Alternatived Products of [ 95635-45-3 ]
Product Details of [ 95635-45-3 ]
| CAS No. : | 95635-45-3 |
MDL No. : | MFCD24849669 |
| Formula : |
C8H6ClFN2O3
|
Boiling Point : |
- |
| Linear Structure Formula : | - |
InChI Key : | - |
| M.W : |
232.60
|
Pubchem ID : | - |
| Synonyms : |
|
Safety of [ 95635-45-3 ]
| Signal Word: | |
Class: | |
| Precautionary Statements: | |
UN#: | |
| Hazard Statements: | |
Packing Group: | |
Application In Synthesis of [ 95635-45-3 ]
* 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.
- Upstream synthesis route of [ 95635-45-3 ]
- Downstream synthetic route of [ 95635-45-3 ]
- 1
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[ 59280-70-5 ]
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[ 95635-45-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
With nitric acid In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; sulfuric acid; water; ethyl acetate |
1 Preparation of N-(4-Chloro-2-fluoro-5-nitrophenyl)acetamide
EXAMPLE 1 Preparation of N-(4-Chloro-2-fluoro-5-nitrophenyl)acetamide To a stirred solution of 375.2 g (2 mole) of N-(4-chloro-2-fluorophenyl)acetamide in 600 mL of concentrated sulfuric acid and 400 mL of oleum (30%) was added 166 mL of a 1:1 mixture of nitric acid (100%) and concentrated sulfuric acid at 0° C. over a period of 1.5 hours. After the addition was complete, the reaction mixture was poured into 11 L of ice water. The precipitate was filtered and the filter cake suspended in 200 mL of water. The solid was redissolved by the addition of 2 L of ethyl acetate and neutralized with aqueous NaOH to pH 7. The two phase mixture was heated to 50° C. and separated. The organic layer was washed with 150 mL of water. 200 mL of ethyl acetate were distilled off and the remaining solution was treated with 12 g of Celite at 70° C., filtered and washed with another 200 mL of ethyl acetate. The filtrate was concentrated to 1080 g and allowed to crystallize at 5° C. overnight. After filtration and drying, 384 g of the title compound was isolated as a solid melting at 145-149° C. (purity: >99.5% by HPLC). A second crystallization from the mother liquor afforded another 45.5 g of the title compound. |
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With Concentrated HNO3 In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; di-isopropyl ether; sulfuric acid; ethyl acetate |
1.A Step A
Step A Preparation of N-(4-chloro-2-fluoro-5-nitrophenyl)acetamide To a stirred solution of N-(4-chloro-2-fluorophenyl)acetamide (180.6 g, 0.96 mol) in concentrated sulfuric acid (1L) was added a mixture of 175 mL of concentrated HNO3 and 175 mL of concentrated sulfuric acid at 0 to 5° C. in 1.5 h. After the addition was finished, the reaction mixture was stirred for another 0.5 h. The solution was poured into 5 L of ice water. After the product precipitated, it was isolated by filtration and then was dissolved in 2.5 L of ethyl acetate. After separation of the water layer, the organic layer was dried over sodium sulfate and then the solvent was evaporated. The crude product was triturated in diisopropyl ether (1.5 L), isolated by filtration, and dried under reduced pressure to afford the title compound of Step A (196.2 g, 87.6%) melting at 145-146° C. 1 H NMR (Me2 SO-d6) δ 10.3-10.2 (s, 1H), 8.9 (d, 1H), 7.9-7.8 (d, 2.2-2.1 (s, 3H). |
|
With nitric acid In sulfuric acid |
29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR109
EXAMPLE 29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR109 A mixture of 4'-chloro-2'-fluoroacetanilide (51 g, 0.272 mol) in concentrated sulfuric acid (100 mL) is cooled to 0° C., treated with nitric acid (90% real, 14 mL, 0.300 mol) over 45 minutes, stirred for 10 minutes, and poured onto ice. The resultant aqueous mixture is filtered to obtain a tan solid which is washed with water, dried overnight, and recrystallized from a chloroform/hexanes (17:1) solution to give the title product as a yellow solid. |
|
With nitric acid In sulfuric acid |
29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR108
EXAMPLE 29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR108 A mixture of 4'-chloro-2'-fluoroacetanilide (51 g, 0.272 mol) in concentrated sulfuric acid (100 mL) is cooled to 0° C., treated with nitric acid (90% real, 14 mL, 0.300 mol) over 45 minutes, stirred for 10 minutes, and poured onto ice. The resultant aqueous mixture is filtered to obtain a tan solid which is washed with water, dried overnight, and recrystallized from a chloroform/hexanes (17:1) solution to give the title product as a yellow solid. |
|
With nitric acid In sulfuric acid |
29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR115
EXAMPLE 29 Preparation of 4'-Chloro-2'-fluoro-5'-nitroacetanilide STR115 A mixture of 4'-chloro-2'-fluoroacetanilide (51 g, 0.272 mol) in concentrated sulfuric acid (100 mL) is cooled to 0° C., treated with nitric acid (90% real, 14 mL, 0.300 mol) over 45 minutes, stirred for 10 minutes, and poured onto ice. The resultant aqueous mixture is filtered to obtain a tan solid which is washed with water, dried overnight, and recrystallized from a chloroform/hexanes (17:1) solution to give the title product as a yellow solid. |
|
With Concentrated HNO3 In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; di-isopropyl ether; sulfuric acid; ethyl acetate |
1.A Step A:
Step A: Preparation of N-(4-chloro-2-fluoro-5-nitrophenyl)acetamide To a stirred solution of N-(4-chloro-2-fluorophenyl)acetamide (180.6 g, 0.96 mol) in concentrated sulfuric acid (1L) was added a mixture of 175 mL of concentrated HNO3 and 175 mL of concentrated sulfuric acid at 0 to 5 °C in 1.5 h. After the addition was finished, the reaction mixture was stirred for another 0.5 h. The solution was poured into 5 L of ice water. After the product precipitated, it was isolated by filtration and then was dissolved in 2.5 L of ethyl acetate. After separation of the water layer, the organic layer was dried over sodium sulfate and then the solvent was evaporated. The crude product was triturated in diisopropyl ether (1.5 L), isolated by filtration, and dried under reduced pressure to afford the title compound of Step A (196.2 g, 87.6%) melting at 145-146 °C. 1H NMR (Me2SO-d6) δ 10.3-10.2 (s, 1H), 8.9 (d, 1H), 7.9-7.8 (d, 1H), 2.2-2.1 (s, 3H). |
Reference：
[1]Current Patent Assignee: EVONIK INDUSTRIES AG - US6384234, 2002, B1
[2]Current Patent Assignee: EVONIK INDUSTRIES AG - US6060432, 2000, A
[3]Current Patent Assignee: BASF SE - US5610120, 1997, A
[4]Current Patent Assignee: BASF SE - US5679791, 1997, A
[5]Current Patent Assignee: BASF SE - US5726126, 1998, A
[6]Current Patent Assignee: EVONIK INDUSTRIES AG - EP862571, 2003, B1
- 2
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conc. H2 SO4
[ No CAS ]
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[ 59280-70-5 ]
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[ 95635-45-3 ]
| Yield | Reaction Conditions | Operation in experiment |
| 63% |
With nitric acid |
22.a a.
a. 4-chloro-2-fluoro-5-nitroacetanilide Into a 500 ml, 3-necked round-bottomed flask equipped with a mechanical stirrer was placed 4-chloro-2-fluoroacetanilide (56.3 g, 0.3 mmol) and conc. H2 SO4 (100 ml). While cooling to 0° C., fuming nitric acid (21 g, 0.33 mol) was added over 30 minutes then the reaction mixture was poured onto 2 liters of ice. When the ice had melted the solid product was collected by filtration, washed with water and dried in vacuo to give 44 g (63% yield) of the nitrated material as a tan solid. |
| 63% |
With nitric acid |
35.a a.
a. 4-chloro-2-fluoro-5-nitroacetanilide Into a 500 ml, 3-necked round-bottomed flask equipped with a mechanical stirrer was placed 4-chloro-2-fluoroacetanilide (56.3 g, 0.3 mmol) and conc. H2 SO4 (100 ml). While cooling to 0° C., fuming nitric acid (21 g, 0.33 mol) was added over 30 minutes and then the reaction mixture was poured onto 2 liters of ice. When the ice had melted the solid product was collected by filtration, washed with water and dried in vacuo to give 44 g (63 % yield) of the nitrated material as a tan solid. |
- 3
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[ 95635-45-3 ]
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[ 7439-89-6 ]
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[ 95635-47-5 ]
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[ 34801-09-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|
In acetic acid; ethyl acetate; |
EXAMPLE 6 Production of the monoacetylphenylenediamine (VIII) from the acetonitroanilide (VII): Iron powder (31.9 g) were suspended in a 5% acetic acid solution (60 ml), and the suspension was heated to 90 C. A solution of 4-(N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene (13.3 g) in acetic acid (100 l ml) and ethyl acetate (70 ml) was dropwise added thereto, and the resultant mixture was refluxed at 80 C. for 2 hours. The reaction mixture was filtered by celite. The filtrate was extracted with ethyl acetate, and the extract was neutralized with a saturated sodium hydrogen carbonate solution. The organic layer was washed with water, dried and concentrated under reduced pressure to give 7.0 g of 4-(N-acetylamino)-2-amino-1-chloro-5-fluorobenzene. M.P., 140.5-141.5 C. |
|
In acetic acid; ethyl acetate; |
EXAMPLE 6 Production of the monoacetylphenylenediamine (VIII) from the acetonitroanilide (VII): Iron powder (31.9 g) were suspended in a 5% acetic acid solution (60 ml), and the suspension was heated to 90 C. A solution of 4-(N-acetylamino)-1-chloro-5-fluoro2-nitrobenzene (13.3 g) in acetic acid (100 ml) and ethyl acetate (70 ml) was dropwise added thereto, and the resultant mixture was refluxed at 80 C. for 2 hours. The reaction mixture was filtered by celite. The filtrate was extracted with ethyl acetate, and the extract was neutralized with a saturated sodium hydrogen carbonate solution. The organic layer was washed with water, dried and concentrated under reduced pressure to give 7.0 g of 4-(N-acetylamino)-2-amino-1-chloro-5-fluorobenzene. M.P., 140.5-141.5 C. |
- 4
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[ 59280-70-5 ]
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[ 95635-45-3 ]
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acetonitroanilide
[ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|
With sulfuric acid; nitric acid |
5 EXAMPLE 5
EXAMPLE 5 Production of the acetonitroanilide (VII) from the acetanilide (VI): To a 20% ice-cooled fuming sulfuric acid (50 g), 4-(N-acetylamino)-1-chloro-3-fluorobenzene (9.4 g) was dissolved, followed by gradual addition of fuming nitric acid (3.5 g) while keeping the temperature at 0° to 5° C. The resultant mixture was stirred at the same temperature for 1 hour and poured into ice (50 g). The precipitated crystals were collected by filteration, and the filtrate was washed with water and dried to give 11.6 g of 4-(N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene. M.P. 124.7°-125.7° C. |
|
With sulfuric acid; nitric acid |
5 EXAMPLE 5
EXAMPLE 5 Production of the acetonitroanilide (VII) from the acetanilide (VI): To 20 % ice-cooled fuming sulfuric acid (50 g), 4-(N-acetylamino)-1-chloro-3-fluorobenzene (9.4 g) was dissolved, followed by gradual addition of fuming nitric acid (3.5 g) while keeping the temperature at 0° to 5° C. The resultant mixture was stirred at the same temperature for 1 hour and poured into ice (50 g). The precipitated crystals were collected by filteration, and the filtrate was washed with water and dried to give 11.6 g of 4-(N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene. M.P., 124.7°-125.7° C. |
- 5
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concentrated HNO3and
[ No CAS ]
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[ 59280-70-5 ]
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[ 95635-45-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; di-isopropyl ether; sulfuric acid; ethyl acetate |
1.A Step A:
Step A: Preparation of N -(4-chloro-2-fluoro-5-nitrophenyl)acetamide To a stirred solution of N-(4-chloro-2-fluorophenyl)acetamide (180.6 g, 0.96 mol) in concentrated sulfuric acid (1L) was added a mixture of 175 mL of concentrated HNO3and 175 mL of concentrated sulfuric acid at 0 to 5 °C in 1.5 h. After the addition was finished, the reaction mixture was stirred for another 0.5 h. The solution was poured into 5 L of ice water. After the product precipitated, it was isolated by filtration and then was dissolved in 2.5 L of ethyl acetate. After separation of the water layer, the organic layer was dried over sodium sulfate and then the solvent was evaporated under reduced pressure. The crude product was triturated in diisopropyl ether (1.5 L), isolated by filtration, and dried under reduced pressure to afford the title compound of Step A (196.2 g, 87.6%) melting at 145-146 °C. 1H NMR ((CD3)2SO): δ 10.3-10.2 (s, 1H), 8.9 (d, 1H), 7.9-7.8 (d, 1H), 2.2-2.1 (s, 3H). |
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