The Synthesis Of Oxazolines And Benzoxazoles With PPh₃/DDQ As The Dehydrating Reagents

Oxazolines and benzoxazoles, existing in natural products, and with a wide range of biological activities, have found extensive applications in organic synthesis, catalysis and material chemistry. Even though there are many synthetic methods to prepare these two kinds of compounds, the exploration of new, concise synthetic methods is still an active research field.In this thesis, a combination of PPh₃ and DDQ was used as dehydrating reagents for the preparation of aromatic and aliphatic oxazolines from N-(2-hydroxyethyl)amides via intramolecular, dehydrate cyclolization. DCM was used as the solvent and the molar ratio of the N-(2-hydroxyethyl) amides to PPh₃/DDQ were 1: 1.5: 1.5. 28 Aromatic (or aliphatic) oxazolines were synthesized, including 14 unreported oxazolines. Their structures were characterized, or confirmed by IR, 1H NMR, 13C NMR, and LRMS or HRMS. In most cases, the yields were in the range of 80% and 99%. Compared with the well known PPh₃/DEAD system, the use of PPh₃/DDQ as dehydrating reagents is cheaper, and the reaction is faster and also high yielding.Reactions of aromatic substrates are faster than their aliphatic analogues. With substrates derived from chiral amino alcohols, the configurations of carbon attached to N for amino alcohol moiety did not change, whereas configuration of chiral carbon attached to OH inversed. The stereochemistry of acyl moiety of substrates from cyclopropanecarboxylic acid was also studied. When 2-phenylcyclopropanecarboxuylic acid amide was used, isomerization was observed for cis-isomer, and no isomerization was observed for the trans one. Isomerization occurred for both cis-, and tans-2-(2-methylpropenyl)-3,3-dimethyl cyclopropaneformyl amide. 12.7% cis-one isomized to tans-one for cis substrates, and 4.6% trans to cis for trans substrate.Benzoxazoles were also synthesized using PPh₃/DDQ and amide derived from 2-aminophenol. Poor yields were obtained when reactions were carried out in a one pot manner. However, good to excellent yields could be gotten from the amides. in refluxing toluene with 2 equivalents excess of PPh₃ and DDQ. 10 aromatic (or aliphatic) benzoxazoles were synthesized, and 1 is a new compound. In the synthesis of benzoxazoles, there was no obvious superiorittes for PPh₃/DDQ system, as compared to the Mistunobu reagent, in both reactivity and reaction time.