* 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 triphenylphosphine In diphenylether at 260℃; for 1 h;
General procedure: In a 50 ml round bottom flask containing magnetic stir bar was charged with o-nitro benzaldehydes (2 mmol), phosphorane (2.2 mmol), triphenyl phosphine (4.6 mmol) and diphenyl ether (10 mL) and heated at 260 oC for 1 h. The reaction mass was then cooled to room temperature and poured on silica column. Products were isolated by eluting with petrolium ether to 3:1 pet ether: ethyl acetate.
Reference:
[1] Zhurnal Obshchei Khimii, 1938, vol. 8, p. 1797,1801[2] Chem. Zentralbl., 1940, vol. 111, # I, p. 370
3
[ 6628-86-0 ]
[ 1099-45-2 ]
[ 4792-67-0 ]
Reference:
[1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 4-5, p. 713 - 718
4
[ 6628-86-0 ]
[ 719-59-5 ]
Reference:
[1] Chemical Communications, 2011, vol. 47, # 33, p. 9513 - 9515
5
[ 6628-86-0 ]
[ 635-21-2 ]
Reference:
[1] Zhurnal Obshchei Khimii, 1938, vol. 8, p. 1797,1801[2] Chem. Zentralbl., 1940, vol. 111, # I, p. 370
6
[ 6628-86-0 ]
[ 27328-68-3 ]
Reference:
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 12, p. 2155 - 2162
7
[ 6628-86-0 ]
[ 395-81-3 ]
Reference:
[1] Patent: US4456772, 1984, A,
8
[ 51282-49-6 ]
[ 6628-86-0 ]
Yield
Reaction Conditions
Operation in experiment
97%
With diisobutylaluminium hydride In dichloromethane at -78℃; for 0.75 h;
Example 114; This example concerns the synthesis of Aldehyde 11: To a stirred solution of 80 (8.20 g, 38.0 mmol) and dry CH2Cl2 (205 mL) was added DIBAL-H (48.0 mL, 48.0 mmol, 1.0 M in CH2Cl2) at -780C. After 45 min, MeOH (20 mL) was added and the solution was allowed to warm to rt. Next, aq. sodium tartrate (200 mL, 10percent w/v) was added and the suspension was left to stir vigorously until a bilayer was distinct. The solution was diluted with CH2Cl2 (100 mL) and washed with H2O (2 x 100 mL), sat. aq. NaCl (2 x 100 mL). The dried (Na2SO4) extract was purified via flash chromatography over silica gel, eluting with 20-50percent EtOAc/Hexanes to give the known aldehyde 13 (6.80 g, 36.7 mmol, 97percent). 1H NMR (400 MHz, CDCl3) δ 10.46 (s, IH), 8.15 (d, J= 8.7 Hz, IH), 7.94 (d, J= 2.3 Hz, IH), 7.74 (dd, J= 2.4, 8.7 Hz, IH); 13C NMR (100 MHz, CDCl3) δ 187.0, 147.5, 141.0, 133.5, 132.7, 129.4, 126.2.
Reference:
[1] Journal of Organic Chemistry, 2007, vol. 72, # 26, p. 9857 - 9865
[2] Patent: WO2008/156656, 2008, A2, . Location in patent: Page/Page column 44; 180
9
[ 587-04-2 ]
[ 6628-86-0 ]
Yield
Reaction Conditions
Operation in experiment
60.6%
at -20 - -10℃; for 0.5 h;
Step A: 5-ch.oro-2-nitrobenzaidehyde 3-Ch.orobenzaldehyde (15 g, 107 mmo.) was added to concentrated sulfuric acid (150 mL) at -20 °C, followed by addition of potassium nitrate (1 1 .9 g, 1 17 mmoi) in portions, keeping the temperature bellow -10 °C. After addition, the mixture was stirred for 30 minutes and then poured into ice-water. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed by brine, dried over anhydrous sodium sulfate, evaporated and purified by silica gel chromatography to afford the product 5-chioro-2-nitrobenza.dehyde (12.0 g, yield 60.6 percent).
