CN115093352A - Preparation method of dithiothreitol - Google Patents
Preparation method of dithiothreitol Download PDFInfo
- Publication number
- CN115093352A CN115093352A CN202210789399.0A CN202210789399A CN115093352A CN 115093352 A CN115093352 A CN 115093352A CN 202210789399 A CN202210789399 A CN 202210789399A CN 115093352 A CN115093352 A CN 115093352A
- Authority
- CN
- China
- Prior art keywords
- filtering
- dithiothreitol
- oxide
- prepare
- diacetylthio
- 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.)
- Granted
Links
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 32
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 24
- ZAXMKKSKBGKALJ-UHFFFAOYSA-N [3-acetyloxy-1,4-bis(acetylsulfanyl)butan-2-yl] acetate Chemical compound CC(=O)SCC(OC(=O)C)C(CSC(C)=O)OC(C)=O ZAXMKKSKBGKALJ-UHFFFAOYSA-N 0.000 claims abstract description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 16
- RMXLHIUHKIVPAB-OWOJBTEDSA-N (e)-1,4-dibromobut-2-ene Chemical compound BrC\C=C\CBr RMXLHIUHKIVPAB-OWOJBTEDSA-N 0.000 claims abstract description 14
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- 238000001914 filtration Methods 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 238000001816 cooling Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 238000007792 addition Methods 0.000 claims description 10
- 239000012286 potassium permanganate Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 235000019270 ammonium chloride Nutrition 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000010025 steaming Methods 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 12
- 230000007794 irritation Effects 0.000 abstract description 5
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 3
- 210000004400 mucous membrane Anatomy 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- XOWDQAHYPSENAC-UHFFFAOYSA-N 1,4-dibromobutane-2,3-diol Chemical compound BrCC(O)C(O)CBr XOWDQAHYPSENAC-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 230000008094 contradictory effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/28—Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/127—Preparation from compounds containing pyridine rings
Abstract
The invention belongs to the technical field of organic synthesis, and discloses a preparation method of dithiothreitol, which comprises the steps of reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, oxidizing the first intermediate under alkaline conditions to prepare a first oxide, reacting acetic anhydride with the first oxide to prepare a second intermediate, reacting the second intermediate with potassium thioacetate to prepare 1, 4-diacetylthio-2, 3-diacetyloxybutane, and hydrolyzing the 1, 4-diacetylthio-2, 3-diacetyloxybutane to prepare the dithiothreitol. The invention has the beneficial effects that: the raw material 1, 4-dibromo-2-butylene reacts with pyridine to generate corresponding quaternary ammonium salt, the quaternary ammonium salt is almost free of irritation, even if the quaternary ammonium salt is not completely oxidized, skin and mucous membrane are not irritated and damaged in subsequent operation, and meanwhile, the quaternary ammonium salt is not easy to hydrolyze, so that the yield is improved.
Description
[ technical field ] A method for producing a semiconductor device
The invention relates to the technical field of organic synthesis, in particular to a preparation method of dithiothreitol.
[ background ] A method for producing a semiconductor device
Dithiothreitol has a plurality of applications in the field of molecular biology because of the unique reducibility, the traditional preparation method is to oxidize 1, 4-dibromo-2-butylene into 1, 4-dibromo-2, 3-butylene glycol by potassium permanganate in a solvent, then protect hydroxyl, then carry out substitution reaction by potassium thioacetate to generate 1, 4-diacetylthio-2, 3-diacetoxybutane, and finally carry out hydrolysis reaction to obtain dithiothreitol. However, potassium hydroxide, which is a strong base, is generated during the oxidation with potassium permanganate, and halogen of 1, 4-dibromo-2, 3-butanediol is hydrolyzed, so that the yield of the step is very low, only 30-40%, and the reaction of the step needs to be carried out under a strong alkaline condition to prevent the product from being oxidized. In addition, the raw material 1, 4-dibromo-2-butene has strong irritation, needs extra care during operation, cannot completely perform oxidation reaction, has a certain residue, and can continuously irritate and hurt skin and mucosa of an operator during subsequent operation. Therefore, there is a need for a method for preparing dithiothreitol, which can reduce the irritation and damage of 1, 4-dibromo-2-butene to skin and mucosa, and can improve the yield of dithiothreitol and increase the enterprise benefit.
