* 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.
The procedure was adopted from ref.1 (Roy et al. 2011) Three-neck flask (250 mL) fitted with a condenser, thermometer and dropping funnel was charged with coumarin (1) (10 g, 68.5 mmol) and 50 mL of concentrated sulfuric acid (0.935 mol). After cooling the solution at -10 °C, the mixture of concentrated sulfuric acid (15 mL, 0.28 mol) and fuming nitric acid (5 mL, 0.12 mol)) was added dropwise during 1 h (temperature kept bellow -5 °C). Consequently, the mixture was poured on ice, the precipitate was filtered off a recrystallized from acetic acid. Yield: 11.26 g (86 percent) of white solid. Mp 191–192.5 °C (ref.2 reports 188 – 190 °C). Proton and carbon NMR data are in accordance with ref.3 1H NMR (400.13 MHz, CDCl3): δ = 6.60 (d, J = 9.5 Hz, 1H); 7.48 (d, J = 9.0 Hz, 1H); 7.83 (d, J = 9.5 Hz, 1H); 8.42 (dd, J = 9.0 Hz; 2.5 Hz, 1H); 8.46 (d, J = 2.5 Hz, 1H) ppm.13C NMR (100.62 MHz, CDCl3): δ = 118.1; 118.8; 118.8; 123.7; 126.6; 142.2; 144.0; 157.5; 158.8 ppm.
Reference：
[1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5894 - 5901
[2] Synthetic Communications, 2001, vol. 31, # 2, p. 301 - 309
[3] Molecular Pharmacology, 1995, vol. 48, # 6, p. 1063 - 1067
[4] Polyhedron, 2011, vol. 30, # 6, p. 913 - 922
[5] Journal of Inorganic Biochemistry, 2011, vol. 105, # 4, p. 577 - 588
[6] Spectroscopy Letters, 2012, vol. 45, # 3, p. 225 - 235
[7] Chemistry - A European Journal, 2014, vol. 20, # 22, p. 6608 - 6612
[8] Journal of Organometallic Chemistry, 2016, vol. 802, p. 60 - 71
[9] Patent: US5219734, 1993, A,
[10] Journal of the Indian Chemical Society, 2005, vol. 82, # 3, p. 258 - 261
[11] Journal of the Chemical Society, 1904, vol. 85, p. 1233
[12] Journal of the Chemical Society, 1910, vol. 97, p. 2106
[13] Journal of the Indian Chemical Society, 1927, vol. 4, p. 197[14] Chem. Zentralbl., 1927, vol. 98, # II, p. 1701
[15] Justus Liebigs Annalen der Chemie, 1846, vol. 59, p. 189
[16] Annales de Chimie (Cachan, France), 1842, vol. <3> 6, p. 345[17] Justus Liebigs Annalen der Chemie, 1843, vol. 45, p. 334
[18] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 10, p. 5377 - 5388
[19] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 20, p. 6087 - 6097
[20] Bioorganic Chemistry, 2014, vol. 52, p. 31 - 43
[21] Journal of Photochemistry and Photobiology A: Chemistry, 2015, vol. 303-304, p. 67 - 79
[22] Applied Organometallic Chemistry, 2016, vol. 30, # 5, p. 323 - 334
2
[ 97-51-8 ]
[ 75-36-5 ]
[ 2725-81-7 ]
Yield
Reaction Conditions
Operation in experiment
62%
With triethylamine In dichloromethane at 10℃; for 9 h; Molecular sieve
General procedure: A mixture of substituted salicylaldehydes (1a-f) (1.0 mmol), triethylamine (3.0 mmol), and freshly distilled acetyl chloride (2.0 mmol) and molecular sieves (~ 0.25 g, 4 Å, in pellet form) in dry CH2Cl2 was stirred for 9 h at 10 °C. The insolubles (presumed to be triethylamine hydrochloride and molecular sieves) were filtered off on a sintered glass funnel (under water-jet suction). The filtrate was washed with ice cold water, the separated organic layer dried (Na2SO4) and concentrated in vacuo to obtain the corresponding coumarins (2a-f). These were purified by column chromatography on silica gel eluting with 20percent ethyl acetate-hexane, and identified by m.p., and spectra as described below.
