The influence of aza-substitution on azole aromaticity

• Published in: Tetrahedron 2010-04, Vol.66 (14), p.2695-2699
• Main Author: Ramsden, Christopher A.
• Format: Article
• Language: English
• Subjects: Aromaticity; ASE; Azoles; Chemical reactivity; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; HOMA; NICS; Organic chemistry; Preparations and properties; Reactivity and mechanisms
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.02.019

A homogeneous set of values for the aromaticity indices ASE (Aromatic Stabilisation Energy), HOMA (Harmonic Oscillator Model of Aromaticity) and NICS(1) (Nucleus-Independent Chemical Shift) for azoles has been investigated using multiple linear regression analysis. Statistically-significant relationships were found between the aromaticity indices and the number of nitrogen atoms at positions 2/5 and 3/4 of the ring. Aza-derivatives of pyrrole, furan and thiophene all gave similar relationships. For all three indices aza-substitution at positions 2 and/or 5 increases aromaticity. However, aza-substitution at positions 3 and/or 4 decreases classical aromaticity (ASE and HOMA) but increases magnetic aromaticity (NICS(1)). These indices appear to be measuring different properties of the azoles. The influence of aza-substitution on these different aspects of aromaticity is tentatively rationalized in terms of either bond length equalization or uniformity of π electron distribution. [Display omitted]