[ summary of the invention ]
The invention discloses a preparation method of dithiothreitol, which can effectively solve the technical problems related in the background technology.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a method for preparing dithiothreitol comprises the following steps:
s1: reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, wherein the structural formula of the first intermediate is as follows:
s2: preparing the first intermediate into a first oxide under the catalysis of an oxidant, wherein the first oxide has a structural formula as follows:
s3: reacting acetic anhydride with the first oxide to produce a second intermediate having the formula:
s4, reacting the second intermediate with potassium thioacetate to prepare 1, 4-diacetylthio-2, 3-diacetoxybutane;
s5, and hydrolyzing the 1, 4-diacetylthio-2, 3-diacetyloxy butane to prepare dithiothreitol.
As a preferred improvement of the present invention: the specific process of step S1 is as follows: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine while stirring, controlling the temperature below 35 ℃, continuously stirring for 10 hours after the addition, cooling and filtering to obtain a first intermediate.
As a preferred improvement of the present invention: the oxidant in step S2 is potassium permanganate.
As a preferred improvement of the present invention: the specific process of step S2 is as follows: dissolving the first intermediate in water, cooling to 0 ℃, slowly adding potassium permanganate, keeping the temperature at 0-5 ℃, continuing to keep the temperature and stir for 5 hours, filtering, adding hydrochloric acid to adjust the pH value to 6-7, after partial evaporation of water, slowly adding ammonium chloride until solid is separated out, cooling to 0 ℃, filtering and drying to obtain the first oxide.
As a preferred improvement of the present invention: the specific process of step S3 is as follows: placing acetic anhydride and pyridine into a reaction vessel, slowly adding the first oxide after the temperature is raised to 50 ℃, continuing to perform heat preservation reaction for 5 hours, adding ethyl acetate and water for extraction, washing the extract liquid to be neutral by using an aqueous solution of ammonium chloride and sodium bicarbonate, then steaming the extract liquid to be oily, adding ethanol for cooling crystallization, filtering and drying to obtain a second intermediate.
As a preferred improvement of the present invention: the specific process of step S4 is as follows: and adding the second intermediate into DMF, heating to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for reaction for 5 hours after the addition is finished, adding the reaction liquid into water, stirring to separate out a solid, dissolving the solid by using ethanol after filtration, freezing and crystallizing after the filtration, and filtering and drying to obtain the 1, 4-diacetylthio-2, 3-diacetoxybutane.
As a preferred improvement of the present invention: the specific process of step S5 is as follows: adding 1, 4-diacetylthio-2, 3-diacetoxybutane into methanol, adding sulfuric acid, performing reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to form syrup, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, re-filtering, and finally drying the solid in the dry environment to obtain dithiothreitol.
The invention has the following beneficial effects:
according to the invention, the raw material 1, 4-dibromo-2-butylene reacts with pyridine to generate corresponding quaternary ammonium salt, the quaternary ammonium salt is almost free from irritation, even if the quaternary ammonium salt is not completely oxidized, skin and mucous membrane are not irritated and damaged in subsequent operation, and meanwhile, the quaternary ammonium salt is not easy to hydrolyze, so that the yield is improved.
[ detailed description ] embodiments
The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and 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.
It should be noted that all the directional indicators (such as up, down, left, right, front, and rear … …) in the embodiment of the present invention are only used to explain the relative position relationship between the components, the motion situation, and the like in a specific posture, and if the specific posture is changed, the directional indicator is changed accordingly.
In addition, the descriptions related to "first", "second", etc. in the present invention are only for descriptive purposes and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.
In the present invention, unless otherwise expressly stated or limited, the terms "connected," "secured," and the like are to be construed broadly, and for example, "secured" may be a fixed connection, a removable connection, or an integral part; can be mechanically or electrically connected; they may be directly connected or indirectly connected through intervening media, or they may be connected internally or in any other suitable relationship, unless expressly stated otherwise. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
In addition, the technical solutions in the embodiments of the present invention may be combined with each other, but it must be based on the realization of those skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination of technical solutions should not be considered to exist, and is not within the protection scope of the present invention.
The invention provides a preparation method of dithiothreitol, which comprises the following steps:
s1: reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, wherein the structural formula of the first intermediate is as follows:
the specific process of step S1 is as follows: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine under stirring, controlling the temperature to be below 35 ℃, continuously stirring for 10 hours after the addition, cooling and filtering to obtain a first intermediate.
S2: preparing a first intermediate into a first oxide under the catalysis of an oxidant, wherein the first oxide has a structural formula:
preferably, the oxidant in step S2 is potassium permanganate, and the specific process in step S2 is as follows: dissolving the first intermediate in water, cooling to 0 ℃, slowly adding potassium permanganate, keeping the temperature at 0-5 ℃, continuing to keep the temperature and stir for 5 hours, filtering, adding hydrochloric acid to adjust the pH value to 6-7, after partial evaporation of water, slowly adding ammonium chloride until solid is separated out, cooling to 0 ℃, filtering and drying to obtain the first oxide.
S3: reacting acetic anhydride with the first oxide to produce a second intermediate having the formula:
the specific process of step S3 is: placing acetic anhydride and pyridine into a reaction vessel, slowly adding the first oxide after the temperature is raised to 50 ℃, continuing to perform heat preservation reaction for 5 hours, adding ethyl acetate and water for extraction, washing the extract liquid to be neutral by using an aqueous solution of ammonium chloride and sodium bicarbonate, then steaming the extract liquid to be oily, adding ethanol for cooling crystallization, filtering and drying to obtain a second intermediate.
S4, reacting the second intermediate with potassium thioacetate to prepare the 1, 4-diacetylthio-2, 3-diacetoxybutane, wherein the specific process of the step S4 is as follows: adding the second intermediate into DMF (dimethylformamide), heating to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for 5 hours after the addition, adding the reaction solution into water, stirring to separate out a solid, dissolving the solid in ethanol after filtering, freezing and crystallizing after filtering, and filtering and drying to obtain the 1, 4-diacetylthio-2, 3-diacetyloxybutane.
S5, hydrolyzing 1, 4-diacetylthio-2, 3-diacetoxybutane to prepare dithiothreitol, wherein the specific process of the step S5 is as follows: adding 1, 4-diacetylthio-2, 3-diacetoxybutane into methanol, adding sulfuric acid, performing reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to be syrup-shaped, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, performing refiltering, and finally drying the solid in a dry environment to obtain dithiothreitol.
The first embodiment is as follows:
100g of 1, 4-dibromo-2-butene is added into 200g of ethanol, 80g of pyridine is slowly added under stirring, the temperature is controlled to be lower than 35 ℃, heat preservation is continuously carried out at about 30 ℃ after the addition of the pyridine, the mixture is stirred for 10 hours, the mixture is cooled to about 0 ℃, and then the mixture is filtered and dried to obtain 163g of a corresponding first intermediate with the yield of 94%.
Taking 80g of the first intermediate, dissolving the first intermediate in 200g of water, cooling to about 0 ℃, slowly adding 35g of potassium permanganate, and maintaining the temperature between 0 and 5 ℃. After the addition, the temperature is kept and the stirring is continued for 5 hours, the mixture is filtered, hydrochloric acid is added to adjust the pH value to 6 to 7, after 2 minutes of water is evaporated, ammonium chloride is slowly added until solid is separated out, the mixture is frozen to about 0 ℃, and the mixture is filtered and dried to obtain 76g of first oxide, wherein the yield is 87 percent and the integral yield of the oxidation is 81 percent.
Taking 70g of acetic anhydride, adding 1g of pyridine, placing the mixture into a three-necked bottle, slowly adding 76g of first oxide when the temperature rises to about 50 ℃, continuously keeping the temperature for reaction for 5 hours after the addition, adding 100g of ethyl acetate, adding 100g of water, stirring, standing, taking an oil layer, extracting a water layer for 2 times by using 50g of ethyl acetate, washing the oil layer to be neutral by using ammonium chloride (about 20 percent) and aqueous solution of sodium bicarbonate, evaporating the oil layer to be oily, adding 50g of ethanol, cooling, crystallizing, filtering and drying to obtain 83g of second intermediate, wherein the yield is 91 percent.
And adding the second intermediate into 160g of DMF, raising the temperature to 30-35 ℃, slowly adding 40g of potassium thioacetate, keeping the temperature for reaction for 5 hours after the addition, adding the reaction solution into 150g of water, stirring to separate out a solid, dissolving the solid by using 100g of ethanol after filtering, freezing and crystallizing after filtering, filtering and drying to obtain 48g of 1, 4-diacetylthio-2, 3-diacetyloxybutane, wherein the yield is 87%.
Adding the obtained 1, 4-diacetylthio-2, 3-diacetoxybutane into 150g of methanol, adding 4.8g of sulfuric acid, performing reflux reaction for 10 hours, adjusting the pH to about 5, steaming the methanol to obtain a syrup, adding 100g of diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, filtering again, drying the solid in the air under a drying environment (the temperature is lower than 25 ℃), and obtaining 19g of dithiothreitol with the yield of 82 percent and the overall yield of about 55 percent.