Reference：
[1] Journal of the Indian Chemical Society, 2005, vol. 82, # 3, p. 258 - 261
[2] Journal of the Indian Chemical Society, 1927, vol. 4, p. 197[3] Chem. Zentralbl., 1927, vol. 98, # II, p. 1701
21
[ 100-02-7 ]
[ 2725-81-7 ]
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 22, p. 11544 - 11550
Stage #1: coumarin With sulfuric acid at 4℃; for 0.166667h;
Stage #2: With guanidine nitrate
Synthesis of 6-nitro-coumarin a
6-nitro-coumarin a was synthesied accroding to the lit (Wang et al. 2015). The concentrated sulphuric acid (29 mL) was added to coumarin (0.1 mol, 14.6 g) at 4 °C, and the mixture was stirred for 10 min. Then guanidine nitrate (0.1 mol, 12.2 g) was added slowly. The reaction was monitored by TLC. After completion of the reaction, the resulting mixture was slowly poured into crushed ice and the resulting solid was separated by filtration and washed successively with water. The product was dried to get white compound a in yield of 98%; HPLC>98.0%
92%
With ammonium cerium(IV) nitrate; acetic acid at 20℃; for 2h;
90%
With sulfuric acid; nitric acid at -20℃; for 1h;
88%
With sulfuric acid; nitric acid at -5 - 20℃;
88%
With sulfuric acid; nitric acid at 20℃; for 1h;
88%
With sulfuric acid; nitric acid at -50 - 20℃; for 1h;
88%
With sulfuric acid; nitric acid at 0℃; for 1h;
3.2. 6-Nitrocoumarin
Coumarin was nitrated with mixed acid in an ice bath. Coumarin (1.00 g, 7.1 mmol) was dissolvedin conc. H2SO4 (5 mL) and temperature was maintained at 0 C and then 5 mL mixed acid (HNO3and H2SO4 (conc.) in 1:3 volume ratio) was added. The mixture was stirred keeping at 0 C for 1 h.Water at 0 C (50 mL) was added to precipitate obtaining A white precipitate of 6-nitrocoumarin.It was then filtered and washed thorough with cold water (10 mL). The compounds were dried a 60 Covernight. The identity of the compound was determined by 1H NMR and used as was obtained.Yield, 1.20 g (88%). 1H NMR (400.133 MHz, CDCl3) /ppm H50 8.43 (d, 4J50-70 = 2.4 Hz, 1H), H70 8.40(dd, 3J7’-80 = 9.0, 4J70-50 = 2.5 Hz, 1H), H40 7.80 (d, 3J40-30 = 9.7 Hz, 1H), H80 7.47 (d, 3J80-70 = 9.0 Hz, 1H),H30 6.59 (d, 3J30-40 = 9.7 Hz, 1H). (Figure S3).
86%
With sulfuric acid; nitric acid at 0 - 20℃; for 1h;
86%
With sulfuric acid; nitric acid at -10 - -5℃; for 1h;
6-Nitrocoumarin (2)
The procedure was adopted from ref.1 (Roy et al. 2011) Three-neck flask (250 mL) fitted with a condenser, thermometer and dropping funnel was charged with coumarin (1) (10 g, 68.5 mmol) and 50 mL of concentrated sulfuric acid (0.935 mol). After cooling the solution at -10 °C, the mixture of concentrated sulfuric acid (15 mL, 0.28 mol) and fuming nitric acid (5 mL, 0.12 mol)) was added dropwise during 1 h (temperature kept bellow -5 °C). Consequently, the mixture was poured on ice, the precipitate was filtered off a recrystallized from acetic acid. Yield: 11.26 g (86 %) of white solid. Mp 191-192.5 °C (ref.2 reports 188 - 190 °C). Proton and carbon NMR data are in accordance with ref.3 1H NMR (400.13 MHz, CDCl3): δ = 6.60 (d, J = 9.5 Hz, 1H); 7.48 (d, J = 9.0 Hz, 1H); 7.83 (d, J = 9.5 Hz, 1H); 8.42 (dd, J = 9.0 Hz; 2.5 Hz, 1H); 8.46 (d, J = 2.5 Hz, 1H) ppm.13C NMR (100.62 MHz, CDCl3): δ = 118.1; 118.8; 118.8; 123.7; 126.6; 142.2; 144.0; 157.5; 158.8 ppm.
