CN108373404B - Synthesis method of 4-iodoanisole - Google Patents
Synthesis method of 4-iodoanisole Download PDFInfo
- Publication number
- CN108373404B CN108373404B CN201810353390.9A CN201810353390A CN108373404B CN 108373404 B CN108373404 B CN 108373404B CN 201810353390 A CN201810353390 A CN 201810353390A CN 108373404 B CN108373404 B CN 108373404B
- Authority
- CN
- China
- Prior art keywords
- iodoanisole
- sodium
- iodine
- anisole
- sodium hypochlorite
- 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
- 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
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B7/00—Halogens; Halogen acids
- C01B7/24—Inter-halogen compounds
Abstract
The invention relates to the technical field of synthesis of drug intermediates, in particular to a method for synthesizing 4-iodoanisole, which takes phenyl ether as a substrate, and simultaneously dropwise adds a sodium hypochlorite solution and a sodium iodide solution according to a proportion, wherein high-activity fresh iodine chloride generated by the sodium hypochlorite and the sodium iodide is dissolved in an anisole layer and iodinated to generate a product; the byproduct hydrogen chloride enters the water layer and is neutralized by the byproduct sodium hydroxide of iodine chloride. Naturally splitting phases after the reaction is finished, wherein an organic phase is 4-iodoanisole and anisole; the 4-iodoanisole is obtained by post treatment. The method is a reaction extraction process, the iodizing agent-iodine chloride with high activity is generated and iodine is consumed instantly, and the iodine chloride by-product and the iodine by-product react to form sodium chloride instantly; the reaction is green, efficient, safe and controllable.
Description
Technical Field
The invention relates to the technical field of synthesis of drug intermediates, in particular to a synthesis method of 4-iodoanisole.
Background
4-iodoanisole is white needle crystal, has melting point of 51-52 deg.C and boiling point of 237 deg.C (96.8kPa), is soluble in organic solvent such as alcohol and ether, is insoluble in water, and can be easily separated to obtain iodine by light. 4-iodoanisole is an important general chemical reagent, is a key synthetic intermediate in pharmacy, liquid crystal, scientific research and the like, and has wide application in the field of organic synthesis.
4-iodoanisole is generally synthesized by the reflux reaction of anisole and iodine chloride in acetic acid. Iodine chloride is a toxic, corrosive, volatile solid, sensitive to air, light and moisture, and releases HCl gas when meeting water; unstable, and difficult to obtain a source of stable quality.
Disclosure of Invention
The invention aims to provide a method for synthesizing 4-iodoanisole, which solves the problems of complex synthetic route, unstable reactant iodine chloride and the like in the prior art.
In order to achieve the purpose, the invention provides the following technical scheme:
a synthetic method of 4-iodoanisole comprises the following steps:
(1) preparing a NaI aqueous solution A and a sodium hypochlorite aqueous solution B for later use;
(2) adding anisole into a four-neck flask, and heating to 60-70 ℃ under stirring; then, under stirring, simultaneously dropwise adding a sodium iodide solution and a sodium hypochlorite solution, wherein the molar ratio of sodium iodide to sodium hypochlorite is 1:1 to 1.1; the molar ratio of the anisole to the sodium iodide is 2.5-3: 1;
(3) after the dropwise addition, heating to 75-80 ℃, and stirring for 1 hour to obtain a light yellow reaction solution; cooling to room temperature, standing and phase splitting; washing the organic phase with water, drying and filtering to obtain an anisole solution of 4-iodoanisole, rectifying, cooling and solidifying to obtain white blocky crystals, namely 4-iodoanisole.
The invention discloses a synthesis method of 4-iodoanisole, wherein in the step (1), the mass fraction of NaI aqueous solution A is 20%.
The invention discloses a synthesis method of 4-iodoanisole, wherein in the step (1), the mass fraction of a sodium hypochlorite aqueous solution B is 8-10%.
The invention discloses a synthesis method of 4-iodoanisole, wherein in the step (2), the molar ratio of anisole to sodium iodide is 2.7-2.8: 1.
the invention relates to a synthesis method of 4-iodoanisole, wherein in the step (2), the molar ratio of sodium iodide to sodium hypochlorite is 1: 1.05.
the reaction equation of the present invention is as follows:
HCl+NaOH→H2O+NaCl
compared with the prior art, the invention has the beneficial effects that:
(1) the invention uses sodium hypochlorite and sodium iodide which are manufactured in scale, are relatively safe and environment-friendly as iodinating reagents, uses water as a reaction medium, abandons toxic, corrosive, volatile, rotten and unstable iodine chloride and organic acid (acetic acid) reaction media, has safe and controllable reaction, and is simple and convenient in post-treatment, environment-friendly, safe, environment-friendly and efficient in preparation of 4-iodoanisole.
