CN113045390A - Method for preparing triclosan by Baeyer-Villiger oxidation - Google Patents
Method for preparing triclosan by Baeyer-Villiger oxidation Download PDFInfo
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- CN113045390A CN113045390A CN202110287411.3A CN202110287411A CN113045390A CN 113045390 A CN113045390 A CN 113045390A CN 202110287411 A CN202110287411 A CN 202110287411A CN 113045390 A CN113045390 A CN 113045390A
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- acetophenone
- phenoxy
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- 238000000034 method Methods 0.000 title claims abstract description 25
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 title claims description 6
- 229960003500 triclosan Drugs 0.000 title claims description 6
- 238000006220 Baeyer-Villiger oxidation reaction Methods 0.000 title description 4
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 claims abstract description 19
- BKJJUYLJGFBZJC-UHFFFAOYSA-N 2-(3,4-dichlorophenoxy)-1-phenylethanone Chemical compound C1=C(Cl)C(Cl)=CC=C1OCC(=O)C1=CC=CC=C1 BKJJUYLJGFBZJC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000007800 oxidant agent Substances 0.000 claims abstract description 13
- 230000001590 oxidative effect Effects 0.000 claims abstract description 12
- 239000012442 inert solvent Substances 0.000 claims abstract description 11
- 229940078916 carbamide peroxide Drugs 0.000 claims abstract description 8
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 claims abstract description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
- 238000007171 acid catalysis Methods 0.000 claims description 2
- 238000005815 base catalysis Methods 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 20
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 5
- -1 alkali metal amides Chemical class 0.000 description 4
- 229940117389 dichlorobenzene Drugs 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- BYNQFCJOHGOKSS-UHFFFAOYSA-N diclosan Chemical group OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1 BYNQFCJOHGOKSS-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/39—Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester
- C07C67/42—Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester by oxidation of secondary alcohols or ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing dichlorohydrin by using carbamide peroxide as an oxidant, which comprises the following steps: (1) oxidizing 5-chloro-2- (4-chloro-phenoxy) -acetophenone in an inert solvent with carbamide peroxide as an oxidizing agent to obtain an intermediate I; (2) and hydrolyzing the intermediate I to obtain the dichloro-raw material. The method has safe production process and mild reaction, and is suitable for industrial production.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly provides a preparation method of triclosan.
Background
Dichloro-raw, chemical name is 5-chloro-2- (4-chlorophenoxy) -phenol, is an active bactericide with wide application, and can be used as a bactericidal component in coatings, paints, adhesives, detergents and surface cleaners. It can effectively inhibit 23 kinds of bacteria such as gram-positive bacteria, gram-negative bacteria, bacteria and mould.
At present, the synthesis method of dichlorohenzene mainly uses p-dichlorobenzene as raw material, and the dichlorohenzene is obtained by Friedel-crafts, substitution, oxidation and hydrolysis. Among them, Baeyer-Villiger oxidation is a key step, and is also studied more. Armando et al (WO 0183418A1) use m-chloroperoxybenzoic acid as an oxidant, which is not only more costly, but also has a lower reaction yield (39%). The oxidant used by Lourens et al (WO 9910310A1) is hydrogen peroxide, but the concentration requirement is high (49.2-62.5%), and the reaction risk is high. The method is improved by Jonjt et al (university of east China school of Industrial science, 2007, 33, 75-78), the concentration of hydrogen peroxide is reduced to 30%, but the reaction process releases heat severely, and the solvent cannot be recovered, so that the requirement of mass production cannot be met.
In conclusion, the field lacks a method for preparing the dichloro-raw material, which has safe production process and mild reaction and is suitable for industrial production.
Disclosure of Invention
The invention aims to provide a method for preparing dichlorohydrin, which has safe production process and mild reaction and is suitable for industrial production.
The invention provides a method for preparing dichlorohydrin by adopting carbamide peroxide as an oxidant. Carbamide peroxide (UHP) is a complex resulting from strong hydrogen bonding between urea and hydrogen peroxide. It converts unstable hydrogen peroxide into solid which is easy to operate, safe and stable at room temperature, and has low price. UHP shows different oxidation capacities under different solvents and catalysts, is an important oxidation reagent in organic synthesis, is successfully applied to the synthesis of the dichlorohydrin, and has advantages in cost and safety compared with the existing synthesis method.
In a first aspect of the present invention, there is provided a process for the preparation of triclosan, the process comprising the steps of:
(1) oxidizing 5-chloro-2- (4-chloro-phenoxy) -acetophenone with an oxidizing agent in an inert solvent to obtain an intermediate I;
(2) hydrolyzing the intermediate I to obtain dichloro raw;
in another preferred embodiment, in the step (1), the oxidant is selected from the group consisting of: sodium persulfate, m-CPBA, UHP, or combinations thereof.
In another preferred embodiment, said step (1) is carried out under acid or base catalysis, and said acid is selected from the group consisting of: concentrated sulfuric acid, concentrated hydrochloric acid, acetic acid, trifluoroacetic acid, or a combination thereof; the alkali is NaHCO3。
In another preferred example, the step (1) is carried out under the catalysis of concentrated sulfuric acid.
In another preferred embodiment, the molar ratio of the 5-chloro-2- (4-chloro-phenoxy) -acetophenone to the oxidant is 1: 2-5.
In another preferred embodiment, the molar ratio of the 5-chloro-2- (4-chloro-phenoxy) -acetophenone to the oxidant is 1: 3-4.
In another preferred embodiment, the molar ratio of the 5-chloro-2- (4-chloro-phenoxy) -acetophenone to the acid is 10-30: 1.
In another preferred embodiment, the molar ratio of the 5-chloro-2- (4-chloro-phenoxy) -acetophenone to the acid is 15-25: 1.
In another preferred embodiment, the inert solvent is selected from the group consisting of: dichloromethane, acetonitrile, dimethylformamide, or combinations thereof.
In another preferred embodiment, the inert solvent is dichloromethane.
In another preferred embodiment, said step (1) is carried out at 0-40 ℃.
In another preferred embodiment, said step (2) is performed under acidic condition or alkaline condition.
In another preferred embodiment, in the step (2), the acidic condition is provided by a reagent selected from the group consisting of: a mineral acid, a sulfonic acid, a lewis acid, a solid acid, or a combination thereof.
In another preferred embodiment, in the step (2), the alkaline condition is provided by a reagent selected from the group consisting of: alkali metal hydroxides, alkali metal amides, alkali metal alkoxides, alkaline earth metal hydroxides, alkaline earth metal amides, alkaline earth metal alkoxides, and organic bases.
In another preferred embodiment, in the step (2), the acidic condition is provided by an acid selected from the group consisting of: hydrochloric acid, sulfuric acid, trifluoroacetic acid, formic acid, or a combination thereof.
In another preferred embodiment, in the step (2), the alkaline condition is provided by an alkali selected from the group consisting of: sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, or a combination thereof.
In another preferred embodiment, in the step (2), the alkaline condition is provided by adding 20-40 wt% sodium hydroxide solution.
In another preferred embodiment, said step (2) is carried out in an inert solvent.
In another preferred embodiment, the inert solvent is selected from the group consisting of: toluene, benzene, xylene, or combinations thereof.
In another preferred embodiment, said step (2) is carried out at reflux temperature.
In a second aspect of the present invention, there is provided a process for the preparation of a compound of formula I, as shown in the following formula, said process comprising the steps of:
(1) oxidizing 5-chloro-2- (4-chloro-phenoxy) -acetophenone with an oxidizing agent in an inert solvent to obtain an intermediate I;
it is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Compared with the prior art, the invention has the advantages that:
the invention provides a method for preparing triclosan by Baeyer-Villiger oxidation. Compared with the prior art, the method has the advantages of simple operation, mild reaction conditions, high yield, low cost and recoverable solvent, and is suitable for industrial production.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
Example 1:
to a 50mL reaction flask were added dichloromethane (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and concentrated sulfuric acid (0.05g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (1.88g, 20mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. And cooling the reaction solution to room temperature, and adjusting the pH value to 2-5 by using a 15% hydrochloric acid solution. Standing, separating, removing the water phase, and washing the organic phase with 10% sodium bicarbonate and water respectively. The solvent was evaporated to dryness under reduced pressure and recrystallized from n-hexane to give dichloro-raw (1.35g, 53%).1H NMR(CDCl3，400MHz)δ5.33(s，1H)；6.78(d，1H,J＝6.64Hz)；6.84(d，1H,J＝6.65Hz)；6.94(d，2H,J＝8.94Hz)；7.06(s，1H)；7.30(d，2H,J＝8.94Hz)。
Example 2:
to a 50mL reaction flask were added dichloromethane (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and concentrated sulfuric acid (0.05g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (2.82g, 30mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. Dichlorobenzene (1.58g, 62%) was obtained by the workup of example 1.
Example 3:
to a 50mL reaction flask were added dimethylformamide (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and concentrated sulfuric acid (0.05g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (2.82g, 30mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. Toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the reaction and refluxed for 2 h. Dichlorobenzene (1.05g, 41%) was obtained by the workup of example 1.
Example 4:
to a 100mL reaction flask were added acetonitrile (50mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (5.62g, 20mmol), and concentrated sulfuric acid (0.10g, 1mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (5.64g, 60mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. Dichlorobenzene (2.37g, 46%) was obtained by the workup of example 1.
Example 5:
to a 50mL reaction flask were added dichloromethane (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and trifluoroacetic acid (0.06g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (2.82g, 30mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. Dichlorobenzene (0.84g, 33%) was obtained by the workup of example 1.
Comparative example 1:
to a 50mL reaction flask were added dichloromethane (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and concentrated sulfuric acid (0.05g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (0.92g, 10mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. And cooling the reaction solution to room temperature, and adjusting the pH value to 2-5 by using a 15% hydrochloric acid solution. Standing, separating, removing the water phase, and washing the organic phase with 10% sodium bicarbonate and water respectively. The solvent was evaporated to dryness under reduced pressure and recrystallized from n-hexane to yield dichloro-raw (1.18g, 46%).
The results show that the reaction yield is significantly reduced when the amount of carbamide peroxide is reduced.
Example 6:
to a 50mL reaction flask were added dichloromethane (25mL), 5-chloro-2- (4-chloro-phenoxy) -acetophenone (2.81g, 10mmol), and concentrated sulfuric acid (0.05g, 0.5mmol) in that order. The temperature was reduced to 0 ℃ with stirring, and urea peroxide (4.6g, 50mmol) was added to the reaction mixture in portions. After the addition was complete, the temperature was raised to room temperature and stirring was continued for 24 h. The solvent was distilled off under reduced pressure, and then toluene (15mL) and 30% sodium hydroxide solution (5mL) were added to the residue, and refluxed for 2 h. And cooling the reaction solution to room temperature, and adjusting the pH value to 2-5 by using a 15% hydrochloric acid solution. Standing, separating, removing the water phase, and washing the organic phase with 10% sodium bicarbonate and water respectively. The solvent was evaporated to dryness under reduced pressure and recrystallized from n-hexane to yield dichloro-raw (1.23g, 48%).
The results show that with 5 equivalents of carbamide peroxide, a reduction in the reaction yield of the process occurs, probably due to the production of by-products during the oxidation.
Claims (10)
1. A method for preparing triclosan, comprising the steps of:
(1) oxidizing 5-chloro-2- (4-chloro-phenoxy) -acetophenone with an oxidizing agent in an inert solvent to obtain an intermediate I;
(2) hydrolyzing the intermediate I to obtain dichloro raw;
2. the method of claim 1, wherein in step (1), the oxidizing agent is selected from the group consisting of: sodium persulfate, m-CPBA, UHP, or combinations thereof.
3. The method of claim 1, wherein step (1) is performed under acid or base catalysis, and the acid is selected from the group consisting of: concentrated sulfuric acid, concentrated hydrochloric acid, acetic acid, trifluoroacetic acid, or a combination thereof; the alkali is NaHCO3。
4. The method of claim 1, wherein step (1) is carried out under catalysis of concentrated sulfuric acid.
5. The method of claim 1, wherein the molar ratio of 5-chloro-2- (4-chloro-phenoxy) -acetophenone to carbamide peroxide is 1: 2-5.
6. The method of claim 1, wherein the molar ratio of the 5-chloro-2- (4-chloro-phenoxy) -acetophenone to the acid is 10-30: 1.
7. The method of claim 1, wherein the inert solvent is selected from the group consisting of: dichloromethane, acetonitrile, dimethylformamide, or combinations thereof.
8. The process of claim 1 wherein the inert solvent is methylene chloride.
9. The method of claim 1, wherein step (1) is performed at 0-40 ℃.
10. A process for the preparation of a compound of formula I, comprising the steps of:
(1) oxidizing 5-chloro-2- (4-chloro-phenoxy) -acetophenone in an inert solvent with carbamide peroxide as an oxidizing agent to obtain an intermediate I;
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1320516A1 (en) * | 2000-05-04 | 2003-06-25 | Ciba SC Holding AG | Process for the preparation of halogenated hydroxydiphenyl compounds |
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