* 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 8-quinolinol; sodium hydroxide; copper dichloride In water at 20℃; for 0.333333 h; Sealed tube; Microwave irradiation
General procedure: In a 10 mL glass tube 2-iodobenzoic acid (1.0 mmol), acetamidine hydrochloride (1.2 mmol), CuCl2 (0.1 mmol), L2 (0.1 mmol), and NaOH (4.0 equiv.) and 3.0 mL water were placed. The vessel was then sealed with a septum and placed into the microwave cavity. Initial microwave irradiation of 120 W by using a CEM Discover microwave synthesizer was used at the room temperature for 20 min. The reaction mixture was stirred continuously during the reaction. After completion of the reaction, the solvent was removed in vacuo. The residue was purified by silica gel column chromatography to afford the corresponding product. All the products were confirmed by NMR and MS spectroscopic analysis.
Reference:
[1] Journal of the American Chemical Society, [2] Journal of the American Chemical Society, 2009, vol. 131, p. 251 - 262
[3] Organic Letters, 2011, vol. 13, # 24, p. 6488 - 6491
[4] Tetrahedron, 2005, vol. 61, # 42, p. 10113 - 10121
[5] Magnetic Resonance in Chemistry, 1989, vol. 27, # 11, p. 1007 - 1011
[6] Tetrahedron, 2000, vol. 56, # 27, p. 4777 - 4792
[7] Organic and Biomolecular Chemistry, 2014, vol. 12, # 27, p. 5031 - 5037
[8] Patent: WO2014/189370, 2014, A1, . Location in patent: Page/Page column 28-29
[9] Organic Letters, 2018, vol. 20, # 2, p. 345 - 348
3
[ 88-67-5 ]
[ 19230-50-3 ]
Yield
Reaction Conditions
Operation in experiment
42%
at 135℃; for 1 h;
During this preparation up to 25 mmol I2 are formed. Therefore, the synthesis has to be conducted in a well-ventilated fume cupboard. Prepared according to literature procedure [10]. 2-Iodobenzoic acid (4, 10 g, 40.3 mmol, 1 equiv) was added to a mixture of HNO3 (35 mL, 65percent) and H2SO4 (85 mL, 95percent). The solution was heated to 135 °C and stirred for 1 h. Subsequently, the resulting brown slurry was poured onto ice and the grey precipitate was filtered off and washed with copious amounts of water. Then, the filtrate was suspended in water (100 mL), heated to 100 °C and treated with a solution of KI (8.5 g, 51.2 mmol, 1.3 equiv) and H2SO4 (5 drops) in water (10 mL) over the course of 1 h. Finally, the brown suspension was filtered hot and washed with water to afford the pure product (5 g, 42percent) as a brown solid. If impure product is obtained, boiling with water followed by hot filtration can be applied.
Reference:
[1] Journal of Organic Chemistry, 2005, vol. 70, # 12, p. 4778 - 4783
[2] Synlett, 2013, vol. 24, # 13, p. 1707 - 1711
[3] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 1 - 6
[4] Organic Letters, 2011, vol. 13, # 3, p. 518 - 521
[5] Helvetica Chimica Acta, 1930, vol. 13, p. 310,311[6] Helvetica Chimica Acta, 1932, vol. 15, p. 1102
[7] Chemische Berichte, 1893, vol. 26, p. 2473
[8] Patent: US6225323, 2001, B1,
4
[ 88-67-5 ]
[ 19230-50-3 ]
[ 5398-69-6 ]
Reference:
[1] Dalton Transactions, 2013, vol. 42, # 2, p. 355 - 358
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 45, p. 9680 - 9684
5
[ 17420-30-3 ]
[ 19230-50-3 ]
Reference:
[1] Magnetic Resonance in Chemistry, 1989, vol. 27, # 11, p. 1007 - 1011
6
[ 400-75-9 ]
[ 19230-50-3 ]
Reference:
[1] Journal of the Chemical Society, 1951, p. 3459,3463[2] Journal of the Chemical Society, 1954, p. 1071,1074
7
[ 344-62-7 ]
[ 19230-50-3 ]
Reference:
