CN109369458A - The preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride - Google Patents
The preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride Download PDFInfo
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- CN109369458A CN109369458A CN201811073782.6A CN201811073782A CN109369458A CN 109369458 A CN109369458 A CN 109369458A CN 201811073782 A CN201811073782 A CN 201811073782A CN 109369458 A CN109369458 A CN 109369458A
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- ethyl
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- dimethylaminopropyl
- carbodiimide hydrochloride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/14—Dithiocarbamic acids; Derivatives thereof
- C07C333/18—Esters of dithiocarbamic acids
- C07C333/20—Esters of dithiocarbamic acids having nitrogen atoms of dithiocarbamate groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C267/00—Carbodiimides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/16—Isothiocyanates
- C07C331/18—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms
- C07C331/20—Isothiocyanates having isothiocyanate groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of preparation methods of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, belong to medicine intermediate technical field.The preparation method includes that reaction generates EDTC, EITC crude product is made, distillation fractionation, intermediate is made, seven steps such as EDC and obtained target product are made.The characteristics of preparation method provided by the present invention has high product yield and purity, and operating procedure is simple, easy to implement, is suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of preparation methods of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, belong to
Medicine intermediate technical field.
Background technique
1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, abbreviation EDC hydrochloride, molecular formula C8H17N3
HCl is a kind of water-soluble peptide coupling agent and general carbonyl-activating reagent, can be used for being bonded in amide with secondary amine, can and phosphorus
Acid groups reaction, protein and nucleic acid are crosslinked, preparation such as immunoconjugate, for carbonyl modified etc. in protein.
Use ethamine to prepare ethyl isorhodanide for raw material in Japan Patent JPH08198836A in 1996, then with N, N-
The reaction of dimethyl -1,3- propane diamine, is then made product, yield 32% using hypochlorite oxidation desulfurization.But this method is received
Rate is relatively low, is not suitable for industrialized production.
N is used in Chinese patent CN104193654A in 2014, N- dimethyl -1,3- propane diamine and carbon disulfide are raw material
React to obtain intermediate, then using ethyl chloroformate reaction through oxidation, condensation, oxidation sweetening, at salt four-step reaction, yield is
80%.The method step is relatively complicated, complicated for operation, and uses a large amount of organic solvent, is not suitable for industrialized production.
Summary of the invention
In view of the deficiencies of the prior art, the object of the present invention is to provide a kind of 1- ethyl-(3- dimethylaminopropyl) carbon
The preparation method of diimmonium salt hydrochlorate has high product yield and purity, and operating procedure is simple, easy to implement, is suitble to industry
Metaplasia produces.
The preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride of the present invention, including with
Lower step:
1) ethamine is added dropwise in carbon disulfide and 40% mass concentration liquid alkaline mixed solution, insulation reaction generates EDTC；
It is added dropwise and holding temperature control is at 10-30 DEG C, time for adding is controlled in 0.5~1h, and soaking time is in 1~3h；
2) carbonic acid trichloromethyl ester solution is added dropwise in the EDTC reaction solution of generation, EITC crude product is made, be added dropwise and protect
Temperature control is at 15-30 DEG C, and time for adding is controlled in 1-3h, and soaking time is in 1-3h；
3) EITC crude product oil bath obtained to be distilled, takes fraction in separatory funnel liquid separation, upper oil is EITC fine work,
Oil bath temperature is controlled at 100~150 DEG C；
4) EITC fine work obtained is added dropwise to N, in N- dimethyl -1,3- propane diamine aqueous solution, obtains intermediate 1, wherein
It is added dropwise and holding temperature control is at 0~30 DEG C, time for adding is controlled in 1~3h, and soaking time is in 1~3h；
5) carbonic acid trichloromethyl ester solution is added dropwise to intermediate 1, obtains intermediate 2, wherein being added dropwise and holding temperature control
System is at 10~30 DEG C, and time for adding is controlled in 1~3h, and soaking time is in 0.5~2h；
6) organic solvent extraction, liquid separation is added in intermediate 2, obtains oily intermediate 3, depressurizes, is concentrated to get EDC,
Middle decompression, thickening temperature are 30~60 DEG C；
7) obtained EDC and hydrochloride are carried out to salt exchange reaction in aprotic polar solvent, 1- ethyl-(3- is made
Dimethylaminopropyl) carbodiimide hydrochloride, reaction time control is in 1~3h, and temperature control is at 10~30 DEG C.
The molar ratio of ethamine and carbon disulfide is 1:1.1-1.3 in the step 1.
In the step 1, liquid alkaline is sodium hydroxide, and the quality of liquid alkaline is 1-1.2 times of carbon disulfide quality.
In the step 2, the molar ratio of carbonic acid trichloromethyl ester and carbon disulfide is 1:4-4.5.
In the step 4, EITC and N, the molar ratio of N- dimethyl -1,3- propane diamine are 1:1.1~1.2；The body of water
Product is 3 times of EITC.
In the step 5, the molar ratio of intermediate 1 and carbonic acid trichloromethyl ester is 1:0.55~0.5.
In the step 6, organic solvent is one of hexamethylene or petroleum ether；The volume of organic solvent is EITC's
2.5 again.
In the step 7, hydrochloride is one of triethylamine hydrochloride or arsenic thiamine hydrochloride；Aprotic polar solvent
For one of acetonitrile, dimethylformamide, DMI or dimethyl sulfoxide；Aprotic polar solvent volume is 5-10 times of EDC.
In the step 7, pyridine or triethylamine and HCL mass ratio are 3~7:1.
In the step 7, the molar ratio of EDC and hydrochloride is 1:0.95-1.
The present invention is reacted and N is made using ethylamine and carbon disulfide as raw material, N- dimethyl propyl sulfydryl thiocarbamide, then
With carbonic acid trichloromethyl ester desulfurization be made N, N- dimethyl propyl isothiocyanates, then and N, N- dimethyl -1,3- propane diamine it is anti-
Answer, again pass by carbonic acid trichloromethyl ester desulfurization be made 1- ethyl-(3- dimethylaminopropyl) carbodiimide, crude product with it is organic
Hydrochloride or inorganic hydrochloride carry out salt exchange reaction and product 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride are made
Salt.
Correlated response formula is as follows:
Compared with prior art, the invention has the following beneficial effects:
1. preparation method described in makees solvent using single water, avoids mixed solvent to post-processing bring trouble；
2. the first step and second step use carbonic acid trichloromethyl ester as desulfurizing agent in the present invention, side reaction is few, yield
Height, obtained product purity are high, it is easier to realize industrialized production；
Preparation method described in 3., it is scientific and reasonable, it is simple and easy, operating procedure is greatlied simplify, save the cost is easy to real
It applies.
Specific embodiment
The present invention will be further explained with reference to the examples below.
Carbon disulfide 200g is added into 2000ml reaction flask, 40% mass concentration liquid alkaline 240g is slowly dropped into ethamine
167g maintains the temperature at 20 DEG C, time for adding 30min, and stirring heat preservation 120min, reaction generates EDTC；Separately by three chloromethane of carbonic acid
Base ester 149g is dissolved in 280g petroleum ether, is slowly dropped into EDTC reaction solution, maintains the temperature at 20 DEG C, feed time 120min,
Keep the temperature 120min.
Material is transferred to oil bath pan to distill, 125 DEG C of oil bath temperature or so distillations take fraction to leak in liquid separation up to not going out
Liquid separation is carried out in bucket, upper oil EITC obtains product 197.6g, yield 92%, purity 99.5%.
Water 600g is added into 2000ml reaction flask, N is added, N- dimethyl -1,3- propane diamine 300g is slowly added dropwise
EITC200g guarantees temperature at 15 DEG C, and 120min is added dropwise, and keeps the temperature 120min, intermediate 1 is obtained, by carbonic acid trichloromethyl ester
160g is dissolved in 300g petroleum ether, is slowly added dropwise in intermediate 1, guarantees 15 DEG C of temperature, feed time control is protected in 120min
After temperature stirring 60min, intermediate 2 is obtained, 500g petroleum ether extraction, liquid separation is added, it is dense to obtain 3, the 45 DEG C of decompressions of oily intermediate
Contracting, obtains product E DC213.6g, purity 99.5%.
Triethylamine hydrochloride 1100g, acetonitrile 1000g are added into 3000ml reaction flask, wherein triethylamine and HCL mass ratio
For 5:1, EDC213.6g is slowly added dropwise, at 15 DEG C, time for adding control obtains EDC hydrochloric acid in 60min, filtering for temperature control
Salt, purity 99.5%, yield 92%.
Embodiment 2
Carbon disulfide 195g is added into 2000ml reaction flask, ethamine is slowly added dropwise in 40% mass concentration liquid alkaline 198g
143g maintains the temperature at 25 DEG C, time for adding 60min, and stirring heat preservation 90min, reaction generates EDTC；Separately by carbonic acid trichloromethyl
Ester 172g is dissolved in 240g hexamethylene, is slowly dropped into EDTC reaction solution, maintains the temperature at 20 DEG C, feed time 90min, heat preservation
150min。
Material is transferred to oil bath pan to distill, 120 DEG C of oil bath temperature or so distillations take fraction to leak in liquid separation up to not going out
Liquid separation is carried out in bucket, upper oil EITC obtains product 197g, yield 89%, purity > 99%.
Water 600g is added into 2000ml reaction flask, N is added, N- dimethyl -1,3- propane diamine 273g is slowly added dropwise
EITC197g guarantees temperature at 18 DEG C, and 60min is added dropwise, and keeps the temperature 120min, intermediate 1 is obtained, by carbonic acid trichloromethyl ester
160g is dissolved in 300g hexamethylene, is slowly added dropwise in intermediate 1, guarantees 15 DEG C of temperature, feed time control is protected in 90min
After temperature stirring 60min, intermediate 2 is obtained, the extraction of 500g hexamethylene, liquid separation is added, it is dense to obtain 3, the 40 DEG C of decompressions of oily intermediate
Contracting, obtains product E DC211.6g, purity 99.5%.
Pyridine hydrochloride 1266g, dimethyl sulfoxide 1000g are added into 3000ml reaction flask, wherein pyridine and HCL mass
Than EDC211.6g for 6:1, is slowly added dropwise, at 20 DEG C, time for adding control obtains EDC hydrochloric acid in 30min, filtering for temperature control
Salt, purity 99.5%, yield 89%.
Embodiment 3
Carbon disulfide 200g is added into 2000ml reaction flask, 40% mass concentration liquid alkaline 240g is slowly dropped into ethamine
167g maintains the temperature at 15 DEG C, time for adding 30min, and stirring heat preservation 90min, reaction generates EDTC；Separately by carbonic acid trichloromethyl
Ester 149g is dissolved in 280g petroleum ether, is slowly dropped into EDTC reaction solution, maintains the temperature at 27 DEG C, feed time 90min, heat preservation
120min。
Material is transferred to oil bath pan to distill, 130 DEG C of oil bath temperature or so distillations take fraction to leak in liquid separation up to not going out
Liquid separation is carried out in bucket, upper oil EITC obtains product 200g, yield 90%, purity > 99%.
Water 600g is added into 2000ml reaction flask, N is added, N- dimethyl -1,3- propane diamine 300g is slowly added dropwise
EITC200g guarantees temperature at 26 DEG C, and 30min is added dropwise, and keeps the temperature 120min, intermediate 1 is obtained, by carbonic acid trichloromethyl ester
160g is dissolved in 300g petroleum ether, is slowly added dropwise in intermediate 1, guarantees 25 DEG C of temperature, feed time control is protected in 60min
After temperature stirring 60min, intermediate 2 is obtained, 500g petroleum ether extraction, liquid separation is added, it is dense to obtain 3, the 47 DEG C of decompressions of oily intermediate
Contracting, obtains product E DC220g, purity 99.5%.
Triethylamine hydrochloride 1100g, acetonitrile 1100g are added into 3000ml reaction flask, wherein triethylamine and HCL mass ratio
For 5:1, EDC220g is slowly added dropwise, at 20 DEG C, time for adding control obtains EDC hydrochloride in 90min, filtering for temperature control,
Purity 99.5%, yield 90%.
Claims (10)
1. a kind of preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, it is characterised in that: including with
Lower step:
1) ethamine is added dropwise in carbon disulfide and 40% mass concentration liquid alkaline mixed solution, insulation reaction generates EDTC；It is added dropwise
With holding temperature control at 10-30 DEG C, time for adding is controlled in 0.5~1h, and soaking time is in 1~3h；
2) carbonic acid trichloromethyl ester solution is added dropwise in the EDTC reaction solution of generation, EITC crude product is made, be added dropwise and heat preservation is warm
Degree control is at 15-30 DEG C, and time for adding is controlled in 1-3h, and soaking time is in 1-3h；
3) EITC crude product oil bath obtained is distilled, takes fraction in separatory funnel liquid separation, upper oil is EITC fine work, oil bath
Temperature is controlled at 100~150 DEG C；
4) EITC fine work obtained is added dropwise to N, in N- dimethyl -1,3- propane diamine aqueous solution, intermediate 1 is obtained, wherein being added dropwise
With holding temperature control at 0~30 DEG C, time for adding is controlled in 1~3h, and soaking time is in 1~3h；
5) carbonic acid trichloromethyl ester solution is added dropwise to intermediate 1, obtains intermediate 2, existed wherein being added dropwise with holding temperature control
10~30 DEG C, time for adding is controlled in 1~3h, and soaking time is in 0.5~2h；
6) organic solvent extraction, liquid separation is added in intermediate 2, obtains oily intermediate 3, depressurize, be concentrated to get EDC, wherein subtracts
Pressure, thickening temperature are 30~60 DEG C；
7) obtained EDC and hydrochloride are carried out to salt exchange reaction in aprotic polar solvent, 1- ethyl-(3- diformazan is made
Base aminopropyl) carbodiimide hydrochloride, reaction time control is in 1~3h, and temperature control is at 10~30 DEG C.
2. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: the molar ratio of ethamine and carbon disulfide is 1:1.1-1.3 in step 1.
3. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: the quality of liquid alkaline is 1-1.2 times of carbon disulfide quality.
4. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 2, the molar ratio of carbonic acid trichloromethyl ester and carbon disulfide is 1:4-4.5.
5. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 4, EITC and N, the molar ratio of N- dimethyl -1,3- propane diamine are 1:1.1~1.2；The volume of water is
3 times of EITC.
6. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 5, the molar ratio of intermediate 1 and carbonic acid trichloromethyl ester is 1:0.55~0.5.
7. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 6, organic solvent is one of hexamethylene or petroleum ether；The volume of organic solvent is the 2.5 of EITC
Times.
8. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 7, hydrochloride is one of triethylamine hydrochloride or arsenic thiamine hydrochloride；Aprotic polar solvent is second
One of nitrile, dimethylformamide, DMI or dimethyl sulfoxide；Aprotic polar solvent volume is 5-10 times of EDC.
9. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
Be characterized in that: in step 7, pyridine or triethylamine and HCL mass ratio are 3~7:1.
10. the preparation method of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride according to claim 1,
It is characterized by: the molar ratio of EDC and hydrochloride is 1:0.95-1 in step 7.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113004182A (en) * | 2019-12-21 | 2021-06-22 | 顺毅股份有限公司 | Preparation method of trifluoro-isothiocyanethane |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5208378A (en) * | 1990-07-19 | 1993-05-04 | Research Association For Utilization Of Light Oil | Process for production of water-soluble carbodiimide |
| JPH08198836A (en) * | 1995-01-26 | 1996-08-06 | Sanshin Chem Ind Co Ltd | Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide |
| CN102408355A (en) * | 2011-11-24 | 2012-04-11 | 浙江工业大学 | Method for synthesizing dicyclohexylcarbodiimide compound |
| CN103922970A (en) * | 2014-04-10 | 2014-07-16 | 李娜 | Synthesis method of dicyclohexyl carbodiimide |
| CN104193654A (en) * | 2014-09-03 | 2014-12-10 | 山东金城医药化工股份有限公司 | Preparation method of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride |
| CN104193653A (en) * | 2014-08-07 | 2014-12-10 | 山东汇海医药化工有限公司 | Novel synthesis method of N, N'-dicyclohexylcarbo-diimide |
| WO2015122216A1 (en) * | 2014-02-12 | 2015-08-20 | 公立大学法人大阪市立大学 | Method for producing carbodiimide compound |
| CN104892529A (en) * | 2015-05-27 | 2015-09-09 | 烟台大学 | Thiourea compound containing quinazoline structure as well as preparation method and application of thiourea compound |
| CN105503656A (en) * | 2016-02-25 | 2016-04-20 | 新疆康润洁环保科技股份有限公司 | Preparation method of carbodiimide |
-
2018
- 2018-09-14 CN CN201811073782.6A patent/CN109369458A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5208378A (en) * | 1990-07-19 | 1993-05-04 | Research Association For Utilization Of Light Oil | Process for production of water-soluble carbodiimide |
| JPH08198836A (en) * | 1995-01-26 | 1996-08-06 | Sanshin Chem Ind Co Ltd | Production of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide |
| CN102408355A (en) * | 2011-11-24 | 2012-04-11 | 浙江工业大学 | Method for synthesizing dicyclohexylcarbodiimide compound |
| WO2015122216A1 (en) * | 2014-02-12 | 2015-08-20 | 公立大学法人大阪市立大学 | Method for producing carbodiimide compound |
| CN103922970A (en) * | 2014-04-10 | 2014-07-16 | 李娜 | Synthesis method of dicyclohexyl carbodiimide |
| CN104193653A (en) * | 2014-08-07 | 2014-12-10 | 山东汇海医药化工有限公司 | Novel synthesis method of N, N'-dicyclohexylcarbo-diimide |
| CN104193654A (en) * | 2014-09-03 | 2014-12-10 | 山东金城医药化工股份有限公司 | Preparation method of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride |
| CN104892529A (en) * | 2015-05-27 | 2015-09-09 | 烟台大学 | Thiourea compound containing quinazoline structure as well as preparation method and application of thiourea compound |
| CN105503656A (en) * | 2016-02-25 | 2016-04-20 | 新疆康润洁环保科技股份有限公司 | Preparation method of carbodiimide |
Non-Patent Citations (2)
| Title |
|---|
| WEIKE SU ET AL: "Novel Synthesis of 2,4-Dihydro-5-amino[1,2,4]triazol-3-ones from 1,3-Disubstituted Thioureas", 《SYNLETT》 * |
| 陈伟荣: "异硫氰酸酯的合成方法及应用", 《浙江化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113004182A (en) * | 2019-12-21 | 2021-06-22 | 顺毅股份有限公司 | Preparation method of trifluoro-isothiocyanethane |
| CN113004182B (en) * | 2019-12-21 | 2024-01-12 | 顺毅股份有限公司 | Preparation method of trifluoro-isothiocyanato ethane |
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Application publication date: 20190222 |