CN106631825A - Preparation method of 3,3,5,5-tetramethyl benzidine - Google Patents
Preparation method of 3,3,5,5-tetramethyl benzidine Download PDFInfo
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- CN106631825A CN106631825A CN201611014357.0A CN201611014357A CN106631825A CN 106631825 A CN106631825 A CN 106631825A CN 201611014357 A CN201611014357 A CN 201611014357A CN 106631825 A CN106631825 A CN 106631825A
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- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
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Abstract
The invention discloses a preparation method of 3,3,5,5-tetramethyl benzidine. The preparation method of the 3,3,5,5-tetramethyl benzidine particularly comprises the following steps: (1) adding 2,6-dimethylaniline into absolute ethanol, adding an deionized water solution, in which a catalyst is dissolved, conducting reaction at the temperature being less than 35 DEG C, adding an oxidizing agent dropwise, and performing suction filtration on solid to obtain activated 2,6-dimethylaniline; (2) adding a tetrahydrofuran solution, in which the activated 2,6-dimethylaniline is dissolved, into an ammonium chloride aqueous solution, adding glacial acetic acid and a metal catalyst, separating out the tetrahydrofuran layer after the reaction is conducted completely, adding the tetrahydrofuran layer into a hydrochloric acid solution and performing suction filtration on solid to obtain a 3,3,5,5-tetramethyl benzidine crude product; (3) adding the 3,3,5,5-tetramethyl benzidine crude product into methanol, adding zink powder, increasing the temperature to 50 to 70 DEG C for reaction, performing suction filtration when the material is hot, concentrating, adding ethanol, continuously increasing the temperature and dissolving, filtering, and concentrating the filtrate to obtain a 3,3,5,5-tetramethyl benzidine pure product. The preparation method of the 3,3,5,5-tetramethyl benzidine is effective and simple in operation, avoids use of raw materials which are dangerous to operate, and is high in product yield and suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation side of 3,3,5,5- tetramethyl benzidines
Method.
Background technology
3,3,5,5- tetramethyl benzidines are a kind of important chromogen reagents, with traditional chromogen reagent（Such as benzidine）Phase
Than, there is detection sensitivity height and good stability, and using safety, without carcinogenic, mutagenesis.Current 3,3,5,
5- tetramethyl benzidines are progressively replacing traditional chromogen reagent, are applied to clinical assay, forensic medical examination, criminal detection and ring
Monitor field in border.Especially in terms of biochemistry test, 3,3,5,5- tetramethyl benzidines as peroxidase new substrate,
Obtain a wide range of applications in enzyme immunoassay (EIA) and enzyme linked immunosorbent assay method.But its is expensive, therefore, study it
Synthetic method have very important significance.At present, both at home and abroad with regard to 3, the study on the synthesis of 3,5,5- tetramethyl benzidines has
Some reports, main method has：1st, with 2,6- dimethylanilines for raw material, 3 are obtained through acylation, bromination, deprotection and coupling,
3,5,5- tetramethyl benzidines, gross production rate is 16%；2nd, it is oxidized with four cerium sulfate hydrates with 2,6- dimethylanilines for raw material
Coupling reaction is obtained 3,3,5,5- tetramethyl benzidines, and yield is 20%；3rd, with 2,6- dimethylanilines be raw material, pass through into salt,
Bromination, hydrolysis and coupling are obtained 3,3,5,5- tetramethyl benzidines, and yield is 43%.It is not high all to there is yield in above method, product
The shortcomings of separating difficult.
The content of the invention
Present invention solves the technical problem that there is provided it is a kind of operation is simple, raw material is cheap and easy to get, reaction efficiency compared with
The preparation method of high and reproducible 3,3,5,5- tetramethyl benzidines.
The present invention is to solve above-mentioned technical problem to adopt the following technical scheme that, a kind of system of 3,3,5,5- tetramethyl benzidines
Preparation Method, it is characterised in that concretely comprise the following steps：
（1）2,6- dimethylanilines are added in absolute ethyl alcohol, add be dissolved with the deionized water solution of catalyst after
Thermotonus less than 35 DEG C, is then added dropwise oxidant, and stirring after completion of dropping is separated out up to solid, and suction filtration solid is used respectively
2, the 6- dimethylanilines after being activated are dried after water and ethanol washing, wherein catalyst is sodium tungstate, ammonium tungstate, sodium molybdate
Or ammonium molybdate, oxidant is hypochlorite solution or hydrogen peroxide solution；
（2）The tetrahydrofuran solution of 2, the 6- dimethylanilines being dissolved with after activation is added in the aqueous solution of ammonium chloride, then is added
Enter glacial acetic acid and metallic catalyst, after reaction completely tetrahydrofuran layer is separated and is added in hydrochloric acid solution, stirring is until solid
Body is separated out, and suction filtration solid obtains 3,3,5,5- tetramethyl biphenyl crude products, and wherein metallic catalyst is zinc powder, palladium or iodate
Nickel；
（3）By 3,3,5,5- tetramethyl biphenyl crude products are added in methyl alcohol, add zinc powder, are warming up to 50-70 DEG C of reaction, while hot
Suction filtration, adds in ethanol after concentration, continues rising temperature for dissolving, and filtrate is concentrated to give 3,3,5,5- tetramethyl biphenyl sterlings after filtration.
Further preferably, step（1）Described in catalyst consumption be 1L 2,6- dimethylanilines correspondence catalyst matter
Measure as 50g.
Further preferably, step（2）Described in metallic catalyst be zinc powder when, 2, the 6- dimethylanilines and zinc after activation
The mass ratio of powder is 3:4, when the metallic catalyst is palladium, the quality of 2, the 6- dimethylanilines after activation and palladium
Than for 10:1, when described metallic catalyst is nickel iodide, 2, the 6- dimethylanilines after activation are with the mass ratio of nickel iodide
10:1。
Further preferably, step（3）Described in the mass ratio of 3,3,5,5- tetramethyl biphenyls crude product and zinc powder be 10:1.
The present invention devises the 3 of a suitable industrialized production, the synthetic route of 3,5,5- tetramethyl benzidines, with 2,6-
Dimethylaniline is raw material, and after activating into salt, under metallic catalyst and acid condition effect, direct oxidation is coupled and obtains
3,3,5,5- tetramethyl benzidines, it is not only effectively simple to operate, it is to avoid the use of the raw material of operational hazards, and product yield
It is higher, it is adapted to industrialized production.
Specific embodiment
The above of the present invention is described in further details by the following examples, but this should not be interpreted as this
The scope for inventing above-mentioned theme is only limitted to below example, and all technologies realized based on the above of the present invention belong to this
Bright scope.
Embodiment 1
2,6- dimethylaniline 1L are added in absolute ethyl alcohol 3L in reaction bulb, add dissolved with sodium tungstate 50g go from
Sub- water 3L, stirring a period of time under conditions of temperature is less than 35 DEG C, then hydrogen peroxide solution is slowly added dropwise until emitting without bubble
Go out, the use of hydrogen peroxide is about 1.4L, continue to be filtered after uniform stirring 3h, wash filter cake 2 times with water, finally again with reclaiming ethanol
Wash and dried after a filter cake（Lucifuge is dried naturally）, 2, the 6- dimethylaniline 1.0kg after being activated.
Embodiment 2
2,6- dimethylaniline 1L are added in absolute ethyl alcohol 3L in reaction bulb, add dissolved with ammonium tungstate 50g go from
Sub- water 3L, stirring a period of time under conditions of temperature is less than 35 DEG C, then hydrogen peroxide solution is slowly added dropwise until emitting without bubble
Go out, the use of hydrogen peroxide is about 1.4L, continue to be filtered after uniform stirring 3h, wash filter cake 2 times with water, finally again with reclaiming ethanol
Wash and dried after a filter cake（Lucifuge is dried naturally）, 2, the 6- dimethylaniline 0.9kg after being activated.
Embodiment 3
2,6- dimethylaniline 1L are added in absolute ethyl alcohol 3L in reaction bulb, add dissolved with ammonium molybdate 50g go from
Sub- water 3L, stirring a period of time under conditions of temperature is less than 35 DEG C, then hydrogen peroxide solution is slowly added dropwise until emitting without bubble
Go out, the use of hydrogen peroxide is about 1.4L, continue to be filtered after uniform stirring 3h, wash filter cake 2 times with water, finally again with reclaiming ethanol
Wash and dried after a filter cake（Lucifuge is dried naturally）, 2, the 6- dimethylaniline 1.2kg after being activated.
Embodiment 4
2,6- dimethylaniline 1L are added in absolute ethyl alcohol 3L in reaction bulb, add dissolved with sodium molybdate 50g go from
Sub- water 3L, stirring a period of time under conditions of temperature is less than 35 DEG C, then hydrogen peroxide solution is slowly added dropwise until emitting without bubble
Go out, the use of hydrogen peroxide is about 1.4L, continue to be filtered after uniform stirring 3h, wash filter cake 2 times with water, finally again with reclaiming ethanol
Wash and dried after a filter cake（Lucifuge is dried naturally）, 2, the 6- dimethylaniline 0.9kg after being activated.
Embodiment 5
2,6- dimethylaniline 1L are added in absolute ethyl alcohol 3L in reaction bulb, add dissolved with ammonium molybdate 50g go from
Sub- water 3L, stirring a period of time under conditions of temperature is less than 35 DEG C, then hypochlorite solution is slowly added dropwise until emitting without bubble
Go out, the use of hydrogen peroxide is about 1.4L, continue to be filtered after uniform stirring 3h, wash filter cake 2 times with water, finally again with reclaiming ethanol
Wash and dried after a filter cake（Lucifuge is dried naturally）, 2, the 6- dimethylaniline 0.85kg after being activated.
Embodiment 6
In the aqueous solution 1.3L dissolved with ammonium chloride 430g, the tetrahydrochysene furan of 2, the 6- dimethylaniline 150g after adding dissolved with activation
Mutter solution 2L, adds glacial acetic acid 70mL and zinc powder 200g, is slowly stirred, and acutely, temperature is quickly to start heat release when reaction
50 DEG C are increased to, it is slow to adjust temperature to 10-12 DEG C.After continuing to react a period of time, tetrahydrofuran layer is separated, be added to salt
In acid solution 1.3L, stirring has solid to separate out, and suction filtration solid obtains 3,3,5,5- tetramethyl benzidine crude product 100g.
Embodiment 7
In the aqueous solution 1.3L dissolved with ammonium chloride 430g, the tetrahydrochysene furan of 2, the 6- dimethylaniline 150g after adding dissolved with activation
Mutter solution 2L, adds glacial acetic acid 70mL and palladium 15g, is slowly stirred, and acutely, temperature is quickly to start heat release when reaction
50 DEG C are increased to, it is slow to adjust temperature to 10-12 DEG C.After continuing to react a period of time, tetrahydrofuran layer is separated, be added to salt
In acid solution 1.3L, stirring has solid to separate out, and suction filtration solid obtains 3,3,5,5- tetramethyl benzidine crude product 95g.
Embodiment 8
In the aqueous solution 1.3L dissolved with ammonium chloride 430g, the tetrahydrochysene furan of 2, the 6- dimethylaniline 150g after adding dissolved with activation
Mutter solution 2L, adds glacial acetic acid 70mL and nickel iodide 15g, is slowly stirred, and acutely, temperature is quickly to start heat release when reaction
50 DEG C are increased to, it is slow to adjust temperature to 10-12 DEG C.After continuing to react a period of time, tetrahydrofuran layer is separated, be added to salt
In acid solution 1.3L, stirring has solid to separate out, and suction filtration solid obtains 3,3,5,5- tetramethyl benzidine crude product 73g.
Embodiment 9
By 3,3,5,5- tetramethyl benzidine crude product 50g are added in methyl alcohol 300mL, add zinc powder 5g, after being warming up to 60 DEG C,
Reaction 1h, while hot suction filtration, adds in ethanol 200mL after concentration, continues rising temperature for dissolving, and filtrate is concentrated to give 3,3,5,5- after filtration
Tetramethyl benzidine sterling 46g.
General principle, principal character and the advantage of the present invention is embodiment above describes, the technical staff of the industry should
Understand, the present invention is not restricted to the described embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope without departing from the principle of the invention, the present invention also has various changes and modifications, and these changes and improvements each fall within
In the scope of protection of the invention.
