A preparation method and application of 3,4,5,6-tetrachloropicolinic acid

Abstract

The present invention belongs to the technical field of organic synthesis, and specifically relates to a preparation method and application of 3,4,5,6-tetrachloropyridine carboxylic acid (compound of formula 3). The preparation method comprises the following steps: compound 1 reacts with a sulfuric acid solution to obtain compound 2; compound 2 reacts with nitrosyl sulfuric acid to obtain a diazonium salt solution; and the diazonium salt is hydrolyzed with a sulfuric acid solution to obtain a compound of formula 3. Compared with the prior art, the preparation method of the present invention has the advantages of less acid usage, less waste acid generation, low reaction temperature, low energy consumption, high product purity and yield, and is suitable for industrial production. #imgabs0#

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a preparation method and application of 3,4,5,6-tetrachloropicolinic acid. Background Art

[0002] 3,4,5,6-Tetrachloropyridine carboxylic acid is a key intermediate in the production of herbicides such as picloram, clopyralid, and aminopyralid. Its preparation method generally uses 3,4,5,6-tetrachlorocyanopyridine as a raw material and obtains the product through a hydrolysis reaction. Usually under acidic or alkaline conditions, the cyano group in 3,4,5,6-tetrachlorocyanopyridine is easily hydrolyzed into amide, but to completely convert it into carboxylic acid, a higher activation energy is required, which also brings many side reactions.

[0003]

[0004] RU2273635C2 discloses a process for preparing 3,4,5,6-tetrachloropyridinecarboxylic acid using 3,4,5,6-tetrachlorocyanopyridine as a raw material, with a reaction temperature of 120°C-140°C and a product content of 92%-97%. However, the process produces a large amount of waste acid, consumes a lot of energy, and the purity of the obtained 3,4,5,6-tetrachloropyridinecarboxylic acid is low, which has a great impact on the quality of downstream products.

[0005] There are few reports on the preparation method of 3,4,5,6-tetrachloropicolinic acid. In view of the problems existing in the existing preparation methods, it is necessary to develop a preparation method of 3,4,5,6-tetrachloropicolinic acid with less waste acid, low energy consumption and high product purity. Summary of the invention

[0006] Problem that the invention aims to solve

[0007] The present invention aims to provide a preparation method of 3,4,5,6-tetrachloropyridine carboxylic acid and application thereof. Specifically, the preparation method produces less waste acid, has low energy consumption, and has high product purity and yield, is suitable for industrial production, and can be used for the synthesis of herbicides such as picloram, clopyralid, and aminopyralid.

[0008] Solutions for solving problems

[0009] In order to solve the above problems, the present invention provides a method for preparing 3,4,5,6-tetrachloropicolinic acid (i.e., compound 3), which comprises the following steps:

[0010]

[0011] (1) Compound 1 reacts with sulfuric acid aqueous solution 1 to obtain a reaction solution containing compound 2;

[0012] (2) reacting the reaction solution containing compound 2 with nitrosyl sulfuric acid to obtain a diazonium salt solution;

[0013] (3) The diazonium salt solution reacts with the sulfuric acid aqueous solution 2 to obtain a reaction solution containing compound 3.

[0014] Preferably, in step (1), the molar ratio of sulfuric acid in the aqueous sulfuric acid solution 1 to the compound 1 is 1.5-9:1, more preferably 1.7-5.8:1, and further preferably 2.0-3.0:1;

[0015] Preferably, the molar ratio of water in the aqueous sulfuric acid solution 1 to the compound 1 in step (1) is 1-2:1, more preferably 1-1.5:1, and further preferably 1:1.

[0016] Preferably, the concentration of the aqueous sulfuric acid solution 1 in step (1) is 90%-94%.

[0017] Preferably, the heating temperature in step (1) is 50°C-110°C, more preferably 70°C-110°C, further preferably 70°C-90°C.

[0018] Preferably, the reaction time in step (1) is 1 h-4 h, more preferably 2 h-4 h.

[0019] Preferably, the molar ratio of the nitrosyl sulfuric acid in step (2) to the compound 1 in step (1) is 1-1.5:1, more preferably 1.2-1.5:1.

[0020] Preferably, the reaction temperature in step (2) is -5°C to 90°C, more preferably 20°C to 60°C, further preferably 30°C to 60°C.

[0021] Preferably, the reaction time in step (2) is 0.5h-6h.

[0022] Preferably, step (2) further comprises the step of adding urea to the diazonium salt solution.

[0023] More preferably, the molar amount of the urea is 0.02-0.03 times that of the nitrosyl sulfuric acid, and further preferably 0.026 times.

