CN114181177A - Production method of novel alpha-bromo-gamma-butyrolactone - Google Patents
Production method of novel alpha-bromo-gamma-butyrolactone Download PDFInfo
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- CN114181177A CN114181177A CN202111409117.1A CN202111409117A CN114181177A CN 114181177 A CN114181177 A CN 114181177A CN 202111409117 A CN202111409117 A CN 202111409117A CN 114181177 A CN114181177 A CN 114181177A
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- Prior art keywords
- butyrolactone
- bromine
- bromo
- gamma
- catalyst
- 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.)
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Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 24
- LFJJGHGXHXXDFT-UHFFFAOYSA-N 3-bromooxolan-2-one Chemical compound BrC1CCOC1=O LFJJGHGXHXXDFT-UHFFFAOYSA-N 0.000 title claims abstract description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 51
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims abstract description 30
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000002994 raw material Substances 0.000 claims abstract description 13
- 229930188620 butyrolactone Natural products 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims abstract description 4
- 229910021575 Iron(II) bromide Inorganic materials 0.000 claims abstract description 3
- 229910021577 Iron(II) chloride Inorganic materials 0.000 claims abstract description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims abstract description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims abstract description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical group ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 19
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 9
- 239000007789 gas Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000001704 evaporation Methods 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 4
- 238000007670 refining Methods 0.000 claims description 4
- 238000007689 inspection Methods 0.000 claims description 3
- 238000007789 sealing Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- XQURFOAQULEYEO-UHFFFAOYSA-N C1(CCCO1)=O.[Br] Chemical compound C1(CCCO1)=O.[Br] XQURFOAQULEYEO-UHFFFAOYSA-N 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000005086 pumping Methods 0.000 description 3
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- DMXVIRCAGMRKKJ-UHFFFAOYSA-N 2,4-dibromobutanoyl bromide Chemical compound BrCCC(Br)C(Br)=O DMXVIRCAGMRKKJ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
Abstract
The invention relates to the technical field of organic chemical synthesis, and discloses a production method of novel alpha bromo-gamma butyrolactone, which has the following disadvantages: the method has the advantages of low yield, high cost and low purity, the market mainly contains 98% at present, the mass production is difficult to realize, kilogram-grade sales are provided through market consultation at present, hundreds of kilograms or tons of grades are rarely available, and a bromine source, a catalyst, a raw material and a solvent are prepared for later use, wherein the bromine source is bromine or HBr, the raw material is butyrolactone, the catalyst is PCl3、FeCl3、FeCl2CuBr or FeBr2The solvent is any one of dichloromethane, dichloroethane, toluene, ethanol or methanol. The alpha bromine-gamma butyrolactone produced by the method has the main content of more than 99.2 percent, the yield is improved to more than 80 percent, the single batch reaches 800kg, the tonnage supply is provided by the market, and the production method has lower production cost, wider application range, certain market popularization prospect and application value.
Description
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a production method of novel alpha bromine-gamma butyrolactone.
Background
The synthesis of alpha-bromo-gamma-butyrolactone does not form a slightly large-scale production at the present stage, and two organic routes are available for chemical synthesis: firstly, butyrolactone is used as a raw material; secondly, 2, 4-dibromobutyryl bromide is used as a raw material, in addition, a biological method is used for synthesizing alpha-bromo-gamma-butyrolactone, and a single contrast experiment is utilized to optimize the fermentation conditions of the screened strain which has certain stereoselectivity and hydrolytic activity and can produce lactone, so that the optimal fermentation conditions of the strain are obtained.
The alpha bromine-gamma butyrolactone prepared by the existing production method has the following disadvantages:
1: the yield is low and the cost is high;
2: the purity is low, and the market is mainly based on 98 percent content at present;
3: the mass production is difficult to realize, and the kilogram-level sales are provided through market consultation at present, and the hundred kilogram-level or ton-level sales are rarely available. Accordingly, those skilled in the art have provided a novel method for producing α bromo- γ butyrolactone to solve the problems set forth in the background art described above.
Disclosure of Invention
The invention aims to provide a novel production method of alpha bromine-gamma butyrolactone, the alpha bromine-gamma butyrolactone produced by the method has the main content of more than 99.2 percent, the yield is improved to more than 80 percent, the single batch reaches 800kg, the market provides ton-grade supply, and the production method has lower production cost, wider application range and certain market popularization prospect and application value.
In order to achieve the purpose, the invention provides the following technical scheme:
a method for producing novel alpha-bromo-gamma-butyrolactone comprises the following steps:
s1, preparing a bromine source, a catalyst, a raw material and a solvent for later use, wherein the bromine source is bromine or HBr, the raw material is butyrolactone, and the catalyst is PCl3、FeCl3、FeCl2CuBr or FeBr2The solvent is any one of dichloromethane, dichloroethane, toluene, ethanol or methanol;
s2, weighing a proper amount of bromine in a constant dropping funnel, sealing for later use, adding a proper amount of gamma-butyrolactone into a three-necked bottle, stirring at room temperature, adding a catalyst, transferring the three-necked bottle into an oil bath, heating, setting a reaction temperature, and then beginning to dropwise add the prepared bromine;
s3: cooling to below 30 ℃ after the reaction is qualified, vacuumizing by using a water pump, removing bromine and hydrogen bromide gas, adding a proper amount of water and a proper amount of toluene, stirring for 30min at the temperature of below 20 ℃, then adding a pH value regulator in batches slowly to separate an organic phase from an upper layer, adding 20ml of toluene into a water phase for extraction, combining the organic phases, adding 13.3g of anhydrous sodium sulfate for drying for 2h, paving kieselguhr for filtering, evaporating toluene by using a water pump at 55 ℃, and refining unreacted raw materials and products by using an oil pump under high vacuum.
As a still further scheme of the invention: the reaction temperature is 40-80 ℃, the reaction time is 8-12h, the dropping time of bromine is 12-14h, and the sample is taken for inspection after the dropping and heat preservation reaction is finished for 2 h.
As a still further scheme of the invention: the molar ratio of butyrolactone to bromine is 1 (1.2-1.5), and the molar ratio of butyrolactone to HBr is 1 (2.2-2.5).
As a still further scheme of the invention: the pH value regulator is Na2CO3NaOH or KOH, and the addition amount of the pH value regulator is 75g, and the pH value is 6-7.
As a still further scheme of the invention: the molar ratio of the catalyst is 0.1-0.4 times that of butyrolactone.
Compared with the prior art, the invention has the beneficial effects that: the alpha bromine-gamma butyrolactone produced by the method has the main content of more than 99.2 percent, the yield is improved to more than 80 percent, the single batch reaches 800kg, the tonnage supply is provided by the market, and the production method has lower production cost, wider application range, certain market popularization prospect and application value.
Detailed Description
Example 1
A method for producing novel alpha-bromo-gamma-butyrolactone comprises the following steps:
s1, weighing 240.79g of bromine in a constant-dropping funnel, sealing for later use, adding 86.09g of gamma-butyrolactone into a three-necked bottle, and adding 1.6g of PCl under stirring at room temperature3Then transferring the three-mouth bottle into an oil bath pan to heat up, wherein the temperature reaches 50 ℃, the oil temperature is set to heat up to 55 ℃, and simultaneously, dropwise adding the prepared bromine, wherein the dropwise adding speed is suitable that no red color appears in a condenser on the reaction bottle, the dropwise adding time is 12-14 hours, the temperature-keeping reaction is finished for 2 hours after the dropwise adding, sampling and inspecting are carried out, the reaction is qualified, the next step of treatment is carried out, and if the reaction is unqualified, the experimental operation is repeated until the product of the sampling and inspecting is qualified;
s2, after the reaction is qualified, cooling to below 30 ℃, vacuumizing by a water pump, pumping out bromine and hydrogen bromide gas, adding 100ml of water and 100ml of toluene, stirring for 30min, heating to below 20 ℃, adding solid sodium hydroxide in batches, slowly adding sodium hydrogen oxide to prevent overheating, determining the adding amount of the sodium hydrogen oxide according to the pH value of the system, adding 75g of sodium hydrogen oxide, separating an organic phase from an upper layer, adding 20ml of toluene into an aqueous phase for extraction, combining the organic phases, adding 13.3g of anhydrous sodium sulfate for drying for 2h, spreading diatomite for filtration, evaporating the toluene by a water pump at 55 ℃, then refining by a high vacuum oil pump to obtain unreacted raw materials and products, obtaining a front fraction at the temperature of 90 ℃, receiving a main fraction at the temperature of 90-110 ℃ as 132g of the product, obtaining the GC content of 99.5% and obtaining the yield of 80%.
Example 2
A method for producing novel alpha-bromo-gamma-butyrolactone comprises the following steps:
s1, adding 86.09g of gamma-butyrolactone into a three-neck bottle, and adding 29.6g of FeBr under stirring at room temperature3Then transferring the three-mouth bottle into an oil bath pan to heat up, wherein the temperature reaches 46 ℃, the oil temperature is set to heat up to 45 ℃, and simultaneously, 240g of prepared bromine is dripped, the dripping speed is suitable for no red bromine in a condenser on the reaction bottle, the dripping time is 12-14 hours, the heat preservation reaction is finished for 2 hours after dripping, sampling and inspection are carried out, the reaction is qualified, the next step of treatment is carried out, and if the reaction is unqualified, the experimental operation is repeated until the product sampled and inspected is qualified;
s2, after the reaction is qualified, cooling to below 20 ℃, vacuumizing by a water pump, pumping bromine and hydrogen bromide gas, adding 100ml of water and 100ml of toluene, stirring for 10 minutes to obtain light yellow, heating to below 20 ℃, adding solid sodium carbonate in batches, slowly adding sodium carbonate to prevent excessive gas and liquid overflow, wherein the adding amount of the sodium carbonate is determined according to the pH value of a system, the pH value is 6-7, the mass of the sodium carbonate is 47g, the organic phase is on the upper layer, separating two phases, adding 20ml of toluene into the aqueous phase for extraction, combining the organic phases, adding 13.3g of anhydrous sodium sulfate for drying for 2 hours, spreading kieselguhr for filtration, evaporating toluene by a water pump at 55 ℃, then carrying out high-vacuum distillation by an oil pump to obtain unreacted raw materials and products, wherein the former fraction is the former fraction at 90 ℃, receiving the main fraction at 90-110 ℃ to obtain 135.3g of the product with the GC content of 99.6%, and the yield of 82%.
Example 3
A method for producing novel alpha-bromo-gamma-butyrolactone comprises the following steps:
s1, adding 86.09g of gamma-butyrolactone and 200g of dichloroethane into a three-mouth bottle, adding 16g of CuBr under stirring at room temperature, then transferring the three-mouth bottle into an oil bath pan, heating to reflux, starting dropwise adding prepared HBr334.8g at the same time, wherein the dropwise adding speed is suitable for no red color in a condenser on the reaction bottle, the dropwise adding time is 10 hours, the temperature preservation reaction is finished for 2 hours, sampling and inspecting are carried out, the reaction is qualified, the next step of treatment is carried out, and if the reaction is unqualified, the experimental operation is repeated until the product sampled and inspected is qualified;
s2, after the reaction is qualified, cooling to below 10 ℃, vacuumizing by a water pump, pumping bromine and hydrogen bromide gas, adding 100ml of water, stirring for 10 minutes, removing bromine color of the system, showing light yellow, heating to below 10 ℃, adding solid sodium hydroxide in batches, slowly adding sodium hydroxide, wherein the adding amount of the sodium hydroxide is determined according to the pH value of the system, the pH value is between 6 and 7, the mass of the added sodium hydroxide is 35g, the organic phase is at the lower layer, separating two phases, adding 20ml of toluene into the water phase for extraction, combining the organic phases, adding 13.3g of anhydrous sodium sulfate for drying for 2 hours, paving kieselguhr for filtration, evaporating toluene by a water pump at 55 ℃, and then refining by an oil pump in high vacuum to distill unreacted raw materials and products, wherein the former fraction is at the temperature of 90 ℃, the main fraction is received at the temperature of 90-110 ℃ and is 132g of the product, the GC content is 98.6%, and the yield is 80%.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed.
Claims (5)
1. A production method of novel alpha-bromo-gamma-butyrolactone is characterized by comprising the following steps:
s1, preparing a bromine source, a catalyst, a raw material and a solvent for later use,wherein the bromine source is bromine or HBr, the raw material is butyrolactone, and the catalyst is PCl3、FeCl3、FeCl2CuBr or FeBr2The solvent is any one of dichloromethane, dichloroethane, toluene, ethanol or methanol;
s2, weighing a proper amount of bromine in a constant dropping funnel, sealing for later use, adding a proper amount of gamma-butyrolactone into a three-necked bottle, stirring at room temperature, adding a catalyst, transferring the three-necked bottle into an oil bath, heating, setting a reaction temperature, and then beginning to dropwise add the prepared bromine;
s3: cooling to below 30 ℃ after the reaction is qualified, vacuumizing by using a water pump, removing bromine and hydrogen bromide gas, adding a proper amount of water and a proper amount of toluene, stirring for 30min at the temperature of below 20 ℃, then adding a pH value regulator in batches slowly to separate an organic phase from an upper layer, adding 20ml of toluene into a water phase for extraction, combining the organic phases, adding 13.3g of anhydrous sodium sulfate for drying for 2h, paving kieselguhr for filtering, evaporating toluene by using a water pump at 55 ℃, and refining unreacted raw materials and products by using an oil pump under high vacuum.
2. The method for producing the novel alpha-bromo-gamma-butyrolactone according to claim 1, wherein the reaction temperature is 40-80 ℃, the reaction time is 8-12h, the dropping time of the bromine is 12-14h, and the sample is taken for inspection after the dropping and heat preservation reaction is finished for 2 h.
3. The method for producing α bromo- γ butyrolactone in accordance with claim 1, wherein the molar ratio of butyrolactone and bromine is 1 (1.2-1.5), and the molar ratio of butyrolactone and HBr is 1 (2.2-2.5).
4. The method for producing α bromo- γ butyrolactone in accordance with claim 1, wherein said pH regulator is Na2CO3NaOH or KOH, and the addition amount of the pH value regulator is 75g, and the pH value is 6-7.
5. The method for producing a novel α bromo- γ butyrolactone according to claim 1, wherein the molar ratio of said catalyst is 0.1 to 0.4 times that of butyrolactone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111409117.1A CN114181177A (en) | 2021-11-25 | 2021-11-25 | Production method of novel alpha-bromo-gamma-butyrolactone |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111409117.1A CN114181177A (en) | 2021-11-25 | 2021-11-25 | Production method of novel alpha-bromo-gamma-butyrolactone |
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| Publication Number | Publication Date |
|---|---|
| CN114181177A true CN114181177A (en) | 2022-03-15 |
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Family Applications (1)
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| CN202111409117.1A Pending CN114181177A (en) | 2021-11-25 | 2021-11-25 | Production method of novel alpha-bromo-gamma-butyrolactone |
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| Country | Link |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232644A (en) * | 2018-09-30 | 2019-01-18 | 武汉工程大学 | The synthetic method of glufosinate-ammonium |
| CN112876394A (en) * | 2021-02-09 | 2021-06-01 | 中国科学院福建物质结构研究所 | Preparation method of DL-hydroxyselenomethionine |
-
2021
- 2021-11-25 CN CN202111409117.1A patent/CN114181177A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232644A (en) * | 2018-09-30 | 2019-01-18 | 武汉工程大学 | The synthetic method of glufosinate-ammonium |
| CN112876394A (en) * | 2021-02-09 | 2021-06-01 | 中国科学院福建物质结构研究所 | Preparation method of DL-hydroxyselenomethionine |
Non-Patent Citations (2)
| Title |
|---|
| 崔庆等: "Cedarmycins A 和B 及其类似物的首次合成", 有机化学 * |
| 曾凡亮等: "高丝氨酸的合成研究", 精细化工中间体 * |
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Application publication date: 20220315 |