CN104744382B - A kind of preparation method of homopiperazine - Google Patents
A kind of preparation method of homopiperazine Download PDFInfo
- Publication number
- CN104744382B CN104744382B CN201510077009.7A CN201510077009A CN104744382B CN 104744382 B CN104744382 B CN 104744382B CN 201510077009 A CN201510077009 A CN 201510077009A CN 104744382 B CN104744382 B CN 104744382B
- Authority
- CN
- China
- Prior art keywords
- homopiperazine
- retort
- reaction
- sodium hydroxide
- heated
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of homopiperazine; it is using ethylenediamine as raw material; in n-butanol solvent N is obtained with tolysulfonyl chlorine acylation; the p-toluenesulfonyl ethylenediamines of N ' two; product from reaction solution without separating; directly under sodium hydroxide effect; N is obtained with bromo-chloropropane ring-closure reaction; the p-toluenesulfonyl homopiperazines of N ' two; then take off sulfonyl under hydrobromic acid and phenol effect and obtain homopiperazine hydrobromate, most afterwards through sodium hydroxide is free, toluene obtains high-purity with water homopiperazine.The production technology have it is simple to operate, it is cost-effective, be easy to big production, and high-purity, homopiperazine in high yield can be obtained.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of widely used middle preparation, and in particular to synthesis
The new technology of homopiperazine.
Background technology
Homopiperazine not only can be widely applied to field of fine chemical, such as antioxidant, foaming agent, cosmetic emulsifier, high energy
Metric density material etc., while homopiperazine or a kind of important drug synthesis intermediate, by its structural modification and transformation,
The illnesss such as allergy, inflammation, mental disease have good efficacy, are mainly used in Fasudic hydrochloride, homopiperazine hydrochloride, Sai Keli
The production of the medicines such as piperazine, carbamazepine, quinolone and chloreyclizine.Therefore, the homopiperazine market demand is huge, with good application
Prospect.
1961, Poppeludorf etc. was reported using N- (2- cyanoethyls) ethylenediamine as raw material, and Ge Dele G-49A are catalysis
Agent, under the pressurization of hydrogen, N- (2- cyanoethyls) ethylenediamine hydrogenation ring-closure reaction obtains homopiperazine, and yield is 32.4%
(Poppeludorf.Fand R.C.Mjerly,A Novel Synthesis of Homopiperazine and Its
Mono-methyl Deriva-tives[J].J.Org.Chem.,1961,26(1):131-134.), the advantage of the technique is anti-
Short between seasonable, accessory substance is few, but because pressure is high, medium is explosion hazard gases, and operation is whard to control, and equipment requirement is harsh.
, the report such as Ichikawa F.Y (US in 1962:3040029) using N- (2 '-aminoethyl) propane diamine as raw material, pass through
The ammonia formation unsaturated compound that a molecule is sloughed in imines intramolecular cyclization entered catalytic hydrogenating reduction into homopiperazine, production again
Rate 32%.Although the technique technique is simple, consumption of raw materials is high, it is necessary to be carried out under high-temperature and high-pressure conditions, and equipment requirement is high.
2006, the report such as Dezhi L. with N- (beta-hydroxy) -1,3- propane diamine for raw material, using Cu-Cr-Ba-Al to urge
Agent, cyclization obtains homopiperazine, yield 90% (Hefang.W, Ligng.C, Dezhi L, et in high-temperature high-pressure reaction kettle
al.A continuous process for the synthesis of homo-piperazine catalyzed by Cu-
based catalysts[J].Reaction Kinetics and Catalysis Letters 2006,89(2):201-
208.).The reaction yield is high, but condition is harsh, and catalyst is difficult to prepare, and cost of material is higher, post catalyst reaction with it is anti-
Product is answered to be not readily separated.
