CN118084680A - Preparation method of 2, 6-dichloroaniline - Google Patents
Preparation method of 2, 6-dichloroaniline Download PDFInfo
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- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 50
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 48
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 claims abstract description 34
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 33
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 31
- 238000006277 sulfonation reaction Methods 0.000 claims abstract description 20
- 239000002516 radical scavenger Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000005869 desulfonation reaction Methods 0.000 claims abstract description 18
- 239000003085 diluting agent Substances 0.000 claims abstract description 16
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 11
- 150000003254 radicals Chemical class 0.000 claims abstract description 10
- FOUDIUBFAMPYQA-UHFFFAOYSA-N 4-amino-3,5-dichlorobenzenesulfonic acid Chemical compound NC1=C(Cl)C=C(S(O)(=O)=O)C=C1Cl FOUDIUBFAMPYQA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000010438 heat treatment Methods 0.000 claims abstract description 9
- 229940123457 Free radical scavenger Drugs 0.000 claims abstract description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 22
- 229950000244 sulfanilic acid Drugs 0.000 claims description 17
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 5
- WAMKWBHYPYBEJY-UHFFFAOYSA-N duroquinone Chemical compound CC1=C(C)C(=O)C(C)=C(C)C1=O WAMKWBHYPYBEJY-UHFFFAOYSA-N 0.000 claims description 4
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 3
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000002994 raw material Substances 0.000 abstract description 12
- NATVSFWWYVJTAZ-UHFFFAOYSA-N 2,4,6-trichloroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1Cl NATVSFWWYVJTAZ-UHFFFAOYSA-N 0.000 abstract description 8
- 239000006227 byproduct Substances 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 5
- 238000005580 one pot reaction Methods 0.000 abstract description 4
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 3
- 238000007865 diluting Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 18
- 229910052801 chlorine Inorganic materials 0.000 description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 9
- 125000000542 sulfonic acid group Chemical group 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- -1 chlorine radicals Chemical class 0.000 description 3
- 230000006326 desulfonation Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229960001699 ofloxacin Drugs 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 229940097420 Diuretic Drugs 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000000110 cooling liquid Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 229960002422 lomefloxacin Drugs 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940072132 quinolone antibacterials Drugs 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 2, 6-dichloroaniline, which comprises the following steps: dripping aniline into concentrated sulfuric acid solution, and heating to carry out sulfonation reaction after dripping is finished to obtain reaction liquid containing sulfanilic acid; diluting with water to obtain a diluent; adding a free radical capturing agent and a chlorinating agent into the diluent to carry out chlorination reaction to obtain a reaction solution containing 2, 6-dichloro-4-sulfoaniline; then carrying out desulfonation reaction to obtain 2, 6-dichloroaniline. The method takes the aniline which is cheap and easy to obtain as the initial raw material, the sulfonation, chlorination and desulfonation reaction are completed in a one-pot method, and the generation of the 2,4, 6-trichloroaniline by-product is inhibited by innovatively adding the free radical scavenger in the chlorination reaction, and the reaction solvent is not needed to be added in the reaction process, so the method has the advantages of high yield, low cost, high preparation efficiency and less three wastes pollution.
Description
Technical Field
The invention belongs to the field of organic synthesis, and relates to a preparation method of 2, 6-dichloroaniline.
Background
2, 6-Dichloroaniline is an important intermediate of medicines and pesticides, is mainly used for synthesizing lomefloxacin, ofloxacin, diuretic acid, clonidine and the like which are quinolone antibacterial medicines in the medicine field, and is mainly used for synthesizing herbicides and bactericides in the pesticide industry. In recent years, with the rise of novel antibacterial drugs containing fluoroquinolones, particularly the mass production of ofloxacin and marketing, the annual demand of the initial raw material 2, 6-dichloroaniline is continuously increased, and simultaneously, higher requirements are put forward on the production technology and the product quality of the 2, 6-dichloroaniline.
The synthesis methods reported in the literature to date mainly include the following methods:
1. Aniline is used as a raw material, and is firstly converted into diphenyl urea, and then 2, 6-dichloroaniline is obtained through sulfonation, chlorination and desulfonation.
2. The p-aminobenzene sulfonamide is taken as a raw material, and is subjected to chlorination by concentrated hydrochloric acid and hydrolysis by sulfuric acid to obtain the 2, 6-dichloroaniline.
3. The p-aminobenzoic acid (or ester) is subjected to chlorination, hydrolysis and decarboxylation to obtain the 2, 6-dichloroaniline.
4. The amino group of the 2,4, 6-trichloroaniline is protected by two acetyl groups, and is reduced, dechlorinated and hydrolyzed to obtain the 2, 6-dichloroaniline.
5. And (3) chloridizing, reducing and debrominating the p-bromoaniline to obtain the 2, 6-dichloroaniline.
6. Cyclohexanone is taken as a raw material to obtain 2, 6-dichloroaniline through chlorination, ammoniation and dehydrogenation.
7. The method takes sulfanilic acid as an initial raw material, and prepares the 2, 6-dichloroaniline after chloridizing, hydrolyzing and desulfonating groups. For example, literature (Zhang Xiangzhu, wu Mingshu, J. Of the Chinese medical industry, 1996,27 (7); 330) reports that 2, 6-dichloro-4-sulfoanilines are prepared by chloridizing sulfanilic acid as a starting material with chlorine under the catalysis of ferric trichloride and sulfuric acid, and then heating reflux water under the action of sulfuric acid to release the sulfonic acid groups. However, the preparation yield of the method is low, the yield is only 49.4%, the chlorination process needs to be heated to 100-110 ℃, the reaction condition is severe, and compared with aniline, the cost of the raw material of the sulfanilic acid is relatively high.
Therefore, how to prepare 2, 6-dichloroaniline with high yield from cheap and easily available raw materials is a technical problem to be solved in the field.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of 2, 6-dichloroaniline, which takes low-cost and easily available aniline as a starting material, ensures that sulfonation, chlorination and desulfonation reactions are completed in a one-pot method, and is innovatively added with a free radical scavenger in the chlorination reaction to inhibit the generation of 2,4, 6-trichloroaniline byproducts, and reaction solvents are not required to be added in the reaction process. Therefore, the method has the advantages of high yield, low cost, high preparation efficiency and less three wastes pollution.
The invention provides a preparation method of 2, 6-dichloroaniline, which comprises the following steps:
dripping aniline into concentrated sulfuric acid solution, and heating to carry out sulfonation reaction after dripping is finished to obtain reaction liquid containing sulfanilic acid;
Adding water to dilute the reaction solution containing sulfanilic acid to obtain a diluent;
Adding a free radical capturing agent and a chlorinating agent into the diluent to carry out chlorination reaction to obtain a reaction solution containing 2, 6-dichloro-4-sulfoaniline;
And (3) performing desulfonation reaction on the reaction solution containing the 2, 6-dichloro-4-sulfoaniline to obtain the 2, 6-dichloroaniline.
In an alternative embodiment, the radical scavenger is selected from one or more of hydrogen peroxide, 2, 6-tetramethylpiperidine oxide, t-butyl peroxide, p-benzoquinone, tetramethyl benzoquinone.
In an alternative embodiment, the free radical scavenger is added in an amount of 0.05 to 1.2 times the molar amount of the aniline.
In an alternative embodiment, the temperature of the chlorination reaction is between 10 and 70 ℃.
In an alternative embodiment, the temperature of the chlorination reaction is 20 to 30 ℃.
In an alternative embodiment, the chlorinating agent is selected from one or more of chlorine, sodium hypochlorite, a mixture of hydrochloric acid and hydrogen peroxide, sulfonyl chloride.
In an alternative embodiment, the concentrated sulfuric acid solution has a mass concentration of 70% to 98%;
and/or the mass concentration of the sulfuric acid in the diluent is 10-70%.
In an alternative embodiment, the molar amount of sulfuric acid in the concentrated sulfuric acid solution is 1.5 to 10 times the molar amount of aniline.
In an alternative embodiment, the sulfonation reaction is carried out at a temperature of 140 to 220 ℃.
In an alternative embodiment, the temperature of the desulfonation reaction is 140 to 220 ℃ for a period of 2 to 10 hours.
The implementation of the invention has at least the following advantages:
1) According to the preparation method, in the chlorination stage, the free radical capturing agent is added into the reaction liquid to inhibit the generation of free radicals, so that the generation of 2,4, 6-trichloroaniline byproducts is avoided, and the preparation yield of 2, 6-dichloroaniline is improved.
2) The preparation method of the invention takes the aniline which is cheap and easy to obtain as the raw material, so that the sulfonation, chlorination and desulfonation reactions are completed in a one-pot method, and the steps of purification and separation of intermediates are avoided, thus having the advantages of high preparation efficiency and low reaction cost.
3) According to the preparation method disclosed by the invention, an organic solvent is not required to be added in the reaction process, so that the pollution of three wastes is reduced.
Drawings
FIG. 1 is a 1 H NMR chart of 2, 6-dichloroaniline obtained in example 1 of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention provides a preparation method of 2, 6-dichloroaniline, which comprises the following steps:
dripping aniline into concentrated sulfuric acid solution, and heating to carry out sulfonation reaction after dripping is finished to obtain reaction liquid containing sulfanilic acid;
Adding water into the reaction solution containing sulfanilic acid for dilution treatment to obtain a diluent;
adding a free radical capturing agent and a chlorinating agent into the diluent to carry out chlorination reaction to obtain a reaction solution containing 2, 6-dichloro-4-sulfoaniline;
And (3) performing desulfonation reaction on the reaction solution containing the 2, 6-dichloro-4-sulfoaniline to obtain the 2, 6-dichloroaniline.
The preparation method can be represented by the following reaction formula:
The preparation method of the invention uses aniline as a starting material, firstly converts aniline into p-aminobenzenesulfonic acid under the action of concentrated sulfuric acid, then chloridizes the ortho position of amino through the positioning effect of amino and sulfonic acid groups under the action of a chlorinating agent, and finally heats under an acidic condition to remove sulfonic acid groups to obtain the target product 2, 6-dichloroaniline.
In addition, after the sulfonation reaction is finished, the reaction solution is diluted by adding water, so that on one hand, the diluted acid concentration is favorable for catalyzing the chlorination reaction, and on the other hand, the acid concentration can provide proper acidic hydrolysis conditions for the desulfonation reaction.
The inventor finds that when chlorine gas and sulfanilic acid react normally, a great amount of 2,4, 6-trichloroaniline byproducts are generated, and the yield of the 2, 6-trichloroaniline is reduced, the mechanism is probably that chlorine gas is homolytic to form chlorine free radicals in the reaction process, and the chlorine free radicals have high reactivity and attack amino ortho-para positions to replace sulfonic acid groups.
Based on the method, a free radical scavenger is added to the chlorine radical scavenger during the chlorination reaction to destroy the generation of chlorine free radicals, so that after chlorine is isosplit, the chlorine positive ions are made to electrophilically attack the ortho position of the amino group and the meta position of the sulfonic acid group under the substituent positioning effect of the strong electron donating group amino group and the strong electron withdrawing group sulfonic acid group in the form of chloridion, so that the 2, 6-dichloro-4-sulfonic acid aniline can be prepared in a higher yield, and then the sulfonic acid group is removed by heating under an acidic condition, so that the 2, 6-dichloroaniline can be prepared in a higher yield.
In summary, the preparation method of the invention takes the aniline which is cheap and easy to obtain as the initial raw material, so that sulfonation, chlorination and desulfonation are carried out in one-pot reaction, reaction solvents are not needed in the reaction process, the reaction cost and the generation of three wastes are reduced, the preparation efficiency is improved, and the generation of chlorine free radicals is inhibited by adding the free radical scavenger in the chlorination reaction stage, so that the generation of 2,4, 6-trichloroaniline byproducts is avoided, and the reaction yield is further improved. Therefore, the preparation method of the invention has the advantages of high product yield, high preparation efficiency, low reaction cost and less three-waste pollution.
The kind of the radical scavenger is not particularly limited as long as it can inhibit the generation of chlorine radicals, including but not limited to one or more of hydrogen peroxide, 2, 6-tetramethylpiperidine oxide, t-butyl peroxide, p-benzoquinone, and tetramethyl benzoquinone.
The amount of the radical scavenger is not particularly limited, and the amount of the catalyst may be any amount. In a preferred embodiment, when the amount of the radical scavenger added is 0.05 to 1.2 times that of aniline, the formation of chlorine radicals can be preferably suppressed to avoid the occurrence of side reactions.
It is worth mentioning that the invention can inhibit the generation of 2,4, 6-trichloroaniline by-product by adding the free radical scavenger, and can reduce the severity of chlorination reaction, so that the reaction can be carried out at 10-70 ℃, more preferably, the reaction can be carried out at room temperature of 20-30 ℃, and the reaction energy consumption is greatly reduced.
The time of the chlorination reaction is not particularly limited, and the chlorine gas can be stopped as long as the basic conversion of the sulfanilic acid is detected, and according to experience, the chlorination reaction is usually completed within 2-8 hours, preferably about 4 hours.
The chlorinating agent used in the chlorination reaction is not particularly limited, and any chlorinating agent conventionally used in the art may be used, including but not limited to one or more of chlorine gas, sodium hypochlorite, a mixture of hydrochloric acid and hydrogen peroxide, and sulfonyl chloride.
The sulfonation reaction in the first stage can be referred to as aniline sulfonation reaction conditions conventional in the art.
In a preferred embodiment, the concentrated sulfuric acid solution has a mass concentration of 70% to 98%, which may also be fuming sulfuric acid, more preferably 98% by mass, and the hydrolysis of the sulfanilic acid product is avoided by using a high concentration of concentrated sulfuric acid.
For cost reasons, a suitable excess of sulfuric acid in the concentrated sulfuric acid solution may be used in the sulfonation reaction, on the one hand to promote complete conversion of aniline, and on the other hand the excess acid may also provide an acidic environment for subsequent chlorination and sulfonation reactions to promote the reaction. Preferably, the molar amount of sulfuric acid in the concentrated sulfuric acid solution is 1.5 to 10 times the molar amount of aniline.
In a specific embodiment, the temperature of the sulfonation reaction is 140 to 220 ℃, preferably 160 ℃.
Further, one molecule of water is generated in the sulfonation reaction, and the water separated can be removed by a water separator to promote the forward progress of the reaction, or the progress of the reaction can be judged by recording the water separated.
Similarly, the desulfonation reaction in the third stage can refer to the conventional benzene ring desulfonation reaction condition in the field, namely heating hydrolysis under the condition of dilute acid to remove the sulfonic acid group.
In order to make the reaction system have proper acid concentration during the desulfonation, the mass concentration of sulfuric acid in the diluted solution after the water dilution treatment can be 10-70%.
In addition, a large amount of heat is released in the process of diluting the reaction solution with water, and in order to avoid side reactions caused by overhigh temperature, the reaction solution containing sulfanilic acid is cooled and then diluted by dripping water. Preferably, the temperature is reduced to 80 ℃ and then water is added dropwise, and the reaction temperature should be controlled to be not more than 80 ℃ in the dropping process.
In a specific embodiment, the temperature of the desulfonation reaction is 140 to 220 ℃ for 2 to 10 hours, preferably 160 ℃ for 3 hours.
Specifically, the progress of the reaction at each stage can be detected using methods conventional in the art, including but not limited to TLC, HPLC, NMR, or the like.
In the sulfonation reaction stage, the completion of the reaction can be judged after disappearance of the aniline raw material is detected; in the chlorination reaction stage, the completion of the reaction can be judged when the disappearance of the sulfanilic acid in the reaction liquid is detected; in the desulfonation reaction, the completion of the reaction can be judged when the disappearance of the 2, 6-dichloro-4-sulfoaniline in the reaction liquid is detected.
After the desulfonation reaction is finished, the reaction system is also required to be subjected to post-treatment to obtain a high-purity 2, 6-dichlorophenylamine product. 2, 6-dichloroaniline is a solid with a melting point of 36-38 ℃ and a boiling point of only 228 ℃, so that the 2, 6-dichloroaniline product with high purity can be obtained by rectification and purification, and the temperature of cooling liquid in a condenser is controlled to be higher than the melting point of the product during rectification.
In a specific embodiment, the post-treatment process comprises: cooling the reaction liquid to 0-20 ℃ to precipitate solids, filtering, and leaching a filter cake (crude product) with water to obtain a crude product; and rectifying and refining (crystallizing) the crude product to obtain the 2, 6-dichloroaniline product.
The method for preparing 2, 6-dichloroaniline provided by the invention will be further described with reference to specific examples.
In the examples described below, the experimental methods used, unless otherwise specified, may be those conventional in the art.
In the examples which follow, all starting materials, unless otherwise specified, are prepared by commercial or conventional methods.
Example 1
The embodiment provides a preparation method of 2, 6-dichloroaniline, which comprises the following steps:
1) Adding 300g of concentrated sulfuric acid (with the mass concentration of 98 percent and 3 mol) into a three-neck flask connected with a dropping funnel and a water diversion device, dropwise adding 93g (1 mol) of aniline into the three-neck flask in a stirring state, heating to 160 ℃ after the dropwise adding is finished, carrying out sulfonation reaction until the separated water reaches 18g, and sampling to detect disappearance of aniline raw materials;
2) Cooling the reaction system to 80 ℃, and dropwise adding 300g of water into the reaction system to dilute the acid concentration, wherein the temperature of the system is controlled to be not more than 80 ℃ in the dropwise adding process, so as to obtain a diluent;
3) Adding 10.8g (0.1 mol) of p-benzoquinone into the diluent, cooling to 25 ℃, and continuously introducing chlorine until the complete conversion of the p-aminobenzenesulfonic acid is detected, and stopping introducing the chlorine;
4) Heating the reaction system to 160 ℃ and continuously stirring for 3 hours, and sampling and detecting the end of the reaction;
5) Cooling the reaction solution to 10 ℃ to precipitate solids, filtering and collecting the precipitated solids, eluting with water to obtain a crude product, rectifying and crystallizing the crude product to obtain a pure 2, 6-dichloroaniline product with the mass of 134g and the yield of 83%.
The obtained 2, 6-dichloroaniline was subjected to nuclear magnetic resonance hydrogen spectrum characterization, fig. 1 is a nuclear magnetic resonance hydrogen spectrum of 2, 6-dichloroaniline prepared in example 1, and as shown in fig. 1, the hydrogen spectrum of fig. 1 was subjected to attribution analysis, so that the hydrogen spectrum data of 2, 6-dichloroaniline can be obtained as follows:
1H NMR(400MHz,CDCl3)δ7.17(d，J＝8.0Hz，2H)，6.61(t，J＝8.0Hz，1H)，4.43(s,2H).
Example 2
This example provides a process for the preparation of 2, 6-dichloroaniline, which essentially corresponds to example 1, except that the radical scavenger is replaced by tetramethylbenzoquinone (0.1 mol) from p-benzoquinone (0.1 mol) and the yield of 2, 6-dichloroaniline is 79%.
Example 3
This example provides a process for the preparation of 2, 6-dichloroaniline, which essentially corresponds to example 1, except that the radical scavenger is replaced by 2, 6-tetramethylpiperidine oxide (0.1 mol) from p-benzoquinone (0.1 mol), and the yield of 2, 6-dichloroaniline is 85%.
Example 4
This example provides a process for the preparation of 2, 6-dichloroaniline, which essentially corresponds to example 1, except that the radical scavenger is replaced by tert-butyl peroxy alcohol (0.1 mol) from p-benzoquinone (0.1 mol), and the yield of 2, 6-dichloroaniline is 76%.
Example 5
This example provides a process for the preparation of 2, 6-dichloroaniline, which is substantially identical to example 1, except that the chlorinating agent is replaced by sulfonyl chloride (2 mol) from chlorine, i.e. step 3) is performed as follows: 10.8g (0.1 mol) of p-benzoquinone was added to the dilution, cooled to 25℃and 270g (2 mol) of sulfonyl chloride was added thereto to continue the reaction until complete conversion of sulfanilic acid was detected. The yield of the finally obtained 2, 6-dichloroaniline was 72%.
Example 6
The present embodiment provides a method for preparing 2, 6-dichloroaniline, which has the same preparation steps as those of embodiment 1, except that the chlorinating agent is replaced by a mixed solution of concentrated hydrochloric acid and hydrogen peroxide from chlorine, namely, the process of step 3) is as follows: 10.8g (0.1 mol) of p-benzoquinone is added into the diluted solution, the temperature is reduced to 25 ℃, and 500mL (5 mol, the molar concentration is 10 mol/L) of concentrated hydrochloric acid solution and 200mL of hydrogen peroxide with the mass concentration of 35% are added into the diluted solution to continue to react until the complete conversion of the p-aminobenzenesulfonic acid is detected. The yield of the finally obtained 2, 6-dichloroaniline was 65%.
Example 7
This example provides a process for preparing 2, 6-dichloroaniline, which essentially corresponds to example 1, except that the amount of radical scavenger added is changed from 0.1mol to 0.5mol, and the yield of 2, 6-dichloroaniline is 86%.
Example 8
This example provides a process for preparing 2, 6-dichloroaniline, which essentially corresponds to example 1, except that the amount of radical scavenger added is changed from 0.1mol to 1mol, and the yield of 2, 6-dichloroaniline is 88%.
Example 9
This example provides a process for the preparation of 2, 6-dichloroaniline, which is substantially identical to example 1, except that the temperature of the chlorination reaction is replaced by 70 ℃ from 25 ℃, i.e. the procedure of step 3) is: 10.8g (0.1 mol) of p-benzoquinone is added into the diluent, the temperature is reduced to 70 ℃, and the chlorine is continuously introduced into the diluent until the complete conversion of the p-aminobenzenesulfonic acid is detected, and the introduction of the chlorine is stopped. The yield of the finally obtained 2, 6-dichloroaniline was 68%.
Comparative example 1
This comparative example provides a process for the preparation of 2, 6-dichloroaniline, which is substantially identical to example 1, except that no radical scavenger is added during the chlorination reaction, i.e. step 3) is carried out as follows: cooling the diluent to 25 ℃, and continuously introducing chlorine into the diluent until the complete conversion of the sulfanilic acid is detected, and stopping introducing the chlorine. The yield of the finally obtained 2, 6-dichloroaniline was 38%.
Comparative example 2
This comparative example provides a process for the preparation of 2, 6-dichloroaniline, which is substantially identical to example 1, except that the p-benzoquinone (0.1 mol) in step 3) is replaced with ferric trichloride (0.1 mol). The yield of the finally obtained 2, 6-dichloroaniline was 51%.
The above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (10)
1. The preparation method of the 2, 6-dichloroaniline is characterized by comprising the following steps:
dripping aniline into concentrated sulfuric acid solution, and heating to carry out sulfonation reaction after dripping is finished to obtain reaction liquid containing sulfanilic acid;
Adding water to dilute the reaction solution containing sulfanilic acid to obtain a diluent;
Adding a free radical capturing agent and a chlorinating agent into the diluent to carry out chlorination reaction to obtain a reaction solution containing 2, 6-dichloro-4-sulfoaniline;
And (3) performing desulfonation reaction on the reaction solution containing the 2, 6-dichloro-4-sulfoaniline to obtain the 2, 6-dichloroaniline.
2. The preparation method according to claim 1, wherein the free radical scavenger is one or more selected from hydrogen peroxide, 2, 6-tetramethylpiperidine oxide, t-butyl peroxide, p-benzoquinone and tetramethyl benzoquinone.
3. The method according to claim 1 or 2, wherein the free radical scavenger is added in an amount of 0.05 to 1.2 times the molar amount of the aniline.
4. The process according to claim 1, wherein the temperature of the chlorination reaction is 10 to 70 ℃.
5. The process according to claim 4, wherein the temperature of the chlorination reaction is 20 to 30 ℃.
6. The preparation method according to claim 1, wherein the chlorinating agent is one or more selected from chlorine gas, sodium hypochlorite, a mixture of hydrochloric acid and hydrogen peroxide, and sulfonyl chloride.
7. The preparation method according to claim 1, wherein the mass concentration of the concentrated sulfuric acid solution is 70% -98%;
and/or the mass concentration of the sulfuric acid in the diluent is 10-70%.
8. The method according to claim 1 or 7, wherein the molar amount of sulfuric acid in the concentrated sulfuric acid solution is 1.5 to 10 times the molar amount of aniline.
9. The method according to claim 1, wherein the sulfonation reaction is carried out at a temperature of 140 to 220 ℃.
10. The method according to claim 1, wherein the temperature of the desulfonation reaction is 140-220 ℃ for 2-10 hours.
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