CN109485614A - The synthesis piperazine technique of tricyclic - Google Patents
The synthesis piperazine technique of tricyclic Download PDFInfo
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- CN109485614A CN109485614A CN201710810237.XA CN201710810237A CN109485614A CN 109485614 A CN109485614 A CN 109485614A CN 201710810237 A CN201710810237 A CN 201710810237A CN 109485614 A CN109485614 A CN 109485614A
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- triazine ring
- technique
- tricyclic
- methanol
- crude product
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members 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
- C07D253/075—Two hetero atoms, in positions 3 and 5
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The invention discloses a kind of synthesis piperazine techniques of tricyclic, and methyl hydrazine aqueous solution is reacted with ammonium thiocyanate, amino methyl thiocarbamide methanol solution then is made with methanol；By amino methyl thiocarbamide methanol solution and dimethyl oxalate, sodium methoxide cyclization reaction, end being reacted with salt acid for adjusting pH value and removes excessive sodium methoxide, triazine ring sodium salt is made using filtering；Triazine ring sodium salt is obtained into triazine ring crude product through acid out；Triazine ring crude product is washed with hot water stirs, crystallisation by cooling, filtering, dries obtained triazine ring fine work.High income of the present invention, cost of material is low, reduces labor intensity of workers, reduces three-waste pollution.
Description
Technical field
The present invention relates to a kind of synthesis piperazine techniques of tricyclic.
Background technique
Triazine ring
English name: Thiotriazinone
CAS NO:58909-39-0
Molecular weight: 159.16
EC NO:261-490-1
Molecular formula: C4H5N3O2S
Product introduction: physico-chemical property: fusing point >=245 DEG C
Purposes: the intermediate as drugs such as Ceftriaxone Sodium, ceftriaxone sodiums
Alias: Thiotriazinone；Thiotriazinone
Existing triazine ring synthetic method is complicated for operation, and the three wastes are more, and yield is low, and cost of material is higher.
Summary of the invention
The purpose of the present invention is to provide a kind of high income, cost of material is low, reduces the synthesis piperazine of the tricyclic of three-waste pollution
Technique.
The technical solution of the invention is as follows:
A kind of synthesis piperazine technique of tricyclic, it is characterized in that: successively including the following steps:
(1) addition reaction: methyl hydrazine aqueous solution is reacted with ammonium thiocyanate, amino methyl thiocarbamide first then is made with methanol
Alcoholic solution；
(2) cyclization reaction: by amino methyl thiocarbamide methanol solution and dimethyl oxalate, sodium methoxide cyclization reaction, reaction knot
Beam hydrochloric acid adjusts pH value and removes excessive sodium methoxide, and triazine ring sodium salt is made using filtering；
(3) triazine ring sodium salt acid precipitation reaction: is obtained into triazine ring crude product through acid out；
(4) it refines: triazine ring crude product being washed with hot water stirs, crystallisation by cooling, filtering, dries obtained triazine ring fine work.
In step (1) methyl hydrazine and ammonium thiocyanate in molar ratio 1: 1-1.1 ratio feed intake mixing, reaction temperature is 80~
110℃。
Amino methyl thiocarbamide and the molar ratio of dimethyl oxalate, sodium methoxide, methanol are 1: 1-1.2: 2-2.2: 5-7, cyclization
Reaction temperature is 40-80 DEG C, and the cyclization reaction time is 4-10 hours.
When adjusting the pH value excessive sodium methoxide of removing with hydrochloric acid in step (2), adjusting pH value is 6-7.
When triazine ring sodium salt being obtained triazine ring crude product through acid out in step (3), adjusting pH value with hydrochloric acid is 1-2.
High income of the present invention, cost of material is low, reduces labor intensity of workers, reduces three-waste pollution.
Specific embodiment
Embodiment 1:
1. putting into 500ml reaction flask, being heated to reflux, reaction temperature 40g methyl hydrazine aqueous solution, 29g ammonium thiocyanate
Control is at 85-90 DEG C, after moisture content is removed in negative pressure drawing, 180g methanol is added and obtains amino methyl hydrazine methanol solution.
2. 50g dimethyl oxalate, 118g sodium methoxide are added into completely reacted amino methyl hydrazine methanol solution, it is heated to reflux
6 hours, reaction temperature was controlled at 65-75 DEG C, removes excessive sodium methoxide with hydrochloric acid tune pH value 6-7 after reaction, was filtered, filter
Liquid (triazine ring sodium salt solution) carries out sour suction with hydrochloric acid tune pH value again for 1~2, and filtering obtains triazine ring crude product.
3. triazine ring crude product is added in hot water, stirring, crystallisation by cooling is filtered, and drying obtains 41g triazine ring, yield
70%.
Embodiment 2:
1. 40g methyl hydrazine aqueous solution, 29g ammonium thiocyanate are put into 500ml reaction flask, it is heated to reflux, reaction temperature
Degree control is at 95-100 DEG C, after moisture content is removed in negative pressure drawing, 200g methanol is added and obtains amino methyl hydrazine methanol solution.
2. 52g dimethyl oxalate, 122g sodium methoxide are added into completely reacted amino methyl hydrazine methanol solution, it is heated to reflux
6 hours, reaction temperature was controlled at 65-75 DEG C, and after reaction with hydrochloric acid tune pH value 6-7, filtering, filtrate is again with hydrochloric acid tune pH value
It is 1~2, filtering, filter cake, that is, triazine ring crude product.
3. triazine ring crude product is added in suitable hot water, stirring, crystallisation by cooling is filtered, and drying obtains 44g triazine ring, is received
Rate 75%.
Claims (5)
1. the synthesis piperazine technique of a kind of tricyclic, it is characterized in that: successively including the following steps:
1) addition reaction: methyl hydrazine aqueous solution is reacted with ammonium thiocyanate, and it is molten that amino methyl thiocarbamide methanol then is made with methanol
Liquid；With dimethyl oxalate, sodium methoxide cyclization reaction, reacts end hydrochloric acid and adjust the excessive sodium methoxide of pH value removing
2) by amino methyl thiocarbamide methanol solution, triazine ring sodium salt cyclization reaction: is made using filtering；
3) triazine ring sodium salt acid precipitation reaction: is obtained into triazine ring crude product through acid out；
4) it refines: triazine ring crude product being washed with hot water stirs, crystallisation by cooling, filtering, dries obtained triazine ring fine work.
2. the synthesis piperazine technique of tricyclic according to claim 1, it is characterized in that: step
1) in methyl hydrazine and ammonium thiocyanate in molar ratio 1: 1-1.1 ratio feed intake mixing, reaction temperature is 80~110 DEG C.
3. the synthesis piperazine technique of tricyclic according to claim 1 or 2, it is characterized in that: amino methyl thiocarbamide and oxalic acid diformazan
Ester, sodium methoxide, methanol molar ratio be 1: 1-1.2: 2-2.2: 5-7, cyclization reaction temperature is 40-80 DEG C, the cyclization reaction time
It is 4-10 hours.
4. the synthesis piperazine technique of tricyclic according to claim 1 or 2, it is characterized in that: adjusting pH value with hydrochloric acid in step (2)
When removing excessive sodium methoxide, adjusting pH value is 6-7.
5. the synthesis piperazine technique of tricyclic according to claim 1 or 2, it is characterized in that: passing through triazine ring sodium salt in step (3)
When acid out obtains triazine ring crude product, adjusting pH value with hydrochloric acid is 1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710810237.XA CN109485614A (en) | 2017-09-11 | 2017-09-11 | The synthesis piperazine technique of tricyclic |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710810237.XA CN109485614A (en) | 2017-09-11 | 2017-09-11 | The synthesis piperazine technique of tricyclic |
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| CN109485614A true CN109485614A (en) | 2019-03-19 |
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| CN201710810237.XA Withdrawn CN109485614A (en) | 2017-09-11 | 2017-09-11 | The synthesis piperazine technique of tricyclic |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110734407A (en) * | 2019-12-19 | 2020-01-31 | 山东汇海医药化工有限公司 | method for preparing triazine ring by pot method |
| CN110950814A (en) * | 2019-12-11 | 2020-04-03 | 山东汇海医药化工有限公司 | Method for recovering 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring refining wastewater |
| CN110950775A (en) * | 2019-12-11 | 2020-04-03 | 山东汇海医药化工有限公司 | Method for decomposing and recycling methyl hydrazine from triazine ring residues |
| CN110981823A (en) * | 2019-12-27 | 2020-04-10 | 山东汇海医药化工有限公司 | Method for preparing 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring |
| CN111039840A (en) * | 2019-12-11 | 2020-04-21 | 山东汇海医药化工有限公司 | Method for synthesizing 2-methyl thiosemicarbazide |
| CN111057017A (en) * | 2019-12-27 | 2020-04-24 | 山东汇海医药化工有限公司 | Method for recovering 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring cyclization mother liquor |
| CN112694448A (en) * | 2020-12-30 | 2021-04-23 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
| CN112759558A (en) * | 2020-12-30 | 2021-05-07 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
| CN113214176A (en) * | 2021-05-17 | 2021-08-06 | 山东汇海医药化工有限公司 | Preparation method of triazine ring product |
-
2017
- 2017-09-11 CN CN201710810237.XA patent/CN109485614A/en not_active Withdrawn
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110950814A (en) * | 2019-12-11 | 2020-04-03 | 山东汇海医药化工有限公司 | Method for recovering 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring refining wastewater |
| CN110950775A (en) * | 2019-12-11 | 2020-04-03 | 山东汇海医药化工有限公司 | Method for decomposing and recycling methyl hydrazine from triazine ring residues |
| CN110950775B (en) * | 2019-12-11 | 2022-06-28 | 山东汇海医药化工有限公司 | Method for decomposing and recycling methyl hydrazine from triazine ring residues |
| CN111039840A (en) * | 2019-12-11 | 2020-04-21 | 山东汇海医药化工有限公司 | Method for synthesizing 2-methyl thiosemicarbazide |
| CN110734407A (en) * | 2019-12-19 | 2020-01-31 | 山东汇海医药化工有限公司 | method for preparing triazine ring by pot method |
| CN110981823B (en) * | 2019-12-27 | 2021-08-03 | 山东汇海医药化工有限公司 | Method for preparing 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring |
| CN111057017B (en) * | 2019-12-27 | 2021-07-30 | 山东汇海医药化工有限公司 | Method for recovering 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring cyclization mother liquor |
| CN111057017A (en) * | 2019-12-27 | 2020-04-24 | 山东汇海医药化工有限公司 | Method for recovering 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring cyclization mother liquor |
| CN110981823A (en) * | 2019-12-27 | 2020-04-10 | 山东汇海医药化工有限公司 | Method for preparing 3-mercapto-5-methyl-1, 2, 4-triazole from triazine ring |
| CN112694448A (en) * | 2020-12-30 | 2021-04-23 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
| CN112759558A (en) * | 2020-12-30 | 2021-05-07 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
| CN112759558B (en) * | 2020-12-30 | 2022-06-14 | 山东金城柯瑞化学有限公司 | Process for the preparation of triazine rings |
| CN113214176A (en) * | 2021-05-17 | 2021-08-06 | 山东汇海医药化工有限公司 | Preparation method of triazine ring product |
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Application publication date: 20190319 |