CN102250017A - Synthesizing method of dicyclanil - Google Patents
Synthesizing method of dicyclanil Download PDFInfo
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- CN102250017A CN102250017A CN2011101596920A CN201110159692A CN102250017A CN 102250017 A CN102250017 A CN 102250017A CN 2011101596920 A CN2011101596920 A CN 2011101596920A CN 201110159692 A CN201110159692 A CN 201110159692A CN 102250017 A CN102250017 A CN 102250017A
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Abstract
The invention relates to a synthesizing method of dicyclanil, and especially relates to a chemical synthesizing method of dicyclanil which serves as an insect growth modulator. According to the invention, sodium ethoxide is adopted as a catalyst; dithio cyanodithioiminocarbonate and malononitrile are subject to a reaction, such that 2-cyano-3-cyanamide-3-methylthio acrylonitrile is obtained; 2-cyano-3-cyanamide-3-methylthio acrylonitrile is subject to an amination reaction with ammonia water, such that an amino substance is obtained; the amino substance is subject to a cyclization reaction in an aqueous solution of acid, such that a cyclized substance is obtained; the cyclized substance is subject to a reaction with rolicypram, and ethanol is removed through distillation; water is added to the material, and the material is cooled and filtered, such that dicyclanil is obtained. The synthesizing method provided by the invention has advantages of mild condition, simple technology, and reasonable technology. With the method, dicyclanil product can be obtained conveniently with a relatively high yield. The total yield of the reaction is 38%.
Description
Technical field
The present invention relates to the chemical synthesis process of a kind of novel insect growth regulator(IGR) Dicyclanil (dicyclanil).
Background technology
Dicyclanil (dicyclanil) has another name called the third worm pyridine, the chinesization formal name used at school is called 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile, English chemical name is 4,6-Diamino-2-(cyclopropylamino)-5-pyrimidinecarbonitrile is a kind of moulting hormone analogue-pyrimidines.It is a kind ofly to form the novel insect growth regulator(IGR) cause effect by the interference insect epidermis, emphasizes pest population is controlled and regulated, simultaneously effective pest control optionally.Dipteral insect and flea there are the height kill activity, can stop larvae development pupa worm and the adult of various flies, mosquito and flea.In addition, this medicine is difficult for tolerance, and residual value is low, has very high Ecological Society benefit, meets the requirement and the target of current environment friendly agricultural.
The method of at present synthetic Dicyclanil mainly is to be catalyzer with the sodium ethylate, with cyanamide base dithiocarbonic acid dimethyl ester and propane dinitrile reaction, obtains 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide; Ring-closure reaction takes place and generates 2-chloro-4-amino-6-methylthiopyrimidine-5-nitrile in 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide in aqueous hydrochloric acid; 2-chloro-4-amino-6-methylthiopyrimidine-5-nitrile and cyclopropylamine reaction generate 2-cyclopropylamino-4-amino-6-methylthiopyrimidine-5-nitrile; Under high-temperature and high-pressure conditions, obtain Dicyclanil at last with ammoniacal liquor generation ammoxidation.Prepare the process of Dicyclanil by this method, product yield is low; The ammoxidation condition is a High Temperature High Pressure, is difficult for realizing in generative process, and has certain potential safety hazard.
Summary of the invention
The object of the invention provides the chemical synthesis process of a kind of Dicyclanil (dicyclanil), to overcome the long or demanding inconvenience of synthesis condition of synthetic route that existing industrial production Dicyclanil is adopted.
The present invention includes following steps:
1) under 20～50 ℃ of temperature condition, be catalyzer with the sodium ethylate, with cyanamide base dithiocarbonic acid dimethyl ester and propane dinitrile reaction, after washing with alcohol, obtain 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide;
2) under 100～150 ℃ of temperature condition, with 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and ammoniacal liquor generation ammoxidation, reduce to room temperature after, solid phase is answered in negate, obtains amino substance after washing with water;
3) under 20～40 ℃ of temperature condition, ring-closure reaction is taken place in amino substance in aqueous acid, after filtration,, obtain cyclocomplex with water and sodium bicarbonate washing leaching cake;
4) under 50～90 ℃ of temperature condition, with cyclocomplex and cyclopropylamine reaction, distill out ethanol then, add entry again, the cooling after-filtration obtains Dicyclanil.
Synthetic method mild condition of the present invention, technology is simple, reasonable, can obtain the Dicyclanil product easily, keeps relative higher product yield simultaneously, and overall yield of reaction is 38%～40%.
In the step 1) of the present invention, the molar ratio of cyanamide base dithiocarbonic acid dimethyl ester and propane dinitrile is 1.0 ︰ 1.0～1.2, and the reaction times is 6～10h.
In the described step 1), the volumetric molar concentration of described sodium ethylate is 11～15%.
In the described step 1), the temperature condition of described reaction is 30 ℃.
Described step 2) in, the mass ratio that feeds intake of 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and ammoniacal liquor is 1.0 ︰ 5.0～10.0, and the reaction times is 5～10h.
In the described step 3), described acid is that mass concentration is 30～36% aqueous hydrochloric acid, and the mass ratio that feeds intake of described amino substance and hydrochloric acid soln is 1.0 ︰ 5.0～8.0, and the reaction times is 10～20h.
In the described step 4), the molar ratio of described cyclocomplex and cyclopropylamine is 1 ︰ 1.1～1.8, and the reaction times is 5～9h.
In the described step 4), the temperature condition of described reaction is 60～81 ℃.
In the described step 4), earlier described cyclocomplex is dissolved in the ethanol, drops into cyclopropylamine again.
Embodiment
Embodiment 1
1, the preparation of step 1:2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide:
Reaction formula:
In the 500ml reaction flask, add 240g ethanol as solvent, open agitator, cool to 20 ℃, add 30.5g sodium ethylate (volumetric molar concentration is 12%), after being stirred to it and dissolving fully, add the 21.8g propane dinitrile, stir 30min, add 43.8g cyanamide base dithiocarbonic acid dimethyl ester again, under 30 ℃ of conditions, react 5～8h.
With reacting liquid filtering, use 50ml washing with alcohol 2 times, obtain 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide.
2, the preparation of step 2:2-cyano group-3-cyanogen amino-3-aminoacrylonitrile:
Reaction formula:
In the 500ml autoclave, add 33.7g2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and 150g ammoniacal liquor, elevated temperature to 100 ℃, the reaction times is 10h, cool to room temperature, reacting liquid filtering with 50ml water washing 2 times, obtains 2-cyano group-3-cyanogen amino-3-aminoacrylonitrile.
3, step 3:2-chloro-4, the preparation of 6-di-amino-pyrimidine-5-nitrile:
Reaction formula
In the 500ml reaction flask, add 23g 2-cyano group-3-cyanogen amino-3-aminoacrylonitrile and 75ml water, open agitator, cool to 20 ℃, dropping 160ml mass percent concentration is 36% technical hydrochloric acid, at 20 ℃ of insulation reaction 10～15h, reacting liquid filtering, with 50ml water washing filter cake 3 times, use 50ml saturated sodium bicarbonate washing leaching cake more once, obtain 2-chloro-4,6-di-amino-pyrimidine-5-nitrile.
4, step 4:4, the preparation of 6-diamino-2-cyclopropylamino pyrimidine-5-nitrile:
Reaction formula
Add 32g2-chloro-4 in the 500ml reaction flask, 6-di-amino-pyrimidine-5-nitrile and 200ml ethanol are warmed up to 80 ℃, drip the 18.5g cyclopropylamine, 2-chloro-4 in this example, and the mol ratio of 6-di-amino-pyrimidine-5-nitrile, cyclopropylamine is 1:1.69.
Behind 80 ℃ of insulation reaction 7h, change water distilling apparatus into, distill out 150ml ethanol, and then add 200ml water, cool to 5 ℃,, use 50ml water washing filter cake 2 times, obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 22g, product yield 39% reacting liquid filtering.
Embodiment 2
In this example, step 1: in the 500ml reaction flask, add 240g ethanol, open agitator, cool to 20 ℃, add the 25g sodium ethylate, be stirred to it and dissolve fully, add the 21.8g propane dinitrile, stir 30min, add 43.8g cyanamide base dithiocarbonic acid dimethyl ester, under 30 ℃ of conditions, react 5～8h.
With reacting liquid filtering, use 50ml washing with alcohol 2 times, obtain 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide.
Other steps are identical with embodiment 1, can obtain 4 equally, 6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 15g, product yield 26%.
Embodiment 3
In this example, step 1: in the 500ml reaction flask, add 240g ethanol, start stirring, cool to 20 ℃, add the 30.5g sodium ethylate, be stirred to it and dissolve fully, add the 19.2g propane dinitrile, stir 30min, add 43.8g cyanamide base dithiocarbonic acid dimethyl ester, under 30 ℃ of conditions, react 5～8h.
With reacting liquid filtering, use 50ml washing with alcohol 2 times, obtain 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide.
Other steps are identical with embodiment 1, can obtain 4 equally, 6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 13g, product yield 22.7%.
Embodiment 4
In example, step 1,3 identical with embodiment 1 with 4.
Different is: in the step 2: add 33.7g2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and 150g ammoniacal liquor in the 500ml autoclave, elevated temperature to 150 ℃, reaction times is 5h, cool to room temperature, reacting liquid filtering, with 50ml water washing 2 times, obtain 2-cyano group-3-cyanogen amino-3-aminoacrylonitrile.
Obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 10g, product yield 17.5%.
Embodiment 5
In this example, step 1,2 identical with embodiment 1 with 4.
In step 3, in the 1L reaction flask, add 23g 2-cyano group-3-cyanogen amino-3-aminoacrylonitrile and 150ml water, open agitator, cool to 20 ℃, dropping 160ml mass percent concentration is 20% hydrochloric acid, at 20 ℃ of insulation reaction 10～15h, reacting liquid filtering is used 50ml water washing filter cake 3 times, uses 50ml saturated sodium bicarbonate washing leaching cake more once, obtain 2-chloro-4,6-di-amino-pyrimidine-5-nitrile.
Obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 18g, product yield 31%.
Embodiment 6
In this example, step 1,2 identical with embodiment 1 with 4.
In the step 3, in the 1L reaction flask, add 23g2-cyano group-3-cyanogen amino-3-aminoacrylonitrile and 50ml water, open agitator, cool to 20 ℃, dropping 160ml mass percent concentration is 36% hydrochloric acid, at 20 ℃ of insulation reaction 10～15h, reacting liquid filtering is used 50ml water washing filter cake 3 times, uses 50ml saturated sodium bicarbonate washing leaching cake more once, obtain 2-chloro-4,6-di-amino-pyrimidine-5-nitrile.
Obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 20g, product yield 35%.
Embodiment 7
In this example, step 1,2 identical with embodiment 1 with 3.
In the step 4, in the 500ml reaction flask, add 32g2-chloro-4,6-di-amino-pyrimidine-5-nitrile and 200ml ethanol, be warmed up to 80 ℃, drip the 12g cyclopropylamine, 2-chloro-4, the mol ratio of 6-di-amino-pyrimidine-5-nitrile and cyclopropylamine is 1:1.102, changes water distilling apparatus into behind 80 ℃ of insulation reaction 7h, distill out 150ml ethanol, and then add 200ml water, cool to 5 ℃, with reacting liquid filtering, with 50ml water washing filter cake 2 times, obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 16g, product yield 28%.
Embodiment 8
In this example, step 1,2 identical with embodiment 1 with 3.
In the step 4, in the 500ml reaction flask, add 32g2-chloro-4,6-di-amino-pyrimidine-5-nitrile and 250ml ethanol, be warmed up to 50～70 ℃, drip the 18.4g cyclopropylamine, control 0.5h is added dropwise to complete 2-chloro-4, the mol ratio of 6-di-amino-pyrimidine-5-nitrile, cyclopropylamine is 1:1.69, behind 80 ℃ of insulation reaction 7h, change water distilling apparatus into, distill out 150ml ethanol, and then add 200ml water, cool to 5 ℃, with reacting liquid filtering, use 50ml water washing filter cake 2 times, obtain 4,6-diamino-2-cyclopropylamino pyrimidine-5-nitrile 22.5g, product yield 39.2%.
Claims (9)
1. a kind of synthetic method of Dicyclanil is characterized in that may further comprise the steps:
1) under 20～50 ℃ of temperature condition, be catalyzer with the sodium ethylate, with cyanamide base dithiocarbonic acid dimethyl ester and propane dinitrile reaction, after washing with alcohol, obtain 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide;
2) under 100～150 ℃ of temperature condition, with 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and ammoniacal liquor generation ammoxidation, reduce to room temperature after, solid phase is answered in negate, obtains amino substance after washing with water;
3) under 20～40 ℃ of temperature condition, ring-closure reaction is taken place in amino substance in aqueous acid, after filtration,, obtain cyclocomplex with water and sodium bicarbonate washing leaching cake;
4) under 50～90 ℃ of temperature condition, with cyclocomplex and cyclopropylamine reaction, distill out ethanol then, add entry again, the cooling after-filtration obtains Dicyclanil.
2. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: in the described step 1), the molar ratio of cyanamide base dithiocarbonic acid dimethyl ester and propane dinitrile is 1.0 ︰ 1.0～1.2, and the reaction times is 6～10h.
3. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: in the described step 1), the volumetric molar concentration of sodium ethylate is 11～15%.
4. according to a kind of synthetic method of claim 1 or 3 described Dicyclanils, it is characterized in that: in the described step 1), the temperature condition of described reaction is 30 ℃.
5. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: described step 2), the mass ratio that feeds intake of 2-cyano group-3-cyanogen amino-3-methylthio group vinyl cyanide and ammoniacal liquor is 1.0 ︰ 5.0～10.0, and the reaction times is 5～10h.
6. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: in the described step 3), described acid is that mass concentration is 30～36% aqueous hydrochloric acid, and the mass ratio that feeds intake of described amino substance and aqueous hydrochloric acid is 1.0 ︰ 5.0～8.0, and the reaction times is 10～20h.
7. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: in the described step 4), the molar ratio of described cyclocomplex and cyclopropylamine is 1 ︰ 1.1～1.8, and the reaction times is 5～9h.
8. according to a kind of synthetic method of the described Dicyclanil of claim 1, it is characterized in that: in the described step 4), the temperature condition of described reaction is 60～81 ℃.
9. according to a kind of method of claim 1 or 7 or 8 described Dicyclanils, it is characterized in that: in the described step 4), earlier described cyclocomplex is dissolved in the ethanol, drops into cyclopropylamine again.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102379288A (en) * | 2011-10-26 | 2012-03-21 | 广东中迅农科股份有限公司 | Pesticide composition containing dicyclanil and spinosad |
| CN103880759A (en) * | 2014-01-28 | 2014-06-25 | 东南大学 | Dicyclanil drug crystal form I and preparation method thereof |
| CN104649982A (en) * | 2015-02-26 | 2015-05-27 | 齐鲁晟华制药有限公司 | Preparation method of dicyclanil |
| CN111018792A (en) * | 2019-12-23 | 2020-04-17 | 常州齐晖药业有限公司 | Synthesis method of dicyclanil |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87103168A (en) * | 1986-04-30 | 1987-12-16 | 希巴-盖格公司 | The pyrimidines that replaces |
| CN1128024A (en) * | 1993-07-26 | 1996-07-31 | 希巴-盖吉股份公司 | Process for the preparation of substituted 4,6-diamino-5-cyanopyrimidines |
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2011
- 2011-06-15 CN CN2011101596920A patent/CN102250017A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87103168A (en) * | 1986-04-30 | 1987-12-16 | 希巴-盖格公司 | The pyrimidines that replaces |
| CN1128024A (en) * | 1993-07-26 | 1996-07-31 | 希巴-盖吉股份公司 | Process for the preparation of substituted 4,6-diamino-5-cyanopyrimidines |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102379288A (en) * | 2011-10-26 | 2012-03-21 | 广东中迅农科股份有限公司 | Pesticide composition containing dicyclanil and spinosad |
| CN103880759A (en) * | 2014-01-28 | 2014-06-25 | 东南大学 | Dicyclanil drug crystal form I and preparation method thereof |
| CN103880759B (en) * | 2014-01-28 | 2016-04-20 | 东南大学 | A kind of Dicyclanil drug crystal forms I and preparation method thereof |
| CN104649982A (en) * | 2015-02-26 | 2015-05-27 | 齐鲁晟华制药有限公司 | Preparation method of dicyclanil |
| CN104649982B (en) * | 2015-02-26 | 2016-12-07 | 齐鲁晟华制药有限公司 | A kind of preparation method of Dicyclanil |
| CN111018792A (en) * | 2019-12-23 | 2020-04-17 | 常州齐晖药业有限公司 | Synthesis method of dicyclanil |
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Application publication date: 20111123 |