* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
POCl3 (4.73 mL, 50.79 mmol) was slowly added to a solution of DMF (6.56 mL, 84.75 mmol) while the temperature was maintained below 40 °C. Then, benzofuran 1 (2.00 g,16.93 mol) was added dropwise to this reaction mixture below 40 °C, over a period of 15 min. The mixture was heated at 80 °C for 24 h. The reaction mixture was then poured into ice-water and carefully quenched with a solution of sodium hydroxide. The organic material was separated, and the aqueous layer was extracted with ethyl acetate. It was washed with brine and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and was purified on silica gel column (petroleum ether: EtOAc = 10:1) to give product 2 (2.27 g, 90percent) as brown oil. 1H NMR (400 MHz,CDCl3): δ 9.83 (1H, s, COH), 7.75-7.70 (1H, m, H-4), 7.56-7.54 (2H, m, H-6,7), 7.46 (1H, s, H-3), 7.32-7.28 (1H, m, H-5). 13C NMR (100 MHz, CDCl3): δ 179.63 (COH), 156.03 (C-7a), 152.52 (C-2), 129.07 (C-3a), 126.51 (C-6), 124.05 (C-5), 123.58 (C-4), 117.93 (C-3), 112.44 (C-7).
80%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: at 20℃;
1. To a solution of benzofuran (1.5 g, 12.69 mmol) in 60 mL of THF, was added 5.08 mL(12.69 mmol) of n-BuLi solution in hexanes (2.5 M) at -78 °C. After 1 hr at -78 °C, the reaction mixture was added DMF (3.43 mL). After overnight at RT, the reaction was quenched with saturated ammonium chloride, and extracted with EtOAc (x3). The combined organic extracts were dried (MgS04), filtered, and concentrated. Flash chromatography (10 percentEtOAc/Hexanes) gave benzofuran-2-carbaldehyde (1.48 g, 80percent). *H NMR (400 MHz, CDC13) δ ppm: 9.88 (s, IH), 7.76 (d, J=8.4 Hz, IH), 7.62 (d, J=8.4 Hz, IH), 7.57 (s, IH), 7.52 (td, J=7.2, 1.2 Hz IH), 7.35 (td, J=7.2, 1.2 Hz, IH).
61%
Stage #1: With n-butyllithium; ammonium chloride In tetrahydrofuran; hexane at -78℃; for 0.5 h; Inert atmosphere Stage #2: at -78℃; for 1 h;
Step 1: benzofuran-2-carbaldehyde To a solution of benzofuran (10 g, 84.7 mmol) in dry THF was added n-BuLi (2.5 M solution in hexane, 33.9 mL, 84.7 mmol) dropwise at -78° C. under nitrogen, the mixture was stirred at -78° C. for 0.5 h, and then added DMF (19.6 mL, 254 mmol). The resulted mixture was kept at -78° C. and stirred for 1 h. The reaction was quenched by addition of saturated NH4Cl aqueous solution (20 mL), and then added ethyl acetate (300 mL) and H2O (100 mL), the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with water and brine, dried over sodium sulfate and concentrated under vacuum, the residue was purified by column chromatography on silica gel (ethyl acetate:petroleum ether=10:1) to afford benzofuran-2-carbaldehyde (7.5 g, yield: 61percent) as yellow oil. 1H NMR (400 MHz, CDCl3): δ 9.90 (s, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.59 (s, 1H), 7.53-7.57 (m, 1H), 7.35-7.39 (m, 1H).
40%
at 80℃;
Preparation of 2,3-Benzofuran-5-carboxaldehyde 39[0201] To a DMF (0.580 mL) solution of 2,3-benzofuran 38 (0.331 mL, 3.0 mmol) was added phosphorous oxychloride (0.302 mL, 3.3 mmol). The reaction mixture was stirred overnight at 80 °C, then the excess solvent was removed in vacuo. The residue was diluted with ethyl acetate (100 mL), then washed with water (2 X 20 mL). The organic layer was dried with brine and MgSC>4, then concentrated in vacuo. Flash column chromatography on silica gel (n-hexanes : ethyl acetate = 50:1) of the residue afforded the desired product 39 in 40percent yield (172 mg, yellow oil). LH NMR (400 MHz, CDC13): 9.88 (s, 1H), 7.76 (d, J= 7.2 Hz, 2H), 7.62 (dd, J= 8.4, 0.8 Hz, 1H), 7.54 (d, J= 0.8 Hz, 1H), 7.53 (td, J= 12, 1.2 Hz, 1H), 7.35 (td, J= 7.2, 0.8 Hz, 1H).
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POCl3 (4.73 mL, 50.79 mmol) was slowly added to a solution of DMF (6.56 mL, 84.75 mmol) while the temperature was maintained below 40 C. Then, benzofuran 1 (2.00 g,16.93 mol) was added dropwise to this reaction mixture below 40 C, over a period of 15 min. The mixture was heated at 80 C for 24 h. The reaction mixture was then poured into ice-water and carefully quenched with a solution of sodium hydroxide. The organic material was separated, and the aqueous layer was extracted with ethyl acetate. It was washed with brine and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and was purified on silica gel column (petroleum ether: EtOAc = 10:1) to give product 2 (2.27 g, 90%) as brown oil. 1H NMR (400 MHz,CDCl3): delta 9.83 (1H, s, COH), 7.75-7.70 (1H, m, H-4), 7.56-7.54 (2H, m, H-6,7), 7.46 (1H, s, H-3), 7.32-7.28 (1H, m, H-5). 13C NMR (100 MHz, CDCl3): delta 179.63 (COH), 156.03 (C-7a), 152.52 (C-2), 129.07 (C-3a), 126.51 (C-6), 124.05 (C-5), 123.58 (C-4), 117.93 (C-3), 112.44 (C-7).
80%
1. To a solution of benzofuran (1.5 g, 12.69 mmol) in 60 mL of THF, was added 5.08 mL(12.69 mmol) of n-BuLi solution in hexanes (2.5 M) at -78 C. After 1 hr at -78 C, the reaction mixture was added DMF (3.43 mL). After overnight at RT, the reaction was quenched with saturated ammonium chloride, and extracted with EtOAc (x3). The combined organic extracts were dried (MgS04), filtered, and concentrated. Flash chromatography (10 %EtOAc/Hexanes) gave benzofuran-2-carbaldehyde (1.48 g, 80%). *H NMR (400 MHz, CDC13) delta ppm: 9.88 (s, IH), 7.76 (d, J=8.4 Hz, IH), 7.62 (d, J=8.4 Hz, IH), 7.57 (s, IH), 7.52 (td, J=7.2, 1.2 Hz IH), 7.35 (td, J=7.2, 1.2 Hz, IH).
61%
Step 1: benzofuran-2-carbaldehyde To a solution of benzofuran (10 g, 84.7 mmol) in dry THF was added n-BuLi (2.5 M solution in hexane, 33.9 mL, 84.7 mmol) dropwise at -78 C. under nitrogen, the mixture was stirred at -78 C. for 0.5 h, and then added DMF (19.6 mL, 254 mmol). The resulted mixture was kept at -78 C. and stirred for 1 h. The reaction was quenched by addition of saturated NH4Cl aqueous solution (20 mL), and then added ethyl acetate (300 mL) and H2O (100 mL), the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with water and brine, dried over sodium sulfate and concentrated under vacuum, the residue was purified by column chromatography on silica gel (ethyl acetate:petroleum ether=10:1) to afford benzofuran-2-carbaldehyde (7.5 g, yield: 61%) as yellow oil. 1H NMR (400 MHz, CDCl3): delta 9.90 (s, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.59 (s, 1H), 7.53-7.57 (m, 1H), 7.35-7.39 (m, 1H).
