Materials and methods
All melting points were measured on a Gallenkamp melting point apparatus. The infrared spectra were recorded in potassium bromide discs on a Pye Unicam SP 3–300 and Shimadzu FT IR 8101 PC infrared spectrophotometers. The NMR spectra were recorded in deuterated chloroform (CDCl3) or dimethyl sulfoxide (DMSO-d
6
). On a Varian Mercury VXR-300 NMR spectrometer. Chemical shifts were related to that of the solvent. Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX mass spectrometer at 70 eV. Elemental analyses were recorded on a Elementar-Vario EL automatic analyzer at the Micro-analytical Centre of Cairo University, Giza, Egypt. Formamidine 3 is prepared according to our pervious reported work [39] (Scheme 6). The Microwave irradiation was carried out on a CEM mars machine. CEM has several vessel types that are designed for their ovens: Closed-system vessels including the HP-500 (500 psig material design pressure and 260 °C), pictured below, have liners are composed of PFA and are ideal for many types of samples. HP-500 Plus vessels are ideal for routine digestion applications. Process up to 14 high-pressure vessels per run with temperatures up to 260 °C or pressures up to 500 psi (Scheme 7).
Synthesis of the Pd(II)-complex (4)
A solution of sodium tetrachloropalladate (1 mmol), in methanol (2 mL) was added dropwise to a stirred solution of the formamidine 3 (1 mmol) in methanol (10 mL). After stirring for 1 h, the yellow precipitate was filtered off, washed with methanol and dried. The complex 4 was obtained as yellow powder (70%). mp 250 °C; 1H NMR (DMSO-d
6
) δ 356 (s, 6H, 2CH3), 6.53–6.55 (m, 2H, Py-H), 7.25–7.27 (d, 1H, Py-H), 7.46–7.48 (d, 1H, Py-H), 8.35 (s, 1H, CH); Anal. Calcd for C16H14Cl2N2OPdS: C, 41.80; H, 3.07; N, 6.09. Found: C, 41.68; H, 3.31; N, 6.03.
Suzuki coupling of simple aryl halides
Effect of concentration of the Pd-complex 4 on the Suzuki coupling of 4-bromoacetophenone with phenylboronic acid in water under thermal conditions
A mixture of 4-bromoacetophenone (5) (199 mg, 1 mmol) and phenylboronic acid (6a) (146 mg, 1.2 mmol), tetrabutylammonium bromide (TBAB) (194 mg, 0.6 mmol), Pd-complex 4 (1 mol%), KOH (112 mg, 2 mmol) and water (10 mL) was stirred at 110 °C under open air for 2 h to give 4-acetyl-1,1′-biphenyl (7). The same experiment was repeated using Pd-complex 4 in 0.75 mol%. The amount (mol%) of the Pd-complex 4 was changed with respect to 4-bromoacetophenone (0.5, 0.25, 0.125, 0.05, 0.025, and 0.005 mol% of Pd-complex 4 with scales: 1, 1, 2, 5, 10, and 20 mmol of 4-bromoacetophenone, respectively). The molar ratio of the reaction components were, in all cases, as follows; 4-bromoacetophenone, phenylboronic acid, TBAB, KOH, water: 1/1.2/0.6/2/10 mL water (Scheme 8). The yield% versus concentration of Pd-complex 4 is outlined in Table 1.
4-Acetyl-1,1′-biphenyl (
7a
) White solid; mp. 118–120 °C (lit. mp. 119–120 °C); 1H NMR (CDCl3) δ 2.64 (s, 3H, CO CH3), 7.38–7.52 (m, 3H), 7.66–7.70 (d, 2H, J = 6.9 Hz), 7.71 (d, 2H, J = 7.5 Hz), 8.03 (d, 2H, J = 7.5 Hz); MS m/z (%) 196 (49.3, M+), 181 (100), 152 (61.4), 127 (5.2), 76 (9).
Effect of base and solvent on Suzuki cross-coupling of 4-bromoacetophenone with phenylboronic acid under thermal heating
A mixture of 4-bromoacetophenone (5) (199 mg, 1 mmol) and phenylboronic acid (6a) (146 mg, 1.2 mmol), TBAB (194 mg, 0.6 mmol) (in case of using water as a solvent), Pd-complex 4 (0.25 mol%), a base (2 mmol) and solvent (10 mL) was stirred under reflux in open air for 2 h to give acetyl-1,1′-biphenyl (7). The molar ratio of the reaction components were, in all cases, as follows; 4-bromoacetophenone, phenylboronic acid, tetrabutylammonium bromide (in case of water), base, solvent: 1/1.2/0.6/2/10 mL. The yield% versus different solvents and bases is outlined in Table 2.
