CN103360337A - Preparation method of 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole - Google Patents
Preparation method of 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole Download PDFInfo
- Publication number
- CN103360337A CN103360337A CN2013102936030A CN201310293603A CN103360337A CN 103360337 A CN103360337 A CN 103360337A CN 2013102936030 A CN2013102936030 A CN 2013102936030A CN 201310293603 A CN201310293603 A CN 201310293603A CN 103360337 A CN103360337 A CN 103360337A
- Authority
- CN
- China
- Prior art keywords
- sulfydryl
- thiadiazoles
- preparation
- methyl
- isophthalic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Cephalosporin Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
The invention relates to a preparation method of 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole. The preparation method of the 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole, provided by the invention, comprises the following steps of: (1) placing the weighted hydrazine hydrate and ammonium hydroxide into a reaction vessel to be uniformly mixed, dropwise adding carbon disulfide at low temperature, after the dropwise adding operation is ended, stirring and preserving the heat to obtain a water solution of diazanyl dithiocarbamate; (2) adding acetonitrile into the reaction vessel, reacting while stirring, heating, stirring, preserving heat and reflowing to obtain a water solution of 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole aluminum salt; and (3) when the reaction vessel in the step (2) is cooled to be below 40 DEG C, dropwise adding hydrochloric acid for acidifying to obtain a 2-methyl-5-sulfydryl-1, 3, 4-thiadiazole suspension, filtering and washing to obtain milk white crystal powder, namely a crude product of the 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole, and then, purifying and drying the crude product to obtain white crystal powder, namely the 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole. The preparation method has the characteristics of simplicity and convenience in process operation, short reaction time, low production cost and few wastes and pollutants.
Description
Technical field
The present invention relates to medicine, chemical technology field, a kind of 2-sulfydryl-5-methyl isophthalic acid particularly, the preparation method of 3,4-thiadiazoles.
Background technology
2-sulfydryl-5-methyl isophthalic acid, 3,4-thiadiazoles is a kind of white crystalline powder, is the important intermediate of synthetic antibiotic medicine cephazolin sodium, has important industry and medical value.
Existing 2-sulfydryl-5-methyl isophthalic acid, 3, it is raw material that the preparation method of 4-thiadiazoles mainly adopts hydrazine hydrate, ethyl acetate, methyl alcohol or alcohol solvent, alkali lye, dithiocarbonic anhydride, acid solution, wherein, solvent adopts methyl alcohol or ethanol, alkali lye adopts potassium hydroxide or liquefied ammonia, and acid solution adopts the vitriol oil or concentrated hydrochloric acid, is got through hydrazine, addition, cyclization, hydrolysis by ethyl acetate.Existing 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles exists long reaction time, power consumption is large, and complicated operation is loaded down with trivial details, and production cost is high, easily produces simultaneously the weak point of more waste and pollutent.
Summary of the invention
The object of the invention is to for existing 2-sulfydryl-5-methyl isophthalic acid, 3, the existing long reaction time of the preparation method of 4-thiadiazoles, power consumption are greatly, complicated operation is loaded down with trivial details, production cost is high, easily produces simultaneously the weak point of more waste and pollutent, provides that a kind of technological operation is easy, the reaction times is short, production cost is low, waste and pollutent produce few 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles.
Technical scheme of the present invention realizes in the following way: a kind of 2-sulfydryl-5-methyl isophthalic acid, and the preparation method of 3,4-thiadiazoles, this 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles may further comprise the steps:
⑴ put into reaction vessel with the hydrazine hydrate that takes by weighing and ammoniacal liquor and mix, and drips dithiocarbonic anhydride under the condition that is lower than 5 ℃ of temperature, dropwises rear stirring insulation 0.5～1h, obtains the aqueous solution of diazanyl dithio ammonium formiate, and its reaction formula is as follows:
⑵ add acetonitrile in reaction vessel, then stirring reaction 1～2h rises to reacting liquid temperature 85～90 ℃, stirs insulation backflow 0.5～1h, obtains 2-sulfydryl-5-methyl isophthalic acid, 3,4-thiadiazoles ammonium salt aqueous solution, and its reaction formula is as follows:
⑶ when treat below the greenhouse cooling to 40 ℃ of the reaction vessel among the step ⑵, drip hcl acidifying and obtain 2-methyl-5-sulfydryl-1,3,4-thiadiazoles suspension liquid, filtration washing obtain the oyster white crystal powder and are 2-sulfydryl-5-methyl isophthalic acid, 3,4-thiadiazoles crude product, purified drying obtains white crystalline powder 2-sulfydryl-5-methyl isophthalic acid, 3 again, the 4-thiadiazoles, its reaction formula is as follows:
At above-mentioned a kind of 2-sulfydryl-5-methyl isophthalic acid, among the preparation method of 3,4-thiadiazoles, in step ⑴, the mass ratio of described ammoniacal liquor and hydrazine hydrate is 2～2.4:1.
At above-mentioned a kind of 2-sulfydryl-5-methyl isophthalic acid, among the preparation method of 3,4-thiadiazoles, in step ⑵, the mass ratio of described acetonitrile and hydrazine hydrate is 1.9～2.2:1.
At above-mentioned a kind of 2-sulfydryl-5-methyl isophthalic acid, among the preparation method of 3,4-thiadiazoles, in step ⑶, described concentration of hydrochloric acid is 35%～38%.
The present invention and existing 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles compares, and has following characteristics:
1, raw materials used relative minimizing, processing step are simplified, and one step of building-up process goes down, and has not only shortened the production cycle, has reduced raw materials cost, have also improved product yield and quality product is true.
2, in building-up process, without organic solvents such as methanol/ethanol, reaction is become with the reaction of water as solvent.In the water solvent reaction with organic solvent in the reacting phase ratio, at water as under the solvent condition, operation is simple, do not need again with separated from solvent out, save energy, the loss that has prevented simultaneously intermediate product is run off, and has improved product yield, has prevented the generation of waste and the advantage of poisonous and hazardous material environmental pollution.
Embodiment
Below by embodiment the present invention is made further and to specify, but the present invention is not limited only to these embodiment.
Embodiment 1:
Put into successively 50 grams, 100% hydrazine hydrate in 500 milliliters of building-up reactions bottles, 120 restrain 20% ammoniacal liquor, stir temperature is dropped to below 5 ℃ under the frozen water cooling.Begin to drip dithiocarbonic anhydride 90 grams, finish to continue again to remain on below 5 ℃ and stirred 1 hour.Obtain the aqueous solution of diazanyl dithio ammonium formiate.
Solution obtained above is changed over to 1000 milliliters reaction flask, add 100 gram acetonitriles, naturally stir half hour, be warming up to again 85～90 ℃ of insulations 1 hour.Then solution is cooled to below 40 ℃, drips 30% hydrochloric acid in 30 ℃ to 35 ℃ scopes, transfer pH to 4 to 4.5, stir half an hour, suction filtration is washed 3 times, obtains the wet product 130g of thiadiazoles.
The wet product that obtain with ammonia solvent, decolouring, insulation, filtration, acidifying, suction filtration, dry to get thiadiazoles elaboration 79g.Through HPLC liquid phase analysis, product content 99.8%.
Embodiment 2:
Put into successively 50 grams, 100% hydrazine hydrate in 500 milliliters of building-up reactions bottles, 120 restrain 20% ammoniacal liquor, stir temperature is dropped to below 5 ℃ under the frozen water cooling.Begin to drip dithiocarbonic anhydride 80 grams, finish to continue again to remain on below 5 ℃ and stirred 1 hour.Obtain the aqueous solution of diazanyl dithio ammonium formiate.
Solution obtained above is changed over to 1000 milliliters reaction flask, add 100 gram acetonitriles, naturally stir half hour, be warming up to again 85～90 ℃ of insulations 1 hour.Then solution is cooled to below 40 ℃, drips 35% hydrochloric acid in 30 ℃ to 35 ℃ scopes, transfer pH to 4 to 4.5, stir half an hour, suction filtration is washed 3 times, obtains the wet product 142g of thiadiazoles.
The wet product that obtain with ammonia solvent, decolouring, insulation, filtration, acidifying, suction filtration, dry to get thiadiazoles elaboration 85g.Through HPLC liquid phase analysis, product content 99.9%.
Embodiment 3:
Put into successively 50 grams, 100% hydrazine hydrate in 500 milliliters of building-up reactions bottles, 120 restrain 20% ammoniacal liquor, stir temperature is dropped to below 5 ℃ under the frozen water cooling.Begin to drip dithiocarbonic anhydride 80 grams, finish to continue again to remain on below 5 ℃ and stirred 1 hour.Obtain the aqueous solution of diazanyl dithio ammonium formiate.
Solution obtained above is changed over to 1000 milliliters reaction flask, add 105 gram acetonitriles, naturally stir half hour, be warming up to again 85～90 ℃ of insulations 1 hour.Then solution is cooled to below 40 ℃, drips 35% hydrochloric acid in 30 ℃ to 35 ℃ scopes, transfer pH to 4 to 4.5, stir half an hour, suction filtration is washed 3 times, obtains the wet product 135g of thiadiazoles.
The wet product that obtain with ammonia solvent, decolouring, insulation, filtration, acidifying, suction filtration, dry to get thiadiazoles elaboration 82g.Through HPLC liquid phase analysis, product content 99.9%.
Claims (4)
1. 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles is characterized in that this 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles may further comprise the steps:
⑴ put into reaction vessel with the hydrazine hydrate that takes by weighing and ammoniacal liquor and mix, and drips dithiocarbonic anhydride under the condition that is lower than 5 ℃ of temperature, dropwises rear stirring insulation 0.5～1h, obtains the aqueous solution of diazanyl dithio ammonium formiate, and its reaction formula is as follows:
⑵ add acetonitrile in reaction vessel, then stirring reaction 1～2h rises to reacting liquid temperature 85～90 ℃, stirs insulation backflow 0.5～1h, obtains 2-sulfydryl-5-methyl isophthalic acid, 3,4-thiadiazoles ammonium salt aqueous solution, and its reaction formula is as follows:
⑶ when treat below the greenhouse cooling to 40 ℃ of the reaction vessel among the step ⑵, drip hcl acidifying and obtain 2-methyl-5-sulfydryl-1,3,4-thiadiazoles suspension liquid, filtration washing obtain the oyster white crystal powder and are 2-sulfydryl-5-methyl isophthalic acid, 3,4-thiadiazoles crude product, purified drying obtains white crystalline powder 2-sulfydryl-5-methyl isophthalic acid, 3 again, the 4-thiadiazoles, its reaction formula is as follows:
2. a kind of 2-sulfydryl according to claim 1-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles is characterized in that in step ⑴ the mass ratio of described ammoniacal liquor and hydrazine hydrate is 2～2.4:1.
3. a kind of 2-sulfydryl according to claim 1 and 2-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles is characterized in that in step ⑵ the mass ratio of described acetonitrile and hydrazine hydrate is 1.9～2.2:1.
4. a kind of 2-sulfydryl according to claim 1 and 2-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles is characterized in that in step ⑶ described concentration of hydrochloric acid is 35%～38%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310293603.0A CN103360337B (en) | 2013-07-11 | 2013-07-11 | A kind of 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310293603.0A CN103360337B (en) | 2013-07-11 | 2013-07-11 | A kind of 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103360337A true CN103360337A (en) | 2013-10-23 |
| CN103360337B CN103360337B (en) | 2016-04-27 |
Family
ID=49362688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310293603.0A Expired - Fee Related CN103360337B (en) | 2013-07-11 | 2013-07-11 | A kind of 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103360337B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303077A (en) * | 2020-03-13 | 2020-06-19 | 山东鲁抗和成制药有限公司 | Preparation method of 2-mercapto-5-methyl-1, 3, 4-thiadiazole |
| CN111925340A (en) * | 2019-12-16 | 2020-11-13 | 山东金城柯瑞化学有限公司 | Preparation process of methyl mercapto thiadiazole |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0304330A1 (en) * | 1987-08-19 | 1989-02-22 | SHIONOGI SEIYAKU KABUSHIKI KAISHA trading under the name of SHIONOGI & CO. LTD. | Carbamoylpyrrolidone derivatives, their use and preparation |
| JPH01160976A (en) * | 1987-12-18 | 1989-06-23 | Tsumura & Co | 1,3,4-thiadiazole derivative and antiulcer agent containing said derivative as active component |
| JPH058970A (en) * | 1991-07-02 | 1993-01-19 | Hitachi Building Syst Eng & Service Co Ltd | Hydraulic circuit for hydraulic elevator |
| WO1997002023A1 (en) * | 1995-06-30 | 1997-01-23 | Smithkline Beecham Corporation | USE OF Stat 6 SH2 DOMAIN SPECIFIC COMPOUNDS TO TREAT ALLERGIC REACTIONS |
| WO1998027092A1 (en) * | 1996-12-18 | 1998-06-25 | Sugen, Inc. | Thiazole compounds and methods of modulating signal transduction |
| CN102108515A (en) * | 2011-04-11 | 2011-06-29 | 李佃场 | Application of environment-friendly corrosion inhibitor to copper in seawater |
| CN102115892A (en) * | 2011-04-18 | 2011-07-06 | 李佃场 | Application of environment-friendly copper seawater corrosion inhibitor |
| CN102372681A (en) * | 2011-10-28 | 2012-03-14 | 中国科学院海洋研究所 | Environment-friendly thiazole compound as well as preparation and application thereof |
| CN102659715A (en) * | 2012-04-17 | 2012-09-12 | 黑龙江豪运精细化工有限公司 | Preparation method of 5-methyl-2-mercapto-1,3,4-thiadiazole |
| CN103145645A (en) * | 2013-03-18 | 2013-06-12 | 陆宏庆 | Preparation technology of mercapto-5-methyl-1,3,4-thiadiazole |
-
2013
- 2013-07-11 CN CN201310293603.0A patent/CN103360337B/en not_active Expired - Fee Related
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0304330A1 (en) * | 1987-08-19 | 1989-02-22 | SHIONOGI SEIYAKU KABUSHIKI KAISHA trading under the name of SHIONOGI & CO. LTD. | Carbamoylpyrrolidone derivatives, their use and preparation |
| JPH01160976A (en) * | 1987-12-18 | 1989-06-23 | Tsumura & Co | 1,3,4-thiadiazole derivative and antiulcer agent containing said derivative as active component |
| JPH058970A (en) * | 1991-07-02 | 1993-01-19 | Hitachi Building Syst Eng & Service Co Ltd | Hydraulic circuit for hydraulic elevator |
| WO1997002023A1 (en) * | 1995-06-30 | 1997-01-23 | Smithkline Beecham Corporation | USE OF Stat 6 SH2 DOMAIN SPECIFIC COMPOUNDS TO TREAT ALLERGIC REACTIONS |
| WO1998027092A1 (en) * | 1996-12-18 | 1998-06-25 | Sugen, Inc. | Thiazole compounds and methods of modulating signal transduction |
| CN102108515A (en) * | 2011-04-11 | 2011-06-29 | 李佃场 | Application of environment-friendly corrosion inhibitor to copper in seawater |
| CN102115892A (en) * | 2011-04-18 | 2011-07-06 | 李佃场 | Application of environment-friendly copper seawater corrosion inhibitor |
| CN102372681A (en) * | 2011-10-28 | 2012-03-14 | 中国科学院海洋研究所 | Environment-friendly thiazole compound as well as preparation and application thereof |
| CN102659715A (en) * | 2012-04-17 | 2012-09-12 | 黑龙江豪运精细化工有限公司 | Preparation method of 5-methyl-2-mercapto-1,3,4-thiadiazole |
| CN103145645A (en) * | 2013-03-18 | 2013-06-12 | 陆宏庆 | Preparation technology of mercapto-5-methyl-1,3,4-thiadiazole |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925340A (en) * | 2019-12-16 | 2020-11-13 | 山东金城柯瑞化学有限公司 | Preparation process of methyl mercapto thiadiazole |
| CN111303077A (en) * | 2020-03-13 | 2020-06-19 | 山东鲁抗和成制药有限公司 | Preparation method of 2-mercapto-5-methyl-1, 3, 4-thiadiazole |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103360337B (en) | 2016-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107473949B (en) | Synthesis process of 3, 5-dichloro-2-pentanone | |
| CN104356146B (en) | A kind of preparation method of cefotiam chloride | |
| CN103613672A (en) | Method for preparing cellulose acetate by employing ionic liquid as catalyst | |
| CN101357911A (en) | Method for synthesizing (z)-2-(alpha-methoxyimino)furan-ammonium acetate | |
| CN103360337A (en) | Preparation method of 2-sulfydryl-5-methyl-1, 3, 4-thiadiazole | |
| CN103951557B (en) | A kind of method with inorganic base for catalyst preparing fenofibrate | |
| CN102659715A (en) | Preparation method of 5-methyl-2-mercapto-1,3,4-thiadiazole | |
| CN103450013A (en) | Industrial preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride | |
| CN101423231A (en) | Purification method of solid cyanamide | |
| CN103145645B (en) | The preparation technology of methyl mercapto thiadiazoles | |
| CN108997305A (en) | A kind of new compound 3- methyl -4,5- dichloro-thiophene -2- carboxylic acid and preparation method thereof | |
| CN105585539B (en) | The method of one pot process cefotaxime side chain acetoacetic ester | |
| CN102746209A (en) | A synthetic method for 3-(2-(4-chlorophenoxy)phenyl )-1-methyl-2,4-dione | |
| CN104355990B (en) | Method for recycling and mechanically using L- (+) -tartaric acid in D-ethyl ester production | |
| CN103172530B (en) | Preparation method of tolfenamic acid | |
| CN107383418B (en) | A kind of uvioresistant plastic additive and preparation method thereof | |
| CN102409354A (en) | Electrolytic synthesis method of 2-pyridinecarboxylic acid | |
| CN104829478A (en) | Preparation process of D-phenylglycine methyl ester hydrochloride crystals | |
| CN104557685A (en) | Method for producing nicotinic acid by using nicotinamide mother solution | |
| CN103224437A (en) | Amino acid methyl ester hydrochloride preparation | |
| CN107986959B (en) | Preparation method and preparation system of ammonium adipate | |
| CN103626695B (en) | New method for preparing fluazinam by using mixed solvent as medium | |
| CN103755609A (en) | Novel crystal form of valnemulin hydrogen tartrate and preparation method thereof | |
| CN103896757A (en) | Cis-trans isomerization method of 2 or 4-substituted naphthenic acid compound | |
| CN102924396B (en) | Method for crystal transformation from alpha-HMX to beta-HMX |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 324004 Zhejiang province Kecheng District of Quzhou City Green Road No. 18 Applicant after: ZHEJIANG HAILAN CHEMICAL GROUP CO., LTD. Address before: 324004 Zhejiang province Kecheng District of Quzhou City Green Road No. 18 Applicant before: Zhejiang Hailan Chemical Co., Ltd. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: ZHEJIANG HAILAN CHEMICAL CO., LTD. TO: ZHEJIANG HAILAN CHEMICAL GROUP CO., LTD. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160427 Termination date: 20170711 |