Structure of 611-03-0
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CAS No. : | 611-03-0 |
Formula : | C7H8N2O2 |
M.W : | 152.15 |
SMILES Code : | O=C(O)C1=CC=C(N)C=C1N |
MDL No. : | MFCD00189383 |
InChI Key : | LDQMZKBIBRAZEA-UHFFFAOYSA-N |
Pubchem ID : | 69134 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H341 |
Precautionary Statements: | P501-P202-P201-P264-P280-P308+P313-P337+P313-P305+P351+P338-P302+P352-P332+P313-P362-P405 |
* 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 ammonium sulfate; In ethanol; at 100℃; for 1.08333h;Microwave irradiation; | First, 80 g of phthalic anhydride was added to a 500 mL four-necked flask, and 180 mL of concentrated sulfuric acid was slowly added thereto. After stirring for 10 minutes, the mixture was placed in a water bath and 60 g of fuming nitric acid was added dropwise at 70 C. After the completion of the dropwise addition, the reaction was stirred at 70 C for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature with an ice bath and filtered. The residue was washed three times with water and then dissolved in 100 mL of distilled water. Keeping at 55 C for 1 h, filtering, drying the residue to obtain 4-nitrophthalic acid; 100g of 4-nitro phthalic acid added to four-necked flask, to which was added 30mL of acetic anhydride, stirred until solid was completely dissolved at 90 deg.] C, temperature was raised to 120 deg.] C and dissolved,Stirring at 90 C until all the solid dissolved, dissolved and heated to 120 C and maintained at this temperature for 2h, and side reaction while stirring, after cooling the reaction to room temperature, filtration, take the filter cake washed with ether 2, Dried at 40 C for 4 hours to obtain 4-nitrophthalic anhydride; 20 g of urea was added to a 500-mL three-necked flask, placed in a water bath, and the 4-nitrophthalic anhydride was added to the flask in 3 portions at a controlled temperature of 5 C, And the temperature was gradually raised to 70 C after the completion of the addition, so that 4-nitrophthalic anhydride was completely dissolved, and the temperature was lowered to 45 C. The flask was evacuated and 10 mL of the solid was precipitated when no more solid precipitated And then the mixture was stirred for 20 min at 400 rpm. After stirring, the mixture was cooled to room temperature, filtered, washed with distilled water and dried at 50 C. Giving 4-nitro-2-carbamoylbenzoic acid; To a 500 mL four-necked flask, 40 mL of a 10% aqueous solution of sodium hypochlorite was placed in an ice bath, and 100 g of the 4-nitro-2-carbamoylbenzoic acid obtained above was added thereto at 0 C. The temperature was increased to 30 C, After the reaction, the reaction was cooled to -5 C, and immediately after cooling, the mixture was suction filtered and the residue was dried at 60 C to obtain 2-amino-4-nitrobenzoic acid. To a 250 mL three-necked flask, 15 g of the 2-amino-4-nitrobenzoic acid obtained above was added, and 90 mL of absolute ethanol was added thereto. The mixture was refluxed at 100 C for 1 hour. After refluxing, 50 mL of 9% Ammonium sulfate solution, in the 800W microwave heating continue to return under 5min, hot filter, wash the residue to pH 7, the combined filtrate, pour 50g ice water and stir quickly, standing 5min after the crude product precipitation, with the quality The crude product was dissolved in 30% hydrochloric acid and filtered. The filtrate with 30% ammonia water quality adjusted to pH 3, solid precipitation after the filter, the residue placed 60 drying, can be 2,4-diaminobenzoic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Nonlimiting examples of suitable aromatic diamines, aminophenols, polyhydric phenols and derivatives thereof, respectively, are the following compounds: ... m-phenylenediamine, 2-nitro-p-phenylenediamine, 1,3,5-triaminobenzene, 2-hydroxy-p-phenylenediamine, 2,4-diaminobenzoic acid, sodium 2,4-diaminobenzoate, calcium di-(2,4-aminobenzoate), ammonium 2,4-diaminobenzoate, ... | ||
methylamine, ... 1,3-diamino-6-methylbenzene-4-sulfonic acid, 3-(3'- or 4'-aminobenzoylamino)-1-aminobenzene-6-sulfonic acid, 1-(4'-aminobenzylamino)-4-aminobenzene-2,5-disulfonic acid, 1,4-diaminobenzene-2-carboxylic acid, 1,3-diaminobenzene-4-carboxylic acid, 1,2-diaminobenzene-4-carboxylic acid, 1,3-diaminobenzene-5-carboxylic acid, 1,4-diamino-2-methylbenzene, ... | ||
Specific examples of formula (A) compounds are: ... 2-chloro-p-phenylenediamine 2-iodo-p-phenylenediamine 1,3,5-triaminobenzene 2-hydroxy-p-phenylenediamine 2,4-diaminobenzoic acid sodium 2,4-diaminobenzoate calcium di-2,4-diaminobenzoate ammonium 2,4-diaminobenzoate ... |
Nonlimiting examples of suitable aromatic diamines, aminophenols, naphthols, polyhydric phenols and derivatives thereof, respectively, are the following compounds: ... m-phenylenediamine, 2-nitro-p-phenylenediamine, 1,3,5-triaminobenzene, 2-hydroxy-p-phenylenediamine, 2,4-diaminobenzoic acid, sodium 2,4-diaminobenzoate, calcium di-(2,4-aminobenzoate), ammonium 2,4-diaminobenzoate, ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 150℃; for 20.0h; | General procedure: Anthranilic acids (3, 29.1 mmol, 1 eq) and urea (582.8 mmol, 20 eq) were poured into 100 mL round bottom flask. Then, the reaction mixture was heated at 150 oC for 20 h. The reaction was monitored by TLC. After the reaction was completed, it cooled down to room temperature. Then, 60 mL water was poured and the reaction mixture was heated at 100 oC for 1 h. The reaction mixture was cooled in ice bath and the white solid was precipitated. The white solid was filtered and washed with water and hexane. The residue (4, 28.3 mmol, 97%) was dried in vacuo and used next step without further purification. The chemical yield of first reaction was usually around 90%. The compound 4 (28.3 mmol, 1 eq) was dissolved in triethylamine (56.6 mmol, 2 eq). Then, POCl3 (254.5 mmol, 9 eq) was slowly added to the reaction mixture. The reaction mixture was heated at 115 oC for 17 h. The reaction was monitored by TLC. After the completion of the reaction, the reaction solvents were evaporated with toluene several times. The residue was diluted with water and extracted with ethyl acetate several times. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude 5 (25.2 mmol) was used in next step without further purification. The crude 5 (25.2 mmol) was dissolved in 2 N NaOH solution (75.6 mmol, 38 mL, 3 eq) and was stirred at room temperature for 20 h. The reaction mixture was cooled to room temperature. Acetic acid (75.6 mmol, 3 eq) was added to the reaction mixture. The aqueous phase was extracted with ethyl acetate and the combined organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford crude 6 (19.4 mmol), which was used in next step without further purification. To a 25 mL round bottom flask were added crude 6 (0.93 mmol), anilines (7, 2.8 mmol, 3 eq), and DMF (3.1 mL). The reaction mixture was stirred at 85 oC for 16 h. The reaction mixture was cooled to room temperature and precipitates were formed. The precipitates were washed with water and hexane thoroughly. The residue (8, 0.88 mmol, 94%) was dried in vacuo. If the precipitates were not formed, the reaction mixture was purified by prep HPLC (Shim-pack PREP-ODS, H2O:CH3CN:CH3OH=40:30:30 to H2O:CH3CN:CH3OH=1:49.5:49.5, flow rate=12 mL/min, 40 oC, λ=254 nm, retention time : 30 min). The chemical yields for each final products are described below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 137℃; for 14.0h; | To a 25 mL round bottom flask, 2-amino-4-amino benzoic acid (1.51g, 10mmmol) and acetic anhydride (2.9mL, 30mmol) were charged and heated at 137 C for 2hrs. Then, the reaction mixture was poured into crushed ice and stirred for 12hrs. Finally, the reaction mixture was worked-up by suction filtration, followed by a wash with methanol and drying over magnesium sulfate to afford 2-acetylamido-4- methyl-5-nitrobenzoic acid. 2-acetylamido-4-methyl-5-nitrobenzoic acid (3.37g, 17.4 mmol) was dissolved in 42.3 mL of sulfuric acid and the reaction mixture was lowered to 0C. Then, using addition funnel, 4.92 mL of fuming nitric acid was added dropwise and the reaction mixture is stirred for 12hrs in ice bath. Finally, the reaction mixture is worked up by pouring it over crushed ice, filtering, and vacuum drying it overnight to afford 5-nitro-4-methylanthranilic acid. To a microwave vial containing 5-nitro-3- methylanthranilic acid (98.0 g, 0.5 mmol) and N-Boc-D-proline (0.140 g, 0.65 mmol) was added dry pyridine (1.5 mL). Triphenyl phosphite (0.4 mL, 1.5 mmol) was added to the vial, and the reaction mixture was heated at 100 C with MWI for 60 min. After cooling the vial, 4-methoxyaniline (74 mg, 1.2 mmol) was added, and the reaction mixture was heated at 60 C with MWI for 30 min. Pyridine was removed in vacuo, and the residue was diluted with CH2Cl2 (50 mL), and then the organic layer was washed sequentially with 10% citric acid (20 mL) and brine (50 mL). The separated organic extract was dried over MgSO4, filtered, and concentrated in vacuo under reduced pressure. The crude mixture was purified by flash chromatography (3% Ethyl acetate/DCM) to afford the N-Boc intermediate as a yellow solid. The solid (0.119 g, 0.248 mmol ) was dissolved in dry dioxane (1.5 mL), cooled to 0 C, and 4M HCl/dioxane (0.31 mL, 1.24 mmol) was added. After the addition was complete, the reaction mixture was stirred at rt for 8h. Solvent was removed in vacuo under reduced pressure, and CH2Cl2 (10 mL) was added, followed by sequential washing with saturated Na2CO3 (5 mL) and brine (5 mL). The separated organic extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo under reduced pressure. The crude mixture was purified by flash chromatography (0% MeOH/ CH2Cl2~10% MeOH / CH2Cl2) to afford 2hh (59 mg, 62%) as a yellow solid.1H NMR (400 MHz, Chloroform- d) d 8.83 (s, 1H), 7.63 (s, 1H), 7.24 - 7.12 (m, 2H), 7.10 - 7.01 (m, 2H), 3.88 (s, 3H), 3.25 (ddd, J = 11.0, 7.7, 3.7 Hz, 1H), 2.91 - 2.75 (m, 3H), 2.73 (s, 3H), 1.75 (qdd, J = 12.3, 6.6, 3.4 Hz, 4H). MS (ESI) m/z: 381.2 (M+1)+. |
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