Claims (4)
1. one kind 3, the preparation method of 3,5,5- tetramethyl benzidines, it is characterised in that concretely comprise the following steps：
（1）2,6- dimethylanilines are added in absolute ethyl alcohol, add be dissolved with the deionized water solution of catalyst after
Thermotonus less than 35 DEG C, is then added dropwise oxidant, and stirring after completion of dropping is separated out up to solid, and suction filtration solid is used respectively
2, the 6- dimethylanilines after being activated are dried after water and ethanol washing, wherein catalyst is sodium tungstate, ammonium tungstate, sodium molybdate
Or ammonium molybdate, oxidant is hypochlorite solution or hydrogen peroxide solution；
（2）The tetrahydrofuran solution of 2, the 6- dimethylanilines being dissolved with after activation is added in the aqueous solution of ammonium chloride, then is added
Enter glacial acetic acid and metallic catalyst, after reaction completely tetrahydrofuran layer is separated and is added in hydrochloric acid solution, stirring is until solid
Body is separated out, and suction filtration solid obtains 3,3,5,5- tetramethyl biphenyl crude products, and wherein metallic catalyst is zinc powder, palladium or iodate
Nickel；
（3）By 3,3,5,5- tetramethyl biphenyl crude products are added in methyl alcohol, add zinc powder, are warming up to 50-70 DEG C of reaction, while hot
Suction filtration, adds in ethanol after concentration, continues rising temperature for dissolving, and filtrate is concentrated to give 3,3,5,5- tetramethyl biphenyl sterlings after filtration.
2. according to claim 13, the preparation method of 3,5,5- tetramethyl benzidines, it is characterised in that：Step（1）In
It is 50g that the consumption of the catalyst is the quality of 1L 2,6- dimethylanilines correspondence catalyst.
3. the preparation method of according to claim 13,3,5,5- tetramethyl benzidine crude products, it is characterised in that：Step
（2）Described in metallic catalyst when being zinc powder, the mass ratio of 2, the 6- dimethylanilines after activation and zinc powder is 3:4, the gold
When metal catalyst is palladium, 2, the 6- dimethylanilines after activation are 10 with the mass ratio of palladium:1, described metal is urged
When agent is nickel iodide, 2, the 6- dimethylanilines after activation are 10 with the mass ratio of nickel iodide:1.
4. according to claim 13, the preparation method of 3,5,5- tetramethyl benzidines, it is characterised in that：Step（3）In
The 3,3,5,5- tetramethyl biphenyls crude product is 10 with the mass ratio of zinc powder:1.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652187A (en) * | 2017-10-20 | 2018-02-02 | 荆楚理工学院 | A kind of biochemical preparation TMB synthetic method |
| CN108997139A (en) * | 2018-07-12 | 2018-12-14 | 南京艾普特生物医药有限公司 | A kind of synthetic method of 3,3`, 5,5`- tetramethyl benzidine and its hydrochloride |
| CN111751365A (en) * | 2020-07-01 | 2020-10-09 | 厦门斯坦道科学仪器股份有限公司 | Preparation method of antioxidant flour benzoyl peroxide detection test paper |
| CN114935572A (en) * | 2022-07-25 | 2022-08-23 | 香港科技大学深圳研究院 | Visual uric acid detection method based on nano material |
| 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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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652187A (en) * | 2017-10-20 | 2018-02-02 | 荆楚理工学院 | A kind of biochemical preparation TMB synthetic method |
| CN107652187B (en) * | 2017-10-20 | 2020-10-30 | 荆楚理工学院 | Synthesis method of biochemical preparation TMB |
| CN108997139A (en) * | 2018-07-12 | 2018-12-14 | 南京艾普特生物医药有限公司 | A kind of synthetic method of 3,3`, 5,5`- tetramethyl benzidine and its hydrochloride |
| CN108997139B (en) * | 2018-07-12 | 2020-11-10 | 南京艾普特生物医药有限公司 | Synthetic method of 3,3',5,5' -tetramethyl benzidine and hydrochloride thereof |
| CN111751365A (en) * | 2020-07-01 | 2020-10-09 | 厦门斯坦道科学仪器股份有限公司 | Preparation method of antioxidant flour benzoyl peroxide detection test paper |
| CN114935572A (en) * | 2022-07-25 | 2022-08-23 | 香港科技大学深圳研究院 | Visual uric acid detection method based on nano material |
| 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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