Effect of base and solvent on Suzuki cross-coupling of 4-bromoacetophenone with phenylboronic acid under microwave heating
A mixture of 4-bromoacetophenone (5) (199 mg, 1 mmol) and phenylboronic acid (6a) (146 mg, 1.2 mmol), TBAB (194 mg, 0.6 mmol), Pd-complex 4 (0.25 mol%), KOH (112 mg, 2 mmol) and water (10 mL) was lunched in the specified CEM reaction vessel HP-500 at a given temperature for 5 min to give acetyl-1,1′-biphenyl (7).
Suzuki cross-coupling of other aryl halides with phenylboronic acid in water under thermal heating
General procedure
A mixture of the appropriate aryl halides 5 or 8 (1 mmol), and phenylboronic acid (6a) (146 mg, 1.2 mmol), tetrabutylammonium bromide (194 mg, 0.6 mmol), Pd-complex 4 (0.25 mol%), KOH (112 mg, 2 mmol), and distilled water (5–10 mL) was stirred at 110 °C in open air until the reaction was complete (TLC-monitored) as listed in Tables 3 and 4. The cross-coupled product was then extracted with ethyl acetate (3 × 20 mL). The combined organic extracts were dried over anhydrous MgSO4 then filtered and the solvent was evaporated under reduced pressure. The residue was then subjected to separation via flash column chromatography with n-hexane/EtOAc (9:1) as an eluent to give the corresponding pure cross-coupled products 7b–g.
Suzuki cross-coupling of aryl bromides with phenylboronic acid in water under microwave irradiation
General procedure
A mixture of the appropriate aryl bromides 5 (1 mmol), and phenylboronic acid (6a) (146 mg, 1.2 mmol), tetrabutylammonium bromide (194 mg, 0.6 mmol), Pd-complex 4 (0.25 mol%), KOH (112 mg, 2 mmol), and distilled water (10 mL) were mixed in the specified CEM reaction vessel HP-500. The mixture was heated under microwave irradiating conditions at 110 °C and 300 Watt for 10 min. After the reaction was complete (monitored by TLC), the reaction mixture was extracted with ethyl acetate (3 × 20 mL). The combined organic extracts were dried over anhydrous MgSO4 then filtered and the solvent was evaporated under reduced pressure. The products 7b–g were purified by flash column chromatography as described above. The yields% are outlined in Table 3.
1,1′-Biphenyl (
7b
)
1H NMR (CDCl3) δ 7.34–7.40 (m, 2H), 7.45-7.56 (m, 6H), 8.26 (d, 2H, J = 8.1 Hz); MS m/z (%) 154 (36.8, M+), 77 (100), 50 (42.1).
2-Acetylbiphenyl (
7c
)
1H NMR (400 MHz, CDCl3) δ: 7.57–7.49 (m, 4H); 7.45–7.38 (m, 3H); 7.37–7.33 (m, 2H); 2.01–1.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 205.0, 141.2, 140.9, 140.8, 130.9, 130.5, 129.1, 128.9, 128.1, 127.7, 30.6; MS: 196 (M+), 181, 152.
4-Methoxy-1,1′-biphenyl (
7d
)
1H NMR (CDCl3) δ 3.87 (s, 3H, –OCH3), 6.99 (d, 2H, J = 8.7 Hz), 7.31–7.45 (m, 3H), 7.54 (d, 2H, J = 9 Hz), 7.57 (d, 2H, J = 7.2 Hz); MS (m/z) (%) 184 (100, M+), 169 (54.0), 141 (37.4), 115 (16.6), 89 (12.5), 76 (49.8), 63 (25.7).
4-phenylbenzoic acid (
7e
)
1H NMR (500 MHz, DMSO-d6): δ (ppm) 13.17(s, 1H), 8.03 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.74 (t, J = 4.2 Hz, 2H), 7.51 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.2 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): δ (ppm) 167.4, 143.8, 139.1, 130.5, 129.9, 129.0, 128.2, 126.9, 126.6.
4-Methylbiphenyl (
7f
)
1H NMR (400 MHz, CDCl3) δ: 7.67–7.26 (m, 9H); 2.492.41 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 141.5, 138.7, 137.3, 129.8, 129.0, 127.3, 127.3, 21.4; MS: 168 (M+), 152.
