Practical and Efficient Synthesis of N-Formylbenzotriazole 1. ProcedureA 500-mL, 3-necked, round-bottomed flask (Note 1) equipped with a 5 cm Teflon-coated cylindrical magnetic stir bar, an internal thermometer, a rubber septum, and a Vigreux condenser capped with a rubber septum with an argon inlet, is charged with acetic anhydride (26.5 mL, 28.6 g, 280 mmol, 1.0 equiv) (Note 2). The contents are cooled to –10 °C by means of a Dewar filled with isopropanol and an immersion cooler (Neslab CC 100) (Note 3), then 100% formic acid (21.1 mL, 25.8 g, 560 mmol, 2.0 equiv) (Note 4) is added in portions to the flask over 3 min via a measuring cylinder [Caution: exotherm from –10 °C to 1 °C]. The resulting colorless reaction mixture is then heated in an oil bath on a hot plate to 43 °C (internal temperature) over 25 min. The reaction mixture is stirred vigorously for 3 h (42–44 °C, internal temperature) and monitored by 1H NMR analysis (Note 5).1H NMR analysis of crude reaction aliquots is employed to determine the quantity of acetic formic anhydride in the reaction mixture (18.1 g, 206 mmol). Formic anhydride (2.4 g, 32 mmol) was also present (Notes 6 and 7). The crude anhydride mixture is then cooled to 5 °C over 30 min using an ice bath. While maintaining a positive pressure of argon, the Vigreux condenser is removed and replaced with a rubber septum with an argon inlet.A 500-mL, two-necked round-bottomed flask, equipped with a 5 cm Teflon-coated magnetic stir bar, an internal thermometer, and a rubber septum with an argon inlet, is charged with benzotriazole (23.8 g, 200 mmol, 0.84 equiv relative to formylating agents (Notes 6 and 8). Anhydrous tetrahydrofuran (100 mL) is added to the benzotriazole via a measuring cylinder and the resulting light yellow solution is cooled to –15 °C (internal temperature) over 20 min by means of an ice/salt water bath. The crude mixed anhydride is then added to the benzotriazole solution via cannula over 12 min, ensuring that the internal temperature does not exceed –5 °C (Note 9). Upon completion of addition, the reaction mixture is cooled to –15 °C (internal temperature) by means of a Dewar filled with isopropanol and an immersion cooler (Neslab CC 100) (Note 3) and vigorously stirred until completion by TLC analysis (2 h) (Note 10), at which point the reaction mixture is thick and cream colored.The reaction mixture is transferred to a single-necked, 1-L round-bottomed flask and concentrated to dryness by rotatory evaporation (40 °C bath temperature, 20 mmHg). Chloroform (50 mL) (Notes 11 and 12) is added to the flask and the solution is concentrated again (40 °C bath temperature, 20 mmHg). The dilution and concentration procedure is repeated 3 times, yielding a white solid. The solid is dried at room temperature, under 0.75 mmHg for 12 h. The white solid is ground with a glass rod and dried at room temperature, under 0.75 mmHg for a further 48 h to afford 29.3 g (99.7%) of N-formylbenzotriazole (Notes 13, 14, and 15) What are the special precautions or purificationsof the reagents requires? What are the limiting and excess reagents? is excess neccesary? Describe the procedure thouroughly, include details about the reaction workup.What method did the author use to prove they have the right material. How is the product purified
Practical and Efficient Synthesis of N-Formylbenzotriazole
1. Procedure
A 500-mL, 3-necked, round-bottomed flask (Note 1) equipped with a 5 cm Teflon-coated cylindrical magnetic stir bar, an internal thermometer, a rubber septum, and a Vigreux condenser capped with a rubber septum with an argon inlet, is charged with acetic anhydride (26.5 mL, 28.6 g, 280 mmol, 1.0 equiv) (Note 2). The contents are cooled to –10 °C by means of a Dewar filled with isopropanol and an immersion cooler (Neslab CC 100) (Note 3), then 100% formic acid (21.1 mL, 25.8 g, 560 mmol, 2.0 equiv) (Note 4) is added in portions to the flask over 3 min via a measuring cylinder [Caution: exotherm from –10 °C to 1 °C]. The resulting colorless reaction mixture is then heated in an oil bath on a hot plate to 43 °C (internal temperature) over 25 min. The reaction mixture is stirred vigorously for 3 h (42–44 °C, internal temperature) and monitored by 1H NMR analysis (Note 5).
1H NMR analysis of crude reaction aliquots is employed to determine the quantity of acetic formic anhydride in the reaction mixture (18.1 g, 206 mmol). Formic anhydride (2.4 g, 32 mmol) was also present (Notes 6 and 7). The crude anhydride mixture is then cooled to 5 °C over 30 min using an ice bath. While maintaining a positive pressure of argon, the Vigreux condenser is removed and replaced with a rubber septum with an argon inlet.
A 500-mL, two-necked round-bottomed flask, equipped with a 5 cm Teflon-coated magnetic stir bar, an internal thermometer, and a rubber septum with an argon inlet, is charged with benzotriazole (23.8 g, 200 mmol, 0.84 equiv relative to formylating agents (Notes 6 and 8). Anhydrous tetrahydrofuran (100 mL) is added to the benzotriazole via a measuring cylinder and the resulting light yellow solution is cooled to –15 °C (internal temperature) over 20 min by means of an ice/salt water bath. The crude mixed anhydride is then added to the benzotriazole solution via cannula over 12 min, ensuring that the internal temperature does not exceed –5 °C (Note 9). Upon completion of addition, the reaction mixture is cooled to –15 °C (internal temperature) by means of a Dewar filled with isopropanol and an immersion cooler (Neslab CC 100) (Note 3) and vigorously stirred until completion by TLC analysis (2 h) (Note 10), at which point the reaction mixture is thick and cream colored.
The reaction mixture is transferred to a single-necked, 1-L round-bottomed flask and concentrated to dryness by rotatory evaporation (40 °C bath temperature, 20 mmHg). Chloroform (50 mL) (Notes 11 and 12) is added to the flask and the solution is concentrated again (40 °C bath temperature, 20 mmHg). The dilution and concentration procedure is repeated 3 times, yielding a white solid. The solid is dried at room temperature, under 0.75 mmHg for 12 h. The white solid is ground with a glass rod and dried at room temperature, under 0.75 mmHg for a further 48 h to afford 29.3 g (99.7%) of N-formylbenzotriazole (Notes 13, 14, and 15)
What are the special precautions or purificationsof the reagents requires? What are the limiting and excess reagents? is excess neccesary? Describe the procedure thouroughly, include details about the reaction workup.What method did the author use to prove they have the right material. How is the product purified
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