CN113292391B - Preparation method of 2-bromoiodobenzene - Google Patents
Preparation method of 2-bromoiodobenzene Download PDFInfo
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- CN113292391B CN113292391B CN202110653214.9A CN202110653214A CN113292391B CN 113292391 B CN113292391 B CN 113292391B CN 202110653214 A CN202110653214 A CN 202110653214A CN 113292391 B CN113292391 B CN 113292391B
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- bromoiodobenzene
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- triphenylphosphine
- bromophenol
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- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000003756 stirring Methods 0.000 claims abstract description 25
- 150000001412 amines Chemical class 0.000 claims abstract description 17
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 239000011261 inert gas Substances 0.000 claims abstract description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 3
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000001914 filtration Methods 0.000 claims abstract description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 13
- 229910052740 iodine Inorganic materials 0.000 claims description 13
- 239000011630 iodine Substances 0.000 claims description 13
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims description 6
- 238000004321 preservation Methods 0.000 claims description 4
- 239000000047 product Substances 0.000 abstract description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- -1 Angewandte Chemie Chemical compound 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- OFGJZUBGZYMANZ-UHFFFAOYSA-N (2-bromophenoxy)boronic acid Chemical compound OB(O)OC1=CC=CC=C1Br OFGJZUBGZYMANZ-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 1
- QCOGKXLOEWLIDC-UHFFFAOYSA-N N-methylbutylamine Chemical compound CCCCNC QCOGKXLOEWLIDC-UHFFFAOYSA-N 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-bromoiodobenzene, which comprises the following steps: adding triphenylphosphine into an organic solvent under the protection of inert gas, adding organic amine under the stirring condition, and then preserving heat and stirring for 1-2 hours at 50-75 ℃; then adding iodine, and stirring for 2-4.5 hours at the temperature of 60-80 ℃; finally, adding 2-bromophenol and stirring for 5-10 hours under reflux; and naturally cooling the obtained reaction liquid to the temperature of less than or equal to 40 ℃, adding sodium methoxide, stirring, filtering, and performing aftertreatment on the filtrate to obtain the 2-bromoiodobenzene. The preparation method of 2-bromoiodobenzene has the characteristics of simple process and high product yield.
Description
Technical Field
The invention belongs to the field of chemical industry, and particularly relates to a preparation method of 2-bromoiodobenzene.
Background
The 2-bromoiodobenzene is an organic synthesis intermediate and a medical intermediate, and has wider application. The prior preparation method mainly comprises the following steps:
1) Diazotizing and iodizing o-amino bromobenzene to prepare 2-bromoiodobenzene (such as Angewandte Chemie, international Edition,51 (49), 12343-12347;2012 A) is provided;
2) 2-bromoiodobenzene (e.g., synlett,29 (12), 1572-1577;2018 A) is provided;
3) The o-bromophenyl boric acid is iodized to prepare 2-bromoiodobenzene (such as Tetrahedron Letters,56 (21), 2699-2703; 2015).
The existing reaction process has the problems of more waste water, complex reagent, low product yield and the like; in addition, scheme 3) has the defects of expensive raw materials, difficult purchase and the like.
Disclosure of Invention
The invention aims to provide a preparation method of 2-bromoiodobenzene with simple process and high product yield.
In order to solve the technical problems, the invention provides a preparation method of 2-bromoiodobenzene, which comprises the following steps:
1) Adding triphenylphosphine into an organic solvent under the protection of inert gas (such as nitrogen), adding organic amine under the stirring condition, and then carrying out heat preservation and stirring for 1-2 hours at 50-75 ℃ (preferably 65-75 ℃); then adding iodine into the mixture and stirring the mixture for 2 to 4.5 hours at a temperature of between 60 and 80 ℃ (preferably between 60 and 70 ℃); finally, 2-bromophenol is added and stirred under reflux for 5-10 hours (preferably 5-8 hours);
triphenylphosphine: organic amine: iodine = 1:0.8 to 1.3:0.95 to 1.3 molar ratio, triphenylphosphine: 2-bromophenol=1 to 2:1 (preferably 1.5 to 2:1, more preferably 1.8 to 2:1);
description: the whole step 1) is carried out under the protection of inert gas in the whole process;
2) Naturally cooling the reaction liquid obtained in the step 1) to be less than or equal to 40 ℃, adding sodium methoxide which is 1.05-1.1 times of the mole of the 2-bromophenol obtained in the step 1), stirring for 1+/-0.2 hours, filtering, and carrying out post-treatment on the filtrate to obtain the 2-bromoiodobenzene.
As an improvement of the preparation method of the 2-bromoiodobenzene, the invention: the organic amine is imidazole, 2-methylimidazole, 2-methylpiperidine.
As a further improvement of the process for producing 2-bromoiodobenzene of the present invention: the organic solvent is dichloromethane, tetrahydrofuran, 1, 3-dioxolane, acetonitrile and diethyl ether;
500-1000 ml of organic solvent is added to each 1 mol of triphenylphosphine.
As a further improvement of the process for producing 2-bromoiodobenzene of the present invention: the post-treatment of the step 2) is as follows: the filtrate is distilled first to recover organic solvent and organic amine separately, and then distilled under reduced pressure to collect 2-bromoiodobenzene.
As a further improvement of the process for producing 2-bromoiodobenzene of the present invention: the organic solvent is acetonitrile; the organic amine is 2-methylimidazole;
the step 1) is as follows:
adding triphenylphosphine into acetonitrile under the protection of inert gas, adding 2-methylimidazole under the stirring condition, and then preserving heat and stirring for 2 hours at 66 ℃; then adding iodine, and stirring for 3.5-4 hours at 60-70 ℃ with heat preservation; finally, adding 2-bromophenol and stirring for 5-8 hours under reflux;
triphenylphosphine: organic amine: iodine=1:0.88 to 0.92:0.95 to 1 molar ratio, triphenylphosphine: 2-bromophenol=1.8 to 2:1 molar ratio.
The components of triphenylphosphine, organic amine, 2-bromophenol and iodine used in the invention are all conventional reagents, so that the invention is easier to industrialize. And the organic amine can be recycled, and triphenylphosphine oxide generated by triphenylphosphine can be sold as a byproduct, so that the industrialization cost is greatly reduced, and the generation of three wastes is reduced.
The preparation method of the 2-bromoiodobenzene has the characteristics of simple process, high product selectivity, small influence on the environment and the like, and also has the advantages of simple post-treatment, high product purity and the like.
Detailed Description
The invention will be further described with reference to the following specific examples, but the scope of the invention is not limited thereto:
example 1, preparation of 2-bromoiodobenzene:
150 ml of acetonitrile and 0.225mol (about 59 g) of triphenylphosphine and 0.235mol of imidazole are added into a 500 ml dry anhydrous glass three-necked flask under the protection of nitrogen, stirred at a first temperature control (particularly 75 ℃ C. For 2 hours), then 0.264mol of iodine is added in batches (three batches), then after stirring at a second temperature control (particularly 70 ℃ C. For 3.5 hours), 0.150mol of 2-bromophenol is added, stirred for 7.5 hours under heating reflux, and the mixture is naturally cooled to about 40 ℃, added with 0.158mol of sodium methoxide and stirred for 1 hour, and then filtered, the filtrate is distilled conventionally, thereby respectively recovering an organic solvent and an organic amine, and then 34.3 g of a product fraction at 118-125 ℃ is distilled and recovered under 15mmHg pressure, so that the content of 2-bromoiodobenzene is 98%, and the yield is 79.1%.
Description: the purpose of adding iodine in batches is to control the temperature of the reaction system to be in a controllable state in order to control the temperature and heat release, and if the iodine is added at one time, the iodine is in danger of flushing.
The procedure of examples 2 to 11 is similar to that of example 1:
the molar amount of the 2-bromophenol is kept unchanged; the quality of triphenylphosphine (marked as M1) and the dosage of organic amine and iodine are changed, so that the triphenylphosphine is correspondingly changed: organic amine: the molar ratio of iodine (denoted as X), the kind of organic solvent, the temperature of the first temperature control (denoted as T1) and the stirring time (denoted as T1), the temperature of the second temperature control (denoted as T2) and the stirring time (denoted as T2), and the stirring time under reflux conditions (denoted as T3) were varied, the remainder being equivalent to example 1; the specific parameters are shown in Table 1. The yield of 2-bromoiodobenzene (noted as Y%) is shown in Table 1.
The content of 2-bromoiodobenzene obtained in examples 2 to 11 was 98%.
Table 1, results of examples for preparing 2-bromoiodobenzene
* (1) represents imidazole; (2) represents 2-methylimidazole; (3) represents 2-methylpiperidine.
