* 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.
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4 h;
To a solution of 3-hydroxy-4-nitrobenzaldehyde (2.000 g, 11.98 mmol) in DMF (24 ml) were added K2C03 (1.687 g, 12.22 mmol) and iodomethane (1.52 ml, 24.44 mmol). The reaction mixture was stilTed at room temperature for 4 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organics were washed with asaturated solution of NaHCO3 (3 times), with water, with saturated solution of NaC1, dried over MgSO4, filtered and evaporated to give intermediate ha (2.137 g, 98percent). ‘H NMR (500 MHz, CDC13) ö 10.06 (s, 1H), 7.93 (d, J= 8.1 Hz, 1H), 7.60 (s, 1H), 7.54 (dd, J= 8.1, 1.4 Hz, 1H), 4.04 (s, 3H).
96%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5 h;
Example 39 : Synthesis of (1E,6E)-1-(3-hydroxy-4-methoxyphenyl)-7-(3-methoxy-4-nitrophenyl)hepta-1,6-diene-3,5-dione (CU049); (1) Synthesis of 3-methoxy-4-nitrobenzaldehyde; 3-Hydroxy-4-nitrobenzaldehyde (500 mg, 2.99 mmol) and potassium carbonate (0.42 g, 3.0 mmol) were dissolved in 6.0 mL of N,N-dimethyformamide. After addition of iodemethane (0.38 mL, 6.0 mmol) at room temperature, the mixture was stirred for 5 h at the same temperature. The reaction mixture was diluted with ethyl acetate and water, and separated. The organic layer was washed with brine twice, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate = 4/1 to 1/1) to obtain the title compound as a pale yellow powder (518 mg, 96percent).
75%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 3 h;
3A. 3-Methoxy-4-nitro-benzaldehydeA mixture of 2-hydroxy-4-nitro-benzaldehyde (8.0 g, 47.9 mmol), methyl iodide (10.2 g,71.9 mmol) and potassium carbonate (6.61 g, 47.9 mmol) in DMF (80 mL) was stirred at 60°C for 3 hours. The cooled reaction mixture was diluted with EtOAc (100 mL), washed with water (200 mL), dried (Na2SO4) and evaporated under reduced pressure to give the title compound (6.5 g, 75percent) which was used without further purification.
49.7 g
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 1 h;
(a) . 3-Methoxy-4-nitro-benzaldehyde A mixture of 3-hydroxy-4-nitrobenzaldehyde (51 .3 g), iodomethane (38.3 ml) and potassium carbonate (85 g) in DMF (250 ml) was stirred at 60 °C for 1 h. The reaction mixture was cooled to room temperature and poured into water. The solids were collected by filtration and dried in 10 vacuo (50 °C). Yield: 49.7 g.
12.1 g
Stage #1: With caesium carbonate In N,N-dimethyl-formamide for 0.0833333 h; Sonication Stage #2: at 80℃; for 18 h;
To 20 g (0.12 mol) of 3-hydroxy-4-nitrobenzaldehyde in 200 ml of anhydrous DMF are added 42 g (0.13 mol) of caesium carbonate. The solution obtained is ultrasonicated for 5 minutes, and 9.4 ml (0.29 mol) of methyl iodide are then added. The reaction medium is heated at 80°C for 18 hours and then diluted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. The residue is recrystallized from 300 ml of a hot 1/2 DMF/ethanol mixture. The crystals formed are filtered off, rinsed with cold ethanol and with hexane, and then dried under reduced pressure. 12.1 g of a solid are obtained.
53.4 g
With potassium carbonate In N,N-dimethyl-formamide
Methyl iodide (55.2 g, 389.2 mmol) was added dropwise to a stirred mixture of 3-hydroxy-4- nitrobenzaldehyde (50 g, 288.4 mmol) and potassium carbonate (53.8 g, 389.2 mmol) in DMF (250 ml). The reaction mixture was stirred overnight, poured into ice-cold water, and the precipitated solid was collected by filtration. The resulting solid was dried on a high vacuum overnight to obtain 53.4 g of 3-methoxy-4-nitrobenzaldehyde.1H NMR (CDCI3) 6: 10.06 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 0.8 Hz, 1H), 7.54 (dd, J = 8.2, 1.2 Hz, 1H), 4.02 (s, 3H).
Reference：
[1] Magnetic Resonance in Chemistry, 1992, vol. 30, # 6, p. 497 - 499
5
[ 100-83-4 ]
[ 42123-33-1 ]
[ 704-13-2 ]
Yield
Reaction Conditions
Operation in experiment
47%
With isopropyl nitrate; sulfuric acid; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane at 20℃; for 0.25 h;
To a stirring solution of 3- hydroxybenzaldehyde 23 (618 mg, 5.0 mmol) in dichloromethane (10 mL) was added tetrabutylammoniumhydrogen sulfate (85.0 mg, 0.25 mmol) and isopropyl nitrate (1.27 mL, 12.5 mmol). Concentrated sulfuric acid (610 μ) was added dropwise and the resulting reaction mixture was allowed to stir at room temperature for 15 minutes. The reaction contents were then transferred to a separatory funnel containing 50 mL of an aqueous saturated sodium bicarbonate solution. Dichloromethane was then used to extract the crude product. The combined organic layers were dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting solid was adsorbed onto silica gel and purified via flash column chromatography eluting with 99: 1 to 4: 1 hexanes:ethyl acetate to give isomer 30 (R = 0.44 in 3: 1 hexanes:ethyl acetate) as a yellow solid (201 mg, 24percent yield) followed by the desired product 28 (R/= 0.19 in 3: 1 hexanes:ethyl acetate) as a pale yellow solid (411 mg, 47percent yield). This is a known procedure (D. A. Learmonth (Portela & C.A., S.A., Port.), GB- 2377934, 2003). We were able to obtain 28 (CAS number: 42123-33-1) in 63percent yield during the course of these investigations. Characterization Data for Compound 28: 1H NMR (400 MHz, CDC13): δ 10.40 (s, 1H), 10.30 (s, 1H), 7.67 (ddd, J = 8.3, 7.4, 0.7 Hz, 1H), 7.37 (dd, = 8.3, 1.4 Hz, 1H), 7.31 (dd, J = 7.4, 1.4 Hz, 1H). HRMS (DART): calc. for C7H9N204 (0511) [M+NH4]+: 185.0557, found: 185.0559. MP: 155-158 °C, lit. 157 °C (W. S. Saari, S. W. King, J. Med. Chem. 1974, 17, 1086-1090). Characterization Data for 30: 1H NMR (400 MHz, CDCI3): δ 10.58 (s, 1H), 10.06 (d, J = 0.6 Hz, 1H), 8.28 (d, = 8.7 Hz, 1H), 7.66 (d, = 1.7 Hz, 1H), 7.51 (dd, = 8.7, 1.7 Hz, 1H). Spectral values for 30 identical to previously reported 1H NMR data (A. Tsoukala, L. Liguori, G. Occhipinti, H.R. Bjorsvik, Tet. Lett. 2009, 50, 831-833). MP: 129-131 °C, lit. 127°C (J. Cologne, F. Pierre, Bull. Soc. Chim. Fr. 1964, 12, 3090-3096).
