4-ETHYNYLBENZALDEHYDE

Compound 4 (727 mg, 3.6 mmol) was dissolved in 15 mL of anhydrous THF and 2 mL of aqueous KOH solution was added(298 mg, 4 mmol), reacted at room temperature for 2 h. The THF was spin-dried. The reaction was extracted with EA and washed three times with saturated NaCl solution.The organic phase was dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography with PE and DCM (1:1 by volume) to give 450 mg of compound 5 as a pale yellow solid. The yield is 97percent.B. 4-ethynylbenzaldehyde; A degassed solution of 4-bromobezaldehyde (6.0 g, 32.4 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) in 60 mL of anhydrous triethylamine was added ethynyltrimethylsilane (26.7 mL, 48.6 mmol) followed by palladium (II) acetate (0.072 g, 0.32 mmol) at room temperature under argon atmosphere. The reaction mixture was heated at reflux for 2 h in sealed tube. The reaction mass was cooled to room temperature and the precipitated solid was filtered. The filtrate was concentrated to provide crude compound. The crude compound was purified by column chromatography (silica gel, 100-200 mesh) by using 1percent ethyl acetate in pet-ether as mobile phase to provide 4- ((trimethylsilyl)ethynyl)benzaldehyde (5.2 g, 80percent). This compound was taken up in methanol (100 mL), to which potassium carbonate (0.341 g, 2.47 mmol) was added at room temperature. The reaction mass was stirred for 2 h. The solvent was removed under reduced pressure and the residue was diluted with dichloromethane (50 mL). The organic solution was washed with water (50 mL), brine solution (25 mL), dried over anhydrous magnesium sulfate and evaporated under reduced pressure to get 4-ethynylbenzaldehyde as light brown solid (3.0 g, 94percent).LC-MS: [M+H]+ 131.2 Mass: calculated for C9H6O, 130.15IH NMR (400 MHz, δ ppm, CDC13): δ 10.02 (s, IH), 7.85 (d, 2H), 7.65 (d, 2H), 3.29 (s, IH)4-((Trimethylsilyl)ethynyl)benzaldehyde (2.0 g, 10.0 mmol) and KOH (561 mg, 10.0 mmol) were dissolved in the mixed solvents of CHThis compound (8.00 g, 39.59 mmol) was treated with KThis compound (8.00 g, 39.59 mmol) was treated with KThis compound (8.00 g, 39.59 mmol) was treated with K2CO3 (0.500 g) in methanol (50 mL) at 25 C. for 2 hours, under Argon. The solvent was removed under vacuum and the residue dissolved in dichloromethane (100 mL). This solution was washed once with an aqueous saturated solution of NaHCO3 and once with water, before being dried over anhydrous Na2SO4 and the solvent evaporated under vacuum. The yellow residue was purified by column chromatography using dichloromethane/petroleum ether 1:4 for elution and recrystallization from cold cylohexane to give 4.40 g (85.5percent yied) of the title compound; MS (EI) m/e 130.0; (M+). 1H-NMR (CDCl3) ' ppm: 3.30 (s, 1H, CH), 7.64 (d, 2H, ArH, J=8.1 Hz), 7.84 (d, 2H, ArH, J=8.1 Hz), 10.02 (s, 1H, CHO).A deaerated solution of 4-bromobenzaldehyde (3, 4.87 g, 25 mmol), triphenylphosphine (0.33 g, 1.25 mmol), PdCl2 (45 mg, 0.25 mmol), and Cu(OAc)2 (48 mg, 0.25 mmol) inanhydrous triethylamine (60 mL) was treated with trimethylsilylacetylene (5.5 mL, 38 mmol). The mixture wasbrought to reflux for 6 h. After cooling, the precipitated triethylamine hydrobromide was filtered off, and thesolvent was evaporated. The crude material was purified by silica gel column chromatography (silica gel 120 g, hexanes/ethyl acetate = 90/10), affording 4-((trimethylsilyl)ethynyl)benzaldehyde (4.49 g, 89percent yield) as a yellowsolid. 