* 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.
Reference：
[1] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[2] Chem.Abstr., 1953, p. 9957
[3] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[4] Chem.Abstr., 1953, p. 9957
[5] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[6] Chem.Abstr., 1953, p. 9957
3
[ 97-51-8 ]
[ 39835-28-4 ]
[ 39835-09-1 ]
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 17, p. 8657 - 8667
4
[ 97-51-8 ]
[ 39835-28-4 ]
[ 64037-16-7 ]
Reference：
[1] Gazzetta Chimica Italiana, 1959, vol. 89, p. 1009,1013
5
[ 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] Chemische Berichte, 1887, vol. 20, p. 2110[2] Archiv der Pharmazie (Weinheim, Germany), 1891, vol. 229, p. 82
15
[ 105-39-5 ]
[ 97-51-8 ]
[ 2725-81-7 ]
[ 153136-77-7 ]
Reference：
[1] Journal of Chemical Research - Part S, 2003, # 11, p. 718 - 720
16
[ 127-09-3 ]
[ 108-24-7 ]
[ 97-51-8 ]
[ 2725-81-7 ]
Reference：
[1] Chemische Berichte, 1887, vol. 20, p. 2110[2] Archiv der Pharmazie (Weinheim, Germany), 1891, vol. 229, p. 82
17
[ 97-51-8 ]
[ 39835-28-4 ]
[ 64037-16-7 ]
Reference：
[1] Gazzetta Chimica Italiana, 1959, vol. 89, p. 1009,1013
18
[ 97-51-8 ]
[ 18761-31-4 ]
Reference：
[1] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[2] Chem.Abstr., 1953, p. 9957
[3] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[4] Chem.Abstr., 1953, p. 9957
[5] Nippon Kagaku Zasshi, 1952, vol. 73, p. 282,285[6] Chem.Abstr., 1953, p. 9957
[7] Gazzetta Chimica Italiana, 1956, vol. 86, p. 1257,1267
19
[ 97-51-8 ]
[ 16789-84-7 ]
Yield
Reaction Conditions
Operation in experiment
98%
With bromine In dichloromethane at 20℃; for 1 h;
2-Hydroxy-5-nitro-benzaldehyde (2.0 g, 12 mmol) and dichloromethane (30 mL) were added to a 100 mL two-neck flask, then bromine (2.24 g, 14 mmol) was added dropwise. The mixture was stirred for 1 h at rt. The mixture was quenched with saturated aqueous sodium thiosulfate (100 mL), and the resulting mixture was partitioned. The aqueous phase was extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated brine (80 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/20) to give the title compound as a yellow solid (2.89 g, 98percent).MS (ES-API, pos. ion) m/z: 246.9 [M + 2]t
82%
With N-Bromosuccinimide In acetonitrile at 15 - 30℃;
N-bromosuccinimide (2.12 g, 12.0 mmol)Add to 5-nitrosalicylaldehyde (2.0 g, 11.9 mmol)In a solution of acetonitrile (60 mL),The reaction system was stirred at room temperature overnight.Then add ethyl acetate,Organic phase in turn,Saturated saline solution,Water washing,The organic phase was separated and dried over anhydrous sodium sulfate.filter,concentrate,Methanol was then added to the residue and heated to reflux.Then, water was added dropwise to the reaction system to precipitate a solid, and the mixture was cooled to 0 ° C and stirred for half an hour.filter,The filter cake was dried in vacuo to give compound 26.1 (2.4 g, yield: 82percent) as a yellow solid.
80 %Chromat.
With ammonium metavanadate; perchloric acid; tetrabutylammomium bromide; dihydrogen peroxide In chloroform; water at 20℃; for 0.416667 h;
General procedure: NH4VO3 (5 molpercent) and H2O2 (200 molpercent) were placed in a flask. After complete dissolution of the catalyst, TBAB (3 mmol) was added and the mixture was stirred at room temperature. Then, Et2O (10 ml) and aromatic substrate (1 mmol) were added to the mixture. Finally, by slow drip, 1 ml of 1N HClO4 solution was added. After adding the acid, the colour of the reaction changed from yellow to red due to the formation of oxomonoperoxovanadium. Conversion was followed by TLC and determined by GC. The phases were separated and the aqueous phase was extracted with CH2Cl2 (15 ml x3). The organic phases were pooled, washed with brine, dried over Na2SO4 and filtered. The solvent was removed under reduced pressure and the resulting crude product was purified by column chromatography with Hex:AcOEt.