Reference：
[1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 30, p. 5629 - 5633
[2] Chemische Berichte, 1929, vol. 62, p. 1182[3] Chemische Berichte, 1933, vol. 66, p. 1761,1762
[4] Journal of the Chemical Society, 1925, vol. 127, p. 876,877[5] Journal of the Chemical Society, 1926, p. 150
[6] Chemische Berichte, 1901, vol. 34, p. 4001
[7] Chemische Berichte, 1914, vol. 47, p. 3048
[8] Chemische Berichte, 1901, vol. 34, p. 4000
8
[ 61161-83-9 ]
[ 704-13-2 ]
Reference：
[1] Journal of Organic Chemistry, 1994, vol. 59, # 15, p. 4285 - 4296
With sodium methylate; In N,N-dimethyl-formamide; at 20℃; for 16h;
Example 85A 3-(3-hydroxy-4-nitrophenyl)-acrylic acid methyl ester To an ambient solution of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (1.00 g, 5.99 mmol) and trimethyl phosphonoacetate (0.950 mL, 6.59 mmol) in DMF (8 mL) was added NaOMe (356 mg, 6.59 mmol). The mixture was stirred at room temperature for 16 h and was then slowly quenched by the addition of 1 N HCl (15 mL). The mixture was acidified to pH~1 with concentrated HCl, and the solid was collected and air-dried to provide the title compound. MS (ESI) m/z 224 (M+H)+.
With potassium carbonate; In water; ethyl acetate; N,N-dimethyl-formamide;
SYNTHESIS EXAMPLE 1 Synthesis of 3-(4-amino-3-hydroxy-phenyl)-propionitrile 3-Hydroxy-4-nitrobenzaldehyde (2) (4.18 g, 25 mmol) was dissolved in anhydrous DMF (100 mL). To this solution was added benzyl bromide (3.27 mL, 27.5 mmol) and potassium carbonate (3.8 g, 27.5 mmol). The reaction mixture was stirred at room temperature for 18 h, filtered and evaporated. The residue was taken up into ethyl acetate (250 mL) and water (250 mL). The organic layer was washed with brine (50 mL), dried over MgSO4, filtered and evaporated leaving 3-benzyloxy-4-nitro-benzaldehyde (3) as an orange solid (6.31 g, 98% yield): 1H-NMR (400 MHz, DMSO-d6) delta 10.05 (s, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.45 (m, 5H), 5.40 (s, 2H); 13C-NMR (400 MHz, DMSO-d6) delta 192.4, 151.2, 143.5, 139.9, 135.9, 128.9, 128.6, 127.9, 125.9, 122.7, 115.5, 71.1.
81%
sodium hydride (60% dispersion in oil, 1.4 g, 36 mmol) in portions at 0C. The mixture was stirred for 30 minutes at 0C and then benzyl bromide (5.34 g, 31.5 mmol) was added dropwise. Stirring was continued at 0C for 30 min then at room temperature for 30 min followed by heating at 70C for 2 h. TLC analysis showed the starting materials were consumed. The mixture was poured into ice/water (1 L), stirred for 30 minutes and extracted with EtOAc (300ml x 3). The combined organic layers were washed with brine and dried over Na2S04. The solvent was removed to give the product, A-2, as a brown solid (6.2 g, 81 %). -NMR (400 MHz, d6-DMSO) delta (ppm): 10.0 (s, 1H), 8.05 (d, J=8.0Hz, 1H), 7.92 (s, 1H), 7.67 (d, J=8.0Hz, 1H), 7.47-7.35 (m, 5H), 5.40 (s, 2H).
In ISOPROPYLAMIDE;
D. Synthesis of 4-nitro-3-[(phenylmethyl)oxy]benzaldehyde 2.88 g of a sodium hydride dispersion (55% in oil) is added, portion by portion at 0 C., to a solution of 10.32 g of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> in 180 ml dry dimethylacetamide. The reaction mixture is then stirred for 30 minutes at 0 C. 10.8 g of benzyl bromide is added, drop by drop, to this mixture, and the reaction mixture is then stirred for 30 minutes, followed by 30 minutes at room temperature, and then for 2 hours at 70 C. Subsequently, the reaction mixture is treated with 900 ml of an ice/water mixture and then stirred for another 1 hour. The mixture is filtered, and the precipitate is washed with water and then dried. The yield obtained is 15.68 g of 4-nitro-3-[(phenylmethyl)oxy]benzaldehyde. The crude product obtained is used in the next step without further purification. 1H-NMR (300 MHz, DMSO): 10.07 (s, 1H, COH); 8.10 (d, J=8.1, 1H, H(5)); 7.93 (d, J=1.5,1H, H(2)); 7.68 (dd, J=1.5, J=8.1, 1H, H(6)); 7.48-7.32 (m, 5H, phenyl); 5.41 (s, 2H, CH2-Phenyl).
