CN1006888B - Process for preparing 2, 4-dichloro-5-fluoro-benzoic acid - Google Patents
Process for preparing 2, 4-dichloro-5-fluoro-benzoic acidInfo
- Publication number
- CN1006888B CN1006888B CN 85107015 CN85107015A CN1006888B CN 1006888 B CN1006888 B CN 1006888B CN 85107015 CN85107015 CN 85107015 CN 85107015 A CN85107015 A CN 85107015A CN 1006888 B CN1006888 B CN 1006888B
- Authority
- CN
- China
- Prior art keywords
- fluoro
- dichloro
- chloro
- acetyl chloride
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- KZCWJHUTTSVCRO-UHFFFAOYSA-N 2,4-dichloro-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(Cl)C=C1Cl KZCWJHUTTSVCRO-UHFFFAOYSA-N 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000005917 acylation reaction Methods 0.000 claims abstract description 9
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 8
- BDJZCCWUSOZUQG-UHFFFAOYSA-N 2,4-dichloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Cl BDJZCCWUSOZUQG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- -1 2, 4-dichloro-fluoro-phenyl methyl ketone Chemical compound 0.000 claims abstract description 6
- 230000010933 acylation Effects 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 10
- MIZKCMSSYVUZKD-UHFFFAOYSA-N 2-chloro-5-fluorobenzoic acid Chemical class OC(=O)C1=CC(F)=CC=C1Cl MIZKCMSSYVUZKD-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 239000007844 bleaching agent Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- HVOWRXHAONMBJB-UHFFFAOYSA-N 1-(2-chloro-5-fluorophenyl)propan-1-one Chemical class CCC(=O)C1=CC(F)=CC=C1Cl HVOWRXHAONMBJB-UHFFFAOYSA-N 0.000 claims 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 3
- 239000005708 Sodium hypochlorite Substances 0.000 abstract description 2
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 abstract description 2
- FAKJFAMIABOKBW-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Cl)C=C1Cl FAKJFAMIABOKBW-UHFFFAOYSA-N 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical class [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 3
- ZCJAYDKWZAWMPR-UHFFFAOYSA-N 1-chloro-2-fluorobenzene Chemical compound FC1=CC=CC=C1Cl ZCJAYDKWZAWMPR-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- VZHJIJZEOCBKRA-UHFFFAOYSA-N 1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1 VZHJIJZEOCBKRA-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- IMXLQXHCHYKEEE-UHFFFAOYSA-N benzene;formic acid Chemical class OC=O.C1=CC=CC=C1 IMXLQXHCHYKEEE-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- AYNNSCRYTDRFCP-UHFFFAOYSA-N triazene Chemical compound NN=N AYNNSCRYTDRFCP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Preparation of 2, 4-dichloro-5-fluoro-benzylAn acid method.Acetyl chloride reacts with 2, 4-dichlorofluorobenzene at the temperature of 10-150 ℃ in the presence of an acylation catalyst to obtain 2, 4-dichloro-5-fluoro-phenyl methyl ketone, and the structure of the acetyl chloride is as follows:
Description
The present invention proposes a kind of preparation 2, the novel method of 4-two chloro-5-fluorobenzoic acids, and this compound is intermediates of producing antiseptic-germicide.
Known trihalogenated benzene formic acid can be made by saponification three halos-trihalogenmethyl-benzene.For example, 2,4-two chloro-5-fluoro-phenylformic acid can be by saponification 2,4-two chloro-5-fluoro-benzenyl trichlorides and get (EP-OS(European publication technical specification) 78,362).
Etheride with aliphatic carboxylic acid comes the acidylate phenyl-dihalide, and also known is very difficult.Trihalogenated benzene does not carry out this class reaction (organic chemistry method) (He Ben-Weir-Muller) volume 7/2a according to reports, 43(1973), and (Thieme press, Stuttgart).
In addition, known with 2,4 dichloro fluorobenzene in the presence of aluminum chloride, with carboxylic acid anhydride be that diacetyl oxide carries out acylation reaction and obtains 2 of very low yield, 4-two chloro-5-fluoro-acetophenone (CA58,11243g).
Surprisingly, 2,4 dichloro fluorobenzene in the presence of 10 °～105 ℃ and acylation catalyst, have diluent free all can, obtain high yield and highly purified 2 with excess acetyl chloride, 4-two chloro-5-fluoro-phenylformic acid, its structural formula is (I).Reaction product 2,4-two chloro-5-fluoro-phenyl methyls
Ketone, its structural formula are (II), can separate also can be directly and chlorine bleach liquor's (so-called chlorinated soda solution) be 0 °～140 ℃ reactions down in temperature.
Can make 2,4 dichloro fluorobenzene and carboxylic acid chloride carry out acylation reaction according to method of the present invention, and obtain to have more electronegative halogen be between the position product.This is very unusual; because according to report; when the acidylate halogeno-benzene, should obtain having more the product that electronegative halogen is ortho position or contraposition (organic chemistry method) (He Ben-Weir-Muller) volume 7/2a43(1973), (Thieme press, Stuttgart).
Above-mentioned known method has a series of shortcomings.As, in preparation 2, during 4-two chloro-5-fluoro-benzenyl trichlorides, synthesize the triazene that has bad physiological property thereby be difficult to dispose, as intermediates.
In addition, this method preparation 2,4-two chloro-5-fluoro-phenylformic acid need several steps.
Reported in literature, 2, the yield of product is very low when 4-two chloro-5-fluorobenzene and acetic anhydride acylation.
When being raw material with 2,4 dichloro fluorobenzene and Acetyl Chloride 98Min., aluminum chloride is a catalyzer, and during with chlorinated soda solution, reaction sequence can be expressed by following reaction formula:
2,4 dichloro fluorobenzene is a compound known in the organic chemistry.
Temperature of reaction can change in the scope of broad.Be generally 10 °～150 ℃, 20 °～130 ℃ better, is more preferably and carries out acylation reaction under 80～130 ℃.Generally at 0～140 ℃, be preferably 20 °～120 ℃ reactions down with the chlorinated soda solution oxide.Reaction is carried out under normal pressure usually.
Synthetic method of the present invention is not generally used thinner.
The catalyzer that the present invention adopts is an acylation catalyst, iron(ic) chloride (trivalent) for example, and zinc chloride or aluminum chloride are best with aluminum chloride.
It is aqueous sodium hypochlorite solution that the present invention uses so-called chlorinated soda solution, as oxygenant.
According to method of the present invention, the aluminum chloride of normally used mole Acetyl Chloride 98Min. and 1～3 mole is to 1 mole 2,4-two chloro-fluorobenzene.After reaction finished, reaction mixture was poured on ice, extracted with water-fast thinner, for example methylene dichloride or chloroform.But reaction product also can be separated without thinner.If suitable, after removing extraction agent, resistates is in the per molecule raw material, with 2～4 liters, and preferably 2.1～3.3 liter chlorinated soda solution (every liter contains 150 gram reactive chlorine) oxidation.Then, 2,4-two chloro-5-fluoro-phenylformic acid can be used mineral acid, and example hydrochloric acid precipitates, and separates with suction filtration and obtains.
2,4-two chloro-5-fluoro-phenylformic acid can easily make with method of the present invention, and can be used for synthetic antibacterial agents.The derivative of high-efficiency antimicrobial compound Oxoquinoline carboxylic acid just can be by this acid preparation like this.For example, can obtain (seeing EP-OS(European publication technical specification) 78,362 by following reaction formula).
The preparation example
23.6 gram (0.3 mole) Acetyl Chloride 98Min.s are added to 33 gram (0.2 moles) 2 under 20～40 ℃, in the mixture of 4-two chloro-fluorobenzene and 66.8 gram (0.5 mole) aluminum chlorides, reactant stirred 2 hours down at 120 ℃.Be poured in the 250 gram ice oily matter dichloromethane extraction then while hot.Steam solvent, resistates adds 450 milliliters of chlorinated soda solution (every liter contains reactive chlorine 150 grams), and mixture is heated and stirred one hour not, and reheat refluxed 2 hours.After removing chloroform, add 300 ml waters, reactant is handled with the sodium bisulfite of 10 milliliter of 40% intensity, adds concentrated hydrochloric acid again and equals 1 until the pH value.
Make 2 as stated above, 4-two chloro-5-fluoro-phenylformic acid 33.5 grams (yield 80%), it is a kind of colourless powder, fusing point is 139 ℃.
Claims (4)
1, a kind of preparation 2, the method for 4-two chloro-5-fluorobenzoic acids, the structure of this compound such as formula I
The feature of this method is in the presence of 10～150 ℃ and acylation catalyst, have diluent free all can, 2,4 dichloro fluorobenzene and excess acetyl chloride must products 2,4-two chloro-5-fluorophenyl ethyl ketones, its structure such as formula II
This product reacts down at 0～140 ℃ with chlorine bleach liquor's (claiming chlorinated soda solution again) after separating, and separates through usual way, can get the formula I compound.
2, by the method for claim 1, it is characterized in that, make acylation catalyst with aluminum chloride.
3, by the method for claim 1 or 2, it is characterized in that, and being reflected between 20～130 ℃ of Acetyl Chloride 98Min. carried out.
4, by the method for claim 1 or 2, it is characterized in that,, between 20～120 ℃, carry out with the reaction of clorox (chlorinated soda solution).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 85107015 CN1006888B (en) | 1985-09-19 | 1985-09-19 | Process for preparing 2, 4-dichloro-5-fluoro-benzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 85107015 CN1006888B (en) | 1985-09-19 | 1985-09-19 | Process for preparing 2, 4-dichloro-5-fluoro-benzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85107015A CN85107015A (en) | 1987-04-01 |
| CN1006888B true CN1006888B (en) | 1990-02-21 |
Family
ID=4795401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 85107015 Expired CN1006888B (en) | 1985-09-19 | 1985-09-19 | Process for preparing 2, 4-dichloro-5-fluoro-benzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1006888B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041419C (en) * | 1993-07-21 | 1998-12-30 | 齐春莲 | Mitomycin C-dextran and its preparing method |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2009009760A (en) * | 2007-03-13 | 2009-09-24 | Oculus Innovative Sciences Inc | Antimicrobial solutions containing dichlorine monoxide and methods of making and using the same. |
| CN102249881B (en) * | 2011-05-09 | 2016-03-09 | 滨海永太医化有限公司 | A kind of take orthodichlorobenzene as the method for raw material coproduction quinolones key intermediate |
| CN107501089A (en) * | 2017-10-20 | 2017-12-22 | 河南红东方化工股份有限公司 | A kind of synthetic method of Mediben active compound |
| CN110903182A (en) * | 2018-09-14 | 2020-03-24 | 北京艾德旺科技发展有限公司 | Simple and environment-friendly chemical synthesis method of 4-fluoro-2-methylbenzoic acid |
-
1985
- 1985-09-19 CN CN 85107015 patent/CN1006888B/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041419C (en) * | 1993-07-21 | 1998-12-30 | 齐春莲 | Mitomycin C-dextran and its preparing method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN85107015A (en) | 1987-04-01 |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C13 | Decision | ||
| GR02 | Examined patent application | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
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