Structure of 50765-19-0
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CAS No. : | 50765-19-0 |
Formula : | C8H6INO4 |
M.W : | 307.04 |
SMILES Code : | O=C(OC)C1=CC([N+]([O-])=O)=CC(I)=C1 |
MDL No. : | MFCD00463865 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
With ethanol; tin(ll) chloride; In tetrahydrofuran; for 0.5h;Heating / reflux; | Tin chloride (88.6 g, 392 mmol) inEtOH (50mL) was refluxed and the nitrobenzoate from step A (24.1 g, 78.4 mmol) in 1 :1 THF :EtOH (100mL) was added dropwise. The reaction mixture was refluxed for 30 minutes then cooled to 0 C. The resulting solution was basified to pH 8-9 with aq.Na2C03. The aqueous layer was extracted three times with EtOAc (700 mL) and the combined extracts were washed with saturatedNaHC03 then brine. The organics were dried over Na2SO4 and concentrated to afford the desired aniline which was used without further purification. | |
With tin(ll) chloride; In tetrahydrofuran; ethanol; for 0.5h;Heating / reflux; | Step B: Tin chloride (88.6 g, 392 mmol) in EtOH (50 mL) was refluxed and the nitrobenzoate from stepA (24.1 g, 78.4 mmol) in 1:1 THF:EtOH (100 mL) was added dropwise. The reaction mixture wasrefluxed for 30 min then cooled to 0 C. The resulting solution was basified to pH 8-9 with aq. Na2CO3.The aqueous layer was extracted three times with EtOAc (700 mL) and the combined extracts werewashed with saturated NaHCOs then brine. The organics were dried over Na2SC>4 and concentrated toafford the crude aniline which was used without further purification. | |
Step B: Nitro Reduction; Tin chloride (88.6 g, 392 mmol) in EtOH (50 mL) was refluxed and the nitrobenzoate from step A (24.1 g, 78.4 mmol) in 1:1 THF:EtOH (100 mL).was added dropwise. The reaction mixture was refluxed for 30 minutes then cooled to 0C. The resulting solution was basified to pH 8-9 with aq. Na2C03. The aqueous layer was extracted three times with EtOAc (700 mL) and the combined extracts were washed with saturated NaHC03 then brine. The organics were dried over Na2S04 and concentrated to afford 21.7 g of the crude aniline which was used without further purification. |
Step B: Tin chloride (88.6 g, 392 mmol) in ETOH (50 mL) was refluxed and a 1: 1 THF : ETOH (100 mL) solution of the nitrobenzoate from step A (24.1 g, 78.4 mmol) was added dropwise. The reaction mixture was refluxed for 30 minutes then cooled to 0C. The solution was basified to pH 8-9 with aq. NA2CO3. The aqueous layer was extracted with EtOAc (3 x 700 mL). The combined organics were washed with saturated NAHC03 then brine. The organics were dried over NA2S04 AND concentrated affording the crude aniline. LCMS [M + H] = 278.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With potassium acetate;PdCl2(dpf)2; In dimethyl sulfoxide; at 80.0℃; for 2.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester To a stirred solution of 3-Iodo-5-nitro-benzoic acid methyl ester (5.0 g, 0.016 mol), bis(pinacolato)diborane (4.55 g, 0.018 mol) and KOAc (4.80 g, 0.049 mol) in DMSO (50 mL) was added PdCl2(dpf)2 (0.40 g, 0.50 mmol). The mixture was flushed with N2 and heated to 80 C. for 2 h. After the reaction mixture was cooled down to room temperature, H2O (20 mL) was added and the mixture was extracted with Et2O (3*30 mL). The organic layer was separated and washed with H2O, brine and dried over Na2SO4. Solvent was removed and the residue was purified by column chromatography (EtOAc/hexane=1:3) to afford 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester as a white solid (3.30 g, 67%) MS (M+H)=308. |
67% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 2.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic Acid Methyl Ester; To a stirred solution of 3-Iodo-5-nitro-benzoic acid methyl ester (5.0 g, 0.016 mol), bis(pinacolato)diborane (4.55 g, 0.018 mol) and KOAc (4.80 g, 0.049 mol) in DMSO (50 mL) was added PdCl2(dpf)2 (0.40 g, 0.50 mmol). The mixture was flushed with N2 and heated to 80 C for 2 h. After the reaction mixture was cooled down to room temperature, H2O (20 mL) was added and the mixture was extracted with Et2O (3×30 mL). The organic layer was separated and washed with H2O, brine and dried over Na2SO4. Solvent was removed and the residue was purified by column chromatography (EtOAc/hexane=1:3) to afford 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester as a white solid (3.30 g, 67%) MS (M+H)=308. |