Reference:
[1] Chemical Communications, 2011, vol. 47, # 36, p. 10133 - 10135
[2] Tetrahedron, 2010, vol. 66, # 38, p. 7544 - 7561
[3] Patent: WO2012/92880, 2012, A1, . Location in patent: Page/Page column 49-50
[4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 1, p. 146
[5] Justus Liebigs Annalen der Chemie, 1891, vol. 262, p. 149[6] Zeitschrift fuer Kristallographie, Kristallgeometrie, Kristallphysik, Kristallchemie, 1894, vol. 23, p. 470
[7] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 1, p. 143
[8] Journal of Organic Chemistry, 1960, vol. 25, p. 1542 - 1547
[9] Patent: US4415572, 1983, A,
[10] Organic Letters, 2008, vol. 10, # 2, p. 173 - 175
[11] Journal of Organic Chemistry, 2008, vol. 73, # 21, p. 8608 - 8611
[12] Chinese Journal of Chemistry, 2012, vol. 30, # 7, p. 1571 - 1574
[13] European Journal of Organic Chemistry, 2014, vol. 2014, # 26, p. 5827 - 5835,9
[14] Patent: CN103467300, 2016, B,
[15] Patent: DE30329, , ,
[16] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 1, p. 146
10
[ 73033-58-6 ]
[ 6628-86-0 ]
[ 2516-95-2 ]
Yield
Reaction Conditions
Operation in experiment
60%
With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48 h; Schlenk technique
General procedure: To a Schlenk tube were added Fe(NO3)3·9H2O (40.6 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and DCE (4.0 mL) sequentially under an atmosphere of oxygen (gas bag, commercial size: 2 L, which could be expanded to 5 L). The mixture was then stirred at 25 °C until completion of the reaction as monitored by TLC (petroleum ether/EtOAc = 5:1) (48h). The crude reaction mixture was filtered through a short column of silica gel (height: 2 cm, diameter: 3 cm) eluting with Et2O (3 × 25 mL). After evaporation, the residue was purified by chromatography on silica gel [petroleum ether/EtOAc = 15:1 (500 mL) to 2:1 (300 mL)] to afford benzoic acid (2a)14 (69.9 mg, 57percent) as a pale yellow solid. Yields of 57percent of 2a and 38percent of benzaldehyde (3a)15 were observed by NMR analysisof the crude product using CH2Br2 as an internal standard and by comparison with spectra reported in the literature.
Reference:
[1] Journal of the American Chemical Society, 2011, vol. 133, # 42, p. 16901 - 16910
[2] Journal of Medicinal Chemistry, 1992, vol. 35, # 14, p. 2688 - 2696
12
[ 89303-10-6 ]
[ 6628-86-0 ]
Reference:
[1] Journal of Organic Chemistry, 2001, vol. 66, # 15, p. 5022 - 5026
[2] Liebigs Annalen der Chemie, 1991, # 6, p. 537 - 538
13
[ 30669-50-2 ]
[ 6628-86-0 ]
Reference:
[1] Tetrahedron Letters, 1987, vol. 28, # 26, p. 3021 - 3022
[2] Journal of Organic Chemistry, 1989, vol. 54, # 21, p. 5094 - 5100
14
[ 2516-95-2 ]
[ 6628-86-0 ]
Reference:
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 14, p. 2688 - 2696
[2] Patent: WO2008/156656, 2008, A2,
15
[ 100-00-5 ]
[ 6628-86-0 ]
Reference:
[1] Journal of Organic Chemistry, 1989, vol. 54, # 21, p. 5094 - 5100
[2] Tetrahedron Letters, 1987, vol. 28, # 26, p. 3021 - 3022
16
[ 1012328-95-8 ]
[ 6628-86-0 ]
Reference:
[1] European Journal of Organic Chemistry, 2014, vol. 2014, # 26, p. 5827 - 5835,9
17
[ 33499-36-4 ]
[ 6628-86-0 ]
Reference:
[1] Patent: CN103467300, 2016, B,
18
[ 99-61-6 ]
[ 6628-86-0 ]
Reference:
[1] Justus Liebigs Annalen der Chemie, 1891, vol. 262, p. 149[2] Zeitschrift fuer Kristallographie, Kristallgeometrie, Kristallphysik, Kristallchemie, 1894, vol. 23, p. 470
19
[ 73033-58-6 ]
[ 6628-86-0 ]
[ 2516-95-2 ]
Yield
Reaction Conditions
Operation in experiment
60%
With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48 h; Schlenk technique
General procedure: To a Schlenk tube were added Fe(NO3)3·9H2O (40.6 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and DCE (4.0 mL) sequentially under an atmosphere of oxygen (gas bag, commercial size: 2 L, which could be expanded to 5 L). The mixture was then stirred at 25 °C until completion of the reaction as monitored by TLC (petroleum ether/EtOAc = 5:1) (48h). The crude reaction mixture was filtered through a short column of silica gel (height: 2 cm, diameter: 3 cm) eluting with Et2O (3 × 25 mL). After evaporation, the residue was purified by chromatography on silica gel [petroleum ether/EtOAc = 15:1 (500 mL) to 2:1 (300 mL)] to afford benzoic acid (2a)14 (69.9 mg, 57percent) as a pale yellow solid. Yields of 57percent of 2a and 38percent of benzaldehyde (3a)15 were observed by NMR analysisof the crude product using CH2Br2 as an internal standard and by comparison with spectra reported in the literature.