40%
With trichlorophosphate; at 80℃;
Preparation of 2,3-<strong>[271-89-6]Benzofuran</strong>-5-carboxaldehyde 39[0201] To a DMF (0.580 mL) solution of 2,3-benzofuran 38 (0.331 mL, 3.0 mmol) was added phosphorous oxychloride (0.302 mL, 3.3 mmol). The reaction mixture was stirred overnight at 80 C, then the excess solvent was removed in vacuo. The residue was diluted with ethyl acetate (100 mL), then washed with water (2 X 20 mL). The organic layer was dried with brine and MgSC>4, then concentrated in vacuo. Flash column chromatography on silica gel (n-hexanes : ethyl acetate = 50:1) of the residue afforded the desired product 39 in 40% yield (172 mg, yellow oil). LH NMR (400 MHz, CDC13): 9.88 (s, 1H), 7.76 (d, J= 7.2 Hz, 2H), 7.62 (dd, J= 8.4, 0.8 Hz, 1H), 7.54 (d, J= 0.8 Hz, 1H), 7.53 (td, J= 12, 1.2 Hz, 1H), 7.35 (td, J= 7.2, 0.8 Hz, 1H).
Stage #1: 2-formylbenzo[b]furan With sodium tetrahydridoborate In methanol at 0 - 20℃; for 1.25h;
Stage #2: With water monomer In methanol for 0.25h;
10.A
A. To a stirred solution of benzofuran-2-carbaldehyde (0.39 mL, 3.2 mmol) in MeOH (10 mL) at 00C was added NaBH4 (60. mg, 1.6 mmol) portion wise. The mixture was stirred at 00C for 15 min. and then at ambient temperature for 1 hour 15 min. A small amount of water was added and the mixture was stirred for 15 min before rotary evaporation. The residue was purified to afford 2- (hydroxymethyl)benzofuran (479 mg, pale oil, 100%).
98%
With methanol; sodium tetrahydridoborate for 1h; Cooling with ice;
9.2 Step 2: benzothran-2-ylmethanol
Step 2: benzofuran-2-ylmethanol To an ice-cooling solution of benzofuran-2-carbaldehyde (4.0 g, 27.4 mmol) in methanol (40 mL) was added NaBH4 (1.55 g) in small portions. The resulted mixture was stirred for 1 h, and then the reaction was diluted with ethyl acetate (100 mL), the organic layer was washed with H2O (50 mL*3) and brine, dried over sodium sulfate, filtered and concentrated under vacuum to afford benzofuran-2-ylmethanol (4.0 g, yield: 98%) as yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.57-7.59 (m, 1H), 7.48-7.50 (m, 1H), 7.23-7.33 (m, 2H), 6.66 (s, 1H), 4.78 (s, 2H), 2.03 (brs, 1H).
98.9%
With hydrogenchloride; sodium tetrahydridoborate
6.1 3-(1-(1-(Benzofuran-2-ylmethyl)-1H-indole-7-carboxamido)cyclopropyl)bicyclo[1.1.1]pentane-1-carboxylic Acid 6
Step 1: Synthesis of benzofuran-2-ylmethanol 6-1 Benzofuran-2-carbaldehyde (3 g, 20.5 mmol) and anhydrous methanol (40 ml) were added successively to a reaction flask, and the resulting mixture was cool to 0° C. Sodium borohydride (0.545 g, 14.4 mmol) was added thereto in batches, and the the temperature was kept below 25° C. After completion of the addition, the reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was removed under reduced pressure. 1 N aqueous HCl solution (15 ml) was added, and the resulting mixture was stirred at room temperature for 5 minutes. The mixture was adjusted to the pH 8-9 with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate (10 ml*3). The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent and obtain compound 6-1 (3.0 g, 20.27 mmol, yield: 98.9%) as a yellow oil. MS (ESI): 149.1 [M+1]+. 1H NMR (400 MHz, CDCl3) δ: 7.55 (dd, J=8.4, 7.2 Hz, 1H), 7.47 (dd, J=8.8, 7.6 Hz, 1H), 7.29-7.19 (m, 2H), 6.66 (s, 1H), 4.77 (d, J=4.8 Hz, 2H).
98.9%
With methanol; sodium tetrahydridoborate at 0 - 25℃; for 1h;
6.1 Step 1: Synthesis of benzofuran-2-ylmethanol 6-1
Benzofuran-2-carbaldehyde (3 g, 20.5 mmol) and anhydrous methanol (40 ml) were added successively to a reaction flask, and the resulting mixture was cool to 0° C. Sodium borohydride (0.545 g, 14.4 mmol) was added thereto in batches, and the the temperature was kept below 25° C. After completion of the addition, the reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was removed under reduced pressure. 1 N aqueous HCl solution (15 ml) was added, and the resulting mixture was stirred at room temperature for 5 minutes. The mixture was adjusted to the pH 8-9 with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate (10 ml×3). The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent and obtain compound 6-1 (3.0 g, 20.27 mmol, yield: 98.9%) as a yellow oil. MS (ESI): 149.1 [M+1]+.1H NMR (400 MHz, CDCl3) δ: 7.55 (dd, J=8.4, 7.2 Hz, 1H), 7.47 (dd, J=8.8, 7.6 Hz, 1H), 7.29-7.19 (m, 2H), 6.66 (s, 1H), 4.77 (d, J=4.8 Hz, 2H)
98.9%
With methanol; sodium tetrahydridoborate at 0 - 25℃; for 1h;
6.1 Step 1: Synthesis of benzofuran-2-ylmethanol 6-1
Benzofuran-2-carbaldehyde (3 g, 20.5 mmol) and anhydrous methanol (40 ml) were added successively to a reaction flask, and the resulting mixture was cool to 0° C. Sodium borohydride (0.545 g, 14.4 mmol) was added thereto in batches, and the the temperature was kept below 25° C. After completion of the addition, the reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was removed under reduced pressure. 1 N aqueous HCl solution (15 ml) was added, and the resulting mixture was stirred at room temperature for 5 minutes. The mixture was adjusted to the pH 8-9 with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate (10 ml×3). The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent and obtain compound 6-1 (3.0 g, 20.27 mmol, yield: 98.9%) as a yellow oil. MS (ESI): 149.1 [M+1]+.1H NMR (400 MHz, CDCl3) δ: 7.55 (dd, J=8.4, 7.2 Hz, 1H), 7.47 (dd, J=8.8, 7.6 Hz, 1H), 7.29-7.19 (m, 2H), 6.66 (s, 1H), 4.77 (d, J=4.8 Hz, 2H)
96%
With sodium tetrahydridoborate In methanol at 0 - 20℃; for 2.25h;
3.2. Synthesis of benzofuran-2-ylmethanol (3)
To a stirred solution of compound 2 (2.27 g, 14.30 mmol) in methanol (20 mL) at 0 °C sodium borohydride (0.65 g, 17.16 mmol) was added in three portions over a period of 15 minutes, and then at room temperature for 2 h. TLC was used to monitor the reaction progress. A small amount of dilute HCl (1N) was added and the mixture was stirred for 20 min. The solvent was evaporated under vacuum and the residue was purified on silica gel column (petroleum ether:EtOAc = 5:1) to give product 3 (2.03 g, 96%) as white powder. 1H NMR (400 MHz, CDCl3): δ 7.45-7.35 (2H, m, H-4,7), 7.20-7.10 (2H, m, H-5,6), 6.46 (1H, s, H-3), 4.60 (2H,s, CH2), 4.34 (1H, br. s, OH). 13C NMR (100 MHz, CDCl3): δ 156.83 (C-7a), 155.32 (C-2), 128.34 (C-3a), 124.32 (C-6), 122.84 (C-5), 121.18 (C-4), 111.27 (C-7), 104.07 (C-3), 57.66 (CH2).
