CN107325073A - A kind of new synthetic method of DL homocysteine thiolactones hydrochloride - Google Patents
A kind of new synthetic method of DL homocysteine thiolactones hydrochloride Download PDFInfo
- Publication number
- CN107325073A CN107325073A CN201710695613.5A CN201710695613A CN107325073A CN 107325073 A CN107325073 A CN 107325073A CN 201710695613 A CN201710695613 A CN 201710695613A CN 107325073 A CN107325073 A CN 107325073A
- Authority
- CN
- China
- Prior art keywords
- synthetic method
- new synthetic
- reaction
- thiolactone hydrochloride
- methionine
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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 to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of new synthetic method of DL homocysteine thiolactones hydrochloride, with metallic sodium reduction reaction occurs for DL methionine, and reduzate is through except after salt treatment, concentration removes water to obtain DL homocysteine thiolactone hydrochlorides under the conditions of watery hydrochloric acid.The present invention uses methionine one-step synthesis DL homocysteine, DL homocysteine is concentrated in acid condition is directly changed DL homocysteine thiolactone hydrochlorides, therefore avoiding current technology is transformed into the process that DL homocystine is restored with DL methionine, shorten reactions steps, avoid the pyroreaction condition of harshness, the release of hypertoxic gas and the generation of a large amount of high-salt wastewaters are reduced, three waste discharge is reduced, has saved substantial amounts of energy consumption；Medium used in simultaneous reactions, which is recycled, to be applied mechanically, cost-effective.The inventive method meets the requirement of environmental protection technique, and simple to operate, preparation is convenient, cost is low, mass produced suitable for industrialization.
Description
Technical field
The present invention relates to the synthesis technical field of compound, particularly a kind of homocysteinic acid thiolactone hydrochloride
New synthetic method.
Background technology
Homocysteinic acid thiolactone hydrochloride (DL-HCT) is a kind of important biochemical reagents and pharmaceutical intermediate, can
For preparing Citiolone, the medicine such as Erdosteine, Erdosteine is used for caused by acute and chronic bronchitis thick sputum
Respiratory tract obst ruction, in Italy, South Korea etc. largely lists.
In the prior art, often gone back when chemical combination method synthesizes the product with metallic zinc or tin and hydrochloric acid with DL- homocystine
Original reaction is made.Because the method produces substantial amounts of hydrogen, zinc salt or pink salt and substantial amounts of waste water during the course of the reaction, not only environment
Pollution is extremely serious, and operating process is very cumbersome, dangerous also larger, therefore chemical reduction method technique is substantially domestic
Outer producer eliminates.It is now domestic that the production high half Guang ammonia of DL- is substantially carried out using the method for electrochemical reduction DL- homocystine
Sour thiolactone hydrochloride (DL-HCT).And the synthesis of DL- homocystine is to use DL- METHIONINE high in 9-18N sulfuric acid solution
Warm demethylation oxidative coupling is obtained, but the technical process of production DL- homocystine needs high temperature (130 DEG C), while discharging big
The dimethyl sulphide of amount, the toxic gas such as sulfur dioxide, post processing produces substantial amounts of high-salt wastewater, easily causes environmental pollution, gives
Manufacturing enterprise brings higher environmentally friendly cost pressure.
The content of the invention
It is an object of the invention to overcome the shortcoming of prior art directly to be synthesized with DL- METHIONINE one-step method there is provided one kind
The new synthetic method of homocysteinic acid thiolactone hydrochloride, homocysteinic acid is easily changed into during post processing
Homocysteinic acid thiolactone hydrochloride.
The purpose of the present invention is achieved through the following technical solutions：A kind of conjunction of homocysteinic acid thiolactone hydrochloride
Into new method, with metallic sodium reduction reaction occurs for DL- METHIONINE, and reduzate is dense under the conditions of watery hydrochloric acid through except after salt treatment
Contracting removes water to obtain homocysteinic acid thiolactone hydrochloride.
Further, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:3~10.
Further, the reaction medium of the reduction reaction is the mixed system of liquefied ammonia or liquefied ammonia and water.
Further, the reaction temperature of the reduction reaction is -20 DEG C~-80 DEG C.
Further, the reaction time of the reduction reaction is 5~20h.
Further, the desalination is processed as：Reduzate is shifted by vacuum or tipping separates solid-liquid two-phase
Material, the liquid-phase system addition ammonium chloride of separation is quenched the excessive metallic sodium dissolved in system, by the reaction system being quenched certainly
So the liquefied ammonia in heating removing system, will remove remaining solid mixture water after ammonia and dissolves, upper cationic ion-exchange resin
Ammonium salt and sodium salt are removed, eluent is collected.
Further, the ammonia is reclaimed using low temperature and is used.
Further, the method for the concentration water removal is：Reduzate is through except after salt treatment, with the pH of concentrated hydrochloric acid tune solution
Value, using vacuum concentration, obtains homocysteinic acid thiolactone hydrochloride to 1~2.
The present invention synthetic route be：
The present invention has advantages below：The new synthetic method for the homocysteinic acid thiolactone hydrochloride that the present invention is provided
Using methionine one-step synthesis homocysteinic acid, homocysteinic acid is concentrated in acid condition is directly changed DL- height half
Cystine thiolactone hydrochloride, is transformed into DL- homocystine with DL- METHIONINE inventive process avoids current technology and restores
Process, shorten reactions steps, it is to avoid harsh pyroreaction condition, reduce the release of hypertoxic gas and a large amount of high salts
The generation of waste water, reduces three waste discharge, has saved substantial amounts of energy consumption；Medium used in simultaneous reactions can be saved with recycled
About cost.The inventive method meets the requirement of environmental protection technique, and simple to operate, preparation is convenient, cost is low, suitable for industry
Change large-scale production.
Embodiment
With reference to embodiment, the present invention will be further described, and protection scope of the present invention is not limited to following institute
State：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, reduzate is through except after salt treatment, concentration removes water to obtain homocysteinic acid thiolactone hydrochloride under the conditions of watery hydrochloric acid.Close
It is as follows into route：
Embodiment 1：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:3, reaction medium is liquefied ammonia, and reaction temperature is -20 DEG C, reduction
The reaction time of reaction is 20h, and by reduzate by vacuum transfer separation solid-liquid two-phase material, the liquid-phase system of separation is added
Enter ammonium chloride and the excessive metallic sodium dissolved in system is quenched, the liquefied ammonia in removing system that the reaction system being quenched is heated up naturally,
Ammonia is reclaimed using low temperature and is used, and will be removed remaining solid mixture water after ammonia and is dissolved, upper cation exchange tree
Fat removes ammonium salt and sodium salt, collects eluent.The pH value that eluent adjusts solution with concentrated hydrochloric acid, using vacuum concentration, is obtained to 1
Homocysteinic acid thiolactone hydrochloride.
Embodiment 2：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:10, reaction medium is the mixed system of liquefied ammonia and water, reaction
Temperature is -80 DEG C, and the reaction time of reduction reaction is 5h, and reduzate is separated into solid-liquid two-phase material by tipping, will be divided
From liquid-phase system add ammonium chloride the excessive metallic sodium that is dissolved in system be quenched, the reaction system being quenched is heated up naturally removing
Liquefied ammonia in system, ammonia is reclaimed using low temperature and is used, and will be removed remaining solid mixture water after ammonia and is dissolved, on
Cationic ion-exchange resin removes ammonium salt and sodium salt, collects eluent.Eluent with concentrated hydrochloric acid adjust solution pH value to 2, using true
Sky concentration, obtains homocysteinic acid thiolactone hydrochloride.
Embodiment 3：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:4, reaction medium is liquefied ammonia, and reaction temperature is -40 DEG C, reduction
The reaction time of reaction is 10h, and by reduzate by vacuum transfer separation solid-liquid two-phase material, the liquid-phase system of separation is added
Enter ammonium chloride and the excessive metallic sodium dissolved in system is quenched, the liquefied ammonia in removing system that the reaction system being quenched is heated up naturally,
Ammonia is reclaimed using low temperature and is used, and will be removed remaining solid mixture water after ammonia and is dissolved, upper cation exchange tree
Fat removes ammonium salt and sodium salt, collects eluent.The pH value that eluent adjusts solution with concentrated hydrochloric acid, using vacuum concentration, is obtained to 1
Homocysteinic acid thiolactone hydrochloride.
Embodiment 4：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:6, reaction medium is the mixed system of liquefied ammonia and water, reaction temperature
Spend for -50 DEG C, the reaction time of reduction reaction is 14h, by reduzate by vacuum transfer separation solid-liquid two-phase material, will divide
From liquid-phase system add ammonium chloride the excessive metallic sodium that is dissolved in system be quenched, the reaction system being quenched is heated up naturally removing
Liquefied ammonia in system, ammonia is reclaimed using low temperature and is used, and will be removed remaining solid mixture water after ammonia and is dissolved, on
Cationic ion-exchange resin removes ammonium salt and sodium salt, collects eluent.Eluent with concentrated hydrochloric acid adjust solution pH value to 2, using true
Sky concentration, obtains homocysteinic acid thiolactone hydrochloride.
Embodiment 5：
A kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, the molal weight ratio of the DL- METHIONINE and metallic sodium is 1:8, reaction medium is liquefied ammonia, and reaction temperature is -70 DEG C, reduction
The reaction time of reaction is 17h, and reduzate is separated into solid-liquid two-phase material by tipping, the liquid-phase system of separation is added
The excessive metallic sodium dissolved in system is quenched in ammonium chloride, the liquefied ammonia in removing system that the reaction system being quenched is heated up naturally, ammonia
Gas is reclaimed using low temperature and is used, and will be removed remaining solid mixture water after ammonia and is dissolved, upper cationic ion-exchange resin
Ammonium salt and sodium salt are removed, eluent is collected.The pH value that eluent adjusts solution with concentrated hydrochloric acid, using vacuum concentration, obtains DL- to 1
Homocysteine thiolactone hydrochloride.
Experimental example 1：
To 50 grams of DL- METHIONINEs of addition in -40 DEG C of 2 liters of three-necked flasks are cooled in advance with dry ice-acetonitrile, dry ammonia is passed through
Gas, untill DL- METHIONINE is completely dissolved by the liquefied ammonia of condensation, is added portionwise 30 grams of metallic sodiums of chopping, controlling reaction temperature
In -35 DEG C~-40 DEG C, liquid phase tracking reaction carry out situation.After reaction terminates, stop stirring, stand, it is small that upper strata is reacted into the stillness of night
Being transferred in another three-necked flask for the heart, adds ammonium chloride and reaction is quenched, warm naturally to room temperature, treat that ammonia overflows completely
Afterwards, the solid obtained contains homocysteinic acid sodium salt and sodium chloride, and ammonium chloride hands over solid mixture with resin cation
Change and remove sodium ion and ammonium ion, eluent adjusts pH to 1 to concentrate with concentrated hydrochloric acid, obtains homocysteinic acid thiolactone hydrochloride
38.5 grams, yield 75%.
Experimental example 2：
To 100 grams of DL- METHIONINEs of addition in -40 DEG C of 3 liters of low-temp reaction kettles are cooled in advance with dry ice-acetonitrile, drying is passed through
Ammonia, untill DL- METHIONINE is completely dissolved by the liquefied ammonia of condensation, be added portionwise 60 grams of metallic sodiums of chopping, control reaction
Temperature is in -35 DEG C~-40 DEG C, liquid phase tracking reaction carry out situation.After reaction terminates, stop stirring, stand, upper strata is reacted clear
Night being transferred in another three-necked flask carefully, adds ammonium chloride and reaction is quenched, warm naturally to room temperature, treat that ammonia is complete
After spilling, obtained solid contains homocysteinic acid sodium salt and sodium chloride, ammonium chloride, by solid mixture with cation tree
Ester exchange removes sodium ion and ammonium ion, and eluent adjusts pH to 1 to concentrate, obtains homocysteinic acid thiolactone salt with concentrated hydrochloric acid
81 grams of hydrochlorate, yield 79%.
Experimental example 3：
To 500 grams of DL- METHIONINEs of addition in -40 DEG C of 10 liters of low-temp reaction kettles are cooled in advance with dry ice-acetonitrile, drying is passed through
Ammonia, untill DL- METHIONINE is completely dissolved by the liquefied ammonia of condensation, be added portionwise 300 grams of metallic sodiums of chopping, control reaction
Temperature is in -35 DEG C~-40 DEG C, liquid phase tracking reaction carry out situation.After reaction terminates, stop stirring, stand, upper strata is reacted clear
Night being transferred in another three-necked flask carefully, adds ammonium chloride and reaction is quenched, warm naturally to room temperature, treat that ammonia is complete
After spilling, obtained solid contains homocysteinic acid sodium salt and sodium chloride, ammonium chloride, by solid mixture with cation tree
Ester exchange removes sodium ion and ammonium ion, and eluent adjusts pH to 1 to concentrate, obtains homocysteinic acid thiolactone salt with concentrated hydrochloric acid
395 grams of hydrochlorate, yield 77%.
Claims (8)
1. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride, it is anti-that with metallic sodium reduction occurs for DL- METHIONINE
Should, reduzate is through except after salt treatment, concentration removes water to obtain homocysteinic acid thiolactone hydrochloride under the conditions of watery hydrochloric acid.
2. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
The molal weight ratio of the DL- METHIONINE and metallic sodium is 1:3~10.
3. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
The reaction medium of the reduction reaction is the mixed system of liquefied ammonia or liquefied ammonia and water.
4. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
The reaction temperature of the reduction reaction is -20 DEG C~-80 DEG C.
5. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
The reaction time of the reduction reaction is 5~20h.
6. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
The desalination is processed as：Reduzate is shifted by vacuum or tipping separates solid-liquid two-phase material, by the liquid phase of separation
System adds ammonium chloride and the excessive metallic sodium dissolved in system is quenched, in removing system that the reaction system being quenched is heated up naturally
Liquefied ammonia, will remove remaining solid mixture water after ammonia and dissolves, upper cationic ion-exchange resin removes ammonium salt and sodium salt, collects
Eluent.
7. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 6, it is characterised in that
The ammonia is reclaimed using low temperature and is used.
8. a kind of new synthetic method of homocysteinic acid thiolactone hydrochloride as claimed in claim 1, it is characterised in that
It is described concentration water removal method be：Reduzate is through except after salt treatment, with the pH value of concentrated hydrochloric acid tune solution to 1~2, using vacuum
Concentration, obtains homocysteinic acid thiolactone hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710695613.5A CN107325073A (en) | 2017-08-15 | 2017-08-15 | A kind of new synthetic method of DL homocysteine thiolactones hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710695613.5A CN107325073A (en) | 2017-08-15 | 2017-08-15 | A kind of new synthetic method of DL homocysteine thiolactones hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107325073A true CN107325073A (en) | 2017-11-07 |
Family
ID=60225166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710695613.5A Pending CN107325073A (en) | 2017-08-15 | 2017-08-15 | A kind of new synthetic method of DL homocysteine thiolactones hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107325073A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109824649A (en) * | 2019-03-11 | 2019-05-31 | 南京红杉生物科技有限公司 | Homocysteinic acid thiolactone hydrochloride and its preparation method and application |
| CN110256310A (en) * | 2019-07-01 | 2019-09-20 | 吉尔生化（上海）有限公司 | A kind of preparation method of N- fluorenylmethyloxycarbonyl-S- (4- Methoxytrityl)-L- homocysteine |
| CN110317143A (en) * | 2019-07-26 | 2019-10-11 | 成都百事兴科技实业有限公司 | A kind of preparation method of L-2,4- diaminobutyric acid hydrochloride |
| CN111004209A (en) * | 2019-12-24 | 2020-04-14 | 浙江工业大学 | Continuous production method of DL-homocysteine thiolactone hydrochloride |
| CN114957202A (en) * | 2022-07-28 | 2022-08-30 | 济南宣正药业有限公司 | Preparation method of DL-homocysteine thiolactone hydrochloride |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101144169A (en) * | 2007-08-24 | 2008-03-19 | 湖北新生源生物工程股份有限公司 | Method for producing DL-homocysteine lactone hydrochlorate |
-
2017
- 2017-08-15 CN CN201710695613.5A patent/CN107325073A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101144169A (en) * | 2007-08-24 | 2008-03-19 | 湖北新生源生物工程股份有限公司 | Method for producing DL-homocysteine lactone hydrochlorate |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109824649A (en) * | 2019-03-11 | 2019-05-31 | 南京红杉生物科技有限公司 | Homocysteinic acid thiolactone hydrochloride and its preparation method and application |
| CN110256310A (en) * | 2019-07-01 | 2019-09-20 | 吉尔生化（上海）有限公司 | A kind of preparation method of N- fluorenylmethyloxycarbonyl-S- (4- Methoxytrityl)-L- homocysteine |
| CN110317143A (en) * | 2019-07-26 | 2019-10-11 | 成都百事兴科技实业有限公司 | A kind of preparation method of L-2,4- diaminobutyric acid hydrochloride |
| CN110317143B (en) * | 2019-07-26 | 2022-06-10 | 成都百事兴科技实业有限公司 | Preparation method of L-2, 4-diaminobutyric acid hydrochloride |
| CN111004209A (en) * | 2019-12-24 | 2020-04-14 | 浙江工业大学 | Continuous production method of DL-homocysteine thiolactone hydrochloride |
| CN114957202A (en) * | 2022-07-28 | 2022-08-30 | 济南宣正药业有限公司 | Preparation method of DL-homocysteine thiolactone hydrochloride |
| CN114957202B (en) * | 2022-07-28 | 2022-10-28 | 济南宣正药业有限公司 | Preparation method of DL-homocysteine thiolactone hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107325073A (en) | A kind of new synthetic method of DL homocysteine thiolactones hydrochloride | |
| KR101500821B1 (en) | Method for Production of L-Methionine and Related Products | |
| CN106185810B (en) | A kind of joint disposal technique of acidic copper chloride waste etching solution | |
| EP1167421A3 (en) | Production process of polyphenylene ether | |
| JP6944583B2 (en) | Method of recovering and reusing phosphoric acid from fermentation broth or fermentation effluent | |
| CN102382049B (en) | Method for synthesizing 2-ethoxycarbonylaminosulfonyl-N,N-dimethyl nicotinamide | |
| CN108276296B (en) | Synthesis method of cyanide antidote | |
| CN103709209A (en) | Isopropyl-beta-D-thiogalactoside preparation method | |
| CN103665063B (en) | A kind of method preparing isopropyl-β-D-thiogalactoside(IPTG) | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN106748798A (en) | A kind of synthetic method of 2,4- dinitroanisols | |
| CN111233721B (en) | Synthesis method of 2-alkylthio-6-halogenated alkylbenzene | |
| CN108862334A (en) | A kind of chelating agent for extracting lithium from salt lake brine removes magnesium method | |
| CN104326989A (en) | Preparation method of 2-methyl-4-amino-5-(aminomethyl) pyrimidine | |
| CN101514154A (en) | Synthetic method for aliphatic alpha-calcium picrolonate | |
| CN107473271A (en) | A kind of preparation method of PAFS | |
| CN107417545B (en) | The aftertreatment technology of condensation liquid in a kind of Bentazon preparation process | |
| IL131770A (en) | Method of preparing 2- and 4-hydroxymandelic acid | |
| CN102030697B (en) | Method for preparing DL-tryptophan from remaining solution of split tryptophan | |
| CN105175294A (en) | Method for synthesizing sulfanilamide by using chlorobenzene as raw material | |
| CN101343230B (en) | 2,4-dinitrophenol inhibitor purification process | |
| CN102796062B (en) | Method for preparing flumorph | |
| CN110372634B (en) | Method for synthesizing 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole | |
| CN103694286B (en) | Prepare the method for isopropyl-β-D-thiogalactoside(IPTG) | |
| CN107955018A (en) | A kind of method for preparing D-Biotin thiolactone intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171107 |
|
| RJ01 | Rejection of invention patent application after publication |