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;
Example 44 3- [3-Hydroxy-4- (1, 1, 4-trioxo- [1, 2,5] thiadiazolidin-2-yl)-benzyl]-3, 4-dihydro-1 H- benzo [1,4] diazepine-2, 5-dione A. 3-Benzyloxy-4-nitro-benzaldehyde; <strong>[704-13-2]<strong>[704-13-2]3-Hydroxy-4-nitro-benzaldehyd</strong>e</strong> (4. 68g, 28 mmol) is dissolved in DMF (27 mL) and to the solution is added with stirring powdered potassium carbonate (4.27 g, 30.1 mmol) and benzyl bromide (3.34 mL, 28.1 mmol). The mixture is stirred at RT overnight, diluted with water (200 mL) and extracted three times with EtOAc. The organic extracts are washed with 10% potassium carbonate and brine, dried over anhydrous MgS04, decolorized with charcoal, filtered and evaporated to give 3-benzyloxy-4-nitro-benzaldehyde as an oil which is used in the next step without purification.
With potassium carbonate; at 20℃;
To a stirred solution of benzyl bromide (6.9 g, 40.3 mmol) and 3-hydroxy-4- nitrobenzaldehyde (9.7 g, 58.0 mmol) is added K2CO3 (8.9 g, 64.4 mmol). The mixture is stirred at ambient temperature overnight, diluted with water and extracted with EtOAc. The organic phase is washed with aqueous K2CO3 and brine, dried over MgSO4, filtered and concentrated to afford 3-benzyloxy-4-nitrobenzaldehyde as a yellow solid: MS (M+H)+ = 258.
1. 1-(3,4-Dichlorophenyl)-3-hydroxy-3-(3-hydroxy-4-nitrophenyl)-propan-1-one Sodium hydroxide (4.88 g, 0.122 mmol) is dissolved in water (80 mL) and 95% EtOH (80 mL) and cooled to 0 C. with an ice-H2O bath. 1-(3,4-Dichlorophenyl)ethanone (23.10 g, 0.122 mol) is added in one portion. After the addition, the mixture is warmed to 15 C. <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (20.42 g, 0.122 mol) is then added with rigorous stirring. After stirring for 5 minutes, the reaction mixture is diluted with 95% EtOH (300 mL). The resulting tan mixture is stirred at room temperature overnight. The reaction mixture is acidified with 3N HCl and stirred for 30 minutes. The resulting yellow solid is filtered off, washed with H2O, washed with 5% MeOH/CH2Cl2, and oven dried (40 C.) to yield a yellow solid (25.00 g, 0.074 mol, 61%) of the title compound; mp 163-166 C. Analysis for C15H9Cl2NO5: Calcd: C 50.59; H 3.11; N 3.93. Found: C 50.61; H 2.81; N 3.81.
To a solution of 2,4-thiazolidinedione (3.50 g, 30.0 mmol) in ethanol (120 mL) was added <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (5.00 g, 30.0 mmol) and piperidine (0.44 mL, 4.50 mmol). The mixture was stirred at reflux for 15 hours and then cooled to 0 C. The resulting precipitate was collected and washed with cold ethanol to afford 3.53 g of the desired compound as a brown solid. Further concentration and precipitation of the mother liquor afforded an additional 3.1 g of the product. This was used without further purification in the next reaction. 1H NMR (CDCl3) 8.20 (1H, d, J = 8.8 Hz), 7.75 (1H, s), 7.26 (1H, s), 7.12 (1H, d, J=8.8 Hz).
68.1 In analogy to Example 64.1, from <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> and ethyl iodide there was obtained 3-ethoxy-4-nitro-benzaldehyde.
With potassium carbonate; In DMF (N,N-dimethyl-formamide);
To a suspension of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (7.0 g) and potassium carbonate (8.1 g) in DMF (100 ml), iodoethane (8.3 g) was added dropwise under nitrogen atmosphere. The mixture was stirred overnight, water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water once and saturated brine once, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 1:1), and recrystallized from hexane-ethyl acetate, to give 3-ethoxy-4-nitrobenzaldehyde (5.7 g) as yellow crystals. 1H-NMR (200 MHz, CDCl3) delta 1.50 (3H, t, J = 7.0 Hz), 4.27 (2H, q, J = 7.0 Hz), 7.53 (1H, dd, J = 8.0, 1.6 Hz), 7.58 (1H, d, J = 1.4 Hz), 7.90 (1H, d, J = 8.0 Hz), 10.04 (1H, s). Elemental Analysis C9H9NO4 Calcd. C, 55.39; H, 4.65; N, 7.18; Found. C, 55.41; H, 4.43; N, 7.06.
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere;
[00521] 3-Ethoxy-4-nitro-benzaldehyde (54): To a magnetically stirred solution of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> 53 (0.65 g, 3.89 mmol) in anhydrous DMF (3 mL) was added K2CO3 (1.5 g, 10.5 mmol) at room temperature, followed by ethyl iodide (410 muL, 5.1 mmol) and the mixture was allowed to stir overnight at 8O0C under nitrogen atmosphere. Upon completion, water was added and the aqueous layer extracted with ethyl acetate several times. The combined organic phases were dried with sodium sulfate and concentrated in vacuo. The residue thus obtained was further purified by silica gel flash chromatography (0-20% ethyl acetate/hexane) to yield 3-ethoxy-4-nitrobenzaldehyde 54 for which the structure was established based on proton NMR and mass spectroscopy.
With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 18h;
(a). 3 -Ethoxy-4-nitro-benzaldehyde; At 20 0C iodoethane (3.78 g) was added to a suspension of K2CO3 (1.09 g) and 3- hydroxy-4-nitro-benzaldehyde (1.0 g) in DMF (5 ml). The reaction mixture was stirred at 70 0C for 18 h, poured into water and then extracted with ethyl acetate. The organic EPO <DP n="62"/>phases were combined, dried (MgSO4) and concentrated in vacuo. The title product was obtained as a yellow solid. Yield: 1.17 g. MS-ESI: [M+H]+ = 196.
With piperidine; In ethanol; isopropyl alcohol; at 70℃;
Intermediate 6: ethyl 2-(3-hydroxy-4-nitrophenyl)-8,9-dimethoxy-3-methyl-5,6-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate A mixture of 830 mg (2.99 mmol) of ethyl (2E)-(6,7-dimethoxy-3,4-dihydro-1(2H)-isoquinolinylidene)-ethanoate (Intermediate 2.1 above), 450 mg (5.98 mmol) of nitroethane, 0.71 ML (7.18 mmol) of piperidine, and 1.00 g (5.98 mmol) of <strong>[704-13-2]3-hydroxy-4-nitro-benzaldehyde</strong> in 15 ML of ethanol and 15 ML of isopropanol was heated at 70 C. overnight.The solution was allowed to cool to room temperature.Some slightly yellow solid precipitated out and was collected by filtration to give 1.10 g (81%) pure product. MS (HPLC/ES): m/z=453.0 (M+1). HPLC RT: 3.54 min.
A mixture of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (1. 24 g, 7.4 MMOL) and (carbethoxy- methylene) triphenylphophorane (2.6 g, 7.4 MMOL) were dissolved in THF (60 mL) and stirred at 60 C for 2 hours. The mixture was then concentrated and purified by flash column chromatography, using hexane in ethyl acetate (70 %) as the eluent, to obtain a the trans-cinnamate ester derivative as a pure yellow solid (1.73 g).
In DMF (N,N-dimethyl-formamide); at 100℃; for 16h;
5-CHLORO-4-METHYLPYRIDINE-2,] 3-diamine (prepared by a method similar to Example 206a) (2.0 g, [12.] 7 mmol) was dissolved in DMF (40 ml) and heated to [ 100 C.] 3-Hydroxy-4- nitrobenzaldehyde (2.10 g, 12.7 mmol) dissolved in DMF (10 ml) was added slowly (10 min). Air was bubbled through the reaction mixture. After 16 h, the DMF was evaporated off and the residue was purified by column chromatography [(ETOAC/METHANOL,] 10: 1) giving the title compound (0.7 [G, 18%).] APCI-MS m/z: 305 0,307. 0 [MH+]
To a solution of <strong>[704-13-2]3-hydroxy-4-nitro-benzaldehyde</strong> (15g, 90mmol) and intermediate 15 (38.62g, 90mmol) in THF (200ml) and iPrOH (200ml) was added cesium carbonate (88g, 27mmol) and the mixture was stirred at room temperature overnight. The mixture was acidified to pH3 by addition of a solution of 4N HCI, and allowed to stir at room temperature for 2 hours and then poured into water. After neutralisation with a solution of 1N NaOH, the aqueous phase was extracted with CH2CI2, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with CH2CI2/MeOH (8/2). The title compound was obtained as an orange solid (15g, 61.4%); m.p. 128-130C.
61.4%
To a solution of <strong>[704-13-2]3-hydroxy-4-nitro-benzaldehyde</strong> (15g, 90mmol) and intermediate 18 (38.62g, 90mmol) in THF (200ml) and iPrOH (200ml) was added cesium carbonate (88g, 27mmol) and the mixture was stirred at room temperature overnight. The mixture was acidified to pH3 by addition of 4N HCI, and allowed to stir at room temperature for 2 hours and then poured in water. After neutralisation with 1N NaOH, the aqueous phase was extracted with CH2CI2, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with CH2CI2/MeOH (8/2). The title compoundwas obtained as an orange solid (15g, 61.4%); m.p. 128-130C.
With triphenylphosphine; In dichloromethane; chloroform;
A. Synthesis of 5-(2,2-dibromoethenyl)-2-nitrophenol A solution of 7.9 g of triphenylphosphine in 70 ml of dry methylene chloride is added, drop by drop at 0 C., to a solution of 1.67 g of 3-hydroxy4-nitrobenzaldehyde and 5 g of carbon tetrabromide in 70 ml of dry methylene chloride. The reaction mixture is stirred at 0 C. for 1.5 hours, then the solvent is distilled off on a rotary evaporator, and the mixture is treated with 20 ml of chloroform. The precipitated product is filtered and the filtrate is evaporated. The crude product obtained is purified on silica gel with heptane/ethyl acetate (8: 1). The yield was 2.0 g of 5-(2,2-dibromoethenyl)-2-nitrophenol obtained as a yellow powder. 1H-NMR (300 MHz, DMSO): 10.52 (s, 1H, OH); 8.03 (d, J=9.0, 1H, H(3)); 7.39 (s, 1H, ethenyl H); 7.29 (d, J=1.8, 1H, H(6)); 7.05 (dd, J=1.8, J=9.0, 1H, H(4)).
Example 3; Grignard Reaction of Benzaldehydes; General Procedure.; To a solution of 4-nitrobenzaldehydes (10 mmol) in anhydrous THF (30 mL) was slowly added Grignard reagent such as methylmagnesium bromide in diethyl ether (25 mmol) at -500C over 45 minutes. The temperature of the reaction mixture was maintained below -400C during the addition Grignard reagent. The reaction mixture was allowed to warm to room temperature and stirred for 3.5 hours. The reaction mixture was cooled to -10C, and quenched with 5% hydrochloric acid (25 mL). The reaction mixture was diluted with water (25 mL) and the product was extracted with ethyl acetate (3 x 15 mL). The combined organic extracts were washed with water to pH 5, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel, eluting with 25% ethyl acetate in hexanes. After evaporated and dried in vacuum, the alpha-alkyl 4-notrobenzyl alcohol was obtained.; 1-(3-Hydroxy-4-notrophenyl)ethyl alcohol (14).; Following the general procedure, <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (90.0 g, 539 mmol) gave the desired product 14 (40.0 g, 41%) as red oil. EPO <DP n="25"/>1H NMR (300 MHz, CDCI3) delta 1.50 (d, J = 6.6 Hz, 3H), 2.06 (br s, 1 H), 4.93 (q, J = 6.3 Hz, 1 H), 6.98 (dd, J = 8.8, 1.9 Hz, 1 H), 7.17 (d, J = 1.7 Hz, 1 H), 8.08 (d, J = 8.8 Hz, 1 H), 10.6 (s, 1 H).13C NMR (75 MHz, CDCI3) delta 25.3, 69.5, 1 16.3, 1 17.6, 125.5, 155.5, 156.9.
7-hydroxymethyl-4-methyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazine[ No CAS ]
[ 704-13-2 ]
[ 61161-83-9 ]
Yield
Reaction Conditions
Operation in experiment
With sodium borohydrid; In ethanol;
The 7-hydroxymethyl-4-methyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazine used as a starting material was obtained as follows:- Sodium borohydride (3 g) was added to a solution of 5-formyl-2-nitrophenol (7 g) in a mixture of 1,4-dioxan (80 ml) and ethanol (16 ml). The mixture was stirred at ambient temperature for 2 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and 2N aqueous hydrochloric acid. The organic phase was washed with water, dried (MgSO4) and evaporated. There was thus obtained 5-hydroxymethyl-2-nitrophenol (7 g) which was used without further purification.
3-(3-Hydroxy-4-nitro-benzylamino)-4-methoxy-N-phenyl-benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example 228 3-(3-Hydroxy-4-nitro-benzylamino)-4-methoxy-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 3-hydroxy-4-nitrobenzaldehyde as starting materials which are commercially available from Aldrich; m.p. 140-143 C.
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h;
To a solution of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (2.000 g, 11.98 mmol) in DMF (24 ml) were added K2C03 (1.687 g, 12.22 mmol) and iodomethane (1.52 ml, 24.44 mmol). The reaction mixture was stilTed at room temperature for 4 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organics were washed with asaturated solution of NaHCO3 (3 times), with water, with saturated solution of NaC1, dried over MgSO4, filtered and evaporated to give intermediate ha (2.137 g, 98%). ?H NMR (500 MHz, CDC13) oe 10.06 (s, 1H), 7.93 (d, J= 8.1 Hz, 1H), 7.60 (s, 1H), 7.54 (dd, J= 8.1, 1.4 Hz, 1H), 4.04 (s, 3H).
98%
With potassium carbonate;
Preparation of 3-methoxy-4-nitrobenzaldehyde (IIa) To a solution of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (2.000 g, 11.98 mmol) in DMF (24 ml) were added K2CO3 (1.687 g, 12.22 mmol) and iodomethane (1.52 ml, 24.44 mmol). The reaction mixture was stirred at room temperature for 4 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organics were washed with a saturated solution of NaHCO3 (3 times), with water, with saturated solution of NaCl, dried over MgSO4, filtered and evaporated to give intermediate IIa (2.137 g, 98%). 1H NMR (500 MHz, CDCl3) delta 10.06 (s, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.60 (s, 1H), 7.54 (dd, J=8.1, 1.4 Hz, 1H), 4.04 (s, 3H).
96%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 5h;
Example 39 : Synthesis of (1E,6E)-1-(3-hydroxy-4-methoxyphenyl)-7-(3-methoxy-4-nitrophenyl)hepta-1,6-diene-3,5-dione (CU049); (1) Synthesis of 3-methoxy-4-nitrobenzaldehyde; 3-Hydroxy-4-nitrobenzaldehyde (500 mg, 2.99 mmol) and potassium carbonate (0.42 g, 3.0 mmol) were dissolved in 6.0 mL of N,N-dimethyformamide. After addition of iodemethane (0.38 mL, 6.0 mmol) at room temperature, the mixture was stirred for 5 h at the same temperature. The reaction mixture was diluted with ethyl acetate and water, and separated. The organic layer was washed with brine twice, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate = 4/1 to 1/1) to obtain the title compound as a pale yellow powder (518 mg, 96%).
75%
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h;
3A. 3-Methoxy-4-nitro-benzaldehydeA mixture of 2-hydroxy-4-nitro-benzaldehyde (8.0 g, 47.9 mmol), methyl iodide (10.2 g,71.9 mmol) and potassium carbonate (6.61 g, 47.9 mmol) in DMF (80 mL) was stirred at 60C for 3 hours. The cooled reaction mixture was diluted with EtOAc (100 mL), washed with water (200 mL), dried (Na2SO4) and evaporated under reduced pressure to give the title compound (6.5 g, 75%) which was used without further purification.
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1h;
A mixture of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (51.3 g), iodomethane (38.3 ml) and K2CO3 (85 g) in DMF (250 ml) was stirred at 6O0C for 1 h. The reaction mixture was cooled to room temperature and poured into water (600 ml). The solids were collected by filtration and dried in vacuo (50 0C).Yield: 49.7 g.
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1h;
A mixture of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (51.3 g), iodomethane (38.3 ml) and K2CO3 (85 g) in DMF (250 ml) was stirred at 6O 0C for 1 h. The reaction mixture was cooled to room temperature and poured into water (600 ml). The solids were collected by filtration and dried in vacuo (50 0C). Yield: 49.7 g. 1H-NMR (CDCl3) delta 4.04 (s, 3H, OCH3), 7.55, 7.6, 7.9 (m, 3H, ArH), 10.08 (s, IH, CHO).
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1h;
(a). 3-Methoxy-4-nitro-benzaldehyde A mixture of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (51.3 g), iodomethane (38.3 ml) and K2CO3 (85 g) in DMF (250 ml) was stirred at 60 C. for 1 h. The reaction mixture was cooled to room temperature and poured into water (600 ml). The solids were collected by filtration and dried in vacuo (50 C.). Yield: 49.7 g. 1H-NMR (CDCl3) delta 4.04 (s, 3H, OCH3), 7.55, 7.6, 7.9 (m, 3H, ArH), 10.08 (s, 1H, CHO).
49.7 g
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 1h;
(a) . 3-Methoxy-4-nitro-benzaldehyde A mixture of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (51 .3 g), iodomethane (38.3 ml) and potassium carbonate (85 g) in DMF (250 ml) was stirred at 60 C for 1 h. The reaction mixture was cooled to room temperature and poured into water. The solids were collected by filtration and dried in 10 vacuo (50 C). Yield: 49.7 g.
12.1 g
To 20 g (0.12 mol) of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> in 200 ml of anhydrous DMF are added 42 g (0.13 mol) of caesium carbonate. The solution obtained is ultrasonicated for 5 minutes, and 9.4 ml (0.29 mol) of methyl iodide are then added. The reaction medium is heated at 80C for 18 hours and then diluted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. The residue is recrystallized from 300 ml of a hot 1/2 DMF/ethanol mixture. The crystals formed are filtered off, rinsed with cold ethanol and with hexane, and then dried under reduced pressure. 12.1 g of a solid are obtained.