4-Hydroxy-1,1′-biphenyl (
7g
)
1H NMR (CDCl3) δ 5.05 (s, 1H, OH), 6.92 (d, 2H, J = 7.8 Hz), 7.30–7.38 (m, 1H), 7.40–7.45 (m, 2H), 7.49 (d, 2H, J = 8.1 Hz), 7.56 (d, 2H, J = 8.4 Hz); MS m/z (%) 170 (100, M+), 141 (32.3), 115 (20.0), 63 (10.3), 51 (12.9).
Suzuki coupling of 2-bromothiophene with phenylboronic acid in water under thermal conditions
A mixture of 2-bromothiophene 9 (1 mmol) and phenylboronic acid (6a) (1.2 mmol), tetrabutylammonium bromide (TBAB) (194 mg, 0.6 mmol), the Pd-complex 4 (1 mol%), KOH (112 mg, 2 mmol) in water (10 mL) was stirred at 110 °C in open air and the reaction was monitored by TLC. After the reaction was completed, the cross-coupling products were then extracted with ethyl acetate (3 × 20 mL). The combined organic extracts were dried over anhydrous MgSO4 then filtered and the solvent was evaporated under reduced pressure. The residue was then subjected to a flash column chromatography with n-hexane/EtOAc (10:1) as an eluent to give the corresponding pure 2-phenylthiophene 10.
2-Phenylthiophene (
10
)
1H NMR (CDCl3) δ 7.02 (d, 1H, J = 3.0 Hz), 7.06 (d, 1H, J = 3.6 Hz), 7.08–7.17 (m, 3H), 7.33–7.40 (m, 2H), 7.49 (d, 1H, J = 7.8 Hz), 7.59 (d, 1H, J = 7.8 Hz); MS m/z (%) 160 (M+, 100), 134 (33.8), 115 (56.1), 102 (14. 7), 63 (35.5), 45 (56.2).
Suzuki coupling of 4-bromoacetophenone with arylboronic acids in water under microwave irradiation condition
A mixture of 4-bromoacetophenone (5) (1 mmol) and the appropriate arylboronic acid 6 (1.2 mmol), tetrabutylammonium bromide (TBAB) (194 mg, 0.6 mmol), the Pd-complex 4 (0.25 mol%), KOH (112 mg, 2 mmol) in water (10 mL) was refluxed (under thermal conditions) or mixed in a process glass vial (under microwave irradiation conditions). After the reaction was complete, the cross-coupled products were then extracted with EtOAc (3 × 20 mL). The combined organic extracts were dried over anhydrous MgSO4 then filtered and the solvent was evaporated under reduced pressure. The residue was then subjected to separation via flash column chromatography with n-hexane/EtOAc (10:1) as an eluent to give the corresponding pure cross-coupled products 11a–e (Table 5).
4-Acetyl-4′-Methy-1,1′-biphenyl (
11a) 1H NMR (CDCl3) δ 2.42 (s, 3H, Ar CH3), 2.64 (s, 3H, CO CH3), 7.26 (d, 2H), 7.53 (d, 2H), 7.68 (d, 2H), 8.03 (d, 2H); MS m/z (%)210 (70.9, M+).
4-Acetyl-4′-Chloro-1,1′-biphenyl (
11b) 1H NMR (CDCl3) δ 2.64 (s, 3H, CO CH3), 7.33(d, 2H), 7.63 (d, 2H), 7.76 (d, 2H), 8.02 (d, 2H); MS m/z (%) 230 (59, M+).
4-Acetyl-4′-fluoro-1,1′-biphenyl (
11c
)
1H NMR (CDCl3) δ 2.64 (s, 3H, CO CH3), 7.14–7.16 (m, 2H), 7.57–7.65 (m, 4H), 8.202 (d, 2H); MS m/z (%) 214 (47, M+).
4-Acetyl-3′-amino-1,1′-biphenyl (
11d
)
1H NMR (CDCl3) δ 2.63 (s, 3H, CO CH3), 3.74 (br, 2H), 6.73 (d, 1H), 6.93 (s, 1H), 7.00–7.03 (1, 2H), 7.25–7.28 (t, 1H), 7.66 (d, 2H), 8.01 (d, 2H); MS m/z (%) 211 (64, M+).
4-Acetyl-2′,4′,6′-trimethyl-1,1′-biphenyl (
11e
)
1H NMR (CDCl3) δ 2.01 (s, 6H, 2 Ar–CH3), 2.53 (s, 3H, Ar–CH3), 2.66 (s, 3H, CO–CH3), 6.97 (s, 2H), 7.28 (d, 2H), 8.05 (d, 2H); MS m/z (%) 238 (31.6, M+).