CN116462568A - Method for removing triethyloxysilane in reaction for preparing 1-benzyl-4-bromobenzene - Google Patents
Method for removing triethyloxysilane in reaction for preparing 1-benzyl-4-bromobenzene Download PDFInfo
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- CN116462568A CN116462568A CN202310478682.6A CN202310478682A CN116462568A CN 116462568 A CN116462568 A CN 116462568A CN 202310478682 A CN202310478682 A CN 202310478682A CN 116462568 A CN116462568 A CN 116462568A
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- Prior art keywords
- reaction
- triethyloxysilane
- bromobenzene
- benzyl
- solvent
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Links
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 25
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 title claims abstract description 20
- NNEOYCMCJMLRSD-UHFFFAOYSA-N 1-benzyl-4-bromobenzene Chemical compound C1=CC(Br)=CC=C1CC1=CC=CC=C1 NNEOYCMCJMLRSD-UHFFFAOYSA-N 0.000 title claims abstract description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 62
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims abstract description 22
- KEOLYBMGRQYQTN-UHFFFAOYSA-N (4-bromophenyl)-phenylmethanone Chemical compound C1=CC(Br)=CC=C1C(=O)C1=CC=CC=C1 KEOLYBMGRQYQTN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000005292 vacuum distillation Methods 0.000 claims abstract description 10
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims abstract description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 2
- 238000010791 quenching Methods 0.000 abstract description 5
- 230000000171 quenching effect Effects 0.000 abstract description 5
- 238000004440 column chromatography Methods 0.000 abstract description 4
- 230000003321 amplification Effects 0.000 abstract description 2
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WVMSIBFANXCZKT-UHFFFAOYSA-N triethyl(hydroxy)silane Chemical compound CC[Si](O)(CC)CC WVMSIBFANXCZKT-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
- C07C17/383—Separation; Purification; Stabilisation; Use of additives by distillation
Abstract
The invention relates to a method for removing triethyloxysilane in a reaction for preparing 1-benzyl-4-bromobenzene, which comprises the following steps: (1) 4-bromobenzoyl benzene reacts with trifluoromethanesulfonic acid and triethylsilane in a solvent; (2) Quenching the reaction with saturated sodium bicarbonate solution after the reaction is finished, extracting with dichloromethane, removing the solvent, and removing triethyloxysilane from oily liquid after the solvent is removed by vacuum distillation to obtain 1-benzyl-4-bromobenzene; the method can avoid using column chromatography, can effectively remove triethyloxysilane, can achieve the purity of more than 98 percent, is particularly suitable for large-scale treatment of kilogram level and more, is not only limited to small-scale tests, saves cost in process amplification, and has good application prospect and industrial value.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for removing triethyloxysilane in a reaction for preparing 1-benzyl-4-bromobenzene.
Background
At present, the conventional method for removing triethyloxysilane in the reaction is to break Si-H bonds in molecules under the action of alkaline water, release hydrogen to generate triethylsilanol, extract the organic phase product and remove the triethyloxysilane to achieve the purification state of the product. However, in the reaction of preparing 1-benzyl-4-bromobenzene from 4-bromobenzoyl benzene, the above-mentioned removal method was found to be difficult to achieve mass purification by using triethylsilane as a reducing agent.
Accordingly, in view of the above shortcomings, there is a need to provide a new method to solve the problem of failure of mass purification.
Disclosure of Invention
The technical problem to be solved by the invention is that triethyloxysilane cannot be removed in the existing reaction for preparing 1-benzyl-4-bromobenzene from 4-bromobenzoyl benzene, and the method for removing triethyloxysilane in the reaction for preparing 1-benzyl-4-bromobenzene is provided aiming at the defects in the prior art.
In order to solve the technical problems, the invention provides a method for removing triethyloxysilane in a reaction for preparing 1-benzyl-4-bromobenzene, which comprises the following steps:
(1) 4-bromobenzoyl benzene reacts with trifluoromethanesulfonic acid and triethylsilane in a solvent;
(2) After the reaction is finished, the reaction is quenched by saturated sodium bicarbonate solution, the solvent is removed after dichloromethane extraction, and the oily liquid after the solvent removal is distilled in vacuum to remove triethyloxysilane to obtain 1-benzyl-4-bromobenzene.
The method provided by the invention does not use column chromatography for purification, and can remove a large amount of triethyloxysilane. Conventional column chromatography cannot separate (5 g or more) triethyloxysilane and 1-benzyl-4-bromobenzene. In addition, the conventional post-treatment method uses ammonium chloride or sodium hydroxide to wash the organic phase with alkali, but the effect of washing out triethyloxysilane is not achieved, and a large amount of triethyloxysilane contained in the product can be effectively removed by vacuum distillation.
Preferably, the molar ratio of the 4-bromobenzoyl benzene, the trifluoromethanesulfonic acid and the triethylsilane in the step (1) is 1:0.2-0.4:3-4, for example, 1:0.2:3, 1:0.3:3.5, 1:0.4:4, etc.
Preferably, the solvent in step (1) is dichloromethane.
Preferably, the reaction time in step (1) is 10 to 15 hours, and may be, for example, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, or the like.
Preferably, the reaction in step (1) is carried out under anhydrous conditions.
Preferably, the temperature of the vacuum distillation in the step (2) is 120 to 130 ℃, and for example, 120 ℃, 122 ℃, 125 ℃, 128 ℃, 130 ℃ or the like can be used.
Preferably, the temperature of the vacuum distillation in step (2) is 125 ℃. In the present invention, triethylsilane has a boiling point of 107 to 108℃and, after searching, it was found that the impurity (triethyloxysilane) can be distilled out at 125 ℃. The impurities are not distilled out at low temperature, and the products at higher temperature are deteriorated and the impurity peaks appear.
The implementation of the invention has the following beneficial effects:
the method can avoid using column chromatography, can effectively remove triethyloxysilane, can achieve the purity of more than 98 percent, is particularly suitable for large-scale treatment of kilogram level and more, is not only limited to small-scale tests, saves cost in process amplification, and has good application prospect and industrial value.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention are clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
4-bromobenzoyl benzene (500 g) was dissolved in anhydrous dichloromethane (5000 ml), triethylsilane (720 g) was dissolved in an appropriate amount of dichloromethane, and the system was slowly poured in; trifluoromethanesulfonic acid (88 g) was dissolved in a large amount of methylene chloride, and the mixture was slowly poured into the reaction system. Stirring fully; the reaction time was 12 hours. TLC: PE: EA (petroleum ether: ethyl acetate) =5:1, after completion of the reaction, quenching the reaction with saturated sodium bicarbonate; then extracting for multiple times by using water and dichloromethane to obtain an organic phase which is subjected to vacuum rotary evaporation; then vacuum distillation is adopted for purification, after the organic phase is dried by spin, transparent colorless liquid is distilled at 125 ℃, and the residual product is the 1-benzyl-4-bromobenzene, the quality is 170g, the yield is 35.92%, and the purity is 98%. HNMR DMSO delta 7.50-7.45 (m, 2H), 7.32-7.26 (m, 2H), 7.25-7.16 (m, 5H), 3.92 (s, 1H).
Example 2
4-bromobenzoyl benzene (398 g) was dissolved in anhydrous dichloromethane (5000 ml), triethylsilane (619.82 g) was dissolved in an appropriate amount of dichloromethane, and the system was slowly poured in; trifluoromethanesulfonic acid (80 g) was dissolved in a large amount of methylene chloride, and the mixture was slowly poured into the reaction system. Stirring fully; the reaction time was 12 hours. TLC: PE: EA (petroleum ether: ethyl acetate) =5:1, after completion of the reaction, quenching the reaction with saturated sodium bicarbonate; then extracting for multiple times by using water and dichloromethane to obtain an organic phase which is subjected to vacuum rotary evaporation; then purifying by vacuum distillation, and distilling off transparent colorless liquid at 122 ℃ after spin-drying the organic phase, wherein the residual product is 1-benzyl-4-bromobenzene, the quality is 135g, the yield is 35.87%, and the purity is 98%.
