CN114805065A - Preparation method of oxalyl chloride monoester - Google Patents
Preparation method of oxalyl chloride monoester Download PDFInfo
- Publication number
- CN114805065A CN114805065A CN202210404496.3A CN202210404496A CN114805065A CN 114805065 A CN114805065 A CN 114805065A CN 202210404496 A CN202210404496 A CN 202210404496A CN 114805065 A CN114805065 A CN 114805065A
- Authority
- CN
- China
- Prior art keywords
- optionally
- oxalic acid
- monoester
- reaction
- salt
- 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
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of oxalyl chloride monoester, which comprises the following steps: 1) oxalic acid diester (I) and bicarbonate are used as raw materials and hydrolyzed in anhydrous alcohol solvent to generate oxalate monoester salt (II); 2) the salt (II) of the oxalic acid monoester is chlorinated to produce oxalyl chloride monoester (III). The invention selects bicarbonate to react with oxalic acid diester, after the reaction is finished, the salt of oxalic acid monoester can be separated by centrifugation, only the alcoholic solvent (such as methanol or ethanol) needs to be dried, and the drying time and the heat energy can be saved by more than 80 percent relative to the drying moisture.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to a preparation method of oxalyl chloride monoester.
Background
The oxalyl chloride monomethyl ester/monoethyl ester is a fine chemical intermediate with wide application range, and is widely applied to the fields of medicines and pesticides. The production process mainly comprises two types.
Route 1: reaction of oxalyl chloride with methanol/ethanol
Reaction of oxalyl chloride with methanol or ethanol is the predominant synthesis method for oxalyl chloride monomethyl/monoethyl ester. Such as EP2940010, CN111978243, CN107417714, CN1891688, CN101638364 and CN 101638365.
In this route, the expensive starting material oxalyl chloride is used. Oxalyl chloride is generally prepared by reacting oxalic acid with phosphorus pentachloride, the yield is 40-60%, a large amount of phosphorus-containing acidic waste is generated, and the environmental protection pressure is huge.
Route 2: reaction of potassium oxalate monoester with thionyl chloride
A two-step synthesis of oxalyl chloride monomethyl ester is reported by Southwick, Philip L. on the Journal of the American Chemical Society,1949,71, 2532-8: firstly, dimethyl oxalate is hydrolyzed into monopotassium salt of oxalic acid monoester in methanol under the action of potassium acetate, and methyl acetate is a byproduct. The monopotassium salt then reacts with thionyl chloride to form oxalyl chloride monomethyl ester.
The same route was also reported for the synthesis of oxalyl chloride monoethyl ester in Organic & Biomolecular Chemistry,2011, 9(8), 2702-2714.
However, in the process for preparing the monopotassium salt of oxalic acid monoester reported in the above documents, a certain amount of water is added to the reaction system in order to make the reaction proceed smoothly. In the post-treatment, in order to isolate the monopotassium salt of the oxalic acid monoester, a large amount of organic solvent such as ethyl acetate is added to separate out a solid product such as CN 105439883; alternatively, all the solvent may be distilled off under reduced pressure and then dried, for example in WO 2005/53609. Both of these treatments have certain drawbacks. The former needs to consume more organic solvent, and needs to distill and separate by-products of methanol and methyl acetate (the boiling point of methyl acetate is 58 ℃, the boiling point of methanol is 65 ℃, the boiling points of the two are close, so the distillation and separation have great difficulty), and the process is complicated. In the latter, although no additional solvent is added into the system, the by-product methyl acetate still needs to be rectified and separated; moreover, because the subsequent chlorination reaction has higher requirement on the anhydrous system, the drying time of the water-containing monopotassium salt is 3-5 times longer than that of the solvent which is simply dried, and the production cost and the energy consumption are higher.
In conclusion, no synthesis process of oxalyl chloride monomethyl ester/monoethyl ester, which is economical, environment-friendly and simple and convenient to operate, exists.
Disclosure of Invention
Object of the Invention
In order to overcome the defects, the invention aims to provide a preparation method of oxalyl chloride monoester.
The invention selects bicarbonate to react with oxalic acid diester, after the reaction is finished, the salt of oxalic acid monoester can be separated by centrifugation, only the alcoholic solvent (such as methanol or ethanol) needs to be dried, and the drying time and the heat energy can be saved by more than 80 percent relative to the drying moisture. The solvent methanol or ethanol used in the reaction can be directly applied in the subsequent production process without special treatment.
Solution scheme
In order to realize the purpose of the invention, the technical scheme adopted by the invention is as follows:
in one aspect, the present invention provides a method for preparing oxalyl chloride monoester, which comprises the following steps:
1) oxalic acid diester (I) and bicarbonate are used as raw materials and hydrolyzed in anhydrous alcohol solvent to generate oxalate monoester salt (II);
2) chlorination reaction of the salt (II) of the oxalic acid monoester to generate oxalyl chloride monoester (III);
the reaction routes of steps 1) and 2) are as follows:
wherein, R, R 1 The same or different, are respectively and independently selected from C1-C5 alkyl.
R and R 1 And meanwhile, the difficulty of separating and drying the solvent can be reduced.
Further, R is selected from-CH 3 or-CH 2 CH 3 Alternatively, R and R 1 The same is true. R is-CH 3 When the oxalic acid diester (I) is dimethyl oxalate, the prepared oxalyl chloride monoester (III) is oxalyl chloride monomethyl ester. R is-CH 2 CH 3 When the oxalic acid diester (I) is diethyl oxalate, the prepared oxalyl chloride monoester (III) is oxalyl chloride monoethyl ester. Oxalyl chloride monomethyl ester or oxalyl chloride monoethyl ester is a fine chemical intermediate with wide application.
Further, the bicarbonate is selected from sodium bicarbonate and/or potassium bicarbonate.
Further, in the hydrolysis reaction in the step 1), mixing oxalic acid diester (I), bicarbonate and alcohol solvent, refluxing, cooling after the reaction is finished, carrying out solid-liquid separation on sodium salt (II) of oxalic acid monoester, and drying the solid for the next reaction; the solid-liquid separation comprises centrifugal separation and/or filtration separation.
Further, in the hydrolysis reaction of step 1), carbon dioxide and alcohol are by-products. After the first step of solid-liquid separation, a small amount of unreacted raw materials and by-products methanol or ethanol are left in the mother liquor and can be applied to the production of the next batch.
Further, the molar ratio of oxalic acid diester (I) to bicarbonate is 1: (1-1.5), optionally 1 (1-1.2), optionally 1: 1.
Further, the volume ratio of the alcohol solvent to the oxalic acid diester (I) is 1: (0.5-5), optionally 1: (1-5), optionally 1: (1-2), optionally 1: 1.
further, in the chlorination reaction of step 2), a chlorinating agent is used to react with the salt of oxalic acid monoester (II).
Further, the molar ratio of the salt of oxalic acid monoester (II) to the chlorine in the chlorinating reagent is 1: (2-8), optionally 1: (2.1-6), optionally 1: (2.1-4), optionally 1: (2.1-3), optionally 1: (2.1-2.5), optionally 1: (2.1-2.3).
Further, the chlorinating agent is selected from one or more of thionyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and triphosgene.
Further, the chlorinating agent was added dropwise to the reaction system under stirring.
Further, the chlorination reaction of step 2) is carried out in a solvent selected from a chlorine-containing organic solvent or a benzene-based organic solvent, optionally, the chlorine-containing organic solvent comprises dichloromethane and/or dichloroethane; alternatively, the benzene-based organic solvent comprises toluene and/or xylene.
Further, in the chlorination reaction of step 2), the temperature of the chlorination reaction is 30-120 ℃, alternatively 44-120 ℃, alternatively 55-100 ℃, alternatively 60-100 ℃.
Further, after chlorination of the salt (II) of oxalic acid monoester, oxalyl chloride monoester was obtained by distillation under reduced pressure.
The reaction scheme involved in the reaction scheme of the present invention is as follows:
two reaction routes in the chlorination reaction may be:
advantageous effects
(1) The invention selects bicarbonate to react with oxalic acid diester, after the reaction is finished, the salt of oxalic acid monoester can be separated by centrifugation, only the alcoholic solvent (such as methanol or ethanol) needs to be dried, and the drying time and the heat energy can be saved by more than 80 percent relative to the drying moisture. The solvent methanol or ethanol used in the reaction can be directly applied in the subsequent production process without special treatment. The method has the advantages of cheap and easily obtained raw materials, simple and convenient operation, high yield and environmental friendliness.
(2) The method can prepare the oxalyl chloride monomethyl ester or oxalyl chloride monoethyl ester, simplify the production process and improve the yield.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Furthermore, in the following detailed description, numerous specific details are set forth in order to provide a better understanding of the present invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, elements, methods, means, and the like that are well known to those skilled in the art are not described in detail in order to not unnecessarily obscure the present invention.
Throughout the specification and claims, unless explicitly stated otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or component but not the exclusion of any other element or component.
The following examples dimethyl oxalate/diethyl oxalate are commercially available.
GC in the following examples refers to gas chromatography.
Example 1
118 g of dimethyl oxalate (1mol) were dissolved in 120 ml of methanol, 84 g of sodium bicarbonate (1mol) were added, and after refluxing for 14 hours, GC analysis showed that the starting dimethyl oxalate remained less than 1%. Cooling to about 5 ℃, centrifuging, filtering, leaching with 10 ml of cold methanol, combining the filtrate and the leacheate, and applying the filtrate and the leacheate in the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 124 g of crude product in 98% yield.
124 g of the crude methyl oxalate monosodium salt (the molar amount of the methyl oxalate monosodium salt is determined to be 984mmol by liquid chromatography) are suspended in 250 ml of dichloromethane, 129 g (1.08mol) of thionyl chloride is added dropwise, and the mixture is refluxed for 6 hours. According to the requirement of environmental protection, secondary water absorption (possibly containing trace hydrogen chloride) is carried out, and the by-product sulfur dioxide is absorbed by the primary liquid alkali. The product is subjected to reduced pressure distillation, and 118-120 ℃ fractions are collected to obtain 116 g of oxalyl chloride monomethyl ester product, the content is 99.5 percent by GC detection, and the total yield of the two steps is 95 percent.
Example 2:
118 g of dimethyl oxalate (1mol) were dissolved in 120 ml of methanol (filtrate from example 1), 84 g of sodium bicarbonate (1mol) were added, and after refluxing for 14 hours, GC analysis showed that the starting dimethyl oxalate remained less than 1%. Cooling to about 5 ℃, centrifuging, filtering, leaching with 10 ml of cold methanol, combining the filtrate and the leacheate, and applying the filtrate and the leacheate in the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 123 g of crude product in 98% yield.
123 g of the crude methyl oxalate monosodium salt (the molar amount of methyl oxalate monosodium salt determined by liquid chromatography is 976mmol) are suspended in 120 ml of dichloroethane, 129 g (1.08mol) of thionyl chloride is added dropwise, and the mixture is refluxed for 4 hours. According to the requirement of environmental protection, secondary water absorption (possibly containing trace hydrogen chloride) is carried out, and the by-product sulfur dioxide is absorbed by the primary liquid alkali. The product is subjected to reduced pressure distillation, and 118-120 ℃ fractions are collected to obtain 115 g of oxalyl chloride monomethyl ester product, the content is 99.4 percent by GC detection, and the two-step total yield is 94 percent.
Example 3:
118 g of dimethyl oxalate (1mol) were dissolved in 200 ml of methanol, 84 g of sodium bicarbonate (1mol) were added, and after refluxing for 10 hours, GC analysis showed that the starting dimethyl oxalate remained less than 1%. Cooling to about 5 ℃, centrifuging, filtering, leaching with 10 ml of cold methanol, combining the filtrate and the leacheate, and applying the filtrate and the leacheate in the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 120 g of crude product with a yield of 95%.
120 g of the crude methyl oxalate monosodium salt (the molar amount of methyl oxalate monosodium salt determined by liquid chromatography is 952mmol) are suspended in 50 ml of toluene, 146 g (1.22mol) of thionyl chloride is added dropwise with stirring, and the reaction is carried out at an internal temperature of 60 ℃ for 4 hours. According to the requirement of environmental protection, secondary water absorption (possibly containing trace hydrogen chloride) is carried out, and the by-product sulfur dioxide is absorbed by the primary liquid alkali. The product is distilled under reduced pressure, and the fraction at 120 ℃ of 118 ℃ is collected to obtain 114 g of oxalyl chloride monomethyl ester product with the content of 99.6 percent by GC detection and the total yield of the two steps of 93 percent.
Example 4
146 g diethyl oxalate (1mol) is dissolved in 200 ml ethanol, 100 g potassium bicarbonate (1mol) is added, and after refluxing for 10 hours, GC detection shows that the raw material diethyl oxalate residue is less than 2%. Cooling to about 5 ℃, centrifuging, filtering, leaching with 10 ml of cold ethanol, and combining the filtrate and the leacheate for application in the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 148 g of crude product with a yield of 95%.
133 g of the crude ethyl oxalate monopotassium salt (the molar weight of the ethyl oxalate monopotassium salt is determined to be 952mmol by liquid chromatography) are suspended in 150 ml of xylene, 125 g (1.05mol) of thionyl chloride is added dropwise with stirring, and the reaction is carried out at an internal temperature of 60 ℃ for 4 hours. According to the requirement of environmental protection, secondary water absorption (possibly containing trace hydrogen chloride) and primary liquid caustic soda absorption (sulfur dioxide) are carried out. The product is distilled under reduced pressure, the fraction at 135 ℃ of 133-.
Example 5
146 g diethyl oxalate (1mol) were dissolved in 200 ml ethanol (mother liquor from example 4), 100 g potassium bicarbonate (1mol) were added, and after 10 hours of reflux GC detection showed less than 2% of the starting diethyl oxalate remaining. Cooling to about 5 ℃, centrifuging, leaching with 10 ml of cold ethanol, and combining the filtrate and the leacheate for the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 132 g of crude product in 90% yield.
132 g of the crude ethyl oxalate monosodium salt (the molar amount of the ethyl oxalate monosodium salt is determined to be 904mmol by liquid chromatography) are suspended in 50 ml of dichloromethane, 98 g of triphosgene (330mmol) is added dropwise with stirring and dissolved in 140 ml of dichloromethane solution, and the reaction is carried out at an internal temperature of 60 ℃ for 4 hours. And performing secondary water absorption (possibly containing trace hydrogen chloride) and primary liquid alkali absorption according to the environmental protection requirement. The product is subjected to reduced pressure distillation, and the fraction at 135 ℃ of 133-.
Comparative example 1
118 g of dimethyl oxalate (1mol) are dissolved in 120 ml of methanol, 98 g of potassium acetate (1mol) are added, and after refluxing for 14 hours, HPLC detection shows that the raw material dimethyl oxalate can not be reacted further. Cooling to about 5 ℃, centrifuging, filtering, leaching with 10 ml of cold methanol, combining the filtrate and the leacheate, and applying the filtrate and the leacheate in the next batch. The filter cake was dried at 60 ℃ for 2 hours to give 124 g of crude product, 81% yield, 93% content.
124 g of crude methyl oxalate monopotassium salt (the molar weight of the methyl oxalate monopotassium salt is determined to be 812mmol by liquid chromatography) is suspended in 250 ml of dichloromethane, 129 g (1.08mol) of thionyl chloride is dropwise added, the mixture is refluxed for 6 hours, secondary water absorption (possibly containing trace hydrogen chloride) is carried out according to the requirement of environmental protection, and the primary liquid alkali absorbs the byproduct sulfur dioxide. The product is subjected to reduced pressure distillation, and 118-120 ℃ fractions are collected to obtain 89 g of oxalyl chloride monomethyl ester product, the content is 99 percent by GC detection, and the total yield of the two steps is 72 percent.
Comparative example 1 illustrates that dimethyl oxalate and potassium acetate have poor reaction yields in an anhydrous environment, which may be caused by incomplete hydrolysis of dimethyl oxalate by potassium acetate.
In addition, in the comparative example 1, a byproduct methyl acetate is generated in the preparation process of the crude methyl oxalate monopotassium salt, the boiling points of the methyl acetate and the solvent methanol are relatively close, the methanol is difficult to separate and recycle, and the recycling cost of the methanol is increased.
Comparative example 2
118 g dimethyl oxalate (1mol) is dissolved in 1000 ml water, 98 g potassium acetate (1mol) is added, after 12 hours of reflux, HPLC is used for central control tracking reaction, about 800 g water is distilled off under reduced pressure, 1000 ml acetone is added, the product monomethyl oxalate monopotassium salt is separated out, filtration is carried out, the wet product of monomethyl oxalate monopotassium salt is obtained, after 12 hours, drying is carried out, and 128 g dry product is obtainedAnd detecting the content of the monopotassium oxalate containing 92 percent of dipotassium oxalate (C) by liquid phase detection 2 O 4 K 2 ) The calculated yield after purification was 83%.
Comparative example 2 is a conventional method for preparing monomethyl oxalate monopotassium, which shows that potassium acetate can improve the yield of the final product to a certain extent in the presence of water, but the final product contains a byproduct of dipotassium oxalate which is difficult to remove, so that the purification cost is increased and waste salt is generated.
In addition, the comparative example 2 can also produce a byproduct of methyl acetate in the reaction process, the boiling points of the methyl acetate and the solvent acetone are relatively close, the acetone is difficult to separate and recover, and the recovery cost of the acetone is increased.
The present inventors have unexpectedly found that a hydrolysis reaction without adding water, in which a bicarbonate salt is reacted with an oxalic acid diester in an anhydrous environment, can be performed with high selectivity to the degree of a mono-salt of oxalic acid monoester, and that not only the yield is improved, but also the purity of the product is high, which is much more than the inventors have expected. And the resulting MCl salt and CO as the bicarbonate starting materials 2 Easy to remove (in the reaction system, MCl salt has low solubility in the system and is easy to separate out, CO 2 Can escape from the reaction system), greatly simplifying the process steps. In addition, the product oxalic acid monoester salt is easy to dry, and the solvent for reaction can be applied to subsequent production without being purified by a special means, so that the production is very favorable, and the production cost is greatly reduced. The inventor of the invention also finds that MOH and M are adopted 2 CO 3 、M 2 PO 4 The alkali can cause the oxalic acid diester to be easily hydrolyzed to generate more oxalic acid (di) salt, and the reaction result and the purification step are influenced.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present 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 solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A preparation method of oxalyl chloride monoester comprises the following steps:
1) oxalic acid diester (I) and bicarbonate are used as raw materials and hydrolyzed in anhydrous alcohol solvent to generate oxalate monoester salt (II);
2) chlorination reaction of the salt (II) of the oxalic acid monoester to generate oxalyl chloride monoester (III);
the reaction routes of steps 1) and 2) are as follows:
wherein, R, R 1 The same or different, are respectively and independently selected from C1-C5 alkyl.
2. The method of claim 1, wherein R is selected from-CH 3 or-CH 2 CH 3 Alternatively, R and R 1 The same;
and/or the bicarbonate is selected from sodium bicarbonate and/or potassium bicarbonate.
3. The preparation method according to claim 1 or 2, wherein in the hydrolysis reaction in step 1), the oxalic acid diester (I), the bicarbonate and the alcohol solvent are mixed and refluxed, after the reaction is finished, the mixture is cooled, the sodium salt (II) of the oxalic acid monoester is subjected to solid-liquid separation, and the solid is dried and then used for the next reaction; the solid-liquid separation comprises centrifugal separation and/or filtration separation.
4. The production method according to any one of claims 1 to 3, wherein the by-products in the hydrolysis reaction of step 1) are carbon dioxide and alcohol.
5. The process according to any one of claims 1 to 4, wherein the molar ratio of oxalic acid diester (I) to the bicarbonate is 1: (1-1.5), optionally 1 (1-1.2), optionally 1: 1.
6. The process according to any one of claims 1 to 5, wherein the volume ratio of the alcohol solvent to the oxalic acid diester (I) is 1: (0.5-5), optionally 1: (1-5), optionally 1: (1-2), optionally 1: 1.
7. the process according to any one of claims 1 to 6, wherein in the chlorination reaction of step 2), a chlorinating agent is used to react with the salt of oxalic acid monoester (II);
alternatively, the molar ratio of the salt of oxalic acid monoester (II) to the chlorine in the chlorinating reagent is 1: (2-8), optionally 1: (2.1-6), optionally 1: (2.1-4), optionally 1: (2.1-3), optionally 1: (2.1-2.5), optionally 1: (2.1-2.3);
optionally, the chlorinating agent is selected from one or more of thionyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and triphosgene;
alternatively, the chlorinating agent is added dropwise to the reaction system with stirring.
8. The process according to any one of claims 1 to 7, wherein the chlorination reaction of step 2) is carried out in a solvent selected from a chlorine-containing organic solvent or a benzene-based organic solvent, optionally the chlorine-containing organic solvent comprises dichloromethane and/or dichloroethane; alternatively, the benzene-based organic solvent comprises toluene and/or xylene.
9. The process of any one of claims 1 to 8, wherein the chlorination reaction of step 2) is carried out at a temperature of from 30 ℃ to 120 ℃, optionally from 44 ℃ to 120 ℃, optionally from 55 ℃ to 120 ℃, optionally from 60 ℃ to 100 ℃.
10. The production process according to any one of claims 1 to 9, wherein the oxalyl chloride monoester is obtained by distillation under reduced pressure after chlorination of the salt of oxalic acid monoester (II).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210404496.3A CN114805065A (en) | 2022-04-18 | 2022-04-18 | Preparation method of oxalyl chloride monoester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210404496.3A CN114805065A (en) | 2022-04-18 | 2022-04-18 | Preparation method of oxalyl chloride monoester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114805065A true CN114805065A (en) | 2022-07-29 |
Family
ID=82537031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210404496.3A Pending CN114805065A (en) | 2022-04-18 | 2022-04-18 | Preparation method of oxalyl chloride monoester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114805065A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747226A (en) * | 2008-12-12 | 2010-06-23 | 叶蕴华 | N-oxalic acid acyl amino acid derivatives and N-oxalic acid acyl dipeptide derivatives as well as applications thereof in preparation of consciousness-promoted drugs |
| CN102199134A (en) * | 2011-03-23 | 2011-09-28 | 山东大学 | Thiadiazole histone deacetylase inhibitors and application thereof |
-
2022
- 2022-04-18 CN CN202210404496.3A patent/CN114805065A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747226A (en) * | 2008-12-12 | 2010-06-23 | 叶蕴华 | N-oxalic acid acyl amino acid derivatives and N-oxalic acid acyl dipeptide derivatives as well as applications thereof in preparation of consciousness-promoted drugs |
| CN102199134A (en) * | 2011-03-23 | 2011-09-28 | 山东大学 | Thiadiazole histone deacetylase inhibitors and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| BURRELL, RICHARD C.，等: "Carbon-14 labeled methyl 2-chloro-2-oxoacetate: a convenient carbon-14 labeled oxalyl chloride equivalent", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS》, vol. 52, no. 13, pages 549 - 552 * |
| PENG GUAN，等: "Design, synthesis and preliminary bioactivity studies of 1, 3, 4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY》, vol. 20, no. 12, pages 3865 - 3872 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3841834B2 (en) | Malonic acid and its esters | |
| WO2013026392A1 (en) | 3-(α-methoxyl) methylene benzofuran-2(3h)-ketone synthesis method | |
| CN111454216B (en) | Process for the preparation of HMG-CoA reductase inhibitors and intermediates thereof | |
| US4647689A (en) | Preparation of alkyl trifluoroacetoacetate | |
| CN114805065A (en) | Preparation method of oxalyl chloride monoester | |
| CN101113153A (en) | Process for the preparation of boronic acids and derivatives thereof | |
| CN111269149B (en) | Production process of 5- (3,3-dimethylguanidino) -2-oxopentanoic acid | |
| US6353126B1 (en) | Process for the production of malononitrile | |
| RU2423343C2 (en) | Method of producing high-purity, halogen-free o- phthalaldehyde | |
| JP5798141B2 (en) | Production method of high-purity tartaric acid dialkyl ester | |
| CN113912535B (en) | Preparation method of 6-chloro-4-trifluoromethyl-3-cyanopyridine | |
| GB1561464A (en) | Oxidation of alkaryl compounds | |
| CN103476763B (en) | 3,5-dioxo capronate is prepared with two steps | |
| KR20120086012A (en) | Preparation of p-Chloromethylbenzoic acid and Benzoic acid from by-products in method for processing dimethyl terephthalate | |
| CN109096113B (en) | Method for aromatizing synthetic oak moss | |
| CN111484407B (en) | Preparation method of 1-halogenated-2-methyl-4-substituted carbonyloxy-2-butene | |
| JP4185182B2 (en) | Method for producing imidazole derivative | |
| EP2844644B1 (en) | Process for preparation of 4-methyloxazole-5-carboxylic ester | |
| CN114105819A (en) | Method for synthesizing chloroacetonitrile through photochlorination | |
| CN116947609A (en) | Method for preparing 2, 2-dibromoacetophenone by C-S bond cleavage | |
| EP0410758A2 (en) | Process for producing optically active propionic acid derivatives | |
| CN117903069A (en) | Synthesis method of fampicin intermediate 2-bromo-5-chloropyrazine | |
| JPH0768161B2 (en) | Method for producing high-purity alkoxymethylbenzaldehyde | |
| IE50863B1 (en) | Process for preparing acetic acid derivatives | |
| JPH07145162A (en) | Production of 4h-pyran-4-one |
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 |