Synthesis method of intermediate N-hydroxy-2-methylaniline of pyraclostrobin

Abstract

The invention relates to the technical field of synthesis of intermediates, in particular to a synthesis method of an intermediate N-hydroxy-2-methylaniline of pyraclostrobin, which comprises the following steps: by using a bidentate NN type cobalt complex as a catalyst and an ammonia borane compound and an alcohol solvent as hydrogen donors, reacting for 12-18 hours at normal temperature and normal pressure in an inert gas protection atmosphere, thereby obtaining the intermediate N-hydroxy-2-methylaniline of pyraclostrobin. And adding a catalyst to obtain the N-hydroxy-2-methylaniline. The synthesis method disclosed by the invention has the advantages of good selectivity, high yield and high process safety coefficient.

Description

Technical Field

[0001] The invention relates to the technical field of intermediate synthesis, and in particular to a method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin. Background Art

[0002] Pyraclostrobin, also known as pyraclostrobin, has the following chemical formula:

[0003] It is a broad-spectrum, systemic methoxy acrylic acid fungicide, belonging to the pyrazole class of compounds. It is widely used in agriculture, mainly for the prevention and treatment of fungal diseases on various crops, such as diseases of wheat, soybeans, corn, cotton, grapes, etc. It was first synthesized by BASF in 1993 and used as a fungicide. It is currently the most widely used broad-spectrum fungicide in China and has great market prospects.

[0004] As disclosed in patents such as WO1996 / 001256, US5869517, EPO0624155B1, US8816096B2, WO2012038392, W02012120029, CN102399190, CN104211641, CN105218450, CN104592117, CN106117143, CN105949125, etc., there are currently two main synthesis processes for pyraclostrobin:

[0005] Route (I)

[0006]

[0007] Although the two methods have different synthetic pathways, the key steps are both the selective reduction of nitrobenzene to synthesize hydroxyaniline. In Route I, due to the strong electron-withdrawing effect of the ortho-nitro group, the methyl group is more likely to undergo substitution reactions and to generate polybrominated byproducts. Therefore, Route II is more suitable than Route I. In these reported patents, nitrobenzene is synthesized into hydroxyaniline through a catalytic hydrogenation reaction with hydrogen. On the one hand, catalytic hydrogenation needs to be carried out through pressure equipment, which has high requirements for equipment and operation. On the other hand, the reduction process is often difficult to control, and impurities such as oxidized azobenzene, hydrogenated azobenzene and aniline will be generated, resulting in a lower yield. Summary of the invention

[0008] The invention solves the problems in the related art and provides a method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, by using a bidentate NN-type cobalt complex as a catalyst and borane and an alcohol solvent as a hydrogen donor. The method has the advantages of good selectivity, high yield and high process safety factor.

[0009] In order to solve the above technical problems, the present invention is achieved through the following technical scheme: a method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, using a bidentate NN-type cobalt complex as a catalyst, an ammonia borane compound and an alcohol solvent as a hydrogen donor, reacting for 12-18 hours under normal temperature and pressure and an inert gas protection atmosphere to obtain N-hydroxy-2-methylaniline.

[0010] As a preferred embodiment, the bidentate NN type cobalt complex is one of 4,4'-di-tert-butyl-2,2'-bipyridyl cobalt chloride, 2,2'-bipyridyl cobalt chloride, o-phenanthroline cobalt chloride, 1,2-bis(diphenylphosphine)ethane cobalt chloride, and bis(2-diphenylphosphinophenyl)ether cobalt chloride.

[0011] As a preferred embodiment, the molar ratio of the catalyst to the raw material 2-nitrotoluene is (1-2):100.

[0012] As a preferred embodiment, the ammonia borane compound is one of ammonia borane, dimethylamino borane and diethylamino borane.

[0013] As a preferred embodiment, the molar ratio of the ammonia borane compound to 2-nitrotoluene is (2-3):1.

[0014] As a preferred embodiment, the alcohol solvent is at least one of methanol or ethanol.

[0015] Compared with the prior art, the present invention has the following beneficial effects: the present invention uses a bidentate NN-type cobalt complex as a catalyst, and ammonia borane and an alcohol solvent as a hydrogen donor, and has good selectivity and high yield compared with the traditional synthesis method; in addition, compared with the traditional catalytic hydrogenation reaction to synthesize N-hydroxy-2-methylaniline, no additional pressure equipment is required, and the process safety factor is higher. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is the nuclear magnetic hydrogen spectrum of N-hydroxy-2-methylaniline of the present invention;

[0017] Figure 2 It is the nuclear magnetic carbon spectrum of N-hydroxy-2-methylaniline of the present invention. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] Example 1

