CN115093352B - Preparation method of dithiothreitol - Google Patents
Preparation method of dithiothreitol Download PDFInfo
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- CN115093352B CN115093352B CN202210789399.0A CN202210789399A CN115093352B CN 115093352 B CN115093352 B CN 115093352B CN 202210789399 A CN202210789399 A CN 202210789399A CN 115093352 B CN115093352 B CN 115093352B
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- 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 abstract description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 24
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 15
- RMXLHIUHKIVPAB-OWOJBTEDSA-N (e)-1,4-dibromobut-2-ene Chemical compound BrC\C=C\CBr RMXLHIUHKIVPAB-OWOJBTEDSA-N 0.000 claims abstract description 14
- 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 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
- 238000001914 filtration Methods 0.000 claims description 34
- 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
- 238000001816 cooling Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 18
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 238000002425 crystallisation Methods 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- 239000012286 potassium permanganate Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 238000010025 steaming Methods 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000001273 butane Substances 0.000 claims description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 13
- 230000007794 irritation Effects 0.000 abstract description 8
- 210000004400 mucous membrane Anatomy 0.000 abstract description 5
- 230000006378 damage Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 208000014674 injury Diseases 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
- 238000005516 engineering process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- -1 1, 4-diacetyl-2, 3-diacetoxy butane Chemical compound 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 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
- 230000003993 interaction Effects 0.000 description 1
- 238000004321 preservation Methods 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 preparing a first intermediate by reacting 1, 4-dibromo-2-butene with pyridine, preparing the first intermediate into a first oxide under alkaline condition, preparing a second intermediate by reacting acetic anhydride with the first oxide, preparing 1, 4-diacetylthio-2, 3-diacetoxybutane by reacting the second intermediate with potassium thioacetate, and preparing dithiothreitol by hydrolyzing 1, 4-diacetylthio-2, 3-diacetoxybutane. The invention has the beneficial effects that: the raw material 1, 4-dibromo-2-butene is reacted with pyridine to generate the corresponding quaternary ammonium salt, and the quaternary ammonium salt has almost no irritation, even if the quaternary ammonium salt is not completely oxidized, the quaternary ammonium salt does not cause irritation and damage to skin and mucous membrane during subsequent operation, and the quaternary ammonium salt is not easy to hydrolyze, so that the yield is improved.
Description
[ Field of technology ]
The invention relates to the technical field of organic synthesis, in particular to a preparation method of dithiothreitol.
[ Background Art ]
The dithiothreitol has a plurality of applications in the field of molecular biology due to the unique reducibility, the traditional preparation method is that 1, 4-dibromo-2-butene is oxidized into 1, 4-dibromo-2, 3-butanediol by potassium permanganate in a solvent, hydroxyl is protected, then potassium thioacetate is used for substitution reaction to generate 1, 4-diacetyl-2, 3-diacetoxy butane, and finally hydrolysis reaction is carried out to obtain the dithiothreitol. However, when potassium permanganate is used for oxidation, strong alkali potassium hydroxide is generated, 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 is required to be carried out under the strong alkaline condition, so that the product is prevented from being peroxidized. In addition, the raw material 1, 4-dibromo-2-butene has strong irritation, the operation needs to be carried out with extra care, the oxidation reaction can not be completely carried out, certain residues are left, and the operation personnel can be continuously injured by skin and mucous membrane during the subsequent operation. Therefore, it is necessary to provide a preparation method of dithiothreitol, which can reduce the irritation injury of 1, 4-dibromo-2-butene to skin and mucous membrane, improve the yield of dithiothreitol and increase the benefit of enterprises.
[ 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 above purpose, the technical scheme of the invention is as follows:
A method for preparing dithiothreitol, comprising the following steps:
s1: reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, wherein the first intermediate has the structural formula:
s2: preparing a first intermediate into a first oxide under the catalysis of an oxidant, wherein the first oxide has the structural formula:
S3: reacting acetic anhydride with the first oxide to prepare a second intermediate having the structural formula:
S4, reacting the second intermediate with potassium thioacetate to prepare 1, 4-diacetylthio-2, 3-diacetoxybutane;
S5, 1, 4-diacetyl thio-2, 3-diacetoxy butane is hydrolyzed to prepare dithiothreitol.