[1] Journal of the Chemical Society, 1951, p. 3459,3463[2] Journal of the Chemical Society, 1954, p. 1071,1074
8
[ 121-01-7 ]
[ 19230-50-3 ]
Reference:
[1] Journal of the Chemical Society, 1951, p. 3459,3463[2] Journal of the Chemical Society, 1954, p. 1071,1074
9
[ 395-68-6 ]
[ 19230-50-3 ]
Reference:
[1] Journal of the Chemical Society, 1951, p. 3459,3463[2] Journal of the Chemical Society, 1954, p. 1071,1074
10
[ 88-67-5 ]
[ 7664-93-9 ]
[ 7697-37-2 ]
[ 19230-50-3 ]
Reference:
[1] Helvetica Chimica Acta, 1930, vol. 13, p. 310,311[2] Helvetica Chimica Acta, 1932, vol. 15, p. 1102
11
[ 88-67-5 ]
[ 19230-50-3 ]
[ 5398-69-6 ]
Reference:
[1] Dalton Transactions, 2013, vol. 42, # 2, p. 355 - 358
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 45, p. 9680 - 9684
During this preparation up to 25 mmol I2 are formed. Therefore, the synthesis has to be conducted in a well-ventilated fume cupboard. Prepared according to literature procedure [10]. 2-Iodobenzoic acid (4, 10 g, 40.3 mmol, 1 equiv) was added to a mixture of HNO3 (35 mL, 65%) and H2SO4 (85 mL, 95%). The solution was heated to 135 C and stirred for 1 h. Subsequently, the resulting brown slurry was poured onto ice and the grey precipitate was filtered off and washed with copious amounts of water. Then, the filtrate was suspended in water (100 mL), heated to 100 C and treated with a solution of KI (8.5 g, 51.2 mmol, 1.3 equiv) and H2SO4 (5 drops) in water (10 mL) over the course of 1 h. Finally, the brown suspension was filtered hot and washed with water to afford the pure product (5 g, 42%) as a brown solid. If impure product is obtained, boiling with water followed by hot filtration can be applied.
With nitric acid; In sulfuric acid;
EXAMPLE 1 2-Iodo-5-Nitrobenzoic Acid 2-Iodobenzoic acid (100 g) was dissolved in 400 mL of concentrated sulphuric acid and placed in a 2 liter 3 necked flask. The flask was fitted with reflux condenser, a thermometer and an addition funnel. Fuming nitric acid (400 ml) was added drop by drop. The addition was adjusted in such a way that the temperature was allowed to raise to 80 C. over a period of 2 hours. During the addition, the reaction mixture was stirred vigorously and maintained the temperature at 80 C. for an additional 2 hours. After the completion of the reaction, the reaction mixture was poured slowly into crushed ice (3 Kg). The contents were allowed to settle and were filtered. The yellow precipitate was collected and dried at 30 C. The yield was 90 grams.
With sulfuric acid; nitric acid; at 0 - 130℃; for 1.75h;
Prepared according to literature procedure. The 2-iodobenzoic acid (1,000 mg, 4.03 mmol) was pre-cooled at 0 C and then a solution of Conc. HNO3 (1.50 mL) and Conc. H2SO4 (4.50 mL) was added slowly. The mixture was allowed to stir at 0 C for 15 minutes, ice bath was moved, stirred at room temperature for 30 minutes, and followed by to stir the mixture at 130 C for 1 hour. The mixture was yellow, cooled with ice bath, then filtered with suction flask and Buchner funnel. The light yellow solid was obtain. 1H NMR (300 MHz, CDCl3) delta 8.12 (d, J = 2.3 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.33 (dd, J = 8.4, 2.3 Hz, 1H). Other data was identical to the literature values.
Previously, the 3-aminopropyltriethoxysilane (APTES) linker was installed into <strong>[19230-50-3]2-iodo-5-nitrobenzoic acid</strong> through the acid chloride. Accordingly, it was imagined that the linker could be installed similarly into NBP-aci.