2006, kingly way woods etc. was reported using ethylenediamine as raw material, through sulfonylation, cyclisation, acid detosylation three-step reaction
Homopiperazine is synthesized, total recovery is up to 78%.In the synthetic method, in the ethylenediamine sulfonylation of the first step, turned by adding phase
Shifting catalyst can make product yield significantly improve, and yield is 86%.It is anti-from NaH/DMF in the cyclization of second step
Answer system.Sulfonyl is finally sloughed with 91% yield under the conditions of HBr/HAc/PhOH acid reactions and has obtained final product height
Piperazine.As a result show, this is that a raw material is easy to get, and easy to operate, higher yields obtain the synthesis route of homopiperazine, have
Certain industrial applications prospect (kingly way woods, money Jian Hua, novel synthesis [J] chemical reagent of the homopiperazines such as Liu Lin,
2006,28(5):311-312.).However, the technological operation is more complicated, explosive sodium hydride has been used during cyclization.
Therefore, existing homopiperazine synthesis route is still longer, cause that total recovery is relatively low, final products purity not
It is high.The present invention to the synthesis technique of homopiperazine improve and optimizate there is provided a kind of simple in production process operation, saves into
This, is easy to big production, and can obtain high-purity, the preparation method of homopiperazine in high yield.
The content of the invention
It is an object of the invention to overcome the shortcoming of above-mentioned prior art, it is numerous and diverse to solve existing synthesis technique, reacts bar
The technical problem that part is harsh, total recovery is relatively low, final products purity are not high can obtain high-purity, in high yield there is provided one kind
Homopiperazine synthetic method.
The invention discloses homopiperazine synthetic route chart, accompanying drawing 1 is seen.
As shown in Figure 1, the method for synthesis homopiperazine disclosed by the invention is using ethylenediamine as raw material, in n-butanol solvent
In obtain N with tolysulfonyl chlorine acylation, the p-toluenesulfonyl ethylenediamines of N '-two, product without being separated from reaction solution,
Directly under sodium hydroxide effect, N, the p-toluenesulfonyl homopiperazines of N '-two, then in hydrogen are obtained with bromo-chloropropane ring-closure reaction
De- sulfonyl obtains homopiperazine hydrobromate under bromic acid and phenol effect, most dissociates afterwards through sodium hydroxide, toluene band water obtains height
The homopiperazine of purity.
The method of synthesis homopiperazine disclosed by the invention comprises the following steps：
(1) first step：Take ethylenediamine and n-butanol to be reacted with paratoluensulfonyl chloride, add 50% sodium hydroxide,
Stirring, is heated to reflux, adds bromo-chloropropane and 50% sodium hydroxide solution, react 1-3 hour, centrifugation, obtains N, and N '-
Two p-toluenesulfonyl homopiperazines；
(2) second step：Successively phenol, hydrobromic acid and N, the N p-toluenesulfonyl of '-two homopiperazine are put into retort
Row reaction, is concentrated under reduced pressure, and removes remaining phenol and hydrobromic acid, adds ethanol, and centrifugation obtains homopiperazine hydrobromate；
(3) the 3rd steps：By in homopiperazine hydrobromate and 50% sodium hydroxide solution input retort, it is stirred at room temperature, to
Toluene is added in retort, is flowed back, filtrate is collected in centrifugation, and vacuum distillation, the cut of 90 DEG C -110 DEG C or so of collection obtains height
Piperazine.
The method of synthesis homopiperazine disclosed by the invention comprises the following steps：
(1) first step：Take 20-30kg ethylenediamines and 60-80kg n-butanols to put into retort, at 25 DEG C, add
140-180kg paratoluensulfonyl chlorides and the sodium hydroxides of 70-90kg 50%, stir 10-20 minutes, are heated to reflux, add 60-
The sodium hydroxide solution of 70kg bromo-chloropropanes and 70-90kg 50%, reaction system pH is 10-12, is heated to backflow, reaction
1.5-2.5 hours, N, the p-toluenesulfonyl homopiperazines of N '-two were dried to obtain in centrifugation；
(2) second step：Successively by 60-80kg phenol ,-two pairs of toluene sulphurs of 90-110kg hydrobromic acids and 130-150kg N, N '
In acyl group homopiperazine input retort, back flow reaction 4-6h, is concentrated under reduced pressure under 5mgHg, removes remaining phenol and hydrogen by 120 DEG C
Bromic acid, adds 40-60kg ethanol, and stirred crystallization is stayed overnight, centrifugation, dries to obtain homopiperazine hydrobromate；
(3) the 3rd steps：By 60-80kg homopiperazines hydrobromate and the sodium hydroxide solutions of 20-40kg 50% input retort
In, reaction 0.5-1.5h is stirred at room temperature, then 90-110kg toluene is added into retort, backflow is heated to, while water knockout drum point
Go out the water of reaction solution, until efflux clarification, is cooled to 30 DEG C, centrifugation is collected vacuum distillation under filtrate, 3-5mmHg and collected
100-110 DEG C of cut, obtains homopiperazine.The method of synthesis homopiperazine disclosed by the invention comprises the following steps：
(1) first step：Take 25kg ethylenediamines and 75kg n-butanols to put into 500L retort, at 25 DEG C, add pair
160kg paratoluensulfonyl chlorides and the sodium hydroxides of 80kg 50%, stir 15 minutes, be heated to reflux, add 65kg bromo-chloropropanes and
80kg 50% sodium hydroxide solution, reaction system pH is 12, is heated to backflow, is reacted 2 hours, and N is dried to obtain in centrifugation, N '-
Two p-toluenesulfonyl homopiperazines；
(2) second step：Successively by 70kg phenol, 100kg hydrobromic acids and 140kg N, N '-two p-toluenesulfonyl homopiperazines
Put into 500L retort, back flow reaction 5h, 120 DEG C, be concentrated under reduced pressure under 5mgHg, remove remaining phenol and hydrobromic acid, then add
Enter 50kg ethanol, stirred crystallization is stayed overnight, centrifuge, dry to obtain homopiperazine hydrobromate；
(3) 78kg homopiperazines hydrobromate and the sodium hydroxide solutions of 30kg 50% are added in retort, are stirred at room temperature anti-
1h is answered, then 100kg toluene is added into retort, backflow is heated to, while water knockout drum separates the water of reaction solution, until efflux
Clarification, is cooled to 30 DEG C, centrifugation collects the cut that vacuum distillation under filtrate, 5mmHg collects 100 DEG C, obtains homopiperazine.
It is 45-65% the invention also discloses the hydrobromic acid concentration used in synthesis homopiperazine hydrobromate.
It is enamel reactor or stainless steel reaction tank the invention also discloses retort used in preparation process.
The beneficial effects of the present invention are there is provided can obtain high-purity, the preparation method of homopiperazine in high yield.
It is disclosed by the invention synthesis homopiperazine method be by sulfonation and cyclization " treat different things alike " method synthesize key intermediate N,
The p-toluenesulfonyl homopiperazines of N '-two, simplify production technology, save the energy.
Key intermediate N of the present invention, N '-two p-toluenesulfonyl homopiperazine use bromo-chloropropane for raw material, fill
Point utilize bromine and the faint activity difference of chlorine, effectively inhibit the generation of straight chain accessory substance, thus improve product yield and
Purity.
The described homopiperazine hydrobromate synthesis of the present invention uses the hydrobromic acid and phenol of high concentration for raw material, hydrobromic acid
Concentration preferably 45~65%.
Homopiperazine preparation method of the present invention is reacted using sodium hydroxide and homopiperazine hydrobromate, then through toluene
Dehydration, distillation obtain the homopiperazine of high-purity.
Brief description of the drawings
Fig. 1 homopiperazine synthetic routes.
Embodiment
Embodiment 1：
The method for preparing homopiperazine is as follows：
(1) first step：Take ethylenediamine and n-butanol to be reacted with paratoluensulfonyl chloride, add 50% sodium hydroxide,
Stirring, is heated to reflux, adds bromo-chloropropane and 50% sodium hydroxide solution, react 1-3 hour, centrifugation, obtains N, and N '-
Two p-toluenesulfonyl homopiperazines；
(2) second step：Successively phenol, hydrobromic acid and N, the N p-toluenesulfonyl of '-two homopiperazine are put into retort
Row reaction, is concentrated under reduced pressure, and removes remaining phenol and hydrobromic acid, adds ethanol, and centrifugation obtains homopiperazine hydrobromate；
(3) the 3rd steps：By in homopiperazine hydrobromate and 50% sodium hydroxide solution input retort, it is stirred at room temperature, to
Toluene is added in retort, is flowed back, filtrate is collected in centrifugation, and vacuum distillation, the cut of 90 DEG C -110 DEG C or so of collection obtains height
Piperazine.
Embodiment 2：
The method for preparing homopiperazine is as follows：
(1) first step：Take 20-30kg ethylenediamines and 60-80kg n-butanols to put into retort, at 25 DEG C, add
140-180kg paratoluensulfonyl chlorides and the sodium hydroxides of 70-90kg 50%, stir 10-20 minutes, are heated to reflux, add 60-
The sodium hydroxide solution of 70kg bromo-chloropropanes and 70-90kg 50%, reaction system pH is 10-12, is heated to backflow, reaction
1.5-2.5 hours, N, the p-toluenesulfonyl homopiperazines of N '-two were dried to obtain in centrifugation；
(2) second step：Successively by 60-80kg phenol, 90-110kg hydrobromic acid (contents：45-60%) and 130-150kg
In N, the N p-toluenesulfonyl of '-two homopiperazine input retort, back flow reaction 4-6h, is concentrated under reduced pressure under 5mgHg, removed by 120 DEG C
Remaining phenol and hydrobromic acid, add 40-60kg ethanol, and stirred crystallization is stayed overnight, centrifugation, dry to obtain homopiperazine hydrobromate；
(3) the 3rd steps：By 60-80kg homopiperazines hydrobromate and the sodium hydroxide solutions of 20-40kg 50% input retort
In, reaction 0.5-1.5h is stirred at room temperature, then 90-110kg toluene is added into retort, backflow is heated to, while water knockout drum point
Go out the water of reaction solution, until efflux clarification, is cooled to 30 DEG C, centrifugation is collected vacuum distillation under filtrate, 3-5mmHg and collected
100-110 DEG C of cut, obtains homopiperazine.
Embodiment 3：
The method for preparing homopiperazine is as follows：
(1) first step：Take 25kg ethylenediamines and 75kg n-butanols to put into 500L enamel reactors, at 25 DEG C, add
To 160kg paratoluensulfonyl chlorides and the sodium hydroxides of 80kg 50%, stir 15 minutes, be heated to reflux, add 65kg bromo-chloropropanes
With 80kg 50% sodium hydroxide solution, reaction system pH is 12, is heated to backflow, is reacted 2 hours, and N is dried to obtain in centrifugation,
The p-toluenesulfonyl homopiperazine 143kg of N '-two, yield 91.1%, content 99.1%；
(2) second step：Successively by 70kg phenol, 100kg hydrobromic acid (contents：60%) with 140kg-two pairs of toluene of N, N '
In sulfonyl homopiperazine input 500L enamel reactors, back flow reaction 5h, is concentrated under reduced pressure under 5mgHg, removed remaining by 120 DEG C
Phenol and hydrobromic acid, add 50kg ethanol, and stirred crystallization is stayed overnight, centrifugation, dry to obtain 78.7kg homopiperazine hydrobromates, yield
88.2%, content 99.5% (perchloric acid titration)；
(3) 78kg homopiperazines hydrobromate and the sodium hydroxide solutions of 30kg 50% are added in enamel reactor, room temperature is stirred
Reaction 1h is mixed, then 100kg toluene is added into retort, backflow is heated to, while water knockout drum separates the water of reaction solution, until stream
Go out liquid clarification, be cooled to 30 DEG C, centrifugation collects the cut that vacuum distillation under filtrate, 5mmHg collects 100 DEG C, obtains homopiperazine
24kg, yield 82.5%, content 99.5%.
Embodiment 4：
The method for preparing homopiperazine is as follows：
(1) first step：Take 20kg ethylenediamines and 60kg n-butanols to put into 500L stainless steel reaction tanks, at 25 DEG C, then add
Enter 140kg paratoluensulfonyl chlorides and the sodium hydroxides of 70kg 50%, stir 10 minutes, be heated to reflux, add 60kg bromo-chloropropanes
With 70kg 50% sodium hydroxide solution, reaction system pH is 10, is heated to backflow, is reacted 1.5 hours, and N is dried to obtain in centrifugation,
The p-toluenesulfonyl homopiperazine 127kg of N '-two, yield 90.4%, content 99.2%；
(2) second step：Successively by 60kg phenol, 108kg hydrobromic acid (contents：55%) with 130kg-two pairs of toluene of N, N '
In sulfonyl homopiperazine input 500L stainless steel reaction tanks, back flow reaction 4h, is concentrated under reduced pressure under 5mgHg, removed remaining by 120 DEG C
Phenol and hydrobromic acid, add 40kg ethanol, stirred crystallization is stayed overnight, centrifuge, dry to obtain 71.5kg homopiperazine hydrobromates, receive
Rate 89.6%, content 99.3% (perchloric acid titration)；
(3) the 3rd steps：60kg homopiperazines hydrobromate and the sodium hydroxide solutions of 20kg 50% input 500L stainless steels is anti-
Answer in tank, reaction 0.5h is stirred at room temperature, then 90kg toluene is added into retort, backflow is heated to, while water knockout drum is separated instead
The water of liquid is answered, until efflux clarification, is cooled to 30 DEG C, centrifugation collects vacuum distillation under filtrate, 3mmHg and collects 110 DEG C and evaporates
Point, obtain homopiperazine 18kg, yield 85.0%, content 99.1%.
Embodiment 5：
The method for preparing homopiperazine is as follows：
(1) first step：Take 30kg ethylenediamines and 80kg n-butanols to put into 500L enamel reactors, at 25 DEG C, add
180kg paratoluensulfonyl chlorides and the sodium hydroxides of 90kg 50%, stir 20 minutes, be heated to reflux, add 70kg bromo-chloropropanes and
90kg 50% sodium hydroxide solution, reaction system pH is 12, is heated to backflow, is reacted 2.5 hours, and N is dried to obtain in centrifugation,
The p-toluenesulfonyl homopiperazine 141kg of N '-two, yield 88.1%, content 99.0%；
(2) second step：Successively by 80kg phenol, 1450kg hydrobromic acid (contents：45%) with 150kg-two pairs of toluene of N, N '
In sulfonyl homopiperazine input 500L enamel reactors, back flow reaction 6h, is concentrated under reduced pressure under 5mgHg, removed remaining by 120 DEG C
Phenol and hydrobromic acid, add 60kg ethanol, and stirred crystallization is stayed overnight, centrifugation, dry to obtain 86.9kg homopiperazine hydrobromates, yield
88.7%, content 99.2% (perchloric acid titration)；
(3) the 3rd steps：By 80kg homopiperazines hydrobromate and the sodium hydroxide solutions of 40kg 50% input enamel reactor
In, reaction 1.5h is stirred at room temperature, then 110kg toluene is added into retort, backflow is heated to, while water knockout drum separates reaction solution
Water, until efflux clarification, is cooled to 30 DEG C, the cut that vacuum distillation under filtrate, 4mmHg collects 100 DEG C is collected in centrifugation,
Obtain homopiperazine 37kg, yield 84.7%, content 99.2%.
Above content is to combine specific preferred embodiment further description made for the present invention, it is impossible to assert
The embodiment of the present invention is only limitted to this, for general technical staff of the technical field of the invention, is not taking off
On the premise of from present inventive concept, some simple deduction or replace can also be made, the present invention should be all considered as belonging to by institute
Claims of submission determine scope of patent protection.
Claims (4)
1. a kind of preparation method of homopiperazine, it is characterised in that：Comprise the following steps：
(1) first step：Take 20-30kg ethylenediamines and 60-80kg n-butanols to put into retort, at 25 DEG C, add 140-
180kg paratoluensulfonyl chlorides and the sodium hydroxide solutions of 70-90kg 50%, stir 10-20 minutes, are heated to reflux, add 60-
70kg bromo-chloropropanes and the sodium hydroxide solutions of 70-90kg 50%, reaction system pH are 10-12, are heated to backflow, react 1.5-
2.5 hours, N, the p-toluenesulfonyl homopiperazines of N '-two were dried to obtain in centrifugation；
(2) second step：Successively by 60-80kg phenol, 90-110kg hydrobromic acids and 130-150kg N, N '-two p-toluenesulfonyls
In homopiperazine input retort, back flow reaction 4-6h, is concentrated under reduced pressure under 5mgHg, removes remaining phenol and hydrobromic acid by 120 DEG C,
40-60kg ethanol is added, stirred crystallization is stayed overnight, centrifuge, dry to obtain homopiperazine hydrobromate；
(3) the 3rd steps：60-80kg homopiperazines hydrobromate and the sodium hydroxide solutions of 20-40kg 50% are put into retort,
Reaction 0.5-1.5h is stirred at room temperature, then 90-110kg toluene is added into retort, backflow is heated to, while water knockout drum is separated instead
The water of liquid is answered, until efflux clarification, is cooled to 30 DEG C, centrifugation collects vacuum distillation under filtrate, 3-5mmHg and collects 100-110
DEG C cut, obtain homopiperazine.
2. the preparation method of homopiperazine according to claim 1, it is characterised in that：Comprise the following steps：
(1) first step：Take 25kg ethylenediamines and 75kg n-butanols to put into 500L retort, at 25 DEG C, add to 160kg pairs
Toluene sulfochloride and the sodium hydroxide solutions of 80kg 50%, stir 15 minutes, be heated to reflux, add 65kg bromo-chloropropanes and
The sodium hydroxide solutions of 80kg 50%, reaction system pH is 12, is heated to backflow, is reacted 2 hours, and N, N '-two are dried to obtain in centrifugation
P-toluenesulfonyl homopiperazine；
(2) second step：70kg phenol, 100kg hydrobromic acids and 140kg N, N '-two p-toluenesulfonyls homopiperazine are put into successively
In 500L retort, back flow reaction 5h, is concentrated under reduced pressure under 5mgHg, removes remaining phenol and hydrobromic acid, add by 120 DEG C
50kg ethanol, stirred crystallization is stayed overnight, centrifugation, dries to obtain homopiperazine hydrobromate；
(3) 78kg homopiperazines hydrobromate and the sodium hydroxide solutions of 30kg 50% are added in retort, reaction is stirred at room temperature
1h, then 100kg toluene is added into retort, backflow is heated to, while water knockout drum separates the water of reaction solution, until efflux is clear
Clearly, 30 DEG C are cooled to, centrifugation collects the cut that vacuum distillation under filtrate, 5mmHg collects 100 DEG C, obtains homopiperazine.
3. according to the preparation method of any homopiperazines of claim 1-2, it is characterised in that：Synthesize homopiperazine hydrobromate institute
Hydrobromic acid concentration is 45-65%.
4. according to the preparation method of any homopiperazines of claim 1-2, it is characterised in that：Reaction used in preparation process
Tank is enamel reactor or stainless steel reaction tank.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510077009.7A CN104744382B (en) | 2015-02-12 | 2015-02-12 | A kind of preparation method of homopiperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510077009.7A CN104744382B (en) | 2015-02-12 | 2015-02-12 | A kind of preparation method of homopiperazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104744382A CN104744382A (en) | 2015-07-01 |
| CN104744382B true CN104744382B (en) | 2017-09-15 |
Family
ID=53584731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510077009.7A Active CN104744382B (en) | 2015-02-12 | 2015-02-12 | A kind of preparation method of homopiperazine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104744382B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106699674B (en) * | 2016-11-23 | 2019-06-18 | 苏州百灵威超精细材料有限公司 | A method of homopiperazine is prepared using Trifluoroacetic Acid Ethyl Ester |
| CN113671047B (en) * | 2020-05-13 | 2023-05-23 | 昆药集团股份有限公司 | Method for detecting residues in homopiperazine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735159A (en) * | 2009-12-04 | 2010-06-16 | 大连凯飞精细化工有限公司 | Method for producing monoacetylated homopiperazine |
| CN102120732B (en) * | 2010-01-07 | 2012-12-12 | 成都欣捷高新技术开发有限公司 | Preparation method of homopiperazine and derivative thereof |
| CN102250126A (en) * | 2010-05-18 | 2011-11-23 | 北京化工大学 | Dipurine derivative and synthesis thereof |
-
2015
- 2015-02-12 CN CN201510077009.7A patent/CN104744382B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104744382A (en) | 2015-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103130197B (en) | Continuous-pressure-changing rectification method and device for preparing medicine-level sulfoxide chloride | |
| CN104945299B (en) | A kind of high-efficiency synthesis method of vildagliptin | |
| CN104744382B (en) | A kind of preparation method of homopiperazine | |
| CN105272863B (en) | The preparation method of paraphenetidine | |
| CN107118125B (en) | A kind of preparation method of cyclohexanone oxime | |
| CN103086895B (en) | Method for preparing aromatic amine from mixed nitrochlorobenzene | |
| WO2017076737A1 (en) | Continuous process for preparing brivaracetam | |
| Zhang et al. | Josiphos-type binaphane ligands for the asymmetric Ir-catalyzed hydrogenation of acyclic aromatic N-aryl imines | |
| CN103804267B (en) | A kind of synthesis technique of vildagliptin | |
| CN103641761A (en) | Vildagliptin preparation method | |
| CN114315749B (en) | Method for synthesizing aliskiren intermediate by continuous flow microreactor | |
| CN112694437A (en) | Preparation method of chlorpheniramine maleate impurity | |
| CN101108366B (en) | Method for manufacturing catalyst used for synthesizing 2-picoline | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN102675201A (en) | Method for preparing 2-methyl-8-aminoquinoline from o-nitrophenol | |
| CN101735159A (en) | Method for producing monoacetylated homopiperazine | |
| CN105541542A (en) | Technique for continuously producing decahydronaphthalene from industrial naphthalene | |
| CN104292113A (en) | Preparation method of 3-chloro-4-fluoroaniline | |
| CN114853711A (en) | Method for preparing cannabinol by copper catalysis one-pot method | |
| CN103920522A (en) | Method for preparing catalyst assisting in synthesizing aniline through one-step amination of benzene | |
| KR102500501B1 (en) | Process for producing laurolactam and its synthesis apparatus | |
| EP3904333A1 (en) | Method for preparing (2s,3s)-3-amino-bicyclo[2.2.2]octane-2-carboxylate | |
| CN111004272B (en) | Preparation method of orlistat chiral intermediate | |
| WO2019008594A1 (en) | Continuous process for the preparation of 2-(1h-imidazol-4-yl) ethanamine and pharmaceutically acceptable salts thereof | |
| CN114989168B (en) | Preparation method of 2, 8-diazabicyclo [4,3,0] nonane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |