CN110903263B - Synthesis method of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate - Google Patents
Synthesis method of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate Download PDFInfo
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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Abstract
The invention discloses a synthesis method of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, which comprises the steps of synthesizing 3-methyl-2-benzothiazolinone hydrazone by a one-pot method by using cheap and easily-obtained 2-mercaptobenzothiazole as an initial raw material, and reacting the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with hydrochloric acid to obtain a target product, namely 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate; the process has the advantages of mild reaction conditions, high yield, simple and convenient operation, low production cost, no use of organic solvent, safety and reliability, and suitability for large-scale production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate.
Background
The 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate (phenolic reagent) is a reagent for measuring fatty aldehyde by a photometric method, is also used for measuring hexosamine in mucopolysaccharide, and photometrically measures trace selenium in an environmental sample. Formaldehyde in the air reacts with a phenol reagent to generate oxazine, the oxazine is oxidized by ferric ions in an acid solution to form a blue-green compound, and the concentration of the formaldehyde can be quantified by colorimetry according to the shade of the color. In the national standard GB/T16057-95, the formaldehyde content is quantitatively detected by reacting excessive 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with formaldehyde, so that the method can be used for detecting the formaldehyde content in workshop air and is also suitable for detecting trace formaldehyde.
The formaldehyde is a main pollutant of a newly-decorated house, and the content of the formaldehyde is one of important indexes for acceptance of the house; the formaldehyde test paper produced by the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is a tool for detecting whether formaldehyde exceeds the standard, has high sensitivity and simple and convenient operation, and is very suitable for family self-inspection, so that the market of formaldehyde self-inspection products is continuously expanded. Meanwhile, the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate can also be used for developing color correction in the photographic industry and coloring and toning hair in the hairdressing industry.
For 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, the currently reported synthetic methods mainly include the following three methods:
1. aniline is used as a starting material, and 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate [ Ber.,43,1519-1526] is synthesized through 6 steps of reaction; the reaction steps are long, bromine is needed, the danger is high, and nitroso compound carcinogens are generated in the reaction process, so that the synthetic process is complex to operate, strong in toxicity and difficult to produce in a large scale.
2. 2-mercaptobenzothiazole is used as a raw material, and 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate [ Anal chem.1961,33,93-96] is synthesized through 4 steps of reaction; the method has the advantages of few synthesis steps and high yield, but uses highly toxic dimethyl sulfate, which is not beneficial to scale-up production.
3. N-methylaniline is used as a raw material, and 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate [ CN 1634900A ] is synthesized through 4 steps of reaction; the method is similar to the synthesis process of the method (1), and adopts N-methylaniline as a raw material, so that the synthesis steps can be reduced, but bromine is also used, the method has high risk and complex operation, the large production scale is limited, and the market demand can not be well met.
In view of the good market prospect of the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, the search for a novel synthetic method to realize the industrial production is very meaningful, wherein the key is to solve the key problem of the production process, and the required process is simple and convenient and has ideal cost.
Disclosure of Invention
In view of the above, the invention provides a method for synthesizing the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, which has a simple process, low toxicity and environmental protection.
In order to solve the technical problems, the technical scheme of the invention is to adopt a synthesis method of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, which comprises the following steps:
a. reacting a compound shown in a formula I with benzene sulfonate and hydrazine hydrate under an alkaline condition to generate a compound shown in a formula II;
b. and (3) reacting the compound shown in the formula II with hydrochloric acid to obtain 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate.
Preferably, the reaction temperature in the step a is 80-120 ℃.
Preferably, the basic conditions in step a are formed by one or more basic compounds of the following compounds: potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, strontium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium oxide, zinc oxide, calcium oxide.
Preferably, the basic conditions in step a form potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate from one or more of the following compounds.
Preferably, the mass ratio of the compound shown in the formula I, the alkaline compound, the methyl benzene sulfonate and the hydrazine hydrate is 1: (1.1-1.5): (2-3.5): (2-8).
Preferably, the reaction temperature in the step b is 50-100 ℃.
Preferably, the reaction temperature in step b is: 50-80 ℃.
Preferably, the mass ratio of the compound shown in the formula II to the hydrochloric acid is 1: 2-5.
Preferably, the mass concentration of the hydrochloric acid is 10-36%.
The invention has the advantages that: the invention uses cheap and easily obtained 2-mercaptobenzothiazole as an initial raw material to synthesize 3-methyl-2-benzothiazolinone hydrazone by a one-pot method, and then the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is reacted with hydrochloric acid to obtain a target product. In the reaction process, the reaction activity of the 2-mercaptobenzothiazole and alkali after salification is greatly enhanced, the 2-mercaptobenzothiazole can quickly react with methyl benzenesulfonate to generate 2-methylthiobenzothiazole, and simultaneously reacts with excessive methyl benzenesulfonate to generate quaternary ammonium salt; at the moment, hydrazine hydrate is added, so that the hydrazine hydrate can be fully converted into 3-methyl-2-benzothiazolinone hydrazone, and the 3-step reaction is carried out in a reaction kettle, so that the method is simple and convenient; the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate which is obtained by centrifugation can be obtained through simple acid-base reaction.
The process has the advantages of mild reaction conditions, high yield, simple and convenient operation, low production cost, no use of organic solvent, safety and reliability, and suitability for mass production.
Drawings
FIG. 1 is a nuclear magnetic spectrum of a 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate prepared in an embodiment of the present invention.
Detailed Description
In order that those skilled in the art will better understand the technical solutions of the present invention, the present invention will be further described in detail with reference to the following embodiments.
A method for synthesizing 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate comprises the following steps:
a. reacting a compound shown in a formula I with benzene sulfonate and hydrazine hydrate under an alkaline condition to generate a compound shown in a formula II;
b. and (3) reacting the compound shown in the formula II with hydrochloric acid to obtain 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate.
According to the invention, the reaction is specifically:
the compound shown in the formula I is 2-mercaptobenzothiazole, the compound shown in the formula II is 3-methyl-2-benzothiazolinone hydrazone, and the reaction temperature is 80-120 ℃. The basic conditions are formed by one or more basic compounds of the following compounds: potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, strontium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium oxide, zinc oxide, calcium oxide. More preferably potassium hydroxide, sodium carbonate, potassium bicarbonate, calcium oxide; most preferably potassium hydroxide or sodium hydroxide.
The mass ratio of the compound shown in the formula I, the alkaline compound, the methyl benzenesulfonate and the hydrazine hydrate is 1:
(1.1～1.5)：(2～3.5)：(2～8)。
the reaction temperature in the step b is 50-100 ℃. Preferably: 50-80 ℃. The mass ratio of the compound shown in the formula II to the hydrochloric acid is 1: 2-5. The mass concentration of the added hydrochloric acid is 10-36%.
According to the method provided by the invention, the reaction activity is greatly enhanced after the salt formation of the 2-mercaptobenzothiazole and the alkali, the 2-mercaptobenzothiazole can quickly react with the methyl benzenesulfonate to generate the 2-methylthiobenzothiazole, and simultaneously reacts with the excessive methyl benzenesulfonate to generate the quaternary ammonium salt; at the moment, hydrazine hydrate is added, so that the hydrazine hydrate can be fully converted into 3-methyl-2-benzothiazolinone hydrazone, and the 3-step reaction is carried out in a reaction kettle, so that the method is simple and convenient; the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate which is obtained by centrifugation can be obtained through simple acid-base reaction.
Example 1:
adding 200 g of 2-mercaptobenzothiazole and 500 ml of water into a reaction bottle, adding 55 g of sodium hydroxide while stirring, stirring for 1 hour, and dropwise adding 535 g of methyl benzenesulfonate; after the completion of the dropwise addition, the mixture was refluxed for 4 hours. The reaction solution was cooled to room temperature, and 200 g of 80% hydrazine hydrate was added in one portion and left overnight.
Performing suction filtration, wherein the precipitated solid is a compound shown as a formula II, and washing a small amount of solid with cold water; adding the solid into 500 ml of concentrated hydrochloric acid, stirring overnight at room temperature, cooling with ice water, performing suction filtration, washing the solid for 1 time with a small amount of cold hydrochloric acid, and drying the solid by using an infrared lamp to obtain 178 g of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with the yield of 64%.
Example 2:
adding 200 g of 2-mercaptobenzothiazole, 535 g of methyl benzenesulfonate and 96 g of magnesium oxide into a reaction flask, and heating to 120 ℃ for reaction for 4 hours; 500 ml of water was added thereto, followed by stirring, 200 g of 80% hydrazine hydrate was slowly dropped, and the mixture was left overnight.
Performing suction filtration, wherein the precipitated solid is a compound shown as a formula II, and washing a small amount of solid with cold water; adding the solid into 500 ml of concentrated hydrochloric acid, heating to 80 ℃ for reaction for 2 hours, cooling with ice water, carrying out suction filtration, washing a small amount of cold hydrochloric acid on the solid for 1 time, and drying the solid by using an infrared lamp to obtain 156 g of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with the yield of 56%.
Example 3:
adding 200 g of 2-mercaptobenzothiazole, 535 g of methyl benzenesulfonate and 180 g of sodium carbonate into a reaction bottle, heating to 80 ℃ for reaction for 2 hours, and then heating to 120 ℃ for reaction for 1 hour; 500 ml of water was added thereto, followed by stirring, and 250 g of 80% hydrazine hydrate was slowly dropped and left overnight.
Performing suction filtration, wherein the precipitated solid is a compound shown as a formula II, and washing a small amount of solid with cold water; adding the solid into 500 ml of concentrated hydrochloric acid, heating to 80 ℃ for reaction for 2 hours, cooling with ice water, carrying out suction filtration, washing a small amount of cold hydrochloric acid on the solid for 1 time, and drying the solid by using an infrared lamp to obtain 190 g of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with the yield of 68%.
Example 4:
adding 20L of water and 10 kg of potassium carbonate into a 50L reaction kettle, stirring to dissolve, adding 10 kg of 2-mercaptobenzothiazole, heating to 60 ℃, slowly dripping 31 kg of methyl benzenesulfonate, keeping the temperature at 60 ℃ until the raw materials completely react, and heating and refluxing for 4 hours. After cooling, 25 kg of 80% hydrazine hydrate was added dropwise and the reaction was stirred overnight.
Performing suction filtration, wherein the precipitated solid is a compound shown in a formula II, and washing a small amount of solid with cold water; adding the solid into 30L concentrated hydrochloric acid in batches, heating to 80 ℃ for reaction for 2 hours, cooling with ice water, carrying out suction filtration, washing a small amount of cold hydrochloric acid on the solid for 1 time, and drying the solid by using an infrared lamp to obtain 12.5 kg of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate with the yield of 88%.
Example 5:
adding 50 liters of water and 11.5 kilograms of potassium hydroxide into a reaction kettle, stirring to dissolve, adding 25 kilograms of 2-mercaptobenzothiazole, stirring for 30 minutes, slowly dripping 72 kilograms of methyl benzenesulfonate at room temperature, completely reacting the raw materials, and heating to 90 ℃ for reacting for 6 hours. After cooling, 56 kg of 80% hydrazine hydrate are added dropwise and the reaction is stirred overnight.
Performing suction filtration, wherein the precipitated solid is a compound shown as a formula II, and washing a small amount of solid with cold water; the solid is added into 60L of concentrated hydrochloric acid in batches, heated to 60 ℃, stirred overnight, cooled by ice water, filtered, washed by a small amount of cold hydrochloric acid for 1 time, and dried by an infrared lamp to obtain 32 kg of 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, wherein the yield is 92%.
Comparative example 1:
according to the method of [ Ber.,43,1519-1526], aniline is used as a starting material to synthesize the 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate through 6 steps of reaction, and the yield is 53%.
Comparative example 2:
the product is synthesized by 4 steps of reaction according to the method of (Anal Chem.1961,33, 93-96) and the yield is 60 percent, but the method uses dimethyl sulfide which is a highly toxic medicine and is not beneficial to environmental protection and human health.
Comparative example 3:
the product prepared according to the method of CN 1634900A has the yield of 95%, but bromine is also used, so that the method has high danger and complex operation, limits the scale of large-scale production and cannot well meet the market demand.
According to the three comparative examples, various problems exist in the prior art, and the method provided by the invention solves the problems of complex preparation process, toxic raw materials and the like in the prior art.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.
Claims (9)
1. A method for synthesizing 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is characterized by comprising the following steps:
a. reacting a compound shown in a formula I with benzene sulfonate and hydrazine hydrate under an alkaline condition to generate a compound shown in a formula II;
b. and (3) reacting the compound shown in the formula II with hydrochloric acid to obtain 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate.
2. The method of claim 1, wherein: the reaction temperature in the step a is 80-120 ℃.
3. The process according to claim 2, wherein the basic conditions in step a are formed by one or more of the following compounds: potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, strontium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium oxide, zinc oxide, calcium oxide.
4. A process according to claim 3, characterized in that the basic conditions in step a form potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate from one or more of the following compounds.
5. The method according to claim 3, wherein the mass ratio of the compound represented by the formula I, the basic compound, the methyl benzenesulfonate and the hydrazine hydrate is 1: (1.1-1.5): (2-3.5): (2-8).
6. The method of claim 1, wherein the reaction temperature in step b is 50 to 100 ℃.
7. The method of claim 6, wherein the temperature of the reaction in step b is: 50-80 ℃.
8. The method according to claim 1, wherein the mass ratio of the compound represented by the formula II to the hydrochloric acid is 1: 2-5.
9. The method according to claim 8, wherein the mass concentration of the hydrochloric acid is 10-36%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634900A (en) * | 2004-10-21 | 2005-07-06 | 复旦大学 | Method for preparing 3-methyl-2-benzothiazolinone hydrazone and its hydrochloride |
| CN102382050A (en) * | 2010-08-31 | 2012-03-21 | 上海康莱曼医药科技有限公司 | Preparation method of substituted 1, 2, 3 and 4- tetrahydroquinoline -4-one hydrochloride |
| CN104311507A (en) * | 2013-10-09 | 2015-01-28 | 安徽万邦医药科技有限公司 | Preparation method of (6S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634900A (en) * | 2004-10-21 | 2005-07-06 | 复旦大学 | Method for preparing 3-methyl-2-benzothiazolinone hydrazone and its hydrochloride |
| CN102382050A (en) * | 2010-08-31 | 2012-03-21 | 上海康莱曼医药科技有限公司 | Preparation method of substituted 1, 2, 3 and 4- tetrahydroquinoline -4-one hydrochloride |
| CN104311507A (en) * | 2013-10-09 | 2015-01-28 | 安徽万邦医药科技有限公司 | Preparation method of (6S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole |
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