CN101434567B - Preparation method of lignocaine ethanethiol - Google Patents

Preparation method of lignocaine ethanethiol Download PDF

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CN101434567B
CN101434567B CN200810080197A CN200810080197A CN101434567B CN 101434567 B CN101434567 B CN 101434567B CN 200810080197 A CN200810080197 A CN 200810080197A CN 200810080197 A CN200810080197 A CN 200810080197A CN 101434567 B CN101434567 B CN 101434567B
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thiirane
diethylamine
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ethanethiol
preparation
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CN101434567A (en
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李扬
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Hebei Yuanda Jiufu Biotechnology Co ltd
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Abstract

The invention particularly relates to a preparation method of lignocaine ethanethiol in the field of medical technology. The method includes steps as follows: ethylene carbonate reacts with anhydrous thiocyanate to generate an intermediate product of thiirane, a side product of cyanate and gas of carbon dioxide, and then diethylamine and the intermediate product of thiirane go through an addition reaction to generate lignocaine ethanethiol. In the method, a synthetic route that the thiirane and the diethylamine are adopted for carrying out the addition reaction to generate the lignocaine ethanethiol is characterized by short technological process, simple working operation, high yield, high purity, small power consumption, less pollution and low cost, thus being a synthetic method applicable to enterprise manufacturing.

Description

A kind of preparation method of diethylamino ethanethiol
Technical field
The present invention is specifically related to the preparation method of a kind of diethylamino ethanethiol of medical technical field.
Background technology:
Thiamutilin (Tiamulin) is a kind of two terpenes animal specific microbiotic, is mainly used in control domestic animals and fowls respiratory system disease and promoting animal growth, is one of ten big microbiotic for animals in the world.In recent years, thiamutilin was particularly used in chicken aquaculture and the pig aquaculture in aquaculture in a large number widely.And as the key intermediate of producing thiamutilin, diethylamino ethanethiol has very big demand in the pharmacy corporation of producing thiamutilin.
Summary of the invention
It is high that technical problem to be solved by this invention provides a kind of reactive behavior, and directional property is good, and product purity is high, and yield is high, and operation technological process is short, seldom causes the preparation method of the diethylamino ethanethiol of environmental pollution.
The present invention adopts following technical scheme:
The method of the invention comprises: generate midbody thiirane and by product cyanate and atmospheric carbon dioxide by NSC 11801 and anhydrous rhodanide reaction earlier; Carry out addition reaction with diethylamine and midbody thiirane again and generate diethylamino ethanethiol, said method comprises following concrete steps:
A, be 1: 1~1.5 with NSC 11801 and anhydrous rhodanide reaction mol ratio, in 80 ℃~100 ℃ reactions of temperature, be incubated 4~5 hours, generate thiirane and by product cyanate, atmospheric carbon dioxide can directly discharge:
ASCN+C 2H 4O 2CO→AOCN+C 2H 4S+CO 2
A is a metal-salt;
B, thiirane and diethylamine are carried out addition reaction, mol ratio is 1: 1~1.5, between 60 ℃~75 ℃ of temperature, slowly is warmed up to 60-120 ℃ of ℃ air distillation after back flow reaction 3-4 hour and goes out excessive diethylamine, and residuum is a diethylamino ethanethiol:
C 2H 4S+R 2NH→R 2NCH 2CH 2SH
R:CH3CH2-。
Thiocyanate-according to the invention comprises Rhocya, Sodium Thiocyanate 99 and ammonium thiocyanide:
ASCN+C 2H 4O 2CO→AOCN+C 2H 4S+CO 2
A:Na or K or NH4.
The present invention processes content after the flushing of by product cyanate water can reach the cyanate that the industrial goods done more than 98% sell.
The present invention is because the thiirane boiling point is lower, and toxicity is bigger, reveals for preventing thiirane, and whole process flow is carried out in whole closed system.
Positively effect of the present invention is following:
It is short that the synthetic route that the present invention adopts thiirane and diethylamine addition reaction to generate diethylamino ethanethiol has technical process, and the characteristics that operation is simple, yield is high, purity is high, energy consumption is little, pollution is little, cost is low are suitable for the compound method of enterprise production.
Embodiment
Synthetic route synthetic route of the present invention is short, and technical process is short, less investment, and operation is few, and cost is low, and the diethylamino ethanethiol purity that obtains is high, can use with import reagent rank diethylamino ethanethiol equal parts, is suitable for enterprise's suitability for industrialized production.
Reaction mechanism and equation that the present invention adopts are following:
(1) prepares thiirane and cyanate by NSC 11801 and anhydrous rhodanide reaction.
ASCN+C 2H 4O 2CO→AOCN+C 2H 4S+CO 2
A:Na or K or NH4
(2) by thiirane and diethylamine prepared in reaction diethylamino ethanethiol.
C 2H 4S+R 2NH→R 2NCH 2CH 2SH
R:CH3CH2-
In order to realize the foregoing invention purpose, the present invention takes following technological synthetic schemes:
A kind of preparation method of diethylamino ethanethiol is characterized in that said method comprises: generate midbody thiirane and by product cyanate and carbonic acid gas by NSC 11801 and anhydrous rhodanide reaction earlier.Carry out addition reaction with diethylamine and midbody thiirane again and generate diethylamino ethanethiol.
Particularly, said method comprises following concrete steps:
A, with NSC 11801 and anhydrous rhodanide reaction, in 80 ℃~100 ℃ reactions of temperature, be incubated 4~5 hours, generate thiirane and by product cyanate, atmospheric carbon dioxide can directly discharge.
ASCN+C 2H 4O 2CO→AOCN+C 2H 4S+CO 2
A:Na or K or NH4
B, thiirane and diethylamine are carried out addition reaction, between 60 ℃~75 ℃ of temperature, slowly be warmed up to 120 ℃ of air distillations after back flow reaction 3-4 hour and go out excessive diethylamine, residuum is a diethylamino ethanethiol;
C 2H 4S+R 2NH→R 2NCH 2CH 2SH
R:CH3CH2-
C, by product cyanate water flushing back content can reach more than 98%, can do industrial goods and sell.
D, because the thiirane boiling point is lower, and toxicity is bigger, and technical process is preferably made whole enclosed system, prevent that thiirane from revealing.
Said thiocyanate-comprises Rhocya, Sodium Thiocyanate 99 and ammonium thiocyanide.
Compared with prior art, beneficial effect of the present invention is that the preparation method of this diethylamino ethanethiol is simple directly, technical process is short; Cost is low, and yield is high, three-waste free pollution; Simultaneously, this preparing method's reactive behavior is high, and directional property is good; Easy and simple to handle, yield is up to more than 98%, application promise in clinical practice in pharmaceutical industries.
Embodiment 1
Get 645g Rhocya and 450g NSC 11801 and join in the 1500mL four-hole round-bottomed flask, be warmed up to 80 ℃, be incubated 5 hours, collect the thiirane 300g that distills out around here and in susceptor, seal the cooling storage.
300g thiirane and 365g diethylamine that the last step was obtained join in the 1000mL four-hole boiling flask simultaneously; In temperature is back flow reaction 4 hours between 75 ℃; Between 60 ℃, carry out the air distillation operation then; Steam excessive diethylamine, remaining material is the about 600g of diethylamino ethanethiol finished product in the flask.
Embodiment 2
Get 538g Sodium Thiocyanate 99 and 450g NSC 11801 and join in the 1500mL four-hole round-bottomed flask, be warmed up to 100 ℃, be incubated 4 hours, collect the thiirane 300g that distills out around here and in susceptor, seal the cooling storage.
300g thiirane and 365g diethylamine that the last step was obtained join in the 1000mL four-hole boiling flask simultaneously; In temperature is back flow reaction 4 hours between 60 ℃; Between 120 ℃, carry out the air distillation operation then; Steam excessive diethylamine, remaining material is the about 600g of diethylamino ethanethiol finished product in the flask.
Embodiment 3
Get 505g ammonium thiocyanide and 450g NSC 11801 and join in the 1500mL four-hole round-bottomed flask, be warmed up to 90 ℃, be incubated 4.5 hours, collect the thiirane 300g that distills out around here and in susceptor, seal the cooling storage.
300g thiirane and 365g diethylamine that the last step was obtained join in the 1000mL four-hole boiling flask simultaneously; In temperature is back flow reaction 4 hours between 70 ℃; Between 90 ℃, carry out the air distillation operation then; Steam excessive diethylamine, remaining material is the about 600g of diethylamino ethanethiol finished product in the flask.

Claims (3)

1. the preparation method of a diethylamino ethanethiol is characterized in that said method comprises:
Generate midbody thiirane and by product cyanate and atmospheric carbon dioxide by NSC 11801 and anhydrous rhodanide reaction earlier; Carry out addition reaction with diethylamine and midbody thiirane again and generate diethylamino ethanethiol, said method comprises following concrete steps:
A, be 1: 1~1.5 with NSC 11801 and anhydrous rhodanide reaction mol ratio, in 80 ℃~100 ℃ reactions of temperature, be incubated 4~5 hours, generate thiirane and by product cyanate, atmospheric carbon dioxide can directly discharge:
ASCN+C 2H 4O 2CO→AOCN+C 2H 4S+CO 2
A:Na or K or NH 4
B, thiirane and diethylamine are carried out addition reaction, mol ratio is 1: 1~1.5, between 60 ℃~75 ℃ of temperature, slowly is warmed up to 90-120 ℃ of air distillation after back flow reaction 3-4 hour and goes out excessive diethylamine, and residuum is the ethylamino sulfur alcohol:
C 2H 4S+R 2NH→R 2NCH 2CH 2SH
R:CH 3CH 2-。
2. the preparation method of a kind of diethylamino ethanethiol according to claim 1 is characterized in that after the flushing of by product cyanate water, processing content can reach the cyanate that the industrial goods done more than 98% sell.
3. the preparation method of a kind of diethylamino ethanethiol according to claim 1 it is characterized in that because the thiirane boiling point is lower, and toxicity is bigger, reveals for preventing thiirane, and whole process flow is carried out in whole closed system.
CN200810080197A 2008-12-19 2008-12-19 Preparation method of lignocaine ethanethiol Active CN101434567B (en)

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Publication number Priority date Publication date Assignee Title
CN102153494B (en) * 2011-03-04 2014-04-30 赵云现 Synthesis technology for N,N-diethylamino group ethanethiol
CN103819374A (en) * 2012-11-16 2014-05-28 张丽学 Process for synthesizing diethylaminoethyl mercaptide
CN104447449B (en) * 2014-12-30 2016-06-15 陕西师范大学 The method of one pot process taimulin
CN104672206B (en) * 2015-02-16 2016-09-07 张丽学 A kind of preparation technology of thiirane
CN104774164A (en) * 2015-02-16 2015-07-15 张丽学 Preparation process for 2-diethylaminoethanethiol
CN105152990B (en) * 2015-07-30 2017-03-22 宁夏泰瑞制药股份有限公司 Preparation method for diethylaminoethanethiol
CN105999996A (en) * 2016-06-20 2016-10-12 保定加合精细化工有限公司 Method for recycling thiirane from waste gas
CN107011221B (en) * 2017-03-03 2018-12-28 河北科技大学 A kind of preparation method of diethylamino ethanethiol
CN109134425B (en) * 2017-06-27 2021-04-16 保定加合精细化工有限公司 Method for preparing high-purity ethylene sulfide
CN109134322B (en) * 2017-06-27 2020-08-28 保定加合精细化工有限公司 Method for preparing diethylaminoethanethiol
CN109608365B (en) * 2018-12-10 2021-04-20 万华化学集团股份有限公司 Preparation method of taurine
CN111302989A (en) * 2020-03-11 2020-06-19 新疆浙大阳光生物科技有限公司 Production device for preparing organic intermediate
CN113387854A (en) * 2020-03-11 2021-09-14 新疆上昵生物科技有限公司 Complete method for preparing diethylaminoethanethiol
CN113387922A (en) * 2020-03-11 2021-09-14 新疆上昵生物科技有限公司 Preparation process for synthesizing ethylene sulfide by using sodium thiocyanate and ethylene carbonate
CN113735819B (en) * 2020-05-29 2024-01-12 新疆上昵生物科技有限公司 Preparation process of ethylene sulfide
CN113307751A (en) * 2020-12-31 2021-08-27 保定北瑞甾体生物有限公司 Process for producing aliphatic mercaptan
CN113372248A (en) * 2021-06-11 2021-09-10 保定北瑞甾体生物有限公司 Process for preparing thiols
CN115028559A (en) * 2021-07-12 2022-09-09 新疆上昵生物科技有限公司 Preparation method of diethylaminoethanethiol
CN114315665A (en) * 2021-12-16 2022-04-12 保定加合精细化工有限公司 Preparation method of 2-diethylaminoethanethiol and application of impurities thereof

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EP0289262A2 (en) * 1987-04-27 1988-11-02 Syntex Pharmaceuticals International Limited Omega-quaternary ammonium alkyl esters and thioesters of acidic nonsteroidal antiinflammatory drugs
CN1696109A (en) * 2005-05-16 2005-11-16 北京大学 Derivative of substitutional taurine and preparation method
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