Tautomerism and Regioselectivity of Acylation of 4-Hydroxy-2-mercaptopyridine-N-oxide and 2,4-Dimercaptopyridine-N-oxide: A Computational Study

Abstract

Relative thermodynamic stability and dipole moments of tautomers of 2-mercapto- (1), 4-hydroxy-2-mercapto- (2), 2,4-dimercapto- (3), 4-hydroxy- (4), and 4-mercapto- (5) pyridine-N-oxides were calculated in gas phase at the B3LYP/6-31G(d,p) level of theory. According to the calculations, the general trend in stability of the tautomers follows 2-thiono > 4-thiono/keto > N-oxide. A similar trend is observed in monoacetyl (6 and 7) and diacetyl (8 and 9) derivatives of 2 and 3. Therefore, monoacetylation of 2 or 3 is expected to give the 4-acetyl derivatives and diacetylation the 1,4-diacetyl isomers as the thermodynamic products.

Keywords:

• Acetates
• derivatives
• DFT calculations
• 1-hydroxypyridine-2(1H)-thione
• stability
• tautomerism

Dedicated to Professor Marian Mikołajczyk, CBMiM PAN in Łódź, Poland, on the occasion of his 70th birthday.

Partial financial support for this work was received from the National Science Foundation (DMR-0606317).

Notes

^a B3LYP/6–31G(d,p) level of theory.

^a B3LYP/6-31G(d,p) level of theory. For structures 2, see Figure 3.

^a B3LYP/6–31G(d,p) level of theory. For structures 6, see Figure 4.

^a B3LYP/6-31G(d,p) level of theory. For structures 8, see Figure 5.