[0024] Preferably, the step of contacting the diazonium salt solution with the aqueous sulfuric acid solution 2 in step (3) is: dropwise adding the diazonium salt solution to the aqueous sulfuric acid solution 2; more preferably, the dropping time is 0.5h-2h, further preferably 1h.

[0025] Preferably, the molar ratio of sulfuric acid in the aqueous sulfuric acid solution 2 in step (3) to the compound 1 in step (1) is 1-2:1, more preferably 1.65:1.

[0026] Preferably, the concentration of the aqueous sulfuric acid solution 2 in step (3) is 65%-80%.

[0027] Preferably, the heating temperature in step (3) is 90°C-110°C, more preferably 100°C-110°C.

[0028] Preferably, the preparation method further comprises a post-treatment step after step (3).

[0029] More preferably, the post-treatment step is: cooling the reaction solution containing compound 3 to room temperature, mixing with cold water, filtering, washing with water, and drying to obtain compound 3; further, the cold water is water at 0°C-20°C, preferably water at 0°C-10°C.

[0030] In addition, the present invention also provides a method for preparing picloram as shown in Formula 4, clopyralid as shown in Formula 5 or aminopyralid as shown in Formula 6, which comprises the following steps:

[0031]

[0032] Among them, compound 3 is obtained by the above preparation method.

[0033] Effects of the Invention

[0034] The preparation method of 3,4,5,6-tetrachloropyridine carboxylic acid (i.e., compound 3) of the present invention utilizes nitrosyl sulfuric acid and tetrachloropyridine carboxamide intermediate to carry out diazotization reaction, and then further hydrolyzes to obtain the target product, and simultaneously optimizes various reaction parameters. Compared with the prior art, the preparation method of the present invention uses less acid, produces less waste acid, has low reaction temperature, low energy consumption, high product purity and yield, and is suitable for industrial production. DETAILED DESCRIPTION

[0035] In the present invention, a numerical range expressed using "a numerical value A to a numerical value B" means a range including the numerical values ​​A and B at the end points.

[0036] In the present invention, when "normal temperature" or "room temperature" is used, the temperature may be 10°C-40°C, or 10°C-30°C.

[0037] In the present invention, the cold water refers to water with a temperature of 0°C-20°C, and further refers to water with a temperature of 0°C-10°C.

[0038] In the present invention, "TCPN" is an abbreviation for 3,4,5,6-tetrachlorocyanopyridine.

[0039] In the present invention, "TCPA" is an abbreviation for 3,4,5,6-tetrachloropicolinic acid.

[0040] Nitrosyl sulfuric acid is an important diazotization raw material, mainly used in the dye and pharmaceutical industries. Nitrosyl sulfuric acid can replace the raw material sodium nitrite in the diazotization reaction, effectively increasing the stability of the diazonium salt, so that most diazotization reactions can be carried out at room temperature, without the need to be carried out below 0°C, and no inorganic salts are produced after the reaction, which can not only improve product quality and product stability, but also reduce waste acid emissions and reduce production and treatment costs.

[0041] The preparation method of 3,4,5,6-tetrachloropicolinic acid in the present invention uses nitrosyl sulfuric acid for diazotization, and the specific steps include:

[0042]

[0043] (1) Compound 1 reacts with sulfuric acid aqueous solution 1 to obtain a reaction solution containing compound 2;

[0044] (2) reacting the reaction solution containing compound 2 with nitrosyl sulfuric acid to obtain a diazonium salt solution;

[0045] (3) The diazonium salt solution reacts with the sulfuric acid aqueous solution 2 to obtain a reaction solution containing compound 3.

[0046] In some embodiments, the molar ratio of sulfuric acid in the aqueous sulfuric acid solution 1 in step (1) to the compound 1 is 1.5-9:1; in some preferred embodiments, the molar ratio is 1.7-5.8:1; in some more preferred embodiments, the molar ratio is 2.0-3.0:1.

[0047] In some embodiments, the molar ratio of water in the aqueous sulfuric acid solution 1 to the compound 1 in step (1) is 1-2:1; in some preferred embodiments, the molar ratio is 1-1.5:1, for example 1:1.

[0048] In some embodiments, the concentration of the aqueous sulfuric acid solution 1 in step (1) is 90%-94%.

[0049] In some embodiments, the heating temperature in step (1) is 50°C-110°C; in some preferred embodiments, the heating temperature in step (1) is 70°C-110°C; in some more preferred embodiments, the heating temperature is 70°C-90°C.

