CN105732463B - The preparation method of 6 nitro, 1,2,3,3 tetramethyl indoles - Google Patents

The preparation method of 6 nitro, 1,2,3,3 tetramethyl indoles Download PDF

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CN105732463B
CN105732463B CN201610081897.4A CN201610081897A CN105732463B CN 105732463 B CN105732463 B CN 105732463B CN 201610081897 A CN201610081897 A CN 201610081897A CN 105732463 B CN105732463 B CN 105732463B
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deg
added dropwise
indoles
tetramethyl
nitros
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CN201610081897.4A
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Chinese (zh)
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CN105732463A (en
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顾锋雷
秦振伟
施云龙
肖庆军
朱书荣
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江苏鼎龙科技有限公司
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Abstract

The present invention relates to a kind of preparation method of 1,2,3,3 tetramethyl indoles of 6 nitro, with 1,2,3,3 tetramethyl indoles are raw material, using sulfuric acid as solvent, using the nitration mixture of certain concentration as nitrating agent, nitration mixture is added dropwise within a certain period of time and carries out nitration reaction 6 nitros 1,2,3 of generation, 3 tetramethyl indoles, reaction solution is diluted in a certain amount of frozen water and is filtered to remove byproduct, and the reaction solution after filtering obtains 6 nitros 1 by anti-tune, 2,3,3 tetramethyl indoles.Present invention process is simple, product post processing is easy, environmental pollution is small, 6 nitros 1,2 being prepared, 3,3 tetramethyl indoles product quality qualities are high, and stability is good, and obtained product is in addition to it can be used for general applications, the preparation of high-end resin is can be also used for, is a kind of method of suitable preparation of industrialization.

Description

The preparation method of 6- nitro -1,2,3,3- tetramethyl indoles

Technical field

The present invention relates to a kind of preparation method of organic chemical intermediates, more particularly, to a kind of 6- nitros -1,2,3,3- The preparation method of tetramethyl indoles.

Background technology

6- nitros -1,2,3,3- tetramethyl indoles are the necessary intermediates of dyestuff, plant protection product and medicine synthesis, are works Important raw and processed materials in industry;The product obtained after its hydrotreating can be used for the preparation of electronic material.

On 6- nitros -1,2, the preparation method of 3,3- tetramethyl indoles is less, it is now known that report be: Tolmachev, A.A. etc. deliver with 1,2,3,3- tetramethyl indoles for raw material, be mixed to get with concentrated nitric acid and the concentrated sulfuric acid mixed Acid is nitrating agent, is nitrified with chloroform with liquid nitrogen cooling under the conditions of -8~-15 DEG C, nitration reaction liquid is diluted to frozen water It is middle first to remove the grease that dinitro is formed, then crude product is obtained by filtration with ammonium hydroxide tune pH=3, crude product is recrystallized by pentane To 6- nitros -1,2,3,3- tetramethyl indoles, yield 70% or so.Pass through experimental verification to above scheme, discovery uses the party Method described in case, since reaction temperature is relatively low, thus more difficult implementation industrialized production, the byproduct during simultaneous reactions, It is difficult to be removed by refined, by repeatedly refining, less than 50%, chromatographic content is also only capable of reaching 95% left side actual mass yield The right side, can not meet the chromatographic content demand of electronic grade product.Problem is particularly acute when using this method amplification production.

In order to improve 6- nitros -1,2, the inherent quality of 3,3- tetramethyl indoles, improves yield and the life of product The stability of production, the present invention provide one kind by repeatedly trial and prepare high-quality 6- nitros -1,2,3,3- tetramethyl indoles Method.

The content of the invention

In order to overcome the shortcomings of the prior art, the present invention provides a kind of 6- nitros -1,2,3,3- tetramethyl indoles Preparation method, reduce environmental pollution while product quality quality is improved, clean production, environmental protection, make production Product mass production preferably.

A kind of 6- nitros -1,2, the preparation method of 3,3- tetramethyl indoles, comprise the following steps:

(1) sulfuric acid that mass concentration is 98% is added in a container, is cooled to 5~15 DEG C, 1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to -5~5 DEG C base indoles after finishing, and nitrating agent is added dropwise, and drips 0.2~1.2h of insulation reaction after finishing;

(2) reaction solution is diluted in frozen water, impurity, filtrate drop alkali neutralization to pH is filtered to remove at a temperature of 5~40 DEG C > 7, obtains 6- nitros -1,2,3,3- tetramethyl indoles.

Synthetic route of the present invention is as follows:

The present invention with 1,2,3,3- tetramethyl indoles for raw material, using sulfuric acid as solvent, using the nitration mixture of certain concentration as nitrify Reagent, within a certain period of time, is nitrified within the temperature range of change, and nitrification liquid is diluted in a certain amount of frozen water, a constant temperature Impurity is filtered to remove under degree, filtrate is demodulated to obtain product again with alkali neutralization.

Preferably, mixed liquor of the nitrating agent for sulfuric acid and nitric acid, wherein, the mass concentration of sulfuric acid for 70~ 98%, it is 0.2~1.0 that it, which rolls over hundred dosages and the mass ratio of 1,2,3,3- tetramethyl indoles,:1;The mass concentration of nitric acid for 50~ 98%, it is 0.2~0.65 that it, which rolls over hundred dosages and the mass ratio of 1,2,3,3- tetramethyl indoles,:1.

Preferably, in nitrating agent, the mass concentration of sulfuric acid is 90~98%, it rolls over hundred dosages and 1,2,3,3- tetramethyls The mass ratio of base indoles is 0.4~0.8:1;The mass concentration of nitric acid is 60~70%, it rolls over hundred dosages and 1,2,3,3- tetramethyls The mass ratio of base indoles is 0.3~0.6:1.

Preferably, time for adding control is in 0.2~2.0h, 0.2~1.2h of insulation reaction after drop finishes.

Preferably, allow holding for temperature in time of the nitration reaction temperature control between -5~60 DEG C and in restriction Height of continuing rising, but it is no more than maximum temperature determined by temperature range.

Preferably, frozen water dosage and the weight ratio of 1,2,3,3- tetramethyl indoles are 5~15:1.

Preferably, the frozen water temperature is 0~5 DEG C, filtering and impurity removing matter temperature is 10~30 DEG C.

Preferably, the 6- nitros -1,2, the preparation method of 3,3- tetramethyl indoles, comprise the following steps:

(1) 98% sulfuric acid of 276kg is sucked in 1000L enamel stills, is cooled to 10 DEG C, 50kg1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 0 DEG C base indoles after finishing, and the nitration mixture that 98% sulfuric acid of 29kg and 65% nitric acid of 28.4kg are made into is added dropwise, It is added dropwise in 1.2h, drips insulation reaction 0.5h after finishing;

(2) reaction solution is added dropwise in the 500kg frozen water for be pre-chilled to 0 DEG C and diluted, dilution finish, 18~20 DEG C be filtered to remove it is miscellaneous Matter, filtrate added drop-wise ammonium hydroxide tune pH=8.2, separates out material and obtains 6- nitros -1,2,3,3- tetramethyl indoles.

Present invention process is simple, and product post processing is easy, and environmental pollution is small, the 6- nitros -1,2 being prepared, and 3,3- tetra- Methyl indol product quality quality is high, and stability is good, and obtained product can be also used for high-end in addition to it can be used for general applications The preparation of resin, is a kind of method of suitable preparation of industrialization.

Embodiment

With reference to specific embodiment, the invention will be further described, but invention which is intended to be protected is not limited to This.

Embodiment 1

98% sulfuric acid of 276kg is sucked in 1000L enamel stills, is cooled to 10 DEG C, 50kg1,2,3,3- tetramethyl Yin is added dropwise Into salt, drop continues to be cooled to 0 DEG C diindyl after finishing, and the nitration mixture that 98% sulfuric acid of 29kg and 65% nitric acid of 28.4kg are made into is added dropwise, It is added dropwise in 1.2h, drips insulation reaction 0.5h after finishing, reaction solution is added dropwise in the 500kg frozen water for be pre-chilled to 0 DEG C and diluted, it is dilute Release complete, 18~20 DEG C are filtered to remove impurity, filtrate added drop-wise ammonium hydroxide tune pH=8.2, and material separates out to obtain 6- nitros -1,2,3,3- tetramethyls Base indoles, 53.3kg, HPLC after drying:99.8%, yield:83.3%.

