CN108658895B - Purification method of methylene blue - Google Patents
Purification method of methylene blue Download PDFInfo
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- CN108658895B CN108658895B CN201810373407.7A CN201810373407A CN108658895B CN 108658895 B CN108658895 B CN 108658895B CN 201810373407 A CN201810373407 A CN 201810373407A CN 108658895 B CN108658895 B CN 108658895B
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- methylene blue
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- sodium bicarbonate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/20—[b, e]-condensed with two six-membered rings with hydrogen atoms directly attached to the ring nitrogen atom
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Abstract
The invention relates to the technical field of biological dyeing reagent synthesis and purification, in particular to a methylene blue purification method, which comprises the steps of carrying out double decomposition reaction on a zinc chloride component in dye base lake blue BB and a mixture of sodium bicarbonate and sodium carbonate to generate water-insoluble zinc carbonate, filtering out a zinc carbonate precipitate, adding concentrated hydrochloric acid into filtrate to separate out needle-shaped crystals, filtering out the crystals, centrifugally drying, and drying to obtain bright green needle-shaped methylene blue crystals. The invention selects the zinc removal purification method of the mixture of sodium bicarbonate and sodium carbonate, and has the advantages of universal and feasible method, sufficient raw materials, large operational plasticity and simplicity.
Description
Technical Field
The invention relates to the field of synthetic purification of biological staining reagents, in particular to a purification method of high-purity methylene blue.
Background
Methylene blue is also known as methylene blue, tetramethyl blue, basic lake blue.
The structural formula is as follows:
methylene blue is a bright dark green needle crystal, which is dissolved in water and slightly dissolved in ethanol, and the solution is sky blue.
Methylene blue is widely used, and is used as a nuclear stain in histology, used for vital staining of nerve tissues, used for staining blood together with eosin, used as a medicine for bactericides, antidotes, redox indicators in chemical analysis, adsorption indicators, and measurement of various metals such as mercury and tin.
Analytically pure methylene blue is purified by zinc removal with an industrial dye base lake blue BB as a main raw material.
The industrial dye base lake blue BB is a complex salt, namely a complex salt consisting of methylene blue and zinc chloride, and the specific structural formula is as follows:
the industrial dye base lake blue BB is mainly used for dyeing cotton, acrylic fibers, hemp and silk, and is also used for dyeing paper, coloring bamboo and wood and manufacturing ink and lake.
The industrial dye base lake blue BB contains zinc chloride, and the solubility in double saline is low, especially in alcohol, so that the industrial dye base lake blue BB is not suitable for biological dyeing and drug treatment.
To prepare high purity methylene blue, the zinc chloride in the industrial dye base lake blue BB must be removed.
Because the dye base lake blue BB aqueous solution can be oxidized after being heated, is easier to deeply oxidize particularly under the strong alkali condition, a small amount of lower methyl homologues are inevitably generated, mainly azure A and azure B, and the specific structural formulas are respectively as follows:
due to the presence of the pleochroic methylene blue of azure A and azure B, the quality of the methylene blue is necessarily affected.
Disclosure of Invention
The invention aims to prepare high-content methylene blue, and provides a purification method of the methylene blue, which has the advantages of wide reaction conditions, high purity, high yield and good quality stability, by adopting a sodium bicarbonate and sodium carbonate mixed precipitant dezincification method, so as to solve the problem of high quality control difficulty in the preparation of the high-purity methylene blue in the prior art.
In order to achieve the purpose, the invention provides the following technical scheme:
a process for purifying methylene blue includes such steps as double decomposition reaction of zinc chloride in dye-base lake blue BB with the mixture of sodium bicarbonate and sodium carbonate to generate water-insoluble zinc carbonate, filtering to remove zinc carbonate deposit, adding concentrated hydrochloric acid to filtrate to educe needle crystal, filtering, centrifugal drying and drying.
The invention relates to a purification method of methylene blue, which comprises the following steps:
(1) putting the basic lake blue BB and water into a container, heating to 60-90 ℃, gradually adding a mixture of sodium bicarbonate and sodium carbonate while stirring, controlling the pH to be 7.5-9, and preserving the heat for 30-100 minutes after the addition is finished;
(2) pressing the filtrate into a filter tank through a filter, adding concentrated hydrochloric acid into the filtrate to obtain methylene blue hydrochloride, naturally cooling to separate out glossy dark green crystals, spin-drying by a centrifuge, and drying to obtain high-purity methylene blue.
The invention discloses a purification method of methylene blue, wherein the weight ratio of halokale BB to water in the step (1) is 1: 13-16.
The invention relates to a purification method of methylene blue, wherein the weight ratio of halokale BB to sodium bicarbonate in the step (1) is 1: 0.25-0.35.
The invention provides a purification method of methylene blue, wherein the mass of sodium carbonate in the step (1) is 0.1-2% of the mass of sodium bicarbonate.
The invention relates to a method for purifying methylene blue, wherein in the step (2), when concentrated hydrochloric acid is added into filtrate, the weight ratio of basic lake blue BB to the concentrated hydrochloric acid is 1: 0.4-0.6.
Compared with the prior art, the invention has the beneficial effects that: the invention selects the zinc removal purification method of the mixture of sodium bicarbonate and sodium carbonate, and has the advantages of universal and feasible method, sufficient raw materials, large operational plasticity and simplicity. The method has the advantages of greatly improved production capacity, high purity, high yield and stable quality.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all 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.