95%
Stage #1: 2-formylbenzo[b]furan With sodium tetrahydridoborate In methanol for 0.333333h;
Stage #2: With water monomer In methanol
17.1
Example 17 4-(Benzofuran-2-ylmethoxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[211] 2-Benzofurancarbaldehyde (2.2 g, 15 mmol) was dissolved in 25 mL of methanol. To this solution was added sodium borohydride (0.28 g, 7.5 mmol) in small portions over a period of 20 minutes. Then 2 mL of water were added and the mixture was evaporated. The residue was dissolved in ethyl acetate (75 mL) and washed with water (3 x 75 mL), dried (MgSO4) and evaporated, providing 2.1 g of benzofuran-2-yl-methanol, in 95% yield; 1H NMR (CDCl3) δ 2.03 (t, J = 6.1 Hz, IH), 4.77 (d, J = 6.1 Hz, 2H), 6.66 (s, IH), 7.19-7.32 (m, 2H), 7.45-7.50 (m, IH), 7.53-7.57 (m, IH).
93%
With sodium tetrahydridoborate In methanol at 0 - 20℃; for 4h;
93%
With sodium tetrahydridoborate In ethanol at 20℃;
92%
With 4-methyl-morpholine; tetrahydroxydiborane; 5%-palladium/activated carbon In 1,2-dichloro-ethane at 50℃; for 24h;
91%
With sodium tetrahydridoborate In methanol at -4 - 20℃; for 8h;
90%
With methanol; sodium tetrahydridoborate at 0 - 20℃; for 4h; Inert atmosphere;
83%
With CdS(x)Se(1-x) x:0-1;; caesium acetate; para-thiocresol In toluene Sealed tube; Inert atmosphere; Irradiation;
80%
With lithium tert-butylate In isopropanol at 20℃; for 36h; UV-irradiation;
With potassium hydroxide
With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78℃; for 1h;
With sodium tetrahydridoborate In ethanol; chloroform at 40 - 50℃; for 4h;
With sodium borohydride In methanol; water monomer; ethyl acetate
2.B Method B
Method B Benzofuran-2-carboxaldehyde (10.0 g, 68 mmol) was dissolved in methanol (70 mL) and cooled to 5° C. Sodium borohydride (2.58 g, 68 mmol) was charged portionwise at 5° C. The batch was aged at 5° C. for 40 minutes and allowed to warm to room temperature (22° C.). The reaction was judged complete by tlc (4:1 hexanes/EtOAc) and the reaction mixture was cooled to 5° C. DI water (20 mL) was charged and the solution was concentrated in vacuo. EtOAc (80 mL) was charged and the solution was washed with DI water (2*20 mL). The EtOAc layer was concentrated in vacuo to provide benzofuran-2-carbinol as an oil.
In methanol
2.A Method A
Method A Benzofuran-2-carboxaldehyde (10.0 g, 68 mmol) was dissolved in methanol (90 mL). 5% Pd/C (0.500 g) was charged and the reaction mixture was hydrogenated for 4.5 hours at 40 psi H2. The reaction was judged complete by tlc (4:1 hexanes/EtOAc) and the solution was filtered to remove the Pd/C and concentrated in vacuo to provide benzofuran-2-carbinol as an oil.
With sodium borohydride In methanol; water monomer; ethyl acetate
2.B Method B
Method B Benzofuran-2-carboxaldehyde (10.0 g, 68 mmol) was dissolved in methanol (70 mL) and cooled to 5 C. Sodium borohydride (2.58 g, 68 mmol) was charged portionwise at 5 C. The batch was aged at 5 C. for 40 minutes and allowed to warm to room temperature (22 C.). The reaction was judged complete by tlc (4:1 hexanes/EtOAc) and the reaction mixture was cooled to 5 C. DI water (20 mL) was charged and the solution was concentrated in vacuo. EtOAc (80 ml) was charged and the solution was washed with DI water (2*20 mL). The EtOAc layer was concentrated in vacuo to provide benzofuran-2-carbinol as an oil.
With sodium tetrahydridoborate In methanol at 20℃;
96 %Spectr.
With Aeroxide (Evonik) P25 TiO2, consisting of a 3:1 anatase/rutile mixture In methanol; acetonitrile at 20℃; for 20h; Schlenk technique; Inert atmosphere; UV-irradiation;
With sodium tetrahydridoborate
With sodium tetrahydridoborate In ethanol at 0 - 20℃; Inert atmosphere;
With sodium tetrahydridoborate In methanol at 0 - 20℃; Inert atmosphere;
General Procedure A
General procedure: To a solution of the aldehyde (1.0 equiv) in MeOH (0.50 M) at 0 C wasadded NaBH4 (2.4 equiv) in 5 parts. The resulting mixture was stirred at room temperature untilthe reaction was judged to have reached completion by TLC. A saturated aqueous solution ofNH4Cl was then added to the reaction mixture, the layers were separated and the aqueous phasewas extracted with EtOAc (3x). The combined organic layers were washed with brine (1x), driedover MgSO4 and concentrated under reduced pressure. The crude residue was directly carriedonto the next step and purified if necessary
With 1,3,5,7-tetrakis-(4-(diacetoxyiodo)phenyl)adamantane In dichloromethane at 20℃;
86%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutylammomium bromide; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at 0℃;
81%
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 1h;
81%
With 2,6-dimethylpyridine; 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In dichloromethane at 20℃;
81%
Stage #1: benzofuran-2-yl-methanol With 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In dichloromethane at 20℃;
Stage #2: With 2,6-dimethylpyridine In dichloromethane at 20℃;
55%
With manganese(IV) oxide In tetrachloromethane for 65h;
With manganese dioxide In dichloromethane
R.29 Preparation of 2-formylbenzofuran
Reference Example 29 Preparation of 2-formylbenzofuran A mixture of 2-hydroxymethylbenzofuran (6.91 g) and MnO2 (37.4 g) in CH2Cl2 (250 ml) was stirred at 30° C. for 3 days. Insoluble materials were filtered off and the filtrate was concentrated to give the titled compound (5.01 g) as colorless oil. 1H-NMR (CDCl3) δ: 7.35 (1H, dt, J=1.4, 7.4 Hz), 7.48-7.66 (3H, m), 7.76 (1H, dd, J=1.2, 8.0 Hz), 9.88 (1H, s). IR (KBr): 1682, 1611, 1557, 1289, 1121, 833 cm-1.