[0050] In some embodiments, the reaction time in step (1) is 1 h-4 h; in some preferred embodiments, the reaction time is 2 h-4 h.

[0051] In some embodiments, the molar ratio of nitrosyl sulfuric acid in step (2) to compound 1 in step (1) is 1-1.5:1; in some preferred embodiments, the molar ratio is 1.2-1.5:1.

[0052] In some embodiments, the reaction temperature in step (2) is -5°C to 90°C; in some preferred embodiments, the reaction temperature is 20°C to 60°C; in some more preferred embodiments, the reaction temperature is 30°C to 60°C.

[0053] In some embodiments, the reaction time in step (2) is 0.5h-6h.

[0054] In some embodiments, step (2) further comprises the step of adding urea to the diazonium salt solution.

[0055] In some embodiments, the molar amount of the urea is 0.02-0.03 times, for example, 0.026 times, of the nitrosyl sulfuric acid.

[0056] In some embodiments, the step of contacting the diazonium salt solution with the aqueous sulfuric acid solution 2 in step (3) is: dropwise adding the diazonium salt solution to the aqueous sulfuric acid solution 2; in some embodiments, the dropping time is 0.5h-2h, for example 1h.

[0057] In some embodiments, the molar ratio of sulfuric acid in the aqueous sulfuric acid solution 2 in step (3) to the compound 1 in step (1) is 1-2:1, for example 1.65:1.

[0058] In some embodiments, the concentration of the aqueous sulfuric acid solution 2 in step (3) is 65%-80%.

[0059] In some embodiments, the heating temperature in step (3) is 90°C-110°C; in some preferred embodiments, the heating temperature is 100°C-110°C.

[0060] In some embodiments, the preparation method further comprises a post-treatment step after step (3).

[0061] In some preferred embodiments, the post-treatment step is: cooling the reaction solution containing compound 3 to room temperature, mixing with cold water, filtering, washing with water, and drying to obtain compound 3; in some embodiments, the cold water is water at 0°C-20°C or water at 0°C-10°C.

[0062] In addition, the present invention also provides an application of the above preparation method, that is, the above preparation method can be applied to the synthesis of picloram shown in Formula 4, clopyralid shown in Formula 5 or aminopyralid shown in Formula 6, which comprises the following steps:

[0063]

[0064] Among them, compound 3 is obtained by the above preparation method.

[0065] Example

[0066] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0067] Example 1

[0068] (1) Hydrolysis of 3,4,5,6-tetrachlorocyanopyridine

[0069] To a 500 ml reaction bottle equipped with a mechanical stirrer, a thermometer, and a reflux condenser, sulfuric acid (149.9 g, mass fraction 94%, 1.44 mol) and 3,4,5,6-tetrachlorocyanopyridine (127.3 g, mass fraction 95%, 0.5 mol) were added in sequence, stirring was started, the temperature was raised to 90±2°C, and the reaction was kept warm for 2 hours to obtain the intermediate 3,4,5,6-tetrachloropyridinecarboxamide.

[0070] (2) Diazotization reaction

[0071] Slowly add nitrosyl sulfuric acid solution (190.6 g, mass fraction 40%, 0.6 mol) to the above reaction solution, keep warm at 90°C for 0.5 hour after the addition is complete to obtain a diazonium salt solution, add 0.95 g urea and stir for standby use.

[0072] (3) Hydrolysis of diazonium salt

[0073] Add sulfuric acid (101.25 g, mass fraction 80%, 0.83 mol) to a 1000 ml reaction bottle equipped with mechanical stirring, a thermometer, and a reflux condenser, heat to 100°C, add the diazonium salt solution dropwise, and keep warm for 1 hour after the addition is complete. The reaction is completed when the residual intermediate 3,4,5,6-tetrachloropyridinecarboxamide is less than 0.5% by HPLC.

[0074] (4) Post-processing

[0075] The reaction solution after the hydrolysis of diazonium salt was cooled to room temperature and then added dropwise to 300 g of cold water for dilution and filtered. The filter cake was washed twice with 100 g of water respectively and dried to obtain 3,4,5,6-tetrachloropicolinic acid with a purity of 99.11% and a yield of 93.66%.

[0076] Embodiments 2 to 4

[0077] According to the method of Example 1, the hydrolysis conditions of 3,4,5,6-tetrachlorocyanopyridine (TCPN) were adjusted, and the reaction results are listed in Table 1 below.

[0078] Table 1

[0079]

[0080] Embodiments 5 to 11

[0081] According to the method of Example 1, the diazotization reaction conditions were adjusted and the reaction results are listed in Table 2 below.