Reference:
[1] Zhurnal Obshchei Khimii, 1938, vol. 8, p. 1797,1801[2] Chem. Zentralbl., 1940, vol. 111, # I, p. 370
21
[ 6628-86-0 ]
[ 20028-53-9 ]
Yield
Reaction Conditions
Operation in experiment
60%
With sodium dithionite; sodium carbonate In methanol; water at 45 - 65℃; for 0.416667 h;
Example 3 Preparation of N-(4-chloro-2-formylphenyl)trifluoromethanesulfonamide (Formula 24) The following compounds were prepared according to the reaction scheme illustrated by FIG. 6. a) To a solution of Na2S2O4 (tech., 85percent) (29.72 g, 145.09 mmol) and Na2CO3 (12.98 g, 122.46 mmol) in H2O (500 mL) at 45° C. was added dropwise 5-chloro-2-nitrobenzaldehyde (tech., 80percent) (5.31 g, 22.89 mmol) in MeOH (100 mL) over 25 min. The reaction mixture was heated to 65° C., allowed to cool to RT and extracted three times with CH2Cl2. The combined organics were washed with H2O, dried and the solvent concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 4:1) and the solvent concentrated under reduced pressure to afford 2-amino-5-chlorobenzaldehyde 23 (2.12 g, 60percent), as a yellow oil.
46%
With 1,1'-bis-(diphenylphosphino)ferrocene; formic acid; N-ethyl-N,N-diisopropylamine In toluene at 150℃; for 4 h; Inert atmosphere
A mixture of 5-chloro-2-nitrobenzaldehyde (7c, 95.6 mg, 0.5 mmol), HCO2H (159 μL, 3.0 mmol), DIPEA (374 μL, 2.25 mmol), and dppf (14.1mg, 0.025 mmol) in toluene (1.0 mL) was stirred at 150 °C (screwcapped vial) for 4 h under argon, cooled to r.t., then water (5 mL) was added. The two layers were separated, and the aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed by brine, dried (anhyd Na2SO4), filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 100–200 mesh) to afford 8c (35.8 mg, 46percent) as a yellow solid; mp 72–73 °C. FTIR (film): 3465, 3352, 1689, 1660, 1617, 1590, 1551, 1474, 1388,1311, 1186, 1157, 904, 819, 728, 642 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.78 (s, 1 H), 7.42 (s, 1 H), 7.23 (d, J =8.8 Hz, 1 H), 6.60 (d, J = 8.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 192.8, 148.3, 135.2, 134.2, 120.7,119.2, 117.6. Anal. Calcd for C7H6ClNO: C, 54.04; H, 3.89; N, 9.00. Found: C, 54.26;H, 3.71; N, 9.15.
