CN108084102A

CN108084102A - A kind of preparation method of cyromazine

Info

Publication number: CN108084102A
Application number: CN201711207000.9A
Authority: CN
Inventors: 张华刚; 万毅; 李贵欣
Original assignee: Henan Hou Yi Pharmaceutical Co Ltd
Current assignee: Henan Hou Yi Pharmaceutical Co Ltd
Priority date: 2017-11-27
Filing date: 2017-11-27
Publication date: 2018-05-29
Anticipated expiration: 2037-11-27
Also published as: CN108084102B

Abstract

A kind of preparation method of cyromazine, comprises the following steps：1) under stirring condition, at 0~5 DEG C, Cyanuric Chloride is dissolved in organic solvent, industrial ammonia is added dropwise again, is warming up to 40~45 DEG C, 5 6.5h of insulation reaction, obtain reaction solution, solvent is isolated, purified water is added into raffinate, stirs 1 1.5 h, drop to room temperature, it filters, wash, is dry, obtaining intermediate, intermediate is 2 chlorine, 4.6 diamino 1.3.5 triazines；2) at room temperature, by step 1）The intermediate of preparation is added in purified water, adds cyclopropylamine, is warming up to 90~95 DEG C, and acid binding agent is added dropwise, and adjusts pH to 7.5 8.5；Then at 98 100 DEG C, 3.5 4.5 h are reacted, decoloration, filtering obtain reaction solution；40 50 DEG C are cooled to, crystallizes 1 2h, continues to be cooled to 5~0 DEG C, is filtered, after washing, it is dry, obtain cyromazine.The preparation method of the present invention, simple for process, safe, at low cost, convenient for industrialized production, and product purity is high, impurity content is low, stability is good.

Description

A kind of preparation method of cyromazine

Technical field

The invention belongs to pesticide, veterinary drug technical fields, and in particular to a kind of preparation method of cyromazine.

Background technology

Cyromazine (Cyromazine) is a kind of compound in triazine class, and chemical name is 2- cyclopropyl amino -4,6- diaminos Base -1,3,5-triazines (N-Cyclopropyl-1,3,5-triazine-2,4,6-triamine) is adjusted with insect growth Effect, desinsection specificity feature, can be no residual hazard, safe to use, free from environmental pollution through microbial degradation, belongs to new and effective, low Poison, nitrogen heterocyclic ring insecticides, because it, which also has, kills fly effect, it is also known as cyromazines.

At present, the method for preparing cyromazine is mainly the following：

1) using Cyanuric Chloride, cyclopropylamine, industrial ammonia (20%) and liquefied ammonia as raw material, three steps synthesis cyromazine synthesized Journey is as follows：

Three steps of the technique point prepare target product, first, Cyanuric Chloride and cyclopropylamine are dissolved in chlorobenzene, in preparation Then bis- chloro-1,3,5-triazines of mesosome 2- cyclopropyl aminos -4,6- are reacted with ammonium hydroxide, prepare 2- cyclopropyl amino -4- amino -6- two Then chloro-1,3,5-triazines are reacted with liquefied ammonia in autoclave pressure, cyromazine is made.Its deficiency is, chlorobenzene boiling point used High, recycling hardly possible, strong toxicity, furthermore, liquefied ammonia and pressure vessel are used, industrial production is dangerous greatly, production cost is high.

2) using melamine and cyclopropane bromide as raw material one-step synthesis cyromazine, building-up process is as follows：

This method synthesis route is simple, and melamine raw material are easy to get, but cyclopropane bromide manufacturer is few, and valency Lattice are expensive, and domestic and international synthetic method report is less, currently without industrialized production is realized, is substituted by other methods.

3) it is solvent by raw material, acetone of Cyanuric Chloride, 2,4-, bis- amido -6- are made in industrial ammonia (25.0%) ammonification Chloro-1,3,5-triazines, then using water as solvent, base catalysis prepares cyromazine crude product, then obtains the third ammonia of ring with ethyl alcohol recrystallization Piperazine.This method deficiency is that, in the industrial production using acetone and ethyl alcohol, danger coefficient is high, especially acetone, inflammable and explosive, Very big security risk is brought to industrial production.

The content of the invention

Present invention aims at the preparation methods for providing a kind of good, simple for process, the safe cyromazine of stability.

Based on above-mentioned purpose, the present invention takes following technical scheme：

A kind of preparation method of cyromazine, comprises the following steps：

1) under stirring condition, at 0~5 DEG C, Cyanuric Chloride is dissolved in organic solvent, then industrial ammonia is added dropwise, is risen To 40~45 DEG C, insulation reaction 5-6.5h obtains reaction solution, isolates solvent temperature, and purified water is added into raffinate, stirs 1- 1.5h drops to room temperature, filters, washes, is dry, obtains intermediate, and intermediate is the chloro- 4.6- diaminostilbenes .3.5- triazines of 2-；

2) intermediate at room temperature, prepared by step 1) is added in purified water, is added cyclopropylamine, is warming up to 90~95 DEG C, acid binding agent is added dropwise, adjusts pH to 7.5-8.5；Then at 98-100 DEG C, 3.5-4.5h is reacted, decoloration, filtering must react Solution；40-50 DEG C is cooled to, crystallizes 1-2h, continues to be cooled to -5~0 DEG C, is filtered, after washing, it is dry, obtain cyromazine.

Reaction equation is as follows：

In step 1), the mass ratio of Cyanuric Chloride and 25% industrial ammonia is 1:(2.0~2.5)；Organic solvent is trichlorine The mass ratio of ethylene or 1,2- dichloroethanes, Cyanuric Chloride and organic solvent is 1：(5~6)；The matter of Cyanuric Chloride and purified water Amount is than being 1：(6~7).

In step 1), when dry, at 50~55 DEG C, 7~8h is dried in vacuo.

In step 2), the mass ratio of intermediate and cyclopropylamine is 1：(0.45~0.5).

In step 2), the mass ratio of intermediate and purified water is 1:(7~8)；Acid binding agent is water-soluble for sodium carbonate or potassium carbonate Liquid.

In step 2), during decoloration, decolorising agent is added in, at 95~100 DEG C, decolourize 0.5-1.0h.

In step 2), decolorising agent is activated carbon, and the mass ratio of intermediate and activated carbon is 1:(0.03~0.06).

In step 2), when dry, at 90~100 DEG C, 6~8h is dried in vacuo.

Compared with prior art, the invention has the advantages that：

The preparation method of the present invention, two-step reaction prepare cyromazine, simple for process, equipment investment is few, at low cost, are convenient for Industrialized production, and product purity is high, impurity content is low, stability is good；Particularly without using organic molten in product crystallization process Agent not only reduces cost, and safety coefficient is high, is effectively prevented from residual organic dissolution pollution on the environment.

Description of the drawings

Fig. 1 is the cyromazine liquid phase detection level collection of illustrative plates of embodiment 3；

Fig. 2 is the cyromazine infared spectrum of embodiment 3.

Specific embodiment

Embodiment 1

A kind of preparation method of cyromazine, comprises the following steps：

1) under stirring condition, in 0 DEG C, 30g Cyanuric Chlorides are dissolved in 155g trichloro ethylenes, the work of 60g 25% is added dropwise Industry ammonium hydroxide；It is warming up at 40 DEG C, reacts 6h, obtain reaction solution, under similary temperature conditionss, after vacuum distillation separation trichloro ethylene, add Enter 180g purified waters, when stirring 1 is small, then be down to 25 DEG C, filter, washing, at 50 DEG C, be dried in vacuo 8h, obtain among 22.5g Body, intermediate are the chloro- 4.6- diaminostilbenes .3.5- triazine dry products of 2-, and the mass yield of intermediate is 95%；

2) 165ml purified waters are added in step 1) 22.5g intermediates, adds 10.5g cyclopropylamines, be heated to 90 DEG C, aqueous sodium carbonate (aqueous solution made of 8.8g sodium carbonate is dissolved in 27ml purified waters) is added dropwise, adjusts pH=7.5- At 8.5,100 DEG C, insulation reaction 4h adds 1.0g activated carbons, and at 98 DEG C, heat preservation decoloration 0.5h, filtering must react molten Liquid is cooled to 45 DEG C, crystallizes growing the grain 2h, is then cooled to 0 DEG C, filters, washing, at 93 DEG C, is dried in vacuo 8h, obtains 22.7g Cyromazine, the mass yield of cyromazine are 88.6%, and product is white crystalline powder, HPLC contents 99.5%.

Embodiment 2

A kind of preparation method of cyromazine, comprises the following steps：

1) under stirring condition, in 5 DEG C, 20g Cyanuric Chlorides is dissolved in 120g 1, in 2- dichloroethanes, 40g is added dropwise 25% industrial ammonia；It is warming up at 45 DEG C, reacts 6h, obtain reaction solution, under similary temperature conditionss, vacuum distillation separation 1,2- bis- After chloroethanes, 120g purified waters are added in, when stirring 1 is small, then are down to 25 DEG C, filtered, washing, at 55 DEG C, be dried in vacuo 6h, obtain 14.8g intermediates, intermediate are the chloro- 4.6- diaminostilbenes .3.5- triazine dry products of 2-, and the mass yield of intermediate is 94%；

2) 120ml purified waters are added in into step 1) intermediate, add 7.2g cyclopropylamines, are heated to 95 DEG C, drop Add wet chemical (aqueous solution being configured in 28ml purified waters is dissolved in by 7.8g potassium carbonate), adjust pH=7.5-8.5, At 100 DEG C, insulation reaction 4h adds 0.7g activated carbons, and at 95 DEG C, heat preservation decoloration 0.5h, filtering obtains reaction solution, drops Temperature crystallizes 2h to 40 DEG C, is then cooled to -2 DEG C, filters, washing, at 90 DEG C, is dried in vacuo 8h, obtains 15.2g cyromazines, The mass yield of cyromazine is 90.1%, and product is white crystalline powder, HPLC contents 99.4%.

Embodiment 3

A kind of preparation method of cyromazine, comprises the following steps：

1) under stirring condition, in 3 DEG C, 30g Cyanuric Chlorides is dissolved in 160g 1, in 2- dichloroethanes, 60g is added dropwise 25% industrial ammonia；It is warming up at 42 DEG C, reacts 6h, obtain reaction solution, under similary temperature conditionss, vacuum distillation separation 1,2- bis- After chloroethanes, 180g purified waters are added in, when stirring 1 is small, then are down to 25 DEG C, filtered, washing, at 52 DEG C, be dried in vacuo 7h, obtain 22.8g intermediates (the chloro- 4.6- diaminostilbenes .3.5- triazines dry products of 2-), the mass yield of intermediate is 96%；

2) 170ml purified waters are added in into step 1) intermediate, add 10.8g cyclopropylamines, are heated to 92 DEG C, drop Add wet chemical (aqueous solution being formulated in 30ml purified waters is dissolved in by 9.0g potassium carbonate), adjust pH=7.5- At 8.5,100 DEG C, insulation reaction 4h adds 1.0g activated carbons, and at 100 DEG C, heat preservation decoloration 0.5h, filtering must react molten Liquid is cooled to 50 DEG C, crystallizes 1h；Then 0 DEG C is cooled to, is filtered, washing, at 95 DEG C, 7h is dried in vacuo, obtains 22.6g rings third Ammonia piperazine, the mass yield of cyromazine are 88.0%, and product is white crystalline powder, HPLC contents 99.88%.

Liquid chromatogram and infrared detection are carried out to the cyromazine sample of embodiment 3, test map is as illustrated in fig. 1 and 2.Liquid Phase chromatography and infrared detection method foundation《Veterinary drug national standard》First chemicals, middle powder stick 2013 editions methods of page 56 inspection It surveys, infrared detection instrument：It is prepared by Thermo, experiment：Pressing potassium bromide troche.The results are shown in Table 1 at the peak of liquid chromatogram.

1 liquid chromatogram peak result of table

Title	Retention time/min	Area/microvolt second	Highly/microvolt	Area/%
					Impurity	1.627	4797	458	0.12
Cyromazine	2.523	4106550	401272	99.88

Claims

1. a kind of preparation method of cyromazine, it is characterised in that：Comprise the following steps：

1) under stirring condition, at 0~5 DEG C, Cyanuric Chloride is dissolved in organic solvent, then industrial ammonia is added dropwise, is warming up to 40~45 DEG C, insulation reaction 5-6.5h obtains reaction solution, isolates solvent, and purified water is added into raffinate, stirs 1-1.5 h, Room temperature is dropped to, filters, wash, is dry, obtains intermediate, intermediate is the chloro- 4.6- diaminostilbenes .3.5- triazines of 2-；

2) at room temperature, by step 1）The intermediate of preparation is added in purified water, adds cyclopropylamine, is warming up to 90~95 DEG C, drop Add acid binding agent, adjust pH to 7.5-8.5；Then at 98-100 DEG C, 3.5-4.5 h are reacted, decoloration, filtering obtain reaction solution； 40-50 DEG C is cooled to, crystallizes 1-2h, continues to be cooled to -5~0 DEG C, is filtered, after washing, it is dry, obtain cyromazine.

2. the preparation method of cyromazine as described in claim 1, it is characterised in that：Step 1）In, Cyanuric Chloride and 25% work The mass ratio of industry ammonium hydroxide is 1:（2.0~2.5）；Organic solvent be trichloro ethylene or 1,2- dichloroethanes, Cyanuric Chloride with it is organic The mass ratio of solvent is 1：（5~6）；Cyanuric Chloride and the mass ratio of purified water are 1：（6~7）.

3. the preparation method of cyromazine as claimed in claim 2, it is characterised in that：Step 1）In, when dry, in 50 ~ 55 At DEG C, 7~8 h are dried in vacuo.

4. the preparation method of cyromazine as described in claim 1, it is characterised in that：Step 2）In, intermediate and cyclopropylamine Mass ratio be 1：（0.45~0. 5）.

5. the preparation method of cyromazine as claimed in claim 4, it is characterised in that：Step 2）In, intermediate and purified water Mass ratio be 1:（7~8）；Acid binding agent is sodium carbonate or wet chemical.

6. the preparation method of cyromazine as claimed in claim 5, it is characterised in that：Step 2）In, during decoloration, add in decoloration Agent, at 95~100 DEG C, decolourize 0.5-1.0h.

7. the preparation method of cyromazine according to claim 6, it is characterised in that：Step 2）In, decolorising agent is activity The mass ratio of charcoal, intermediate and activated carbon is 1:（0. 03~0.06）.

8. the preparation method of cyromazine according to claim 7, it is characterised in that：Step 2）In, when dry, in 90 At~100 DEG C, 6~8 h are dried in vacuo.