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Jang, Mingyeong ; Lim, Taeho ; Park, Byoung Yong ; Han, Min Su ;
Abstract: In this study, we developed a metal-free and highly chemoselective method for the reduction of aromatic nitro compounds. This reduction was performed using tetrahydroxydiboron [B2(OH)4] as the reductant and 4,4'-bipyridine as the organocatalyst and could be completed within 5 min at room temperature. Under optimal conditions, nitroarenes with sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen, were converted into the corresponding anilines with excellent selectivity while avoiding the undesirable reduction of the sensitive functional groups.
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Purchased from AmBeed: 607-35-2 ; 578-66-5 ; 613-50-3 ; 100-19-6 ; 579-71-5 ; 3034-94-4 ; 5683-43-2 ; 99-92-3 ; 13534-97-9 ; 5676-60-8 ; 5470-18-8 ; 619-45-4 ; 553-26-4 ; 580-15-4 ; 611-34-7 ; 619-72-7 ; 100-13-0 ; 540-37-4 ; 1849-25-8 ; 4487-59-6 ; 555-16-8 ; 6298-19-7 ; 556-08-1 ; 953-26-4 ; 54060-30-9 ; 62-23-7 ; 607-34-1 ; 3867-18-3 ; 873-74-5 ; 3544-24-9 ; 94-52-0 ; 1520-21-4 ; 5470-34-8 ; 619-50-1 ; 586-39-0 ; 934-22-5 ; 402-54-0 ; 15411-43-5 ; 455-14-1 ; 17763-80-3 ; 3085-54-9 ; 1942-30-9 ; 1694-20-8 ; 6305-66-4 ; 41656-75-1 ; 6393-17-5 ; 4309-66-4
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| CAS No. : | 556-08-1 |
| Formula : | C9H9NO3 |
| M.W : | 179.17 |
| SMILES Code : | CC(=O)NC1=CC=C(C=C1)C(O)=O |
| English Name : | 4-Acetamidobenzoic acid |
| MDL No. : | MFCD00002534 |
| InChI Key : | QCXJEYYXVJIFCE-UHFFFAOYSA-N |
| Pubchem ID : | 19266 |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With sulfuric acid; potassium nitrate at -5 - 0℃; for 2h; | |
| 80% | With nitric acid at 0℃; for 1h; | |
| 61% | With nitric acid at -15℃; for 0.5h; |
| 61.11% | With sulfuric acid; nitric acid at 10℃; for 0.0888333h; | S1-S3 S1. Dissolve 4-acetamidobenzoic acid (25g, 0.1523mol) in 98% sulfuric acid (125mL, 2.3000mol) and 65% nitric acid (48mL, 0.6923mol) in 98% sulfuric acid (39mL, 0.7176mol);S2, control the flow rate of 4-acetamidobenzoic acid sulfuric acid solution to be 0.4mL/min, and the flow rate of nitric-sulfur mixed acid to be 0.2mL/min, inject materials into the microchannel reaction tube, and control the reaction temperature to be 20°C to ensure the microchannel reaction The liquid holding capacity of the tube is 3.2mL;S3. The reaction solution was quenched and precipitated with an aqueous ice solution, filtered with suction, and the filter cake was washed with water and then dried in vacuo to obtain a yellow solid, which was 4-acetamido-3-nitrobenzoic acid. |
| With nitric acid | ||
| 84 % | With sulfuric acid; nitric acid at 0 - 20℃; | For 4-Acetamido-3-nitrobenzoic acid (17): 4-acetamidobenzoic acid (24) (2.5 g, 14 mmol) was addedslowly to a mixture (1:1) of HNO3 and conc. H2SO4 (40 mL) with stirring for 10 min at 0 °C. After,the mixture was stirred for 30 min at room temperature. The reaction mixture was poured into icewater and neutralized by adding 15 mL of 5% Na2CO3. The product was obtained by filtration andwashed with an excess of H2O. The crude was purified by recrystallization with ethanol, yielding (17)(84%). IR (KBr): 3324 (NH); 2912 (CH); 1717 and 1672 (C=O); 773 (NO2) cm1. 1H-NMR (400 MHz,DMSO-d6) δ ppm: 2.1 (s, 3H, CH3); 7.8 (s, 1H, C6H3NO2); 8.1 (s, 1H, C6H3NO2); 8.3 (s, 1H, C6H3NO2);10.2 (s, 1H, NH); 12.6 (s, 1H, COOH). Calculated analysis for C9H8N2O5: C, 48.22; H, 3.60; N, 12.50.Found: C, 47.90; H, 3.30; N, 12.20. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With cholinesterase enzymatic hydrolysis; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide | |
| 66% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h; | 7 Preparation and Characterization of Crystalline Tacedinaline Form C To the extent possible, the procedure set forth in Thomas, M. et al., Bioorganic & Medicinal Chemistry 2008, 16, 8109-8116, was followed as described herein. To a stirred solution of 4-acetamido benzoic acid 7.4 (2.5 g, 13.95 mmol, 1.0 eq.) in N,N-dimethylformamide (50 mL) was added o-phenyldiamine 7.7 (4.53 g, 41.9 mmol, 3.0 eq.), followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.48 g, 18.14 mmol, 1.3 eq.) and catalytic 4-(dimethylamino)pyridine (0.18 g, 1.47 mmol, 0.1 eq.). The reaction mixture was stirred at room temperature for 16 hours. The solvents were removed under reduced pressure at 58° C. The crude residue was diluted with dichloromethane (100 mL) and kept in the refrigerator overnight. The resulting precipitate was filtered, washed with hot dichloromethane (100 mL), and dried under vacuum to afford 4-acetamido-N-(2-aminophenyl)benzamide 7.6 as an off-white solid. Yield 7.6=2.48 g (66%). |
| With sodium hydride; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate |
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h; | 7 To the extent possible, the procedure set forth in Thomas, M. et al., Bioorganic & Medicinal Chemistry 2008, 16, 8109-8116, was followed as described herein. To a stirred solution of 4-acetamido benzoic acid 7.4 (2.5 g, 13.95 mmol, 1.0 eq.) in N,N-dimethylformamide (50 mL) was added o-phenyldiamine 7.7 (4.53 g, 41.9 mmol, 3.0 eq.), followed by N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (3.48 g, 18.14 mmol, 1.3 eq.) and catalytic 4-(dimethylamino)pyridine (0.18g, 1.47 mmol, 0.1 eq.). The reaction mixture was stirred at room temperature for 16 hours. The solvents were removed under reduced pressure at 58 °C. The crude residue was diluted with dichloromethane (100 mL) and kept in the refrigerator overnight. The resulting precipitate was filtered, washed with hot dichloromethane (100 mL), and dried under vacuum to afford 4-acetamido-N-(2-aminophenyl)benzamide 7.6 as an off-white solid. Yield 7.6 = 2.48g (66%). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1: 38 percent / QHSO4, NaOH / H2O; CHCl3 / 22 h / Ambient temperature 2: 73 percent / fuming nitric acid 3: 41 percent / LiAlH4 / diethyl ether; tetrahydrofuran / 2 h / Ambient temperature 4: 9 M HCl / 0.5 h / Heating 5: H2 / Pd/C / ethanol |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With oxygen; potassium acetate; palladium diacetate; C19H24N2O; p-benzoquinone In N,N-dimethyl-formamide at 110℃; for 24h; regioselective reaction; | |
| 52% | With oxygen; potassium acetate; palladium diacetate; p-benzoquinone In N,N-dimethyl acetamide at 115℃; for 15h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1.1: triethylamine; chloroformic acid ethyl ester / tetrahydrofuran / 0.33 h / -15 - -10 °C 1.2: 1 h / -15 - -10 °C 2.1: toluene / 80 °C 3.1: dichloromethane / 1 h / 20 °C 4.1: sodium tetrahydridoborate; iodine / tetrahydrofuran / 4 h / 0 °C / Reflux |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 1 h / 100 °C 2.1: ethanol / 20 min / Cooling with ice 2.2: 2 h / 80 °C 3.1: magnesium sulfate; acetic acid / ethanol / 16 h / 90 °C 3.2: 15 min / 230 - 250 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 1 h / 100 °C 2.1: ethanol / 20 min / Cooling with ice 2.2: 2 h / 80 °C 3.1: magnesium sulfate; acetic acid / ethanol / 16 h / 90 °C 3.2: 15 min / 230 - 250 °C 4.1: trichlorophosphate / toluene / 2 h / 110 °C |
[ 851392-68-2 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 935-13-7 ]
[ 71989-18-9 ]
[ 556-08-1 ]
[ 71989-23-6 ]
[ 167393-62-6 ]
[ CAS Unavailable ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 20℃; Automated synthesizer; Stage #2: With piperidine In N,N-dimethyl-formamide Automated synthesizer; Stage #3: Fmoc-Dab(Mtt)-OH; Fmoc-Leu-OH; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; 3-(2-furyl)propanoic acid; Fmoc-Glu(OtBu)-OH; p-(acetylamino)benzoic acid; Fmoc-Ile-OH Further stages; |