Preparation and application of 3-amino-2-chloropyridine_Industrial additives

Preparation and application background and overview of 3-amino-2-chloropyridine

3-Amino-2-chloropyridine is a key intermediate of two compounds, chlorantraniliprole and pirenzepine, and has broad market development prospects. 3-Amino-2-chloropyridine can be obtained by chlorination of 3-aminopyridine.

Preparation and application of 3-amino-2-chloropyridine

Preparation and application report of 3-amino-2-chloropyridine 1.

Dissolve 188g (2mol) of 3-aminopyridine in 10% hydrochloric acid: 900g (content 10%, 2.46mol). After completely dissolved and mixed, mix this solution with dichloromethane: g, sodium hypochlorite solution: 800g ( content 10%, 1.07mol) as the preset volume ratio per unit time, and then according to the volume ratio per unit time at normal temperature (the specific temperature range of normal temperature is the same as 10°C-30°C) Separately and simultaneously, they are continuously pumped into the first-stage extraction centrifuge for extraction and centrifugation; after that, the organic phase and the aqueous phase are separated, and the organic phase is retained. The aqueous phase, industrial hydrochloric acid: 59g (content 31%, 0.5mol), dichloride The volume ratio of methane: 200g, and sodium hypochlorite solution: g (content 10%, 0.54mol) is used as the preset volume ratio per unit time, and then the four are continuously pumped in separately and simultaneously at room temperature according to the volume ratio per unit time. Extraction and centrifugation are carried out in the second-stage extraction centrifuge; after that, the organic phase and the aqueous phase are separated, and the organic phase is retained, and the aqueous phase is put into the next-stage extraction centrifuge; the amount of hydrochloric acid, dichloromethane used in each subsequent stage of the extraction centrifuge The amount of sodium hypochlorite solution and the amount of sodium hypochlorite solution were gradually halved, and a total of five stages of continuous extraction reaction were performed (the extraction and centrifugation reaction time of each stage was 3 hours respectively), and then the organic phases were combined to obtain the 3-amino-2-chloropyridine solution; a total of 962g of the solution was obtained. Using liquid chromatography, external standard method analysis, the calculated content of the external standard method is 24.4%, the converted weight of 3-amino-2-chloropyridine: 234.5g, the molar yield of 3-amino-2-chloropyridine is 91.3% (based on 3- Aminopyridine), purity 98.4%.

Preparation and application report of 3-amino-2-chloropyridine dipyridinecarbonitrile

Add 3-aminopyridine into the chlorination kettle, add a certain amount of hydrogen peroxide, pass the frozen brine through the jacket to cool it to 10°C, then slowly add hydrochloric acid dropwise to perform the chlorination reaction, and control the reaction temperature to 25°C. The reaction pressure is normal pressure. After the chlorination reaction is completed, 3-amino-2-chloropyridine is obtained.

Preparation and application of 3-amino-2-chloropyridine

Preparation and application of 3-amino-2-chloropyridine Application 1.

CN201310729463.7 reports a production method of pirenzepine. The specific steps are as follows: 3.86g compound 3-amino-2-chloropyridine (I) and triethylamine are dissolved in benzene, and 5.85g o-mica nitrate is added dropwise The benzene solution of benzoyl chloride was used to obtain 6.17g of the acylation product (II); 5.0g of the compound (II) was dissolved in 27ml of acetic acid, and a concentrated hydrochloric acid solution containing excess stannous chloride was slowly added to obtain 4.1g of the reduced product (III ); 8.0g compound (Ⅲ), treated with alcohol to obtain 4.1g cyclization product (Ⅳ); 3.17g compound (Ⅳ) was dissolved in dioxane, and 3.4ml triethylamine and 1.9ml chloroacetyl chloride were added dropwise to obtain 3.58g compound (V); 3.01g compound (V) and 8.2ml N-methylpiperazine were dissolved in 60ml benzene to obtain 3.29g crude pirenzepine dihydrochloride. The production method of pirenzepine has low manufacturing cost, simple production process and high output.

Preparation and application of 3-amino-2-chloropyridine Application 2.

CN200580002691.8 discloses a method for preparing 2,3-dichloropyridine, wherein in the presence of an aqueous hydrochloric acid solution, 3-amino-2-chloropyridine is contacted with an alkali metal nitrite to form a diazonium salt; and subsequently The diazonium salt is decomposed in the presence of a copper catalyst in which at least about 50% of the copper is in the copper(II) oxidation state.

References

[1] [Chinese invention] CN201911265233.3 A preparation method of 2-chloro-3-aminopyridine

[2] CN201310729463.7 A production method of pirenzepine

[3] CN200580002691.8 Method for preparing 2,3-dichloropyridine

[4] [Invented in China] CN201510807194.0 A dichloropyridine production process