CN113501499A - Preparation method and application of high-purity anhydrous deuterium bromide gas - Google Patents
Preparation method and application of high-purity anhydrous deuterium bromide gas Download PDFInfo
- Publication number
- CN113501499A CN113501499A CN202110921587.XA CN202110921587A CN113501499A CN 113501499 A CN113501499 A CN 113501499A CN 202110921587 A CN202110921587 A CN 202110921587A CN 113501499 A CN113501499 A CN 113501499A
- Authority
- CN
- China
- Prior art keywords
- deuterium
- bromide
- gas
- purity
- bromide gas
- 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.)
- Pending
Links
Classifications
-
- 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
- C01B7/09—Bromine; Hydrogen bromide
- C01B7/093—Hydrogen bromide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/07—Preparation of halogenated hydrocarbons by addition of hydrogen halides
- C07C17/08—Preparation of halogenated hydrocarbons by addition of hydrogen halides to unsaturated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Abstract
The invention relates to a preparation method of high-purity anhydrous deuterium bromide gas, which comprises the following steps: (1) dissolving the dried sodium bromide or potassium bromide solid in deuterium water to form a mixed solution, and then dropwise adding a deuterium sulfate aqueous solution at a low temperature to obtain high-purity deuterium bromide gas; (2) and introducing the obtained high-purity deuterium bromide gas into a cold trap, and performing water removal operation to obtain the high-purity anhydrous deuterium bromide gas. The invention can gently generate high-purity deuterium bromide gas without bromine, the speed of the generated gas is related to the dropping speed of the deuterated sulfuric acid, the reaction is mild, all substrates are stable when the gas is added at any time, the high-purity anhydrous deuterium bromide gas can be continuously or discontinuously generated, and the reaction process is easy to control. The deuterium-substituted sulfuric acid and the deuterium water are cheap and easy to obtain, the utilization rate of the deuterium is high, the obtained anhydrous deuterium bromide gas is low in cost and high in reliability, and impurities such as bromine, water and the like are few, so that almost all use scenes of the deuterium bromide can be met.
Description
Technical Field
The invention relates to a method for synthesizing high-purity anhydrous deuterium bromide gas, in particular to a method for synthesizing high-purity anhydrous deuterium bromide by directly using cheap deuterated sulfuric acid, deuterium water and the like which are self-prepared by the company as raw materials.
Background
The high-purity anhydrous deuterium bromide is an important precursor compound for preparing the deuterated bromide, has important application value in the field of deuterated isotope labeling, and especially has important significance in the synthesis processes of obtaining ortho-deuterium brominated compounds (such as intermediates of mono-deuterated bromoethane, deuterated dibromoethane and the like) and anhydrous deuterium sources (such as organic solution of deuterium bromide) by double bond and triple bond addition, and the like. Meanwhile, as anhydrous deuterium bromide is a gas, the conventional deuterium bromic acid is relatively expensive, and as the anhydrous deuterium bromide is a deuterium aqueous solution, the conventional deuterium bromic acid cannot be directly used in an anhydrous reaction process, so that the use is inconvenient. Meanwhile, the anhydrous deuterium bromide gas has strong corrosivity and is complicated in storage and transportation processes, and the dosage of the anhydrous deuterium bromide gas is not large in the labeling and synthesis processes of most stable isotopes, so that the method for developing the high-purity anhydrous deuterium bromide gas prepared immediately after use is more meaningful.
The existing methods for synthesizing anhydrous deuterium bromide mainly comprise a deuterium bromic acid bubbling method, a deuterated phosphoric acid acidolysis method, a deuterium hydrolysis method and the like.
The deuterium bromic acid bubbling method is to take out deuterium bromide from deuterium bromic acid (40% deuterium aqueous solution) by using nitrogen or argon, then to obtain a nitrogen or argon mixture of the deuterium bromide after drying through a drying agent, and then to inject the nitrogen or argon mixture into an organic solution to form a solution or directly react with a substrate.
The acid hydrolysis method of deuterated phosphoric acid is characterized by that the deuterated phosphoric acid is dropped into the solid sodium bromide or potassium bromide, then the deuterium bromide gas is produced at high temperature. However, this method results in deuterium bromide gas which is extremely inefficient and requires high temperatures.
Deuterium hydrolysis, which comprises hydrolyzing phosphorus bromide (phosphorus tribromide, phosphorus pentabromide or a mixture of bromine and red phosphorus) and organic acid bromide (acetyl bromide, benzoyl bromide, etc.), is based on the principle of hydrolyzing these substrates with deuterium water to produce deuterium bromide, which is then dried and used.
The methods either use expensive deuterium bromic acid, deuterated phosphoric acid and other deuterium sources, have low utilization rate of the deuterium bromic acid and can generate a large amount of high-concentration deuterium bromic acid waste liquid, or have violent reaction, the substrates hydrolyzed by deuterium water are all compounds with high activity, the reaction is extremely difficult to control smoothly, the acyl bromide compounds are expensive and cannot be prepared in large quantity, and the deuterium bromide obtained by the methods contains a certain amount of bromine, so that the use of the deuterium bromide gas is limited.
In conclusion, the development of a preparation method of high-purity anhydrous deuterium bromide gas with high efficiency, low cost, mild reaction and easy control has important practical significance.
Disclosure of Invention
In view of the above disadvantages, the present invention aims to provide a method for synthesizing high-purity anhydrous deuterium bromide by directly using deuterated sulfuric acid and deuterated water as deuterium sources and bromides such as sodium bromide or potassium bromide as bromine sources, i.e., directly using sodium bromide or potassium bromide as raw materials, using cheap and easily available deuterated sulfuric acid (self-made) and deuterated water as deuterium sources, preparing high-purity deuterium bromide gas without bromine at low temperature, and then drying at low temperature to obtain the high-purity anhydrous deuterium bromide gas.
The technical scheme of the invention is as follows:
a preparation method of high-purity anhydrous deuterium bromide gas comprises the following steps:
(1) dissolving the dried sodium bromide or potassium bromide solid in deuterium water to form a mixed solution, and then dropwise adding a deuterium sulfate aqueous solution at a low temperature to obtain high-purity deuterium bromide gas;
(2) and introducing the obtained high-purity deuterium bromide gas into a cold trap, and performing water removal operation to obtain the high-purity anhydrous deuterium bromide gas.
The bromide is dissolved in deuterium water and then directly reacts with deuterated sulfuric acid at low temperature, so that high-purity deuterium bromide gas without bromine can be generated smoothly, the gas generation speed is related to the dropping speed of the deuterated sulfuric acid, the reaction is mild, all substrates are stable when the bromide is added at any time, the high-purity anhydrous deuterium bromide gas can be generated continuously or discontinuously, and the reaction process is easy to control. The deuterium-substituted sulfuric acid and the deuterium water are cheap and easy to obtain, the utilization rate of the deuterium is high, the obtained anhydrous deuterium bromide gas is low in cost and high in reliability, and impurities such as bromine, water and the like are few, so that almost all use scenes of the deuterium bromide can be met.
In order to improve the purification efficiency and save the reaction cost, deuterated sulfuric acid with corresponding concentration can be prepared by a company as a deuterium source in the reaction process, so that the synthesis cost can be reduced, the complicated process of diluting the commercially available deuterated sulfuric acid and deuterium water is avoided, and the deuterium abundance of the product is also prevented from being influenced by excessive operation.
The specific synthetic route of the invention is as follows:
M＝Li,Na,K et.al.
preferably, in the step (1), the mass ratio of the sodium bromide or potassium bromide solid to the deuterium water is 1: 0.5 to 50.
Preferably, in the step (1), the temperature of the low-temperature condition is-50 to 10 ℃.
Preferably, in the step (1), the concentration of the deuterated deuterium sulfate aqueous solution is 40-98%.
Preferably, the temperature of the cold trap is-196 ℃ to 0 ℃, and the pressure is-101.3 KPa to 100 KPa.
More specifically, the steps of the present invention are as follows:
(1) dissolving the dried sodium bromide or potassium bromide solid in deuterium water with the mass of 0.5-50 times to form a mixed solution, cooling to-50-10 ℃ under vacuum, then adding a deuterium sulfate aqueous solution with the concentration of 40-98% into the mixed solution, and keeping the temperature unchanged at-50-10 ℃ until colorless gas is slowly generated. The rate of formation of deuterium bromide gas can be controlled by the rate of addition of deuterated sulfuric acid.
(2) And introducing the generated high-purity deuterium bromide gas into a cold trap cooled to-196-0 ℃, and controlling the system pressure to be-101.3-100 KPa to obtain the colorless high-purity anhydrous deuterium bromide gas. The anhydrous deuterium bromide gas is directly synthesized into deuterated dibromoethane with ethynylation, or synthesized into deuterated bromohexane with cyclohexene, and the like, and bromine is not found.
The invention also provides an application of the method, in particular to a preparation method of deuterated 1, 2-dibromoethane, which comprises the following steps:
(1) obtaining high-purity anhydrous deuterium bromide gas according to the method;
(2) reacting the high-purity anhydrous deuterium bromide gas obtained in the step (1) with deuterated acetylene to obtain deuterated 1, 2-dibromoethane.
The method has the advantages of cheap and easily-obtained reaction raw materials, simple and easily-controlled reaction process, easy operation, convenient product purification, stable and quick gas generation, high yield and low cost.
The invention has the advantages that:
1. the invention directly uses the deuterated sulfuric acid and the deuterated water as deuterium sources, has low cost and easy obtainment, and is easy to control the gas generation speed;
2. the invention has the characteristics of high utilization rate of deuterium and stable and quick generation of gas, is easy to prepare in situ, can prepare a certain amount of deuterium, and does not need to store and transport highly corrosive deuterium bromide gas. Meanwhile, all substrates have good chemical stability and high reaction rate, so that the preparation process can be stopped and restarted at any time, namely the deuterium bromide gas can be continuously prepared or discontinuously prepared.
3. The invention avoids high-activity acyl bromide and other compounds, avoids using deuterated phosphoric acid and other compounds which need high temperature to slowly generate a small amount of deuterium bromide gas, fundamentally solves the problem that the methods are easy to generate bromine, does not need to use carrier gas for diversion, and can improve the utilization efficiency and the application range of the anhydrous deuterium bromide gas.
Detailed Description
Example 1
Adding 2.5g of sodium bromide dried in advance into a 50mL single-neck flask connected with a dropping funnel (the dropping funnel is added with 10mL of 65% deuterated sulfuric acid in advance and then connected with a cold trap with the constant temperature of-100 to-60 ℃), replacing the sodium bromide by an oil pump for three times, adding 10mL of deuterium water, stirring and dissolving, vacuumizing the system, slowly dropping the deuterated sulfuric acid into the dropping funnel, and generating colorless gas after approximately half of the deuterated sulfuric acid is dropped until the gas is not generated any more, thus finishing the reaction. And then, connecting an about 100mL eggplant-shaped bottle with a cold trap at the pressure of 100KPa, transferring the generated gas into the eggplant-shaped bottle at the temperature of-120 to-80 ℃, and collecting about 200mL of high-purity anhydrous deuterium bromide gas, wherein the purity of the product is more than 98.5 percent, and the abundance of deuterium is more than 98 percent.
Example 2
Adding 2.8g of potassium bromide dried in advance into a 50mL single-neck flask connected with a dropping funnel (the dropping funnel is added with 2.5mL of 96-98% deuterated sulfuric acid in advance and then connected with a cold trap with the constant temperature of-100 to-60 ℃), replacing an oil pump for three times, adding 6mL of deuterium water, stirring and dissolving, vacuumizing a system, slowly dropping the deuterated sulfuric acid from the dropping funnel, and after about half of the deuterated sulfuric acid is dropped, generating colorless gas until the gas is not generated any more, and finishing the reaction. And then, connecting an about 100mL eggplant-shaped bottle with a cold trap, transferring the generated gas into the eggplant-shaped bottle at-120 to-80 ℃, and collecting about 180mL of high-purity anhydrous deuterium bromide gas (under the standard condition), wherein the purity of the product is more than 98.5 percent, and the abundance of deuterium is more than 98 percent.
Application example 1
The deuterium acetylene (prepared from 250mg of calcium carbide) prepared and dried in advance is introduced into a eggplant-shaped bottle which is vacuumized, then about 180mL of anhydrous deuterium bromide gas prepared according to the method in example 2 is introduced into the eggplant-shaped bottle, a small amount of air is added for catalysis, the eggplant-shaped bottle is irradiated by strong light, the pressure in the bottle rises firstly and then drops rapidly, and the reaction is initiated. After the reaction is finished (the pressure in the eggplant-shaped bottle is not changed any more), nitrogen is put into the bottle to ensure that the pressure in the eggplant-shaped bottle is normal pressure, then saturated sodium bicarbonate solution is added, dichloromethane is used for extraction for three times (10mL multiplied by 3), organic phases are combined, anhydrous sodium sulfate is used for drying, the solvent is dried in a spinning mode, and the pure deuterated 1, 2-dibromoethane 688mg is obtained, the yield is about 92%, the gas phase purity is 99%, and the abundance is more than 98%.
Claims (6)
1. A preparation method of high-purity anhydrous deuterium bromide gas is characterized by comprising the following steps:
(1) dissolving the dried sodium bromide or potassium bromide solid in deuterium water to form a mixed solution, and then dropwise adding a deuterium sulfate aqueous solution at a low temperature to obtain high-purity deuterium bromide gas;
(2) and introducing the obtained high-purity deuterium bromide gas into a cold trap, and performing water removal operation to obtain the high-purity anhydrous deuterium bromide gas.
2. The method for preparing high-purity anhydrous deuterium bromide gas according to claim 1, wherein in the step (1), the mass ratio of the solid sodium bromide or potassium bromide to the deuterium solution is 1: 0.5 to 50.
3. The method for preparing high-purity anhydrous deuterium bromide gas according to claim 1, wherein in the step (1), the temperature under the low-temperature condition is-50 to 10 ℃.
4. The method as claimed in claim 1, wherein in step (1), the concentration of the deuterium (H) sulfate solution is 40-98%.
5. The method of claim 1, wherein the temperature of the cold trap is-196-0 ℃, and the pressure is-101.3-100 KPa.
6. A preparation method of deuterated 1, 2-dibromoethane is characterized by comprising the following steps:
(1) obtaining high-purity anhydrous deuterium bromide gas according to the method of any one of claims 1 to 5;
(2) reacting the high-purity anhydrous deuterium bromide gas obtained in the step (1) with deuterated acetylene to obtain deuterated 1, 2-dibromoethane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110921587.XA CN113501499A (en) | 2021-08-11 | 2021-08-11 | Preparation method and application of high-purity anhydrous deuterium bromide gas |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110921587.XA CN113501499A (en) | 2021-08-11 | 2021-08-11 | Preparation method and application of high-purity anhydrous deuterium bromide gas |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113501499A true CN113501499A (en) | 2021-10-15 |
Family
ID=78016283
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110921587.XA Pending CN113501499A (en) | 2021-08-11 | 2021-08-11 | Preparation method and application of high-purity anhydrous deuterium bromide gas |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113501499A (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1332425A (en) * | 1970-12-30 | 1973-10-03 | Kao Corp | Process for preparing hydrogen bromide |
| US6623718B1 (en) * | 2001-12-15 | 2003-09-23 | Erc Incorporated | Process for the chemical generation of singlet delta oxygen |
| CN101058408A (en) * | 2007-06-07 | 2007-10-24 | 浙江闰土股份有限公司 | Method of reclaiming and using high-pollution low-concentration waste acid |
| US20150361066A1 (en) * | 2013-01-22 | 2015-12-17 | Celgene Corporation | Processes for the preparation of isotopologues of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable salts thereof |
| CN110392695A (en) * | 2016-12-09 | 2019-10-29 | Ose免疫疗法 | For the antibody and polypeptide of CD127 |
| CN110981686A (en) * | 2019-12-31 | 2020-04-10 | 中国船舶重工集团公司第七一八研究所 | Preparation method and preparation device of 1,1,2, 2-tetradeuteroethylene |
| CN111285330A (en) * | 2018-12-07 | 2020-06-16 | 华东理工大学 | Method for preparing hydrobromic acid by bipolar membrane electrodialysis method |
| CN111994873A (en) * | 2020-10-27 | 2020-11-27 | 苏州金宏气体股份有限公司 | Method and device for producing high-purity hydrobromic acid by adopting industrial grade hydrogen bromide gas |
| CN112490320A (en) * | 2019-09-12 | 2021-03-12 | 意法半导体有限公司 | Optical sensor package |
-
2021
- 2021-08-11 CN CN202110921587.XA patent/CN113501499A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1332425A (en) * | 1970-12-30 | 1973-10-03 | Kao Corp | Process for preparing hydrogen bromide |
| US6623718B1 (en) * | 2001-12-15 | 2003-09-23 | Erc Incorporated | Process for the chemical generation of singlet delta oxygen |
| CN101058408A (en) * | 2007-06-07 | 2007-10-24 | 浙江闰土股份有限公司 | Method of reclaiming and using high-pollution low-concentration waste acid |
| US20150361066A1 (en) * | 2013-01-22 | 2015-12-17 | Celgene Corporation | Processes for the preparation of isotopologues of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable salts thereof |
| CN110392695A (en) * | 2016-12-09 | 2019-10-29 | Ose免疫疗法 | For the antibody and polypeptide of CD127 |
| CN111285330A (en) * | 2018-12-07 | 2020-06-16 | 华东理工大学 | Method for preparing hydrobromic acid by bipolar membrane electrodialysis method |
| CN112490320A (en) * | 2019-09-12 | 2021-03-12 | 意法半导体有限公司 | Optical sensor package |
| CN110981686A (en) * | 2019-12-31 | 2020-04-10 | 中国船舶重工集团公司第七一八研究所 | Preparation method and preparation device of 1,1,2, 2-tetradeuteroethylene |
| CN111994873A (en) * | 2020-10-27 | 2020-11-27 | 苏州金宏气体股份有限公司 | Method and device for producing high-purity hydrobromic acid by adopting industrial grade hydrogen bromide gas |
Non-Patent Citations (2)
| Title |
|---|
| 何译人编译: "《无机制备化学手册（增订第二版）上册》", 28 February 1975, 燃料化学工业出版社 * |
| 杨玉兰: "五元双环二酰胺类化合物及3-氧戊二酰胺萃取剂的合成及其萃取性能的研究", 《中国优秀博硕士学位论文全文数据库（硕士）工程科技Ⅰ辑》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4869947B2 (en) | Method for synthesizing isotopically enriched borohydride and method for synthesizing isotopically enriched boranes | |
| Soai et al. | Asymmetric autocatalysis of pyrimidyl alkanol and related compounds. Self-replication, amplification of chirality and implication for the origin of biological enantioenriched chirality | |
| CN116063145B (en) | High-purity and high-yield 4-bromofluorobenzene synthesis method | |
| CN113501499A (en) | Preparation method and application of high-purity anhydrous deuterium bromide gas | |
| CN106542982A (en) | A kind of preparation method of the deuterium-labeled acetone of stable isotope | |
| CN101585519A (en) | Method for preparing <15>N-hydroxylamine hydrochloride by hydrolyzing <15>N-nitromethane | |
| CN113292402A (en) | Method for synthesizing 3, 8-dimethyl-3, 5, 7-octatriene-1, 10-dialdehyde | |
| CN104744305A (en) | Synthesis method of 2,4-dichloro-3-cyan-5-fluorobenzoic acid | |
| CN111303192A (en) | Industrial production method of 3-chloro-2-naphthalene boric acid | |
| CN103483366B (en) | Preparation method of methoxy diethyl borane | |
| Mishra et al. | Preparation, absolute configuration, and thermolysis of (3R: 5R)-(+)-trans-3, 5-dimethyl-1-pyrazoline | |
| CN1730127B (en) | Process for preparing clean highly effective gas fire-extinguishing medium | |
| CN111205205B (en) | Preparation method of O-18 labeled urea | |
| CN112778090A (en) | Preparation method of 3, 5-difluorophenol | |
| CN112174166A (en) | Method for preparing high-purity ammonia | |
| CN111454114A (en) | One kind is used13C2High purity of geraniol synthesis13C2Method for producing myrcene | |
| JP2020082071A (en) | Method for separating carbon isotope and method for concentrating carbon isotope | |
| US5693306A (en) | Production process for refined hydrogen iodide | |
| US2692276A (en) | Process for the manufacture of acrylonitrile | |
| CN113087592B (en) | Synthetic method of 4,4' -dibromo octafluoro biphenyl | |
| CN102372660A (en) | N-phenylisatin and preparation method thereof | |
| JP2011162363A (en) | Method for producing diborane | |
| CN102942582A (en) | Preparation method of entecavir key intermediate | |
| JP2729593B2 (en) | Method for producing hydrogen iodide | |
| CN116947666A (en) | Preparation method of carbon isotope labeled glycine |
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 | ||
| CB02 | Change of applicant information |
Address after: No. 70 Dongsheng West Road, Jiangyin City, Wuxi City, Jiangsu Province, 214434 Applicant after: WUXI BEITA PHARMATECH Co.,Ltd. Address before: 214434 floor C7, No. 6, Dongsheng West Road, Jiangyin City, Wuxi City, Jiangsu Province Applicant before: WUXI BEITA PHARMATECH Co.,Ltd. |
|
| CB02 | Change of applicant information |