With thionyl chloride; for 2h;Reflux;
2-Amino-5-nitrobenzoic acid (500 mg, 2.75 mmol) was dissolved in 0.5 M NaOH (5 mL) at 70 C. The resulting solution was allowed to cool to 0 C and the treated with concentrated HCl (1mL). To the mixture was added dropwise a solution of sodium nitrite (196 mg, 2.84 mmol) in water (2.5 mL). After stirring for 0.5 h, a solution of potassium iodide (913 mg, 5.5 mmol) inwater (2.5 mL) was added dropwise to the mixture. The resulting solution was stirred for 1 h and allowed to warm to room temperature. After stirring for 12 h, the precipitate was collected by filtration, washed with water, and dried invacuo. The residue was purified by silica gel column chromatography (eluent: hexane/EtOAc = 1/1) to give <strong>[19230-50-3]5-nitro-2-iodobenzoic acid</strong> [5] (453 mg, 56%) as a pale yellow solid: 1H NMR (400 MHz, CDCl3) delta 8.80 (1H, d, J = 2.8Hz), 8.29 (1H, d, J = 8.7 Hz), 8.03 (1H, dd, J = 8.7, 2.8 Hz). A solution of <strong>[19230-50-3]5-nitro-2-iodobenzoic acid</strong> (293 mg, 1.0mmol) in thionyl chloride (1.3 mL) was heated at reflux with stirring for 2 h. The resulting solution was concentrated under reduced pressure. The remaining thionyl chloride was removed by azeotropic distillation with benzene. The residue was dissolved in anhydrous CH2Cl2 (3.3 mL). To the mixture were added isopropylamine (71 mg, 1.2 mmol)and triethylamine (304 mg, 3.0 mmol) at 0 C under a nitrogen atmosphere. After stirring at room temperature for 21 h,the resulting solution was diluted with EtOAc. The mixture was washed with 10% HCl, saturated aqueous NaHCO3, water, and brine; dried over Na2SO4; filtered; and concentrated under reduced pressure. The residue was purified by recrystallization from hexane and CHCl3 to give 22 (69 mg, 21% in 2 steps) as colorless needles.
2-Amino-5-nitrobenzoic acid (500 mg, 2.75 mmol) was dissolved in 0.5 M NaOH (5 mL) at 70 C. The resulting solution was allowed to cool to 0 C and the treated with concentrated HCl (1mL). To the mixture was added dropwise a solution of sodium nitrite (196 mg, 2.84 mmol) in water (2.5 mL). After stirring for 0.5 h, a solution of potassium iodide (913 mg, 5.5 mmol) inwater (2.5 mL) was added dropwise to the mixture. The resulting solution was stirred for 1 h and allowed to warm to room temperature. After stirring for 12 h, the precipitate was collected by filtration, washed with water, and dried invacuo. The residue was purified by silica gel column chromatography (eluent: hexane/EtOAc = 1/1) to give 5-nitro-2-iodobenzoic acid [5] (453 mg, 56%) as a pale yellow solid: 1H NMR (400 MHz, CDCl3) delta 8.80 (1H, d, J = 2.8Hz), 8.29 (1H, d, J = 8.7 Hz), 8.03 (1H, dd, J = 8.7, 2.8 Hz). A solution of 5-nitro-2-iodobenzoic acid (293 mg, 1.0mmol) in thionyl chloride (1.3 mL) was heated at reflux with stirring for 2 h. The resulting solution was concentrated under reduced pressure. The remaining thionyl chloride was removed by azeotropic distillation with benzene. The residue was dissolved in anhydrous CH2Cl2 (3.3 mL). To the mixture were added isopropylamine (71 mg, 1.2 mmol)and triethylamine (304 mg, 3.0 mmol) at 0 C under a nitrogen atmosphere. After stirring at room temperature for 21 h,the resulting solution was diluted with EtOAc. The mixture was washed with 10% HCl, saturated aqueous NaHCO3, water, and brine; dried over Na2SO4; filtered; and concentrated under reduced pressure. The residue was purified by recrystallization from hexane and CHCl3 to give 22 (69 mg, 21% in 2 steps) as colorless needles.
2-Amino-5-nitrobenzoic acid (6d, 1.82 g, 10 mmol) was dissolved in DMSO (50 mL) and 30% H2S04 (50 mL) was added. The resulting mixture was heated for two hours at 50 C. The reaction was cooled to 0 C and a solution of NaN02 (970 mg, 14 mmol) in water (25 mL) was added. The mixture was stirred at 0 C for one hour, whereupon a solution of KI (5.0 g, 30 mmol) in H20 (10 mL) was added and the mixture was stirred for 1 hour at room temperature. Next, another portion of KI (5 g, 30 mmol) in H20 (10 mL) was added and the mixture was stirred for an additional hour. EtOAc (100 mL) was added and the reaction was quenched with saturated aqueous NaHS03 (100 mL). The organic layer was washed with water (2 x 100 mL) and brine (100 mL) and subsequently dried over MgS04. The solvents were evaporated under reduced pressure and the crude product was obtained as yellow solid (12.0 g, 120%). 7d was not further purified and used as a crude in the following reaction. 1H-NMR (400 MHz, CD3OD) delta: 8.54 (d, J = 2.7 Hz, 1H), 8.29 (d, J = 8.6 Hz, 1H), 8.01 (dd, J = 8.7, 2.7 Hz, 1H). 13C-NMR (75 MHz, CD3OD) delta: 168.0, 149.2, 144.1, 139.2, 127.1, 125.8, 103.0, 49.6, 49.3, 49.1, 48.8, 48.5. FT-IR max (cm"1): 2932, 1722, 1588, 151, 1342, 1295, 1022, 1234, 728. HRMS (EI+) m/z calcd for C7H4N04I [M]'+ 292.9185, found 292.9184.
