Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 3-Methyl-1H-1,2,4-triazole
A solution of compound 1 (30 g, 0.13 mol) in THF (1.5 L) was cooled to 78 C. Vinylmagnesium in THF (508 mL, 1N, 0.51 mol) was added dropwise to the above solution and the temperature was maintained below 40 C. The mixture was stirred for 3 h at 78 C before being quenched with saturated aqueous NH4Cl solution. The layers were separated, the aqueous layer was extracted with EtOAc (3 500 mL), and the combined organic layer was washed with brine and concentrated.The crude product was purified by silica gel column chromatography to obtain compound 2 (5 g,17%). Compound 2 (4.0 g, 17.2 mmol) was dissolved in freshly prepared NaOMe (20 mL). CuI(3.2 g, 17.2 mmol) was added and the mixture was microwave-irradiated at 110 C and stirred for3 h. After reaction completion, EtOAc and H2O were added, then the suspension was filtered andthe filtrate was separated. The organic layer was concentrated to give crude product, which waspurified by column chromatography to give compound 3 (1.8 g, 45%). A mixture of compound 3(0.7 g, 3.8 mmol), 3-methyl-1,2,4-triazole (6.4 g, 76.8 mmol), copper powder (0.49 g, 7.68 mmol), and KOH (0.43 g, 7.68 mmol) was heated to melt at 170-175 C while being protected by N2 atmosphere. After consumption of the starting material, EtOAc and H2O were added to the mixture, and the suspension was filtered and the filtrate was collected. The organic layer was concentrated to give the crude product, which was purified by column chromatography to give compound 4 (0.23 g, 26%).A solution of compound 4 (0.23 g, 1 mmol) in THF (12 mL) was cooled to 10 C, and EtMgBr (0.47 g,3.5 mmol) was added dropwise at 10 C, followed by the addition of pyridine (0.3 mL). The slurrywas cooled to 45 C, and the ethyl 2-chloro-2-oxoacetate (0.55 g, 4 mmol) was added dropwise at 45 C. The temperature was allowed to rise to 10 C and the mixture was stirred for 1h. Afterreaction completion, the mixture was quenched with IPA (2 mL) and H2O (20 mL). The mixture wasextracted with EtOAc, and the organic layer was washed with brine and concentrated to the givecrude product which was purified by column chromatography to give compound 5 (0.17 g, 52%).Compound 5 (0.17 g, 0.52 mmol) was dissolved in MeOH (5 mL). NaOH (0.041 g, 1.03 mmol) and H2O(2 mL) were added and the mixture was stirred at 25 C for 6 h. HCl (1N) was added to adjust the pH to 6, and the mixture was concentrated to give compound 6 (0.29 g) as crude product.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Article; Meuser, Megan E.; Murphy, Michael B.; Rashad, Adel A.; Cocklin, Simon; Molecules; vol. 23; 8; (2018);,
1,2,3-Triazole – Wikipedia,
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