[0020] A method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, comprises the following specific steps: under nitrogen protection, dissolving 2.0 mg of 4,4'-di-tert-butyl-2,2'-bipyridyl cobalt chloride, 61.6 mg of 2-nitrotoluene and 30.9 mg of ammonia borane in 1 mL of methanol, reacting at room temperature for 12 hours under nitrogen protection, removing the solvent under reduced pressure after the reaction, and performing silica gel column chromatography to obtain the N-hydroxy-2-methylaniline product, with a separation yield of 95% and a purity of 98.5%. The reaction formula is as follows:

[0021]

[0022] like Figure 1 and 2 As shown, the obtained product was characterized by H NMR and C NMR. 1 HNMR(400MHz,DMSO-d6,ppm):8.19(s,1H),7.90(s,1H),7.07-7.06(m,2H),6.97-6.95(m,1H),6.70-6.66(m,1H),2.06(s,3H); 13 C NMR (100MHz, DMSO-d6, ppm): 150.0, 129.8, 126.6, 122.2, 119.4, 112.4, 17.2.

[0023] Example 2

[0024] The difference from Example 1 is that the catalyst is bipyridyl cobalt chloride, the dosage is 1.4 mg, and the yield of N-hydroxy-2-methylaniline product is 84%.

[0025] Example 3

[0026] The difference from Example 1 is that the catalyst is o-phenanthroline cobalt chloride, the dosage is 1.7 mg, and the yield of N-hydroxy-2-methylaniline product is 28%.

[0027] Example 4

[0028] The difference from Example 1 is that the catalyst is 1,2-bis(diphenylphosphino)ethanecobalt chloride, the dosage is 2.7 mg, and the yield of N-hydroxy-2-methylaniline product is 75%.

[0029] Example 5

[0030] The difference from Example 1 is that the catalyst is bis(2-diphenylphosphinophenyl)ether cobalt chloride, the dosage is 3.4 mg, and the yield of N-hydroxy-2-methylaniline product is 16%.

[0031] Example 6

[0032] The difference from Example 1 is that the ammonia borane compound is NH(CH3)2BH3, the dosage is 57 mg, and the yield of N-hydroxy-2-methylaniline product is 58%.

[0033] Example 7

[0034] The difference from Example 1 is that the ammonia borane compound is NH(CH2CH3)2BH3, the dosage is 85 mg, and the yield of the N-hydroxy-2-methylaniline product is 63%.

[0035] Example 8

[0036] The difference from Example 1 is that ethanol is used as the solvent in an amount of 1 mL, and the yield of the N-hydroxy-2-methylaniline product is 88%.

[0037] Example 9

[0038] A method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, comprises the following specific steps: under nitrogen protection, dissolving 58.1 mg of 4,4'-di-tert-butyl-2,2'-bipyridyl cobalt chloride, 1.0 g of 2-nitrotoluene and 676.7 mg of ammonia borane in 16 mL of methanol, reacting at room temperature for 18 hours under nitrogen protection, removing the solvent under reduced pressure after the reaction is completed, and performing silica gel column chromatography to obtain the N-hydroxy-2-methylaniline product, with a separation yield of 92% and a purity of 99%.

[0039] The above are preferred implementation modes of the present invention. Those skilled in the art to which the present invention belongs can also change and modify the above implementation modes. Therefore, the present invention is not limited to the above specific implementation modes. Any obvious improvements, substitutions or modifications made by those skilled in the art on the basis of the present invention belong to the protection scope of the present invention.

Claims

1. A method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, characterized in that: A bidentate NN-type cobalt complex is used as a catalyst, an ammonia borane compound and an alcohol solvent are used as hydrogen donors, and the reaction is carried out at room temperature and pressure in an inert gas protection atmosphere for 12-18 hours to obtain N-hydroxy-2-methylaniline.

2. The method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, according to claim 1, characterized in that: The bidentate NN type cobalt complex is one of 4,4'-di-tert-butyl-2,2'-bipyridyl cobalt chloride, 2,2'-bipyridyl cobalt chloride, o-phenanthroline cobalt chloride, 1,2-bis(diphenylphosphine)ethane cobalt chloride and bis(2-diphenylphosphinophenyl)ether cobalt chloride.

3. The method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, according to claim 2, characterized in that: The molar ratio of the catalyst to the raw material 2-nitrotoluene is (1-2):

100.

4. The method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, according to claim 1, characterized in that: The ammonia borane compound is one of ammonia borane, dimethylamino borane and diethylamino borane.

5. The method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, according to claim 4, characterized in that: The molar ratio of the ammonia borane compound to 2-nitrotoluene is (2-3):

1.

6. The method for synthesizing N-hydroxy-2-methylaniline, an intermediate of pyraclostrobin, according to claim 1, characterized in that: The alcohol solvent is at least one of methanol or ethanol.

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