137.2 mg
With 5-bromo-3-oxo-1λ3-benzo[d][1,2]iodaoxol-1(3H)-yl acetate In chloroform at 60℃; for 24h;
With 5-bromo-3-oxo-1λ3-benzo[d][1,2]iodaoxol-1(3H)-yl acetate In chloroform at 60℃; for 24h;
Multi-step reaction with 2 steps
1: 1H-imidazole / dichloromethane / 20 °C
2: 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate / acetonitrile / 72 h / 40 °C
With manganese(IV) oxide In dichloromethane at 23℃;
With fluorosulfonyl fluoride; potassium carbonate; dimethyl sulfoxide at 20℃;
With sodium acetate In acetic acid for 0.75h; Heating;
84%
With piperidine In ethanol at 70℃; for 16h;
General procedure A for the Knoevenagel condensation of aldehydes with rhodanine
General procedure: The requisite aldehyde (0.560 mmol) was dissolved in EtOH (3 mL) before sequential addition of piperidine (0.056 mmol) and rhodanine (0.560 mmol). The flask was sealed, heated to 70 °C for 16 h and cooled to room temperature. Water (10 mL) was added and the resulting precipitate filtered, washing with water, ice-cooled EtOH and Et2O. The remaining solid was collected and dried under vacuum.
62%
With propylamine In neat (no solvent) at 80℃; for 1h; Microwave irradiation;
With sodium acetate In acetic acid at 135℃; for 12h;
General Procedure of the Knoevenagel condensation of arylaldehydes with various thiazolidin-4-ones, for example, preparation of (Z)-2-imino-5-((5-phenylfuran-2-yl)methylene)thiazolidin-4-one, 7a
General procedure: To a solution of the pseudothiohydantoin 6a (139 mg, 1.2 mmol), and sodium acetate (328 mg, 4.0 mmol) in acetic acid (5 ml) was added 5-phenyl-2-furaldehyde 5a (172 mg,1.0 mmol) at 25°C. The solution was refluxed at 135°C for 12 h. The precipitate was filtered and washed with water and diethyl ether. The filter cake was dried under high vacuum to afford 230 mg (85%) of compound 7a as an orange solid.
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium perchlorate; acetic acid; lithium hexamethyldisilazane; In acetonitrile; for 15h;Electrochemical reaction;
General procedure: Preparative electrolysis experiments were performed using 263 APotentiostat/Galvanostat (Princeton Applied Research, USA). 0.1 MNaClO4-CH3CN solution (10 mL) containing aldehydes (1 mmol),TEMPO (0.1 mmol), HMDS (2.5mmol) and AcOH (2.5mmol) was electrolyzedwith stirring in an undivided cell (30 mL) equipped with twoplatinum sheets as anode (1.5 cm2) and cathode (3.0 cm2) respectivelyat a constant potential of 1.5 V vs Ag/Ag+ (0.1MAgNO3 in acetonitrile).The electrode separation was 1 cm. When the reaction was finished,10mL of saturatedNa2SO3 solution was added into the reactionmixtureand stirred for 15 min. Then the mixture was extracted with CH2Cl2(20 mL × 3). The organic layer was dried with anhydrous Na2SO4 andconcentrated in a rotary evaporator. The productswere obtained via purificationof column chromatography and their structures were confirmedby 1H NMR, 13C NMR and MS. NMR was performed on a BrukerAvance III spectrometer. GC-MS was performed on the Thermo TraceISQ instrument with TG 5MS capillary column.
77%
With trifluorormethanesulfonic acid; trimethylsilylazide; In acetonitrile; at 20℃; for 0.333333h;Sealed tube; Inert atmosphere;
General procedure: To a solution of an aromatic aldehyde 1 (0.500 mmol, 1.0 equiv) and TMSN3 (115 mg, 1.00 mmol,2.0 equiv) in a premixed HFIP/ACN mixture (2.0 mL, 1:1) in a nitrogen-flushed two dram vial wasadded triflic acid (TfOH; 17.7 L, 0.200 mmol, 0.40 equiv) (exotherm and brisk effervescence due tonitrogen gas evolution was immediately observed). The vial was capped and the reaction mixture wasallowed to stir at rt for 20-75 min. The reaction mixture was concentrated under nitrogen. The residueobtained was suspended in CH2Cl2/hexanes mixture and loaded on a silica gel in a 5 g samplecartridge. Purification using a normal phase silica flash column on a CombiFlash purification systemafforded a corresponding aromatic nitrile 2 upon concentration of appropriate fractions.
72%
With tert.-butylhydroperoxide; ammonium acetate; iodine; sodium carbonate; In ethanol; at 50℃; for 5h;
In a 25 mL two-necked round bottom flask equipped with a thermometer and a magnetic stirrer4 mmolofBenzofuran-2-carbaldehyde (1-19), 6 mmol of NH4OAc, 4 mmol of Na2CO3, 4.4 mmol of TBHP, 0.1 mmol of I2, 5 mL of absolute ethanol Solvent, followed by placing the reaction flask in an oil bath preheated to 50 C and opening the magnetic stirrer for 5 h. The reaction solution By adding sodium thiosulfate solution, stirring, and then extracting with ether, separating the organic layer, and removing the solvent under reduced pressure, The eluate was collected with the mixture of ethyl acetate / petroleum ether in a volume ratio of 1: 100 as the eluent, and the eluate containing the target compound was collected. The solvent was distilled off to give benzofuran-2-carbonitrile with an isolated yield of 72%.
(E)-4-Benzofuran-2-yl-but-3-enoic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: 2-formylbenzo[b]furan; (2-carboxyethyl)triphenylphosphonium chloride With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 23℃; for 2.5h;
Stage #2: dimethyl sulfate In tetrahydrofuran at 23℃; for 15h;
With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium chloride In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; acetonitrile
1 3-(Benzo[d]furan-2-yl)acrylic Acid Methyl Ester
3-(Benzo[d]furan-2-yl)acrylic Acid Methyl Ester To a stirred suspension of lithium chloride (1.02 g; 24.1 mmol) in dry MeCN (200 mL) under nitrogen at room temperature was added drop-wise at 15 min intervals trimethyl phosphonoacetate (4.39; 24.0 mmol) in dry MeCN (15 mL), DBU (3.05 g; 20.0 mmol) in dry MeCN (10 mL) and finally benzo[b]furan-2-carboxaldehyde (2.92 g; 20.0 mmol) in dry MeCN (15 mL). The reaction was allowed to stir at room temperature until completion, as determined by TLC. The reaction mixture was filtered and concentrated under reduced pressure. The resulting yellow oil was dissolved in DCM (50 mL) and washed with distilled water (3*20 mL) and saturated sodium chloride solution (3*20 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give an off-white solid. Purification by recrystallization with hexanes gave an off-white crystalline solid (3.98; 98%): mp 84-86° C.; Rf0.60 (E); Rf0.51 (C); νmax (KBr): 3116, 1699, 1657, 1268, 1185, 956, 758 cm-1; m/z (EI): 202.0, 171.0, 143.0, 130.9, 88.8; δH (CDCl3, 200 MHz): 3.82 (3 H, s), 6.58 (1 H, d, J=15.8), 6.94 (1 H, s), 7.23 (1 H, td, J=7.2 and 1.2), 7.36 (1 H, td, J=7.2 and 1.6), 7.48 (1 H, dq, J=8.8 and 0.8), 7.56 (1 H, d, J=16.0), 7.58 (1 H, dq, J=7.8 and 0.8); δC (CDCl3, 126 MHz): 51.6, 111.0, 111.2, 118.3, 121.6, 123.1, 126.3, 128.2, 131.3, 152.1, 155.4, 166.9; m/z calculated for C12H10O3: 202.0630 (M+), found 202.0638 (M+).
