CN108997139B - Synthetic method of 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof - Google Patents
Synthetic method of 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof Download PDFInfo
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- CN108997139B CN108997139B CN201810765630.6A CN201810765630A CN108997139B CN 108997139 B CN108997139 B CN 108997139B CN 201810765630 A CN201810765630 A CN 201810765630A CN 108997139 B CN108997139 B CN 108997139B
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 52
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000010189 synthetic method Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 13
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- 239000012286 potassium permanganate Substances 0.000 claims abstract description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 45
- XBEAJNFYXLTYFG-UHFFFAOYSA-N bis(2,6-dimethylphenyl)diazene Chemical compound CC1=CC=CC(C)=C1N=NC1=C(C)C=CC=C1C XBEAJNFYXLTYFG-UHFFFAOYSA-N 0.000 claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- OBWSOTREAMFOCQ-UHFFFAOYSA-N 4-(4-amino-3,5-dimethylphenyl)-2,6-dimethylaniline;hydrochloride Chemical compound Cl.CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 OBWSOTREAMFOCQ-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- -1 3,3',5,5' -tetramethylbenzidine hydrochloride 3,3',5,5' -tetramethylbenzidine Chemical compound 0.000 claims 1
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- XEPNJJFNSJKTSO-UHFFFAOYSA-N azanium;zinc;chloride Chemical compound [NH4+].[Cl-].[Zn] XEPNJJFNSJKTSO-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000004537 pulping Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- QGLAYJCJLHNIGJ-UHFFFAOYSA-N 4-bromo-2,6-dimethylaniline Chemical compound CC1=CC(Br)=CC(C)=C1N QGLAYJCJLHNIGJ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052595 hematite Inorganic materials 0.000 description 1
- 239000011019 hematite Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- LIKBJVNGSGBSGK-UHFFFAOYSA-N iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Fe+3].[Fe+3] LIKBJVNGSGBSGK-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100001081 no carcinogenicity Toxicity 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
- C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
- C07C245/08—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/54—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof, belonging to the technical field of organic synthesis. 2, 6-dimethylaniline is used as a raw material, firstly, 2',6,6' -tetramethyl azobenzene is obtained through the oxidation of potassium permanganate, and then, 2',6,6' -tetramethyl azobenzene is directly reduced, rearranged and treated by a one-step method of zinc powder and concentrated hydrochloric acid to obtain 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof. The raw materials used in the invention are cheap and easily available, the operation process is simple and convenient, the reaction conditions are mild, and the yield is high.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof.
Background
At present, Enzyme Immunoassay (EIA) technology is widely applied to quantitative or qualitative detection and analysis of antigens, haptens or antibodies. Horse Radish Peroxidase (HRP) and its conjugate are commonly used in enzyme-linked immunoassay, and 3,3',5,5' -Tetramethylbenzidine (TMB) has higher sensitivity and no carcinogenicity in the color reaction system of HRP than other chromogens, so that it is widely used. TMB is mainly applied to enzyme-linked immunosorbent assay (ELISA), immuno-dot hybridization or immunohistochemistry and detection and analysis of chlorine and hydrogen peroxide.
The synthesis of 3,3',5,5' -tetramethylbenzidine and its hydrochloride or its intermediate has been reported less, and there are mainly the following methods.
4-bromo-2, 6-dimethylaniline is used as a raw material and is coupled by palladium carbon and the like to obtain the 3,3',5,5' -tetramethyl benzidine.
2, 6-dimethylaniline is used as a raw material, and the 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof are obtained through oxidation, reduction and rearrangement reactions.
CN1056304 is oxidized with hematite, reduced with zinc ammonium chloride powder system, and synthesized by rearrangement with hydrochloric acid; the Soviet Union patent RU2086536 uses hydrogen peroxide as oxidant, uses ammonium chloride zinc powder system to reduce, uses sulfuric acid to rearrange and synthesize.
CN107652187A this patent is similar to [0005] except that 2,2',6,6' -azotetramethylaniline-N, N-dioxide as an intermediate is first produced, then reduced to 2,2',6,6' -tetramethyldiphenylhydrazine with sodium thiosulfate and sodium hydrosulfide, and then rearranged with acid to obtain the desired product.
Some of the synthesis methods use palladium carbon and the like, and have higher cost, and some of the synthesis methods use complicated steps or have low yield, or are only limited to small-scale research and are not suitable for industrial scale-up production.
Disclosure of Invention
The invention aims to provide a method for synthesizing 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof.
Another object of the present invention is to provide a method for synthesizing 2,2',6,6' -tetramethylazobenzene, which is a key intermediate of 3,3',5,5' -tetramethylbenzidine and its hydrochloride.
The invention is realized by a method for synthesizing 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof, which comprises the following steps:
(1) synthesis of 2,2',6,6' -tetramethylazobenzene
Dissolving a compound 2, 6-dimethylaniline serving as a raw material in ethyl acetate, adding potassium permanganate, stirring to react for 24 hours, performing suction filtration after the reaction is finished, washing a filter cake by using ethyl acetate, combining filtrates, and concentrating to obtain the 2,2',6,6' -tetramethyl azobenzene.
(2) Synthesis of 3,3',5,5' -tetramethylbenzidine
Dissolving 2,2',6,6' -tetramethyl azobenzene in ethyl acetate to obtain a solution which is dark brown red, adding hydrochloric acid and zinc powder to react, wherein the reaction system is colorless and clear firstly, then white solid is generated, adding a sodium hydroxide aqueous solution after the reaction is finished, adjusting to be neutral to alkaline, layering, washing an organic layer with water, drying and concentrating to obtain the 3,3',5,5' -tetramethyl benzidine.
(3) Synthesis of 3,3',5,5' -tetramethylbenzidine hydrochloride
Dissolving 3,3',5,5' -tetramethyl benzidine in organic solvent, slowly adding concentrated hydrochloric acid while stirring, and generating solid, namely 3,3',5,5' -tetramethyl benzidine hydrochloride.
The molar ratio of the 2, 6-dimethylaniline to the potassium permanganate in the step (1) is 1: 1-2.
The reaction temperature in the step (1) is 10-50 ℃.
The concentration of the hydrochloric acid in the step (2) is 6-12M.
The molar ratio of the 2,2',6,6' -tetramethylazobenzene to the hydrochloric acid to the zinc in the step (2) is 1: 3-4: 2.
the alkali liquor in the step (2) is sodium hydroxide or potassium hydroxide aqueous solution, and can also be potassium carbonate or sodium carbonate aqueous solution.
The mass fraction of the concentrated hydrochloric acid in the step (3) is 25-38%.
In the step (3), the organic solvent is one of ethyl acetate, dichloromethane or trichloromethane.
The invention has the significance that a new oxidant, namely potassium permanganate, is adopted to oxidize 2, 6-dimethylaniline to prepare 2,2',6,6' -tetramethyl azobenzene, then the reduction and rearrangement of the 2,2',6,6' -tetramethyl azobenzene are completed by one step under the acidic condition, and the 3,3',5,5' -tetramethyl benzidine is obtained after treatment. The synthetic route of the invention is as follows:
the specific implementation mode is as follows:
the present invention will be described in detail below by way of examples.
Example 1
Step 1:
synthesis of 2,2',6,6' -tetramethyl azobenzene
121 g (1 mol) of 2, 6-dimethylaniline and 1000mL of ethyl acetate are added into a 2000mL three-necked glass bottle, stirring is carried out, 237 g (1.5 mol) of potassium permanganate is added, stirring and reaction are carried out for 24 hours at room temperature, after the reaction is finished, suction filtration is carried out, a filter cake is washed by ethyl acetate, filtrate is combined and concentrated to obtain 114 g of 2,2',6,6' -tetramethyl azobenzene, the yield is 95.8%, and the next reaction can be directly carried out.
Step 2:
synthesis of 3,3',5,5' -tetramethylbenzidine
Dissolving 95.2 g (0.4 mol) of 2,2',6,6' -tetramethyl azobenzene in 800mL of ethyl acetate in a 2000mL three-necked glass bottle to obtain a dark brown red solution, adding 200mL (1.2 mol) of 6M hydrochloric acid and 52 g (0.8 mol) of zinc powder, stirring at room temperature to perform reaction, gradually changing the original brown color from dark to light, then changing the color to colorless and clear, then generating white solid, after the reaction is finished, adding an aqueous solution of sodium hydroxide, adjusting the solution to be neutral to alkaline, layering, washing an organic layer with water, drying anhydrous sodium sulfate, concentrating the organic layer, and pulping n-heptane to obtain 92 g of white crystalline solid 3,3',5,5' -tetramethyl benzidine, and melting point: 169 ℃ and 170 ℃, the yield is 96 percent, and the nuclear magnetic data are consistent with the literature.
And step 3:
synthesis of 3,3',5,5' -tetramethylbenzidine hydrochloride
In a 2000mL three-necked glass bottle, 120 g (0.5 mol) of 3,3',5,5' -tetramethylbenzidine and 1000mL of ethyl acetate were added, stirred to completely dissolve the mixture to obtain a clear and transparent solution, 30% concentrated hydrochloric acid was slowly added to generate a solid, and after 120mL of 30% hydrochloric acid was added, stirring was further carried out for 30 minutes, followed by suction filtration to obtain a white solid, which was recrystallized from water to obtain 133 g of 3,3',5,5' -tetramethylbenzidine hydrochloride as a white crystalline solid with a yield of 85%, and the nuclear magnetic data were in accordance with the literature.
Example 2
Step 1:
synthesis of 2,2',6,6' -tetramethylazobenzene
121 g (1 mol) of 2, 6-dimethylaniline and 1000mL of ethyl acetate are added into a 2000mL three-necked glass bottle, stirring is carried out, 316 g (2 mol) of potassium permanganate is added, stirring and reaction are carried out for 24 hours at room temperature, after the reaction is finished, suction filtration is carried out, a filter cake is washed by ethyl acetate, filtrate is combined and concentrated to obtain 116 g of 2,2',6,6' -tetramethyl azobenzene, the yield is 97.5%, and the next reaction can be directly carried out.
Step 2:
synthesis of 3,3',5,5' -tetramethylbenzidine
Dissolving 95.2 g (0.4 mol) of 2,2',6,6' -tetramethyl azobenzene in 800mL of ethyl acetate in a 2000mL three-necked glass bottle to obtain a dark brown red solution, adding 150mL (1.2 mol) of 8M hydrochloric acid and 52 g (0.8 mol) of zinc powder, stirring at room temperature to perform reaction, gradually changing the original brown color from dark to light, then changing the brown color into colorless and clear, then generating white solid, after the reaction is finished, adding an aqueous solution of sodium hydroxide, adjusting the solution to be neutral to alkaline, layering, concentrating an organic layer, pulping n-heptane to obtain 92 g of white crystalline solid, namely 3,3',5,5' -tetramethyl benzidine, and melting point: 169 ℃ and 170 ℃ and the yield is 96 percent.
And step 3:
synthesis of 3,3',5,5' -tetramethylbenzidine hydrochloride
In a 2000mL three necked glass bottle, 120 g (0.5 mol) of 3,3',5,5' -tetramethylbenzidine and 1000mL of dichloromethane were added and stirred to dissolve completely to a clear and transparent solution, 37% concentrated hydrochloric acid was slowly added to generate a solid, and after 120mL of 37% hydrochloric acid was added, stirring was further carried out for 30 minutes, followed by suction filtration to obtain a white solid, which was recrystallized from water to obtain 133 g of 3,3',5,5' -tetramethylbenzidine hydrochloride as a white crystalline solid with a yield of 85%.
Claims (6)
1. A method for synthesizing 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof is characterized by comprising the following steps:
(1) 2,2',6,6' -tetramethyl azobenzene is synthesized by taking 2, 6-dimethyl aniline as a raw material, dissolving the raw material in ethyl acetate, adding potassium permanganate, and stirring for reaction; after the reaction is finished, carrying out suction filtration, washing a filter cake by using ethyl acetate, combining filtrates, and concentrating to obtain 2,2',6,6' -tetramethyl azobenzene; the molar ratio of the 2, 6-dimethylaniline to the potassium permanganate is 1: 1-2;
(2) 3,3',5,5' -tetramethylbenzidine synthesis 2,2',6,6' -tetramethylazobenzene is dissolved in ethyl acetate, hydrochloric acid and zinc powder are added for reaction, after the reaction is finished, alkaline aqueous solution is added, the mixture is adjusted to be alkaline, layering is carried out, an organic layer is concentrated, and 3,3',5,5' -tetramethylbenzidine is obtained; the mol ratio of the 2,2',6,6' -tetramethyl azobenzene to the hydrochloric acid to the zinc is 1: 3-4: 2;
(3) synthesis of 3,3',5,5' -tetramethylbenzidine hydrochloride 3,3',5,5' -tetramethylbenzidine was dissolved in organic solvent, and concentrated hydrochloric acid was slowly added with stirring to obtain 3,3',5,5' -tetramethylbenzidine hydrochloride after treatment.
2. The method for synthesizing 3,3',5,5' -tetramethylbenzidine and hydrochloride thereof according to claim 1, wherein: the reaction temperature in the step (1) is 10-50 ℃.
3. The method for synthesizing 3,3',5,5' -tetramethylbenzidine and hydrochloride thereof according to claim 1, wherein: the concentration of the hydrochloric acid in the step (2) is 6-12M.
4. The method for synthesizing 3,3',5,5' -tetramethylbenzidine and hydrochloride thereof according to claim 1, wherein: the alkaline aqueous solution in the step (2) is selected from a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, a sodium carbonate aqueous solution or a potassium carbonate aqueous solution.
5. The method for synthesizing 3,3',5,5' -tetramethylbenzidine and hydrochloride thereof according to claim 1, wherein: the mass fraction of the concentrated hydrochloric acid in the step (3) is 25-38%.
6. The method for synthesizing 3,3',5,5' -tetramethylbenzidine and hydrochloride thereof according to claim 1, wherein: and (3) the organic solvent is ethyl acetate, dichloromethane or chloroform.
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| US11028044B2 (en) * | 2019-10-16 | 2021-06-08 | SLR Biosciences, LLC | Versatile, concise and convenient process for the commercial scale preparation of highest pure 3,3′5,5′-tetramethylbenzidine (TMB) and its salts, a chromogenic substrate used in staining procedures in immunohistochemistry and visualizing reagent in enzyme-linked immunosorbent assays |
| CN113956276A (en) * | 2020-07-20 | 2022-01-21 | 中国科学院上海有机化学研究所 | Polysubstituted alkylaryl azo compound, and synthesis method and application thereof |
| CN115572232A (en) * | 2022-10-18 | 2023-01-06 | 江苏至纯科技新材料有限公司 | Preparation method of 3,3', 5' -tetramethyl benzidine |
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