A method for preparing pyridylpyrazole acyl chloride from pyridylpyrazole aldehyde and its application

Abstract

The present application belongs to the field of organic synthesis, and particularly relates to a method for preparing pyridyl pyrazole acid chloride from pyridyl pyrazole aldehyde and application thereof, and a reaction formula is as follows: definitions of various substituents in the general formula are shown in the description. The method takes general formula (I) as a raw material, and reacts with a chlorinating reagent to obtain an acid chloride shown in general formula (II). The present application also includes application of pyridyl pyrazole acid chloride in preparation of amide compounds. The present application provides a new method for preparing pyrazole acid chloride. Pyrazole acid chloride prepared by the method can be applied to preparation of various amide compounds with application value.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for preparing pyridylpyrazole acyl chloride from pyridylpyrazole aldehyde, and its application in the preparation of amide compounds. Background Technology

[0002] Pyridylpyrazolyl chloride is an important organic synthetic intermediate that can be used to prepare amide compounds. For example, the reaction of pyridylpyrazolyl chloride with aniline can produce highly efficient and safe novel amide insecticides such as chlorantraniliprole, bromonitrile chlorantraniliprole, tetrazolium chlorantraniliprole, cyclobrombutanil, thiofenoxam, flufenoxuron diamide, or tetrachlorantraniliprole. Chinese patent ZL200810103211.2 discloses "a method for preparing 3-halo-1-(3-chloro-2-pyridyl)-1H-pyrazol-5-formyl halide".

[0003] The method for preparing acyl chloride by reacting pyrazolaldehyde with a chlorinating agent, as shown in this invention, has not been disclosed. Summary of the Invention

[0004] The purpose of this invention is to provide a new method for preparing pyridylpyrazole acyl chloride.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A method for preparing pyridylpyrazolyl chloride (II) from pyridylpyrazolaldehyde (I) is given by the following reaction formula:

[0007]

[0008] In formula I or II:

[0009] X is selected from H or Cl;

[0010] Y is selected from bromine or

[0011] The pyridylpyrazolaldehyde of general formula (I) is reacted with a chlorinating agent to prepare the pyridylpyrazolyl chloride of general formula (II).

[0012] The pyridylpyrazolaldehyde of general formula (I) is reacted with 1 to 10 moles of a chlorinating agent in a solvent, with or without a catalyst, for 0.5 to 48 hours at a temperature ranging from -10°C to the boiling point of the solvent, to prepare pyridylpyrazolyl chloride of general formula (II); wherein the molar amount of the solvent is 2 to 500 times that of the pyridylpyrazolaldehyde of general formula (I).

[0013] The chlorinating agent is selected from sulfonyl chloride, chlorine, N-chlorosuccinimide, dichlorohydantoin or trichloroisocyanuric acid, preferably sulfonyl chloride;

[0014] The catalyst is selected from azobisisobutyronitrile, azobisisoheptanenitrile, dimethyl azobisisobutyrate or benzoyl peroxide, preferably azobisisobutyronitrile or benzoyl peroxide;

[0015] The solvent is selected from dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, chlorobenzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, or dimethyl sulfoxide, preferably chlorobenzene, toluene, acetonitrile, dioxane, or hexane.

[0016] Furthermore, the molar ratio of pyridylpyrazolaldehyde of the general formula (I) to the chlorinating agent and the catalyst is 1:1 to 5:0 to 0.1, the reaction temperature is between 50°C and the boiling point of the solvent, and the reaction time is 1 to 10 hours.

[0017] The present invention also includes the application of pyridylpyrazole acyl chloride obtained by the above preparation method in the preparation of amide compounds.

[0018] The reaction of pyridylpyrazolyl chloride (II) with substituted aniline of general formula (IV) can prepare amide compounds of general formula (III).

[0019]

[0020] In formula II, formula III or formula IV,

[0021] X is selected from H or Cl;

[0022] Y is selected from bromine or

[0023] W is selected from O or S;

[0024] R1 is selected from chlorine, bromine, or methyl;

[0025] R2 is selected from chlorine or cyano groups;

[0026] R3 is selected from hydrogen or fluorine;

[0027] R4 is selected from hydrogen, methyl, isopropyl, or...

[0028] The reaction of the pyridylpyrazolyl chloride with the substituted aniline involves a condensation reaction of the pyridylpyrazolyl chloride of general formula (II) with the substituted aniline of general formula (IV) to prepare an amide compound of general formula (III). Table 1 lists the structures of some compounds of general formula (III).

[0029] Table 1. Structures of some compounds of general formula (III)

[0030]

[0031]

[0032] Advantages of this invention:

[0033] This invention provides a novel method for preparing pyrazolyl chloride. The pyrazolyl chloride obtained by the method described in this invention can be applied to the preparation of a variety of amide compounds with practical applications.

[0034] It should be clearly stated that various modifications and alterations can be made within the scope defined by the claims of this invention. Detailed Implementation

[0035] The following synthetic examples are used to further illustrate the present invention, but are not intended to limit the invention.

[0036] Example 1

[0037] Synthesis of 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-formyl chloride

[0038] (1) Synthesis of 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-carboxaldehyde

[0039]

[0040] 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-methanol (37.4 g, 116 mmol, prepared according to the method in J. Heterocyclic Chem., 23, 897 (1986)) and 200 mL of dichloromethane were added sequentially to a reaction flask. Pyridinium chlorochromate (50 g, 232 mmol) was added in portions with stirring at room temperature. The mixture was refluxed for 4 hours after the addition was complete. After the reaction was complete, 20 g of a white solid was obtained by column chromatography, with a yield of 53.8%, a normalized purity of 95% by HPLC, and a melting point of 107-109 °C.

[0041] 1 H NMR (600MHz, CDCl3): 9.79 (s, 1H), 8.45 (d, 1H), 7.96 (d, 1H), 7.10 (s, 1H).

[0042] (2) Synthesis of 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-carboxyl chloride

[0043]

[0044] 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-carboxaldehyde (3.46 g, 10 mmol), 50 mL of chlorobenzene, and azobisisobutyronitrile (16 mg, 0.1 mmol) were added sequentially to a reaction flask. Sulfonyl chloride (3.37 g, 25 mmol) was slowly added dropwise with stirring at room temperature. After the addition was complete, the reaction was carried out at 80 °C for 8 hours. The solvent was evaporated under reduced pressure to obtain 3.5 g of red oil, with a yield of 99%.

[0045] 1 H NMR (600MHz, CDCl3): 8.44 (d, 1H), 7.94 (d, 1H), 7.29 (s, 1H).

[0046] Application Example 1

[0047] Synthesis of 3-bromo-N-(2,4-dichloro-6-(methanoyl)phenyl)-1-(3,5-dichloro-2-pyridyl)-1H-pyrazole-5-carboxamide (the insecticide tetrachlorantraniliprole)

[0048]

[0049] To a reaction flask, 2-amino-3-5-dichlorobenzoylmethylamine (2.1 g, 9.5 mmol) and 20 mL of acetonitrile were added sequentially. 1-(3,5-dichloro-2-pyridyl)-3-bromo-1-H-pyrazole-5-carboxyl chloride (3.5 g, 9.9 mmol) obtained in Example 1 was dissolved in 20 mL of acetonitrile and slowly added dropwise to the above reaction solution. After stirring at room temperature for 10 minutes, the mixture was slowly heated to reflux and refluxed for 2.5 hours. Column chromatography purification yielded 5 g of a white solid, with a yield of 93.5%, a normalized purity of 95.6% by HPLC, and a melting point of 188-190 °C.

[0050] 1 H NMR (600MHz, CDCl3): 9.98(s,1H),8.39(d,1H),7.84(d,1H),7.31(s,1H),7.19(d,1H),7.11(d,1H),6.47(d,1H),2.86(d,3H).

[0051] Other amide insecticides of general formula (III) can also be prepared using the above preparation method.

Claims

1. A process for the preparation of a pyridyl pyrazole acid chloride from a pyridyl pyrazole aldehyde, characterized by: ； To a reaction flask was added 1-(3,5-dichloro-2-pyridinyl)-3-bromo-1-H-pyrazole-5- carboxaldehyde 3.46 g, 50 mL chlorobenzene, azobisisobutyronitrile 16 mg, and sulfuryl chloride 3.37 g was added dropwise with stirring at room temperature. The reaction was heated at 80°C for 8 hours.

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