122 2-(Benzofuran-2-ylmethoxy)-3-(1-piperazinyl)pyrazine, Hydrochloride*
Example 122 2-(Benzofuran-2-ylmethoxy)-3-(1-piperazinyl)pyrazine, Hydrochloride* Yield 44%; mp 160-161° C. Anal. (C17H18N4O2.HCl) C, H, N. *The starting material benzofuran-2-ylmethanol was obtained from benzofuran-2-carboxaldehyde by reduction with sodium borohydride.
With sodium acetate; In acetic acid; at 135℃; for 12h;
General procedure: To a solution of the <strong>[556-90-1]pseudothiohydantoin</strong> 6a (139 mg, 1.2 mmol), and sodium acetate (328 mg, 4.0 mmol) in acetic acid (5 ml) was added 5-phenyl-2-furaldehyde 5a (172 mg,1.0 mmol) at 25C. The solution was refluxed at 135C for 12 h. The precipitate was filtered and washed with water and diethyl ether. The filter cake was dried under high vacuum to afford 230 mg (85%) of compound 7a as an orange solid.
General Synthetic Procedure for Final Analogues (2i-5vi)
General procedure: A mixture of appropriate piperazine base (i-vi, 1 mmol), aldehydes (1a-1d, 1 mmol) and around 1.1-1.3 mmol quantity of TMSCN was taken in 5-8 mL water. After stirring for a while, 10 mg Indium powder was added to the reaction mixture and the resulted reaction mass was allowed to stir at room temperature for 45 min-2.5 h. After the completion ofthe reaction as monitored by Thin Layer Chro-matography using toluene: acetone (8:2) or ethyl acetate: n-nexane (8:2) solvent system, after treatment with diethyl ether or ethyl acetate, solution was filtered and washed with water and brine followed by anhydrous sodium sulphate treatment to dry. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane) to afford compounds 2i-5vi.
General procedure: A mixture of appropriate piperazine base (i-vi, 1 mmol), aldehydes (1a-1d, 1 mmol) and around 1.1-1.3 mmol quantity of TMSCN was taken in 5-8 mL water. After stirring for a while, 10 mg Indium powder was added to the reaction mixture and the resulted reaction mass was allowed to stir at room temperature for 45 min-2.5 h. After the completion ofthe reaction as monitored by Thin Layer Chro-matography using toluene: acetone (8:2) or ethyl acetate: n-nexane (8:2) solvent system, after treatment with diethyl ether or ethyl acetate, solution was filtered and washed with water and brine followed by anhydrous sodium sulphate treatment to dry. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane) to afford compounds 2i-5vi.
(E)-3-(benzofuran-2-yl)-1-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With sodium hydroxide In methanol at 20℃; for 72h; Inert atmosphere;
General Experimental Procedure for the Synthesis ofChalcone Derivatives (1a-1l)
General procedure: To a methanol solution containing apocynin (300 mg,1.80 mmol) was added sodium hydroxide (7.20 mmol) followedby the addition of benzaldehydes (a-l) (1.90 mmol)and the contents were stirred at room temperature for 24h-72h. The reaction mixture was diluted with water and acidifiedto pH = 3 using 1N HCl and extracted with ethyl acetate.The organic layer was washed with water followed bybrine solution, dried over anhydrous sodium sulphate, filteredand concentrated under reduced pressure, to obtain thepure compounds. Yields of the products varied between 78and 98%.
1-(benzofuran-2-yl)-2-(4-(methylthio)phenyl)ethanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
134 mg
Stage #1: 1-(chloromethyl)-4-methylthiobenzene With lithium manganese chloride; magnesium In tetrahydrofuran at 0℃; for 1.5h; Schlenk technique; Inert atmosphere;
Stage #2: 2-formylbenzo[b]furan In tetrahydrofuran at 0 - 25℃; Schlenk technique; Inert atmosphere;
Stage #3: With ammonium chloride In tetrahydrofuran; water Schlenk technique; Inert atmosphere;
General procedure: A dry and argon flushed Schlenk-flask, equipped with a magnetic stirring bar and a rubber septum was charged with magnesium (175 mg, 2.40 equiv), followed by dry THF (1 mL) or MTBE (1.9 mL) and a solution of MnCl2·2LiCl (3.75 mL, 1.25 equiv; 1.0 M in THF). The mixture was cooled to 0 °C, the benzyl chloride (3.0 mmol, 1.0 equiv) was added at once and the reaction was maintained at 0 °C still complete conversion of the starting material was observed (reaction of aliquots with iodine followed by GC analysis). When the insertion reaction was complete, the solution of benzyl manganese chloride was separated from the resulting salts via a syringe equipped with a filter and transferred to another Schlenk-flask, dry and argon flushed, before being titrated against iodine. A dry and argon flushed Schlenk-flask, equipped with a magnetic stirring bar and a rubber septum was charged with the electrophile (1.0 equiv), followed by dry THF. The benzyl manganese chloride solution (1.05-1.10 equiv) was added dropwise at 0 °C and the reaction mixture was slowly warmed up to 25 °C and stirred overnight. Sat. aq. NH4Cl (4 mL) and water (2 mL) were added and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over Na2SO4 and filtered. Evaporation of the solvents in vacuo and purification by flash column chromatography afforded the expected products.
2-amino-4-(benzofuran-2-yl)-5-benzoyl-6-methoxy-4H-pyran-3-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With iodine In water at 25℃; for 0.166667h; Sonication; Green chemistry;
2.2 General procedure for the synthesis of derivatives in water under ultrasound irradiation
General procedure: A 50mL flask was charged with aldehyde (1 mmol), malononitrile (1 mmol), 1,3-diketone (1 mmol) and iodine (0.2 mmol) in water (3 mL). The mixture was sonicated (35 kHz, constant frequency) at 25 °C for 10 min. After completion of the reaction [monitored by TLC, using hexane:ethyl acetate (9:1) as eluent], the reaction mixture was quenched with ice and the precipitate formed was filtered, washed, dried and recrystallized from ethanol to get the pure product. The structures of all the products were confirmed by IR, 1H NMR, 13C NMR, ESI-MS and CHN analysis.
2-amino-4-(benzofuran-2-yl)-6-methyl-5-(2′,2′,2′-trifluoroacetyl)-4H-pyran-3-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With iodine In water at 25℃; for 0.166667h; Sonication; Green chemistry;
2.2 General procedure for the synthesis of derivatives in water under ultrasound irradiation
General procedure: A 50mL flask was charged with aldehyde (1 mmol), malononitrile (1 mmol), 1,3-diketone (1 mmol) and iodine (0.2 mmol) in water (3 mL). The mixture was sonicated (35 kHz, constant frequency) at 25 °C for 10 min. After completion of the reaction [monitored by TLC, using hexane:ethyl acetate (9:1) as eluent], the reaction mixture was quenched with ice and the precipitate formed was filtered, washed, dried and recrystallized from ethanol to get the pure product. The structures of all the products were confirmed by IR, 1H NMR, 13C NMR, ESI-MS and CHN analysis.
(Z)-3-(benzofuran-2-yl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium methylate; In methanol;Reflux;
General procedure: A mixture of carbaldehyde (1.0 mole) and the appropriate substituted phenylacetonitrile (1.1 mole) in 5% sodium methoxide/methanol was heated under reflux for 3-6 h. The resulting solution was cooled to room temperature and poured into ice-cold water to afford a crude yellow solid. The solid was filtered off, washed with water, and finally washed with cold methanol. The obtained crude solid was recrystallized from methanol to afford the desired condensation product as a pure yellow crystalline solid.
1-(benzofuran-2-yl)-2-(1,3-dioxolan-2-yl)ethanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
General procedure: A dry and argon-flushed 10 mL Schlenk tube, equipped with a stirring bar and septum, wascharged with 2-(vinyloxy)ethanol (5, 132 mg, 1.50 mmol, 1.50 equiv) in Et2O (1.5 mL). Then,iPrMgBr (1.55 mmol, 1.55 equiv) was added dropwise at 25 C. After 5 min of stirring,Sc(OTf)3 (49.2 mg, 0.10 mmol, 0.10 equiv) and aldehyde 6 (1.00 mmol, 1.00 equiv) weresuccessively added and the reaction mixture was stirred at 40 C for the given time. After afull conversion was detected by GC-analysis, sat. aq. NH4Cl (15 mL) was added and theaqueous layer was extracted with EtOAc (3 x 15 mL). The combined organic layers weredried over Na2SO4, filtered and solvent was removed under reduced pressure. Purification viacolumn chromatography (SiO2) afforded expected products 4.
With caesium carbonate; In dimethyl amine; at 20℃;Glovebox;
In the glove box,Cs2CO3 (0.6 mmol) and benzofuran-2-carbaldehyde (0.2 mmol) were weighed into 25 mL of the reaction tube,Measure the amount of DMA (1 mL) into the reaction tube.A bromodifluoromethylphosphonium salt (0.6 mmol) was weighed,Treated with DMA (2 mL)Inhalation into the syringe.Stirred at room temperature,A DMA solution of bromodifluoromethylphosphonium salt was injected into the reaction tube at a rate of 0.5 mL / h with a syringe pump.After the injection, the reaction is over. The solution in the reaction tube was transferred to a separatory funnel, 15 mL of water was added, extracted three times with dichloromethane (10 mL x 3), and the organic phases were combined and washed three times with water (10 mL x 3). The final obtained organic phase was dried over anhydrous sodium sulfate, and the solid was filtered off, the solvent removed by rotary evaporation, on a silica gel column with n-pentane and ethyl acetate as eluent, to give the final isolated product difluoromethyl, yield 72%, purity> 99.9%.
methyl 4-[2-(1-benzofuran-2-yl)-4-oxo-1,3-thiazolidin-3-yl]-3-methylbenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
17%
Example 475 Methyl 4-[2-(1-benzofuran-2-yl)-4-oxo-1,3-thiazolidin-3-yl]-3-methylbenzoate To a solution of <strong>[18595-14-7]methyl 4-amino-3-methylbenzenecarboxylate</strong> (0.300 g, 1.82 mmol), Na2SO4 (0.310 g, 2.18 mmol) and benzofuran-2-carbaldehyde (0.330 mL, 2.73 mmol) in toluene (10.0 mL) was stirred at 110 C. for 7 h, followed by addition of thioglycolic acid (0.250 mL, 3.63 mmol) in one portion. The reaction mixture was refluxed overnight, then partitioned between ethyl acetate and H2O. The organic layer was dried over MgSO4 (s) and concentrated to give a crude product which was purified by Isco Combi-Flash Companion column chromatography (0-30% ethyl acetate in n-hexane) to give methyl 4-[2-(1-benzofuran-2-yl)-4-oxo-1,3-thiazolidin-3-yl]-3-methylbenzoate (0.115 g, 17%). 1H NMR (CDCl3, 400 MHz) delta 7.91 (br s. 1H), 7.74 (br d, 1H), 7.52-7.46 (m, 2H), 7.33 (t, 1H), 7.24-7.20 (m, 1H), 6.95 (br s, 1H), 6.54 (s, 1H), 5.92 (br s, 1H), 4.23 (d, 1H), 3.93-3.81 (m, 4H), 2.32 (br s, 3H); LC-MS (ESI) m/z 368.2 [M+H]+.
(E)-2-(2-fluoro-2-(phenylsulfonyl)vinyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
Stage #1: fluoromethyl phenyl sulfone With diethyl chlorophosphate; lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h;
Stage #2: 2-formylbenzo[b]furan In tetrahydrofuran at -78 - 20℃; for 18h;
N-(benzofuran-2-ylmethyl)-4-methoxy-2-iodoaniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
Stage #1: 2-formylbenzo[b]furan; 2-iodo-4-methoxylaniline With tetramethylorthosilicate; trifluoroacetic acid at 20℃; for 0.5h;
Stage #2: With sodium tetrahydroborate In ethanol Cooling;
ethyl 4-(benzofuran-2-yl(hydroxy)methyl)quinoline-1(4H)-carboxylate[ No CAS ]
C21H19NO4[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diethylzinc; palladium diacetate; triphenylphosphine; In toluene; at 20℃; for 4h;Inert atmosphere;
General procedure: A solution of a quinoline derivative 1 (0.3 mmol), Pd(OAc)2 (3.4 mg,0.015 mmol), PPh3 (7.9 mg, 0.03 mmol), 1 M Et2Zn in toluene (1.2 mL,1.2 mmol, 4.0 equiv), and an electrophile (0.45 mmol, 1.5 equiv) intoluene (2.0 mL) was stirred for 4 h under argon. The resulting mixturewas treated with saturated aqueous NH4Cl and extracted withCH2Cl2. The combined organic layer was dried over Na2SO4 and concentratedin vacuo, and the residue was chromatographed on flashsilica gel (hexane/EtOAc) to afford the desired product as an inseparablemixture of diastereomers (where applicable).
2-(benzofuran-2-yl)-2,3-dihydrofuro[2,3-b]pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With tetrabutyl ammonium fluoride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 60℃; for 18.0h;
General procedure: To a stirred mixture of 1.00 mmol of nitropicoline 35 or 63, 1.20 mmol of the appropriate benzaldehyde, and 1.5 mmol of Huenig's base in THF (7 mL/g of nitropicoline 35/63) was added 1.3 mmol of a 1 M THF solution of TBAF. The resulting mixture was heated 60 C for 1.5e2.0 h in the case of 2,3-dihydrofuro[3,2-c] pyridines or for 18 h in the case of 2,3-dihydrofuro[2,3-b]pyridines. After cooling to room temperature, the reactions were quenched with sat. aqueous NH4Cl. The solution was extracted with EtOAc, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography as specified above.
(E)-3-(benzofuran-2-yl)-2-(thiophen-2-yl)acrylonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With sodium hydroxide In ethanol; water at 20℃; for 24h;
General Synthesis of (TACNBNF)compound was depicted schematicallyin Scheme 1.
The 2-(thiophen-2-yl) acetonitrile (1 g, 8.118mmole), benzofuran-2-carbaldehyde (1.2 g, 8.118 mmol), and 2 g ofNaOH were dissolved in 45 ml of ethanol. Then, these reactionmixtures were stirred vigorously at normal room temperature for24 h. The improvement of the reactionwas monitored by TLC. Aftercompletion of the reaction, the mixtures were poured into ice coldwater. The solid product was filtered, washed with cold ethanol toremove excess benzofuran-2-carbaldehyde, and dried in a vacuumchamber to collect the green colouredcrude product. The precipitatewas allowed to purify by column chromatography techniqueusing the mixture of Hexane: Ethyl Acetate (2/8): eluent. Rectangularslabsof green colour crystals (yield was 88%) of the TACNBNFwas grown using slow evaporation method by DCM (2 ml) andmethanol (1 ml) mixture solvents.
2'(tert-butylamino)-5'-hydroxy-6'-undecyl[2,3'-bibenzofuran]-4',7'-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With ethylenediaminediacetic acid; In 1,2-dichloro-ethane; at 180℃; for 0.25h;Irradiation;
General procedure: To a mixture of 0.1 mmol of the corresponding isocyanide,0.1 mmol of the corresponding aldehyde, and 10 mol % of EDDA in2 mL of DCE, were added 30 mg of <strong>[550-24-3]embelin</strong> (0.1 mmol). The reactionmixture was stirred and irradiated for 15 min at 180 C. The solvent wasremoved under vacuum, and the crude product was purified by preparative-TLC to yield the corresponding furan derivative.
2'-(cyclohexylamino)-5'-hydroxy-6'-undecyl-[2,3'-bibenzofuran]-4',7'-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
With ethylenediaminediacetic acid; In 1,2-dichloro-ethane; at 180℃; for 0.25h;Irradiation;
General procedure: To a mixture of 0.1 mmol of the corresponding isocyanide,0.1 mmol of the corresponding aldehyde, and 10 mol % of EDDA in2 mL of DCE, were added 30 mg of <strong>[550-24-3]embelin</strong> (0.1 mmol). The reactionmixture was stirred and irradiated for 15 min at 180 C. The solvent wasremoved under vacuum, and the crude product was purified by preparative-TLC to yield the corresponding furan derivative.
2'-(benzylamino)-5'-hydroxy-6'-undecyl[2,3'-bibenzofuran]-4',7'-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With ethylenediaminediacetic acid; In 1,2-dichloro-ethane; at 180℃; for 0.25h;Irradiation;
General procedure: To a mixture of 0.1 mmol of the corresponding isocyanide,0.1 mmol of the corresponding aldehyde, and 10 mol % of EDDA in2 mL of DCE, were added 30 mg of <strong>[550-24-3]embelin</strong> (0.1 mmol). The reactionmixture was stirred and irradiated for 15 min at 180 C. The solvent wasremoved under vacuum, and the crude product was purified by preparative-TLC to yield the corresponding furan derivative.
With 1,2,2,3,4,4-hexamethylphosphetane 1-oxide; phenylsilane; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 48h; stereoselective reaction;
(E)-N-(benzofuran-2-ylmethylene)anthracen-1-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With acetic acid In ethanol at 20℃;
3.2. Synthesis of Schiff base derivatives, A1-A6 and P1-P6
General procedure: All Schiff bases were synthesized according to the same procedure. 1-aminoanthracene or 1-aminopyrene (1.0mmol) and aldehyde (1.0 mmol) were dissolved in 5 mL ethanol. Acetic acid (2-3 drops) was added to themixture and stirred overnight at room temperature. The solid product was fi ltered, washed several times withethanol and dried in vacuum.
3.2. Synthesis of Schiff base derivatives, A1-A6 and P1-P6
General procedure: All Schiff bases were synthesized according to the same procedure. 1-aminoanthracene or 1-aminopyrene (1.0mmol) and aldehyde (1.0 mmol) were dissolved in 5 mL ethanol. Acetic acid (2-3 drops) was added to themixture and stirred overnight at room temperature. The solid product was fi ltered, washed several times withethanol and dried in vacuum.
With sodium hydroxide; In ethanol; water; at 20℃; for 12h;
In 1.46g 1-1 (about 10mmol), 1.91g (about 10mmol) p-ethylamine basic ethyl ketone And 30mL of pure ethanol mixed solution, Slowly add 10 mL of sodium hydride aqueous solution (containing 2.00 g of sodium hydroxide). After 12 hours of reaction at room temperature, suction filtration. A yellow solid was obtained, washed with cold ethanol, and dried under vacuum. 2.59 g of compound 2-1 was obtained (a yield of about 81%).
In tetrahydrofuran; n-heptane; ethylbenzene for 1h; Cooling with ice;
Typical experimental procedure for one-pot preparation of aryl or heteroaryl-bearing acrylates (4).Methyl (E)-3-(benzo[b]thiophen-2-yl)acrylate (4a):6 (Table 1, entry 2)
General procedure: To a solution of 3a (161 mg, 1.20 mmol) in THF (4.0 mL) was added dropwise lithium diisopropylamide(1.93 M solution in THF/heptane/ethylbenzene, 0.68 mL, 1.3 mmol) at dry ice-acetone bath temperaturewith stirring for 1 h. To the solution was added dropwise DMF (0.10 mL, 1.3 mmol), and the reactionmixture was allowed to warm to ice-bath temperature and stirred for 30 min. Trimethyl phosphonoacetate(0.21 mL, 1.5 mmol) was added and stirring at ice-bath temperature was continued for 1 h. Aqueous 5%HCl (2 mL) and water (4 mL) were added successively and the mixture was extracted with EtOAc (10mL). The organic layer was separated and washed with water (10 mL), dried over anhydrous sodiumsulfate, and concentrated. The residual oil was subjected to column chromatography (silica gel) to give 4a(229 mg, 87%) as a white solid;
2,5-di(benzo[b]furan-2-yl)thiazolo[5,4-d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
In N,N-dimethyl-formamide at 130℃; for 5h;
4.2. General procedure of the Ketcham reaction General procedure A
General procedure: A solution of furan-2-carbaldehyde (1a) (2.4 g, 2.0 mL, 24 mmol) or furan-3-carbaldehyde (1b) (2.4 g, 2.0 mL, 24 mmol) or benzo[b]furan-2-carbaldehyde (1f) (3.4 g, 3.0 mL, 24 mmol) and dithiooxamide (2) (1.5 g, 12.0 mmol) in N,N-dimethylformamide (60 mL) were heated to 130 °C and stirred for 5 h. After completion (monitored by TLC, eluent n-hexanes/ethylacetate = 6/4), the reaction mixture was cooled down to room temperature and petroleum ether was added (60-100 mL) to obtain the precipitates. Crude product was purified by repeated crystallization from ethanol in a manner, that the solution which have been formed during the heating was filtered hot throughout the active carbon. Insoluble residue was upon 5 times repeated cycle of heating up in ethanol and getting rid of the dissolved portions pure thiazolo[5,4-d]thiazole 6a,b and 6f. The combined ethanolic layers were concentrated to 2/3 of the volume and left to crystallize for 5-7 days while being cooled to freezing temperatures. The crystallized products were combined yielding the final amount of the desired product.
diethyl (E)-2-(benzofuran-2-ylmethylene)succinate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With 1,2,2,3,4,4-hexamethylphosphetane 1-oxide In acetic acid butyl ester at 120℃; for 24h; Inert atmosphere; Schlenk technique; stereoselective reaction;
Stage #1: Diethyl allylphosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere;
Stage #2: 2-formylbenzo[b]furan In tetrahydrofuran; mineral oil at 0℃; for 16h; Inert atmosphere;
4'-(benzofuran-2-yl)-3,2':6',3''-terpyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
Stage #1: methyl-3-pyridylketone; 2-formylbenzo[b]furan In ethanol at 20℃; for 0.25h;
Stage #2: With ammonium hydroxide; potassium hydroxide In ethanol; water at 20℃; for 6h;
Synthesis of 4'-(benzofuran-2-yl)-2,2':6',2''-terpyridine(TP1).
General procedure: Benzofuran-2-carbaldehyde (A1)(0.5 mmol, 81.5 mg), dissolved in 2 mL ethanol, was added to the solution of 2-acetyl pyridine (K1)(1 mmol; 121 mg) in 3 mL ethanol. The solution was stirred at room temperature for 15 min. Then a small piece of KOH pellet (~0.05 mg) was added followed by 25% (w/v) aqueous ammonia (1.5 mL) and the resultant mixture was stirred at room temperature for 6 h. The reaction was monitored on TLC. After completion of reaction, the obtained solid product was filtered under vacuum onto a sintered funnel. The solid was washed with ice-cold ethanol until the washings are colourless and recrystallized from CHCl3. Greenish white solid, yield 180 mg (98%)
4'-(benzofuran-2-yl)-4,2':6',4''-terpyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
Stage #1: methyl (4-pyridyl) ketone; 2-formylbenzo[b]furan In ethanol at 20℃; for 0.25h;
Stage #2: With ammonium hydroxide; potassium hydroxide In ethanol; water at 20℃; for 6h;
Synthesis of 4'-(benzofuran-2-yl)-2,2':6',2''-terpyridine(TP1).
General procedure: Benzofuran-2-carbaldehyde (A1)(0.5 mmol, 81.5 mg), dissolved in 2 mL ethanol, was added to the solution of 2-acetyl pyridine (K1)(1 mmol; 121 mg) in 3 mL ethanol. The solution was stirred at room temperature for 15 min. Then a small piece of KOH pellet (~0.05 mg) was added followed by 25% (w/v) aqueous ammonia (1.5 mL) and the resultant mixture was stirred at room temperature for 6 h. The reaction was monitored on TLC. After completion of reaction, the obtained solid product was filtered under vacuum onto a sintered funnel. The solid was washed with ice-cold ethanol until the washings are colourless and recrystallized from CHCl3. Greenish white solid, yield 180 mg (98%)
General procedures of target compounds (2a-2l)
General procedure: Corresponding aldehyde derivatives (0.002 mol) and appropriate isothiocyanatederivative (0.002 mol) in EtOH (25 mL) were refluxed for 8 h. The mixture was cooled inan ice-bath, precipitated product was filtered, dried, and recrystallized from EtOH.
2.2. Synthesis of resveratrol analogs
General procedure: The synthesis of the resveratrol analogs was performed in two steps.First, the intermediate was obtained by the amidation reaction of 2-amino-polysubstituted-benzoic acid (1 eq) with ammonia under thecatalysts including EDCI (1.5 eq), HOBT (1.5 eq) and NMM (1.5 eq).Then, resveratrol analogs were achieved by Cyclization of the intermediate(1 eq) with different aldehyde (1.1 eq) in the presence of a catalystCuCl2 (1.7 eq). The synthetic route to resveratrol analogs was shown inScheme 1.
16(E)-(2-benzofuryliden)-17-oxo-5-androsten-3b-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With potassium hydroxide In ethanol; water at 20℃;
2.1. General procedure for the synthesis of the 16(E)-hetereoarylidene steroids (1a-g)
General procedure: The concentrated aqueous solution of 12.5 mmol (0.49 g)KOH was added to the solution of 1.0 mmol (0.29 g) DHEA inethanol (10 mL). Then, 2.2 mmol of the corresponding aldehydewas added to the reaction mixture. The mixture wasstirred at room temperature for 3 hours. After completing thereaction, the resulting solution was poured into ice water.The resulting solid was filtered and washed with water untilthe pH value of 7, and then dried under vacuum. The hetereoarylidenederivatives of DHEA were recrystallizedfrom methanol.
With tetrahydropyrrole In ethanol at 20℃; diastereoselective reaction;
General procedure for the synthesis of cyclohexanolderivatives (3a-3t).
General procedure: The Claisen-Schmidt condensationof aryl and hetaryl carbaldehydes 2a-2e (10 mmol, 1 equiv.) in ethanol (5 mL) was performed with differentacetyl pyridine (1a-1c) or acetophenone (1d-1g)derivatives (15 mmol, 1.5 equiv.) dissolved in ethanol(2-3 mL). The reaction mixture was allowed to stir atroom temperature for an additional 10 min, during whichit turned to a homogeneous solution. Then pyrrolidine(1 equiv.) was added dropwise and the resultant mixturewas stirred at room temperature till the reaction wascompleted (3-4 h). The precipitated product wasthen filtered off. The crude product was purified byrecrystallization from chloroform-methanol (1 : 1 v/v,10 mL). Structures of all the novel compounds wereconfirmed by NMR, IR, and HRMS analysis. Thestructure of earlier reported derivatives was supported byTLC. Their spectral data were similar to those reportedearlier [22].
With tetrahydropyrrole In ethanol at 20℃; diastereoselective reaction;
General procedure for the synthesis of cyclohexanolderivatives (3a-3t).
General procedure: The Claisen-Schmidt condensationof aryl and hetaryl carbaldehydes 2a-2e (10 mmol, 1 equiv.) in ethanol (5 mL) was performed with differentacetyl pyridine (1a-1c) or acetophenone (1d-1g)derivatives (15 mmol, 1.5 equiv.) dissolved in ethanol(2-3 mL). The reaction mixture was allowed to stir atroom temperature for an additional 10 min, during whichit turned to a homogeneous solution. Then pyrrolidine(1 equiv.) was added dropwise and the resultant mixturewas stirred at room temperature till the reaction wascompleted (3-4 h). The precipitated product wasthen filtered off. The crude product was purified byrecrystallization from chloroform-methanol (1 : 1 v/v,10 mL). Structures of all the novel compounds wereconfirmed by NMR, IR, and HRMS analysis. Thestructure of earlier reported derivatives was supported byTLC. Their spectral data were similar to those reportedearlier [22].
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