* 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.
Stage #1: With hydrogenchloride; sodium nitrate In water for 3.33333 h; Cooling Stage #2: With urea; potassium iodide In water at 20℃; for 20 h;
3-Aminophthalic acid (5.00 g, 27.6 mmol) was dissolved in 8.4 mol/L hydrochloric acid (60 mL), and the solution was added with an aqueous solution (10 mL) of sodium nitrate (2.0 g, 29 mmol) by drops under ice-cooling for 20 minutes, followed by stirring at the same temperature for 3 hours. Then, an aqueous solution (10 mL), in which potassium iodide (6.9 g, 41 mmol) and urea (291 mg) were dissolved, is added by drops to the mixture, followed by stirring at room temperature for 20 hours. The reaction mixture was added with 10percent aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was washed with chloroform to obtain 3-iodophthalic acid (5.0 g, yield 62percent).
Reference：
[1] Patent: EP2108642, 2009, A1, . Location in patent: Page/Page column 110
[2] Journal fuer Praktische Chemie (Leipzig), 1896, vol. <2> 53, p. 383
[3] Journal of the Chemical Society, 1914, vol. 105, p. 2480
[4] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 22, p. 6366 - 6379
2
[ 102928-38-1 ]
[ 6937-34-4 ]
Yield
Reaction Conditions
Operation in experiment
93%
Stage #1: With sodium hydroxide In tetrahydrofuran; water Stage #2: With hydrogenchloride In tetrahydrofuran; water
[0030] The synthesis of mIBX is readily accomplished from commercially available 3-nitrophtalic acid as follows: esterification of 3-nitrophtalic acid via the corresponding acid chloride to give nitrodiester (100percent), which upon catalytic hydrogenation provides the aminodiester (100percent). Diazotization is then performed, followed by iodination of the aminodiester to provide dimethyl 3-iodophthalate in about 91 percent yield. This is followed by saponification, then acidification of dimethyl 3-iodophthalate to give 3-iodophthalic acid in about 93 percent yield. 3-iodophthalic acid is then oxidized to form the water-soluble MIBX. This process is carried out using KBrO3 in 0.73H2SO4 at 55-60° C. as follows: KBrO3 (5 g, 30 mmol) is added in portions to a suspension of 3-iodophthalic acid (5 g, 17.1 mmol) in 70 ML of 0.73 M H2SO4 over a period of 20 minutes; The mixture is then maintained at 55-60° C. for 12 hours and the resulting clear orange solution is evaporated to yield an off-white solid, which is triturated with 30 ML of water at 0° C. for 2 hours and filtered to obtain a white solid.This is further triturated with hexane (100 ML) for 6 hours and filtered to give MIBX (3.9 g, 71percent) as a white solid with a melting point of 258-260° C. The approximately 70percent yield for the conversion of 3-iodophthalic acid to MIBX is the isolated yield of MIBX, with the actual conversion near quantitative as evident from monitoring the oxidation of 3-iodophthalic acid to MIBX by 1H NMR spectroscopy. Water-soluble MIBX is isolated as an analytically pure white solid.The synthesis of MIBX from 3-nitrophthalic acid is illustrated in . The physical properties of MIBX are as follows: mp 258-260° C.; IR (KBr), 3503 3469, 3050, 1708, 1631, 1588, 1369, 730, 700 cm-1; 1H NMR (D2O), 300 MHz): δ 8.35 (dd, J=7.9, 1.0 Hz, 1H), 8.09 (t, J=7.9 Hz, 1H), 7.94 (dd, J=7.9, 1.0 Hz, 1H); 13C NMR (D2O, 75 MHz): δ 125.5, 127.5, 132.5, 134.7, 137.0, 147.1 (ring carbons), 168.9, 172.9 (carbonyl carbons).
3-Aminophthalic acid (5.00 g, 27.6 mmol) was dissolved in 8.4 mol/L hydrochloric acid (60 mL), and the solution was added with an aqueous solution (10 mL) of sodium nitrate (2.0 g, 29 mmol) by drops under ice-cooling for 20 minutes, followed by stirring at the same temperature for 3 hours. Then, an aqueous solution (10 mL), in which potassium iodide (6.9 g, 41 mmol) and urea (291 mg) were dissolved, is added by drops to the mixture, followed by stirring at room temperature for 20 hours. The reaction mixture was added with 10% aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was washed with chloroform to obtain 3-iodophthalic acid (5.0 g, yield 62%).
With acetic anhydride; In tetrahydrofuran; at 20 - 85℃; for 6h;
[0591] To a solution of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> (5.0 g, 17.1 mmol) in THF (75 mL) was added acetic anhydride (25 mL) at rt. The mixture was heated to 85C and stirred for 6 hrs. The reaction was cooled to rt and concentrated, providing 4-iodoisobenzofuran-1,3- dione (4.59 g, 98% yield) as a yellow solid. MS (ESI) m/z = 275 [M+H]+. 1H NMR (DMSO-d6, 400 MHz) ^: 8.39 (d, J = 8.0 Hz, 1 H), 8.06 (d, J = 7.2 Hz, 1 H), 7.66 (t, J = 7.6 Hz, 1 H).
96%
With acetic acid; at 145℃; for 1h;
3-Iodophthalic acid (4.00 g, 13.7 mmol) was dissolved in anhydrous acetic acid, and the solution was stirred at 145 C for 1 hour. The solvent of the reaction mixture was evaporated under reduced pressure and the residue was purified by slurry using diisopropylether to obtain <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> anhydride (3.6 g, yield 96%). FAB-MS m/z: 275 [M+H]+; 1H-NMR (CDCl3)delta(ppm): 7.56 (dd, J = 7.6, 7.6 Hz, 1H), 8.01 (dd, J = 0.8, 7.4 Hz, 1H), 8.30 (dd, J = 0.7, 7.9 Hz, 1H).
65%
With acetic anhydride;Heating / reflux;
A solution of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> (0.9 g, 3.08 mmol) in acetic anhydride (5 mL) was heated to reflux under nitrogen overnight. After cooling, the solvent was removed in vacuo and the residue purified by trituration with ethanol to give 4-iodo-2-benzofuran-1,3-dione (0.55 g, 65%).
With acetic anhydride;Heating / reflux;
Commercially available 3-iodo-l,2-benzendicarboxylic acid Compound 17a was cyclized to 4-iodophthalic anhydride Compound 17b in refluxing acetic anhydride. 1H NMR (300 MHz, CDCl3) 7.57 (t, J = 7.7 Hz, IH), 8.01 (d, J = 7.6 Hz, IH), 8.30 (d, J = 7.7 Hz, IH); MS (ESI) m/z: 275 (MH+).
With acetic anhydride; at 140℃; for 4h;
(a) 4-Iodoisobenzofuran-l,3-dione. A solution of 3- <strong>[6937-34-4]iodophthalic acid</strong> (5.00 g, 17 mmol, commercially available from Fluorchem Products, West Columbia, SC) and acetic anhydride (15 mL) was placed in a sealed flask and then heated in an oil bath at 1400C for 4 hours. The solution was cooled to room temperature, and then placed in an ice bath. The solids were collected by filtration, washed with cold ether, and dried under vacuum.
2.73 g
With toluene-4-sulfonic acid; In toluene; at 100℃; for 3h;
(1) Adding 2.92 g of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> and 100 ml of toluene,0.0146g of p-toluenesulfonic acid, stirred and heated to 100 C reflux, after the system is dissolved,The mixture was kept under reflux for 3 h, and the reaction was stopped after the medium-controlled liquid chromatography <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> was 1%.2.73g of 3-iodophthalic anhydride is formed,Obtaining a 3-iodophthalic anhydride solution.
With potassium bromate; sulfuric acid; In water; at 55 - 60℃; for 12h;
[0030] The synthesis of mIBX is readily accomplished from commercially available 3-nitrophtalic acid as follows: esterification of 3-nitrophtalic acid via the corresponding acid chloride to give nitrodiester (100%), which upon catalytic hydrogenation provides the aminodiester (100%). Diazotization is then performed, followed by iodination of the aminodiester to provide dimethyl 3-iodophthalate in about 91 % yield. This is followed by saponification, then acidification of dimethyl 3-iodophthalate to give <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> in about 93 % yield. <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> is then oxidized to form the water-soluble MIBX. This process is carried out using KBrO3 in 0.73H2SO4 at 55-60 C. as follows: KBrO3 (5 g, 30 mmol) is added in portions to a suspension of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> (5 g, 17.1 mmol) in 70 ML of 0.73 M H2SO4 over a period of 20 minutes; The mixture is then maintained at 55-60 C. for 12 hours and the resulting clear orange solution is evaporated to yield an off-white solid, which is triturated with 30 ML of water at 0 C. for 2 hours and filtered to obtain a white solid.This is further triturated with hexane (100 ML) for 6 hours and filtered to give MIBX (3.9 g, 71%) as a white solid with a melting point of 258-260 C. The approximately 70% yield for the conversion of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> to MIBX is the isolated yield of MIBX, with the actual conversion near quantitative as evident from monitoring the oxidation of <strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> to MIBX by 1H NMR spectroscopy. Water-soluble MIBX is isolated as an analytically pure white solid.The synthesis of MIBX from 3-nitrophthalic acid is illustrated in . The physical properties of MIBX are as follows: mp 258-260 C.; IR (KBr), 3503 3469, 3050, 1708, 1631, 1588, 1369, 730, 700 cm-1; 1H NMR (D2O), 300 MHz): delta 8.35 (dd, J=7.9, 1.0 Hz, 1H), 8.09 (t, J=7.9 Hz, 1H), 7.94 (dd, J=7.9, 1.0 Hz, 1H); 13C NMR (D2O, 75 MHz): delta 125.5, 127.5, 132.5, 134.7, 137.0, 147.1 (ring carbons), 168.9, 172.9 (carbonyl carbons).
[0030] The synthesis of mIBX is readily accomplished from commercially available 3-nitrophtalic acid as follows: esterification of 3-nitrophtalic acid via the corresponding acid chloride to give nitrodiester (100%), which upon catalytic hydrogenation provides the aminodiester (100%). Diazotization is then performed, followed by iodination of the aminodiester to provide dimethyl 3-iodophthalate in about 91 % yield. This is followed by saponification, then acidification of dimethyl 3-iodophthalate to give 3-iodophthalic acid in about 93 % yield. 3-iodophthalic acid is then oxidized to form the water-soluble MIBX. This process is carried out using KBrO3 in 0.73H2SO4 at 55-60 C. as follows: KBrO3 (5 g, 30 mmol) is added in portions to a suspension of 3-iodophthalic acid (5 g, 17.1 mmol) in 70 ML of 0.73 M H2SO4 over a period of 20 minutes; The mixture is then maintained at 55-60 C. for 12 hours and the resulting clear orange solution is evaporated to yield an off-white solid, which is triturated with 30 ML of water at 0 C. for 2 hours and filtered to obtain a white solid.This is further triturated with hexane (100 ML) for 6 hours and filtered to give MIBX (3.9 g, 71%) as a white solid with a melting point of 258-260 C. The approximately 70% yield for the conversion of 3-iodophthalic acid to MIBX is the isolated yield of MIBX, with the actual conversion near quantitative as evident from monitoring the oxidation of 3-iodophthalic acid to MIBX by 1H NMR spectroscopy. Water-soluble MIBX is isolated as an analytically pure white solid.The synthesis of MIBX from 3-nitrophthalic acid is illustrated in . The physical properties of MIBX are as follows: mp 258-260 C.; IR (KBr), 3503 3469, 3050, 1708, 1631, 1588, 1369, 730, 700 cm-1; 1H NMR (D2O), 300 MHz): delta 8.35 (dd, J=7.9, 1.0 Hz, 1H), 8.09 (t, J=7.9 Hz, 1H), 7.94 (dd, J=7.9, 1.0 Hz, 1H); 13C NMR (D2O, 75 MHz): delta 125.5, 127.5, 132.5, 134.7, 137.0, 147.1 (ring carbons), 168.9, 172.9 (carbonyl carbons).
3-iodo-N<SUP>1</SUP>-(2-methoxy-4-(perfluoropropan-2-yl)phenyl)-N<SUP>2</SUP>-(2-methyl-1-((N-methylenecyanamidyl)methylthio)propan-2-yl)phthalamide[ No CAS ]
<strong>[6937-34-4]3-<strong>[6937-34-4]iodophthalic acid</strong></strong> (292.0 g, L Omol) and dimethyl sulfoxide (100 mL) were added to the three-necked flask, and stirring was started.Sodium ethoxide (408.5 g, 6.0 mol) was added during the reaction,And copper trifluoromethanesulfonate (3.68, 0.02111 01),Heating to 120 C incubation reaction 3 hours;TLC monitoring (methanol: dichloromethane = 1: 1, v / v) to complete reaction, drop to room temperature, filter;The filtrate with 6. 0m0l / L of hydrochloric acid to adjust the pH value of between 1.0 to 2.0,The filtrate was transferred to a three-necked flask and, with stirring,A solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (465. 7 g, 3. Omol)Heated to 130 C insulation reaction 4. 5 hours;TLC (methanol: dichloromethane = 1: 1, v / v) until the reaction was complete and reduced to room temperature;(1000mLX3). The organic phase was combined, dried over anhydrous magnesium sulfate and filtered to give 247.9g of 3-hydroxyphthalic anhydride as a white solid with a conversion of 84.9% and HPLC purity of 96.1% . (M.p. 200 to 201 C)v
N-(4-(2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamido)butyl)-3-(2-((S)-2,7-dioxoazepan-3-yl)-1,3-dioxoisoindolin-4-yl)propanamide[ No CAS ]
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