Preparation method of nicotinamide fungicide namely boscalid

Abstract

The invention discloses a preparation method of a nicotinamide fungicide namely boscalid. The preparation method comprises the following steps: starting from a raw material namely para chlorobromobenzene, performing Grignard reaction, and synthesizing p-chlorobenzeneboronic acid; starting from ortho-nitroaniline, synthesizing o-nitro halogenated benzene, or directly synthesizing o-amino halogenated benzene; and under the action of specific catalysts, enabling p-chlorophenylboronic acid to perform a series of reactions such as coupling, reduction, amidation and the like with o-nitro halogenated benzene or o-amino halogenated benzene to prepare boscalid. The preparation method disclosed by the invention is simple to operate, high in yield, small in pollution, low in cost and high in purity, and is very suitable for industrial production.

Description

technical field [0001] The invention relates to the field of pesticide fungicides, in particular to a preparation method of a nicotinamide broad-spectrum fungicide boscalid and an intermediate thereof. Background technique [0002] Boscalid is a new type of nicotinamide fungicide developed by BASF in Germany. It is mainly used to prevent gray mold, powdery mildew, various rots, brown rots and root rots. Registered in Germany and Switzerland. Boscalid belongs to the succinate coenzyme Q reductase inhibitor in the mitochondrial respiratory chain, which has a strong inhibitory ability to spore germination and has no cross-resistance with other fungicides. Boscalid is a new type of nicotinamide fungicide with a wide bactericidal spectrum and is active against almost all types of fungal diseases. It is very effective in preventing and controlling powdery mildew, gray mold, sclerotinia and various rot diseases, etc. It is also effective for resistant bacteria to other chemicals,...

AI Technical Summary

Problems solved by technology

[0008] 1) Through the benzidine intermediate 4-chloro-2'-aminobiphenyl, using o-chloronitrobenzene as a raw material, undergoes a Suziki coupling reaction with p-chlorophenylboronic acid under the catalysis of palladium (II) to obtain the intermediate 4-chloro -2′-Nitrobiphenyl: Adv. Syn. & Cat. 252, 3089-3097, 2010, reported with Pd(PPh 3 ) 4 As a catalyst, n-butanol was used as a solvent, reacted at 160 °C for 15 minutes, and the yield was 91%. WO2006092429 reported using PdCl 2 As a catalyst, triphenylphosphine is used as an auxiliary catalyst, THF is used as a solvent, and the yield is 99% at 66 °C for 18 hours. The amount of catalyst used is very large, making the preparation cost very expensive and not suitable for industrial production.

Tetrahedron, 66, 2301~2305, 2010, reported using PdCl 2 Loaded on 4A molecular sieve as a catalyst, DMF as a solvent, reacted at 120 °C for 18 hours, and the yield was 90%. However, a large number of experiments found that it is difficult to implement the catalyst, and it is not suitable for a little scale-up experiment

[0009] 4-Chloro-2′-nitrobiphenyl and then through iron powder (Adv. Synth. Catal. 2009, 351, 649-655) or SnCl 2 (Chem.Commun. 2007,2926-2928) Reduction to obtain the intermediate 4-chloro-2'-aminobiphenyl, and the yields reported in the above literature are 94% and 88%, respectively, relative to the reaction of equivalent conversion Yields are still somewhat low

[0012] 2) Using o-iodoaniline or o-bromoaniline as a raw material, EP0545099 reported that o-iodoaniline and p-chlorophenylboronic acid undergo Suzuki reaction to prepare intermediate 4-chloro-2′-aminobiphenyl, and US20100184739 reported o-bromoaniline and p-chloro The intermediate 4-chloro-2′-aminobiphenyl is prepared by Suzuki reaction of phenylboronic acid, but it uses extremely expensive Pd 2 (dba) 3 As a catalyst, the dosage is very large, and P(t-Bu) is added at the same time 3 as a co-catalyst

[0014] 3) Synlett, (14), 2064-2068, 2011, reported the selective Mg insertion substituted chlorinated aromatics method: starting from the cheap raw material 1,4-dichlorobenzene, the Grignard reagent was prepared by LiCl catalysis, but we The preparation of this kind of scheme is found to be unsatisfactory, the reaction is not complete, the yield is low, and it is not suitable for scale-up reactions

When we adopted this scheme, we found that the route was longer, the waste liquid was more, and the reaction yield of the first few steps was low, the side reactions were too many, and the total yield was low, resulting in high cost

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