Reference：
[1] Organic Letters, 2011, vol. 13, # 1, p. 26 - 29
[2] Tetrahedron Letters, 2005, vol. 46, # 51, p. 8959 - 8963
[3] Patent: WO2017/36404, 2017, A1, . Location in patent: Page/Page column 115
[4] Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5867 - 5869
[5] Patent: CN108623615, 2018, A, . Location in patent: Paragraph 0332; 0547; 0548; 0549
[6] Journal of the American Chemical Society, 1949, vol. 71, p. 3602,3604
[7] Journal of Organic Chemistry USSR (English Translation), 1967, vol. 3, p. 1566 - 1569[8] Zhurnal Organicheskoi Khimii, 1967, vol. 3, # 9, p. 1608 - 1613
[9] Magnetic Resonance in Chemistry, 1992, vol. 30, # 11, p. 1128 - 1131
[10] South African Journal of Chemistry, 2006, vol. 59, p. 125 - 128
[11] Tetrahedron Letters, 2016, vol. 57, # 50, p. 5644 - 5648
20
[ 107-30-2 ]
[ 97-51-8 ]
[ 16644-30-7 ]
Reference：
[1] RSC Advances, 2013, vol. 3, # 22, p. 8308 - 8317
[2] Journal of Organic Chemistry, 2002, vol. 67, # 2, p. 533 - 540
[3] Patent: US5252742, 1993, A,
[4] Patent: EP529100, 1993, A1,
[5] Patent: EP530369, 1993, A1,
[6] European Journal of Organic Chemistry, 2006, # 4, p. 1050 - 1056
[7] Dyes and Pigments, 2010, vol. 86, # 1, p. 74 - 80
[8] Chemistry Letters, 1991, # 2, p. 209 - 212
[9] Chemistry Letters, 1991, # 11, p. 1873 - 1876
[10] Patent: US2004/230044, 2004, A1, . Location in patent: Page 5-6
21
[ 97-51-8 ]
[ 16644-30-7 ]
Reference：
[1] Patent: US5521269, 1996, A,
22
[ 90-02-8 ]
[ 5274-70-4 ]
[ 97-51-8 ]
Reference：
[1] Organic Process Research and Development, 2012, vol. 16, # 8, p. 1430 - 1435
[2] Chemische Berichte, 1887, vol. 20, p. 1928
[3] Justus Liebigs Annalen der Chemie, 1865, vol. 135, p. 169
[4] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1876, p. 488
[5] Berzelius'Jahresber., vol. 20, p. 314
[6] Chemische Berichte, 1887, vol. 20, p. 2110[7] Archiv der Pharmazie (Weinheim, Germany), 1891, vol. 229, p. 82
[8] Chemische Berichte, 1887, vol. 20, p. 1928
[9] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1876, p. 488
[10] Journal of Organic Chemistry, 2011, vol. 76, # 19, p. 8088 - 8094
Reference：
[1] Justus Liebigs Annalen der Chemie, 1865, vol. 135, p. 169
[2] Berzelius' Jahresb., vol. 20, p. 314
[3] Gazzetta Chimica Italiana, 1876, vol. 6, p. 460[4] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1876, p. 488
25
[ 7697-37-2 ]
[ 90-02-8 ]
[ 64-19-7 ]
[ 5274-70-4 ]
[ 97-51-8 ]
Reference：
[1] Chemische Berichte, 1887, vol. 20, p. 1928
26
[ 97-51-8 ]
[ 74-88-4 ]
[ 25016-02-8 ]
Yield
Reaction Conditions
Operation in experiment
94%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12 h;
2-Hydroxy-5-nitrobenzaldehyde (1) (2 g, 12.0 mmol) was methylated using methyl iodide (1.7 g, 36 mmol) and anhydrous potassium carbonate (1.7 g, 36 mmol) in DMF (7 mL), by stirring at room temperature for 12 h. After the TLC showed complete disappearance of the starting material, the reaction mixture was poured in to crushed ice leading to the precipitation of the product. This was further purified by column chromatography over silica gel using 1:10 ethyl acetate/hexane to obtain a yield of 94percent (2.04 g) of compound (2). For characterization, the spectroscopic data was consistent with what has been previously reported (Yang et al., 2007, Org. Lett. 9:5287).1H NMR (CDCl3, 500 MHz): δ 10.48 (1H, s), 8.7 (1H, d, J=3.0 Hz), 8.47 (1H, dd, J=9 Hz), 7.05 (1H, d, 9 Hz), 4.04 (3H, s); 13C NMR (CDCl3, 100 MHz): 187.8, 165.8, 141.8, 130.9, 124.8, 112.5, 57.0.
87.8%
With NaH In N,N-dimethyl-formamide
Synthesis of 5-(N-methyl-N-methylsulfonylamino)-o-anisaldehyde To a solution of 5-nitrosalicylaldehyde (1.00 g, 6.0 mmol) in DMF (20 ml) was added NaH (246 mg) and methyl iodide (2.56 g, 18 mmol) at 0° C. The mixture was stirred for 8.5 hr at 60° C. After the reaction mixture was extracted with ether, the extract was washed with aqueous NaHCO3, brine and 5percent-HCl/aq.NaCl, dried over MgSO4 and concentrated in vacuo to afford 2-methoxy-5-nitrobenzaldehyde (0.95 g, 87.8percent) as a yellow needle. 1 H NMR (CDCl3) δ: 10.45 (s, 1H), 8.70 (d, J=2.9 Hz, 1H), 8.45 (dd, J=8.8, 2.9 Hz, 1H), 7.14 (d, J=8.8 Hz, 1H), 4.08 (s, 3H).
93.0%
With sodium carbonate In <i>N</i>-methyl-acetamide
Example 9 2-Methoxy-5-nitrobenzaldehyde 2-Hydroxy-5-nitrobenzaldehyde (2.40 g, 14.0 mmol) was dissolved in dimethylformamide (50 mL). To this was added iodomethane (4.48 ml, 72.0 mmol) and sodium carbonate (3.04 g, 28.0 mmol). This mixture was stirred for 24 hours and was poured into water. The solid was collected by filtration to give 2.38 g (93.0percent). Mp 88-89° C.;1 H NMR (CDCl3): d, 10.46 (s,1H), 8.69 (d,1H), 8.45 (dd,1H), 7.15 (d,1H), 4.10 (s,3H). MS (DCl): 182 (MH+). C8 H7 NO4.
Reference：
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 15, p. 3435 - 3438
[2] Patent: US2013/261295, 2013, A1, . Location in patent: Paragraph 0166; 0167
[3] Journal of the American Chemical Society, 2017, vol. 139, # 19, p. 6654 - 6662
[4] Patent: US5837711, 1998, A,
[5] Journal of the Chemical Society, 1951, p. 2462,2466
[6] Patent: US5994563, 1999, A,
[7] Journal of the American Chemical Society, 2018,
27
[ 97-51-8 ]
[ 2912-78-9 ]
Reference：
[1] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7590 - 7593
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;
2-Hydroxy-5-nitrobenzaldehyde (1) (2 g, 12.0 mmol) was methylated using methyl iodide (1.7 g, 36 mmol) and anhydrous potassium carbonate (1.7 g, 36 mmol) in DMF (7 mL), by stirring at room temperature for 12 h. After the TLC showed complete disappearance of the starting material, the reaction mixture was poured in to crushed ice leading to the precipitation of the product. This was further purified by column chromatography over silica gel using 1:10 ethyl acetate/hexane to obtain a yield of 94% (2.04 g) of compound (2). For characterization, the spectroscopic data was consistent with what has been previously reported (Yang et al., 2007, Org. Lett. 9:5287).1H NMR (CDCl3, 500 MHz): delta 10.48 (1H, s), 8.7 (1H, d, J=3.0 Hz), 8.47 (1H, dd, J=9 Hz), 7.05 (1H, d, 9 Hz), 4.04 (3H, s); 13C NMR (CDCl3, 100 MHz): 187.8, 165.8, 141.8, 130.9, 124.8, 112.5, 57.0.
87.8%
With NaH; In N,N-dimethyl-formamide;
Synthesis of 5-(N-methyl-N-methylsulfonylamino)-o-anisaldehyde To a solution of 5-nitrosalicylaldehyde (1.00 g, 6.0 mmol) in DMF (20 ml) was added NaH (246 mg) and methyl iodide (2.56 g, 18 mmol) at 0 C. The mixture was stirred for 8.5 hr at 60 C. After the reaction mixture was extracted with ether, the extract was washed with aqueous NaHCO3, brine and 5%-HCl/aq.NaCl, dried over MgSO4 and concentrated in vacuo to afford 2-methoxy-5-nitrobenzaldehyde (0.95 g, 87.8%) as a yellow needle. 1 H NMR (CDCl3) delta: 10.45 (s, 1H), 8.70 (d, J=2.9 Hz, 1H), 8.45 (dd, J=8.8, 2.9 Hz, 1H), 7.14 (d, J=8.8 Hz, 1H), 4.08 (s, 3H).
87.4%
With potassium carbonate; In N,N-dimethyl-formamide; at 15 - 50℃;Large scale;
Into a 20 L round-bottom flask was charged 2-hydroxy-5-nitrobenzaldehyde (1.6 kg, 1.0 eq) and DMF (8.0 L, 5.0 v/w). K2CO3 (2.6 kg, 2.0 eq.) was added into the mixture followed by the dropwise addition of CH3I (1.5 kg, 1.1 eq.) at 15~35C.The reaction was heated to 40-50C. The reaction was monitored by HPLC until 2-hydroxy-5-nitrobenzaldehyde was present in less than 5.0%. Water (16 L, 10 v/w) was added into the mixture. The reaction was stirred for 12 hours at 20±5C. The reaction was filtered and the filter cake was washed with water (3.2 L, 2.0 v/w) twice. The filter cake was col lected and dried under vacuum at 40-50C. This resulted in an off-white product (1.52 kg, purity: 99.7%, yield: 87.4%).
2.38 g (93.0%)
With sodium carbonate; In N-methyl-acetamide;
Example 9 2-Methoxy-5-nitrobenzaldehyde 2-Hydroxy-5-nitrobenzaldehyde (2.40 g, 14.0 mmol) was dissolved in dimethylformamide (50 mL). To this was added iodomethane (4.48 ml, 72.0 mmol) and sodium carbonate (3.04 g, 28.0 mmol). This mixture was stirred for 24 hours and was poured into water. The solid was collected by filtration to give 2.38 g (93.0%). Mp 88-89 C.;1 H NMR (CDCl3): d, 10.46 (s,1H), 8.69 (d,1H), 8.45 (dd,1H), 7.15 (d,1H), 4.10 (s,3H). MS (DCl): 182 (MH+). C8 H7 NO4.
2-Hydroxy-5-nitro-benzaldehyde (2.0 g, 12 mmol) and dichloromethane (30 mL) were added to a 100 mL two-neck flask, then bromine (2.24 g, 14 mmol) was added dropwise. The mixture was stirred for 1 h at rt. The mixture was quenched with saturated aqueous sodium thiosulfate (100 mL), and the resulting mixture was partitioned. The aqueous phase was extracted with ethyl acetate (100 mL x 2). The combined organic phases were washed with saturated brine (80 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/20) to give the title compound as a yellow solid (2.89 g, 98%).MS (ES-API, pos. ion) m/z: 246.9 [M + 2]t
82%
With N-Bromosuccinimide; In acetonitrile; at 15 - 30℃;
N-bromosuccinimide (2.12 g, 12.0 mmol)Add to 5-nitrosalicylaldehyde (2.0 g, 11.9 mmol)In a solution of acetonitrile (60 mL),The reaction system was stirred at room temperature overnight.Then add ethyl acetate,Organic phase in turn,Saturated saline solution,Water washing,The organic phase was separated and dried over anhydrous sodium sulfate.filter,concentrate,Methanol was then added to the residue and heated to reflux.Then, water was added dropwise to the reaction system to precipitate a solid, and the mixture was cooled to 0 C and stirred for half an hour.filter,The filter cake was dried in vacuo to give compound 26.1 (2.4 g, yield: 82%) as a yellow solid.
80%Chromat.
With ammonium metavanadate; perchloric acid; tetrabutylammomium bromide; dihydrogen peroxide; In chloroform; water; at 20℃; for 0.416667h;
General procedure: NH4VO3 (5 mol%) and H2O2 (200 mol%) were placed in a flask. After complete dissolution of the catalyst, TBAB (3 mmol) was added and the mixture was stirred at room temperature. Then, Et2O (10 ml) and aromatic substrate (1 mmol) were added to the mixture. Finally, by slow drip, 1 ml of 1N HClO4 solution was added. After adding the acid, the colour of the reaction changed from yellow to red due to the formation of oxomonoperoxovanadium. Conversion was followed by TLC and determined by GC. The phases were separated and the aqueous phase was extracted with CH2Cl2 (15 ml x3). The organic phases were pooled, washed with brine, dried over Na2SO4 and filtered. The solvent was removed under reduced pressure and the resulting crude product was purified by column chromatography with Hex:AcOEt.
EXAMPLE 1 While cooling a mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether in an ice bath, 43.9 g of anhydrous aluminum chloride was added in small portions to the mixture, followed by stirring at room temperature for 10 minutes and thereafter by refluxing with heating for 22 hours. The reaction mixture was then cooled in an ice bath, and 200 ml of water was added to the mixture with full stirring, whereby white crystals were separated out. The white crystals were collected and dissolved in hot hexane, and the solution was filtered. The mother liquor was thereafter cooled, giving 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde in the form of white needlelike crystals (yield 72%). 1 H-NMR(CDCl3); deltappm 4.72(s, 2H, --CH2 Cl), 8.56(s, 2H, ArH), 10.00(s, 1H, CHO), 12.10(s, 1H, OH).
