WO2004014829A1 - Procedimiento de preparacion de 2, 4, 6-triyodofenol - Google Patents
Procedimiento de preparacion de 2, 4, 6-triyodofenol Download PDFInfo
- Publication number
- WO2004014829A1 WO2004014829A1 PCT/ES2002/000390 ES0200390W WO2004014829A1 WO 2004014829 A1 WO2004014829 A1 WO 2004014829A1 ES 0200390 W ES0200390 W ES 0200390W WO 2004014829 A1 WO2004014829 A1 WO 2004014829A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- triiodophenol
- preparation
- phenol
- preparing
- addition
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- VAPDZNUFNKUROY-UHFFFAOYSA-N 2,4,6-triiodophenol Chemical compound OC1=C(I)C=C(I)C=C1I VAPDZNUFNKUROY-UHFFFAOYSA-N 0.000 title claims abstract description 13
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GNOYQZRQXNVAKE-UHFFFAOYSA-N 2,4,6-triiodoaniline Chemical compound NC1=C(I)C=C(I)C=C1I GNOYQZRQXNVAKE-UHFFFAOYSA-N 0.000 description 1
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- -1 propyl alcohols Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
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
- C07C37/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Definitions
- the present invention relates to a new process for the preparation of 2, 6-triiodophenol (I), of formula I, (CAS Reg No. 609-23-4).
- 2, 4, 6-triiodophenol has been known for many years, e.g. Rosenthaler, C. Pharm. Act Helv. 1946, 21: 225. It is a yellowish powder, whose melting point is 158 ° C. It is poorly soluble in water, somewhat soluble in organic solvents, such as for example ethyl and propyl alcohols, acetone and sulfuric ether and is very soluble in chloroform and dichloromethane. It is also soluble in alkaline solutions.
- ES8602575 describes the preparation of 2,4,6-triiodophenol by reacting the phenol with periodic acid and potassium iodide in the presence of concentrated sulfuric acid.
- ES8605140 describes a process for the preparation of 2,4,6-triiodophenol from the reaction of 2,4,6-triiodoaniline with sodium nitrite, in an acid medium and at a low temperature, passing through the intermediate diazo derivative, which It is hydrolyzed to obtain the product.
- US3182089 describes a process for the preparation of phenolic compounds 2,4,6-triiodinated by the addition of iodine dissolved in N, N-dimethylformamide.
- DE1134084 describes the preparation of di- and triiodophenols by the addition of aqueous NH3 with ICl in aqueous NaCl to phenol.
- DD32567 describes the preparation of triiodophenols by treating a phenol solution with a suspension of iodine sprayed in aqueous NaCl.
- the compound of formula I is prepared by iodination of the phenol with potassium iodide in the presence of hydrogen peroxide in acetic medium.
- a three mouth reactor was charged, equipped with heating, stirring, reflux coolant, thermometer and funnel of addiction, with 15 1 acetic acid, then 1 Kg of phenol was introduced and 5.3 Kg of potassium iodide was loaded, after which the addition of 8 1 of hydrogen peroxide was carried out in 1 hour. After the addition was left under stirring for 6 hours from the start of the addition, the reaction crude was loaded into the centrifuge and 3 washes were performed, the first with water, the second with sodium bisulfite and the third with water.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
La presente invención se refiere a un nuevo procedimiento de preparación del 2, 4, 6-triyodofenol (I), de fórmula I, (CAS Reg No. 609-23-4).
Description
TITULO DE LA INVENCIÓN
Procedimiento de preparación de 2 , 4 , 6-triyodofenol
La presente invención se refiere a un nuevo procedimiento de preparación del 2 , , 6-triyodofenol (I), de fórmula I, (CAS Reg No. 609-23-4).
ESTADO DE LA TÉCNICA ANTERIOR
El 2 , 4 , 6-triyodofenol es conocido desde hace muchos años, p.e. Rosenthaler, C. Pharm. Acta Helv. 1946, 21: 225. Se trata de un polvo amarillento, cuyo punto de fusión es 158 °C. Es poco soluble en agua, algo soluble en disolventes orgánicos, como por ejemplo alcoholes etílico y propílico, acetona y éter sulfúrico y es muy soluble en cloroformo y diclorometano . También es soluble en soluciones alcalinas.
El interés comercial de este producto se debe a su acción farmacológica como inhibidor de la 5- lipooxigenasa, y por lo tanto útil como agente analgésico y antiinflamatorio.
En ES8507448 se describe un procedimiento de preparación a partir de la adicción de yodo al fenol en presencia de peróxido de hidrógeno en medio poco hidratante y ácido.
En ES8602575 se describe la preparación del 2 , 4 , 6-triyodofenol haciendo reaccionar el fenol con ácido peryodico y yoduro potásico en presencia de ácido sulfúrico concentrado.
En ES8605140 se describe un procedimiento de preparación de 2 , 4 , 6-triyodofenol a partir de la reacción de la 2 , 4 , 6-triyodoanilina con nitrito sódico, en medio ácido y a baja temperatura, pasando a través del diazoderivado intermedio, el cual se hidroliza para obtener el producto.
En US3182089 se describe un procedimiento de preparación de compuestos fenólicos 2 , 4 , 6-triiodados mediante la adicción de yodo disuelto en N,N- dimetilformamida .
En DE1134084 se describe la preparación de di- y triiodofenoles mediante la adicción de NH3 acuoso con ICl en NaCl acuoso al fenol.
En DD32567 se describe la preparación de triiodofenoles por tratamiento de una solución de fenol con una suspensión de yodo pulverizado en NaCl acuoso.
Todo ello nos ha inducido a desarrollar un nuevo procedimiento de preparación del 2 , 4 , 6-triiodofenol , que nos permite obtener el producto con gran pureza, mediante un proceso sencillo y con elevados rendimientos .
DESCRIPCIÓN DETALLADA DE LA INVENCIÓN
De acuerdo con el proceso descrito en la presente invención el compuesto de fórmula I se prepara mediante la yodación del fenol con yoduro potásico en presencia de peróxido de hidrógeno en medio acético.
Para facilitar la comprensión del procedimiento objeto de la presente invención, se presenta el ejemplo siguiente, el cual no debe considerarse como limitativo .
EJEMPLO 1.
Se cargó un reactor de tres bocas, provisto de calefacción, agitación, refrigerante a reflujo, termómetro y embudo de adicción, con 15 1 de ácido acético, a continuación se introdujo 1 Kg de fenol y se cargó 5,3 Kg de yoduro potásico, tras lo cual se realizó la adición de 8 1 de peróxido de hidrógeno en 1 hora. Finalizada la adición se dejó bajo agitación durante 6 horas contadas a partir del inicio de la adición, el crudo de reacción se cargó en la centrífuga y se realizaron 3 lavados, el primero con agua, el segundo con bisulfito sódico y el tercero con agua.
Tras filtrar y secar el precipitado, se recristalizó el crudo en isopropanol, obteniéndose un polvo amarillento de p.f.: 158 ± 1 °C y densidad aparente inferior a 0,8 g cm"3 . Se realizó un control del mismo por NIR por comparación con el registro de referencia para 2,4,6- triiodofenol, correspondiendo las bandas características .
Claims
1. Procedimiento para la obtención de 2,4,6- triiodofenol, de fórmula I:
caracterizado porque se hace reaccionar el fenol con yoduro potásico en presencia de peróxido de hidrógeno en medio acético.
2. Procedimiento para la obtención de 2,4,6- triiodofenol, según la reivindicación 1, caracterizado porque tras lavar el crudo de reacción y el posterior filtrado y secado del precipitado obtenido, se recristaliza en isopropanol .
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/ES2002/000390 WO2004014829A1 (es) | 2002-08-01 | 2002-08-01 | Procedimiento de preparacion de 2, 4, 6-triyodofenol |
| AU2002321320A AU2002321320A1 (en) | 2002-08-01 | 2002-08-01 | Method of preparing 2, 4, 6-triiodophenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/ES2002/000390 WO2004014829A1 (es) | 2002-08-01 | 2002-08-01 | Procedimiento de preparacion de 2, 4, 6-triyodofenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004014829A1 true WO2004014829A1 (es) | 2004-02-19 |
Family
ID=31502885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/ES2002/000390 WO2004014829A1 (es) | 2002-08-01 | 2002-08-01 | Procedimiento de preparacion de 2, 4, 6-triyodofenol |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2002321320A1 (es) |
| WO (1) | WO2004014829A1 (es) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658733A (zh) * | 2018-04-19 | 2018-10-16 | 国药集团化学试剂有限公司 | 一种2,4,6-三碘间苯二酚的制备方法 |
| CN114213268A (zh) * | 2021-12-27 | 2022-03-22 | 安康市农业科学研究院 | 一种泛影酸关键中间体的合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929907A (en) * | 1972-06-06 | 1975-12-30 | Degussa | Halogenation of phenolic compounds |
| EP0147892A2 (en) * | 1983-12-16 | 1985-07-10 | Bislak, S.A. | Process for preparing and therapeutical applications of the 2,4,6-triiodophenol |
-
2002
- 2002-08-01 AU AU2002321320A patent/AU2002321320A1/en not_active Abandoned
- 2002-08-01 WO PCT/ES2002/000390 patent/WO2004014829A1/es not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929907A (en) * | 1972-06-06 | 1975-12-30 | Degussa | Halogenation of phenolic compounds |
| EP0147892A2 (en) * | 1983-12-16 | 1985-07-10 | Bislak, S.A. | Process for preparing and therapeutical applications of the 2,4,6-triiodophenol |
Non-Patent Citations (2)
| Title |
|---|
| LUBBECKE ET AL.: "Halogenation of phenols with hydrogen halides/H2O2", TETRAHEDRON, vol. 34, 1978, pages 1577 - 1579 * |
| NOMEN ET AL.: "Optimization in fine chemistry: response surface of the reaction of triodination of phenol", AFINIDAD, vol. 45, 1988, pages 408 - 410 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658733A (zh) * | 2018-04-19 | 2018-10-16 | 国药集团化学试剂有限公司 | 一种2,4,6-三碘间苯二酚的制备方法 |
| CN108658733B (zh) * | 2018-04-19 | 2021-05-25 | 国药集团化学试剂有限公司 | 一种2,4,6-三碘间苯二酚的制备方法 |
| CN114213268A (zh) * | 2021-12-27 | 2022-03-22 | 安康市农业科学研究院 | 一种泛影酸关键中间体的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002321320A1 (en) | 2004-02-25 |
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