Scheme 4.12 reaction of phosphorus oxychloride with triethylamine89 – Phosphorus oxychloride and triethylamine were pre-mixed before being injected into the flow machine to avoid the formation of precipitate. A 0.5 M solution of formamide 125 in dichloromethane was injected into input A and the pre-mixed solution of 0.55 M triethylamine and 0.55 M phosphorus oxychloride in dichloromethane was injected into input B. Reactions were performed at different flow rates and reactor temperatures: (Table 4.7) Table 4.7 Synthesis of isocyanide 157 using phosphorus oxychloride and triethylamine – Residence time [min] Reactor temperature Yield [%]a [oC] 10 30 9 10 40 24 10 50 57 10 60 0b 15 40 0b 15 50 0b 15 60 0b 20 30 0b 20 40 0b a of isolated product b precipitate blocked the reactor – Highest yields were obtained at a combined flow rate of 1 (residence time of 10 minutes) and a reactor temperature of 50 oC giving isocyanide in 57 % yield. The 157 reaction generated stoichiometric amounts of triethylammonium chloride as a by-product that blocked the reactor. Above 50 oC the precipitate blocked the reactor, and reactions performed at a flow rate below 1 mL/min also caused the reactor to block. The yield obtained therefore is a compromise between obtaining a reasonable yield and creating a repeatable procedure. The conditions were applied to several formamides, but again yields were either moderate or the reaction was unsuccessful: (Table 4.8)
Scheme 4.12 – reaction of phosphorus oxychloride with triethylamine89 Phosphorus oxychloride and triethylamine were pre-mixed before being injected into the flow machine to avoid the formation of precipitate. A 0.5 M solution of formamide 125 in dichloromethane was injected into input A and the pre-mixed solution of 0.55 M triethylamine and 0.55 M phosphorus oxychloride in dichloromethane was injected into input B. Reactions were performed at different flow rates and reactor temperatures: (Table 4.7) Table 4.7 – Synthesis of isocyanide 157 using phosphorus oxychloride and triethylamine Residence time [min] Reactor temperature [oC] Yield [%]a 10 30 9 10 40 24 10 50 57 10 60 0b 15 40 0b 15 50 0b 15 20 20 60 30 40 0b 0b 0b a of isolated product b – precipitate blocked the reactor Highest yields were obtained at a combined flow rate of 1 (residence time of 10 minutes) and a reactor temperature of 50 oC giving isocyanide 157 in 57 % yield. The reaction generated stoichiometric amounts of triethylammonium chloride as a by-product that blocked the reactor. Above 50 oC the precipitate blocked the reactor, and reactions performed at a flow rate below 1 mL/min also caused the reactor to block. The yield obtained therefore is a compromise between obtaining a reasonable yield and creating a repeatable procedure. The conditions were applied to several formamides, but again yields were either moderate or the reaction was unsuccessful: (Table 4.8)
Complete_thesis_with_corrections.docx