72%
aluminium trichloride; In hexane; water;
Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals were collected, dissolved in hot hexane and filtered and the mother liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH)
72%
aluminium trichloride; In hexane; water;
Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals are collected, dissolved in hot hexane and filtered and the motor liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH)
With aluminum (III) chloride;
A compound having the structure shown as the final product in the scheme detailed in FIG. 4 was synthesized and characterized. Reaction step (1) (shown in isolation in FIG. 6) proceeds well and the product was characterized by 1H NMR spectroscopy (peak obtained at MW=214). This product was readily purified by recrystallization from hot n-hexane. The yield of this reaction in our hands was not established. The literature value is 89% isolated yield. L. D. Taylor and R. B. Davis, J. Org. Chem. 1963, 28, 1713. [0074] Reaction step (2) (shown in isolation in FIG. 7) also proceeded and the crude product was purified by recrystallization from ethanol/tetrahydrofuran. Small, square-shaped orange crystals were obtained over a period of two days in ca. 12% yield. Analysis of these crystals via 1H NMR spectroscopy suggests that their crystal structure may contain tetrahydrofuran (see FIG. 8). Mass spectroscopy yielded an m/z peak at 352. Further addition of tetrahydrofuran to the ethanol mixture yielded a second crop of similar crystals. However, this second crop was coated in orange-colored viscous oil, characteristic of material that had come out of solution too quickly. This material is to be further recrystallized to improve product yield. [0075] Reaction step (3) (shown in isolation in FIG. 9) was carried out under reflux (approximately 80 C.) proceeded well and yielded a solid product as expected. Previous attempts to synthesize this compound have yielded viscous oil. Purification of the product from reaction (2) appears to lead to a purer product from reaction (3) as we obtained a solid instead of an oil. This product was analyzed by 1H NMR and by ES mass spectral analysis: FW ca. 506, [M]+504 (100%). [0076] Reaction step (4) (shown in isolation in FIG. 10) was conducted overnight at pH=10-11. However, the pH dropped to a value of 9 after 24 h. Thus, the pH was again raised to a value of ca. 10 and allowed to react for a further 24 h, during which time the reaction mixture maintained its pH value of ca. 10. It appears that at least 48 hours are necessary for the reaction to go to completion as indicated by the lack of further pH change. ES mass spectral analysis indicated a prominent peak at 701 (expected mass of the ligand+Na+). [0077] Reaction step 5 (i.e., the final reaction step shown in FIG. 4) involves the insertion of the metal to the macrocycle. The sample was run through a Chelex 100 column after first neutralizing the reaction mixture to pH=7. However, upon eluting with water, only pale yellow oil was obtained. This did not display the characteristic absorbances of ca. 510 and 550 nm upon exposure to UV-light irradiation. In addition, it was observed that a band of purple-colored material was trapped at the top of the Chelex column. Various solvents were used to try to pass this band through the column, and ethanol and chloroform each were found to be effective to elute the product. This purple-colored material displayed characteristic color changes expected for the final product. UV irradiation (described in the following example) produced a product with absorbances at ca. 510 and 550 nm. Irradiation with white light eliminates these absorbance peaks. Mass spec for the product from step 5 yielded a peak at 835 and also peak at 678 (representing either free ligand or artifactual dissociation of product during electrospray).
With potassium carbonate; In N,N-dimethyl-formamide; at 85 - 90℃; for 15h;Inert atmosphere;
Example-1: Preparation of ethyl 5-nitro-l-benzofuran-2-carboxylate To a solution of DMF (400ml), K2C03 powder (124. lg) and 5-nitro salicylaldehyde (lOOg) was slowly added Diethyl bromomalonate (171.7g) at 30-40C under Nitrogen atmosphere. The reaction mixture was stirred at 85-90C under Nitrogen atmosphere for 15 hours. Cool the reaction mix to 80-85C. Cyclohexane (500ml) was added to the reaction mix at 70-85C within 1 hour and then stirred the reaction mix at 80-85C for 15-30 minutes. The reaction mixture was cooled to 15-20C and process water (1000ml) was added to the reaction mixture at 15-20C within 1 hour. The reaction mixture was stirred at 20-30C for 1-2 hour and then the solid was filtered and washed with process water (100mlx5). Dried at 55-60C. for 8-10 hours. Yield: 95.2%
95.2%
With potassium carbonate; In N,N-dimethyl-formamide; at 30 - 90℃; for 15h;Inert atmosphere;
To a solution of DMF (400 ml), K2CO3 powder (124.1 g) and 5-nitro salicylaldehyde (100 g) was slowly added Diethyl bromomalonate (171.7 g) at 30-40 C. under Nitrogen atmosphere. The reaction mixture was stirred at 85-90 C. under Nitrogen atmosphere for 15 hours. Cool the reaction mix to 80-85 C. Cyclohexane (500 ml) was added to the reaction mix at 70-85 C. within 1 hour and then stirred the reaction mix at 80-85 C. for 15-30 minutes. The reaction mixture was cooled to 15-20 C. and process water (1000 ml) was added to the reaction mixture at 15-20 C. within 1 hour. The reaction mixture was stirred at 20-30 C. for 1-2 hour and then the solid was filtered and washed with process water (100 ml*5). Dried at 55-60 C. for 8-10 hours. Yield: 95.2%
(2E)-N-[(3R)-3-(hydroxymethyl)(2H,3H-benzo[e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 16 (2E)-N-[(3R)-3-(Hydroxymethyl)(2H,3H-benzo[e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide Analogous to the procedure described for Example 15, the title product was prepared starting from (S)-glycidyl tosylate (Aldrich), 2-hydroxy-5-nitrobenzaldehyde (Aldrich) and 4-tert-butyl-trans-cinnamic acid (EMKA Chemie). MP 170-171 C. MS (ESI, pos. ion) m/z: 368 (M+1).
