Phosphoric-Acid-Catalyzed ortho-Selective Intramolecular Cyclodehydration Reaction of Phenols and Anilines
Sukit Chonradeenitchakul1, Takahito Kuribara1,2, Honoka Yuba1
1Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
None:
In this study, we report an organocatalyst-controlled ortho-selective intramolecular cyclodehydration of phenols and anilines. In the presence of 1 mol % of a phosphoric acid catalyst, resorcinol, 3-aminophenol, and 1,3-phenylenediamine derivatives underwent highly regioselective cyclodehydration to afford 4-hydroxybenzofuran, 4-hydroxyindole, 4-aminobenzofuran, and 4-aminoindole derivatives in up to 97% yield and >99:1 regioselectivity. The resulting products were further derivatized and applied in a formal synthesis of tambromycin. Kinetic studies and DFT calculations elucidated the regioselective reaction mechanism.
More Related Videos
Related Concept Videos
Preparation of Acid Anhydrides
The carboxylate ion acts as a nucleophile that attacks the carbonyl carbon of the acid chloride to form a tetrahedral intermediate. Subsequently, the re-formation of the carbonyl group with the loss of the chloride ion as a leaving group leads to the formation of an acid...
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Preparation of Diols and Pinacol Rearrangement
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
Alkynes to Aldehydes and Ketones: Acid-Catalyzed Hydration
Analogous to alkenes, alkynes also undergo acid-catalyzed hydration. While the addition of water to an alkene gives an alcohol, hydration of alkynes produces different products such as aldehydes and ketones.
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.


