Method for preparing azoxystrobin

Abstract

The present invention provides a process for preparing azoxystrobin, which is performed by reacting 2-cyanophenol or a salt thereof with a compound represented by formula I under the catalysis of a trimethylamine catalyst to obtain the azoxystrobin represented by formula II, which allows the yield of the product azoxystrobin to reach 98% or more, the yield of separated product to reach 95% or more and the post-processing to be simple. The trimethylamine catalyst can be recycled and reused in synthesizing the target product azoxystrobin, which not only reduces the cost but also reduces the total nitrogen and COD in wastewater. The advantages regarding of cost and environmental protection of the method according to the present invention are significant and thus the method is suitable for industrial production.

Claims

1. A preparation method for azoxystrobin, wherein the preparation method comprises reacting 2-cyanophenol or a salt thereof with a compound represented by formula I under the catalysis of a trimethylamine catalyst to obtain azoxystrobin represented by formula II: ##STR00004## wherein the reaction is performed in the presence of an acid acceptor.

2. The preparation method according to claim 1, wherein the trimethylamine catalyst is trimethylamine, a trimethylamine solution, or a salt of trimethylamine.

3. The preparation method according to claim 2, wherein the trimethylamine solution is any one selected from the group consisting of a trimethylamine solution in water, a trimethylamine solution in methanol, a trimethylamine solution in ethanol, a trimethylamine solution in toluene and a trimethylamine hydrochloride solution, or a combination of at least two selected therefrom.

4. The preparation method according to claim 2, wherein the salt of trimethylamine is any one selected from the group consisting of trimethylamine hydrochloride, trimethylamine sulfate and trimethylamine methanesulfonate, or a combination of at least two selected therefrom.

5. The preparation method according to claim 1, wherein the reaction is performed in a non-polar inert solvent.

6. The preparation method according to claim 5, wherein the non-polar inert solvent is toluene, xylene or butyl acetate.

7. The preparation method according to claim 1, wherein the salt of 2-cyanophenol is potassium 2-cyanophenoxide.

8. The preparation method according to claim 1, wherein the acid acceptor is potassium carbonate and/or sodium carbonate.

9. The preparation method according to claim 1, wherein the amount of the trimethylamine catalyst is 0.5-15 mol % of the compound represented by formula I.

10. The preparation method according to claim 1, wherein the molar ratio of 2-cyanophenol or a salt thereof to the compound represented by formula I is 1:1 to 1.5 to 1.

11. The preparation method according to claim 1, wherein the molar ratio of the acid acceptor to the compound represented by formula I is 0.6:1 to 2:1.

12. The preparation method according to claim 1, wherein the reaction is performed at a temperature of 50-120 C.

13. The preparation method according to claim 1, wherein the reaction is performed for 5-20 h.

14. The preparation method according to claim 1, wherein the preparation method comprises: reacting 2-cyanophenol or a salt thereof with a compound represented by formula I in a non-polar inert solvent at 50-120 C. under the catalysis of a trimethylamine catalyst to obtain the azoxystrobin represented by formula II, in which the amount of the trimethylamine catalyst is 0.5-15 mol % of the compound represented by formula I and the molar ratio of 2-cyanophenol or a salt thereof to the compound represented by the formula I is 1:1 to 1.5:1.

15. The preparation method according to claim 1, wherein the trimethylamine catalyst is recycled trimethylamine.

16. The preparation method according to claim 1 comprising the further step of recycling the trimethylamine catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The technical solutions of the present invention are further described below by using specific embodiments. It should be understood by those skilled in the art that the examples are merely to help understand the present invention and should not be construed as specific limitations to the present invention.

(2) The contents of the raw materials or products are represented by mass percentages in the following examples and the abbreviations of the raw materials involved refer to the following chemical names:

(3) DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene

(4) DMAP: 4-dimethylaminopyridine.

Example 1

(5) In this example, a trimethylamine solution in water with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(6) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 3.58 g (0.02 mol, having a concentration of 33%) of trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 253.59 g of a toluene solution of azoxystrobin, with a content of 40.21% (w/w), which is 98.9% of the theoretical value.

