CN110981702B - Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof - Google Patents
Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof Download PDFInfo
- Publication number
- CN110981702B CN110981702B CN201911070668.2A CN201911070668A CN110981702B CN 110981702 B CN110981702 B CN 110981702B CN 201911070668 A CN201911070668 A CN 201911070668A CN 110981702 B CN110981702 B CN 110981702B
- Authority
- CN
- China
- Prior art keywords
- dibromobenzene
- dibromophenol
- derivatives
- synthesizing
- reaction
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/58—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by oxidation reactions introducing directly hydroxy groups on a =CH-group belonging to a six-membered aromatic ring with the aid of molecular oxygen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
-
- 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 relates to a high-efficiency synthesis method of 2, 3-dibromophenol or derivatives thereof, which comprises the following steps: adding o-dibromobenzene or o-dibromobenzene derivatives and tert-butyl peroxy into water, adding a copper catalyst, reacting at room temperature for 6-12 hours, and separating and purifying to obtain 2, 3-dibromophenol or 2, 3-dibromophenol derivatives. Compared with the prior art, the synthesis process is simple and green, has excellent selectivity and higher yield, is simple in reaction post-treatment, and is environment-friendly and safe by taking water as a solvent. The invention has great application potential in the synthesis of medicaments, natural products and the like.
Description
Technical Field
The invention belongs to the technical field of synthetic chemistry, and relates to a high-efficiency synthesis method of 2, 3-dibromophenol or derivatives thereof.
Background
The phenol compound containing halogen atom substituent is an important organic synthesis and medical intermediate, and is widely applied to the fine chemical industry of synthetic medicines, pesticides and the like. Wherein the 2, 3-dibromophenol and the derivatives thereof are important intermediates for preparing alpha-amino acid derivatives and antispasmodics. At present, the synthesis methods of 2, 3-dibromophenol mainly comprise two methods: the first method is that m-bromophenol is used as a raw material reported by Sanz et al, and a target compound (J Org Chem,2005, 70, 6548) is obtained through four-step reaction, but the raw material in the synthetic route is expensive, the route is long, the yield is low, and the synthetic route is not suitable for industrial production; the second method is that o-dibromobenzene is used as a raw material and reacts with trifluoroacetic acid and triethylamine to obtain a target compound (Tetrahedron, 1996, 52, 3889), which is reported by Fujimoto et al, but the method has poor hydroxylation selectivity, generates a large amount of byproducts, has complex post-treatment and low yield, and is not suitable for industrial production. In addition, a method of preparing the boronic acid derivative through the halide by an indirect method and then oxidizing the boronic acid derivative into the corresponding phenolic compound has also been developed, but the yield of the boronic acid derivative in the first step is low, and the reaction raw material is expensive.
With the development of green synthetic chemistry, how to more efficiently realize the synthesis of 2, 3-dibromophenol and derivatives thereof has gradually attracted the attention of people, and has very important research significance.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a high-efficiency synthesis method of 2, 3-dibromophenol or derivatives thereof, which takes water as a solvent, has a simple and green synthesis process, and has excellent selectivity and high yield.
The purpose of the invention can be realized by the following technical scheme:
a high-efficiency synthesis method of 2, 3-dibromophenol or derivatives thereof comprises the following steps: o-dibromobenzene or o-dibromobenzene derivatives tert-butyl peroxy-alcohol ( t BuOOH) into water, adding a copper catalyst, reacting at room temperature for 6-12 hours, and separating and purifying to obtain the 2, 3-dibromophenol or the 2, 3-dibromophenol derivative.
Furthermore, the o-dibromobenzene derivative comprises one of 4-methyl o-dibromobenzene, 4-methoxy o-dibromobenzene, 4-nitro o-dibromobenzene or 4-dimethylamino o-dibromobenzene.
Further, the copper catalyst is copper acetylacetonate (Cu (acac) 2 )。
Furthermore, the mol ratio of the o-dibromobenzene or the o-dibromobenzene derivative, the tert-butyl peroxide and the copper catalyst is 1.0 (1.2-1.5) to 0.05-0.10.
Further, 0.4-0.6mmol of o-dibromobenzene or an o-dibromobenzene derivative is added to 1mL of water.
As a preferable technical scheme, when 2, 3-dibromophenol is synthesized, the molar ratio of the o-dibromobenzene to the t-butyl peroxy alcohol to the copper catalyst is 1.0 to 1.4, 0.5mmol of o-dibromobenzene is added in every 1mL of water, and the reaction time is 12 hours.
As a preferred technical scheme, when synthesizing the 2, 3-dibromophenol derivative, the mol ratio of the o-dibromobenzene derivative, the tert-butyl peroxide and the copper catalyst is 1.0 to 1.3, 0.5mmol of o-dibromobenzene is added into every 1mL of water, and the reaction time is 6 hours.
Further, the separation and purification process comprises the following steps: after the reaction is finished, the reaction solution is concentrated and then is subjected to column chromatography separation.
The invention is in copper catalyst Cu (acac) 2 In the presence of the catalyst, o-dibromobenzene and tert-butyl peroxide t BuOOH is added into water to react for 6 to 12 hours at room temperature, and then the mixture is separated and purified to obtain the 2, 3-dibromophenol or the derivatives thereof. The synthesis process is simple and green, has excellent selectivity and high yield, and is simple in post-reaction treatment.
Compared with the prior art, the invention has the following characteristics:
1) The synthetic method is simple and green, uses cheap and easily-obtained raw materials and catalysts, has excellent selectivity and high yield, and has great application potential in the synthesis of medicaments, natural products and the like.
2) The invention has mild reaction conditions and simple treatment after reaction, and can obtain corresponding products with high yield by a one-pot method at room temperature.
3) The invention uses water as solvent, which is environment-friendly and green.
Detailed Description
The present invention will be described in detail with reference to specific examples. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
Example 1:
sequentially adding 1.0mmol of o-dibromobenzene, t BuOOH(1.5mmol)、Cu(acac) 2 (0.05 mmol), then adding 2mL of solvent water, reacting for 6 hours at room temperature, concentrating the reaction solution after the reaction is finished, and carrying out column chromatography separation to obtain a corresponding product, wherein the separation yield is 88%. 1 H NMR(400MHz,CDCl 3 ) δ 7.21 (dd, J =7.2,1.5hz, 1h), 7.11 (t, J =7.5hz, 1h), 6.97 (dd, J =7.8,1.5hz, 1h), 5.67 (s, 1H). HRMS theoretical value C 6 H 4 Br 2 O(M) + :251.8608, actual measured value: 251.8611.
example 2:
sequentially adding 1.0mmol of o-dibromobenzene and, t BuOOH(1.2mmol)、Cu(acac) 2 (0.08 mmol), then adding 2mL of solvent water, reacting for 8 hours at room temperature, concentrating the reaction solution after the reaction is finished, and carrying out column chromatography separation to obtain a corresponding product, wherein the separation yield is 90%. 1 H NMR(400MHz,CDCl 3 ) δ 7.21 (dd, J =7.2,1.5hz, 1h), 7.11 (t, J =7.5hz, 1h), 6.97 (dd, J =7.8,1.5hz, 1h), 5.67 (s, 1H). HRMS theoretical value C 6 H 4 Br 2 O(M) + :251.8608, actual measurement: 251.8612.
example 3:
sequentially adding 1.0mmol of o-dibromobenzene and, t BuOOH(1.4mmol)、Cu(acac) 2 (0.10 mmol) and then 2mL of solvent water are added, the reaction is carried out for 12 hours at room temperature, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained by column chromatography separation, wherein the separation yield is 95%. 1 H NMR(400MHz,CDCl 3 ) δ 7.21 (dd, J =7.2,1.5hz, 1h), 7.11 (t, J =7.5hz, 1h), 6.97 (dd, J =7.8,1.5hz, 1h), 5.67 (s, 1H). HRMS theoretical value C 6 H 4 Br 2 O(M) + :251.8608, actual measured value: 251.8605.
example 4:
sequentially adding 1.0mmol of 4-methyl o-dibromobenzene, t BuOOH(1.5mmol)、Cu(acac) 2 (0.06 mmol) and then 2mL of solvent water are added, the reaction is carried out for 10 hours at room temperature, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained by column chromatography separation, wherein the separation yield is 93%. 1 H NMR(400MHz,CDCl 3 ) δ 7.23 (s, 1H), 7.16 (s, 1H), 5.72 (s, 1H), 2.23 (s, 3H). HRMS theoretical value C 7 H 6 Br 2 O(M) + :265.8765, actual measured value: 265.8768.
example 5:
sequentially adding 1.0mmol of 4-methoxy o-dibromobenzene, t BuOOH(1.2mmol)、Cu(acac) 2 (0.08 mmol) and then 2mL of solvent water are added, the reaction is carried out for 8 hours at room temperature, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained by column chromatography separation, wherein the separation yield is 91%. 1 H NMR(400MHz,CDCl 3 ) δ 7.29 (s, 1H), 7.20 (s, 1H), 5.76 (s, 1H), 3.52 (s, 3H). HRMS theoretical value C 7 H 6 Br 2 O 2 (M) + :281.8714, actual measurement: 281.8716.
example 6:
sequentially adding 1.0mmol of 4-nitro-o-dibromobenzene, t BuOOH(1.3mmol)、Cu(acac) 2 (0.10 mmol) and then 2mL of solvent water are added, the reaction is carried out for 6 hours at room temperature, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained by column chromatography separation, wherein the separation yield is 96%. 1 H NMR(400MHz,CDCl 3 ) δ 7.37 (s, 1H), 7.17 (s, 1H), 5.84 (s, 1H). HRMS theoretical value C 6 H 3 Br 2 NO 3 (M) + :296.8459, actual measurements: 296.8463.
example 7:
sequentially adding 1.0mmol of 4-dimethylamino o-dibromobenzene, t BuOOH(1.2mmol)、Cu(acac) 2 (0.10 mmol) and then 2mL of solvent water are added, the reaction is carried out for 12 hours at room temperature, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained by column chromatography separation, wherein the separation yield is 93%. 1 H NMR(400MHz,CDCl 3 ) δ 7.25 (s, 1H), 7.18 (s, 1H), 5.75 (s, 1H), 2.36 (s, 6H). HRMS theoretical value C 8 H 9 Br 2 NO(M) + :294.9030, actual measurement: 294.9026.
the embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make modifications and alterations without departing from the scope of the present invention.
Claims (6)
1. A method for synthesizing 2, 3-dibromophenol or derivatives thereof is characterized in that the method comprises the following steps: adding o-dibromobenzene or o-dibromobenzene derivatives and tert-butyl peroxide into water, adding a copper catalyst, reacting at room temperature for 6-12 hours, and separating and purifying to obtain 2, 3-dibromophenol or 2, 3-dibromophenol derivatives;
the o-dibromobenzene derivative comprises one of 4-methyl o-dibromobenzene, 4-methoxy o-dibromobenzene, 4-nitro o-dibromobenzene or 4-dimethylamino o-dibromobenzene;
the copper catalyst is copper acetylacetonate.
2. The method for synthesizing 2, 3-dibromophenol or derivatives thereof according to claim 1, wherein the molar ratio of the o-dibromobenzene or the o-dibromobenzene derivatives, the tert-butyl peroxy-alcohol and the copper catalyst is 1.0 (1.2-1.5) to (0.05-0.10).
3. The method for synthesizing 2, 3-dibromophenol or a derivative thereof according to claim 2, characterized in that 0.4-0.6mmol of o-dibromobenzene or an o-dibromobenzene derivative is added to every 1mL of water.
4. The method for synthesizing 2, 3-dibromophenol or derivatives thereof according to claim 3, wherein when synthesizing 2, 3-dibromophenol, the molar ratio of the o-dibromobenzene, the t-butyl peroxy alcohol and the copper catalyst is 1.0.
5. The method for synthesizing 2, 3-dibromophenol or derivatives thereof according to claim 3, wherein when synthesizing the 2, 3-dibromophenol derivatives, the molar ratio of the o-dibromophenol derivatives, the tert-butanol peroxide and the copper catalyst is 1.0.
6. The method for synthesizing 2, 3-dibromophenol or a derivative thereof according to claim 1, characterized in that the separation and purification process comprises: after the reaction is finished, the reaction solution is concentrated and then is subjected to column chromatography separation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911070668.2A CN110981702B (en) | 2019-11-05 | 2019-11-05 | Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911070668.2A CN110981702B (en) | 2019-11-05 | 2019-11-05 | Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110981702A CN110981702A (en) | 2020-04-10 |
| CN110981702B true CN110981702B (en) | 2022-10-14 |
Family
ID=70083376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911070668.2A Active CN110981702B (en) | 2019-11-05 | 2019-11-05 | Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110981702B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011162A (en) * | 2017-04-25 | 2017-08-04 | 湖南理工学院 | A kind of method that α acyloxy ketone compounds are prepared with end group acetylene compound |
-
2019
- 2019-11-05 CN CN201911070668.2A patent/CN110981702B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011162A (en) * | 2017-04-25 | 2017-08-04 | 湖南理工学院 | A kind of method that α acyloxy ketone compounds are prepared with end group acetylene compound |
Non-Patent Citations (4)
| Title |
|---|
| 2,3-二溴苯酚的合成;刘雪笛等;《化学研究与应用》;20180615;第30卷(第6期);第1012-1014页 * |
| Direct Hydroxylation and Amination of Arenes via Deprotonative Cupration;Tezuka, Noriyuki等;《Journal of the American Chemical Society》;20160627;第138卷(第29期);第9166-9171页 * |
| Product class: monohydric phenols and corresponding phenolates - synthesis by substitution;Gonzalez-Bello, C.等;《Science of Synthesis》;20071231(第31a期);第277-304页 * |
| Selective and one-pot formation of phenols by anodic oxidation;Fujimoto, Kazuo等;《Tetrahedron》;19960311;第52卷(第11期);第3889-3896页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110981702A (en) | 2020-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110627841B (en) | Iron complex containing m-carborane triazole ligand and preparation and application thereof | |
| WO2023109968A3 (en) | Synthesis method for finerenone and intermediate thereof | |
| CN110981702B (en) | Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof | |
| CN106349194B (en) | A kind of method of cinnamic acid derivative and cyclic ether compounds decarboxylation oxidative coupling | |
| CN114989063A (en) | Synthesis method of beta-halopyrrole compound | |
| CN105237466B (en) | A kind of method for synthesizing three substituted pyridine derivatives | |
| CN114409688A (en) | Synthetic method of 2-boronized benzothiazole derivative | |
| CN110642689B (en) | 3, 6-dibromo-2-methylbenzaldehyde and chemical synthesis method thereof | |
| CN110183453B (en) | Method for preparing 3-phenyl- [1,2,4] triazolo [4,3-a ] pyridine compound under catalysis of no metal | |
| CN108440378B (en) | Preparation method of iodine-hydrogen peroxide promoted 3-amino-2-indolone derivative at room temperature | |
| CN108409630B (en) | Preparation method of 3-hydroxy-2-indolone derivative in aqueous phase | |
| CN108675925B (en) | Production process of cyclopentanecarboxylic acid | |
| CN113754604A (en) | Nitrogen-containing chiral ligand and application thereof in asymmetric oxidation reaction of thioether | |
| CN116462619B (en) | Preparation method of cyclopentenone derivative | |
| CN116444382B (en) | Synthesis method of 4-iodo-2-methylaniline | |
| CN115894335B (en) | Method for synthesizing 2-phenylindole compound by utilizing alkyne halogen and aniline compound | |
| CN110437212B (en) | Synthesis method of N-2-alkyl substituted 1,2,3-triazole | |
| CN111943939B (en) | Synthesis method of chromanone compound and agricultural biological activity thereof | |
| CN109331876B (en) | Sodium-magnesium bimetallic catalyst and preparation method and application thereof | |
| CN110172034B (en) | Preparation method of arylethyl hydrogen peroxide | |
| CN108929226B (en) | Method for preparing benzoyl formate derivative | |
| JP3529876B2 (en) | 3-methyl-3-methoxybutanoic acid. | |
| JP3282357B2 (en) | Piperonal manufacturing method | |
| CN106366054B (en) | A kind of method of alpha, beta-unsaturated carboxylic acid and cyclic ether compounds decarboxylation oxidative coupling | |
| CN118184566A (en) | Preparation method of 1- [2- (1-methylindolyl) ] -2-naphthylamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |