title: Intramolecular Rearrangement of α-Amino Acid Amide Derivatives of 2-Aminobenzothiazoles.
abstract: We have found that α-amino acid amide derivatives of 2-aminobenzothiazoles undergo a time-dependent, thermal rearrangement in which the amine group attacks the 2-position carbon of the thiazole ring to form a 5,5-spiro ring system. This is followed by sulfur leaving and air oxidation to the corresponding symmetrical disulfide. The isolated yields of such products are quite high (>70%) if there is conformational bias to further promote the intramolecular reaction such as for the 2-aminobenzothiazole amides derived from proline or 4-aminopiperidine-4-carboxylic acid. This rearrangement has not been described previously for α-amino acid amide derivatives of 2-aminobenzothiazoles. However, a related reaction involving 2-semicarbazido benzothiazoles has been recently reported.
authors.affiliation: Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd., Doylestown, PA 18902.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Pelletier
authors.affiliation: Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd., Doylestown, PA 18902.
authors.forename: Venkata
authors.initials: V
authors.lastname: Velvadapu
authors.affiliation: Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd., Doylestown, PA 18902.
authors.forename: Mark E
authors.initials: ME
authors.lastname: McDonnell
authors.affiliation: Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd., Doylestown, PA 18902.
authors.forename: Jay E
authors.initials: JE
authors.lastname: Wrobel
authors.affiliation: Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Rd., Doylestown, PA 18902.
authors.forename: Allen B
authors.initials: AB
authors.lastname: Reitz
keywords: 2-aminobenzothiazole; diphenyldisulfide; prodrugs; rearrangement; riluzole amides