CN114262263A - Preparation method of 4-iodophenol - Google Patents
Preparation method of 4-iodophenol Download PDFInfo
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- CN114262263A CN114262263A CN202111630920.8A CN202111630920A CN114262263A CN 114262263 A CN114262263 A CN 114262263A CN 202111630920 A CN202111630920 A CN 202111630920A CN 114262263 A CN114262263 A CN 114262263A
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- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 25
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 23
- 239000010703 silicon Substances 0.000 claims abstract description 23
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000011630 iodine Substances 0.000 claims abstract description 21
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000006266 etherification reaction Methods 0.000 claims abstract description 19
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006192 iodination reaction Methods 0.000 claims abstract description 18
- 239000000126 substance Substances 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 230000009471 action Effects 0.000 claims abstract description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 3
- 238000002444 silanisation Methods 0.000 claims abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 230000007062 hydrolysis Effects 0.000 claims description 19
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 13
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 12
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 claims description 6
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 6
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 5
- MCMFEZDRQOJKMN-UHFFFAOYSA-N 1-butylimidazole Chemical compound CCCCN1C=CN=C1 MCMFEZDRQOJKMN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- IWDFHWZHHOSSGR-UHFFFAOYSA-N 1-ethylimidazole Chemical compound CCN1C=CN=C1 IWDFHWZHHOSSGR-UHFFFAOYSA-N 0.000 claims description 3
- KWYZNESIGBQHJK-UHFFFAOYSA-N chloro-dimethyl-phenylsilane Chemical compound C[Si](C)(Cl)C1=CC=CC=C1 KWYZNESIGBQHJK-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- WBJZTOZJJYAKHQ-UHFFFAOYSA-K iron(3+) phosphate Chemical compound [Fe+3].[O-]P([O-])([O-])=O WBJZTOZJJYAKHQ-UHFFFAOYSA-K 0.000 claims description 3
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 3
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000005955 Ferric phosphate Substances 0.000 claims description 2
- 229940032958 ferric phosphate Drugs 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229910000399 iron(III) phosphate Inorganic materials 0.000 claims description 2
- 238000005475 siliconizing Methods 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 238000000967 suction filtration Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- LRMHFDNWKCSEQU-UHFFFAOYSA-N ethoxyethane;phenol Chemical compound CCOCC.OC1=CC=CC=C1 LRMHFDNWKCSEQU-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006884 silylation reaction Methods 0.000 description 3
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- RKORKXFKXYYHAQ-UHFFFAOYSA-N 2-(4-iodophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(I)C=C1 RKORKXFKXYYHAQ-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical class [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 ferric iron salt Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 229910000398 iron phosphate Inorganic materials 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- DEBPSHDHSJWLHY-UHFFFAOYSA-M potassium;methanol;iodide Chemical compound [K+].[I-].OC DEBPSHDHSJWLHY-UHFFFAOYSA-M 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- OJAJJFGMKAZGRZ-UHFFFAOYSA-N trimethyl(phenoxy)silane Chemical compound C[Si](C)(C)OC1=CC=CC=C1 OJAJJFGMKAZGRZ-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 4-iodophenol, which comprises the following steps: under the action of N-alkyl imidazole, phenol and a silanization reagent are subjected to a silicon etherification reaction; after the silicon etherification reaction is finished, adding trivalent ferric salt and iodine simple substance to carry out iodination reaction; and after the iodination reaction is finished, hydrolyzing and post-treating to obtain the 4-iodophenol. The preparation method of the 4-iodophenol provided by the invention is a one-pot method, the reaction raw materials are easy to obtain, no organic solvent is used in the whole process, the preparation method is environment-friendly and environment-friendly, the raw material utilization rate is high, the yield is high, the operation conditions of each step are mild, and the industrial production is facilitated.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 4-iodophenol.
Background
4-iodophenol is an important organic synthetic intermediate, for example, 4-iodophenol is condensed with chloroacetic acid to obtain p-iodophenoxyacetic acid, which can be used as a plant growth regulator, for fattening pigs, etc.
