CN102718659B - Synthesis method of 4-bromo-2-nitrophenyl acetic acid - Google Patents
Synthesis method of 4-bromo-2-nitrophenyl acetic acid Download PDFInfo
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- CN102718659B CN102718659B CN201210214003.6A CN201210214003A CN102718659B CN 102718659 B CN102718659 B CN 102718659B CN 201210214003 A CN201210214003 A CN 201210214003A CN 102718659 B CN102718659 B CN 102718659B
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- 0 Cc1ccc(*)cc1[N+]([O-])=O Chemical compound Cc1ccc(*)cc1[N+]([O-])=O 0.000 description 1
- GMHILUUZMBKBJE-UHFFFAOYSA-N [O-][N+](c1cc(Br)ccc1CC(C(O)=O)=O)=O Chemical compound [O-][N+](c1cc(Br)ccc1CC(C(O)=O)=O)=O GMHILUUZMBKBJE-UHFFFAOYSA-N 0.000 description 1
- LBZPHZBNFDOCCR-UHFFFAOYSA-N [O-][N+](c1cc(Br)ccc1CC(O)=O)=O Chemical compound [O-][N+](c1cc(Br)ccc1CC(O)=O)=O LBZPHZBNFDOCCR-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a synthesis method of 4-bromo-2-nitrophenyl acetic acid, which comprises the steps of: preparation of 4-bromo-2-nitrotoluene sodium via reaction of 4-bromo-2-nitro-chlorotoluene as a material and metallic sodium in an organic solvent, preparation of 4-bromo-2-nitrobenzyl sodium via heating and rearrangement reaction, preparation of 4-bromo-2-nitrophenyl sodium acetate via reaction with carbon dioxide, and preparation of the 4-bromo-2-nitrophenyl acetic acid via reaction with dilute acid. Compared with the prior art, the synthesis is simple, and reaction conditions are mild; the conversion rate of raw materials is high, the whole yield can reach 70-90 percent, no residues of raw materials can be produced, and no byproducts can be produced in the reaction process; no toxic substances are needed; and only extraction, filtration and other simple separation operations are needed for purification in the post-treatment, and the synthesis method is suitable for industrial production.
Description
Technical field
The invention belongs to technical field of chemistry, relate to a kind of synthetic method of 4-Bromo-2-nitrophenylacetic Acid.
Background technology
4-Bromo-2-nitrophenylacetic Acid (4-Bromo-2-nitrophenylacetic Acid, molecular formula C8H6BrNO4, CAS registration number 6127-11-3) be an important chemical intermediate, one of them is the raw material that can be used as atypical antipsychotic agents-Ziprasidone, and is also widely used in fields such as production agricultural chemicals, dyestuff, spices.The method of domestic and international synthesis 4-Bromo-2-nitrophenylacetic Acid mainly contains following several:
(1) " Bioorganic and Medical Chemistry Letter ", 2006 (16), 421-426 reports, with 4-toluene bromide for raw material, after mixed acid nitrification, the bromo-2-nitrotoluene of 4-is obtained in sulfuric acid solvent, 4-bromo-2-nitrobenzyl bromine is obtained after using N-bromo-succinimide (NBS) bromination again, and then obtain 4-bromo-2-nitro phenethyl cyanogen with sodium cyanide effect, and obtain target compound finally by after the aqueous sulfuric acid hydrolysis of 50%---4-Bromo-2-nitrophenylacetic Acid.Synthetic route is as follows:
The shortcoming of this synthetic route is: with the bromo-2-nitrotoluene of N-bromo-succinimide (NBS) bromination 4-, add equivalent to be difficult to control, therefore unavoidably have and fail the raw material of complete reaction, or the generation of dibromo by product, cause the complexity of purified product 4-bromo-2-nitrobenzyl bromine; And this route need use deadly poisonous compound---sodium cyanide, becomes in product process and there is potential safety hazard, requires higher, cause facility investment large to production equipment.
(2) " Chemical and Pharmaceutical Bulletin ", 198533 (4), 1414-1418 reports, same with 4-toluene bromide for raw material, the bromo-2-nitrotoluene of 4-is obtained after mixed acid nitrification, in the sodium ethylate/ethanolic soln of brand-new, generate 4-bromo-2-oil of mirbane pyruvic acid with oxalic acid diethyl ester reaction again, finally in the basic conditions with after hydrogen peroxide oxidation, then obtain target compound through acidifying---4-Bromo-2-nitrophenylacetic Acid.Synthetic route is as follows:
Although this synthetic route step is shorter, to sodium ethylate be used in operating procedure, use sodium ethylate in anhydrous conditions, will to require high to production unit, not too adapt to suitability for industrialized production; And when producing 4-bromo-2-oil of mirbane pyruvic acid from 4-bromo-2-nitrotoluene, be difficult to accomplish complete reaction, often have part material residue, when purification 4-bromo-2-oil of mirbane pyruvic acid, need through wet distillation or additive method, first bromo-for 4-2-nitrotoluene removing, cause operating procedure complicated, increase production cost.
(3) " chemical reagent ", 199214 (3), 186-187 reports, same with 4-toluene bromide for raw material, the bromo-2-nitrotoluene of 4-is obtained after mixed acid nitrification, then, under the condition of sodium phenylate as alkali, pass into dry carbonic acid gas and obtain target product---4-Bromo-2-nitrophenylacetic Acid.Synthetic route is as follows:
This route uses during sodium phenylate needs anhydrous condition, requires higher, not too adapt to suitability for industrialized production to production unit.
Above-mentioned deficiency still has the place being worth improving.
Summary of the invention
In order to overcome the defect existed in prior art, the invention provides that a kind of synthetic yield is high, synthesis is simple, step is few, to synthesis condition without particular requirement, by product is few, aftertreatment purification operations simple, be applicable to the synthetic method of the 4-Bromo-2-nitrophenylacetic Acid of suitability for industrialized production.
Its technical scheme is as follows:
A kind of synthetic method of 4-Bromo-2-nitrophenylacetic Acid, be raw material by 4-bromo-2-nitroxyl chloride toluene, 4-bromo-2-nitrotoluene base sodium is obtained by reacting in organic solvent with sodium Metal 99.5, then there is rearrangement reaction generation 4-bromo-2-nitrobenzyl sodium in heating, then generate 4-Bromo-2-nitrophenylacetic Acid sodium with carboxylated reagent carbon dioxide reaction, last and olefine acid reaction obtains 4-Bromo-2-nitrophenylacetic Acid.Synthetic route is as follows:
The raw materials used mixture that can be the chloro-4-of 3-bromo-2-nitrotoluene, the chloro-4-of 5-bromo-2-nitrotoluene, the bromo-6-nitrotoluene of the chloro-4-of 2-or their arbitrary proportion.
Described organic solvent is that single solvent is generally normal hexane, isohexane, heptane, hexanaphthene, benzene or ether, as isopropyl ether, butyl ether, tetrahydrofuran (THF), dioxan etc.; Organic molten consumption used is 1 ~ 7 times of 4-bromo-2-nitroxyl chloride toluene molar amount.
The consumption of described sodium Metal 99.5 is 1 ~ 5 times of 4-bromo-2-nitroxyl chloride toluene molar amount.
The temperature of reaction of 4-bromo-2-nitroxyl chloride toluene and sodium Metal 99.5 is 0 ~ 50 DEG C, and rearrangement reaction temperature is 40 ~ 150 DEG C.
Carboxylated reagent used is gaseous state or solid carbon dioxide.
Olefin(e) acid used is dilute sulphuric acid or dilute hydrochloric acid.
Beneficial effect of the present invention: the advantage that the present invention compared with prior art has is: technical solution of the present invention agents useful for same is the chemical reagent that routinizes, cheap; Often walk operation easy, reaction conditions easily reaches, and by product is few, and environmental pollution is little, thus realizes suitability for industrialized production, and can improve the rate of output, in a word, has environmental friendliness, technique is simple, cost is low advantage.
Embodiment
Below in conjunction with specific embodiment, method of the present invention is described in more detail.
Embodiment 1
In the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 11mL hexanaphthene and 2.3g sodium Metal 99.5, add the bromo-6-nitrotoluene of the chloro-4-of 25.1g2-in batches, within 30 minutes, add.Along with the bromo-6-nitrotoluene of the chloro-4-of 2-adds, the bromo-6-nitrotoluene of the chloro-4-of 2-and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 0 DEG C.The chloro-4-of 2-bromo-6-nitrotoluene adds complete, and continue stirring 15 DEG C reaction 30 minutes, the chloro-4-of 2-bromo-6-nitrotoluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 40 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 45 DEG C, and it is 0.8L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 4-bromo-2-nitrobenzyl sodium react and generates 4-Bromo-2-nitrophenylacetic Acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute hydrochloric acid acidifying of 100mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 25.05g, yield is 96.4%.
Embodiment 2
In the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 92mL isohexane and 11.5g sodium Metal 99.5, add the bromo-2-nitrotoluene of the chloro-4-of 25.1g3-in batches, within 30 minutes, add.Along with the bromo-2-nitrotoluene of the chloro-4-of 3-adds, the bromo-2-nitrotoluene of the chloro-4-of 3-and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 50 DEG C.The chloro-4-of 3-bromo-2-nitrotoluene adds complete, and continue stirring 50 DEG C reaction 30 minutes, the chloro-4-of 3-bromo-2-nitrotoluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 150 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 25 DEG C, and it is 0.8L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 4-bromo-2-nitrobenzyl sodium react and generates 4-Bromo-2-nitrophenylacetic Acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute phosphoric acid of 35mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 24.59g, yield is 94.6%
Embodiment 3
67mL butyl ether and 6.9g sodium Metal 99.5 is added in the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 25.1g4-bromo-2-nitroxyl chloride toluene (50% is the bromo-6-nitrotoluene of the chloro-4-of 2-in batches, 50% is the bromo-2-nitrotoluene of the chloro-4-of 3-), within 30 minutes, add.Along with 4-bromo-2-nitroxyl chloride toluene adds, 4-bromo-2-nitroxyl chloride toluene and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 25 DEG C.4-bromo-2-nitroxyl chloride toluene adds complete, and continue stirring 25 DEG C reaction 30 minutes, 4-bromo-2-nitroxyl chloride toluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 95 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 30 DEG C, and it is 1.0L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 2-nitro-4-bromobenzyl sodium react and generates 2-nitro-4-bromo-acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute hydrochloric acid acidifying of 100mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 25.12g, yield is 96.6%.
Embodiment 4
In the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 50mL benzene and 5.4g sodium Metal 99.5, add the bromo-6-nitrotoluene of the chloro-4-of 25.1g2-in batches, within 30 minutes, add.Along with the bromo-6-nitrotoluene of the chloro-4-of 2-adds, the bromo-6-nitrotoluene of the chloro-4-of 2-and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 20 DEG C.The chloro-4-of 2-bromo-6-nitrotoluene adds complete, and continue stirring 30 DEG C reaction 30 minutes, the chloro-4-of 2-bromo-6-nitrotoluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 80 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 25 DEG C, and it is 0.9L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 4-bromo-2-nitrobenzyl sodium react and generates 4-Bromo-2-nitrophenylacetic Acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute hydrochloric acid acidifying of 100mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 24.28g, yield is 93.4%.
Embodiment 5
In the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 50mL normal hexane and 5.4g sodium Metal 99.5, add the bromo-2-nitrotoluene of the chloro-4-of 25.1g5-in batches, within 30 minutes, add.Along with the bromo-2-nitrotoluene of the chloro-4-of 5-adds, the bromo-2-nitrotoluene of the chloro-4-of 5-and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 20 DEG C.The chloro-4-of 5-bromo-2-nitrotoluene adds complete, and continue stirring 30 DEG C reaction 30 minutes, the chloro-4-of 5-bromo-2-nitrotoluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 80 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, add 10g solidified carbon dioxide, controlling temperature of reaction is 20 DEG C, and react 3 hours, carbonic acid gas and 4-bromo-2-nitrobenzyl sodium react and generates 4-Bromo-2-nitrophenylacetic Acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute sulphuric acid acidifying of 25mL2mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 24.47g, yield is 94.1%.
Embodiment 6
In the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 50mL heptane and 5.4g sodium Metal 99.5, add the bromo-2-nitrotoluene of the chloro-4-of 25.1g3-in batches, within 30 minutes, add.Along with the bromo-2-nitrotoluene of the chloro-4-of 3-adds, the bromo-2-nitrotoluene of the chloro-4-of 3-and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 20 DEG C.The chloro-4-of 3-bromo-2-nitrotoluene adds complete, and continue stirring 30 DEG C reaction 30 minutes, the chloro-4-of 3-bromo-2-nitrotoluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 80 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 25 DEG C, and it is 1.0L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 4-bromo-2-nitrobenzyl sodium react and generates 4-Bromo-2-nitrophenylacetic Acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute phosphoric acid of 35mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 24.36g, yield is 93.7%.
Embodiment 7
50mL1 is added in the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, 4-dioxan and 5.4g sodium Metal 99.5, add 25.1g 4-bromo-2-nitroxyl chloride toluene (60% is the bromo-6-nitrotoluene of the chloro-4-of 2-in batches, 40% is the bromo-5-Chloro-2-Nitrobenzene of 4-), within 30 minutes, add.Along with 4-bromo-2-nitroxyl chloride toluene adds, 4-bromo-2-nitroxyl chloride toluene and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 20 DEG C.4-bromo-2-nitroxyl chloride toluene adds complete, and continue stirring 30 DEG C reaction 30 minutes, 4-bromo-2-nitroxyl chloride toluene and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 100 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 25 DEG C, and it is 0.8L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 2-nitro-4-bromobenzyl sodium react and generates 2-nitro-4-bromo-acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute hydrochloric acid acidifying of 100mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 25.04g, yield is 96.3%.
Embodiment 8
50mL tetrahydrofuran (THF) and 5.4g sodium Metal 99.5 is added in the four-hole boiling flask that agitator, thermometer, reflux condensate device and gas duct are housed, add 25.1g4-bromo-2-nitroxyl chloride toluene mixture (40% is the bromo-6-nitrotoluene of the chloro-4-of 2-in batches, 30% is the bromo--2-nitrotoluene of the chloro-4-of 5-, the bromo-2-nitrotoluene of the chloro-4-of 30%3-), within 30 minutes, add.Along with 4-bromo-2-nitroxyl chloride toluene mixture adds, 4-bromo-2-nitroxyl chloride toluene mixture and sodium Metal 99.5 react releases heat, and temperature of reaction constantly raises, and controls temperature of reaction at 20 DEG C.4-bromo-2-nitroxyl chloride toluene mixture adds complete, and continue stirring 30 DEG C reaction 30 minutes, 4-bromo-2-nitroxyl chloride toluene mixture and sodium Metal 99.5 react and generate 4-bromo-2-nitrotoluene base sodium.After completion of the reaction, reaction solution is progressively heated to 100 DEG C, stirring reaction 5 hours, 4-bromo-2-nitrotoluene base sodium is reset and is generated 4-bromo-2-nitrobenzyl sodium.React complete, reaction solution is cooled to room temperature, pass into carbon dioxide gas precursor reactant, temperature of reaction is 25 DEG C, and it is 0.8L/min that carbonic acid gas passes into flow, reacts 3 hours, and carbonic acid gas and 2-nitro-4-bromobenzyl sodium react and generates 2-nitro-4-bromo-acid sodium.In reaction solution, add 50g methyl alcohol at agitation condition after completion of the reaction and make unnecessary sodium Metal 99.5 inactivation.Then the distilled water of reaction solution 50mL extracts 2 times, combining water layer, with the dilute hydrochloric acid acidifying of 100mL1mol/L.The extracted with diethyl ether of the aqueous solution 50mL after acidifying 3 times, combined ether layer.Ether layer distilled water after merging washes 2 times, and underpressure distillation removing ether obtains the clear crystal with aromatic odour---and 4-Bromo-2-nitrophenylacetic Acid 25.22g, yield is 97.0%.
The above; be only the present invention's preferably embodiment; protection scope of the present invention is not limited thereto; anyly be familiar with those skilled in the art in the technical scope that the present invention discloses, the simple change of the technical scheme that can obtain apparently or equivalence are replaced and are all fallen within the scope of protection of the present invention.
Claims (7)
1. a synthetic method for 4-Bromo-2-nitrophenylacetic Acid, is characterized in that,
By
for raw material, be obtained by reacting with sodium Metal 99.5 in organic solvent
then there is rearrangement reaction generation in heating
then generate with carboxylated reagent carbon dioxide reaction
last and diluted acid is obtained by reacting
2. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, is characterized in that, raw materials usedly can be the chloro-4-of 3-bromo-2-nitrotoluene, the chloro-4-of 5-bromo-2-nitrotoluene, the bromo-6-nitrotoluene of the chloro-4-of 2-or their mixture.
3. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, is characterized in that, described organic solvent single solvent is normal hexane, isohexane, heptane, hexanaphthene, benzene, isopropyl ether, butyl ether, tetrahydrofuran (THF), dioxan; Consumption of organic solvent used is
1 ~ 7 times of molar weight.
4. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, it is characterized in that, the consumption of described sodium Metal 99.5 is
1 ~ 5 times of molar weight.
5. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, is characterized in that,
be 0 ~ 50 DEG C with the temperature of reaction of sodium Metal 99.5, rearrangement reaction temperature is 40 ~ 150 DEG C.
6. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, is characterized in that, carboxylated reagent used is gaseous state or solid carbon dioxide.
7. the synthetic method of 4-Bromo-2-nitrophenylacetic Acid according to claim 1, is characterized in that, diluted acid used is dilute sulphuric acid or dilute hydrochloric acid.
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