Embodiment 2

98% sulfuric acid of 300g is added in 500ml four-hole boiling flasks, is cooled to 8 DEG C, 50.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 2 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 40g and 65% nitric acid of 30g are made into is added dropwise, in 0.6h Inside it is added dropwise, drips insulation reaction 0.5h after finishing, reaction solution is poured into 600g frozen water and is diluted, dilution is finished, 15~20 DEG C of filterings Impurity, filtrate added drop-wise ammonium hydroxide tune pH=8.5 are removed, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, after dry 51.2g HPLC:99.3%, yield:80%.

Embodiment 3

98% sulfuric acid of 300g is added in 500ml four-hole boiling flasks, is cooled to 15 DEG C, 50.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 5 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 40g and 70% nitric acid of 30g are made into is added dropwise, in 0.6h Inside it is added dropwise, drips insulation reaction 0.5h after finishing, reaction solution is poured into 400g frozen water and is diluted, dilution is finished, 10~15 DEG C of filterings Impurity, filtrate added drop-wise ammonium hydroxide tune pH=9.5 are removed, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, after dry 49.1g HPLC:99.1%, yield:76.7%.

Embodiment 4

98% sulfuric acid of 400g is added in 500ml four-hole boiling flasks, is cooled to 5 DEG C, 70.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to -5 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 55g and 65% nitric acid of 35g are made into is added dropwise, in 0.8h Inside it is added dropwise, drips insulation reaction 0.5h after finishing, reaction solution is poured into 400g frozen water and is diluted, dilution is finished, 20~25 DEG C of filterings Impurity, filtrate added drop-wise ammonium hydroxide tune pH=7.8 are removed, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, after dry 70.4g HPLC:99.6%, yield:78.6%.

Embodiment 5

98% sulfuric acid of 300kg is sucked in 1000L enamel stills, is cooled to 7 DEG C, 50kg1,2,3,3- tetramethyl Yin is added dropwise Into salt, drop continues to be cooled to 0 DEG C diindyl after finishing, and the nitration mixture that 98% sulfuric acid of 25kg and 60% nitric acid of 25kg are made into is added dropwise, in 1.0h Inside it is added dropwise, drips insulation reaction 1.2h after finishing, reaction solution is added dropwise in 300kg frozen water and is diluted, dilution is finished, 10~12 DEG C of mistakes Decontamination, filtrate added drop-wise ammonium hydroxide tune pH=7.5 are filtered out, material separates out to obtain 6- nitros -1,2 substantially, and 3,3- tetramethyl indoles are dry 45.9kg afterwards, HPLC:99.1%, yield:71.7%.

Embodiment 6

98% sulfuric acid of 300kg is sucked in 1000L enamel stills, is cooled to 12 DEG C, 50kg1,2,3,3- tetramethyl Yin is added dropwise Into salt, drop continues to be cooled to -2 DEG C diindyl after finishing, and the nitration mixture that 95% sulfuric acid of 43kg and 70% nitric acid of 40kg are made into is added dropwise, in 1.5h Inside it is added dropwise, drips insulation reaction 1.0h after finishing, reaction solution is added dropwise in 650kg frozen water and is diluted, dilution is finished, 20~22 DEG C of mistakes Decontamination, filtrate added drop-wise ammonium hydroxide tune pH=8.6 are filtered out, material separates out to obtain 6- nitros -1,2 substantially, and 3,3- tetramethyl indoles are dry 48kg afterwards, HPLC:99.2%, yield:75%.

Embodiment 7

98% sulfuric acid of 250kg is sucked in 1000L enamel stills, is cooled to 10 DEG C, 50kg1,2,3,3- tetramethyl Yin is added dropwise Into salt, drop continues to be cooled to 0 DEG C diindyl after finishing, and the nitration mixture that 98% sulfuric acid of 30kg and 65% nitric acid of 38kg are made into is added dropwise, in 1.0h Inside it is added dropwise, drips insulation reaction 1.0h after finishing, reaction solution is added dropwise in 550kg frozen water and is diluted, dilution is finished, 25~30 DEG C of mistakes Decontamination, filtrate added drop-wise ammonium hydroxide tune pH=8.3 are filtered out, material separates out to obtain 6- nitros -1,2 substantially, and 3,3- tetramethyl indoles are dry 50.7kg afterwards, HPLC:99.3%, yield:79.2%.