Example 3
4-bromobenzoyl benzene (565.46 g) was dissolved in anhydrous dichloromethane (5000 ml), triethylsilane (755.41 g) was dissolved in an appropriate amount of dichloromethane, and the system was slowly poured into; trifluoromethanesulfonic acid (65 g) was dissolved in a large amount of methylene chloride, and the mixture was slowly poured into the reaction system. Stirring fully; the reaction time was 12 hours. TLC: PE: EA (petroleum ether: ethyl acetate) =5:1, after completion of the reaction, quenching the reaction with saturated sodium bicarbonate; then extracting for multiple times by using water and dichloromethane to obtain an organic phase which is subjected to vacuum rotary evaporation; then purifying by vacuum distillation, and distilling off transparent colorless liquid at 127 ℃ after spin-drying the organic phase, wherein the residual product is the 1-benzyl-4-bromobenzene with the mass of 178g, the yield of 33.26% and the purity of 97%.
Example 4
4-bromobenzoyl benzene (282.73 g) was dissolved in anhydrous dichloromethane (5000 ml), triethylsilane (503.61 g) was dissolved in an appropriate amount of dichloromethane, and the system was slowly poured into; trifluoromethanesulfonic acid (65 g) was dissolved in a large amount of methylene chloride, and the mixture was slowly poured into the reaction system. Stirring fully; the reaction time was 12 hours. TLC: PE: EA (petroleum ether: ethyl acetate) =5:1, after completion of the reaction, quenching the reaction with saturated sodium bicarbonate; then extracting for multiple times by using water and dichloromethane to obtain an organic phase which is subjected to vacuum rotary evaporation; then purifying by vacuum distillation, and distilling out transparent colorless liquid at 126 ℃ after spin-drying the organic phase, wherein the residual product is the 1-benzyl-4-bromobenzene, the quality is 88g, the yield is 32.89%, and the purity is 97%.
As can be seen from the results of the above examples, the present invention can maximize the yield and purity of the product after optimizing the post-treatment process. The purity of the product can reach 98 percent at 125 ℃, the product yield can reach 35.92 percent, and compared with the existing method, the method has high yield and higher product purity, and has good application prospect and application value.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (7)
1. A method for removing triethyloxysilane in a reaction for preparing 1-benzyl-4-bromobenzene, which is characterized by comprising the following steps: the method comprises the following steps:
(1) 4-bromobenzoyl benzene reacts with trifluoromethanesulfonic acid and triethylsilane in a solvent;
(2) After the reaction is finished, the reaction is quenched by saturated sodium bicarbonate solution, the solvent is removed after dichloromethane extraction, and the oily liquid after the solvent removal is distilled in vacuum to remove triethyloxysilane to obtain 1-benzyl-4-bromobenzene.
2. The method according to claim 1, characterized in that: the molar ratio of the 4-bromobenzoyl benzene, the trifluoromethanesulfonic acid and the triethylsilane in the step (1) is 1:0.2-0.4:3-4.
3. The method according to claim 1 or 2, characterized in that: the solvent in the step (1) is methylene dichloride.
4. A method according to any one of claims 1-3, characterized in that: the reaction time in the step (1) is 10-15 h.
5. The method according to any one of claims 1-4, wherein: the reaction in step (1) is carried out under anhydrous conditions.
6. The method according to any one of claims 1-5, wherein: the temperature of the vacuum distillation in the step (2) is 120-130 ℃.
7. The method according to claim 6, wherein: the temperature of the vacuum distillation in step (2) was 125 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310478682.6A CN116462568A (en) | 2023-04-28 | 2023-04-28 | Method for removing triethyloxysilane in reaction for preparing 1-benzyl-4-bromobenzene |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310478682.6A CN116462568A (en) | 2023-04-28 | 2023-04-28 | Method for removing triethyloxysilane in reaction for preparing 1-benzyl-4-bromobenzene |
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| Publication Number | Publication Date |
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| CN116462568A true CN116462568A (en) | 2023-07-21 |
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| CN202310478682.6A Pending CN116462568A (en) | 2023-04-28 | 2023-04-28 | Method for removing triethyloxysilane in reaction for preparing 1-benzyl-4-bromobenzene |
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| CN (1) | CN116462568A (en) |
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2023
- 2023-04-28 CN CN202310478682.6A patent/CN116462568A/en active Pending
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