85%
In nitric acid
1.G G.
In greater detail, coumarin (10g, 68 mmol) was nitrated as described in the literature with an excess of fuming nitric acid overnight at room temperature to give 6-nitrocoumarin as the only major product. The 6-nitrocoumarin exhibited the following characteristics: Yield 85%. 1 H NMR (DMSO-d6) 8.74 (d, J=3 Hz, 1H), 8.42 (dd, J=3, 9 Hz, 1H), 8.24 (d, J=10 Hz, 1H), 7.63 (d, J=9 Hz, 1H), 6.70 (d, J=10 Hz, 1H).
85%
With sulfuric acid; nitric acid; acetic acid
64.8%
With sulfuric acid; nitric acid at 0℃; for 2h;
1.1 (1) Synthesis of 6-nitro-2H-benzopyran-2-one (II):
Add HNO3 (1.3g, 20.1mmol) and H2SO4 10mL to a 250mL three-necked flask.Stir under ice salt bath and maintain the temperature at 0 °C.2 mL of H2SO4 dissolved in coumarin (2.9 g, 20 mmol) was added dropwise through a constant pressure dropping funnel, and then the temperature was maintained at 0 ° C for about 2 h.TLC detects the reaction completely,Pour the reaction into a 300 mL ice-water mixture.Stirring while stirring, the solid precipitated after the ice melted, suction filtration, and the filter cake was vacuum dried.Made a yellow solid,The yield was 64.8%.
With sulfuric acid; nitric acid; acetic acid
With sulfuric acid; nitric acid
durch Nitrierung;
With nitric acid
With sulfuric acid; nitric acid; acetic acid
With sulfuric acid; nitric acid
With sulfuric acid; nitric acid
With sulfuric acid; nitric acid
With nitric acid
With sulfuric acid; nitric acid at 0 - 5℃; for 2h;
With sulfuric acid; nitric acid In water at 0 - 20℃; for 1h;
1.14 g
With sulfuric acid; nitric acid at 0 - 20℃; for 1h;
With polyphosphoric acid In N,N-dimethyl-formamide at 145℃; for 6h; Inert atmosphere;
2. General procedure for the preparation of coumarins 3 (3a-3j)
General procedure: To the solution of polyphosphoric acid (PPA, 0.6 mmol) in DMF (0.3 mL) were added salicylaldehydes 1 (0.3 mmol) and acetic anhydride 2 (1.2 mmol) under a nitrogen atmosphere. The reaction mixture was stirred at 145°C 3-6 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution, dried over Na2SO4 and evaporated. The resulting crude compound was purified by silica gel column chromatography, affording the pure coumarins 3.
71%
With polyphosphoric acid In N,N-dimethyl-formamide at 145℃; for 6h; Inert atmosphere;
5 Example 5: A method for synthesizing coumarin derivatives:
Add 0.6mmol PPA and 0.3mL solvent DMF into the flask,Then add 0.3mmol of 5-nitrosalicylaldehyde and 1.2mmol of acetic anhydride in sequence,Stirring reaction in oil bath at 145 under nitrogen protection for 6h;After the reaction, the ethyl acetate was extracted three times, and the organic layer was washed with water and saturated sodium chloride solution successively.The organic layer was dried and washed with anhydrous sodium sulfate, filtered,The residue after the filtrate was concentrated under reduced pressure was separated and purified by silica gel column chromatography (V petroleum ether/V ethyl acetate=50:1),The coumarin derivative I-5 was obtained with a yield of 71%.
With sodium acetate
With sodium acetate at 185℃; for 6h; Inert atmosphere;
(a) General procedure for synthesis of coumarins
General procedure: To a stirred solution of salicylaldehyde (8.19 mmol) in acetic anhydride (1.67 g, 16.32 mmol)was added sodium acetate (1.33 g, 16.32 mmol) under nitrogen. The resulting mixture was heatedto 185 oC and then stirred for 6 h. After cooling, the reaction mixture was quenched with water (15mL) and extracted with ethyl acetate (30 mL). The organic layer was washed with brine (2×50mL), dried with Na2SO4, and concentrated under reduced pressure. The crude product was purifiedby chromatography on a silica gel column to afford the coumarins 1 (0 → 25% ethylacetate/hexane).
diisopropyl (6-nitrocoumarin-3-yl)phosphonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With chromium(III) nitrate nonahydrate; silver nitrate In 1,4-dioxane at 100℃; for 5h;
4 Example 4. R = -CH (CH3) 2, R1 = -H, R2 = -NO2, Preparation of 6-nitrocoumarin-3-diisopropylphosphonate Derivatives
To a 25 mL reaction flask was added 6-nitrosocoumarin (1.0 mmol, 191 mg) And diisopropyl phosphite (2.0 mmol, 232 mg) were dissolved in 5.0 mL of dioxane followed by AgNO3 (0.05 mmol, 8.4 mg) and Cr (NO3) 3 · 9H2O (0.5 mmol, 200 mg). The reaction was carried out by heating under stirring in an oil bath, The reaction temperature was 100 ° C. By TLC tracking the reaction process, Reaction time is 5h, After the reaction, The solvent was distilled off under reduced pressure, To the raffinate was added 10 mL of ethyl acetate, Washed twice with 20 mL of saturated NaHCO3, And then washed with 10 mL of saturated brine once, The solution was concentrated and purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 2/1) To obtain 0.212 g of a pale yellow viscous liquid, Yield 60.0%.
45%
With magnesium(II) nitrate hexahydrate; silver nitrate In acetonitrile at 100℃; for 6h; Inert atmosphere; regioselective reaction;
General experimental procedure for the synthesis of product 3
General procedure: In a Schlenk tube, coumarin 1 (0.5mmol), dialkyl H-phosphite 2 (1.0mmol), AgNO3 (0.025mmol, 4.2mg) and Mg(NO3)2·6H2O (0.25mmol, 64mg) were added and charged with Nitrogen (3 cycles). Anhydrous CH3CN (1mL) was then added. After heating in the oil bath at 100°C for 6h (monitored by TLC), 5mL ethylacetate was added to dilute the reaction solution. The solution was filtrated, and the solvent was distilled under vacuum. The crude product was purified by silica gel column chromatography to give the desired product 3 using ethylacetate/petroleum ether (1:5 to 2:1) as eluant.
41%
With C17H17Br2N3OPd; silver nitrate In acetonitrile at 80℃; for 10h; Schlenk technique; Inert atmosphere; regioselective reaction;
4.4 General procedure for the phosphorylation reaction
General procedure: In a typical reaction, a Schlenk tube charged with coumarins (0.5mmol), dialkyl phosphite (1.0mmol), NHC palladium complex, AgNO3 and solvent (2mL) was heated at 80°C for 10h. The mixture was then cooled, filtered and the filtrate was evaporated. Purification of the residue by column chromatography (silica, petroleum ether/ethylacetate=2/1-1/4, v/v) produced the pure products, which were characterized by 1H NMR and 13C NMR. The analytical data of the products were shown in the Supporting Information.
6-nitro-3-((trifluoromethyl)thio)-2H-chromen-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With iron(III) chloride; sulfur In ethanol at 60℃; for 3h; Sealed tube;
4 Example 4
6mmol of 6-nitrocoumarin was added to the reaction vessel,Sodium trifluoroacetate 1 mmol,Elemental sulfur 1mmol,0.005mmol of ferric chloride and 2ml of ethanol,Sealing reaction at 60 ° C for 3 hours,The reaction column is subjected to column chromatography,Performing a nuclear magnetic spectrum analysis on the above white solid powder,After identification,The spectral data corresponds to the structural formula,Proven synthesis of 3-trifluoromethylthio-6-nitrocoumarinPrime,The yield was 95%.
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