Reference:
[1] Organic Letters, 2010, vol. 12, # 23, p. 5502 - 5505
[2] Patent: US2006/63841, 2006, A1, . Location in patent: Page/Page column 30; 6/12
[3] Chemical Communications, 2011, vol. 47, # 36, p. 10133 - 10135
[4] Synthesis (Germany), 2016, vol. 48, # 22, p. 3985 - 3995
[5] Journal of medicinal chemistry, 1968, vol. 11, # 5, p. 946 - 949
[6] Heterocycles, 2005, vol. 65, # 9, p. 2095 - 2105
[7] Organic Letters, 2008, vol. 10, # 2, p. 173 - 175
[8] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 24, p. 8221 - 8233
[9] Organic Letters, 2010, vol. 12, # 12, p. 2841 - 2843
[10] Chemical Communications, 2010, vol. 46, # 29, p. 5244 - 5246
[11] Chemical Communications, 2011, vol. 47, # 33, p. 9513 - 9515
[12] Chemistry - A European Journal, 2012, vol. 18, # 18, p. 5530 - 5535
[13] ACS Combinatorial Science, 2012, vol. 14, # 5, p. 316 - 322
[14] Patent: US2013/190500, 2013, A1, . Location in patent: Paragraph 0016; 0017
[15] Patent: WO2017/35077, 2017, A1, . Location in patent: Paragraph 00192
[16] Angewandte Chemie - International Edition, 2017, vol. 56, # 35, p. 10573 - 10576[17] Angew. Chem., 2017, vol. 129, # 35, p. 10709 - 10712,4
[18] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 17, p. 4128 - 4132
[19] Synlett, 2017, vol. 28, # 14, p. 1724 - 1728
[20] Patent: CN107522766, 2017, A, . Location in patent: Paragraph 0147; 0148; 0149
[21] Patent: WO2018/39197, 2018, A1, . Location in patent: Paragraph 00194
22
[ 6628-86-0 ]
[ 37585-25-4 ]
Reference:
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 35, p. 10573 - 10576[2] Angew. Chem., 2017, vol. 129, # 35, p. 10709 - 10712,4
[3] Synlett, 2017, vol. 28, # 14, p. 1724 - 1728
23
[ 6628-86-0 ]
[ 73033-58-6 ]
Yield
Reaction Conditions
Operation in experiment
100%
With sodium tetrahydroborate In ethanol at 0℃; for 2 h;
General procedure: To a cooled (ice-bath) solution of aldehyde (1 eq.) in EtOH (0.44 M) was added NaBH4 (1.5 eq.) andthe mixture was stirred for 2 h at 0 °C. After completion (monitored by TLC analysis), carefulevaporation of the solvent gave a semi-solid, which was slowly treated with saturated aqueous ofNH4Cl. After evolution of H2 gas ended, the aqueous phase was extracted four times with CH2Cl2. Thecombined organic phases were washed with water and brine, dried with magnesium sulfate and filtered.Evaporation of the solvent under reduced pressure gave the desired product 12, which was used in thenext step without further purification.
Reference:
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 35, p. 10573 - 10576[2] Angew. Chem., 2017, vol. 129, # 35, p. 10709 - 10712,4
[3] Synlett, 2017, vol. 28, # 14, p. 1724 - 1728
[4] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 16, p. 5562 - 5577
[5] Journal of the American Chemical Society, 1952, vol. 74, p. 536
24
[ 1001-26-9 ]
[ 6628-86-0 ]
[ 375854-57-2 ]
Reference:
[1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3488 - 3491
25
[ 10601-80-6 ]
[ 6628-86-0 ]
[ 375854-57-2 ]
Reference:
[1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3488 - 3491
With sodium tetrahydroborate; In ethanol; at 0℃; for 2h;
General procedure: To a cooled (ice-bath) solution of aldehyde (1 eq.) in EtOH (0.44 M) was added NaBH4 (1.5 eq.) andthe mixture was stirred for 2 h at 0 C. After completion (monitored by TLC analysis), carefulevaporation of the solvent gave a semi-solid, which was slowly treated with saturated aqueous ofNH4Cl. After evolution of H2 gas ended, the aqueous phase was extracted four times with CH2Cl2. Thecombined organic phases were washed with water and brine, dried with magnesium sulfate and filtered.Evaporation of the solvent under reduced pressure gave the desired product 12, which was used in thenext step without further purification.
96%
With sodium tetrahydroborate; copper ferrite; In water; for 0.0125h;Reflux; Green chemistry;
General procedure: For example, in a round-bottom flask (15 mL) equipped with a magnetic stirrer, a mixture of nitrobenzene (1 mmol, 0.123 g) in H2O (2 mL) was prepared. CuFe2O4 (0.2 mmol, 0.048 g) was then added, and the mixture was stirred. At the next step, NaBH4 (2 mmol, 0.076 g.) was added, and the resulting mixture continued to stir at reflux for 50 min. After completion of the reaction (monitored by TLC), the mixture was cooled to room temperature, and the mentioned nanocatalyst was separated by an external magnet. The reaction mixture was extracted with EtOAc (2 x 4 mL) and then dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford the pure liquid aniline in 95% yield.
With vasicine; In ethylene glycol; at 80℃; for 48.0h;
General procedure: The mixture of nitrocompound (0.5 mmol) and vasicine (0.5 mmol) in ethylene glycol (2 mL) was stirred at 80C for 24-48 h. Time was not optimized separately for all substrates. After completion of reaction as monitored by TLC, the reaction mixture was cooled to ambient temperature and extracted with ethyl acetate. The ethyl acetate layer was dried under reduced pressure using rotatory evaporator. The crude was chromatographed over silica gel to afford the desired product.
Stage #1: 4-methoxycarbonylbenzyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran; methanol at 20℃; for 1.5h;
Stage #2: 5-chloro-2-nitrobenzaldehyde at 20℃; for 0.5h;
With diisobutylaluminium hydride; In dichloromethane; at -78℃; for 0.75h;
Example 114; This example concerns the synthesis of Aldehyde 11: To a stirred solution of 80 (8.20 g, 38.0 mmol) and dry CH2Cl2 (205 mL) was added DIBAL-H (48.0 mL, 48.0 mmol, 1.0 M in CH2Cl2) at -780C. After 45 min, MeOH (20 mL) was added and the solution was allowed to warm to rt. Next, aq. sodium tartrate (200 mL, 10percent w/v) was added and the suspension was left to stir vigorously until a bilayer was distinct. The solution was diluted with CH2Cl2 (100 mL) and washed with H2O (2 x 100 mL), sat. aq. NaCl (2 x 100 mL). The dried (Na2SO4) extract was purified via flash chromatography over silica gel, eluting with 20-50percent EtOAc/Hexanes to give the known aldehyde 13 (6.80 g, 36.7 mmol, 97percent). 1H NMR (400 MHz, CDCl3) delta 10.46 (s, IH), 8.15 (d, J= 8.7 Hz, IH), 7.94 (d, J= 2.3 Hz, IH), 7.74 (dd, J= 2.4, 8.7 Hz, IH); 13C NMR (100 MHz, CDCl3) delta 187.0, 147.5, 141.0, 133.5, 132.7, 129.4, 126.2.
With Oxone In water; N,N-dimethyl-formamide at 20℃;
7.1.3. Preparation of the benzimidazoles 13a and 13b
To a stirred solution of N-methyl-1,2-phenylenediamine 11 (0.5 g, 0.004 mol) and 5-chloro-2-nitrobenzaldehyde (0.76 g, 0.004 mol) in DMF (25 mL) and H2O (1 mL) at room temperature, Oxone (1.47 g, 0.0024 mol) was added in portions over 15 min. The mixture was stirred overnight at room temperature. Water (10 mL) was added and the reaction mixture was extracted twice with CH2Cl2 (20 mL). The combined CH2Cl2 layers were washed several times with water, dried (MgSO4) and evaporated giving compound 13b (0.94 g, 83%) as yellow-brown needles, mp 148-150 °C (EtOH) (lit.14 144-145 °C); δΗ (270 MHz; CDCl3) 3.65 (3H, s, -CH3), 7.30-7.45 (2H, m, Ar-H), 7.70 (2H, m, Ar-H), 7.85 (1H, m, Ar-H), 7.80 (1H, m, Ar-H), 8.20 (1H, d, J = 9.4 Hz, Ar-H); δC (68 MHz; CDCl3) 30.8, 109.8, 120.3, 122.8, 123.7, 126.4, 127.9, 131.2, 133.2, 135.7, 140.4, 142.9, 147.1, 148.5.
Preparation of 1-tert-butyl 3-methyl 4-(5-chloro-2-nitrobenzyl)piperazine-1,3-dicarboxylate (52)1.5 g (8.2 mmol) of the aldehyde 51 and 2.0 g (8.2 mmol) of the amine 5 are initially introduced in a mixture of 50 ml of dichloroethane and 50 ml of THF. 0.940 ml of glacial acetic acid are then added, and the mixture is stirred at RT for about 3 h. 5.5 g (24.6 mmol) of NaB(OAc)3 and a further 0.940 ml of acetic acid are subsequently added, and the mixture is stirred overnight at room temperature. The batch is stirred with saturated NaHCO3 solution, diluted with dichloromethane and extracted by shaking. The organic phase is again washed by shaking with water, the aqueous phase is again extracted by shaking with DCM. The combined organic phases are dried over Na2SO4, filtered off with suction and evaporated to dryness in vacuo. The 3.5 g of crude product obtained are dissolved in THF, adsorbed onto Isolute and separated on silica gel 60 (Flashmaster). The relevant fractions are combined and evaporated to dryness in a rotary evaporator, thus giving the desired product 52 (1.6 g, 21% yield) in a purity of 45% (mass: [M+]=414; HPLC method D, RT=3.86 min) as yellow oil, which is reacted further without further purification.
