CN105330607B

CN105330607B - A kind of preparation method of high purity 1 H -1,2,3- triazole

Info

Publication number: CN105330607B
Application number: CN201510818074.0A
Authority: CN
Inventors: 陈学军
Original assignee: Shanghai Jinjing Chemical Co Ltd
Current assignee: Shanghai Jinjing Chemical Co Ltd
Priority date: 2015-11-23
Filing date: 2015-11-23
Publication date: 2019-01-25
Anticipated expiration: 2035-11-23
Also published as: CN105330607A

Abstract

The present invention relates to a kind of high purity 1 Hs -1,2, the preparation method of 3- triazole, comprising the following steps: step 1, using benzotriazole as raw material, potassium permanganate is oxidant, water is solvent, under alkaline condition, high purity 1 H -1,2 is obtained by oxidative cleavage, purification drying, 3- triazole -4,5- dicarboxylic acids；1H-1 obtained in step 2, step 1,2,3- triazole -4,5- dicarboxylic acids are in N, the effect of dinethylformamide solvent catalyst neutralisation is lower to carry out decarboxylic reaction, obtains target product high purity 1 H -1,2 by purification, 3- triazole, wherein catalyst is the mixture of quinoline, pyridine or both.The present invention makees catalyst with pyridine or quinoline in step 2 and traditional oxide with copper powder or copper is replaced to make catalyst, and good reaction selectivity, high income, product purity are high and stability is more preferable.

Description

A kind of preparation method of high purity 1 H -1,2,3- triazole

Technical field

The invention belongs to fine chemistry industry preparation technical fields, and in particular to a kind of system of high purity 1 H-1,2,3-triazole Preparation Method.

Background technique

1H-1,2,3- triazoles are the important intermediates of beta-lactamase inhibitor Tazobactam Sodium, it can also be used to other medicines The synthesis of object, in addition the 1H-1 of high-purity, 2,3- triazoles are also used on the cleaning agent of electronic product.

At present it is known that 1H-1, there are mainly four types of the synthetic methods of 2,3- triazoles:

(1) such as the glyoxal that JP0641092 is generated with 2,2- dichloro acetaldehyde and hydroxyl hydrochloride reaction, monoxime hydrazone or oxime acylhydrazone are Intermediate synthesis；

(2) as during JP05140121 reacts the sulphonyl hydrazone of generation with unifor with 2,2- dichloro acetaldehyde or acylhydrazone is Mesosome synthesis；

(3) as A.1.2.3-Triazole [J] .Ann.chim (Rome) 1,968 58 1507-1509. are direct by Catino It is prepared from hydrazoic acid and alkynes or alkene reaction；

(4) such as J.Berdt chem.Scand 1,959 13 (5) 888-891 and West China pharmaceutical journal 200116 (4): 273- 275, pass through 1,2,3- triazole -4- carboxylic acid or 1, the preparation of 2,3- triazole -4,5- dicarboxylic acids high temperature decarboxylations.The above synthesis For route all directly or indirectly using azide as raw material, such compound not only has severe toxicity, more there is strong explosivity, thus work It skill operational hazards and is difficult to control, final products purity is not high, and wastewater flow rate is big, thus industrialized production difficult to realize.

The patent of invention of Patent No. 200710069580.X specifically discloses a kind of high purity 1 H -1,2,3- triazole Preparation method, by aoxidizing open loop, using acidification, obtains 1H-1 using benzotriazole and potassium permanganate as raw material, and 2,3- tri- Nitrogen azoles -4,5- dicarboxyl acid crude, after the crude product refining under the action of oxide of catalyst copper powder or copper, in 100 DEG C~180 Vacuum decarboxylation at DEG C obtains 1H-1, the crude oil of 2,3- triazoles.The oxide of this preparation method copper powder or copper makees catalyst Reaction selectivity is poor, purity difference, thus product stability is also poor, and aoxidizes, mass production energy consumption low with high-temperature retorting decarboxylation yield Height, production capacity is small, thus produces this height.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a kind of high purity 1 H -1,2,3- The preparation method of triazole makees catalyst with pyridine or quinoline and traditional oxide with copper powder or copper is replaced to make catalyst, does When decarboxylic reaction, good reaction selectivity, high income, product purity are high and stability is more preferable.

In order to solve the above technical problems, a kind of technical solution that the present invention takes is:

A kind of preparation method of high purity 1 H-1,2,3-triazole, specific synthetic route are as follows:

1, the preparation of 1H-1,2,3- triazole -4,5- dicarboxylic acids (b)

2, the preparation of 1H-1,2,3- triazole (c)

The specific steps of preparation method are as follows:

Step 1, using benzotriazole as raw material, potassium permanganate is oxidant, and water is solvent, under alkaline condition, is passed through Oxidative cleavage, purification drying obtain high purity 1 H -1,2,3- triazole -4,5- dicarboxylic acids；

1H-1,2,3- triazole -4,5- dicarboxylic acids is in N,N-dimethylformamide solvent obtained in step 2, step 1 With decarboxylic reaction is carried out under catalyst action, by purification obtain target product high purity 1 H-1,2,3-triazole, wherein urge Agent is the mixture of quinoline, pyridine or both.