Example 1
A method for purifying methylene blue comprises the following steps:
150g of raw material basic lake blue BB is added with 2250g of water, the mixture of sodium bicarbonate and sodium carbonate (40g of sodium bicarbonate and 0.8g of sodium carbonate dissolved in 500ml of water) is gradually added while stirring when the temperature is 60-90 ℃, the pH of the reaction solution is controlled to be 7.5-9, the addition is finished in about 30 minutes, and the mixture is subjected to heat preservation for 30 minutes and then is put into a crystallization tank through a filter. 75g of hydrochloric acid was added to the filtrate, and after stirring for 15 minutes, the filtrate was cooled to precipitate glossy dark green crystals. And (3) carrying out centrifugal drying on the crystals to obtain 64.1g of methylene blue, wherein the content is more than or equal to 98.5 percent, and the yield is 90.7 percent. The result meets the pharmacopoeia requirement and is far higher than the content index of methylene blue for analysis.
Example 2
A method for purifying methylene blue comprises the following steps:
150g of raw material basic lake blue BB, 1950g of water, heating to 60-90 ℃, gradually adding a sodium bicarbonate and sodium carbonate mixed solution (40g of sodium bicarbonate and 0.04g of sodium carbonate dissolved in 500ml of water) while stirring, controlling the pH of the reaction solution to be 7.5-9, completing the addition within about 30 minutes, preserving the temperature for 60 minutes, and then putting the reaction solution into a crystallization tank through a filter. 60g of hydrochloric acid was added to the filtrate, and after stirring for 15 minutes, the filtrate was cooled to precipitate glossy dark green crystals. And (3) carrying out centrifugal drying on the crystals to obtain 63.6g of methylene blue, wherein the content is more than or equal to 98.6 percent, and the yield is 90 percent. The result meets the pharmacopoeia requirement and is far higher than the content index of methylene blue for analysis.
Example 3
A method for purifying methylene blue comprises the following steps:
adding 2400g of water into 150g of raw material basic lake blue BB, heating to 60-90 ℃, gradually adding a sodium bicarbonate and sodium carbonate mixed solution (52.5g of sodium bicarbonate and 0.8g of sodium carbonate dissolved in 500ml of water) while stirring, controlling the pH of a reaction solution to be 7.5-9, finishing the addition within about 30 minutes, preserving the temperature for 100 minutes, and then putting the reaction solution into a crystallization tank through a filter. 90g of hydrochloric acid was added to the filtrate, and after stirring for 15 minutes, the filtrate was cooled to precipitate glossy dark green crystals. And (3) carrying out centrifugal drying on the crystals to obtain 64.5g of methylene blue, wherein the content is more than or equal to 98.5 percent, and the yield is 91.3 percent. The result meets the pharmacopoeia requirement and is far higher than the content index of methylene blue for analysis.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (3)
1. A method for purifying methylene blue is characterized in that: carrying out double decomposition reaction on a zinc chloride component in dye base lake blue BB and a mixture of sodium bicarbonate and sodium carbonate to generate water-insoluble zinc carbonate, filtering out a zinc carbonate precipitate, adding concentrated hydrochloric acid into a filtrate to separate out needle-shaped crystals, filtering out the crystals, centrifugally drying, and drying to obtain bright green needle-shaped methylene blue crystals;
the method specifically comprises the following steps:
(1) putting the basic lake blue BB and water into a container, heating to 60-90 ℃, gradually adding a mixture of sodium bicarbonate and sodium carbonate while stirring, controlling the pH to be 7.5-9, and preserving the heat for 30-100 minutes after the addition is finished; the weight ratio of the basic lake blue BB to the sodium bicarbonate is 1: 0.25-0.35; the mass of the sodium carbonate is 0.1-2% of that of the sodium bicarbonate;
(2) pressing the filtrate into a filter tank through a filter, adding concentrated hydrochloric acid into the filtrate to obtain methylene blue hydrochloride, naturally cooling to separate out glossy dark green crystals, spin-drying by a centrifuge, and drying to obtain high-purity methylene blue.
2. The method for purifying methylene blue according to claim 1, wherein: the weight ratio of the halolake blue BB to the water in the step (1) is 1: 13-16.
3. The method for purifying methylene blue according to claim 2, wherein: in the step (2), when concentrated hydrochloric acid is added into the filtrate, the weight ratio of the basic lake blue BB to the concentrated hydrochloric acid is 1: 0.4-0.6.
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| CN201810373407.7A CN108658895B (en) | 2018-04-24 | 2018-04-24 | Purification method of methylene blue |
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| CN201810373407.7A CN108658895B (en) | 2018-04-24 | 2018-04-24 | Purification method of methylene blue |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006032879A2 (en) * | 2004-09-23 | 2006-03-30 | Wista Laboratories Ltd. | Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (mtc) |
| CN1970548A (en) * | 2006-12-15 | 2007-05-30 | 贵州同济堂制药有限公司 | Medicinal methylene blue synthesis method |
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2018
- 2018-04-24 CN CN201810373407.7A patent/CN108658895B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006032879A2 (en) * | 2004-09-23 | 2006-03-30 | Wista Laboratories Ltd. | Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (mtc) |
| CN103012315A (en) * | 2004-09-23 | 2013-04-03 | 卫思道制药有限公司 | Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC) |
| CN1970548A (en) * | 2006-12-15 | 2007-05-30 | 贵州同济堂制药有限公司 | Medicinal methylene blue synthesis method |
Non-Patent Citations (1)
| Title |
|---|
| 药用亚甲蓝生产工艺的研究;张国玺;《首都师范大学学报(自然科学版)》;20110430;第32卷(第2期);第33-35页 * |
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