(2) The method for synthesizing 4-iodoanisole is a reactive extraction process, the iodizing agent, namely iodine chloride with high activity is generated and iodine is consumed instantly, and an iodine chloride byproduct and an iodine byproduct react instantly to form sodium chloride; the reaction is green, efficient, safe and controllable.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A synthetic method of 4-iodoanisole comprises the following steps:
(1) preparing 2 moles of a 20% NaI aqueous solution A and 2.1 moles of a 8-10% sodium hypochlorite aqueous solution B for later use;
(2) adding 900g of anisole into a 2L four-neck round-bottom flask which is provided with a stirring device, a temperature display device and two constant-pressure dropping funnels, and heating to 60-70 ℃ under stirring; then, under stirring, dropwise adding a sodium iodide solution and a sodium hypochlorite solution at the same time according to the molar ratio of 1: 1.05;
(3) after the dropwise addition, heating to 75-80 ℃, and stirring for 1 hour to obtain a light yellow reaction solution; cooling to room temperature, standing and phase splitting; washing the organic phase with water, drying and filtering to obtain an anisole solution of 4-iodoanisole, rectifying, cooling and solidifying to obtain white massive crystals, namely 4-iodoanisole, the content of which is more than or equal to 98.5 percent, and the yield of which is 93.4 percent.
Example 2
A synthetic method of 4-iodoanisole comprises the following steps:
(1) preparing 2 moles of a 20% NaI aqueous solution A and 2 moles of a 8-10% sodium hypochlorite aqueous solution B for later use;
(2) adding 800g of anisole into a 2L four-neck round-bottom flask which is provided with a stirring device, a temperature display device and two constant-pressure dropping funnels, and heating to 60-70 ℃ under stirring; then, under stirring, dropwise adding a sodium iodide solution and a sodium hypochlorite solution at the same time according to the molar ratio of 1: 1;
(3) after the dropwise addition, heating to 75-80 ℃, and stirring for 1 hour to obtain a light yellow reaction solution; cooling to room temperature, standing and phase splitting; washing the organic phase with water, drying and filtering to obtain an anisole solution of 4-iodoanisole, rectifying, cooling and solidifying to obtain white massive crystals, namely 4-iodoanisole, the content of which is more than or equal to 97 percent, and the yield of which is 91.2 percent.
Example 3
A synthetic method of 4-iodoanisole comprises the following steps:
(1) preparing 2 moles of a 20% NaI aqueous solution A and 2.2 moles of a 8-10% sodium hypochlorite aqueous solution B for later use;
(2) adding 770g of anisole into a 2L four-neck round-bottom flask with stirring, temperature display and two constant-pressure dropping funnels, and heating to 60-70 ℃ under stirring; then, under stirring, dropwise adding a sodium iodide solution and a sodium hypochlorite solution at the same time according to the molar ratio of 1: 1.1;
(3) after the dropwise addition, heating to 75-80 ℃, and stirring for 1 hour to obtain a light yellow reaction solution; cooling to room temperature, standing and phase splitting; washing the organic phase with water, drying and filtering to obtain an anisole solution of 4-iodoanisole, rectifying, cooling and solidifying to obtain white massive crystals, namely 4-iodoanisole, the content of which is more than or equal to 97 percent, and the yield of which is 90.6 percent.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (2)
1. A synthetic method of 4-iodoanisole is characterized by comprising the following steps:
(1) preparing a NaI aqueous solution A and a sodium hypochlorite aqueous solution B for later use; the mass fraction of the NaI aqueous solution A is 20 percent; the mass fraction of the sodium hypochlorite aqueous solution B is 8-10%;
(2) adding anisole into a four-neck flask, and heating to 60-70 ℃ under stirring; then, under stirring, simultaneously dropwise adding a sodium iodide solution and a sodium hypochlorite solution, wherein the molar ratio of sodium iodide to sodium hypochlorite is 1:1 to 1.1; the molar ratio of the anisole to the sodium iodide is 25: 6. 100, and (2) a step of: 27 or 385: 108;
(3) after the dropwise addition, heating to 75-80 ℃, and stirring for 1 hour to obtain a light yellow reaction solution; cooling to room temperature, standing and phase splitting; washing the organic phase with water, drying and filtering to obtain an anisole solution of 4-iodoanisole, rectifying, cooling and solidifying to obtain white blocky crystals, namely 4-iodoanisole.
2. The method for synthesizing 4-iodoanisole according to claim 1, characterized in that: in the step (2), the molar ratio of sodium iodide to sodium hypochlorite is 1: 1.05.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810353390.9A CN108373404B (en) | 2018-04-19 | 2018-04-19 | Synthesis method of 4-iodoanisole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810353390.9A CN108373404B (en) | 2018-04-19 | 2018-04-19 | Synthesis method of 4-iodoanisole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108373404A CN108373404A (en) | 2018-08-07 |
| CN108373404B true CN108373404B (en) | 2021-07-27 |
Family
ID=63032368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810353390.9A Active CN108373404B (en) | 2018-04-19 | 2018-04-19 | Synthesis method of 4-iodoanisole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108373404B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011236087A (en) * | 2010-05-11 | 2011-11-24 | Toho Earthtech Inc | Method for producing iodine monochloride aqueous solution |
| CN106432037A (en) * | 2015-08-05 | 2017-02-22 | 国药集团化学试剂有限公司 | Pollution-free preparation method of N-bromosuccinimide |
| CN107722106A (en) * | 2016-08-11 | 2018-02-23 | 重庆大学 | Hiv inhibitor |
-
2018
- 2018-04-19 CN CN201810353390.9A patent/CN108373404B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011236087A (en) * | 2010-05-11 | 2011-11-24 | Toho Earthtech Inc | Method for producing iodine monochloride aqueous solution |
| CN106432037A (en) * | 2015-08-05 | 2017-02-22 | 国药集团化学试剂有限公司 | Pollution-free preparation method of N-bromosuccinimide |
| CN107722106A (en) * | 2016-08-11 | 2018-02-23 | 重庆大学 | Hiv inhibitor |
Non-Patent Citations (3)
| Title |
|---|
| Studies on the Structure of Colchicine. Syntheses in the Biphenyl Series;H. Richard Frank等;《Journal of the American Chemical Society》;19480731;第70卷;第2314-2320页 * |
| 次卤酸法合成卤代苯氧乙酸的研究（I）4-碘苯氧乙酸（增产灵）的合成;黄建全等;《福州大学学报》;19790615;第61-70页 * |
| 碘代丙炔基正丁氨基甲酸酯的合成研究;徐守林;《精细化工中间体》;20101031;第40卷(第5期);第58-60页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108373404A (en) | 2018-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106187852A (en) | A kind of preparation method of Vonoprazan fumarate intermediate | |
| TWI529176B (en) | A method for producing an ionic metal complex salt containing an organic compound as a complex | |
| CN111454286A (en) | Synthetic method of difluoroalkenyl boron compound | |
| CN108373404B (en) | Synthesis method of 4-iodoanisole | |
| CN104557683A (en) | Preparation method of 2,3-dichloro-5-trifluoromethylpyridine | |
| CN110878104A (en) | Preparation method of chiral 1, 2-bis (2, 5-diphenylphosphino) ethane | |
| CN107324964B (en) | Synthetic method of biphenyl derivative | |
| CN102718662A (en) | Method for preparing cinacalcet hydrochloride | |
| CN103044473B (en) | Method for preparing cyclopropylboric acid | |
| CN104447506B (en) | The preparation method of the alkyl carbazole of 2 acetyl group 9 | |
| JP2005170946A (en) | Process for preparing alkoxy-pure alkaline earth alkoxide | |
| CN104151170A (en) | 4-nitrophenethylamine hydrochloride and preparation method thereof | |
| CN109912396B (en) | Synthetic method of 3-bromo-4-fluorobenzaldehyde | |
| CN103420819B (en) | Method for preparing pesticide midbody 2,2-dichloro-3,3,3-trifluoro-propionaldehyde | |
| CN106810423B (en) | Preparation method of pentafluorophenol | |
| CN104370961B (en) | The method of iso-octyl phosphine monooctyl acid monooctyl ester is prepared in a kind of phase transfer catalysis (PTC) hydrolysis | |
| CN108947868B (en) | Preparation process of 2, 4-difluorobenzonitrile | |
| CN112778089B (en) | New synthetic method of 4, 4-trifluoro-1-butanol and homologs thereof | |
| CN106977535A (en) | One kind synthesis fluorobenzoic boric acid technique of 2 cyano group 3 | |
| CN103265399A (en) | Catalyst-based chlorinated neopentane preparation technology | |
| CN107200751B (en) | Preparation method of macrocyclic dimethyl siloxane compound | |
| CN100491322C (en) | Method for synthesizing tetrapion by hydrogen peroxide solution method | |
| CN108084217A (en) | A kind of preparation method of 2,6- dichloros phenyl boric acid | |
| CN102603777A (en) | Preparation method of nysted reagent | |
| CN102515997B (en) | Method for preparing dimethyl carbonate derivate with ionic liquid as reaction medium |
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 |