Initial reaction between catalyst 127 and methyl formate leads to ionic intermediate 128 where one nitrogen atom is formylated. Deprotonation of the secondary amine by the methoxyl anion leads to intermediate 129 with methanol evolved. Nucleophilic attack by an amine followed by proton transfer regenerates catalyst 127 and evolves the formylated amine. Batch reactions, following the procedure outlined by Deutsch et al. were performed using cyclopropylamine 119, 10 mol % 127 and 4 equivalents of the formylating reagent. The reaction was heated to reflux for 24 hours, yielding formamide 123 in 72 % yield after 24 hours: (Scheme 4.5) Scheme 4.5 batch synthesis of formamide 123 with catalyst 127 – The reaction conditions were then applied to the flow reactor. The system was primed with toluene and a 100 psi back-pressure regulator fitted. A was loaded with a solution of 0.1 M cyclopropylamine 119 and 0.4 M methyl formate in toluene, and input B was loaded with a solution of 0.01 M TBD in toluene. The low concentration of reagents used was 127 due to the poor solubility of catalyst 127 in toluene. Reactions were performed at different flow rates and with different reactor temperatures: (Table 4.2) Table 4.2 Synthesis of formamide 123 with catalyst 127 in toluene – Residence time [min] Reactor temperature Yield [%]a [oC] 10 30 5 10 40 13 10 50 23 20 60 70 20 70 94 20 80 90 20 90 91
Initial reaction between catalyst 127 and methyl formate leads to ionic intermediate 128 where one nitrogen atom is formylated. Deprotonation of the secondary amine by the methoxyl anion leads to intermediate 129 with methanol evolved. Nucleophilic attack by an amine followed by proton transfer regenerates catalyst 127 and evolves the formylated amine. Batch reactions, following the procedure outlined by Deutsch et al. were performed using cyclopropylamine 119, 10 mol % 127 and 4 equivalents of the formylating reagent. The reaction was heated to reflux for 24 hours, yielding formamide 123 in 72 % yield after 24 hours: (Scheme 4.5) Scheme 4.5 – batch synthesis of formamide 123 with catalyst 127 The reaction conditions were then applied to the flow reactor. The system was primed with toluene and a 100 psi back-pressure regulator fitted. A was loaded with a solution of 0.1 M cyclopropylamine 119 and 0.4 M methyl formate in toluene, and input B was loaded with a solution of 0.01 M TBD 127 in toluene. The low concentration of reagents used was due to the poor solubility of catalyst 127 in toluene. Reactions were performed at different flow rates and with different reactor temperatures: (Table 4.2) Table 4.2 – Synthesis of formamide 123 with catalyst 127 in toluene Residence time [min] Reactor temperature [oC] Yield [%]a 10 30 5 10 40 13 10 50 23 20 60 70 20 70 94 20 80 90 20 90 91
Complete_thesis_with_corrections.docx