UNPRECEDENTED OUTCOME OF BASE-PROMOTED NEBER REARRANGEMENT OF O-MESYLOXIME OF 2-ARYL-1,2,3,4-TETRAHYDRO-1-METHYLSUL FONYL-4-QUINOLONE- SYNTHESIS OF 4-AMINO-2-ARYLQUINOLINES

Abstract

O-Mesyloximes derived from 2-aryl-1,2,3,4-tetrahydro-1-methylsulfonyl-4-quinolones react with sodium ethoxide in ethanol to afford the 4-amino-2-arylquinolines in high yield. No traces of the 3-amino-2-aryl-4-quinolones expected from the Neber rearrangement of the substrates were detected or isolated from the reaction mixture. The structures of the products were determined using a combination of ¹H NMR, ¹³C NMR, IR and mass spectroscopic techniques.     

An extended scope synthesis of an artificial safranine cofactor

Safranines hold great promise as artificial flavin-like electron transfer cofactors with tunable properties. We have previously reported the stepwise synthesis of a safranine analogue, p-methoxy safranine. We now report an improved synthetic pathway which enables the synthesis of safranine analogues containing electron donating phenyl substituents. Low potential safranine analogues were synthesized that extend the range of two electron midpoint reduction potentials to 249 mV, or 11.4 kcal/mol. NMR analysis of the safranine series demonstrates that the ¹⁵N chemical shift at the N(5) position correlates with the two-electron reduction midpoint potential.     

Manipulating reduction potentials in an artificial safranin cofactor

Safranines hold great promise as artificial flavin-like electron transfer cofactors with tunable properties. We report the design and chemical synthesis of the p-methoxy derivative of safranine O using a new synthetic route based on the Ulmann condensation. Spectroelectrochemical comparison of the purified parent safranine and this derivative demonstrates that the modification increases its two-electron reduction potential by 125 mV, or 5.75 kcal/mol. This modification also causes redshifts in the absorbance and fluorescence spectra of the cofactor, suggesting that it may find future utility in arrayed sensor applications.