I. 2-Iodo-5-Nitro-Benzamide 2-iodo-5-nitro-benzamide was synthesised by the method previously described for 4-iodo-5-nitro-benzamide using <strong>[19230-50-3]2-iodo-5-nitro benzoic acid</strong> (Chemica Alta Ltd., Edmonton, Alberta, Canada) as the starting material. 1 H NMR Spectrum, in DMSO-d6 delta (ppm) values relative to TMS: 7.742 (1H, singlet); 7.943 (1H, doublet of doublts, J=8.26 Hz, J=2.58 Hz); 8.034 (1H, singlet), 8.064 (1H, doublet, J=2.94 Hz); and 8.191 (1H, doublet, J=8.46 Hz). Mass Spectrum: Low resolution electron impact spectrum (m/z): 292 (M+), 276, 230, 202, 165, 127, 91, 75, 63. High resolution measurement of M+: Calculated for C7 H5 IN2 O3: 291.934494; found: 291.934149 (deviation=1.2 ppm).
H. 2-Iodo-5-Nitroso-Benzamide The synthesis of 2-iodo-5-nitroso-benzamide can be performed similarly to the synthesis of 4-iodo-3-nitroso-benzamide, described above, using <strong>[19230-50-3]2-iodo-5-nitro benzoic acid</strong> (Chemica Alta Ltd., Edmonton, Alberta, Canada) as the starting material.
(N,N-Dimethylaminoethyl)-2-Iodo-5-Nitro-Benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With sodium hydroxide; thionyl chloride; triethylamine; In dichloromethane;
EXAMPLE 4 (N,N-Dimethylaminoethyl)-2-Iodo-5-Nitro-Benzamide (1) <strong>[19230-50-3]2-iodo-5-nitro-benzoic acid</strong> (3 mmoles) was dissolved in a solution of dry dichloromethane-DMF mixture (v/v 4:1, 5 ml). To the ice-cold solution, was added 6 mmoles of thionyl chloride. The reaction mixture was stirred at room temperature for two hours. The solvent was then evaporated using a rotory evaporator. The residue was dried under vacuum at 50 C. for 30 minutes. The residue was dissolved in dry dichlormethane (5 ml) without any purification. The solution was then cooled to 0 C. To this solution, triethylamine (1 ml) and a solution of N,N-dimethylethylenediamine (3 mmole) in dichloromethane was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was poured into water and basified to pH 12 using 2M NaOH. The organic layer was separated and washed with water, dried over anhydrous magnesium sulfate and concentrated. The (N,N-dimethylaminoethyl)-2-iodo-5-nitro-benzamide compound was separated by silica gel chromatography. The yield was 70%. The melting point was 126-128 C. 1H NMR (CDCl3) delta 2.27(s 6H, CH3); 2.55(t J=5.7 Hz, 2H, CH2N-); 3.55(q, J=5.7 Hz, 2H, CONHCH2-); 6.56(br s, 1H, NH); 7.93(dd, J=3.0 Hz, j=8.7 Hz, 1H, phenyl, H=4); 8.21(d, J=3.0 Hz, 1H, phenyl H=6)
EXAMPLE 2 Methyl 2-Iodo-5-Nitro-Benzoate In a 5 liter 3 necked flask, <strong>[19230-50-3]2-iodo-5-nitro-benzoic acid</strong> (100 grams) was dissolved in methanol (3000 ml). The flask was fitted with a reflux condenser and 50 ml of concentrated sulfuric acid was added carefully with cooling. After the completion of the addition, the contents were refluxed for 3 days until completion of the reaction. The reaction was followed by TLC. After the completion of the reaction, the reaction mixture was concentrated to 1000 ml and allowed to cool. The product crystalized as a light yellow colored powder. The solid material was filtered and washed with water and methanol and air-dried. The yield was 90 grams.