53.4 g
With potassium carbonate; In N,N-dimethyl-formamide;
Methyl iodide (55.2 g, 389.2 mmol) was added dropwise to a stirred mixture of 3-hydroxy-4- nitrobenzaldehyde (50 g, 288.4 mmol) and potassium carbonate (53.8 g, 389.2 mmol) in DMF (250 ml). The reaction mixture was stirred overnight, poured into ice-cold water, and the precipitated solid was collected by filtration. The resulting solid was dried on a high vacuum overnight to obtain 53.4 g of 3-methoxy-4-nitrobenzaldehyde.1H NMR (CDCI3) 6: 10.06 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 0.8 Hz, 1H), 7.54 (dd, J = 8.2, 1.2 Hz, 1H), 4.02 (s, 3H).
The Schiff bases under investigation were prepared by mixing an ethanol solution (25 mL) of 4-amino-2-3-dimethyl-1-phenyl-3-pyrazolin-5-one (2.032 g, 0.01 mol) with 3,4-dimethoxybenzaldehyde (1.66 g, 0.01 mol) or <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (1.67 g, 0.01 mol) in the same volume of ethanol and was refluxed for 3 h in water bath and the obtained appropriate precipitate was collected and recrystallized from ethanol.
With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 2h;
To a solution of 3-hydroxy-4-nitro benzaldehyde in DMF (100 ml), chloroacetic acid ethyl ester (7 ml) and potassium carbonate (10 g) were added and heated for 2 hours to 50 C. Water was added to the reaction mixture, and the reaction mixture was extracted with acetic acid ethyl ester:ether. The organic phase was concentrated and the residue was purified by flash chromatography (silica gel, hexane:acetic acid ethyl ester: 4:1, 3:1, 2:1, 1:1) and resulted in the desired product (14.2 g).1H NMR (300 MHz, CDCl3): delta: 10.04 (s, 1H), 7.98 (d, 1H), 7.62 (d, 1H), 7.50 (s, 1H), 4.87 (s, 2H), 4.29 (q, 2H), 1.31 (t, 3H)
To a solution of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (1.67 g, 0.01 mol) in EtOH was added phenylhydrazine (1.08 g, 0.01 mol) dropwise with constant stirring which immediately precipitated to give a solid red Schiff base (L1). The product was filtered, washed with hexane and dried in vacuo.
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;
General procedure: To a 200 mL round-bottomed flask was added 4-hydroxy-3-nitrobenzaldehyde (1.671 g, 10.0 mmol), methyl 2-bromoacetate (0.950 ml, 10.00 mmol), and K2CO3 (1.382 g, 10.00 mmol) in DMF (25 ml). The reaction was stirred at 80 C for 2 hr. The reaction was poured over ice and the resulting solid was isolated by filtration, washed with water and dried in vacuo to give a light yellow solid (2.031 g, 85% yield).
With caesium carbonate; In acetonitrile; at 70℃; for 17h;
Method 18 2-Isopropoxy-4-(4-methylpiperazin-1-ylmethyl)phenylamine 3.0 g of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong>, 30 ml of acetonitrile, 5.9 g of caesium carbonate and 4.1 ml of 2-iodopropane are successively introduced into a three-necked round-bottomed flask under argon. The reaction mixture is heated at 70 C. for 17 h. After cooling to ambient temperature, the mixture is filtered through a sintered glass filter and the filtrate is concentrated to dryness under reduced pressure. The residue is taken up in a mixture of 50 ml of ethyl acetate and 15 ml of water, and then separated by settling out. The aqueous phase is separated and the organic phase is washed with 10 ml of water. The organic phase is then dried over magnesium sulfate and then concentrated to dryness under reduced pressure, so as to obtain 3.6 g of 3-isopropoxy-4-nitrobenzaldehyde in the form of a dark brown liquid.
3.6 g
With caesium carbonate; In acetonitrile; at 70℃; for 17h;Inert atmosphere;
3.0 g of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong>, 30 ml of acetonitrile, 5.9 g of caesium carbonate and 4.1 ml of 2-iodopropane are successively introduced into a three-necked round- bottomed flask under argon. The reaction mixture is heated at 70 ^ for 17 h. After cooling to ambient temperature, the mixture is filtered through a sintered glass filter and the filtrate is concentrated to dryness under reduced pressure. The residue is taken up in a mixture of 50 ml of ethyl acetate and 15 ml of water, and then separated by settling out. The aqueous phase is separated and the organic phase is washed with 10 ml of water. The organic phase is then dried over magnesium sulfate and then concentrated to dryness under reduced pressure, so as to obtain 3.6 g of 3-isopropoxy-4-nitrobenzaldehyde in the form of a dark brown liquid.
N,N′-(1,3-phenylenebis(methylene))bis(2-cyanoacetamide)[ No CAS ]
[ 1567834-55-2 ]
Yield
Reaction Conditions
Operation in experiment
With piperidine; In ethanol; at 20℃; for 18h;
General procedure: The amide 6 from the step1 reaction (5.0mmol), aldehyde 7 (5mmol), and piperidine (five drops) were added and stirred in anhydrous ethanol (10mL). Ethanol was evaporated and solid was triturated with water and dried under high vacuum to give the desired product 8.
With isopropyl nitrate; sulfuric acid; tetra(n-butyl)ammonium hydrogensulfate; In dichloromethane; at 20℃; for 0.25h;
To a stirring solution of 3- hydroxybenzaldehyde 23 (618 mg, 5.0 mmol) in dichloromethane (10 mL) was added tetrabutylammoniumhydrogen sulfate (85.0 mg, 0.25 mmol) and isopropyl nitrate (1.27 mL, 12.5 mmol). Concentrated sulfuric acid (610 mu) was added dropwise and the resulting reaction mixture was allowed to stir at room temperature for 15 minutes. The reaction contents were then transferred to a separatory funnel containing 50 mL of an aqueous saturated sodium bicarbonate solution. Dichloromethane was then used to extract the crude product. The combined organic layers were dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting solid was adsorbed onto silica gel and purified via flash column chromatography eluting with 99: 1 to 4: 1 hexanes:ethyl acetate to give isomer 30 (R = 0.44 in 3: 1 hexanes:ethyl acetate) as a yellow solid (201 mg, 24% yield) followed by the desired product 28 (R/= 0.19 in 3: 1 hexanes:ethyl acetate) as a pale yellow solid (411 mg, 47% yield). This is a known procedure (D. A. Learmonth (Portela & C.A., S.A., Port.), GB- 2377934, 2003). We were able to obtain 28 (CAS number: 42123-33-1) in 63% yield during the course of these investigations. Characterization Data for Compound 28: 1H NMR (400 MHz, CDC13): delta 10.40 (s, 1H), 10.30 (s, 1H), 7.67 (ddd, J = 8.3, 7.4, 0.7 Hz, 1H), 7.37 (dd, = 8.3, 1.4 Hz, 1H), 7.31 (dd, J = 7.4, 1.4 Hz, 1H). HRMS (DART): calc. for C7H9N204 (0511) [M+NH4]+: 185.0557, found: 185.0559. MP: 155-158 C, lit. 157 C (W. S. Saari, S. W. King, J. Med. Chem. 1974, 17, 1086-1090). Characterization Data for 30: 1H NMR (400 MHz, CDCI3): delta 10.58 (s, 1H), 10.06 (d, J = 0.6 Hz, 1H), 8.28 (d, = 8.7 Hz, 1H), 7.66 (d, = 1.7 Hz, 1H), 7.51 (dd, = 8.7, 1.7 Hz, 1H). Spectral values for 30 identical to previously reported 1H NMR data (A. Tsoukala, L. Liguori, G. Occhipinti, H.R. Bjorsvik, Tet. Lett. 2009, 50, 831-833). MP: 129-131 C, lit. 127C (J. Cologne, F. Pierre, Bull. Soc. Chim. Fr. 1964, 12, 3090-3096).
3-(2-Fluoroethoxy)-4-nitrobenzaldehyde (5) [0092] 3-Hydroxy-4-nitro- benzaldehyde (1, 1.0 g, 6.0 mmol) was deprotonated with K2CO3 (1.65 g, 12.0 mmol) in 10 mL dry DMF followed by reaction with 1-fluoro-2- iodoethane (0.8 mL, 9.0 mmol, 2.14 g/mL) at 80C. The reaction was monitored by TLC, and after 6 h no starting material was detected. The reaction mixture was cooled to room temperature, 100 mL ice cold water was added, and the compound was precipitated out, filtered under vacuum, and washed with water and diethyl ether. A yellow amorphous compound was obtained [yield 0.90 g, (70%)] and used without further purification for the next reaction. 1H NMR (400 MHz, chloroform-d) delta 10.05 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.69- 7.54 (m, 2H), 4.82 (d, J = 47.5 Hz, 2H,), 4.45 (d, J = 27.0 Hz, 2H,). 13C NMR (101 MHz, CDCl3) delta 190.3, 139.8, 126.7(2C), 123.6(2C), 114.0, 81.4 (d, JC-F = 173 Hz), 69.4 (d, JC-F = 21 Hz). 19F NMR (376 MHz, CDCl3) delta-90.90--91.16 (C-F coupling) -100.01 (F-decoupling).
2-(5-formyl-2-nitrophenoxy)ethyl 4-methylbenzenesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 6h;
General procedure: General Method For Synthesis (0191) [0089] 3-Hydroxy-4-nitrobenzaldehyde (1) or 4-hydroxy-3-nitrobenzaldehyde (2) (1.5 g, 8.9 mmol) was deprotonated with K2CO3, (2.48 g, 17.9 mmol) in 20 mL DMF followed by dropwise adding alkylene glycol ditosylate (a-b, 1 equiv) dissolved in 10 mL DMF at 80C. The reaction mixtures were heated with continuous stirring for additional 6 h. After completion of the reactions, the mixtures were cooled to room temperature, after 30 min, 200 mL ice cold water added, and extracted with 3 × 50 mL ethyl acetate. The organic phases were combined and washed with 20% sodium bicarbonate (50 mL), 50 mL brine, dried over MgSO4, and evaporated under reduced pressure. The crude products were purified by flash column chromatography in an ethyl acetate-hexane mixture. (0192) 2-(5-Formyl-2-nitrophenoxy)ethyl 4-Methylbenzenesulfonate (3) (0193) [0090] This dull yellow crystalline solid was eluted in 40% EtOAc:hexane, yield 1.2 g, (60%). 1H NMR (400 MHz, chloroform-d) delta 10.07 (s, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.62 (dd, J = 8.1, 1.5 Hz, 1H), 7.56 (d, J = 1.5 Hz, 2H), 7.41 (dq, J = 7.9, 0.7 Hz, 2H), 4.45 (d, J = 1.4 Hz, 4H), 2.49 (s, 3H). 13C NMR (101 MHz, chloroform-d) delta 190.2, 151.6, 145.5, 139.7, 132.5, 130.2, 128.2, 126.3, 123.6, 113.9, 67.6, 67.3, 21.9.
5-(((2-(6-chloropyridin-3-yl)ethyl)amino)methyl)-2-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64.5%
With sodium tetrahydroborate; In methanol; for 3h;Cooling with ice; Reflux;
<strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (167 mg) 2-chloro-5-aminoethylpyridine (156 mg) was added to 20 ml of methanol with stirring, under ice-cooling, NaBH4 150mg was slowly added to the system, heated to reflux for 3 hours, TLC detection reaction is completed, the reaction was stopped, cooled down, the system is to add 1N hydrochloric acid solution to adjust the pH 1-2, refluxed for 1h, the organic layer was washed with sodium bicarbonate and washed with saturated sodium chloride solution. The organic layer was washed with ethyl acetate, dried over anhydrous sodium sulfate, concentrated, purified by column chromatography, petroleum ether: ethyl acetate = 10: 1 to 2: 3, the product (S8) 198 mg, yield 64.5%
5-(4-(diphenylamine)styrene)-2-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57.4%
With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 36h;Inert atmosphere;
Under N2 protection, was added 20g (3.10 × 10 to 50mL three-necked flask-2mol) of Intermediate III, 1.55 × 10-2mol <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong>, 1.55 × 10-2mol K2CO3, 20mL N,N-dimethylacetamide and counter at 50muLAliquat336,100 C for 36h, thin layer chromatography the reaction was complete, 600mL water was added, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and column chromatography (petroleum ether and ethyl acetate acetate = 100: 1 as eluent) separation and purification, to give 1.40g of red solid product, i.e. intermediate IV, yield 57.4%.
