another column containing solid supported amine that scavenged excess acid chloride from the reaction stream:71 (Scheme 2.14) Scheme 2.14 Synthesis of oxazole 104 from isocyanides using a microreactor71 – Using this procedure, oxazole 104 could be synthesised in 92 % yield from acid chloride 102 and isocyanide 101. Using the methodology, 34 different oxazoles were synthesised in yields ranging from 83-94 %, and none of the materials required further purification. Ley et al. also report a reaction to synthesise thiazole 108 from thioisocyanate 105 and isocyanide 106. The reagents were pumped separately through a microreactor to initiate the reaction and again were passed through a column containing solid-supported base 107 that promoted cyclisation. After elution of thiazole 108, alkyl bromide 109 was passed through the solid-supported base yielding imidazole 110 as the sole product:72 (Scheme 2.15) Scheme 2.15 Synthesis of thiazole 108 and imidazole 110 using a microreactor72 – Using this procedure thiazole 108 could be synthesised in 58 % yield from thioisocyanate 105 and isocyanide 106. After elution of thiazole 108, alkyl bromide 109 was passed through the solid-supported base 107 yielding imidazole 110 in 38 % yield. It was speculated that prior to passing through the solid-supported base 107, the reaction stream contained a mixture of vinyl thiolate and 4-thioimidazole spontaneously cyclised to give 111 112. 111 thiazole 108 while 112 remained bound to the column. Alkyl bromide 109 released 112 from the column yielding 110: (Scheme 2.16) Scheme 2.16 Mechanistic rationale for the two products72 – Summary of the chemistry of isocyanides The unusual structure of isocyanides and tendency to participate in a variety of different reactions make them an intriguing functional group. Isoelectronic with carbon
another column containing solid supported amine that scavenged excess acid chloride from the reaction stream:71 (Scheme 2.14) Scheme 2.14 – Synthesis of oxazole 104 from isocyanides using a microreactor71 Using this procedure, oxazole 104 could be synthesised in 92 % yield from acid chloride 102 and isocyanide 101. Using the methodology, 34 different oxazoles were synthesised in yields ranging from 83-94 %, and none of the materials required further purification. Ley et al. also report a reaction to synthesise thiazole 108 from thioisocyanate 105 and isocyanide 106. The reagents were pumped separately through a microreactor to initiate the reaction and again were passed through a column containing solid-supported base 107 that promoted cyclisation. After elution of thiazole 108, alkyl bromide 109 was passed through the solid-supported base yielding imidazole 110 as the sole product:72 (Scheme 2.15) Scheme 2.15 – Synthesis of thiazole 108 and imidazole 110 using a microreactor72 Using this procedure thiazole 108 could be synthesised in 58 % yield from thioisocyanate 105 and isocyanide 106. After elution of thiazole 108, alkyl bromide 109 was passed through the solid-supported base 107 yielding imidazole 110 in 38 % yield. It was speculated that prior to passing through the solid-supported base 107, the reaction stream contained a mixture of vinyl thiolate 111 and 4-thioimidazole 112. 111 spontaneously cyclised to give thiazole 108 while 112 remained bound to the column. Alkyl bromide 109 released 112 from the column yielding 110: (Scheme 2.16) Scheme 2.16 – Mechanistic rationale for the two products72 Summary of the chemistry of isocyanides The unusual structure of isocyanides and tendency to participate in a variety of different reactions make them an intriguing functional group. Isoelectronic with carbon
Complete_thesis_with_corrections.docx