Embodiment 8

98% sulfuric acid of 300g is added in 500ml four-hole boiling flasks, is cooled to 10 DEG C, 50.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 0 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 30g and 65% nitric acid of 20g are made into is added dropwise, in 0.5h Inside it is added dropwise, drips insulation reaction 0.5h after finishing, reaction solution is poured into 500g frozen water and is diluted, dilution is finished, 15~20 DEG C of filterings Remove impurity, filtrate added drop-wise ammonium hydroxide tune pH=8, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, it is dry after 45.1g, HPLC:99.2%, yield:70.5%.

Embodiment 9

98% sulfuric acid of 300g is added in 500ml four-hole boiling flasks, is cooled to 12 DEG C, 50.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 0 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 50g and 65% nitric acid of 40g are made into is added dropwise, in 0.9h Inside it is added dropwise, drips insulation reaction 0.8h after finishing, reaction solution is poured into 500g frozen water and is diluted, dilution is finished, 15~20 DEG C of filterings Impurity, filtrate added drop-wise ammonium hydroxide tune pH=8.2 are removed, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, after dry 45.6g HPLC:99.2%, yield:71.3%.

Embodiment 10

98% sulfuric acid of 300g is added in 500ml four-hole boiling flasks, is cooled to 10 DEG C, 50.0g1,2,3,3- tetramethyls are added dropwise Into salt, drop continues to be cooled to 0 DEG C indoles after finishing, and the nitration mixture that 90% sulfuric acid of 35g and 65% nitric acid of 35g are made into is added dropwise, in 0.7h Inside it is added dropwise, drips insulation reaction 0.7h after finishing, reaction solution is poured into 500g frozen water and is diluted, dilution is finished, 15~20 DEG C of filterings Impurity, filtrate added drop-wise ammonium hydroxide tune pH=8.2 are removed, solid separates out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, after dry 50.1g HPLC:99.5%, yield:78.3%.

Claims (1)

1. a kind of 6- nitros -1,2, the preparation method of 3,3- tetramethyl indoles, it is characterised in that comprise the following steps:
(1)98% sulfuric acid of 276kg is sucked in 1000L enamel stills, is cooled to 10 DEG C, 50kg1,2,3,3- tetramethyl Yin is added dropwise Into salt, drop continues to be cooled to 0 DEG C diindyl after finishing, and the nitration mixture that 98% sulfuric acid of 29kg and 65% nitric acid of 28.4kg are made into is added dropwise, It is added dropwise in 1.2h, drips insulation reaction 0.5h after finishing;
(2)Reaction solution being added dropwise in the 500kg frozen water for be pre-chilled to 0 DEG C and diluted, dilution is finished, and 18~20 DEG C are filtered to remove impurity, Filtrate added drop-wise ammonium hydroxide tune pH=8.2, material separate out to obtain 6- nitros -1,2,3,3- tetramethyl indoles, 53.3kg, HPLC after drying: 99.8%, yield:83.3%.
CN201610081897.4A 2016-02-05 2016-02-05 The preparation method of 6 nitro, 1,2,3,3 tetramethyl indoles CN105732463B (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5543086A (en) * 1987-08-12 1996-08-06 Gentex Corporation Squarylium dyestuffs and compostions containing same
CN104838294A (en) * 2012-12-06 2015-08-12 旭硝子株式会社 Near-infrared blocking filter

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6183255B2 (en) * 2014-03-17 2017-08-23 旭硝子株式会社 Near-infrared cut filter

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5543086A (en) * 1987-08-12 1996-08-06 Gentex Corporation Squarylium dyestuffs and compostions containing same
CN104838294A (en) * 2012-12-06 2015-08-12 旭硝子株式会社 Near-infrared blocking filter

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