Preparation of p-toluenesulfonyl azide_Kain Industrial Additive

Background and Overview

P-Toluenesulfonyl Azide is a chemical intermediate with a wide range of uses.

Preparation^[1]

At room temperature, add 13.8g p-toluenesulfonyl chloride (73mmol), 50mL water and 5.7g sodium azide (87mmol) in sequence in a 500mL flask, stir for 2 hours, and monitor the reaction with TLC until the reaction is complete. Extract 3 times with 50 mL dichloromethane, combine the organic phases, dry over anhydrous sodium sulfate, and concentrate to obtain 12.7 g of p-toluenesulfonyl azide product, with a yield of 88%.

Apply ^[2-5]

1. Used to prepare a copper surface corrosion inhibition assembly film

Copper and its alloys have good thermal, electrical conductivity and mechanical properties, and are widely used in many industries such as electric power, information, and seawater desalination. However, in corrosive media containing Cl^–, SO4^2-, copper and its alloys are prone to corrosion, causing huge economic losses and safety hazards. Therefore, corrosion protection of copper and alloys is very important. As a commonly used anti-corrosion method, corrosion inhibitors are cost-effective and adaptable. Corrosion-inhibition assembly technology provides a method to modify metal surfaces in a set manner, opening up a new way to prevent metal corrosion. It is also the most practical development direction of self-assembly technology. Triazoles are widely used special corrosion inhibitors for copper and its alloys. It is of great significance to develop efficient and environmentally friendly triazole corrosion inhibition films on copper surfaces. CN201610128527.1 provides a method for preparing a copper surface corrosion inhibition assembly film. The preparation method of this copper surface corrosion inhibition assembly film is to solve the technical problem in the prior art that the copper surface is easily corroded in a corrosive environment. The surface of the copper electrode was polished with metallographic sandpaper of different mesh sizes, and then rinsed with absolute ethanol and deionized water to remove surface oil and grease. The pretreated copper electrode was assembled in ethanol solutions with 2-methyl-3-butyn-2-ol concentrations of 0.2mM, 0.5mM, 1.0mM, and 1.5mM for 1 hour, and then correspondingly Click to assemble in ethanol solutions with nitrogen concentrations of 0.2mM, 0.5mM, 1.0mM, and 1.5mM for 30 minutes. After the click assembly is completed, rinse with water and dry to obtain a uniform triazole corrosion inhibition film on the copper surface.

2. Synthesis of α-diazo ester compounds

CN201810771549.9 reports a method for synthesizing α-diazo ester compounds using microwaves and normal pressure. Using ester compounds and p-toluenesulfonyl azide as starting materials, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the catalyst, under microwave-assisted heating conditions, After a one-step diazo transfer reaction, α-diazo ester compounds are generated.

3. Used in the preparation of 4-aminoimine coumarin derivatives

Amines widely exist in the biological world and have extremely important physiological and biological activities. Most drugs used clinically are also amines or amine derivatives. Therefore, mastering the properties and synthesis methods of amines is an important step in studying these complex natural products. and better safeguard human health. Because its amine compounds have very broad application prospects, research on more effective preparation methods has attracted great attention from researchers.

CN201610565065. The method for 4-aminoiminocoumarin derivatives has technical problems such as complex process and low yield. Including the following steps:

1) Weigh the cuprous catalyst, unsubstituted or substituted o-hydroxybenzonitrile, additives, unsubstituted or substituted terminal alkyne compounds, and p-toluenesulfonyl azide. The additives are three Any one of ethylamine, tetramethylethylenediamine, 1,8-diazabicycloundec-7-ene, potassium carbonate or cesium carbonate, the substituted terminal alkyne is 3- Methoxyphenylacetylene, 3-methylphenylacetylene, 4-methylphenylacetylene, 2-chlorophenylacetylene, 2-methoxyphenylacetylene, 3-chlorophenylacetylene, 4-ethylphenylacetylene, 4-amino Any one of phenylacetylene, 2-methylphenylacetylene, 4-fluorophenylacetylene, 4-chlorophenylacetylene, 1-hexyne or 1-octyne; the substituted o-hydroxybenzonitrile is Any one of 3-bromo-2-hydroxybenzonitrile, 5-bromo-2-hydroxybenzonitrile or 2-hydroxy-6-methylbenzonitrile; the p-toluenesulfonyl azide, none The molar ratio of substituted or substituted terminal alkynes and unsubstituted or substituted o-hydroxybenzonitrile is 1~1.2:1~1.2:1~1.2, and the molar number of the cuprous catalyst is none 5% to 10% of the mole number of substituted or substituted terminal alkyne compounds, and the mole number of the additive is 1-2 times the mole number of unsubstituted or substituted terminal alkyne compounds;

2) Add cuprous catalyst, unsubstituted or substituted o-hydroxybenzonitrile into a reaction vessel, replace nitrogen three times and then add organic solvent, and finally add unsubstituted or substituted terminal alkyne compound, p-hydroxybenzonitrile Add tosyl azide and add additives under nitrogen. After the addition is completed, react at room temperature to 110°C for 3h ~ 7h. The reaction process is tracked with thin layer chromatography;

3) After the reaction is completed, the mixture is filtered, then concentrated, and then separated by column chromatography to obtain the final product amine compound.

Compared with the prior art, the technical progress of the present invention is significant. The present invention adopts a “one-pot method” to prepare 4-aminoiminocoumarin derivatives, which greatly improves the reaction efficiency, has simple post-processing, and has good industrialization potential.Use prospects.

4. Used to prepare 3-hydroxyimidazo[1,2-a]pyridine derivatives

Imidazo[1,2-a]pyridine compounds are a class of nitrogen-containing fused heterocyclic compounds with wide applications. Nowadays, derivatives based on imidazo[1,2-a]pyridine have been widely used. In many fields such as chemistry, pharmacy and industry. CN201710025871.2 provides a method for preparing a 3-hydroxyimidazo[1,2-a]pyridine derivative. The preparation method of the 3-hydroxyimidazo[1,2-a]pyridine derivative requires This method solves the technical problems of high cost and low yield of the method for preparing 3-hydroxyimidazo[1,2-a]pyridine in the prior art.

The invention provides a method for preparing 3-hydroxyimidazo[1,2-a]pyridine derivatives, which includes the following steps: 1) Weigh the cuprous catalyst, unsubstituted or substituted 2-amino Pyridine, first additive, unsubstituted or substituted terminal alkyne compound, p-toluenesulfonyl azide, the first additive is triethylamine, tetramethylethylenediamine, 1,8-diazabis Any one of cycloundec-7-ene, potassium carbonate or cesium carbonate, the substituted terminal alkyne is 3-methoxyphenylacetylene, 3-methylphenylacetylene, 4-methylbenzene Acetylene, 2-chlorophenylacetylene, 2-methoxyphenylacetylene, 3-chlorophenylacetylene, 4-ethylphenylacetylene, 4-aminophenylacetylene, 2-methylphenylacetylene, 4-fluorophenylacetylene, 4- Any one of chlorophenylacetylene, 1-hexyne or 1-octyne; the substituted 2-aminopyridine is 2-aminopyridine, 2-amino-5-chloropyridine or 2-amino-5 -Any one of methylpyridines; the molar ratio of the p-toluenesulfonyl azide, unsubstituted or substituted terminal alkynes, unsubstituted or substituted 2-aminopyridine is 1 to 1.2 : 1 ~ 1.2: 1 ~ 1.2, the mole number of the cuprous catalyst is 5% ~ 10% of the mole number of the unsubstituted or substituted terminal alkyne compound, the mole number of the first additive is unsubstituted 1-2 times the number of moles of the base or substituted terminal alkyne compound; 2) Add a cuprous catalyst, unsubstituted or substituted 2-aminopyridine to a reaction vessel, add the first organic solvent after nitrogen replacement, Finally, add the unsubstituted or substituted terminal alkyne compound and p-toluenesulfonyl azide, and add the additives under nitrogen. After the addition is completed, react at room temperature for 2h ~ 5h, and the reaction process is tracked with thin layer chromatography;

3) After the reaction is completed, the mixture is filtered, then concentrated, and then separated by column chromatography to obtain the intermediate product pyridin-2-ylamino compound; 4) Weigh the cuprous catalyst and the intermediate product pyridin-2-ylamino compound compound, iodine, potassium iodide and a second additive, the second additive is triethylamine, tetramethylethylenediamine, 1,8-diazabicycloundec-7-ene, potassium carbonate, cesium carbonate , any one of potassium tert-butoxide or lithium tert-butoxide, the number of moles of the cuprous catalyst is 5% to 10% of the number of moles of the intermediate product, and the number of moles of iodine is the number of moles of the intermediate product 1~1.2 times, the number of moles of potassium iodide is 1~1.5 times the number of moles of the intermediate product, the number of moles of the additive is 1~1.5 times the number of moles of the intermediate product; 5) in a reaction vessel Add the cuprous catalyst, intermediate product pyridin-2-yl amino compound, iodine, potassium iodide and additives. After nitrogen replacement, add the second organic solvent. After completion, react at 60~120°C for 6~14 hours; 6) After the reaction is completed , the mixture was filtered, then concentrated, and then separated by column chromatography to obtain the product 3-hydroxyimidazo[1,2-a]pyridine derivative.

The present invention adopts a “step-by-step method” to prepare 3-hydroxyimidazo[1,2-a]pyridine derivatives, which improves reaction efficiency, product yield, simple post-processing, and good industrialization Application prospects.

Main reference materials

[1] CN201711339751.6 A kind of tetrahydropyran [2,3-b] indole skeleton and its crystals and its preparation method and use

[2] CN201610128527.1 Preparation method of copper surface corrosion inhibition assembly film

[3] CN201810771549.9 A method for synthesizing α-diazo ester compounds using microwave and normal pressure

[4] CN201610565065.X A method for preparing 4-aminoimine coumarin derivatives

[5]CN201710025871.2 A preparation method of 3?hydroxyimidazo[1,2?a]pyridine derivative