With potassium carbonate;tri-1-napthylphosphine; palladium dichloride; In tetrahydrofuran; at 65℃; for 15h;Microwave irradiation; Inert atmosphere; Reflux;
Example 6: Representative synthesis of 2-aminoindoles Scheme 10:Representative Procedures:Scheme 11 :31 A 20 mL capacity microwave vial was loaded with PdCl2 (0.05 equiv, 24 mg), P(l- naphthyl)3 (0.05 equiv, 56 mg), boronic acid 2 (2.0 equiv, 1.153 g), aldehyde 1 (1.0 equiv, 500 mg), K2C03 (3.0 equiv, 1.117 g), and dry THF (12 mL). The vial was sealed and purged with N2 for 5-10 min. The reaction mixture was heated at 65 C for 15 h, cooled to room temperature. Water was added and the reaction mixture was extracted with EtOAc (3 x 40 mL). The combined EtOAc extracts were dried over MgS04, filtered, concentrated in vacuo, and the residue obtained was dissolved in minimal amount of CH2C12 and loaded directly onto the ISCO (silica gel) column (0-20% EtOAc/hexanes) which gave diarylmethanol 3 (500 mg, yield: 52%) as a light yellow oil.
Intermediate 4.1 : (5-chloro-2-nitro-phenyl)-(lH-imidazol-4-yl) methanol To a solution of 4-iodo-lH-imidazole (2 g, 10.3 mmol) in THF (20 mL) was added dropwise isopropylmagnesiumchloride (2 M in THF, 12 mL, 23.7 mmol) at room temperature. The reaction solution was stirred at rt for 2 h. To this solution was added 5-chloro-2-nitro-benzaldehyde (2.9 g, 15.5 mmol) in 10 mL THF. The solution was stirred at room temperature for 2 h. The reaction was quenched with aqueous NH4CI solution. The mixture was extracted twice with EA. The combined organic phases were dried and concentrated in vacuo. The residue was purified silica gel chromatography column (PE/EA, 3/1 to 1/1) to give the title compound as a brown solid
7′,9′-bis(5-chloro-2-nitrophenyl)-3-phenyl-1′,6′,7′,9′-tetrahydro-5H-spiro[isoxazole-4,8′-pyrazolo[3,4-f]quinolin]-5-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
In ethanol at 80℃; for 11h;
5H-Spiro[isoxazole-4,8′-pyrazolo[3,4-f]quinolin]-5-ones 4; General Procedure
General procedure: A dry 25-mL flask was charged with an aromatic aldehyde 1 (2.0 mmol), a 1H-indazol-6-amine 2 (1.0 mmol), a 3-phenylisoxazol-5(4H)-one 3 (1.0 mmol) and EtOH (10.0 mL). The reaction mixture was stirred under reflux for 9-13 h until all the reactant amine was consumed (monitored by TLC). Then, the mixture was allowed to cool to r.t., and the product 4 was collected by filtration without further purification.
Stage #1: 5-chloro-2-nitrobenzaldehyde With hydrogenchloride; iron In ethanol; water at 95℃; for 3h; Inert atmosphere;
Stage #2: 1-(3-Bromophenyl)ethanone With potassium hydroxide In ethanol; water for 2h; Inert atmosphere;
Example of the synthesis of intermediate 1
Under a nitrogen atmosphere, 5-chloro-2-nitrobenzaldehyde (50.8 g), iron powder (38. 8g), ethanol (440 mL), and 0.2N hydrochloric acid (60 mL) were added, and it agitated at 95 degrees C for 3 hours. After returning to a room temperature, the potassium hydrate (19.6g) and 3'-bromoacetophenone (51.2g) were added in order, and were agitated for further 2 hours. Cerite filtration was performed after adding water (50 mL) and a methylene chloride (500 mL). Filtrate was dried and condensed in MgSO4. Silica gel column chromatography refined, reprecipitation was performed from a methylene chloride/methanol, and the synthetic intermediate 1 (g [ 66.2 ], 76% of yield) was obtained. 5-chloro-2-nitrobenzaldehyde was purchased from Tokyo Kasei Kogyo Co., Ltd., and 3'-bromoacetophenone was purchased from sigma Aldrich.
