First, 2-aryl-5-methoxy oxazoles were prepared by the method of Wipf’s protocol*) from methyl N-acyl glycine methyl esters in the presence of Et3N in DCE with PPh3 and I2 at room temperature for 19-24hr. These reactions proceeded in mild condition and gave 2x to 80-97% yield by column chromatography.
Then, we attempted to apply the method of Friedel–Crafts acylation in order to synthesis of acylated oxazoles from 5-methoxy -2-phenyl oxazole (*). The normal conditions which used Lewis acid such as AlCl3 or TiCl4 with TFAA in DCE did not proceed the acylation, however, the reaction of introducing trifluoroacetyl group at the C4-position of oxazole without Lewis acid gave substituted oxazole (**). We optimized the condition of this acylation. …show more content…
We synthesized various derivatives which had substituent aryl group at 2-position of 5-methoxy oxazoles in our optimized condition. The result showed that the derivatives possessing electron donating groups, such as 2b, 2c, 2j, were obtained in 93-98% yield, whereas derivatives possessing electron withdrawing groups, such as 2g, 2h, 2i, were 28-37% yield. This result is considered that oxazole come to cause high electrophilic substitution reaction because of changing to electron rich p-ring by electron donating substituent.
Incidentally, every substituted oxazole (**) as well was not trifluoroacetylated derivative, reaching rearrangement compound in one-pot. We were not able to isolate or detect the 2-aryl-4-trifluoroacetyl oxazoles, though it considered generating as rearrangement precursors in this reaction.
Thus we took an interest in this result that the rearrangement precursors were not observed.
Thereby we planned to obtain this precursor by methylation of enol that is one of azlactone …show more content…
Methyl ether (**) can be generated as cis- and trans- isomers, but was isolated as a single isomer. This compound was stable against heat at 60 degrees and was not transformed into 5-trifluoromethyl oxazole (**), whereas compound (*) was unstable, turned into easily rearrangement oxazole (**) in the middle of isolation. To confirm this rearrangement of compound (*), when we heated at 60 degrees for 30min, compound (*) was observed to convert into oxazole (**) completely.
By the way, major product was mesoion () which was proceeded predominantly N-methylated in this condition. Because the preliminary examination that was using silver salt as base and toluene as solvent at heating gave rich in O-methylated compounds and controlled side reaction of
Then, we attempted to apply the method of Friedel–Crafts acylation in order to synthesis of acylated oxazoles from 5-methoxy -2-phenyl oxazole (*). The normal conditions which used Lewis acid such as AlCl3 or TiCl4 with TFAA in DCE did not proceed the acylation, however, the reaction of introducing trifluoroacetyl group at the C4-position of oxazole without Lewis acid gave substituted oxazole (**). We optimized the condition of this acylation. …show more content…
We synthesized various derivatives which had substituent aryl group at 2-position of 5-methoxy oxazoles in our optimized condition. The result showed that the derivatives possessing electron donating groups, such as 2b, 2c, 2j, were obtained in 93-98% yield, whereas derivatives possessing electron withdrawing groups, such as 2g, 2h, 2i, were 28-37% yield. This result is considered that oxazole come to cause high electrophilic substitution reaction because of changing to electron rich p-ring by electron donating substituent.
Incidentally, every substituted oxazole (**) as well was not trifluoroacetylated derivative, reaching rearrangement compound in one-pot. We were not able to isolate or detect the 2-aryl-4-trifluoroacetyl oxazoles, though it considered generating as rearrangement precursors in this reaction.
Thus we took an interest in this result that the rearrangement precursors were not observed.
Thereby we planned to obtain this precursor by methylation of enol that is one of azlactone …show more content…
Methyl ether (**) can be generated as cis- and trans- isomers, but was isolated as a single isomer. This compound was stable against heat at 60 degrees and was not transformed into 5-trifluoromethyl oxazole (**), whereas compound (*) was unstable, turned into easily rearrangement oxazole (**) in the middle of isolation. To confirm this rearrangement of compound (*), when we heated at 60 degrees for 30min, compound (*) was observed to convert into oxazole (**) completely.
By the way, major product was mesoion () which was proceeded predominantly N-methylated in this condition. Because the preliminary examination that was using silver salt as base and toluene as solvent at heating gave rich in O-methylated compounds and controlled side reaction of