aluminium trichloride; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; chloromethyl methyl ether;
EXAMPLE 1 Synthesis of 3-chloromethyl-5-nitrosalicylaldehyde 5-Nitrosalicylaldehyde (2.42 g, 14.5 mmols) was suspended in 20 ml of chloromethyl methyl ether, and aluminum chloride (7.97 g, 60.0 mmols) was added while cooling in an ice bath. After stirring at room temperature for 10 minutes, the mixture was heated at 60 C. for one hour. Then, the reaction solution was poured into 100 ml of ice water while cooling in an ice bath and the resulting yellow precipitate was filtered. The resulting precipitate was recrystallized from 330 ml of hexane to give 3-chloromethyl-5-nitrosalicylaldehyde (2.49 g, 11.6 mmols) as a yellow needle-like crystal (yield 80%). 1 H-NMR(60 MHz, CDCl3); delta 4.7(s, 2 H, --CH2 Cl), 8.5(s, 2 H, ArH), 10.0(s, 1H, --CHO), 12.1(s, 1 H, --OH)
5-nitro-2-(4-phthalimidobutoxy)benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium iodide; potassium carbonate; In N-methyl-acetamide; ethyl acetate;
The <strong>[4591-55-3]dimethyl pyridine-3,5-dicarboxylate</strong> used as starting material was obtained as follows: A stirred mixture of 5-nitrosalicylaldehyde (8.36 g.), potassium carbonate (11.04 g.), potassium iodide (0.2 g.), N-(4-bromobutyl)phthalimide (15.6 g.) and dimethylformamide (120 ml.) was heated at 100 C. for 48 hours and then cooled to laboratory temperature. Saturated aqueous sodium chloride solution (1200 ml.) and ethyl acetate (300 ml.) were added and the mixture was shaken and filtered, the solid residue being retained. The layers of the filtrate were separated, the aqueous layer was extracted with ethyl acetate (200 ml.) and the combined ethyl acetate solutions were washed three times with saturated aqueous sodium chloride solution (100 ml. each time), dried over magnesium sulphate and evaporated to dryness. The combined residue and retained solid were crystallized from methanol and there was thus obtained 5-nitro-2-(4-phthalimidobutoxy)benzaldehyde, m.p. 145-148 C.
With sodium carbonate; In 1-methyl-pyrrolidin-2-one; at 100℃;
To the solution of 5-nitro salicylaldehyde (1 mmol) in NMP (8 vol), Na2CO3 (2.5 mmol) was added stirred for 1/2 h, followed by addition of ethyl bromo acetate (1.5 mmol) and stirred for overnight at 100 C. RM was dissolved in water and then extracted with ethyl acetate (2 * 100 mL), the combined organic layer was washed with brine solution, dried over Na2SO4 and then evaporated to dryness. Compound purified by column chromatography. Off White solid, 89% yield, mp 176.4-178.4 C, 1H NMR (300 MHz, CDCl3): delta = 8.12 (s, 1H), 7.87 (s, sH), 7.32 (m, 2H), 4.35 (q, J = 7.5, 14.4 Hz, 2H), 1.33 (m, 3H) 6H); 13C NMR (75 MHz, DMSO+CDCl3): 158.6, 157.9, 144.2, 130.6, 119.8, 114.2, 111.5, 110.2, 106.2, 58.8, 13.2. MS calcd for C11H9NO5: 235.1. Found: 236.0, (M+). Anal. Calcd for C11H9NO5: C, 56.17; H, 3.86; N, 5.96. Found: C, 56.15; H, 3.87; N, 5.94.
89%
A solution of 5-nitrosalicylaldehyde (20 g, 0.119 mol), potassium carbonate (33 g, 0.238 mol) was added to DMF (400 mL)The flask was stirred at room temperature for 1 hour and then slowly added dropwiseBromoacetate (20 g, 0.119 mol) and the reaction was heated to 85 C6-7 hours, point plate detection to complete reaction. Cooling to room temperature, stirring with water, a large number of solid precipitation, suction filtration, washing, drying15 g of a yellowish gray solid was obtained 10, 89%.
With cholin hydroxide; In water; at 80℃; for 1h;Green chemistry;
General procedure: In a general procedure, a mixture of indolium iodide 1 (1.0 mmol), 2-hydroxy arylaldehyde 2 (1.0 mmol) and aqueous solution of 40 wt% choline hydroxide (1.5 mmol)was stirred at 80 C for 1 h. Then reaction mixture was cooled to room temperature, the solid product was filtered off and washed with water. The crude product was purified by column chromatography on silica gel with hexane:ethyl acetate (95:05) as the eluent toafford the corresponding spiropyran 3 (Scheme 3).
91%
1,2,3,3-Tetramethylindolindolenium iodide (6.35 g, 21 mmol)was dissolved in anhydrous methanol (100 mL) and heated toreflux. Then triethylamine (1 mL) was added and the solution wasstirred for 15 min. 5-Nitrosalicylaldehyde (3.34 g, 20 mmol) wasadded and the mixture was refluxed for 2 h. After reaction themixture was allowed to cool to room temperature and methanolwas removed by evaporation. The formed orange solid wasrecrystallized with dichloromethane/ethanol. Yellow solid (5.88 g)of the target product 1,3,3-trimethyl-60-nitrospiro[chromene-2,20-indoline] was obtained in 91% yield after filtration and drying. Mp178e180 C (literature [64] value: 178e179 C). 1H NMR (400 MHz,CDCl3) d 8.05e8.03 (m, 2H), 7.25e7.23 (m, 1H), 7.12 (dd, J 7.3,1.3 Hz, 1H), 6.99e6.88 (m, 2H), 6.80 (d, J 8.6 Hz, 1H), 6.59 (d,J 7.7 Hz, 1H), 5.89 (d, J 10.3 Hz, 1H), 2.77 (s, 3H),1.32 (s, 3H),1.22(s, 3H).
General procedure: To a mixture of acetylacetic ester, substituted salicylic aldehyde (2a-h) and aminoheterocycle (1a-c, 6-8) was added 1 drop of piperidine. The mixture was stirred for 15 min after which time acetic acid (5 mL) was added and the reaction mixture was refluxed for 3-12 h. The desired products precipitate upon cooling of the reaction mixtures, and a simple filtration and washing with ethanol provides analytically pure material (>95%).
Dissolve 1- (2-hydroxyethyl) -2,3,3-trimethyl-3H-indole-1-ammonium bromide (2.0g, 7.0mmol) in 20mL of ethanol,Piperidine (0.77mL, 7.7mmol) was addedBenzaldehyde(1.78g, 10.7mmol),The reaction mixture was refluxed for 5 hours.After cooling to room temperature, it was stirred for another hour.Then the precipitated material is separated at 0 C,It was washed with cold ethanol to obtain spiropyran SP1 (1.6 g, 4.5 mmol, 64%) as a violet powder.
rac-(6bR,14S,14aR)-5-nitro-14-phenyl-14,14a-dihydro-6bH-benzo[5',6'][1,2]oxathiino [4',3':4,5]pyrano[3,2-c]quinolin-7(8H)-one 1,1-dioxide[ No CAS ]
rac-(6aR,7S,14bR)-2-nitro-7-phenyl-9,14b-dihydro-6aH-benzo[5',6'][1,2]oxathiino[4',3':4,5]pyrano[2,3-b]quinolin-14(7H)-one 6,6-dioxide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%; 23%
General procedure: To a stirring solution of 2-hydroxybenzaldehyde derivative 1 (1.0 mmol), styrenesulfonyl chloride (0.20 g, 1.0 mmol), and K2CO3 (0.14 g, 1.0 mmol) in H2O (15 mL) for 2 h was added 4-hydroxycoumarin derivative 2 (1.2 mmol) or 4-hydroxyquinolinone (0.19 g, 1.2 mmol) and EDDA (20 mmol%) and the mixture was heated at reflux for 12 h. After completion of the reaction as indicated by TLC, the mixture was cooled to room temperature and the organics were extracted using CH2Cl2 (30 mL). Evaporation of the solvent under reduced pressure followed by column chromatography on silica gel using hexane-ethyl acetate (3:1), afforded products 3 and 4.
The title compound, (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol, was prepared by reflux a mixture of a solution containing 2-hydroxy-5-nitrobenzaldehyde (0.0138 g, 0.082 mmol) in 20 ml ethanol and a solution containing <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (0.0211 g, 0.082 mmol) in 20 ml ethanol. The reaction mixture was stirred for 1 hunder reflux. The crystals of suitable for (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol X-ray analysis were obtained from ethyl alcohol by slow evaporation (yield%35; m.p 198-200 C).
General procedure: Preparation of N?-(2-hydroxybenzylidene)naphthalene-2-sulfonohydrazide (SA78). A methanol (20ml) solution of salicylaldehyde (122mg; 1mmol) and naphthalene-2-sulfonohydrazide (222mg; 1mmol) was refluxed for 2h. Solvent was evaporated at reduced pressure to an oily residue. This residue was mixed with ether (?10ml) and sonicated at 5C for 5min. Ether solution was decanted and mixed with hexane (?50ml). The resulting slightly milky mixture was left at room temperature for 1h. The formed white powdery product was separated by filtration, washed with hexane (3×5ml) and dried on air to give pure product (250mg; 77%).
13,13-di-n-butyl-4-hydroxymethyl-1-methyl-9-nitro-5H-benzo[i]pyrido[4,3-d]-12,14,6,2-dioxazaestanocine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65.3%
With potassium hydroxide; In methanol; toluene; for 8h;Reflux;
General procedure: <strong>[524-36-7]Pyridoxamine dihydrochloride</strong>, potassium hydroxide, the corresponding salicylaldehyde, and dibutyltin oxide were added in a 1:2:1:1 ratio to a mixture of toluene/methanol (4:1 v/v). The reaction mixture was refluxed for 8 h with constant stirring; the reaction mixture was then cooled to room temperature and the solvent was removed under reduced pressure to give the resultant compound. The dried residue was dissolved in dichloromethane and filtered off to remove potassium chloride, and the filtrate was then evaporated to dryness in vacuo.
6-fluoro-2-(2-(2-hydroxy-5-nitrobenzylidene)hydrazino)benzothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation;
General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29.
With Aliquat 336; sodium hydroxide; In dichloromethane; water; for 2h;
In dichloromethane 130 mL, 5-nitrosalicylaldehyde (10.0 g) andAliquat 336 (33.9 g) were dissolvedto prepare an organic phase. In distilled water 150 ml, racemic 4-chlo- rophenylalanine (24.0 g), sodium hydroxide (5.77 g) and copper chloride (CuC12) (1.4 g) were dissolved to prepare an aqueous phase. The organic phase and the aqueous phase were mixed and the resultant two-phase mixture was vigorously stirred for 2 hours, followed by phase separation to obtain an organic layer containing copper metal complex.
2-methoxy-3-(4-methoxycarbonylphenyl)-6-nitro-2-phenyl-2H-1-benzopyran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
28%
General procedure: To a mixture of 5-nitrosalicylaldehyde (0.334 g, 2.0 mmol), diphenylacetylene (0.178 g, 1.0 mmol) and trimethyl orthoformate (0.212 mL, 2.0 mmol) in toluene under nitrogen, trifluoromethanesulfonic acid (0.0176 mL, 20 mol%) was added. After being stirred at reflux for 15 h, methanol (5.0 mL, 0.12 mol) was added. Then the reaction mixture was quenched with H2O. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (hexane/ethyl acetate = 100 : 1 to 20 : 1) to afford product 7.
2-(4,6-dimethylpyrimidin-2-ylimino)methyl-4-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
In methanol; for 6h;Reflux;
A methanolic solution (30 mL) of <strong>[767-15-7]2-amino-4,6-dimethylpyrimidine</strong> (0.1232 g, 1 mmol ) and 5-nitrosalicylaldehyde (0.1671 g, 1 mmol) was refluxed withconstant stirring for 6 h. Yellow solid (HL) was isolated bythe slow evaporation and recrystallized by using ethanol.
2-methoxy-3-(4-methoxycarbonylphenyl)-6-nitro-2-phenyl-2H-1-benzopyran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
28%
With trifluorormethanesulfonic acid; In toluene; at 60℃; for 15h;Inert atmosphere;
General procedure: To a solution of nitrosalicylaldehyde (2.0 mmol), diphenylacetylene (1.0 mmol) and trimethyl orthoformate (2.0 mmol) in toluene (5.0 mL) under nitrogen, trifluoromethanesulfonic acid (18 muL, 0.20 mmol, 20 mol%) was added. After being stirred at reflux for 15 h, methanol (5.0 mL, 0.12 mol) was added. Then the reaction mixture was quenched with H2O. The organic layer was separated and the aqueous layer was extracted with ethylacetate. The combined organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (hexane/ethylacetate = 100: 1 to 20: 1) to afford product.
With formic acid; In tetrahydrofuran; at 40℃; for 24.0h;Schlenk technique;
A 150 mL Schlenk flask was charged with 1.15 mmol of 2,2-bis (4-meryl, 3-amino) phenylpropyl and 2.31 mmol of 5-nitrosalicylaldehyde , 100mL of tetrahydrofuran as a solvent and 0. lmmol of formic acid for catalysisAgent to obtain a reaction system Id. The reaction system Id was stirred at 40 C for 24 hours at 25 C under conditions of cooling the solid was precipitated; then a mixed solvent of anhydrous ethanol and tetrahydrofuran (anhydrous ethanol and tetrahydrofuran in a total volume of 8 OmL, the volume ratio VEto / VTHF 9: 1) recrystallization, vacuum suction filtration, dried in a vacuum oven at 80 C to give 0.44g of yellow-brown crystal ligand L4, ligand L4 yield of 68.75%.
[Cu(5-nitrosalicylaldehyde)(2,2'-bi-1H-imidazole)(ClO<SUB>4</SUB>)][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
In ethanol; at 20℃; for 4h;
General procedure: To an ethanolic solution of copper perchlorate hexahydrate (0.74?g, 2.00?mM), 5-nitrosalicylaldehyde (0.28?g, 2.00?mM) and 2,2'-bipyridyl (0.35?g, 2.00?mM) in ethanol (10?mL) were added consequently with continuous stirring at room temperature for 4?h. The removal of solvent from the resultant dark green solution obtained green precipitate was washed with water, ethanol, ether, and dried under vacuum. The obtained precipitate was recrystallized in acetonitrile solvent by slow evaporation giving X-ray quality single crystals after a few days. Yield: 1.00?g (75%); m.p.: 284?C. Anal. data for C17H12ClCuN3O8 Calc. (%): C, 42.07; H, 2.49; N, 8.66; Cu, 13.09; Found (%): C, 42.12; H, 2.40; N, 8.58; Cu, 13.02; IR (nu, cm-1) (KBr Disc): 1633(nu C=0); 1609(nu C=N); 1573 (nu C-O); 622(nu Cu-O); lambdamax, nm (epsilon, M-1?cm-1) in DMF: : 624(198), 532 (984), 430 (144758), 372 (104638), 312 (100213), 264 (85070); Molar conductivity (Lambdam/S?cm2?mol-1) in CH3CN 17. g??=?2.06, g||?=?2.25 and A||?=?326. Other copper(II) complexes 2-4 were synthesized by a procedure similar to the synthesis of complex 1.
2-((E)-(((R)-2-((S)-2-benzylaziridin-1-yl)-3-phenylpropyl)imino)methyl)-4-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
In toluene; at 20℃; for 12h;Molecular sieve;
Add activated 4A molecular sieve (400 mg) to a 10 mL reaction tube containing magnetons and add 1 mL of dry toluene followed by 5-nitrosalicylaldehyde(50 mg, 0.3 mmol), and (S)-2-benzylazepine(100 mg, 0.75 mmol), the reaction mixture was stirred at room temperature for 12 h.After the reaction is completed, it is filtered.The filtrate was evaporated to give a yellow oil.118 mg, yield 95%
(E)-2-(((3-(tert-butyl)phenyl)imino)methyl)-4-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
In ethanol; at 20℃;
General procedure: To a solution of benzaldehydes (1 equiv) in ethanol (10 mL) wasadded anilines (1 equiv), and the reaction mixture was stirred at roomtemperature overnight. The solid was collected by filtration and washedwith cold ethanol and hexane.
68%
In ethanol; at 20℃;
General procedure: To a solution of benzaldehydes (1 equiv) in ethanol (10 mL) was added anilines (1 equiv), and the reaction mixture was stirred atroom temperature overnight. The solid was collected by filtration,and washed with cold ethanol and hexane. 5.4.1 (E)-2-(((3-ethynylphenyl)imino)methyl)-4-nitrophenol (1) The title compound was prepared according to general procedure (A) using 5-nitrosalicylaldehyde (200mg, 1.20mmol) and 3-aminophenylacetylene 1a (135muL, 1.20mmol, 1 equiv), yielding the pure product as a yellow solid (242mg, 76%),
2-(benzo[d]thiazol-2-yl)-4-((2-hydroxy-5-nitrobenzylidene)amino)phenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With acetic acid; In ethanol; at 20℃; for 8h;
General procedure: In a stirred mixture of 5-amino-2-(benzo[d]thiazol-2-yl) phenol(3a) or 4-amino-2-(benzo[d]thiazol-2-yl) phenol (3b)(1.0 mmol) and substituted salicylaldehyde (1.2m/m of 3aand 3b) in ethanol added few drops of acetic acid. The reactionmixture was stirred at room temperature for 8 h. Theprecipitate was filtered and recrystallized with hot ethanol.
Take a 50 mL flask, install a reflux condenser, add 2.0 mL (12.56 mmol) of 2,3,3-trimethyl-3H-indole, 1.56 mL of methyl iodide (25.12 mmol), and 20 mL of ethanol, and heat to reflux for 5 hours. The heating was stopped, and the reaction system was allowed to cool to room temperature; 1.24 mL (12.56 mmol) of piperidine and 2.1 g (12.56 mmol) of 5-nitrosalicylaldehyde were sequentially added to the above system.Continue the reaction for another 5 minutes and spin dry the solvent.The product was purified by silica gel column chromatography (eluent petroleum ether / ethyl acetate).A yellow solid was obtained in 3158 mg, yield 78%.
1'-(9-bromononyl)-3',3'-dimethyl-6-nitrospiro[benzopyran-2,2'-indoline][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
Take a 50 mL flask and install a reflux condenser.Add 2.0 mL (12.56 mmol) of 2,3,3-trimethyl-3H-indole,2.55mL1,9-dibromodecane (12.56 mmol) and 20 mL of tetrahydrofuran,Heating under reflux for 24 hours;Stop heating and allow the reaction system to cool to room temperature;1534 mg (12.56 mmol) was sequentially added to the above system.4-dimethylaminopyridine and 2.1 g (12.56 mmol) of 5-nitrosalicylaldehyde,Continue the reaction for another 5 minutes and spin dry the solvent.The product was purified by silica gel column chromatography (eluent petroleum ether / ethyl acetate).A yellow solid was obtained in an amount of 3.03 g, yield 47%.
30%
Take a 50 mL flask, install a reflux condenser, and add 2.0 mL (12.56 mmol) of 2,3,3-trimethyl-3H-indole.2.55 mL of 1,9-dibromodecane (12.56 mmol) and 20 mL of tetrahydrofuran, heated to reflux for 24 hours;Stop heating and allow the reaction system to cool to room temperature;704.7 mg (12.56 mmol) of potassium hydroxide and 2.1 g (12.56 mmol) of 5-nitrosalicylaldehyde were sequentially added to the above system, and the reaction was further continued for 10 minutes.The system is neutralized with acid, washed, extracted, and the solvent is dried.The product was purified by silica gel column chromatography (eluent petroleum ether / ethyl acetate).A yellow solid was obtained in an amount of 1.93 g, yield 30%.
(E)-5-nitro-2-((2-(pyrimidin-2-yl)hydrazono)methyl)phenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
In ethanol; at 20℃;
General procedure: Compounds 2 were prepared by the reaction between <strong>[7504-94-1]2-hydrazinylpyrimidine</strong> 1 (0.04 g, 0.36 mmol) and the appropriate aromatic or heteroaromatic aldehyde (1.0 eq., 0.36 mmol) in ethanol (3.0 mL) [27]. The reaction mixture was stirred for between 20 min and 5 h at room temperature. After rotary evaporation, the product was purified by washing with cold ethanol (2.0 mL) and cold diethyl ether (2.0 mL), leading to the pure derivatives 2a-f as solid in 27-75% yields.
5-Nitrosalicylaldehyde (0.167 g, 1 mmol) and <strong>[42826-42-6]pivalohydrazide</strong> (0.116 g, 1 mmol) were stirred in methanol (30 mL) for 30 min. Then, ethyl maltol (0.140 g, 1 mmol) and VOSO4 (0.163 g, 1 mmol) dissolved in methanol (30 mL) were added to the above solution. The mixture was further stirred for 30 min to give a deep brown solution. Single crystals were obtained by slow evaporation of the solution in air. Yield: 61%. IR data(cm-1): 1613 (C=N), 945 (V=O). UV-Vis data (MeOH, lambdamax, nm): 280, 315, 490. Anal.calc. for C19H20N3O8V: C, 48.6; H, 4.3; N, 9.0. Found: C, 48.7; H, 4.2; N, 8.8%. 1H NMR(300 MHz, DMSO-d6) delta 9.24 (s, 1 H, CHN), 8.82 (s, 1 H, ArH), 8.53 (d, 1 H, L'H), 8.34 (d,1 H, ArH), 7.07 (d, 1 H, ArH), 6.78 (s, 1 H, L'H), 3.02 (q, 2 H, CH2), 1.35 (t, 3 H, CH3), 1.15(s, 9 H, C(CH3)3).
(E)-2-(((9H-fluoren-2-yl)imino)methyl)-4-nitrophenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
In ethanol; for 24h;Reflux;
The synthesis of the receptor is shown in Scheme 1. Briefly, <strong>[153-78-6]2-aminofluorene</strong> (0.181 g, 1.0 mmol) was reflux with 2-hydroxy-5-nitrobenzaldehyde (0.162 g, 1.0 mmol) in ethanol (5 mL) taken in the round bottom flask and stirred for 24 h. The reaction progress was examinedusing a mixture of hexane:ethyl acetate (7:3) as the eluent viathin layer chromatography. (E)-2-(((9H-fluoren-2-yl)imino)methyl)-4-nitrophenol was obtained as pale orange color precipitate. Then theprecipitate was separated by vacuum filtration, followed by washingwith ethanol, diethyl ether and dried to obtain receptor in 85% yield.Melting point: 213 C; 1H NMR (CDCl3, 500 MHz, delta ppm) 3.98 (s, 2H,fluorene proton) 7.11-7.09 (d, 1H, J = 9.5 Hz); 7.41-7.40 (m, 3H, J =8.5 Hz); 7.58 7.57 (d, 2H, J = 5.0 Hz);7.82-7.80 (m, 2H, J = 7.5 Hz);8.28-8.26 (d, 1H, J = 9.0 Hz); 8.41 (s, 1H); 8.80 (s, 1H, imine N_H)14.65 (s, 1H, OH proton). (13CNMR, CDCl3, 125 MHz, delta ppm) 36.9,117.89, 118.29, 118.36, 120.18, 120.52, 120.79, 125.18, 127.10, 127.30,128.25, 143.53, 159.38, 167.00. Calculated mass 330.1004; found mass331.1001 (M+1peak) (Supplementary information-S1).
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