The existing synthesis method of 4-iodophenol mainly comprises the following steps: (1) the 4-iodophenol is generated by diazotizing and replacing p-aminophenol which is used as a raw material. (2) And (3) slowly adding an oxidant into the phenylboronic acid and the potassium iodide methanol solution, and reacting to obtain the 4-iodophenol. (3) Phenol is used as a raw material, phenolic hydroxyl is protected by acetyl chloride or methanesulfonyl chloride, iodine monochloride or an iodine simple substance is used as an iodine reagent, and then the protection is carried out under the alkaline condition after iodine is added into dichloromethane or glacial acetic acid, so as to prepare the 4-iodophenol.
The method (1) needs to prepare the diazonium salt intermediate which is active in property and easy to decompose, is complex to operate and difficult to control, has a plurality of byproducts, low yield, high three wastes and is not environment-friendly; the methods (2) and (3) have the disadvantages of more reaction byproducts, low yield and difficult separation and purification.
Therefore, it is an urgent technical problem to provide a method for preparing 4-iodophenol, which has high yield, simple operation and easy control.
Disclosure of Invention
In view of this, the invention provides a preparation method of 4-iodophenol, which is simple to operate, easy to control and high in yield.
In order to achieve the purpose of the invention, the embodiment of the invention adopts the following technical scheme:
a preparation method of 4-iodophenol comprises the following steps:
under the action of N-alkyl imidazole, phenol and a silanization reagent are subjected to a silicon etherification reaction;
after the silicon etherification reaction is finished, directly adding trivalent ferric salt and iodine simple substance to carry out iodination reaction;
and after the iodination reaction is finished, hydrolyzing and post-treating to obtain the 4-iodophenol.
The invention aims to solve the technical problems that the existing method for synthesizing 4-iodophenol has complex operation, is difficult to control, has a plurality of byproducts and is difficult to separate and purify in the preparation process. The improvement of the existing synthesis method aiming at 4-iodophenol is only limited to the optimization of the existing several synthesis routes, but basically has no effect: the yield can reach about 75 percent at most, and an organic solvent is required in the preparation process.
The invention departs from the synthesis thought in the prior art, creatively adopts specific N-alkyl imidazole as an acid-binding agent to promote the silylation reagent to carry out the silicon etherification reaction with the hydroxyl in the phenol to realize the protection of the hydroxyl in the phenol, generates trialkyl silicon-based phenol ether and N-alkyl imidazole hydrochloride after the silicon etherification reaction is finished, generates 4-iodine trialkyl silicon-based phenol ether by the reaction of the trialkyl silicon-based phenol ether and iodine simple substance under the compounding action of the N-alkyl imidazole hydrochloride and trivalent ferric salt, and obtains the 4-iodine phenol after the hydrolysis deprotection of the 4-iodine trialkyl silicon-based phenol ether. The silicon etherification reaction and the iodination reaction do not use an organic solvent, the reaction raw material itself can be used as a solvent, and water added in the hydrolysis step can be used as both a reactant and a solvent.
In addition, the preparation method of the 4-iodophenol provided by the invention is a one-pot method, the subsequent reaction is directly carried out without post-treatment after the silicon etherification reaction and the iodination reaction are finished, and particularly, the yield of the final product, namely the 4-iodophenol, can be greatly reduced if the post-treatment is carried out after the silicon etherification reaction is finished. In addition, reaction raw materials involved in the whole reaction are easy to obtain, and byproducts (aqueous solution containing N-alkyl imidazole hydrochloride and ferric iron salt) can be subjected to subsequent reaction to prepare other types of ionic liquids, so that new economic benefits are generated. The method has the advantages of high raw material utilization rate, high yield, stable process, simple operation, no use of organic solvent in the whole process and environmental friendliness. Therefore, the invention opens up a brand new reaction route for the synthesis of the 4-iodophenol, not only improves the yield and the purity of the product, but also has mild operation conditions of each step, low cost, no waste generation, environmental protection and contribution to industrial production.
The inventor further finds that if imidazole or other acid-binding agents are used for replacing N-alkyl imidazole, other trivalent metal salts or divalent metal salts are used for replacing trivalent iron salts, or other iodine reagents are used for replacing iodine simple substances, the target product 4-iodophenol cannot be obtained finally, or the yield of the target product 4-iodophenol is low and can only reach about 60%.
Optionally, the silicon etherification reaction comprises the following steps:
the silylating agent is added dropwise to the mixture of N-alkyl imidazole and phenol.
Optionally, the molar ratio of the phenol, the silylation agent and the N-alkyl imidazole is 1 (1-1.1) to 1-1.2.
Optionally, the temperature of the silicon etherification reaction is 0 to 50 ℃.
Optionally, the molar ratio of the phenol, the iodine elementary substance and the ferric iron salt is 1 (0.5-0.55) to (0.35-0.5).
Optionally, the temperature of the iodination reaction is 20-50 ℃.
Optionally, the hydrolysis comprises the following steps:
water was added to the system after completion of the iodination reaction.
Optionally, the mass-to-volume ratio of the ferric salt to the water added in the hydrolysis step is 1g (3-5) mL.
Optionally, the temperature of the hydrolysis step is 20-50 ℃.
Optionally, the hydrolysis reaction time is 20-100 min.
The reaction yield and the product purity can be further improved by limiting parameters such as the consumption of reaction raw materials, the reaction temperature and the like in each step, the yield of the 4-iodophenol can reach more than 90 percent, and the purity is more than 99.6 percent.
Optionally, the silylation reagent is at least one of trimethylchlorosilane, triethylchlorosilane, tert-butyldimethylchlorosilane, phenyldimethylchlorosilane and triisopropylchlorosilane;
the N-alkyl imidazole is at least one of N-methyl imidazole, N-ethyl imidazole and N-butyl imidazole;
the ferric salt is at least one of anhydrous ferric trichloride, anhydrous ferric sulfate, anhydrous ferric nitrate and anhydrous ferric phosphate.
Optionally, the post-treatment step comprises filtering and drying;
the drying temperature is 40-60 ℃ and the drying time is 4-6 h.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
Example 1
The embodiment provides a preparation method of 4-iodophenol, which comprises the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 196.8g (2.4mol) of N-methylimidazole are added into a 2000mL three-necked bottle, then 238.9g (2.2mol) of trimethylchlorosilane are dropwise added, the temperature of the system is controlled to be 0-5 ℃ by using an ice-water bath, after the dropwise addition is finished, the reaction is continued for 1h at the temperature until the silicon etherification reaction is finished, 193.6g (0.8mol) of anhydrous ferric nitrate solid and 254.0g (1.0mol) of iodine simple substance are directly added, then the temperature of the system is controlled to be increased to 20-25 ℃ by using the water bath, the reaction is carried out for 4h at the temperature until the iodination reaction is finished, 600mL of water is directly added into the system, the temperature of the system is controlled to be stirred for 30min at 40-45 ℃ until the hydrolysis is finished, 4-iodophenol is continuously separated out in the hydrolysis process, suction filtration is carried out after the hydrolysis reaction is finished, drying is carried out for 6h at 50 ℃ to obtain 404.9g of white-like powder, yield 92.0% and HPLC purity 99.64%.
1H-NMR(400MHz，CDCl3)δ(ppm)：4.68(s,1H),6.63(d,J 8.8Hz,2H),7.52(d,J 8.8Hz,2H)；
MS(EI)m/z:[M]220。
Example 2
The embodiment provides a preparation method of 4-iodophenol, which comprises the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 192.0g (2.0mol) of N-ethylimidazole are added into a 2000mL three-necked bottle, then 302.0g (2.0mol) of triethylchlorosilane is dropwise added, the temperature of the system is controlled to be 45-50 ℃ by using a water bath, after the dropwise addition is finished, the reaction is continued at the temperature for 1h until the silicon etherification reaction is finished, 110.0g (0.73mol) of anhydrous iron phosphate solid and 279.0g (1.1mol) of iodine simple substance are directly added, then the reaction is continued at the temperature for 4h until the iodination reaction is finished, 550mL of water is directly added into the system, the temperature of the water bath is controlled to be 20-25 ℃ and stirred for 100min until the hydrolysis is finished, 4-iodophenol is continuously separated out in the hydrolysis process, after the hydrolysis reaction is finished, suction filtration is carried out, the drying is carried out at 55 ℃ for 4h, and then 402.9g of white-like powder, the yield is 91.6%, and the purity of HPLC is 99.72%.
Example 3
The embodiment provides a preparation method of 4-iodophenol, which comprises the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 272.8g (2.2mol) of N-butylimidazole are added into a 2000mL three-necked bottle, 360.0g (2.1mol) of phenyldimethylchlorosilane are dropwise added, the temperature of the system is controlled to be 20-25 ℃ by using a water bath, after the dropwise addition is finished, the reaction is continued for 1h at the temperature until the silicon etherification reaction is finished, 162.0g (1.0mol) of anhydrous ferric trichloride solid and 270.0g (1.06mol) of iodine simple substance are directly added, the temperature of the system is controlled to be increased to 30-35 ℃ by using the water bath, 700mL of water is directly added into the system after the iodination reaction is finished, the temperature of the system is controlled to be 30-35 ℃ and stirred for 60min until the hydrolysis is finished, 4-iodophenol is continuously separated out in the hydrolysis process, suction filtration is carried out after the hydrolysis reaction is finished, drying is carried out for 5h at 45 ℃, and white-like powder 4-iodophenol 409.6g is obtained, the yield was 93.1% and the HPLC purity was 99.81%.
Example 4
Under the protection of nitrogen, 188.0g (2.0mol) of phenol and 196.8g (2.4mol) of N-methylimidazole are added into a 2000mL three-necked bottle, 331.5g (2.2mol) of tert-butyldimethylchlorosilane are added in batches, the temperature of the system is controlled to be 0-5 ℃ by using an ice-water bath, after the dropwise addition is finished, the reaction is continued for 1h at the temperature until the silicon etherification reaction is finished, 193.6g (0.8mol) of anhydrous ferric nitrate solid and 254.0g (1.0mol) of iodine simple substance are directly added, then the temperature of the system is controlled to be increased to 50 ℃ by the water bath, after the iodination reaction is finished, 600mL of water is directly added into the system, the temperature of the system is controlled to be 20-25 ℃ and stirred for 30min until the hydrolysis is finished, 4-iodophenol is continuously separated out in the hydrolysis process, suction filtration is carried out after the hydrolysis reaction is finished, drying is carried out for 6h at 60 ℃, and white-like powder 4-iodophenol 406.6g is obtained, yield 92.4% and HPLC purity 99.65%.
Example 5
The embodiment provides a preparation method of 4-iodophenol, which comprises the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 272.8g (2.2mol) of N-butylimidazole are added into a 3000mL three-necked bottle, then 238.9g (2.2mol) of trimethylchlorosilane are dropwise added, the temperature of the system is controlled to be 0-5 ℃ by using an ice-water bath, after the dropwise addition is finished, the reaction is continued for 1h at the temperature till the end of the silicon etherification reaction, 320.0g (0.8mol) of anhydrous ferric sulfate solid and 254.0g (1.0mol) of iodine simple substance are directly added, then the temperature of the system is controlled to be increased to 20-25 ℃ by the water bath, the reaction is carried out for 4h at the temperature till the end of the iodination reaction, 1000mL of water is directly added into the system, the temperature of the system is controlled to be stirred for 30min at 40 ℃ till the hydrolysis is completed, 4-iodophenol is continuously separated out in the hydrolysis process, suction filtration is carried out after the hydrolysis reaction is finished, drying is carried out for 6h at 40 ℃ to obtain 4-iodophenol 2g of white-like powder, the yield is 93.9%, HPLC purity 99.77%.
Comparative example 1
The comparative example provides a preparation method of 4-iodophenol, comprising the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 196.8g (2.4mol) of N-methylimidazole are added into a 2000mL three-necked bottle, then 238.9g (2.2mol) of trimethylchlorosilane are dropwise added, the temperature of the system is controlled to be 0-5 ℃ by using an ice-water bath, after the dropwise addition is finished, the reaction is continued for 1h at the temperature until the silicon etherification reaction is finished, dichloromethane is used for extracting reaction liquid (400mL multiplied by 3) after the reaction is finished, the organic phase of dichloromethane is combined, water washing (100mL multiplied by 2) is carried out, the organic phase of dichloromethane is dried, thus obtaining dichloromethane solution containing trimethylsiloxybenzene, then 193.6g (0.8mol) of anhydrous ferric nitrate solid and 254.0g (1.0mol) of iodine simple substance are added into the solution, then the water bath is controlled to carry out reflux reaction for 6h until the iodination reaction is finished, 600mL of water is added into the system, after the liquid separation, the organic phase is steamed, hydrochloric acid aqueous solution (200mL concentrated hydrochloric acid is added into 400mL of the obtained concentrate, stirring at 40 deg.C for 30min until hydrolysis reaction is completed, separating liquid, washing organic phase with water, recrystallizing with petroleum ether, filtering, and drying at 60 deg.C for 6 hr to obtain white powder of 4-iodophenol 318.3g, with yield of 72.3% and HPLC purity of 98.43%.
Comparative example 2
The comparative example provides a preparation method of 4-iodophenol, comprising the following specific steps:
under the protection of nitrogen, 188.0g (2.0mol) of phenol and 189.6g (2.4mol) of pyridine are added into a 2000mL three-necked bottle, 238.9g (2.2mol) of trimethylchlorosilane is dropwise added, the temperature of the system is controlled to be 0-5 ℃ by using an ice-water bath, the reaction is continued for 1h at the temperature after the dropwise addition is finished, 193.6g (0.8mol) of anhydrous ferric nitrate solid and 254.0g (1.0mol) of iodine simple substance are directly added into the system, the temperature of the system is controlled to be increased to 20-25 ℃ by using the water bath, the reaction is carried out for 4h at the temperature until the iodination reaction is finished, 600mL of water is directly added into the system, the temperature of the system is controlled to be stirred for 30min at 40-45 ℃ until the hydrolysis is finished, 4-iodophenol is separated out in the hydrolysis process, the suction filtration is carried out after the hydrolysis reaction is finished, the drying is carried out for 6h at 50 ℃, the white-like powder 4-iodophenol 272.8g is obtained, the yield is 62.0, HPLC purity 94.62%.
Comparative example 3
This comparative example is similar to example 1 except that no ferric nitrate anhydrous solid was added, and no target 4-iodophenol was detected by adding elemental iodine, raising the temperature to 45-50 c and extending the reaction time.
Comparative example 4
This comparative example is similar to example 1 except that anhydrous copper sulfate was used instead of anhydrous ferric nitrate solid, and the target 4-iodophenol was not detected when the temperature was raised to 45-50 ℃ and the reaction time was prolonged after the addition of elemental iodine.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The preparation method of the 4-iodophenol is characterized by comprising the following steps:
under the action of N-alkyl imidazole, phenol and a silanization reagent are subjected to a silicon etherification reaction;
after the silicon etherification reaction is finished, directly adding trivalent ferric salt and iodine simple substance to carry out iodination reaction;
and after the iodination reaction is finished, hydrolyzing and post-treating to obtain the 4-iodophenol.
2. The method of claim 1, wherein the molar ratio of the phenol, the silylating agent and the N-alkylimidazole is 1 (1-1.1) to 1-1.2.
3. The process for producing 4-iodophenol according to claim 1, wherein the temperature of the siliconizing reaction is 0 to 50 ℃.
4. The method of claim 1, wherein the molar ratio of phenol, the iodine, and the ferric salt is 1 (0.5-0.55) to (0.35-0.5).
5. The process for producing 4-iodophenol according to claim 1, wherein the temperature of the iodination reaction is 20 to 50 ℃.
6. The method of claim 1, wherein the mass-to-volume ratio of the ferric salt to the water added in the hydrolysis step is 1g (3-5) mL.
7. The method of preparing 4-iodophenol according to claim 1, wherein the temperature of said hydrolysis step is 20 to 50 ℃.
8. The method of claim 1, wherein the hydrolysis reaction time is 20-100 min.
9. The process for producing 4-iodophenol according to claim 1, wherein the silylating agent is at least one of trimethylchlorosilane, triethylchlorosilane, t-butyldimethylchlorosilane, phenyldimethylchlorosilane and triisopropylchlorosilane; and/or
The N-alkyl imidazole is at least one of N-methyl imidazole, N-ethyl imidazole and N-butyl imidazole; and/or
The ferric salt is at least one of anhydrous ferric trichloride, anhydrous ferric sulfate, anhydrous ferric nitrate and anhydrous ferric phosphate.
10. The process for the preparation of 4-iodophenol according to any one of claims 1 to 9, wherein the post-treatment step comprises filtration, drying;
the drying temperature is 40-60 ℃ and the drying time is 4-6 h.
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