Preparation and application background and overview of 2-amino-3-methylpyridine
2-Amino-3-methylpyridine is an important organic intermediate that can be used to synthesize antibacterial drugs, analgesics, anti-asthmatic drugs, anti-HIV drugs, and is also a nitric oxide synthase inhibitor. 2-Amino-5-methylpyridine is widely used in the fields of pesticides and medicine. It is a highly effective new pesticide for the synthesis of imidacloprid, acetamiprid, flufenopopop, and acefenofop, as well as new fluoropyridine pesticides in the future. important intermediates. 2-Amino-3-methylpyridine is also a nitric oxide synthase inhibitor. It has recently been reported that this compound is an excellent solubilizer that is beneficial to dissolving carbon nanotube materials.
Preparation and application of 2-amino-3-methylpyridine
Preparation and application report of 2-amino-3-methylpyridine 1.
Step 1: Add 50g 2-cyano-3-methylpyridine to 650ml of a mixed solvent of 5% mass fraction NaOH aqueous solution and acetone methylpyridine, and add 10% mass fraction dropwise within 15 minutes while stirring. 125ml of H2O2, raise the temperature to 50°C, continue to stir the reaction for 3.5 hours, stop the tetrahydrofuran to stop the reaction, evaporate the acetone below 50°C, freeze, filter and dry to obtain a white solid 3-methyl-2-pyridinemethyl Amide 47g, yield 85.3%;
Step 2: Cool 320 ml of 12% NaOH aqueous solution to 0~5°C with ice salt water, slowly add 25 ml of liquid bromine dropwise, and keep it warm for 0.5 h to prepare a sodium hypobromite solution; add the white solution obtained in the previous step The solid was put into 250 ml of 12% NaOH aqueous solution, and the newly prepared sodium hypobromite solution was added dropwise at 0°C. After the dropwise addition, the white solid gradually dissolved, and the temperature was raised to 60°C for 0.5 h. The reaction was stopped, and the reaction solution was cooled. Extract 3 times with 250 ml of ethyl acetate, wash the organic phase 2 times with 50 ml of water, dry, and concentrate to obtain a red liquid. The crude product is distilled under reduced pressure. Collect the 107-108.5°C, 2.67 kPa fraction, and lower it to room temperature to obtain 35g of the white final product. , the yield is 88.5%. 1H NMR (CDCl3)δ (×10-6): 2.334 (s ,3H ,CH3 ) ,5.430 (b ,2H ,NH2) ,6.846～8 . 110 (m, 3H, pyridine H).
Preparation and application report 2 of 2-amino-3-methylpyridine,
A mixed aminopyridine composed of 2-amino-3-methylpyridine and 2-amino-5-methylpyridine (the mass fraction of 2-amino-3-methylpyridine is 25%, 2-amino-5-methylpyridine The mass fraction of methylpyridine (75%) is passed into the crystallizer, and the temperature is gradually raised to 85°C. After the mixed aminopyridine is completely dissolved, the temperature is gradually cooled to 35°C at a cooling rate of 25°C/h.
Then filter, wash and dry to obtain 2-amino-5-methylpyridine with a purity of 99.61%.
Pour the crystallization mother liquor into the distillation tower. The top pressure of the distillation tower is 20 KPa, the number of theoretical plates is 42, and the reflux ratio is 7 for distillation. At the top of the tower, 2-amino-3- with a mass fraction of 99.12% is obtained. Methylpyridine.
Preparation and application of 2-amino-3-methylpyridine
Preparation and application of 2-amino-3-methylpyridine Application 1.
CN201610114611.8 discloses a synthesis method of 7-azaindole, which belongs to the field of organic synthesis technology. The present invention optimizes the reaction conditions on the basis of the existing technology, uses 2-amino-3-methylpyridine as the starting material, reacts with di-tert-butyl dicarbonate, and obtains dilithium salt under the action of butyllithium. Dilithium salt is used in dilute hydrochloric acid to catalyze the ring-closing reaction using zirconium dioxide as a catalyst to obtain 7-azaindole. The present invention can effectively reduce the reaction time, and at the same time, zirconium dioxide has good application effect, is non-toxic and harmless, and reduces the heavy metal content of the product. pollution and has high economic benefits.
Preparation and application of 2-amino-3-methylpyridine Application 2.
CN201711090036.3 discloses a preparation method of 2,5-dibromo-3-methylpyridine, which includes the following steps: (1) Add 2-amino-3-methylpyridine and acetic anhydride to four In the flask, raise the temperature to reflux, and follow the reaction with thin layer chromatography; (2) When the temperature of the reaction solution in step (1) drops to 20-25°C, add liquid bromine dropwise, finish the dripping, and react at 50-60°C for 2-3 hours. , add water until all solids are dissolved, add sodium hydroxide solution dropwise, continue the reaction for 30 minutes after addition, filter, dry, and recrystallize to obtain 2-amino 3-methyl-5-bromopyridine; (3) 2-amino- 3-Methyl-5-bromopyridine is added to the hydrogen bromide solution, and under the catalysis of copper bromide, a saturated sodium nitrite solution is added dropwise, the temperature is controlled at -5~10°C, and the reaction is carried out for 2-4 hours to obtain 2, 5-Dibromo-3-methylpyridine. The beneficial effects of the method of the invention are: mild reaction conditions, high yield, low cost, short process route, and suitable for industrial production.
References
[1] [Invented in China] CN201711016134.2 A new synthesis method of 2-amino-3-methylpyridine
[2] [Chinese invention] CN201410702970.6 A method for separating mixed aminopyridines through a coupling process of crystallization and distillation
[3] CN201610114611.8 A synthesis method of 7-azaindole
[4] CN201711090036.3 A preparation method of 2,5-dibromo-3-methylpyridine
