br as PDF file.

 

Acknowledgments

The authors are greatly indebted to Faculty of Science, Cairo University for the financial support.

 

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Submitted: February 28, 2014
Published online: July 15, 2014

 

 

* e-mail: dr_dawood@yahoo.com

 

 

Supplementary Information

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

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