(7) The toluene solution of azoxystrobin described above was distilled under reduced pressure. Distillation was stopped when the temperature in the reaction flask was 110 C., and then the temperature was reduced to 70 C. 70 g of methanol and 5 g of water were added and stirred. The temperature was held at 70-80 C. for 1 h, and then slowly reduced to 0-5 C., holding for 2 h. The mixture was filtered, washed twice with cold methanol (10 g2) and dried to obtain 98.72 g of azoxystrobin as a white solid with a content of 98.21% and a yield of 96.14%.

(8) The resulting product was characterized by NMR, the structure was characterized as follow: .sup.1H NMR (400 MHz, CDCl.sub.3): 3.61 (s, 3H, OCH.sub.3), 3.77 (s, 3H, OCH.sub.3), 6.44 (s, 1H, Py-H), 7.24-7.45 (m, 6H, ArH), 7.51 (s, 1H, CCH), 7.67-7.74 (m, 2H, ArH), 8.42 (s, 1H, Py-H).

Example 2

(9) In this example, a trimethylamine solution in water with the amount of 15 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(10) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 8.96 g (0.0375 mol, having a concentration of 33%) of trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 4 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 247.34 g of a toluene solution of azoxystrobin, with a content of 41.21% (w/w), which is 98.94% of the theoretical value.

(11) The post-processing was performed as Example 1 to provide 98.92 g of azoxystrobin with a content of 98.43% and a yield of 96.55%.

Example 3

(12) In this example, a trimethylamine solution in water with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst and potassium 2-cyanophenoxide was used as a raw material to synthesize azoxystrobin. The specific preparation method was:

(13) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 43.67 g (0.275 mol, 99%) of potassium 2-cyanophenoxide, 8.63 g (0.025 mol, having a concentration of 40%) of potassium carbonate solution in water and 3.58 g (0.02 mol, having a concentration of 33%) of trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 10 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 247.16 g of a toluene solution of azoxystrobin, with a content of 41.24% (w/w), which is 98.94% of the theoretical value.

(14) The post-processing was performed as Example 1 to provide 98.68 g of azoxystrobin with a content of 98.23% and a yield of 96.12%.

Example 4

(15) In this example, a trimethylamine solution in methanol with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(16) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 3.58 g (0.02 mol, having a concentration of 33%) of trimethylamine solution in methanol were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 249.90 g of a toluene solution of azoxystrobin, with a content of 40.97% (w/w), which is 98.5% of the theoretical value.

(17) The post-processing was performed as Example 1 to provide 98.49 g of azoxystrobin with a content of 98.16% and a yield of 95.87%.

Example 5

(18) In this example, a trimethylamine hydrochloride with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(19) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 1.95 g (0.02 mol, having a content of 98%) of trimethylamine hydrochloride were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 250.61 g of a toluene solution of azoxystrobin, with a content of 41.02% (w/w), which is 98.10% of the theoretical value.

(20) The post-processing was performed as Example 1 to provide 97.90 g of azoxystrobin with a content of 98.25% and a yield of 95.38%.

Example 6

(21) In this example, a trimethylamine solution in water with the amount of 0.5 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(22) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 0.22 g (0.00125 mol, having a concentration of 33%) of trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 18 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 252.74 g of a toluene solution of azoxystrobin, with a content of 41.87% (w/w), which is 95.30% of the theoretical value.

(23) The post-processing was performed as Example 1 to provide 95.13 g of azoxystrobin with a content of 98.11% and a yield of 92.55%.

Example 7

(24) In this example, a trimethylamine solution in water with the amount of 0.5 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy] phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(25) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 45.12 g (0.375 mol, 99%) of 2-cyanophenol, 20.91 g (0.15 mol, 99%) of potassium carbonate and 0.22 g (0.00125 mol, having a concentration of 33%) of trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 50 C. and incubated for 20 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 261.07 g of a toluene solution of azoxystrobin, with a content of 40.1% (w/w), 96.33% of the theoretical value.

(26) The post-processing was performed as Example 1 to provide 97.2 g of azoxystrobin with a content of 98.1% and a yield of 94.55%.

Example 8

(27) In this example, a trimethylamine solution in methanol with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy] phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(28) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 30.08 g (0.25 mol, 99%) of 2-cyanophenol, 34.85 g (0.25 mol, 99%) of potassium carbonate and 3.58 g (0.02 mol, having a concentration of 33%) of trimethylamine solution in methanol were added sequentially into a 500 mL reaction flask, stirred, heated to 120 C. and incubated for 5 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 252.29 g of a toluene solution of azoxystrobin, with a content of 40.83% (w/w), which is 97.9% of the theoretical value.

