反应详情

温度

27.5 °C

The crude 2-methyl-4-oxo-3,1-benzoxazine was dissolved in acetic acid (1.9 L). Sodium azide (130.0 g) was added to the solution in portions with stirring. The reaction mixture was cooled in an ice bath to maintain the reaction temperature at 25 to 30° C. during the addition. The reaction mixture was allowed to stir at ambient temperature over the weekend. The acetic acid was removed under vacuum to provide a white solid. The solid was combined with 10% sodium hydroxide (1.4 L) then heated on a steam bath for 1 hour. Additional sodium hydroxide (120 g of 50% sodium hydroxide) was added. The mixture was heated on a steam bath for an additional hour then allowed to cool to ambient temperature overnight. Additional sodium hydroxide (120 g of 50% sodium hydroxide) was added. The mixture was heated on a steam bath for 2 hours then allowed to cool. The reaction mixture was poured with rapid stirring into a mixture of concentrated hydrochloric acid (1.0 L) and ice (3 L). The resulting mixture was stirred at ambient temperature overnight. A precipitate was isolated by filtration, rinsed with water then slurried with water (4 L). The solid was isolated by filtration, rinsed with water then oven dried at 50° C. to provide 278.0 g of crude 2-(5-methyl-1H-tetrazol-1-yl)benzoic acid as a tan solid, m.p. 157-160° C. The crude material was dissolved in 10% sodium hydroxide (2.5 L). The resulting solution was heated (95-99° C.) for 2.5 hours, cooled, then poured with vigorous stirring into a mixture of concentrated hydrochloric acid (500 mL) and ice (5 L). The resulting mixture was allowed to stir for 2 hours. The precipitate was isolated by filtration, rinsed with water, then slurried with water (3 L). The solid was isolated by filtration, rinsed with water then dried overnight at ambient temperature to provide 228 g of 2-(5-methyl-1H-tetrazol-1-yl)benzoic acid, m.p. 164-166° C.

1. temperatureThe reaction mixture was cooled in an ice bath
2. additionduring the addition
3. stirringto stir at ambient temperature over the weekend
4. customThe acetic acid was removed under vacuum
5. customto provide a white solid
6. temperaturethen heated on a steam bath for 1 hour
7. temperatureThe mixture was heated on a steam bath for an additional hour
8. temperatureto cool to ambient temperature overnight
9. temperatureThe mixture was heated on a steam bath for 2 hours
10. temperatureto cool
11. additionThe reaction mixture was poured
12. stirringThe resulting mixture was stirred at ambient temperature overnight
13. customA precipitate was isolated by filtration
14. washrinsed with water
15. customThe solid was isolated by filtration
16. washrinsed with water
17. customoven dried at 50° C.