As a preferred improvement of the present invention: the specific process of the step S1 is as follows: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine under stirring, controlling the temperature below 35 ℃, continuing stirring for 10 hours after the addition is finished, 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 the step S2 is as follows: dissolving the first intermediate in water, cooling to 0 ℃, slowly adding potassium permanganate, maintaining the temperature at 0-5 ℃, continuously preserving heat and stirring for 5 hours, filtering, adding hydrochloric acid to adjust the pH 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 the step S3 is as follows: placing acetic anhydride and pyridine into a reaction container, slowly adding first oxide after the temperature is increased to 50 ℃, continuously preserving heat and reacting for 5 hours, adding ethyl acetate and water for extraction, washing the extract with aqueous solution of ammonium chloride and sodium bicarbonate to be neutral, then steaming the extract 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 the step S4 is as follows: adding the second intermediate into DMF, raising the temperature to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for reaction for 5 hours after the addition, adding the reaction liquid into water, stirring to separate out solid, filtering, dissolving with ethanol, filtering, freezing for crystallization, filtering and drying to obtain the 1, 4-diacetylthio-2, 3-diacetoxybutane.
As a preferred improvement of the present invention: the specific process of the step S5 is as follows: adding 1, 4-diacetylthio-2, 3-diacetoxybutane into methanol, adding sulfuric acid, carrying out reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to syrup, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, filtering again, and finally airing the solid in a dry environment to obtain dithiothreitol.
The beneficial effects of the invention are as follows:
The invention makes the raw material 1, 4-dibromo-2-butene react with pyridine to generate the corresponding quaternary ammonium salt, the quaternary ammonium salt has little irritation, even if not completely oxidized, the quaternary ammonium salt does not cause irritation injury to skin and mucous membrane in the subsequent operation, and the quaternary ammonium salt is not easy to hydrolyze, thereby improving the yield.
[ Detailed description ] of the invention
The technical solutions of the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that all directional indicators (such as up, down, left, right, front, and rear … …) in the embodiments of the present invention are merely used to explain the relative positional relationship between the components, the movement condition, etc. in a specific posture, and if the specific posture is changed, the directional indicators are correspondingly changed.
Furthermore, descriptions such as those referred to as "first," "second," and the like, are provided for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implying an order of magnitude of the indicated technical features in the present disclosure. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present invention, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise.
In the present invention, unless specifically stated and limited otherwise, the terms "connected," "affixed," and the like are to be construed broadly, and for example, "affixed" may be a fixed connection, a removable connection, or an integral body; can be mechanically or electrically connected; either directly or indirectly, through intermediaries, or both, may be in communication with each other or in interaction with each other, unless expressly defined otherwise. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.
In addition, the technical solutions of the embodiments of the present invention may be combined with each other, but it is necessary to be based on the fact that those skilled in the art can implement the technical solutions, and when the technical solutions are contradictory or cannot be implemented, the combination of the technical solutions should be considered as not existing, and not falling within the scope of protection claimed by 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 first intermediate has the structural formula:
The specific process of the step S1 is as follows: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine under stirring, controlling the temperature below 35 ℃, continuing stirring for 10 hours after the addition is finished, 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 the structural formula:
Preferably, the oxidizing agent in the step S2 is potassium permanganate, and the specific process of the step S2 is as follows: dissolving the first intermediate in water, cooling to 0 ℃, slowly adding potassium permanganate, maintaining the temperature at 0-5 ℃, continuously preserving heat and stirring for 5 hours, filtering, adding hydrochloric acid to adjust the pH 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 prepare a second intermediate having the structural formula:
The specific process of the step S3 is as follows: placing acetic anhydride and pyridine into a reaction container, slowly adding first oxide after the temperature is increased to 50 ℃, continuously preserving heat and reacting for 5 hours, adding ethyl acetate and water for extraction, washing the extract with aqueous solution of ammonium chloride and sodium bicarbonate to be neutral, then steaming the extract to be oily, adding ethanol for cooling crystallization, filtering and drying to obtain a second intermediate.
S4, reacting a second intermediate with potassium thioacetate to prepare 1, 4-diacetylthio-2, 3-diacetoxybutane, wherein the specific process of the step S4 is as follows: adding the second intermediate into DMF (dimethylformamide), raising the temperature to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for reaction for 5 hours after the addition, adding the reaction solution into water, stirring to separate out solid, filtering, dissolving with ethanol, filtering, freezing for crystallization, filtering and drying to obtain the 1, 4-diacetylthio-2, 3-diacetoxybutane.
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, carrying out reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to syrup, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, filtering again, and finally airing the solid in a dry environment to obtain dithiothreitol.
Embodiment one:
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 below 35 ℃, the temperature is kept at about 30 ℃ after the addition is finished, the stirring is continued for 10 hours, the cooling is carried out to about 0 ℃, and the corresponding first intermediate 163g is obtained after filtering and drying, and the yield is 94%.
Taking 80g of a first intermediate, dissolving 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 mixture is kept warm and stirred for 5 hours, filtered, added with hydrochloric acid to adjust the pH to 6-7, evaporated for about 3 minutes and then slowly added with ammonium chloride until solid is separated out, frozen to about 0 ℃, filtered and dried to obtain 76g of first oxide, the yield is 87%, and the overall oxidation yield is 81%.
70G of acetic anhydride is taken, 1g of pyridine is added, the mixture is placed in a three-mouth bottle, 76g of first oxide is slowly added until the temperature reaches about 50 ℃, the heat preservation reaction is continued for 5 hours after the addition, 100g of ethyl acetate is added, 100g of water is added, stirring is carried out, an oil layer is taken after standing, the water layer is extracted for 2 times by using 50g of ethyl acetate, the oil layer is washed to be neutral by using an aqueous solution of ammonium chloride (about 20 percent) and sodium bicarbonate, the oil layer is steamed to be oily, 50g of ethanol is added for cooling crystallization, 83g of second intermediate is obtained after filtration and drying, and the yield is 91 percent.
And adding the second intermediate into 160gDMF, 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 solid, filtering, dissolving with 100g of ethanol, filtering, freezing for crystallization, filtering and drying to obtain 48g of 1, 4-diacetylthio-2, 3-diacetoxybutane with the yield of 87%.
The obtained 1, 4-diacetylthio-2, 3-diacetoxybutane is added into 150g of methanol, then 4.8g of sulfuric acid is added, reflux reaction is carried out for 10 hours, the pH is adjusted to about 5, the methanol is distilled to syrup, then 100g of diethyl ether is added, after heating and stirring for 10 minutes, filtration, cooling crystallization and filtration are carried out, the solid is dried under the environment (the temperature is lower than 25 ℃) to obtain 19g of dithiothreitol, and the yield is 82 percent and the overall yield is about 55 percent.
The invention makes the raw material 1, 4-dibromo-2-butene react with pyridine to generate the corresponding quaternary ammonium salt, the quaternary ammonium salt has little irritation, even if not completely oxidized, the quaternary ammonium salt does not cause irritation injury to skin and mucous membrane in the subsequent operation, and the quaternary ammonium salt is not easy to hydrolyze, thereby improving the yield.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown and described, it is well suited to various fields of use for which the invention would be readily apparent to those skilled in the art, and accordingly, the invention is not limited to the specific details and illustrations shown and described herein, without departing from the general concepts defined in the claims and their equivalents.
Claims (2)
1. A method for preparing dithiothreitol, which is characterized by comprising the following steps:
s1: reacting 1, 4-dibromo-2-butene with pyridine to prepare a first intermediate, wherein the first intermediate has the structural formula:
，
The specific process is as follows: adding 1, 4-dibromo-2-butene into ethanol, slowly adding pyridine under stirring, controlling the temperature below 35 ℃, continuing stirring for 10 hours after the addition is finished, 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 the structural formula:
，
The specific process is as follows: dissolving a first intermediate in water, cooling to 0 ℃, slowly adding an oxidant potassium permanganate, maintaining the temperature at 0-5 ℃, continuously preserving heat and stirring for 5 hours, filtering, adding hydrochloric acid to adjust the pH 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 a first oxide;
S3: reacting acetic anhydride with the first oxide to prepare a second intermediate having the structural formula:
，
The specific process is as follows: placing acetic anhydride and pyridine into a reaction container, slowly adding first oxide after the temperature is increased to 50 ℃, continuously preserving heat and reacting for 5 hours, adding ethyl acetate and water for extraction, washing an extract with an aqueous solution of ammonium chloride and sodium bicarbonate to be neutral, then steaming the extract 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 1, 4-diacetylthio-2, 3-diacetoxybutane;
The specific process is as follows: adding the second intermediate into DMF, raising the temperature to 30-35 ℃, slowly adding potassium thioacetate, keeping the temperature for reaction for 5 hours after the addition, adding the reaction solution into water, stirring to separate out solid, filtering, dissolving with ethanol, filtering, freezing for crystallization, filtering and drying to obtain 1, 4-diacetylthio-2, 3-diacetoxybutane;
S5, 1, 4-diacetyl thio-2, 3-diacetoxy butane is hydrolyzed to prepare dithiothreitol.
2. The method for preparing dithiothreitol according to claim 1, wherein the specific process of step S5 is: adding 1, 4-diacetylthio-2, 3-diacetoxybutane into methanol, adding sulfuric acid, carrying out reflux reaction for 10 hours, adjusting the pH to 5, steaming the methanol to syrup, adding diethyl ether, heating and stirring for 10 minutes, filtering, cooling for crystallization, filtering again, and finally airing the solid in a dry environment to obtain dithiothreitol.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1345927A (en) * | 1970-10-02 | 1974-02-06 | Eastman Kodak Co | Preparation of acetothiolesters |
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| 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 |
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2022
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| 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 |
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