According to the invention, 1, 4-dibromo-2-butylene is firstly reacted with pyridine to generate corresponding quaternary ammonium salt, the quaternary ammonium salt is almost free of irritation, even if the quaternary ammonium salt is not completely oxidized, skin and mucous membrane are not irritated and damaged in subsequent operation, and meanwhile, the quaternary ammonium salt is not easy to hydrolyze, so that the yield is improved.
While embodiments of the invention have been disclosed above, it is not limited to the applications set forth in the specification and the embodiments, which are fully applicable to various fields of endeavor for which the invention pertains, and further modifications may readily be made by those skilled in the art, it being understood that the invention is not limited to the details shown and described herein without departing from the general concept defined by the appended claims and their equivalents.
Claims (7)
1. The preparation method of dithiothreitol is characterized by comprising the following steps:
s1: reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, wherein the structural formula of the first intermediate is as follows:
s2: preparing the first intermediate into a first oxide under the catalysis of an oxidant, wherein the first oxide has a structural formula as follows:
s3: reacting acetic anhydride with the first oxide to produce a second intermediate having the formula:
s4, reacting the second intermediate with potassium thioacetate to prepare 1, 4-diacetylthio-2, 3-diacetoxybutane;
s5, 1, 4-diacetylthio-2, 3-diacetyloxy butane is hydrolyzed to prepare dithiothreitol.
2. The method of claim 1, wherein the step S1 comprises the following steps: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine while stirring, controlling the temperature below 35 ℃, continuously stirring for 10 hours after the addition, cooling and filtering to obtain a first intermediate.
3. The method of claim 1, wherein the dithiothreitol is prepared by: the oxidant in step S2 is potassium permanganate.
4. The method of claim 3, wherein the specific process of step S2 is as follows: dissolving the first intermediate in water, cooling to 0 ℃, slowly adding potassium permanganate, keeping the temperature at 0-5 ℃, continuing to keep the temperature and stir for 5 hours, filtering, adding hydrochloric acid to adjust the pH value to 6-7, after partial evaporation of water, slowly adding ammonium chloride until solid is separated out, cooling to 0 ℃, filtering and drying to obtain the first oxide.
5. The method of claim 1, wherein the step S3 comprises the following steps: placing acetic anhydride and pyridine into a reaction vessel, slowly adding the first oxide after the temperature is raised to 50 ℃, continuing to perform heat preservation reaction for 5 hours, adding ethyl acetate and water for extraction, washing the extract liquid to be neutral by using an aqueous solution of ammonium chloride and sodium bicarbonate, then steaming the extract liquid to be oily, adding ethanol for cooling crystallization, filtering and drying to obtain a second intermediate.
6. The method of claim 1, wherein the step S4 comprises the following steps: and adding the second intermediate into DMF, heating to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for 5 hours after the addition, adding the reaction liquid into water, stirring to separate out a solid, dissolving the solid in ethanol after filtering, freezing and crystallizing after filtering, and filtering and drying to obtain the 1, 4-diacetylthio-2, 3-diacetoxybutane.
7. The method of claim 1, wherein the step S5 comprises the following steps: adding 1, 4-diacetylthio-2, 3-diacetoxybutane into methanol, adding sulfuric acid, performing reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to form syrup, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, re-filtering, and finally drying the solid in the dry environment to obtain dithiothreitol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210789399.0A CN115093352B (en) | 2022-07-05 | 2022-07-05 | Preparation method of dithiothreitol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210789399.0A CN115093352B (en) | 2022-07-05 | 2022-07-05 | Preparation method of dithiothreitol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115093352A true CN115093352A (en) | 2022-09-23 |
| CN115093352B CN115093352B (en) | 2024-04-26 |
Family
ID=83297398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210789399.0A Active CN115093352B (en) | 2022-07-05 | 2022-07-05 | Preparation method of dithiothreitol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115093352B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117510383A (en) * | 2023-11-07 | 2024-02-06 | 山东丰金制药有限公司 | Preparation method of 1, 4-dithiothreitol |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1345927A (en) * | 1970-10-02 | 1974-02-06 | Eastman Kodak Co | Preparation of acetothiolesters |
| CN1074718A (en) * | 1993-02-04 | 1993-07-28 | 中国人民解放军军事医学科学院放射医学研究所 | A kind of preparation 1, the method for 4-dithiothreitol dithio |
| CN101503384A (en) * | 2009-03-18 | 2009-08-12 | 重庆铂宁化工有限公司 | Method for synthesizing dithiothreitol |
| CN103073462A (en) * | 2013-01-12 | 2013-05-01 | 江西师范大学 | DDT (dithiothreitol) reparation method |
| CN107235872A (en) * | 2016-12-28 | 2017-10-10 | 华东师范大学 | A kind of preparation method of the red sugar alcohol of two sulphur |
| CN112028799A (en) * | 2020-10-15 | 2020-12-04 | 苏州亚科科技股份有限公司 | Preparation method of 1, 4-dithiothreitol |
-
2022
- 2022-07-05 CN CN202210789399.0A patent/CN115093352B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1345927A (en) * | 1970-10-02 | 1974-02-06 | Eastman Kodak Co | Preparation of acetothiolesters |
| CN1074718A (en) * | 1993-02-04 | 1993-07-28 | 中国人民解放军军事医学科学院放射医学研究所 | A kind of preparation 1, the method for 4-dithiothreitol dithio |
| CN101503384A (en) * | 2009-03-18 | 2009-08-12 | 重庆铂宁化工有限公司 | Method for synthesizing dithiothreitol |
| CN103073462A (en) * | 2013-01-12 | 2013-05-01 | 江西师范大学 | DDT (dithiothreitol) reparation method |
| CN107235872A (en) * | 2016-12-28 | 2017-10-10 | 华东师范大学 | A kind of preparation method of the red sugar alcohol of two sulphur |
| CN112028799A (en) * | 2020-10-15 | 2020-12-04 | 苏州亚科科技股份有限公司 | Preparation method of 1, 4-dithiothreitol |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117510383A (en) * | 2023-11-07 | 2024-02-06 | 山东丰金制药有限公司 | Preparation method of 1, 4-dithiothreitol |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115093352B (en) | 2024-04-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115093352A (en) | Preparation method of dithiothreitol | |
| JPS641456B2 (en) | ||
| CN109988132B (en) | Preparation method of amiodarone hydrochloride | |
| CN101643418A (en) | Preparation method of gallic acid alcohol ester | |
| CN109553550B (en) | Method for synthesizing dihydrooat alkaloid | |
| CN110878101A (en) | Novel method for preparing cefixime mother nucleus 7-AMOCA | |
| CN112707889A (en) | Synthesis method of lansoprazole | |
| Shildneck et al. | The synthesis of polyporic acid and atromentin dimethyl ether | |
| EP2419394A1 (en) | Process for the preparation of 2,4,6-octatriene-1-oic acid and 2,4,6-octatriene-1-ol | |
| Raper | CCXCIII.—The resolution of hydratropic acid | |
| CN107200763A (en) | A kind of method using chenodeoxycholic acid as Material synthesis lithocholic acid | |
| CN112250621A (en) | Synthetic method of clodinafop-propargyl | |
| US4841092A (en) | Preparation of tris(2-cyanoethyl)amine | |
| CN101817765A (en) | Preparation method of ibuprofen arginine salt | |
| CN112592286A (en) | Preparation method of complex of aspirin and basic amino acid | |
| JP3904714B2 (en) | Method for producing 2,2'-bis (hydroxymethyl) alkanoic acid | |
| CN109761801B (en) | Novel method for preparing ketovaline calcium | |
| CN114195761B (en) | Preparation method of high-purity sitafloxacin hydrate 3/2 | |
| CN107417522A (en) | A kind of method for catalyzing and synthesizing the Compritol 888 ATO for pharmaceutic adjuvant | |
| USRE23966E (en) | Conversion of sodium aniline n-d-glucurono- | |
| US2007770A (en) | Polymethylenediguanidine compounds and process of making said compounds | |
| US2069096A (en) | Derivatives of ovarian follicular hormones and process of obtaining same | |
| CN110172038B (en) | Process for preparing analgin magnesium by one-pot method | |
| CN113956154A (en) | D-lactic acid-14C, preparation method and application | |
| Braun | OXIDATION OF UNSATURATED COMPOUNDS. VI. SYNTHESIS OF 3-BROMOTHREONIC ACID. SUPPLEMENT TO THE PROOF OF CONFIGURATION OF dl-1, 2-DIHYDROXYBUTYRIC ACIDS |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |