CN109096213A - A kind of preparation method of 1H-1,2,3- triazole - Google Patents
A kind of preparation method of 1H-1,2,3- triazole Download PDFInfo
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- CN109096213A CN109096213A CN201811136541.1A CN201811136541A CN109096213A CN 109096213 A CN109096213 A CN 109096213A CN 201811136541 A CN201811136541 A CN 201811136541A CN 109096213 A CN109096213 A CN 109096213A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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Abstract
The invention discloses a kind of preparation methods of 1H-1,2,3- triazole.This method is using benzotriazole as raw material, through peroxidating, decarboxylation two-step reaction, using the 1H-1 of rectification and purification to high-purity, 2,3- triazole finished products.The raw material of entire synthetic route is cheap and easy to get, and easy to operate, operating cost is low, and technique is environmentally protective, is quite suitable for industrialized production, has extremely strong industrial application value.
Description
Technical field
The invention belongs to fine chemistry industry preparation technical fields, and in particular to a kind of 1H-1, the preparation method of 2,3- triazoles.
Background technique
1H-1,2,3- triazoles are a kind of important fine pharmaceutical-chemical intermediates, are his azoles of beta-lactamase inhibitor
The important intermediate of Batan, while can be used for the use of other drugs or fine chemical product.
Currently, retrieved by Chinese and Foreign, 1H-1, the synthetic method of 2,3- triazoles substantially there are several types of:
(1) document Cationo A, 1,2,3-Triazole [J] .Ann.chim (Rome) 1968,58,1507~1509 is reported
Road directly reacts preparation from hydrazoic acid and alkynes or alkene under high-temperature and high-pressure conditions.
(2) patent JP06410942 is with the monoxime hydrazone or acyl oxime hydrazone of 1,2- dichloro acetaldehyde and hydroxyl hydrochloride reaction production glyoxal
1H-1,2,3- triazole is synthesized for intermediate.
(3) patent JP05140121 with toluene Huang hydrazides is reacted with 1,2- dichloro acetaldehyde production glyoxal monoxime hydrazone or
Acyl oxime hydrazone is that intermediate synthesizes 1H-1,2,3- triazole.
(4) it is reported in " Chinese Journal of Pharmaceuticals " 2003,34 (8), is with paratoluensulfonyl chloride, hydrazine hydrate, glyoxal
Raw material cyclization preparation.
(5) it is reported in document synlett, 1998,431 and patent CN1539829A, with raw material glyoxal, hydrazine hydrate, salt
Sour azanol, aceticanhydride synthesis.
(6) West China Journal of Pharmaceutical Sciences 2001,16 (4) are reported in 273~275, are raw material through peroxidating using benzotriazole
Decarboxylation preparation.
(7) it is reported in patent CN1011104607A, it is anti-by potassium permanganate oxidation open loop using benzotriazole as raw material
1,2,3- triazole -4,5- dicarboxyl acid crudes should be prepared, then in catalyst copper powder, Cu oxide or copper powder and pyridine or quinoline
Mixed catalytic under reaction decarboxylation preparation.
(8)Chemistry ofHeterocyclic Compounds(New York,NY,United States),
It is reported in 1981, vol.17, #5p.510-515, using benzotriazole as raw material, with chromic acid oxidation preparation one under sulfuric acid
Salt, then at high temperature under high pressure prepared by decarboxylation.
In summary several routes are summarized, and have directly or indirectly all used azido compound in route (1)~(5), such
Compound is not only hypertoxic, and has strong explosivity.Technological operation danger is thus increased, and technological operation is difficult to control,
The problems such as stability is poor, and product quality is not high, and purification difficult, wastewater flow rate is big, complicated component, and environmental protection treatment pressure is big is not suitable for
Industrialized production.Using benzotriazole as raw material in route (6)~(7), potassium permanganate oxidation is used under neutral or acid condition,
Reaction color is deep, and obtained diacid intermediate purity is not high.Decarboxylic reaction below directly uses diacid intermediate in copper or copper
Destructive distillation or wet process decarboxylation under the catalysis of oxide, there are decarboxylation difficulties, and temperature is high, is also easy to produce carbonization phenomenon, and product purity is low, receive
The problems such as rate bottom, is also not suitable for industrial amplification production so as to cause high production cost.In route (8) use chromic acid and
The concentrated sulfuric acid aoxidizes to obtain complex salt, and under high temperature and strong acid condition, benzotriazole color blackening, reaction selectivity is poor, yield
It is low, and toxic wastewater containing chromium is generated, processing is difficult.Toxic solvent benzene is used in decarboxylation procedure, while being needed in high pressure-temperature
Under the conditions of carry out, operational danger is big, and equipment requirement is high, is not suitable for industrialized production.
Summary of the invention
It is easy to operate the purpose of the present invention is to provide a kind of technique production safety, it is easy to purify, yield is higher and implements
The preparation method of lower-cost 1H-1,2,3- triazole.
1H-1, the preparation method of 2,3- triazoles, comprising the following steps:
Step a, using benzotriazole as raw material, potassium permanganate is oxidant, and water is solvent, under the conditions of alkali compounds
Oxidative cleavage adjusts acid at salt, obtains acid salt (chemical formula (II) compound)；
Step b, above-mentioned acid salt in organic solvent react by high temperature decarboxylation, and 1H-1 is obtained after purification, and 2,3- triazoles (are changed
Formula (III) compound) and raw material benzotriazole；
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, alkali compounds described in step a be sodium hydroxide and
At least one of potassium hydroxide.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, benzotriazole described in step a, alkali compounds and
The molar ratio of potassium permanganate is 1:(0.5~3): (2~6).
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, benzotriazole described in step a and water proportion (m/v)
For 1:(10~40).
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, reaction temperature described in step a are 40~100 DEG C, instead
It is 1~6 hour between seasonable.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, agents useful for same is hydrochloric acid or sulfuric acid when adjusting acid in step a.
For example, hydrochloric acid acid concentration used is 5~36%, sulfuric acid concentration is 5~98%.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, it is 20~60 DEG C that temperature when acid is adjusted described in step a,
Adjusting acid pH is 2~3.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, it is 0~25 that crystallization holding temperature after acid is adjusted in step a
℃。
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, further include in step a adjust acid at salt after, acid is obtained by filtration
Formula salt, is dried acid salt.For example, the drying can be dry using vacuum drying or hot air circulation, drying temperature is
70~100 DEG C, drying time 6~8 hours.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, organic solvent described in step b are in DMF and DMAC
It is at least one.The proportion (m/v) of the acid salt and organic solvent is 1:2~10.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, the reaction temperature of decarboxylic reaction described in step b are 130
~180 DEG C, the reaction time is 6~18 hours.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, purification described in step b can use following methods: first
Low-temperature reduced-pressure is distilled to recover solvent, then high-temperature pressure-reduction is distilled to recover crude product, and crude product is evaporated under reduced pressure to obtain sterling using rectifying column
1H-1,2,3- triazole.
Wherein, above-mentioned 1H-1, the preparation method of 2,3- triazoles, benzotriazole described in step b can be with recycling benefits
With.For example, being recycled using following methods: going the vinasse after purification is cold to 40~80 DEG C of interior temperature, water dissolution is added
Afterwards, it is recycled by reaction step a operation.
Compared with prior art, the beneficial effects of the present invention are:
1, all raw material is cheap, convenient sources, simple and easy to get, is not limited by turn of the market.
2, it is aoxidized using alkaline condition, the manganese dioxide rate of recovery of generation is high, and solid waste recycles convenient.Aqueous solution is basic
Colourless, ingredient is simple, and environmental protection treatment is simple and convenient.
3, it is not required to using decolorization and other fine purification treatment process.Product purity is higher, and stability is good, high income.
4, the 1H-1 that oxidation generates, 2,3- triazole -4,5- dicarboxylic acids and benzotriazole are to be complexed salt form precipitation, water
Middle solubility very little loses small, high income, at low cost.
5, decarboxylic reaction reduces the use of raw material without catalyst, simple to operate, reduces environmental protection treatment process, drop
Low production cost.
6, it avoids improving technological operation safety using poisonous reagent, high-temperature and high-pressure conditions, stable operation is suitble to industry
Change amplification production.
Specific embodiment
Further detailed description is done to technical solution of the present invention below in conjunction with specific embodiment.The following example
It is merely illustrative the ground description and interpretation present invention, and is not necessarily to be construed as limiting the scope of the invention.It is all to be based on this hair
In the range of the technology that bright above content is realized is encompassed by the present invention is directed to protect.
Unless otherwise indicated, raw materials and reagents used in the following embodiment are commercial goods, or can be by
Perception method preparation.
Embodiment 1
1, the preparation of acid salt (chemical formula (II) compound)
Benzotriazole 36g (0.3mol) is put into 1L reaction flask, water 360ml, sodium hydroxide 6g (0.15mol),
40 DEG C are warming up to be added portionwise potassium permanganate 94.8g (0.6mol), control in temperature 40 DEG C, finish, 40 DEG C insulation reaction 6 hours.
Ratio is kept the temperature, heat filtering removes manganese dioxide solid, eluted, drained with hot water, and filtrate is cooled to 25 DEG C, and 5% hydrochloric acid is added dropwise will be molten
Liquid tune pH=2 stirs 30min, is then cooled to 0 DEG C and stirs 2 hours.It filters, water elution is drained.70 DEG C of heated-air circulation oven
It is 8 hours dry, obtain off-white powder chemical formula (II) 35.63g, yield 86%.
2, the preparation of 1H-1,2,3- triazole (chemical formula (III) compound)
Chemical formula (II) 1000g is put into 3L flask, DMF 2000ml is put into, stirring is warming up to 150 DEG C, protects
150 DEG C of temperature are reacted 10 hours.End of reaction, cools to 80 DEG C of interior temperature, and reaction solution is evaporated under reduced pressure by the rectifying column of 30cm and collects
Solvent DMF, residual night is evaporated under reduced pressure again collects chemical formula (III) crude product, and gained crude product passes through rectifying column rectification under vacuum again and purifies to obtain
Pure chemical formula (III) 1H-1,2,3- triazole 237g, 99% or more G/C content, yield 95%.
Embodiment 2
1, the preparation of acid salt (chemical formula (II) compound)
Benzotriazole 36g (0.3mol) is put into 1L reaction flask, water 720ml, potassium hydroxide 25.2g
(0.45mol) is warming up to 60 DEG C and is added portionwise potassium permanganate 189.6g (1.2mol), controls interior 60 DEG C of temperature, finishes, 60 DEG C of heat preservations
Reaction 3 hours.Ratio is kept the temperature, heat filtering removes manganese dioxide solid, eluted, drained with hot water, and filtrate is cooled to 20~25 DEG C, drop
Solution tune pH=2 is stirred 30min by enriching sulfuric acid, is then cooled to 0~5 DEG C and is stirred 1~2 hour.It filters, water elution is taken out
It is dry.The drying 7 hours of 80 DEG C of vacuum, obtains off-white powder chemical formula (II) 38g, yield 91%.
2, the preparation of 1H-1,2,3- triazole (chemical formula (III) compound)
Chemical formula (II) 200g is put into 3L flask, DMAC 2000ml is put into, stirring is warming up to 130 DEG C, protects
130 DEG C of temperature are reacted 18 hours.End of reaction, cools to 90 DEG C of interior temperature, and reaction solution is evaporated under reduced pressure by the rectifying column of 30cm and collects
Solvent DMAC, residual night is evaporated under reduced pressure again collects chemical formula (III) crude product, and gained crude product passes through rectifying column rectification under vacuum again and purifies
To pure chemical formula (III) 1H-1,2,3- triazole 45g, 99% or more G/C content, yield 90%.
Embodiment 3
1, the preparation of acid salt (chemical formula (II) compound)
Benzotriazole 36g (0.3mol) is put into 2L reaction flask, water 1440ml, sodium hydroxide 24g (0.6mol),
It is warming up to 80 DEG C to be added portionwise potassium permanganate 284.4g (1.8mol), controls interior 80 DEG C of temperature, finish, 100 DEG C of insulation reactions 1 are small
When.Ratio is kept the temperature, heat filtering removes manganese dioxide solid, eluted, drained with hot water, and filtrate is cooled to 20~25 DEG C, and 5% sulphur is added dropwise
Solution tune pH=2 is stirred 30min by acid, is then cooled to 0 DEG C and is stirred 2 hours.It filters, water elution is drained.100 DEG C of vacuum dry
Dry 6 hours, obtain off-white powder chemical formula (II) 38g, yield 91%.
2, the preparation of 1H-1,2,3- triazole (chemical formula (III) compound)
Chemical formula (II) 200g is put into 3L flask, DMAC 2000ml is put into, stirring is warming up to 180 DEG C, protects
180 DEG C of temperature are reacted 6 hours.End of reaction, cools to 90 DEG C of interior temperature, and reaction solution is collected molten by the rectifying column vacuum distillation of 30cm
Agent DMAC, residual night is evaporated under reduced pressure again collects chemical formula (III) crude product, and gained crude product passes through rectifying column rectification under vacuum again and purifies to obtain
Pure chemical formula (III) 1H-1,2,3- triazole 45g, 99% or more G/C content, yield 90%.
Embodiment 4
1, the preparation of acid salt (chemical formula (II) compound)
By chemical formula (III) 1H-1 in embodiment 2, the vinasse of the preparation of 2,3- triazoles is cooled to 60 DEG C, and water is added
1300ml, sodium hydroxide 42g are warming up to 60 DEG C and potassium permanganate 334g are added portionwise, and control interior 60 DEG C of temperature, finish, 60 DEG C of heat preservations
Reaction 3 hours.Ratio is kept the temperature, heat filtering removes manganese dioxide solid, eluted, drained with hot water, and filtrate is cooled to 20~25 DEG C, drop
Solution tune pH=2 is stirred 30min by enriching hydrochloric acid, is then cooled to 0~5 DEG C and is stirred 1~2 hour.It filters, water elution is taken out
It is dry.The drying 8 hours of 100 DEG C of heated-air circulation oven, obtains off-white powder chemical formula (II) 86g, yield 86%.
2, the preparation of 1H-1,2,3- triazole (chemical formula (III) compound)
Chemical formula (II) 500g is put into 3L flask, DMF 2500ml is put into, stirring is warming up to 150 DEG C, heat preservation 150
DEG C reaction 10 hours.End of reaction, cools to 80 DEG C of interior temperature, and reaction solution collects solvent by the rectifying column vacuum distillation of 30cm
DMAC, residual night be evaporated under reduced pressure again collect chemical formula (III) crude product, gained crude product pass through again rectifying column rectification under vacuum purify to obtain it is pure
Chemical formula (III) 1H-1,2,3- triazole 115g, 99% or more G/C content, yield 92%.
More than, embodiments of the present invention are illustrated.But the present invention is not limited to above embodiment.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in guarantor of the invention
Within the scope of shield.
Claims (10)
1.1H-1, the preparation method of 2,3- triazoles, which is characterized in that method includes the following steps:
Step a, using benzotriazole as raw material, potassium permanganate is oxidant, and water is solvent, is aoxidized under the conditions of alkali compounds
Ring-opening reaction adjusts acid at salt, obtains acid salt (chemical formula (II) compound)；
Step b, above-mentioned acid salt in organic solvent react by high temperature decarboxylation, and 1H-1,2,3- triazole (chemical formulas are obtained after purification
(III) compound) and raw material benzotriazole；
2. preparation method according to claim 1, which is characterized in that alkali compounds described in step a is sodium hydroxide
At least one of with potassium hydroxide.
3. preparation method according to claim 1, which is characterized in that benzotriazole described in step a, alkali compounds
Molar ratio with potassium permanganate is 1:(0.5~3): (2~6)；
Preferably, the benzotriazole and water proportion (m/v) are 1:(10~40).
4. preparation method according to claim 1, which is characterized in that reaction temperature described in step a is 40~100 DEG C,
Reaction time is 1~6 hour.
5. preparation method according to claim 1, which is characterized in that agents useful for same is hydrochloric acid or sulphur when adjusting acid in step a
Acid；Preferably, hydrochloric acid acid concentration used is 5~36%, and sulfuric acid concentration is 5~98%.
6. preparation method according to claim 1, which is characterized in that adjusting temperature when acid described in step a is 20~60
DEG C, adjusting acid pH is 2~3；
Preferably, adjusting crystallization holding temperature after acid is 0~25 DEG C.
7. preparation method according to claim 1, which is characterized in that further include in step a adjust acid at salt after, be obtained by filtration
Acid salt is dried in acid salt；
Preferably, the drying can be dry using vacuum drying or hot air circulation, and drying temperature is 70~100 DEG C, when dry
Between 6~8 hours.
8. preparation method according to claim 1, which is characterized in that organic solvent described in step b is in DMF and DMAC
At least one；
Preferably, the proportion (m/v) of the acid salt and organic solvent is 1:2~10；
Preferably, the reaction temperature of the decarboxylic reaction is 130~180 DEG C, and the reaction time is 6~18 hours.
9. preparation method according to claim 1, which is characterized in that purification described in step b uses following methods: first low
Warm vacuum distillation recovered solvent, then high-temperature pressure-reduction are distilled to recover crude product, and crude product is evaporated under reduced pressure to obtain sterling 1H- using rectifying column
1,2,3- triazole.
10. preparation method according to claim 1, which is characterized in that benzotriazole described in step b can be with recycling
It utilizes；Preferably, it is recycled using following methods: going the vinasse after purification is cold to 40~80 DEG C of interior temperature, water is added
After dissolution, recycled by reaction step a operation.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109651273A (en) * | 2019-01-30 | 2019-04-19 | 齐鲁天和惠世（乐陵）制药有限公司 | A kind of environmentally protective 1-H-1,2,3- triazole preparation method |
| CN111704583A (en) * | 2020-07-30 | 2020-09-25 | 山东泓瑞医药科技股份公司 | Preparation method of 1H-1,2, 3-triazole |
| CN113087676A (en) * | 2021-04-09 | 2021-07-09 | 山东泓瑞医药科技股份公司 | Method for preparing high-purity 1H-1,2, 3-triazole |
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| CN105330607A (en) * | 2015-11-23 | 2016-02-17 | 上海晋景化学有限公司 | Preparation method of high-purity 1H-1,2,3-triazole |
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| CN105330607A (en) * | 2015-11-23 | 2016-02-17 | 上海晋景化学有限公司 | Preparation method of high-purity 1H-1,2,3-triazole |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109651273A (en) * | 2019-01-30 | 2019-04-19 | 齐鲁天和惠世（乐陵）制药有限公司 | A kind of environmentally protective 1-H-1,2,3- triazole preparation method |
| CN109651273B (en) * | 2019-01-30 | 2021-12-31 | 山东安舜制药有限公司 | Green and environment-friendly preparation method of 1-H-1,2, 3-triazole |
| CN111704583A (en) * | 2020-07-30 | 2020-09-25 | 山东泓瑞医药科技股份公司 | Preparation method of 1H-1,2, 3-triazole |
| CN111704583B (en) * | 2020-07-30 | 2021-08-31 | 山东泓瑞医药科技股份公司 | Preparation method of 1H-1,2, 3-triazole |
| CN113087676A (en) * | 2021-04-09 | 2021-07-09 | 山东泓瑞医药科技股份公司 | Method for preparing high-purity 1H-1,2, 3-triazole |
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Application publication date: 20181228 |