Preferably, the reaction temperature in step 1 is 20 DEG C -100 DEG C, reaction time 1.0-5.0h, benzotriazole: hydrogen Sodium oxide molybdena or potassium hydroxide: the molar ratio of potassium permanganate be 1:0.5-3:5-10, m (benzotriazole): V (H₂O)=1:15- 40。

Preferably, it is purified in step 1 using following methods: after completion of the reaction, being filtered to remove manganese dioxide, solution is used 30-50% dioxygen water bleeding removes residual manganese dioxide, cooling；Adjusting pH with concentrated hydrochloric acid or the concentrated sulfuric acid again is 1.5-3.0；Again It is cooled to 0-10 DEG C of crystallization 2.0h, centrifuge dripping, with a small amount of washing.

Preferably, the drying in step 1 is in 60-80 DEG C of temperature range using vacuum drying or forced air drying.

Preferably, the reaction temperature of step 2 is 100 DEG C -165 DEG C, reaction time 2.0-8.0h, and compound (1H-1,2,3- Triazole -4,5- dicarboxylic acids): molar ratio=1:0.01-0.1 of catalyst, m (1H-1,2,3- triazole -4,5- dicarboxylic acids): V (N,N-dimethylformamide)=1:5-30.

Preferably, purified in step 2 using following methods: cold filtration after completion of the reaction first passes through short rectifying pillar, subtracts Receipts n,N-Dimethylformamide is pushed back, then crude product is recovered under reduced pressure, crude product is finally obtained into high purity 1 H -1 by rectifying column, 2,3- triazole.

Due to the use of above technical scheme, the invention has the following advantages over the prior art:

1, benzotriazole, i.e. BTA, cheap and easy to get, especially oxidation reaction finishes under alkaline condition, and filtering, which finishes, to remove Manganese dioxide (manganese dioxide content >=99% can be used for other reactions oxidation), filtrate is with 20~30% dioxygen water bleedings, product Compound 1H-1,2,3- triazole -4,5- dicarboxylic acids are not needed to refine and be decolourized, and product colour is very white, and purity is very high, more special Other is that oxidation reaction yield is very high under alkaline condition；

2, in first step reaction, filtrate needs to be concentrated under reduced pressure a large amount of water before, and energy consumption is very high, and we utilize in alkalinity Under the conditions of oxidation reaction, allow product 1H-1,2,3- triazole -4,5- dicarboxylic acids do not need to be concentrated, can make to be fully crystallized precipitation, Greatly reduce production cost；

3, mother liquor alkali tune PH=6-7, and may be reused, thus environmental protection, basic non-wastewater discharge reduce environment Pollution；

4, making catalyst with pyridine or quinoline in second step reaction replaces traditional oxide with copper powder or copper to be catalyzed Agent, good reaction selectivity, high income, product purity are high and stability is more preferable.

Specific embodiment

The present invention is described in further details below in conjunction with specific embodiment.It should be understood that these embodiments are for saying The bright basic principles, principal features and advantages of the present invention, and the present invention is not by the scope limitation of following embodiment.It is adopted in embodiment Implementation condition can do further adjustment according to specific requirement, and the implementation condition being not specified is usually the item in routine experiment Part.

Embodiment 1

The preparation of compound (b) 1H-1,2,3- triazole -4,5- dicarboxylic acids:

Water 3600L is added in the stainless steel cauldron of 6000L, adds 400 kilograms of benzotriazole, piece alkali 380 Kilogram, 40 DEG C are warming up to, then be slowly added into 2800 kilograms of potassium permanganate, about 2.0h controls temperature at 40-80 DEG C, finishes heat preservation 2h, TLC tracking reaction, are filtered to remove manganese dioxide after the reaction was completed, and solution 30-50% dioxygen water bleeding removes residual Manganese dioxide, filtrate are cooled back to 35 DEG C, with concentrated hydrochloric acid tune PH 2.5, are cooled back to 5 DEG C of crystallization 2.0h, centrifuge dripping, with less 506.6 kilograms, HPLC 99.5% must be expected, molar yield 96.0% in 70 DEG C of vacuum drying 5.0h by measuring water washing filter cake.

The preparation of compound (c) 1H-1,2,3- triazole:

In the glass lined reaction kettle of 5000L, n,N-Dimethylformamide 3800L is added, 300 kilograms of compound (b) are stirred It mixes, then 1L pyridine is added dropwise, be warming up to 120 DEG C, react 4.0h, HPLC tracking is cooled to room temperature after completion of the reaction, filters, and filtrate is logical N,N-Dimethylformamide is recovered under reduced pressure in too short rectifying pillar, the short long 3m of rectifying pillar, and raffinate depressurizes again collects compound (c) Crude product, compound (c) crude product is collected into colorless and transparent fraction by rectifying column decompression, obtains compound (c) finished product 131.4 Kilogram, product purity 99.6% (GC), moisture content 0.2%, molar yield 95.2%.

Embodiment 2:

The preparation of compound (b) 1H-1,2,3- triazole -4,5- dicarboxylic acids:

The mother liquor of embodiment 1 is added in 6000L stainless steel cauldron, adjusts PH in 6-7 with 30% lye, adds 400 kilograms of benzotriazole, 300 kilograms of potassium hydroxide, are warming up to 45 DEG C, then are slowly added into 2800 kilograms of potassium permanganate, about 3.0-4.0h, temperature control finish heat preservation 4h at 40~80 DEG C, and TLC tracks end of reaction, is filtered to remove manganese dioxide, and solution is used 30-50% dioxygen water bleeding removes residual manganese dioxide, and filtrate is cooled back to 30 DEG C, adjusts PH 1.5 with 40% sulfuric acid, then cold But it to 0 DEG C of crystallization 2.0h, filters, a small amount of water washing filter cake must expect 509.3. kilograms, HPLC in 80 DEG C of forced air drying 4.0h 99.2%, molar yield 96.2%.

The preparation of compound (c) 1H-1,2,3- triazole:

In the glass lined reaction kettle of 5000L, n,N-Dimethylformamide 3800L is added, 300 kilograms of compound (b) are stirred It mixes, then 2L quinoline is added dropwise, be warming up to 120 DEG C, react 4.0h, HPLC tracking is cooled to room temperature after completion of the reaction, filters, and filtrate is logical N,N-Dimethylformamide is recovered under reduced pressure in too short rectifying pillar, the short long 3m of rectifying pillar, and raffinate depressurizes again collects compound (c) Crude product, compound (c) crude product is collected into colorless and transparent fraction by rectifying column decompression, obtains compound (c) finished product 131.4 Kilogram, product purity 99.6% (GC), moisture content 0.2%, molar yield 95.2%.

Preparation method of the present invention simplifies technological operation step, shorten reaction time, significantly reduction production cost, subtracts Lack environmental pollution, improves the stability of product quality and product.

The present invention is described in detail above, the explanation of embodiment be merely used to help understand method of the invention and Its core concept, its object is to allow the personage for being familiar with this field technology to can understand the content of the present invention and implement it accordingly, and The protection scope that the present invention cannot be limited in this way.Any equivalent change or modification in accordance with the spirit of the invention should all be contained Lid is within protection scope of the present invention.

Claims

1. a kind of 1H-1, the preparation method of 2,3- triazoles, it is characterised in that: the following steps are included:

Step 1, using benzotriazole as raw material, potassium permanganate is oxidant, and water is solvent, under alkaline condition, passes through oxidation Ring-opening reaction, purification drying obtain 1H-1,2,3- triazole -4,5- dicarboxylic acids；

1H-1,2,3- triazole -4,5- dicarboxylic acids obtained in step 2, step 1 in N,N-dimethylformamide solvent and is urged Agent effect is lower to carry out decarboxylic reaction, obtains target product 1H-1 by purification, 2,3- triazoles, wherein the catalyst is The mixture of quinoline, pyridine or both.

2. 1H-1 according to claim 1, the preparation method of 2,3- triazoles, it is characterised in that: the step 1, with benzene And triazole is raw material, potassium permanganate is oxidant, and water is solvent, in the presence of sodium hydroxide or potassium hydroxide, passes through oxidation Ring-opening reaction, purification drying obtain 1H-1,2,3- triazole -4,5- dicarboxylic acids, and the reaction temperature in the step 1 is 20 DEG C - 100 DEG C, reaction time 1.0-5.0h, benzotriazole: sodium hydroxide or potassium hydroxide: the molar ratio of potassium permanganate is 1: 0.5-3:5-10, m (benzotriazole): V (H₂O)=1:15-40.

3. 1H-1 according to claim 1, the preparation method of 2,3- triazoles, it is characterised in that: used in the step 1 Following methods purification: after completion of the reaction, it is filtered to remove manganese dioxide, solution 30-50% dioxygen water bleeding removes residual two Manganese oxide, it is cooling；Adjusting pH with concentrated hydrochloric acid or the concentrated sulfuric acid again is 1.5-3.0；It is cooled back to 0-10 DEG C of crystallization 2.0h, centrifugal drying It is dry, with a small amount of washing.

4. 1H-1 according to claim 1, the preparation method of 2,3- triazoles, it is characterised in that: the baking in the step 1 It does to use vacuum drying or forced air drying in 60-80 DEG C of temperature range.

5. 1H-1 according to claim 1, the preparation method of 2,3- triazoles, it is characterised in that: the reaction of the step 2 Temperature is 100 DEG C -165 DEG C, reaction time 2.0-8.0h, compound 1H-1,2,3- triazole -4,5- dicarboxylic acids and catalyst Molar ratio is 1:0.01-0.1, m (1H-1,2,3- triazole -4,5- dicarboxylic acids): V (n,N-Dimethylformamide)=1:5-30.

6. 1H-1 according to claim 1, the preparation method of 2,3- triazoles, it is characterised in that: used in the step 2 Following methods purification: cold filtration after completion of the reaction first passes through short rectifying pillar, n,N-Dimethylformamide is recovered under reduced pressure, then Crude product is recovered under reduced pressure, crude product is finally obtained into 1H-1,2,3- triazoles by rectifying column.