46.1%
With Aliquat 336; potassium carbonate; In N,N-dimethyl acetamide; at 140℃; for 26h;
Weigh the intermediate III 3.11g (4.8×10-3 mol),<strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> 0.802g (4.8×10-3 mol),K2CO30.221g (1.6×10-3 mol) and a small amount of catalyst Aliquat336,20mL DMA is used as a solvent,Under reflux of nitrogen at 140 C for 26 h,The TLC tracer reaction was complete, suction filtration, and the filtrate was extracted three times with dichloromethane. The organic layer was dried and separated by column chromatography (yield ratio n-hexane:ethanol = 100:1).A red solid of 0.753 g was obtained in a yield of 46.1%.
2-(1-(7-(N,N-diethylamino)-2-oxo-2H-chromen-3-yl)ethylidene)malononitrile[ No CAS ]
[ 109-77-3 ]
3-amino-5-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3'-hydroxy-4'-nitro-[1,1'-biphenyl]-2,4-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With piperidine; In neat (no solvent); at 80℃; for 0.0333333h;Microwave irradiation;
General procedure: To a mixture of 2a (1 mmol), corresponding aldehyde (1 mmol) and malononitrile (1 mmol), an equiv amount of piperidine was added and swirled thoroughly. The mixture was irradiated in microwave oven at 300 W for 2 min. The solid product was washed with 5 mL of ethanol, filtered, dried, and recrystallized from ethanol to afford the pure product. The compounds 4a, 6a, 10a, 11a, 13-15a were characterized in our previous study.
With sodium ethanolate; In N,N-dimethyl-formamide; at 20℃; for 14h;
After dissolving <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (0.50 g, 2.99 mmol) in N, N-dimethylformamide (5 mL), triethylphosphonoacetate (1.32 mL, 6.59 mmol) Sodium ethoxide (0.45 g, 6.59 mmol) was successively added thereto, followed by stirring at room temperature for 14 hours. The resulting solid was filtered, washed with distilled water and n-hexane, and then dried under reduced pressure to obtain the title compound 16-a (0.52 g, 74%) as a yellow solid.
General procedure: The 10 ml aqueous solution of ethyl oxalate hydrazide was added 100mg benzaldehyde derivatives, stirred at room temperature or heated for 15min-5h. Collecting solids by filtration, the filtrate was washed by water. The product was drained by vacuum pump to afford desired compound. All yields were calculated relative to the benzaldehyde derivatives.
Weigh 3', 4', 5'-trimethoxypropiophenone (22 g, 100 mmol) and <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> (15 g, 100 mmol) in methanol equivalent In a solvent, 8 g of a 50% (ff/V) sodium hydroxide solution was added to the above mixture, and the mixture was stirred at room temperature under a nitrogen atmosphere overnight. TCL check reaction (dichloromethane:Ethyl acetate = 2:1 (v / nu)), after the reaction is completed, add 1 Mu HCl to adjust the pH of the mixture to l-Extract twice with 2,200 ml of dichloromethane. Dry the methylene chloride phase with anhydrous sodium sulfate, concentrate the silica gelPurification by column chromatography (petroleum ether: ethyl acetate = 4:1)Yield 65%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h;
Dissolve 1.07 g (1.0 equivalent) of <strong>[704-13-2]3-hydroxy-4-nitrobenzaldehyde</strong> and 0.9 g (1.2 equivalent) of bromopropyne in 10 mL of DMF, and add 0.2 g (2.0 equivalent) of potassium carbonate. After 4 hours of reaction at room temperature, 5 times the volume of purified water was added and extracted with ethyl acetate. The organic layers were combined and washed with saturated brine, after drying with anhydrous sodium sulfate, mix the sample on the column, The product was eluted with ethyl acetate: petroleum ether 1: 4,1.3 g of a yellow solid product was obtained in a yield of 100%.
(2Z)-2-[(3-hydroxy-4-nitrophenyl)methylidene]benzofuran-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With hydrogenchloride In water; isopropyl alcohol at 80℃;
4.1.4. General procedure of synthesis of aurones 9-15
General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
(2Z)-7-chloro-2-[(3-hydroxy-4-nitrophenyl)methylidene]benzofuran-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%
With hydrogenchloride In water; isopropyl alcohol at 80℃;
4.1.4. General procedure of synthesis of aurones 9-15
General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
(2Z)-7-bromo-2-[(3-hydroxy-4-nitrophenyl)methylene]benzofuran-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
21%
With hydrogenchloride In water; isopropyl alcohol at 80℃;
4.1.4. General procedure of synthesis of aurones 9-15
General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
ethyl (Z)-5-(3-hydroxy-4-nitrobenzylidene)-4-oxo-2-(phenylamino)-4,5-dihydrothiophene-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With piperidine; In ethanol; for 5.0h;Reflux;
General procedure: A mixture of 2a-2n (0.38 mmol), aldehyde 3a-3p and 44 (or ketone 39-43) (0.42 mmol) and piperidine (37.5 µL, 0.38 mmol) in ethanol (3.0 mL) was refluxed for the given time as described individually. The reaction was monitored by TLC. The purification was performed in either of the following two methods. Purification 1. When the product is crystalized as solid during reaction, the reaction mixture was cooled to room temperature slowly. The precipitate is collected by using vacuum filtration with washing cold EtOH. The collected product was dried under low pressured vacuum to give a desired product.
79%
With piperidine; In ethanol; for 5.0h;Reflux;
General procedure: A mixture of 2a-2n (0.38 mmol), aldehyde 3a-3p and 44 (or ketone 39-43) (0.42 mmol) and piperidine (37.5 µL, 0.38 mmol) in ethanol (3.0 mL) was refluxed for the given time as described individually. The reaction was monitored by TLC. The purification was performed in either of the following two methods. Purification 1. When the product is crystalized as solid during reaction, the reaction mixture was cooled to room temperature slowly. The precipitate is collected by using vacuum filtration with washing cold EtOH. The collected product was dried under low pressured vacuum to give a desired product.
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