[0082] Table 2

[0083]

[0084] Embodiments 12 to 15

[0085] According to the method of Example 9, the conditions for hydrolysis of diazonium salt were adjusted, and the reaction results are listed in Table 3 below.

[0086] Table 3

[0087]

[0088] Comparative Example

[0089] Sulfuric acid (300 g, 92% by mass, 2.8 mol) and 3,4,5,6-tetrachlorocyanopyridine (100 g, 95% by mass, 0.4 mol) were added to a 500 ml reaction bottle equipped with a mechanical stirrer, a thermometer and a reflux condenser, and the mixture was heated to 125-135°C and kept for 1.5 hours. The reaction solution was cooled to 50°C and then added dropwise to 400 ml of cold water for dilution, filtered, and the filter cake was washed with 130 g of water and dried to obtain 3,4,5,6-tetrachloropyridine carboxylic acid with a purity of 94.87% and a yield of 90.59%.

Claims

1. A method for preparing 3,4,5,6-tetrachloropicolinic acid as shown in formula 3, comprising the following steps: (1) Compound 1 reacts with sulfuric acid aqueous solution 1 to obtain a reaction solution containing compound 2; (2) reacting the reaction solution containing compound 2 with nitrosyl sulfuric acid to obtain a diazonium salt solution; (3) reacting the diazonium salt solution with the sulfuric acid aqueous solution 2 to obtain a reaction solution containing compound 3; In step (1), the molar ratio of sulfuric acid in the sulfuric acid aqueous solution 1 to the compound 1 is 2.0-3.0:1; The reaction temperature in step (1) is 70°C-110°C; The molar ratio of the nitrosyl sulfuric acid in step (2) to the compound 1 in step (1) is 1.2-1.5:1; The step of contacting the diazonium salt solution with the sulfuric acid aqueous solution 2 in step (3) is: dropwise adding the diazonium salt solution into the sulfuric acid aqueous solution 2; The molar ratio of sulfuric acid in the sulfuric acid aqueous solution 2 in step (3) to the compound 1 in step (1) is 1-2:

1.

2. The preparation method according to claim 1, characterized in that: In step (1), the molar ratio of water in the aqueous sulfuric acid solution 1 to the compound 1 is 1-2:

1.

3. The preparation method according to claim 2, characterized in that: In step (1), the molar ratio of water in the aqueous sulfuric acid solution 1 to the compound 1 is 1-1.5:

1.

4. The preparation method according to claim 3, characterized in that: In step (1), the molar ratio of water in the aqueous sulfuric acid solution 1 to the compound 1 is 1:

1.

5. The preparation method according to claim 1, characterized in that: The reaction temperature in step (1) is 70°C-90°C.

6. The preparation method according to any one of claims 1 to 5, characterized in that: The reaction temperature in step (2) is -5°C to 90°C.

7. The preparation method according to claim 6, characterized in that: The reaction temperature in step (2) is 20°C to 60°C.

8. The preparation method according to claim 7, characterized in that: The reaction temperature in step (2) is 30°C to 60°C.

9. The preparation method according to claim 1, characterized in that: The dropping time in step (3) is 0.5h-2h.

10. The preparation method according to claim 9, characterized in that: The dropping time in step (3) is 1 hour.

11. The preparation method according to any one of claims 1 to 5, characterized in that: The concentration of the aqueous sulfuric acid solution 2 in step (3) is 65%-80%.

12. The preparation method according to claim 11, characterized in that: The molar ratio of sulfuric acid in the sulfuric acid aqueous solution 2 in step (3) to the compound 1 in step (1) is 1.65:

1.

13. The preparation method according to any one of claims 1 to 5, characterized in that: The reaction temperature in step (3) is 90°C-110°C.

14. The preparation method according to claim 13, characterized in that: The reaction temperature in step (3) is 100°C-110°C.

15. The preparation method according to any one of claims 1 to 5, characterized in that: The preparation method further comprises a post-treatment step after step (3).

16. The preparation method according to claim 15, characterized in that: The post-treatment steps are: cooling the reaction solution containing compound 3 to room temperature, mixing with cold water, filtering, washing with water, and drying to obtain compound 3.

17. The preparation method according to claim 16, characterized in that: The cold water is water at 0°C-20°C.

18. The preparation method according to claim 17, characterized in that: The cold water is water at 0°C-10°C.

19. A method for preparing picloram of formula 4, clopyralid of formula 5 or aminopyralid of formula 6, comprising the following steps: Wherein, compound 3 is prepared according to the preparation method according to any one of claims 1-18.

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