CN1398846A - Chemical synthesis process of 4-chloro-2-fluoro nitrobenzene - Google Patents
Chemical synthesis process of 4-chloro-2-fluoro nitrobenzene Download PDFInfo
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- CN1398846A CN1398846A CN 02130089 CN02130089A CN1398846A CN 1398846 A CN1398846 A CN 1398846A CN 02130089 CN02130089 CN 02130089 CN 02130089 A CN02130089 A CN 02130089A CN 1398846 A CN1398846 A CN 1398846A
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Abstract
The present invention is a chemical synthesis process of 4-chloro-2-fluoro nitrobenzene. The synthesis process includes diazotization of 5-chloro-2-nitro benzene as initial raw material, reaction with aqueous solution of phosphofluoric acid to produce corresponding diazotized salt, and then thermal decomposition to prepare 4-chloro-2-fluoro nitrobenzene. The process has the advantages of easy to obtain raw material, mild reaction condition, and high product purity.
Description
Technical field:
The present invention relates to a kind of novel method of synthetic 4-chloro-2-fluoronitrobenzene.This method is to be that starting raw material prepares 4-chloro-2-fluoronitrobenzene with 5-chloro-2-N-methyl-p-nitroaniline.And 5-chloro-2-N-methyl-p-nitroaniline can be a starting raw material with the 3-chloroaniline, makes easily by known method.
Background technology:
4-chloro-2-fluoronitrobenzene is farming important intermediate approximately such as synthetic low toxicity, wide spectrum, ultra-high efficiency weedicide fluthiacetmethyl.Existing synthetic method great majority are with 2, and the 4-dichloronitrobenzene is a starting raw material, prepare 4-chloro-2-fluoronitrobenzene through the halogen replacement(metathesis)reaction.For example English Patent (GB 1514082) reported method is to allow 2,4-dichloronitrobenzene and exsiccant Potassium monofluoride reacted 6-33 hour in 240 ℃ in the tetramethylene sulfone medium, obtain 4-chloro-2-fluoronitrobenzene, 2-chloro-4-fluoronitrobenzene and 2, the mixture of 4-difluoro nitrobenzene.English Patent (GB2058067) has disclosed a kind of in the presence of quaternary ammonium salt, makes above-mentioned reaction (100～175 ℃) method of carrying out at a lower temperature.In the presence of quaternary ammonium salt ALIQUAT336,2,4-dichloronitrobenzene and dry Potassium monofluoride in 100 ℃ of reactions 6 hours, obtain 4-chloro-2-fluoronitrobenzene and 2 in the tetramethylene sulfone medium, the mixture of 4-difluoro nitrobenzene, wherein 4-chloro-2-fluoronitrobenzene yield is 57.5%.But this patent is not reported the method for purification of 4-chloro-2-fluoronitrobenzene.Japanese Patent (spy opens flat 1-168645) has prepared 4-chloro-2-fluoronitrobenzene by similar method, and has obtained 92.7% purity by rectifying.Japanese Patent (spy opens flat 3-109360) has then disclosed with 3, the method for 4-dinitrochlorobenzene and Potassium monofluoride prepared in reaction 4-chloro-2-fluoronitrobenzene in the presence of phthalyl chloride, and yield can reach 90%.The shortcoming of this method is a starting raw material 3, and the 4-dinitrochlorobenzene is not easy to obtain, and price is higher, and industrial goods purity only has 90%.
Summary of the invention:
The objective of the invention is to overcome the shortcoming of existing method, provide that a kind of raw material is easy to get, the chemical synthesis process of the easy and simple to handle and 4-chloro-2-fluoronitrobenzene that product purity is high.
Feature of the present invention is: with 5-chloro-2-N-methyl-p-nitroaniline is starting raw material, also further generates corresponding diazonium salt with the phosphofluoric acid reaction through diazotization reaction, and thermolysis prepares 4-chloro-2-fluoronitrobenzene then.The diazotization reaction of 5-chloro-2-N-methyl-p-nitroaniline is that it is dispersed in 35～37% (w/w) concentrated hydrochloric acid, dripping sodium nitrite in aqueous solution then finishes, the consumption of concentrated hydrochloric acid will influence the dissolution degree of 5-chloro-2-N-methyl-p-nitroaniline, speed of response and yield, its consumption can be 5～50 times of 5-chloro-2-N-methyl-p-nitroaniline weight, wherein with 5～10 times of the bests, the concentration of sodium nitrite in aqueous solution is little to this reaction influence, consider the consumption that reduces water, the concentration of Sodium Nitrite is advisable with 45～50%, the mol ratio of 5-chloro-2-N-methyl-p-nitroaniline and Sodium Nitrite is 1: 1～1.05, reaction can be carried out at-10～20 ℃, but best temperature of reaction is 5～10 ℃.Above-mentioned reaction solution is got settled solution after filtration, be added to then in the phosphofluoric acid aqueous solution, in 5～10 ℃ of stirring reaction 30min, promptly get diazonium hexafluorophosphote, the mol ratio of 5-chloro-2-N-methyl-p-nitroaniline and phosphofluoric acid is 1: 1.4～1.6, used phosphofluoric acid aqueous solution concentration expressed in percentage by weight is 10～60%, wherein with 35-40% phosphofluoric acid best results.The decomposition temperature of diazonium hexafluorophosphote is 150-155 ℃, it can decompose at direct heating under the drying regime, also can be in inert organic solvents ortho-chlorotolu'ene or orthodichlorobenzene thermal degradation, reaction 1h can finish, decomposition in organic solvent is more easy to control, and yield is better.
Reaction formula of the present invention is as follows:
The present invention compared with prior art has the following advantages:
1. the present invention has adopted the abundant and cheap raw material in source; starting raw material 5-chloro-2-N-methyl-p-nitroaniline of the present invention can be from 3-chloroaniline cheap and easy to get, makes easily through acetylize, nitrated and hydrolysis three-step reaction by known method (GB 2018766A).
2. synthetic method of the present invention is simple to operate, and the reaction conditions gentleness is easy to realize industrialization.
3. synthetic method of the present invention has the advantage of the few and product purity height (reaching more than 98%) of by product, has higher using value.
Embodiment:
In order to be easy to further understand the present invention, the following example has been set forth more specific details.
Embodiment 1
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: in the 200ml there-necked flask, add 20.7g (0.12mol) 5-chloro-2-N-methyl-p-nitroaniline and 120ml 36% concentrated hydrochloric acid, stir, ice-water bath is cooled to 5～10 ℃, under this temperature, in 60min, drip the 15ml aqueous solution that contains 8.8g (0.13mol) Sodium Nitrite then, continue at 5～10 ℃ of stirring reaction 1.5h after adding.Suction filtration is removed a small amount of insolubles, filtrate slowly joins in the 63.5g 40% phosphofluoric acid aqueous solution under the ice-water bath cooling, control reaction temperature stirs 30min for 5～10 ℃, suction filtration then, use a little cold water, methanol (1: 10) solution and ether washing successively, vacuum-drying gets 32.9g pale yellow powder shape diazonium hexafluorophosphote, yield 83%.
Embodiment 2
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: except temperature of reaction is controlled at-10～5 ℃, other operational condition is all identical with embodiment 1, gets 27.8g pale yellow powder shape diazonium hexafluorophosphote, yield 71%.
Embodiment 3
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: except temperature of reaction is controlled at 15～20 ℃, other operational condition is all identical with embodiment 1, gets 24.5g pale yellow powder shape diazonium hexafluorophosphote, yield 63%.
Embodiment 4
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: in the 1000ml there-necked flask, add 20.7g (0.12mol) 5-chloro-2-N-methyl-p-nitroaniline and 800ml concentrated hydrochloric acid, other operational condition is all identical with embodiment 1, gets 13.3g pale yellow powder shape diazonium hexafluorophosphote, yield 34%.
Embodiment 5
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: the 63.5g 40% phosphofluoric acid aqueous solution is replaced to the 254g 10% phosphofluoric acid aqueous solution, and other operational condition is all identical with embodiment 1, gets 30.1g pale yellow powder shape diazonium hexafluorophosphote, yield 77%.
Embodiment 6
5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote: the 63.5g 40% phosphofluoric acid aqueous solution is replaced to the 42.5g 60% phosphofluoric acid aqueous solution, other operational condition is all identical with embodiment 1, get 32.6g pale yellow powder shape diazonium hexafluorophosphote, yield 82%.
Embodiment 7
4-chloro-2-fluoronitrobenzene: in the 150ml there-necked flask, add the 100ml orthodichlorobenzene, be heated to 150 ℃, stir, in 20min, add 30g 5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote in batches, add back insulation reaction 1h.Reaction solution is cooled to room temperature, uses 5% sodium carbonate solution (50ml) and water (50ml * 3) washing successively, anhydrous sodium sulfate drying.Filter, 133～136 ℃/30mmHg cut is collected in filtrate decompression rectifying, gets 10.2g light yellow liquid 4-chloro-2-fluoronitrobenzene, yield 64%, purity 99.1%.IR(KBr)：3103，1605，1564，1523，1343，911，860，830，748.MS(m/e)：175(M
+)，145(M
+-NO)，129(M
+-NO
2)，109(129-HF)，93(129-HCl)，74(93-F).
1H-NMR(CDCl
3)：8.076-8.035(1H，m)，7.336-7.264(2H，m).
Embodiment 8
4-chloro-2-fluoronitrobenzene: the 100ml orthodichlorobenzene is replaced to the 100ml ortho-chlorotolu'ene, other operational condition is all identical with embodiment 5, collects 132～136 ℃/30mmHg cut, gets 10.0g light yellow liquid 4-chloro-2-fluoronitrobenzene, yield 63%, purity 98.9%.
Embodiment 9
4-chloro-2-fluoronitrobenzene: 30g 5-chloro-2-N-methyl-p-nitroaniline diazonium hexafluorophosphote is placed the 150ml there-necked flask, connect thermometer, spherical condensation tube and drying tube, oil bath heating then, 150～155 ℃ of reactions of control reaction temperature 1h.Resistates is cooled to room temperature, adds the extraction of 100ml toluene, uses 5% sodium carbonate solution (50ml) and water (50ml * 3) washing successively, anhydrous sodium sulfate drying.Filter, the filtrate decompression precipitation, 133～136 ℃/30mmHg cut is collected in the resistates rectification under vacuum, gets 6.2g light yellow liquid 4-chloro-2-fluoronitrobenzene, yield 39%, purity 98.7%.
Claims (4)
1. the chemical synthesis process of 4-chloro-2-fluoronitrobenzene, it is characterized in that: with 5-chloro-2-N-methyl-p-nitroaniline is starting raw material, also further generate corresponding diazonium hexafluorophosphote with the phosphofluoric acid reactant aqueous solution through diazotization reaction, thermolysis prepares 4-chloro-2-fluoronitrobenzene then.
2. synthetic method according to claim 1, it is characterized in that: the diazotization reaction of 5-chloro-2-N-methyl-p-nitroaniline is that 5-chloro-2-N-methyl-p-nitroaniline is dispersed in concentration expressed in percentage by weight 35～37% concentrated hydrochloric acids, dripping sodium nitrite in aqueous solution then finishes, being reflected at-10～20 ℃ carries out, optimal reaction temperature is 5～10 ℃, the consumption of concentrated hydrochloric acid is 5～50 times of 5-chloro-2-N-methyl-p-nitroaniline weight, wherein with 5～10 times of the bests, the mol ratio of 5-chloro-2-N-methyl-p-nitroaniline and Sodium Nitrite is 1: 1～1.05.
3. synthetic method according to claim 1, it is characterized in that: the temperature of reaction that generates diazonium hexafluorophosphote is 5～10 ℃, the mol ratio of 5-chloro-2-N-methyl-p-nitroaniline and phosphofluoric acid is 1: 1.4～1.6, the phosphofluoric acid aqueous solution is meant that concentration expressed in percentage by weight is 10～60% the phosphofluoric acid aqueous solution, wherein is 35～40% phosphofluoric acid best results with concentration expressed in percentage by weight.
4. synthetic method according to claim 1, it is characterized in that: the thermolysis of diazonium hexafluorophosphote is to be heated to 150～155 ℃ of reaction 1h to finish in inert organic solvents ortho-chlorotolu'ene or orthodichlorobenzene, and perhaps direct heating to 150～155 a ℃ reaction 1h finishes under drying regime.
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| CNB021300895A CN1162393C (en) | 2002-08-28 | 2002-08-28 | Chemical synthesis process of 4-chloro-2-fluoro nitrobenzene |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110305018A (en) * | 2019-06-06 | 2019-10-08 | 浙江普洛家园药业有限公司 | A kind of preparation method of the bromo- 2- fluoronitrobenzene of 3- |
| CN115231996A (en) * | 2021-04-23 | 2022-10-25 | 潍坊市海欣药业有限公司 | Synthetic method of 3-fluoro-4-methylbenzoic acid |
-
2002
- 2002-08-28 CN CNB021300895A patent/CN1162393C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110305018A (en) * | 2019-06-06 | 2019-10-08 | 浙江普洛家园药业有限公司 | A kind of preparation method of the bromo- 2- fluoronitrobenzene of 3- |
| CN110305018B (en) * | 2019-06-06 | 2022-07-15 | 浙江普洛家园药业有限公司 | Preparation method of 3-bromo-2-fluoronitrobenzene |
| CN115231996A (en) * | 2021-04-23 | 2022-10-25 | 潍坊市海欣药业有限公司 | Synthetic method of 3-fluoro-4-methylbenzoic acid |
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