General procedure: To 292 mg (4 mmol) of isobutyraldehyde in 4 ml of MeOH, 530 mg (4 mmol)of tert-butylcarbazatare added and the mixture is stirred at rt for 2 h. Then 1011 mg (4 mmol) of o-iodobenzoic acid and 339 mg (4 mmol) of tert-butylisocyanidare added and the reaction mixture is stirred overnight at rt. After evaporation of the solvent the crude product is purified by column chromatography on silica gel (chloroform/methanol = 99.5/0.5?90/10, Rf = 0.20 [chloroform/methanol = 99.5/0.5]) to yield 1.52 g of the title compound (white solid, 73%).
Synthesized according to a slight modification of two previously reported procedures.18 Neat2-iodobenzoic acid (3.00 g, 12.1 mmol) was cooled down to 0 C, to which was added a mixture offuming HNO3 (3.0 mL) and concentrated H2SO4 (13.5 mL). This mixture was then stirred at 0 C for 1 h,then at rt for 30 min, and finally at 135 C for 2 h, before being cooled back down to rt. The resultingsolution was poured into plenty of ice water and filtered. The solid was transferred to an Erlenmeyer flaskand suspended in water (300 mL), then heated to a boil. A solution of KI (2.41 g, 14.5 mmol) in water (15mL) acidified to pH 3 with a few drops of concentrated H2SO4 was added portion-wise to this boiling suspension (I2 vapors were generated with each portion). Omitting this step as in Subramanian?s reportyields the iodoso analog. The solution was filtered while still boiling, then the filtrate was stored at 4 Cfor 18 h after which time the desired compound precipitated. 2-Iodo-5-nitrobenzoic acid was thencollected by filtration while still cold to afford 1.73 g (49%) as a 13:2 mixture with the undesired2-iodo-3-nitrobenzoic acid isomer. The inseparable mixture was used as is in the next step.Characterization matches the data previously reported in the literature
1-chloro-5-nitro-3H-1λ3,2-benziodaoxol-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
With tert-butylhypochlorite; In dichloromethane; tert-butyl alcohol; at 0℃; for 0.333333h;Darkness;
To asolution of <strong>[19230-50-3]2-iodo-5-nitrobenzoic acid</strong> (5, 1 g, 3.4 mmol, 1 equiv) in DCM/t-BuOH 9:1 (12 mL) at 0 C t-BuOCl (0.42 mL, 3.7 mmol, 1.1 equiv) was added in one portion, taking care to shield this reagent from light. Stirring was continued for 20 min, the suspension was filtered and the filtrate washed with DCM to afford pure product (0.95 g, 86%) as a yellow solid. X-ray quality crystals were obtained by recrystallization from boiling MeCN.
2-Iodo-5-nitrobenzoic acid (7d) (3.0 g, 10.2 mmol) was dissolved in dry THF (100 mL) and the reaction was cooled to 0 C. NEt3 (2.1 mL, 15.4 mmol) and ethyl chloroformate (1.5 mL, 15.4 mmol) were added and the reaction was stirred for 1 hour. Next, a solution of NaBH (0.78 g, 20.5 mmol) in H20 (5 mL) was added and the reaction was stirred for 1.5 hour. After this time, an additional portion of NaBH (0.78 g, 20.5 mmol) in H20 (5 mL) was added and the reaction was stirred for an additional 30 minutes. The reaction was then quenched by the addition of H20 (20 mL). The reaction was diluted with EtOAc (150 mL) and the organic layer was washed with H20 (2 x 100 mL) and brine (100 mL) and subsequently dried over MgSC The solvents were removed in vacuo and the crude product was purified by gradient column chromatography (EtOAc/-heptane, 1 :9 to 1 :3). Compound 8d was obtained as an orange solid (1.32 g, 55% over 2 steps). 1H-NMR (400 MHz, CDC13) delta: 8.36 (d, J = 2.8 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.85 (dd, J = 8.6, 2.8 Hz, 1H), 4.75 (d, J = 3.4 Hz, 2H), 2.10 (t, J = 5.0 Hz, 1H). HRMS (EI+) m/z calcd for C7H6N03I [M]'+ 278.9393, found 278.9396.