(29) The post-processing was performed as Example 1 to provide 97.45 g of azoxystrobin with a content of 98.2% and a yield of 94.89%.

Example 9

(30) In this example, a trimethylamine solution in methanol with the amount of 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate was used as a catalyst to synthesize azoxystrobin. The specific preparation method was:

(31) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 39.11 g (0.325 mol, 99%) of 2-cyanophenol, 69.7 g (0.5 mol, 99%) of potassium carbonate and 3.58 g (0.02 mol, having a concentration of 33%) of trimethylamine solution in methanol were added sequentially into a 500 mL reaction flask, stirred, heated to 100 C. and incubated for 12 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 244.19 g of a toluene solution of azoxystrobin, with a content of 41.8% (w/w), which is 98.8% of the theoretical value.

(32) The post-processing was performed as Example 1 to provide 98.31 g of azoxystrobin with a content of 98.23% and a yield of 95.76%.

Comparative Example 1

(33) Azoxystrobin was synthesized in the absence of any catalyst in this example. The specific preparation method was as following:

(34) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol and 27.88 g (0.2 mol, 99%) of potassium carbonate were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. The reaction was monitored and detected, showing that the conversion rate of the raw material (methyl (E)-2-[2[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate) was only about 10%. 100 g of water was added. Layers were separated to obtain 245.38 g of a toluene solution of azoxystrobin. The content was measured to be 3.32% (w/w), which is 8.08% of the theoretical value. No further crystallization process was performed due to the low content.

(35) It can be seen from Examples 1 to 9 that good yields can be achieved by using a trimethylamine solution in water and in methanol and a trimethylamine hydrochloride.

(36) The yield of the toluene solution obtained by the reaction can reach about 95%, even if the amount of catalyst was reduced to 0.5 mol %. The catalytic effect of trimethylamine was significant. A little of product was generated with a yield lower than 10% of the theoretical value in Comparative Example 1, which has the same reaction conditions as Example 5 except that the Comparative Example 1 was performed in the absence of trimethylamine catalyst.

Examples 1, 4 and 5 and Comparative Examples 2 to 7

(37) The catalysts used, the molar ratio of the catalyst to the reactant (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxypropenoate and the temperature of the reactions in Examples 1, 4 and 5 and Comparative Examples 2 to 7 were shown in the following Table 1. Other conditions during the preparation process were the same as Example 1. The yields of the toluene solution of azoxystrobin obtained were shown in the following Table 1.

(38) TABLE-US-00001 TABLE 1 The yields The The of the amount temperature toluene of the of the solution of catalyst reaction azoxystrobin The names of the catalyst (mol %) ( C.) (%) Comparative N,N,N,N-tetramethylethylenediamine 8 80 7.5 Example 2 Comparative N,N-dimethylpiperazine 8 80 18.6 Example 3 Comparative DMAP 8 80 2.0 Example 4 Comparative N,N-dimethylisopropylamine 8 80 8.8 Example 5 Comparative DBU 8 80 8.2 Example 6 Comparative triethylamine 8 80 5.3 Example 7 Example 1 trimethylamine solution in water 8 80 98.9 Example 4 trimethylamine solution in methanol 8 80 98.5 Example 5 trimethylamine hydrochloride 8 80 98.1

(39) It can be seen from Table 1 that the yield of the product azoxystrobin was extremely decreased when replacing the trimethylamine catalyst with a similar basic substance such as triethylamine, DBU, N,N-dimethylisopropylamine, DMAP, N,N-dimethylpiperazine and N,N,N,N-tetramethylethylenediamine under the same conditions. Therefore, the trimethylamine catalyst was specific for the reaction of the present invention and cannot be replaced by other similar basic substances.

Example 10

(40) The trimethylamine catalyst was recycled in this example with the method as following:

(41) (A) Trimethylamine Absorption Test with Water

(42) Approximate 5 kg of water phase, which was obtained according to Example 1, was collected. The water phase was combined and heated to 50 C. with stirring, and then purged with nitrogen to obtain a gas mixture. The gas mixture was subjected to a three-stage absorption with 200 g of water to obtain 239.55 g of a trimethylamine solution in water with a content of 16.13% and a recycling rate of 95.22%.

(43) (B) Trimethylamine Absorption Test with Methanol

(44) Approximate 5 kg of water phase, which was obtained according to Example 1, was collected. The water phase was combined and heated to 50 C. with stirring, and then purged with nitrogen to obtain a gas mixture. The gas mixture was subjected to a three-stage absorption with 200 g of methanol to obtain 238.54 g of a trimethylamine solution in water with a content of 15.84% and a recycling rate of 93.11%.

(45) (C) Trimethylamine Absorption Test with 15% of Dilute Hydrochloric Acid

(46) Trimethylamine was absorbed by using 200 g of hydrochloric acid solution having a concentration of 15% through a three-stage absorption apparatus according to the procedure of Example 8 to obtain 238.87 g of a trimethylamine solution in dilute hydrochloric acid, with a content of 26.51% and a recycling rate of 96.53%.

Example 11

(47) In this example, a recycled trimethylamine solution in water (having a content of 16.13%) was used as a catalyst to synthesize azoxystrobin, the amount of which is 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate. The specific method was:

(48) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 7.33 g (0.02 mol, having a concentration of 16.13%) of the recycled trimethylamine solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 253.02 g of a toluene solution of azoxystrobin, with a content of 40.58% (w/w), which is 98.22% of the theoretical value.

(49) The post-processing was performed as Example 1 to provide 97.94 g of azoxystrobin with a content of 98.18% and a yield of 95.35%.

Example 12

(50) In this example, a recycled trimethylamine solution in methanol (having a content of 15.84%) was used as a catalyst to synthesize azoxystrobin, the amount of which is 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate. The specific method was:

(51) 150 g of toluene, 80.99 g (0.25 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 7.46 g (0.02 mol, having a concentration of 15.84%) of the recycled trimethylamine solution in methanol were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 248.38 g of a toluene solution of azoxystrobin, with a content of 41.34% (w/w), which is 98.15% of the theoretical value.

(52) The post-processing was performed as Example 1 to provide 98.34 g of azoxystrobin with a content of 98.31% and a yield of 95.87%.

Example 13

(53) In this example, a recycled trimethylamine hydrochloride solution in water (having a content of 26.51%) was used as a catalyst to synthesize azoxystrobin, the amount of which is 8 mol % of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate. The specific method was:

(54) 150 g of toluene, 80.99 g (0.02 mol, 99%) of methyl (E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, 33.09 g (0.275 mol, 99%) of 2-cyanophenol, 27.88 g (0.2 mol, 99%) of potassium carbonate and 7.21 g (0.02 mol, having a concentration of 26.51%) of the recycled trimethylamine hydrochloride solution in water were added sequentially into a 500 mL reaction flask, stirred, heated to 80 C. and incubated for 8 h. When the reaction was completed, 100 g of water was added. Layers were separated to obtain 246.64 g of a toluene solution of azoxystrobin, with a content of 41.66% (w/w), which is 98.15% of the theoretical value.

(55) The post-processing was performed as Example 1 to provide 98.14 g of azoxystrobin with a content of 98.28% and a yield of 95.64%.

(56) It can be seen from Examples 11 to 13 that the trimethylamine was recyclable, and the recycled trimethylamine can also be normally used for the synthesis of azoxystrobin, which also has good catalytic efficiency and leading to a good product yield.

(57) The present invention provides a process for preparing azoxystrobin, which is performed by using 0.5 to 15 mol % of trimethylamine catalyst for catalyzing, allowing 2-cyanophenol or a salt thereof to be reacted with a compound represented by formula I in a non-polar inert solvent to obtain azoxystrobin and allowing the yield of the product azoxystrobin to reach 98% or more, the yield of separated product to reach 95% or more and the post-processing to be simple. The trimethylamine catalyst can be recycled and reused in synthesizing the target product azoxystrobin, which not only reduces the cost but also reduces the total nitrogen and COD in wastewater. The advantages regarding of cost and environmental protection in the method according to the present invention are significant and thus the method is suitable for industrial production.

(58) Detailed methods of the present invention are illustrated by the examples described above in the present invention. However, the present invention is not limited to the detailed methods described above, i.e. it does not mean that the present invention must rely on the detailed methods described above to be implemented. Those skilled in the art should understand that any modifications to the present invention, equivalent replacements of each raw material of the present invention, additions of auxiliary components, selections of specific methods and the like fall within the protection scope and the disclosure scope of the present invention.