4-((Trimethylsilyl)ethynyl)benzaldehyde (4.05 g, 20 mmol) was treated with K2CO3 (2.28 mg, 2 mol) inMeOH (24 mL) at room temperature for 24 h. The solvent was removed in vacuo. The crude material was purifiedby silica gel column chromatography (silica gel 120 g, hexanes/ethyl acetate = 90/10), affording 4-ethynylbenzaldehyde (5; 2.20 g, 85percent yield) as a yellow solid.To a mixture of PdCl2(PPh3)2 (175 mg, 0.3 mmol) andCuI (190 mg, 1.0 mmol) in THF (30 mL), 4-bromobenzaldehyde (1.85 g, 10 mmol), trimethylsilyl acetylene(1.12 mL, 12 mmol), and NEt3 (10 mL) were added.The resulted mixture was stirred for 24 h at room temperature.The solvent was removed and 30 mL CH2Cl2 wasadded. The mixture was washed with water (3 30 mL). Theorganic phase was dried with MgSO4 and the solvent wasremoved by rotary evaporation. Purification by columnchromatography (Silica gel, CH2Cl2/hexane 1:2) gave 4-(2-(trimethylsilyl)ethynyl) -benzaldehyde derivative as whitesolid (yield 85percent).To a stirred solution of 4-(2-(trimethylsilyl)ethynyl) benzaldehyde(5 mmol) in CH3OH (30 mL), K2CO3 (69 mg, 0.5mmol) was added. The mixture was stirred for 24 h at roomtemperature, and the solvent was removed. The residue wasdiluted with 30 mL Et2O and washed with water (3 30mL). The organic phase was dried over MgSO4 and the solventwas removed by rotary evaporation. Purification by aflash colum chromatography (Silica gel, Et2O) provide 5 aswhite solid (546 mg, yield 84percent).1H NMR (400 MHz, CDCl3) 10.04 (s, 1H), 7.87 (d, J =8.0, 2H), 7.67 (d, J = 8.0, 2H), 3.32 (s, 1H).A solution of 545 4-((trimethylsilyl)ethynyl)benzaldehyde (7.5 g, 37.12 mmol) in 124 methanol (100 mL) was charged with 63 potassium carbonate (512 mg, 3.712 mmol) and stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate and separated organic layer was washed with water. The separated organic layers were dried over anhydrous NaA solution of p-bromobenzaldehyde (2 mmol, 370 mg)Was dissolved in 15 ml of anhydrous triethylamine, Vacuum, Replaced with argon three times, Weigh Pd (PPh3) 2Cl2 (0.06 mmol, 43 mg)PPh3 (0.06 mmol, 16 mg), CuI (0.02 mmol, 4 mg) was added.Then, 0.5 ml of trimethylsilylacetylene was injected.Heated to 70 degrees, The reaction was carried out for 6 hours and after cooling to room temperature, Filter out a white solid, Wash the filter cake several times with CH2Cl2.The solvent was removed under reduced pressure.Silica gel column.The resulting brown solid was then dissolved in methanol, K2CO3 (2 mmol, 390 mg)Room temperature reaction for 3 hours, Filter K2CO3, Pressurized to remove methanol, Over silica gel column, EluentFor petroleum ether: dichloromethane (1: 1), To obtain 195 mg, The yield was 75percent.To a solution of 4-Trimethylsilanylethynyl-benzaldehyde (4.0 g, 19.7 mmol) in methanol (50 mL) was added K2CO3 (275 mg, 1.97 mmol) at 25 °C. The reaction mixture stirred at same temperature over a period of 60 min. Methanol was evaporated to the half volume at 35 °C and it was diluted with ethyl acetate (500 mL). The organic layer washed with water (2X100 mL) and dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Ethynyl-benzaldehyde as a light yellow solid (1.8 g, 72 percent)To a solution of 4-Trimethylsilanylethynyl-benzaldehyde (4.0 g, 19.7 mmol) in methanol (50 mL) was added KTo a solution of 4-((trimethylsilyl)ethynyl)benzaldehyde (1.63 g, 8.06 mmol) in CH3OH (15 mL) was added K2CO3 (112 mg, 0.810 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, petroleum benzine ramping to petroleum benzine:EtOAc = 98:2) to give 10 as a pale yellow solid (750 mg, 71percent). RF (EtOAc:hexane = 1:5) 0.56. m.p. 9192 °C (lit. [7] m.p. 87 °C). IR νmax/cm-1 3223, 2837, 2739, 1695, 1601, 1561, 1388, 1294, 1207, 1165, 829. 1H NMR (400 MHz, CDCl3) δ 3.31 (s, 1H, C≡CH), 7.63 (d, 2H, J 8.0, Ph-H), 7.84 (d, 2H, J 8.0, Ph-H), 10.0 (s, 1H, CHO). 13C NMR (100 MHz, CDCl3) δ 81.2, 82.7, 128.4, 129.6, 132.8, 136.1, 191.5 (two carbon signals overlapping or obscured). MS (GC-EI) 101.0 ([MCHO]+, 41percent), 129.0 (M+, 100percent). The spectroscopic data were in agreement with those in the literature [7].A mixture of 4-((trimethylsilyl)ethynyl)benzaldehyde 4 (1g, 4.94 mmol) and potassium carbonate (1g, 7.41 mmol) were stirred in methanol (25 mL) at room temperature for 1 hour. The reaction mixture was diluted with ethylacetate (20 mL) and washed with water (2 x 20 mL) followed by brine solution. The organic solvent was concentrated under reduced pressure to obtain compound 5. Yellow solid; Yield: 0.29 g (90percent); M.p.: 84-86°C;IR (KBr): Umax 3454, 329, 3220, 2836, 2784, 2739, 2098, 1930, 1699, 1686, 1601, 1560, 1408, 1386, 1364, 1303, 1286, 1206, 1163, 1102, 1012, 975, 954, 924, 844, 829, 739, 679, 581, 530, 508 cm-1;1H NMR (400 MHz, CDCl3): d3.30 (1 H, s), 7.66 (d, J = 8.20 Hz, 2H), 7.86 (d, J = 8.20 Hz, 2H), 10.02 (s, 1H).15.0 mmol (2.78 g) of p-bromobenzaldehyde was dissolved in 95 ml of a tetrahydrofuran and triethylamine mixed solution (1: 1 by volume) and placed in a 250 ml single-necked flask, The cells were ventilated for 45 minutes and then 18.0 mmol (1.76 g)Of trimethylsilylacetylene. Adding 97.2 mg of triphenylphosphonium dichloride, 46.5mg cuprous iodide. Under argon, the reaction was carried out for 10 hours.After the reaction was stopped, the solvent was removed by distillation under reduced pressure and purified by silica gel column chromatography (developing solvent: dichloromethane: petroleum ether 1: 4), steamed and dried in vacuo to give 2.19 g of a white solid in 72.3percent yield.B: A solution of 8.0 mmol (1.62 g) of a product was dissolved in 30 mlMethanol and 60 ml of tetrahydrofuran, placed in a 250 ml single-necked round bottom flask, Then add anhydrous potassium carbonate, And the mixture was stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, Silica gel column (developing solvent for petroleum ether and dichloromethane 1: 1 mixed solvent) crude purification;Dried in vacuo to give 0.88 g of a white solid in 85.1percent

Molecular Weight:130.14
XLogP3:1.6
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:130.041864811
Monoisotopic Mass:130.041864811
Topological Polar Surface Area:17.1
Heavy Atom Count:10
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes