CN85107015A - Preparation 2, the benzoic method of 4-two chloro-5-fluoro- - Google Patents
Preparation 2, the benzoic method of 4-two chloro-5-fluoro- Download PDFInfo
- Publication number
- CN85107015A CN85107015A CN85107015.9A CN85107015A CN85107015A CN 85107015 A CN85107015 A CN 85107015A CN 85107015 A CN85107015 A CN 85107015A CN 85107015 A CN85107015 A CN 85107015A
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- CN
- China
- Prior art keywords
- chloro
- fluoro
- preparation
- formula
- soda solution
- 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 - Lifetime
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- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 title abstract description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 7
- 238000005917 acylation reaction Methods 0.000 claims abstract description 7
- BDJZCCWUSOZUQG-UHFFFAOYSA-N 2,4-dichloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Cl BDJZCCWUSOZUQG-UHFFFAOYSA-N 0.000 claims abstract description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 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 abstract description 5
- 230000010933 acylation Effects 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 239000007844 bleaching agent Substances 0.000 claims abstract description 3
- 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 9
- MIZKCMSSYVUZKD-UHFFFAOYSA-N 2-chloro-5-fluorobenzoic acid Chemical class OC(=O)C1=CC(F)=CC=C1Cl MIZKCMSSYVUZKD-UHFFFAOYSA-N 0.000 claims description 6
- -1 clorox (chlorinated soda Chemical class 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- IPTXOGKXXWEFIX-UHFFFAOYSA-N 1-(3-chloro-2-fluorophenyl)propan-1-one Chemical class CCC(=O)C1=CC=CC(Cl)=C1F IPTXOGKXXWEFIX-UHFFFAOYSA-N 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- ZCJAYDKWZAWMPR-UHFFFAOYSA-N 1-chloro-2-fluorobenzene Chemical compound FC1=CC=CC=C1Cl ZCJAYDKWZAWMPR-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-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
- 230000005611 electricity Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product 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
- RJCGZNCCVKIBHO-UHFFFAOYSA-N 1-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1 RJCGZNCCVKIBHO-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
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A kind of preparation 2, the benzoic method of 4-two chloro-5-fluoro-.
Acetyl Chloride 98Min. reacts with 2,4 dichloro fluorobenzene in the presence of 10-150 ℃ and acylation catalyst and obtains 2,4-two chloro-5-fluoro-phenyl ethyl ketones, and its structure is as follows
Description
The present invention proposes a kind of preparation 2, the benzoic novel method of 4-two chloro-5-fluoro-, and this compound is intermediates of producing antiseptic-germicide.
Known three fontanels can carry out saponification by three fontanels generation-three fontanelle methyls-benzene for phenylformic acid and make.For example, 2,4-two chloro-5-fluoro-phenylformic acid can be by 2,4-two chloro-5-fluoro-benzenyl trichlorides carry out saponification and get (EP-OS(European publication technical specification) 78,362).
Known two fontanels are difficult to carry out acidylate with the fontanelle compound of aliphatic carboxylic acid for benzene.Three fontanels do not carry out this class reaction [organic chemistry method] (He Ben-Weir-Muller) volume 7/2a for benzene according to reports, 43(1973), and (Thieme press, Stuttgart).
In addition, known with 2,4 dichloro fluorobenzene in the presence of aluminum chloride, carry out acylation reaction with carboxyanhydrides such as diacetyl oxide, 2, the yield of 4-two chloro-5-fluoro-phenyl ethyl ketones is very low, (CA58,11243g).
Surprisingly now, it is highly purified 2 to extract high yield, 4-two chloro-5-fluorobenzoic acids, i.e. and structure formula I,
Its preparation process is as follows: when temperature is 10-150 ℃, in the presence of acylation catalyst, have diluent free all can, 2,4 dichloro fluorobenzene and excess acetyl chloride obtain 2,4-two chloro-5-fluoro-phenyl ethyl ketones, its structural formula is (II);
The reaction product formula II, have or not through separation all can, be under 0-140 ℃ in temperature, with chlorine bleach liquor's (claiming chlorinated soda solution again) reaction, obtain the formula I product.
Can make 2,4 dichloro fluorobenzene and carboxylic acid chlorine carry out acylation reaction according to method of the present invention, obtain more negative electricity fontanel on the position between phenyl ring.This is very unusual, because according to report, during for benzene, should produce more negative electricity fontanel [organic chemistry method] (He Ben-Weir-Muller) volume 7/2a43(1973 at the acidylate fontanel in ortho position and contraposition), (Thieme press, Stuttgart).
Above-mentioned known method has a series of shortcomings.As, in preparation 2, during 4-two chloro-5-fluoro-benzenyl trichlorides, produce the deleterious triazene intermediates of physiology, its intractable.
In addition, this method preparation 2,4-two chloro-5-fluorobenzoic acids need several steps.
Reported in literature, 2,4-two chloro-5-fluorobenzene carry out acidylate in the presence of diacetyl oxide, and the yield of product is very low.
When being starting 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, the 4-chlorofluorobenzene is a compound known in the organic chemistry.
Temperature of reaction can change in the scope of broad.The acidylate temperature is generally 10-150 ℃, and 20-130 ℃ better, and 80-130 ℃ better.With the temperature that chlorinated soda solution reoxidizes, be generally 0-140 ℃, be preferably 20-120 ℃.Reaction is carried out under normal pressure usually.
By synthetic method of the present invention, preferably do not use 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, common 1 is molar 2, and 4-two chloro-fluorobenzene use molar Acetyl Chloride 98Min. of 1-3 and the molar aluminum chloride of 1-3.After reaction finished, reaction mixture was poured on ice, and with the thinner that is immiscible in water, for example methylene dichloride or chloroform add and give extraction.But reaction product also can be separated without thinner.If suitable, after removing extraction agent, resistates is used the 2-4 liter in every mol raw material, preferably 2.1-3.3 liter chlorinated soda solution (every liter contains 150 gram reactive chlorine) oxidation.Then,, separate with suction filtration again and obtain.
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.High-efficiency antimicrobial compound like this, promptly the derivative of Oxoquinoline carboxylic acid just can be by this acid preparation.For example, can obtain (seeing EP-OS(European publication technical specification) 78,362 by following reaction formula).
R=H, alkyl
The preparation example
23.6 gram (0.3 mol) Acetyl Chloride 98Min.s are added to 33 gram (0.2 mol) 2 under 20-40 ℃, in the mixture of 4-two chloro-fluorobenzene and 66.8 gram (0.5 mol) aluminum chlorides, reactant stirred 2 hours down at 120 ℃.Be poured in the 250 gram ice oily matter dichloromethane extraction of separating 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 boiled 2 hours under reflux state.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 (5)
1, a kind of preparation 2, the method for 4-two chloro-5-fluorobenzoic acids, the structure of this compound is suc as formula (I)
The feature of this method is, 10-150 ℃ and acylation catalyst exist down, have diluent free all can, 2,4 dichloro fluorobenzene and excess acetyl chloride, product 2,4-two chloro-5-fluorophenyl ethyl ketones, based structures such as formula II
If suitable, 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 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 and 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 and 2, it is characterized in that,, between 20-120 ℃, carry out with the reaction of clorox (chlorinated soda solution).
5, by the method for claim 1 to 4, it is characterized in that 2, the 4 two chloro-5-fluorophenyl ethyl ketones that make in this method without separation, react with 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 true CN85107015A (en) | 1987-04-01 |
| CN1006888B 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 (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102249881A (en) * | 2011-05-09 | 2011-11-23 | 滨海永太医化有限公司 | Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material |
| CN101932330B (en) * | 2007-03-13 | 2015-01-14 | 奥古露丝创新科学公司 | Antimicrobial solutions containing dichlorine monoxide and methods of making and using the same |
| 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 |
Families Citing this family (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 |
-
1985
- 1985-09-19 CN CN 85107015 patent/CN1006888B/en not_active Expired
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101932330B (en) * | 2007-03-13 | 2015-01-14 | 奥古露丝创新科学公司 | Antimicrobial solutions containing dichlorine monoxide and methods of making and using the same |
| CN102249881A (en) * | 2011-05-09 | 2011-11-23 | 滨海永太医化有限公司 | Method for coproducing key intermediates of quinolone medicines by using o-dichlorobenzene as raw material |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1006888B (en) | 1990-02-21 |
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