Description: the recovered solvent can be reused for at least 5-8 times, namely, the solvent can be reused for 5-8 times, and the reaction results have no significant difference.
Comparative examples 1 to 7 were similar to example 1 in operation:
the molar amount of the 2-bromophenol is kept unchanged; the quality of triphenylphosphine (marked as M1) and the dosage of organic amine and iodine are changed, so that the triphenylphosphine is correspondingly changed: organic amine: the molar ratio of iodine (denoted as X), the kind of organic solvent, the temperature of the first temperature control (denoted as T1) and the stirring time (denoted as T1), the temperature of the second temperature control (denoted as T2) and the stirring time (denoted as T2), and the stirring time under reflux conditions (denoted as T3) were varied, the remainder being equivalent to example 1; the specific parameters are shown in Table 2. The yield of 2-bromoiodobenzene (noted as Y%) is shown in Table 2.
TABLE 2
* (4) represents N-methylcyclohexylamine; (5) represents N-methylbutylamine.
Finally, it should also be noted that the above list is merely a few specific embodiments of the present invention. Obviously, the invention is not limited to the above embodiments, but many variations are possible. All modifications directly derived or suggested to one skilled in the art from the present disclosure should be considered as being within the scope of the present invention.
Claims (3)
- The preparation method of the 2-bromoiodobenzene is characterized by comprising the following steps:1) Adding triphenylphosphine into an organic solvent under the protection of inert gas, adding organic amine under the stirring condition, and then carrying out heat preservation and stirring for 2 hours at 66 ℃; then adding iodine, and carrying out heat preservation and stirring for 3.5-4 hours at the temperature of 60-70 ℃; finally, adding 2-bromophenol and stirring for 5-8 hours under a reflux condition;triphenylphosphine: 2-methylimidazole: iodine=1:0.88 to 0.92:0.95 to 1 molar ratio, triphenylphosphine: 2-bromophenol=1.8 to 2:1 molar ratio;the organic amine is 2-methylimidazole, and the organic solvent is acetonitrile;2) And (2) naturally cooling the reaction liquid obtained in the step (1) to be less than or equal to 40 ℃, adding sodium methoxide which is 1.05-1.1 times of the 2-bromophenol in the step (1), stirring for 1+/-0.2 hours, filtering, and carrying out post-treatment on the filtrate to obtain the 2-bromoiodobenzene.
- 2. The method for preparing 2-bromoiodobenzene according to claim 1, characterized in that: 500-1000 ml of acetonitrile is added to each 1 mol of triphenylphosphine.
- 3. The method for preparing 2-bromoiodobenzene according to claim 1 or 2, characterized in that:the post-treatment of the step 2) is as follows: the filtrate is distilled first to recover organic solvent and organic amine separately, and then distilled under reduced pressure to collect 2-bromoiodobenzene.
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| CN104081551A (en) * | 2012-02-02 | 2014-10-01 | 巴斯夫欧洲公司 | Method for producing an organic semiconductor device |
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| US6806381B2 (en) * | 2001-11-02 | 2004-10-19 | Bristol-Myers Squibb Company | Process for the preparation of aniline-derived thyroid receptor ligands |
| TW200504021A (en) * | 2003-01-24 | 2005-02-01 | Bristol Myers Squibb Co | Substituted anilide ligands for the thyroid receptor |
| US20040176425A1 (en) * | 2003-01-24 | 2004-09-09 | Washburn William N. | Cycloalkyl containing anilide ligands for the thyroid receptor |
| WO2004103985A2 (en) * | 2003-05-16 | 2004-12-02 | University Of South Carolina | Derivatives of fusarochromanone as therapeutic agents |
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| CN104081551A (en) * | 2012-02-02 | 2014-10-01 | 巴斯夫欧洲公司 | Method for producing an organic semiconductor device |
Non-Patent Citations (3)
| Title |
|---|
| 曾步兵，任江萌编.药物合成反应学习指导.上海：华东理工大学出版社,2013,302-305. * |
| 氟骨三醇含氟中间体片段的合成研究;岳慧娟;中国优秀硕士学位论文全文数据库工程科技Ⅰ辑(第1期);B016-1821 * |
| 绣线菊碱C、D关键BCD三环中间体的不对称合成;孟银娟;合成化学;第25卷(第7期);591-595 * |
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