67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80.0℃; for 2.0h;Inert atmosphere; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester To a stirred solution of 3-Iodo-5-nitro-benzoic acid methyl ester (5.0 g, 0.016 mol), bis(pinacolato)diborane (4.55 g, 0.018 mol) and KOAc (4.80 g, 0.049 mol) in DMSO (50 mL) was added PdCl2(dpf)2 (0.40 g, 0.50 mmol). The mixture was flushed with N2 and heated to 80 C for 2 h. After the reaction mixture was cooled down to room temperature, H2O (20 mL) was added and the mixture was extracted with Et2O (3×30 mL). The organic layer was separated and washed with H2O, brine and dried over Na2SO4. Solvent was removed and the residue was purified by column chromatography (EtOAc/hexane=1:3) to afford 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester as a white solid (3.30 g, 67%) MS (M+H)=308. |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[ 1,3,21 dioxaborolan-2-yl) -benzoic acid methyl ester; A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinaco- lato)diboron (9.1 g, 0.0358 mol), KOAc (9.5 9g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 800C for 4 h under N2 atmosphere. The mixture was cooled to RT and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO/t. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[ 1,3,2] dioxaborolan-2- yl) -benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic Acid Methyl Ester; A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.59 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic Acid Methyl Ester A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.5 9 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.59 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h;Inert atmosphere; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.5 9 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h;Inert atmosphere; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl esterA solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.5 9 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. | |
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80.0℃; for 4.0h;Inert atmosphere; | Step 2 3-Nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester A solution of 3-iodo-5-nitro-benzoic acid methyl ester (10 g, 0.0326 mol), bis(pinacolato)diboron (9.1 g, 0.0358 mol), KOAc (9.5 9 g, 0.098 mol) and PdCl2(dppf) (798 mg, 0.98 mmol) in DMSO (40 ml) was heated to 80 C. for 4 hours under N2 atmosphere. The mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine and dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude 3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester was used without purification in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | A solution of NaNO2 (1.06g, 15.37mmol) in 10mL of water was added dropwise to a stirred, ice-bath cooled solution of 17 (2.00g, 10.20mmol) in 150mL of water acidified with 5mL of conc. H2SO4. The temperature was maintained at 2C and after 1.5h, a solution of KI (5.20g, 31.33mmol) in 15mL of water was added dropwise and the reaction mixture was stirred for 1h at 2C. Then it was allowed to warm to room temperature over 4h period. The crude product was extracted with AcOEt (3×50mL) and the pH of the aqueous fraction was adjusted to 4 with NaHCO3 and extracted with AcOEt (3×50mL). The combined organic fractions were washed with 10% aqueous solution of Na2S2O3·5H2O, brine and dried over MgSO4 and concentrated in vacuo. Purification by silica gel column chromatography (20% AcOEt in hexane) afforded pure product 18 (2.63g, 84%) as a pale yellow solid. 1H data are in agreement with published data.25 1H NMR (400MHz, acetone-d6) delta: 8.76 (1H, dd J 2.2, 1.6Hz, arom.), 8.69 (1H, dd J 2.2, 1.4Hz, arom.), 8.65 (1H, t, J 1.5Hz, arom), 3.98 (3H, s, OMe). 13C NMR (100MHz, acetone-d6) delta: 164.2, 149.6, 144.4, 136.8, 134.0, 124.2, 94.1, 53.4. Rf (20% AcOEt/hexane) 0.54. MS(EI): m/z (%)=308.1 (10), 307.1 (100, M+), 276.0 (77), 261.1 (10), 246.0 (21), 230.0 (15), 218.0 (7), 201.0 (8), 75.1 (33), 74.1 (18). |