76%
Stage #1: 5-chloro-2-nitrobenzaldehyde With hydrogenchloride; iron In ethanol; water at 95℃; for 3h; Inert atmosphere;
Stage #2: 1-(3-Bromophenyl)ethanone With potassium hydroxide In ethanol; water for 2h;
(Synthesis Example of Intermediate 1)
Under a nitrogen atmosphere,5-Chloro-2-nitrobenzaldehyde (50.8 g), iron powder (38.8 g), ethanol (440 mL) and 0.2 N hydrochloric acid (60 mL) were added in order, followed by stirring at 95 ° C. for 3 hours. After returning to room temperature, potassium hydroxide (19.6 g) and 3'-bromoacetophenone (51.2 g) were added in order, and the mixture was further stirred for 2 hours. Water (50 mL) and methylene chloride (500 mL) were added, followed by celite filtration. The filtrate was dried over MgSO 4 and concentrated. Purification by silica gel column chromatography, reprecipitation from methylene chloride / methanol gave synthetic intermediate 1 (66.2 g, yield 76%).
General procedure: For example, in a round-bottom flask (15 mL) equipped with a magnetic stirrer, a mixture of nitrobenzene (1 mmol, 0.123 g) in H2O (2 mL) was prepared. CuFe2O4 (0.2 mmol, 0.048 g) was then added, and the mixture was stirred. At the next step, NaBH4 (2 mmol, 0.076 g.) was added, and the resulting mixture continued to stir at reflux for 50 min. After completion of the reaction (monitored by TLC), the mixture was cooled to room temperature, and the mentioned nanocatalyst was separated by an external magnet. The reaction mixture was extracted with EtOAc (2 x 4 mL) and then dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford the pure liquid aniline in 95% yield.
With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen; In 1,2-dichloro-ethane; at 25℃; for 48h;Schlenk technique;
General procedure: To a Schlenk tube were added Fe(NO3)3·9H2O (40.6 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and DCE (4.0 mL) sequentially under an atmosphere of oxygen (gas bag, commercial size: 2 L, which could be expanded to 5 L). The mixture was then stirred at 25 C until completion of the reaction as monitored by TLC (petroleum ether/EtOAc = 5:1) (48h). The crude reaction mixture was filtered through a short column of silica gel (height: 2 cm, diameter: 3 cm) eluting with Et2O (3 × 25 mL). After evaporation, the residue was purified by chromatography on silica gel [petroleum ether/EtOAc = 15:1 (500 mL) to 2:1 (300 mL)] to afford benzoic acid (2a)14 (69.9 mg, 57%) as a pale yellow solid. Yields of 57% of 2a and 38% of benzaldehyde (3a)15 were observed by NMR analysisof the crude product using CH2Br2 as an internal standard and by comparison with spectra reported in the literature.
With triphenylphosphine; In diphenylether; at 260℃; for 1h;
General procedure: In a 50 ml round bottom flask containing magnetic stir bar was charged with o-nitro benzaldehydes (2 mmol), phosphorane (2.2 mmol), triphenyl phosphine (4.6 mmol) and diphenyl ether (10 mL) and heated at 260 oC for 1 h. The reaction mass was then cooled to room temperature and poured on silica column. Products were isolated by eluting with petrolium ether to 3:1 pet ether: ethyl acetate.
1.2; 1.3
(2) Accurate weighing 5 - chloro -2 - nitrobenzaldehyde (formula (IV) as shown in the) 180.0 mg (0.978 mmol), for 5 ml ethanol is dissolved, accurate weighing of the intermediate 3, 5 - dihydroxy-benzoic acid hydrazide 164.0 mg (0.978 mmol) is added to the ethanol solution, then dropwise 1 - 2 drops (a total of 0.05 - 0.1 ml) concentration of 99% acetic acid solution, stir, react at room temperature for 6 hours, TLC (ethyl acetate: petroleum ether=4:1) monitoring the reaction is complete.(3) After the completion of the reaction, concentrated, filtering, drying, to obtain compound R - 1, and the yield is 87.5%
With sodium methylate In methanol at 15℃; for 0.25h;
Aryl 3-(2-nitrophenyl)oxiran-2-yl ketones 1a-g were synthesizedunder the Darzens condensation conditions as earlierdescribed15 using 0.01 mmol of the starting compounds. Physicochemicalproperties of compounds 1a-d are in agreement withthose published earlier.12,15