Preparation method of aniline compound

Abstract

The invention belongs to the field of organic synthesis, and particularly provides a preparation method of an aniline compound shown as a formula I. According to the method, a compound shown as a formula III reacts with inorganic ammonium salt, and the compound shown as the formula I is obtained. According to the technical scheme, ammonia gas can be prevented from being used as a nitrogen source, the safety of the preparation method is greatly improved, a high-yield product can be obtained, and the yield can reach 97% or above. In addition, according to the technical scheme, reaction conditions are mild, feeding is accurate, operation is easy and convenient, and the method is more suitable for industrial safety production. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis. Specifically, the present invention provides a method for preparing aniline compounds. Background Art

[0002] Aniline compounds of formula I are a very important class of organic compounds. Its representative trifluralin of formula I-a, as a low-toxic herbicide, is widely used for controlling weeds in cereals and non-cultivated land. Trifluralin controls sensitive weeds by inhibiting the growth and development of newly germinated weed seeds, and is used to control various gramineous weeds and broad-leaved weeds, such as annual bluegrass, barnyard grass, crabgrass, green foxtail, redroot amaranth, chickweed, goosegrass, purslane, etc.

[0003]

[0004] Trifluralin is prepared from 2,4-dichlorobenzotrifluoride through two-step nitration, one-step dipropylamination and one-step ammoniation reaction. Among them, for the last step of ammoniation reaction, ammonia gas is used as the nitrogen source in the prior art.

[0005] US3617252A discloses a method for synthesizing trifluralin using ammonia dissolved in ethanol as the nitrogen source. This method is carried out in a pressure-sealed system and reacts at 100 °C for 68 hours. Since a large amount of by-product of 2,4-dinitro-6-trifluoromethyl-1,3-benzenediamine of formula II is generated in this reaction, it seriously affects the product purity, resulting in a very complex and cumbersome product purification operation process, low product yield and large amount of three wastes, and is not suitable for industrial production.

[0006]

[0007] Molla M. Endeshaw et al. reported a method for preparing trifluralin using 1,4-dioxane as the solvent (Bioorganic & Medicinal Chemistry Letters 20(2010)5179–5183). This method uses 3 equivalents of ammonia gas and reacts in a sealed manner at 100 °C, and the yield is about 75%.

[0008] CN101723839B discloses a method for preparing trifluralin using DMF, DMSO, etc. as the solvent. This method reacts by introducing ammonia gas at 70 - 140 °C, and the yield is about 85%.

[0009] There are many problems with the reaction using ammonia as the nitrogen source: Ammonia itself has a strong pungent odor; it causes great damage to mucous membranes and skin. Frequent contact can cause conjunctivitis, bronchitis, pneumonia or pulmonary edema, and contact dermatitis may occur; it can damage internal organs such as the liver and kidneys; it can cause occupational asthma; it is corrosive, and direct contact of the skin and eyes with its liquid can cause burns (Xu Juan et al., Chinese Journal of Organic Chemistry, 2013, 33(11): 2435 - 2439). And those skilled in the art know well that the reaction using ammonia often needs to be carried out in a pressure-sealed system, which easily leads to explosion safety hazards. In addition, ammonia gas is not easy to accurately measure, and it is often used excessively, which easily leads to the generation of by-products, such as the generation of the by-product of 2,4-dinitro-6-(trifluoromethyl)-1,3-phenylenediamine of formula II described in US3617252A.

[0010] Thus, there are still many deficiencies in the preparation of aniline compounds such as trifluralin in the prior art. Summary of the Invention

[0011] The purpose of the present invention is to provide a method for preparing an aniline compound of formula I to overcome the deficiencies in the prior art. The specific method is as follows:

[0012] A method for preparing an aniline compound of formula I, characterized in that a compound of formula III is reacted with an inorganic ammonium salt to obtain a compound of formula I, and the reaction formula is as shown below:

[0013]

[0014] Wherein,

[0015] X is a halogen, preferably Cl or Br;

[0016] R f is a polyfluoroalkyl group, preferably a polyfluoro C1-C8 alkyl group, more preferably a perfluoro C1-C8 alkyl group; more preferably one of CF3, C2F5 or n-C3F7;

[0017] R is one of NR 1 R 2 , CN, COR 3 or COOR 4 wherein, R 1 , R 2 , R 3 and R 4 are each independently selected as an alkyl group, preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group;

[0018] n is 1, 2 or 3, and m is 1, 2 or 3.

[0019] Preferably, the inorganic ammonium salt is at least one of ammonium carbonate, ammonium bicarbonate or ammonium carbamate.

[0020] Preferably, the molar ratio of the inorganic ammonium salt to the compound of formula III is (1 - 3):1, more preferably (1 - 2):1.

[0021] Preferably, the reaction solvent is selected from at least one of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), hexamethylphosphoric triamide (HMPA) or sulfolane.

[0022] Preferably, the reaction temperature is 30 - 100 °C, more preferably 50 - 70 °C.

[0023] Preferably, the reaction time is 1 - 12 hours, more preferably 3 - 5 hours.

[0024] Preferably, the preparation method is characterized in that the compound of formula III-b is reacted with an inorganic ammonium salt to obtain the compound of formula I-b, and the reaction formula is as shown below:

[0025]

[0026] Wherein, X, R f , R 1 , R 2 are defined the same as the above definitions; preferably, the R 1 , R 2 are each independently n-C3H7 or i-C3H7.

[0027] The beneficial effects of the present invention are as follows:

[0028] The present invention provides a preparation method of an aniline-based compound of formula I. Compared with the preparation methods of the compound of formula I disclosed in the prior art, the technical solution of the present invention can avoid using ammonia gas as a nitrogen source, greatly improve the safety of the preparation method, and can obtain a product with a high yield, and the yield can reach more than 97%. In addition, the technical solution of the present invention has mild reaction conditions, accurate feeding, simple operation, and is more suitable for industrial safe production. Detailed Embodiments

[0029] In order to better understand the technical solution of the present invention, the technical solution of the present invention will be further described below in conjunction with specific embodiments. The embodiments are only for helping to understand the present invention and should not be regarded as specific limitations on the present invention.

[0030] Example 1 Preparation of 3-chloro-2,6-dinitro-N3,N3-dipropyl-4-(trifluoromethyl)aniline (Compound of Formula III-a) (refer to the preparation method disclosed in CN101723839B).

[0031]

[0032] Add 100 g of 2,4-dichloro-3,5-dinitrobenzotrifluoride and water into a 500 mL reaction flask, stir, heat up to 40 °C, and simultaneously add dropwise 33 g of di-n-propylamine and 230 g of 20% potassium carbonate aqueous solution. The addition is completed in 25 minutes. After the addition, keep the reaction at 80 °C for 1 hour, separate the layers, and wash with water to obtain 119 g of product, with a yield of 98.2%.

[0033] Example 2-9 Preparation of 2,4-dinitro-N3,N3-dipropyl-6-trifluoromethyl-1,3-diamine (Compound of Formula I-a).

[0034]

[0035] Add 50 g of 3-chloro-2,6-dinitro-N3,N3-dipropyl-4-(trifluoromethyl)aniline and 200 g of solvent into a 500 mL reaction flask, add inorganic ammonium salt, and then heat up. Keep the reaction for 3 - 5 hours, stop stirring, cool, filter, wash the solid with water, and dry to obtain the product of 2,4-dinitro-N3,N3-dipropyl-6-trifluoromethyl-1,3-diamine.

[0036] The inorganic ammonium salts used, their molar equivalents relative to starting material III-a, reaction solvents, reaction temperatures, and reaction times are shown in Table 1 below:

[0037] Table 1

[0038]

[0039]

[0040] Comparative Example 1 Preparation of 2,4-dinitro-N3,N3-dipropyl-6-trifluoromethyl-1,3-diamine (Compound of Formula I-a).

[0041] Add 10 g of 3-chloro-2,6-dinitro-N3,N3-dipropyl-4-(trifluoromethyl)aniline and 40 g of DMF into a 100 mL reaction flask, add 3.4 g of ammonium formate, heat up to 70 °C, and keep the reaction for 12 hours. High performance liquid chromatography detection shows no target product.

Claims

1. A method for preparing an aniline-based compound of formula (I), characterized in that, React the compound of formula (III) with an inorganic ammonium salt to obtain the compound of formula (I), and the reaction formula is shown as follows: Wherein, X is a halogen, preferably Cl or Br; R f is a polyfluoroalkyl group, preferably a polyfluoro C1-C8 alkyl group, more preferably a perfluoro C1-C8 alkyl group; more preferably one of CF3, C2F5 or n-C3F7; R is NR 1 R 2 , CN, COR 3 or COOR 4 is one of, wherein, R 1 , R 2 , R 3 and R 4 are each independently selected as alkyl, preferably C1-C8 alkyl, more preferably C1-C6 alkyl; n is 1, 2 or 3, and m is 1, 2 or 3.

2. The preparation method according to claim 1, characterized in that, The inorganic ammonium salt is at least one of ammonium carbonate, ammonium bicarbonate or ammonium carbamate.

3. The preparation method according to claim 1, characterized in that, The molar ratio of the inorganic ammonium salt to the compound of formula (III) is (1-3):1, more preferably (1-2):

1.

4. The preparation method according to claim 1, characterized in that, The reaction solvent is selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, hexamethylphosphoric triamide or sulfolane.

5. The preparation method according to claim 1, characterized in that, The reaction temperature is 30-100°C, preferably 50-70°C.

6. The preparation method according to claim 1, characterized in that, The reaction time is 1-12 hours, preferably 3-5 hours.

7. The preparation method according to claim 1, characterized in that, React the compound of formula (III-b) with an inorganic ammonium salt to obtain the compound of formula (I-b), and the reaction formula is shown as follows: Among them, X, R f , R 1 , R 2 are defined in the same way as those described in claim 1.

8. The preparation method according to claim 7, characterized in that, The R 1 and R 2 are each independently n-C3H7 or i-C3H7.

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