CN111116313B - Preparation method of deuterated methanol - Google Patents
Preparation method of deuterated methanol Download PDFInfo
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- CN111116313B CN111116313B CN201911413189.6A CN201911413189A CN111116313B CN 111116313 B CN111116313 B CN 111116313B CN 201911413189 A CN201911413189 A CN 201911413189A CN 111116313 B CN111116313 B CN 111116313B
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- gas
- deuterated methanol
- catalyst
- carbon monoxide
- oxide
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000007789 gas Substances 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 13
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 12
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims description 24
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 18
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 11
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 9
- 239000005751 Copper oxide Substances 0.000 claims description 9
- 229910000431 copper oxide Inorganic materials 0.000 claims description 9
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 9
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 claims description 9
- 229910003446 platinum oxide Inorganic materials 0.000 claims description 9
- 239000011787 zinc oxide Substances 0.000 claims description 9
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229910010293 ceramic material Inorganic materials 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 2
- 238000011112 process operation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/15—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of oxides of carbon exclusively
- C07C29/151—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of oxides of carbon exclusively with hydrogen or hydrogen-containing gases
- C07C29/153—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of oxides of carbon exclusively with hydrogen or hydrogen-containing gases characterised by the catalyst used
- C07C29/156—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of oxides of carbon exclusively with hydrogen or hydrogen-containing gases characterised by the catalyst used containing iron group metals, platinum group metals or compounds thereof
- C07C29/157—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of oxides of carbon exclusively with hydrogen or hydrogen-containing gases characterised by the catalyst used containing iron group metals, platinum group metals or compounds thereof containing platinum group metals or compounds thereof
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention relates to a preparation method of deuterated methanol, belonging to the technical field of deuterated methanol preparation. The method takes deuterium gas, carbon monoxide gas and nitrogen as raw materials, the per-pass conversion rate of the reaction reaches more than 80 percent by optimizing reaction conditions, and the prepared deuterated methanol can reach more than 99.9 percent by simple rectification purity. The method disclosed by the invention has the characteristics of high selectivity, high conversion rate, less side reaction and high purity, and is suitable for fine production of deuterated methanol.
Description
Technical Field
The invention relates to a preparation method of deuterated methanol, belonging to the technical field of deuterated methanol preparation.
Background
Deuterated methanol, molecular formula CD 3 OD is methanol (CH) 3 OH) by its isotope deuterium ("D"). In recent years, nuclear magnetic resonance has played an increasingly important role in the fields of chemistry and chemistry, biochemistry and medicine, and is most widely applied in the fields of proteomics/chromonomy and pharmaceutical research. Deuterated reagents are indispensable solvents for nuclear magnetic resonance testing because of the need for very accurate locking of the magnetic field strength inside the nuclear magnetic field, while deuterated reagents are present inNuclear magnetism is mainly used for field locking. The deuterated methanol is a common solvent for nuclear magnetic resonance spectroscopy, and the dosage of the deuterated methanol is larger in the deuterated reagent. With the development of science and technology, deuterated drugs become new research hotspots in recent years. Because the deuterated drugs can improve the safety of the drugs and have the pharmacokinetic advantage, the deuterated drugs are a new direction for drug development, and the deuterated methanol is one of the most main raw materials of the deuterated drugs.
The preparation method of the common methanol is more suitable for the requirement of large-scale industrial production of the methanol, and the production of the fine chemical products of the deuterated methanol which only needs a scale of hundreds of kilograms to a few tons has the problems of low single-pass conversion rate, complex process, low purity and the like.
Disclosure of Invention
In view of the above, the invention provides a preparation method of deuterated methanol, which has the characteristics of simple process operation, high per-pass conversion rate, less side reactions and high product purity, and can meet the requirement of industrial production of deuterated methanol.
The purpose of the invention is realized by the following technical scheme.
A preparation method of deuterated methanol comprises the following steps,
introducing mixed gas of deuterium gas, carbon monoxide gas and nitrogen gas into a reactor filled with a catalyst, reacting at the pressure of 5 MPa-7 MPa and the temperature of 210-290 ℃, and condensing after the reaction is finished to obtain deuterated methanol liquid.
Wherein the catalyst is at least one of zinc oxide, copper oxide, aluminum oxide and platinum oxide.
Further, the catalyst is a mixture of zinc oxide, copper oxide, aluminum oxide and platinum oxide, and the mass percent of each component is as follows based on 100% of the total mass of the catalyst: 20 to 30 percent of zinc oxide, 50 to 60 percent of copper oxide, 5 to 10 percent of aluminum oxide and 5 to 10 percent of platinum oxide.
Further, the catalyst is filled in the reactor to form a catalyst layer by adopting a mode of mixing and filling the catalyst and an inert ceramic material (such as an inert alumina ceramic material), and the mass ratio of the catalyst to the inert ceramic material is 2: (1-3).
Further, the mixed gas of deuterium gas, carbon monoxide gas and nitrogen gas preferably passes through the catalyst layer at a rate of 4L/s to 10L/s, and is preferably circulated in the reactor for not less than 36 hours.
Further, the molar ratio of deuterium gas, carbon monoxide gas and nitrogen gas is preferably (2 to 10) 1: (1-3).
Further, the reaction temperature is preferably 220 to 260 ℃.
Further, a fixed bed reactor is used for the reaction.
Has the advantages that:
by optimizing reaction conditions, the method has the characteristics of high selectivity, high conversion rate, less side reactions and high purity, the per-pass conversion rate reaches more than 80%, the purity of the prepared deuterated methanol can reach more than 99.9% through simple rectification, and the method is simple in process operation and suitable for fine production of the deuterated methanol.
Detailed Description
The invention is further illustrated by the following detailed description, wherein the processes are conventional unless otherwise specified, and the starting materials are commercially available from a public source unless otherwise specified.
Example 1
Preparing copper oxide, zinc oxide, aluminum oxide and platinum oxide into a catalyst according to the mass ratio of 5; mixing a catalyst and inert alumina ceramic balls according to the mass ratio of 2; deuterium gas, carbon monoxide gas and nitrogen gas are mixed according to the molar ratio of 2.
The conversion per pass, calculated as carbon monoxide, was found to be 80%. The purity of the collected deuterated methanol liquid can reach 99.92 percent after rectification.
Example 2
Preparing copper oxide, zinc oxide, aluminum oxide and platinum oxide into a catalyst according to the mass ratio of 6; mixing a catalyst and inert alumina ceramic balls according to the mass ratio of 2; deuterium gas, carbon monoxide gas and nitrogen gas are mixed according to a molar ratio of 3.
The conversion per pass, calculated as carbon monoxide, was found to be 82%. The purity of the collected deuterated methanol liquid can reach 99.91 percent after rectification.
Example 3
Preparing the copper oxide, the zinc oxide, the aluminum oxide and the platinum oxide into a catalyst according to the mass ratio of 6; mixing the catalyst and inert alumina ceramic balls according to the mass ratio of 2; deuterium gas, carbon monoxide gas and nitrogen gas are mixed according to a molar ratio of 5.
The conversion per pass, calculated as carbon monoxide, was found to be 81%. The purity of the collected deuterated methanol liquid can reach 99.91 percent after rectification.
Example 4
Copper oxide, zinc oxide, aluminum oxide and platinum oxide are prepared into a catalyst according to the mass ratio of 5.8; mixing the catalyst and inert alumina ceramic balls according to the mass ratio of 2; deuterium gas, carbon monoxide gas and nitrogen gas are mixed according to the molar ratio of 3.
The conversion per pass, calculated as carbon monoxide, was found to be 82%. The purity of the collected deuterated methanol liquid can reach 99.90 percent after rectification.
In summary, the above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (6)
1. A preparation method of deuterated methanol is characterized by comprising the following steps: the steps of the method are as follows,
introducing mixed gas of deuterium gas, carbon monoxide gas and nitrogen gas into a reactor filled with a catalyst, reacting at the pressure of 5 MPa-7 MPa and the temperature of 210-290 ℃, and condensing after the reaction is finished to obtain deuterated methanol liquid;
the catalyst is a mixture of zinc oxide, copper oxide, aluminum oxide and platinum oxide, and the mass percent of each component is as follows by taking the total mass of the catalyst as 100 percent: 50% -60% of copper oxide, 20% -30% of zinc oxide, 5% -10% of aluminum oxide and 5% -10% of platinum oxide; the mol ratio of the deuterium gas, the carbon monoxide gas and the nitrogen gas is (2-10) and (1-3) respectively.
2. The method of claim 1, wherein the deuterated methanol is prepared by: the reaction temperature is 220-260 ℃.
3. The method of claim 1, wherein the deuterated methanol is prepared by: the reaction is carried out by adopting a fixed bed reactor.
4. The method of any one of claims 1 to 3, wherein: the catalyst and the inert alumina ceramic material are mixed and filled in the reactor to form a catalyst layer, and the mass ratio of the catalyst to the inert ceramic material is 2: (1-3).
5. The method of claim 4, wherein the deuterated methanol is prepared by: the mixed gas of deuterium gas, carbon monoxide gas and nitrogen gas passes through the catalyst layer at a rate of 4L/s to 10L/s.
6. The method of claim 5, wherein the deuterated methanol is prepared by: the mixed gas of carbon monoxide gas and nitrogen gas circularly reacts in the reactor for not less than 36h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911413189.6A CN111116313B (en) | 2019-12-31 | 2019-12-31 | Preparation method of deuterated methanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911413189.6A CN111116313B (en) | 2019-12-31 | 2019-12-31 | Preparation method of deuterated methanol |
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| Publication Number | Publication Date |
|---|---|
| CN111116313A CN111116313A (en) | 2020-05-08 |
| CN111116313B true CN111116313B (en) | 2023-04-14 |
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| CN201911413189.6A Active CN111116313B (en) | 2019-12-31 | 2019-12-31 | Preparation method of deuterated methanol |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321388A (en) * | 2020-11-16 | 2021-02-05 | 徐州亚兴医疗科技有限公司 | Preparation method of deuterated methanol with high conversion rate |
| CN112675875A (en) * | 2021-01-21 | 2021-04-20 | 浙江工业大学 | Catalyst for preparing deuterated methanol and preparation method thereof |
| CN113072421A (en) * | 2021-02-24 | 2021-07-06 | 中国船舶重工集团公司第七一八研究所 | Preparation method of deuterated ethanol |
| CN113600208B (en) * | 2021-08-30 | 2023-08-15 | 浙江工业大学 | CuCoMn/Al 2 O 3 Catalyst, preparation method and application thereof |
| CN116082121B (en) * | 2023-02-23 | 2023-08-15 | 安徽泽升科技有限公司 | Preparation method of deuterated methanol |
| CN115920973B (en) * | 2023-03-10 | 2023-05-26 | 泽升科技(广州)有限公司 | Preparation method of full deuterated methanol |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5137924A (en) * | 1982-12-13 | 1992-08-11 | Imperial Chemical Industries Plc | Catalytic process |
| CN104722305A (en) * | 2013-12-23 | 2015-06-24 | 中国科学院上海高等研究院 | Catalyst applicable to synthesis of methanol by multi-component mixed gas as well as preparation method and application of methanol catalyst |
| CN108250041A (en) * | 2018-02-26 | 2018-07-06 | 上海枢炬化工有限公司 | A kind of preparation method of full deuterated methanol |
| CN109078638A (en) * | 2018-08-30 | 2018-12-25 | 海门海康生物医药科技有限公司 | A kind of catalyst and preparation method thereof synthesizing deuterated methanol |
-
2019
- 2019-12-31 CN CN201911413189.6A patent/CN111116313B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5137924A (en) * | 1982-12-13 | 1992-08-11 | Imperial Chemical Industries Plc | Catalytic process |
| CN104722305A (en) * | 2013-12-23 | 2015-06-24 | 中国科学院上海高等研究院 | Catalyst applicable to synthesis of methanol by multi-component mixed gas as well as preparation method and application of methanol catalyst |
| CN108250041A (en) * | 2018-02-26 | 2018-07-06 | 上海枢炬化工有限公司 | A kind of preparation method of full deuterated methanol |
| CN109078638A (en) * | 2018-08-30 | 2018-12-25 | 海门海康生物医药科技有限公司 | A kind of catalyst and preparation method thereof synthesizing deuterated methanol |
Non-Patent Citations (1)
| Title |
|---|
| 氘标记药物分子的合成进展;宋瑞捧 等;《中国医药工业杂质》;20170628;第48卷(第6期);第809-815页 * |
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| CN111116313A (en) | 2020-05-08 |
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Address after: 056027 No. 17, Exhibition Road, Handan, Hebei Patentee after: 718th Research Institute of China Shipbuilding Corp. Address before: 056027 No. 17, Exhibition Road, Handan, Hebei Patentee before: Handan Purifying Equipment Research Institute |
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Effective date of registration: 20231020 Address after: 056027 Hebei Province, Handan city Congtai District Exhibition Road No. 17 Patentee after: Perry Technology Co.,Ltd. Address before: 056027 No. 17, Exhibition Road, Handan, Hebei Patentee before: 718th Research Institute of China Shipbuilding Corp. |