The Relative Stability of Indole Isomers Is a Consequence of the Glidewell-Lloyd Rule

Abstract

Indole (1) is a heterocyclic aromatic compound consisting of a pyrrole ring (5MR) fused with a benzene ring (6MR). This compound is highly stable, found in several natural products, and used as a building block for the synthesis of novel organic compounds. On the other hand, its isomers isoindole (2) and indolizine (3) are much less stable and are normally isolated when bonded to other stable compounds. The stability of these compounds has been analyzed in terms of local aromaticity using magnetic, geometric, and delocalization criteria. All criteria used indicate that there is a continuing reduction in aromaticity of the 6MR whereas, for the 5MR, the aromaticity increases when going from 1 to 3. This is confirmed by Natural Resonance theory calculations indicating that the resonant structures which retain the aromaticity of 5MR are the ones having the largest contribution.The results obtained suggest that the relative stability of indole isomers is a consequence of the Glidewell-Lloyd rule.

Antiaromaticity–Aromaticity Interplay in Fused Benzenoid Systems Using Molecular Electrostatic Potential Topology

“…It is also possible to explicate the dielectric properties of the network system based on the configuration. The findings of the work could be correlated with the Glidewell−Lloyd rule, 71,72 which is the extension of Clar's πsextet rule. According to the former, total π-electrons in a conjugated polycyclic system tend to form the smallest 4n + 2 groups by avoiding smallest 4n group formation.…”

Theoretical Study on Singlet Fission in Aromatic Diaza s-Indacene Dimers

“…According to Table , A-1 shows a negligible y 0 while A-2 , A-3 , and A-4 show small-to-intermediate y 0 values, suggesting that A-1 is expected to be stable while the latter ones unstable. Very recently, Pino-Rios and Solá have investigated the stabilities of indole isomers, which are composed of a six-membered benzene ring attached with a five-membered pyrrole ring and thus can be viewed as the analogues of A-1 , A-2 , and A-4 . They have pointed out that indole (analogue of A-1 ) is stable while isoindole and indolizine (analogues of A-2 and A-4 , respectively) are unstable on the basis of several calculations on aromaticity, as corroborated by the fact that isoindole was synthesized 80 years later than indole .…”

“…Very recently, Pino-Rios and Solá have investigated the stabilities of indole isomers, which are composed of a six-membered benzene ring attached with a five-membered pyrrole ring and thus can be viewed as the analogues of A-1 , A-2 , and A-4 . They have pointed out that indole (analogue of A-1 ) is stable while isoindole and indolizine (analogues of A-2 and A-4 , respectively) are unstable on the basis of several calculations on aromaticity, as corroborated by the fact that isoindole was synthesized 80 years later than indole . In these respects, A- m molecules except for A-1 are predicted not to be synthesized easily, but recent developments for the synthetic root of sp 2 -hybritized aza compounds including isoindole , are expected to pave a way for the synthesis of the promising A- m molecules.…”

Nickel-Catalyzed Dearomative Arylboration of Indoles: Regioselective Synthesis of C2- and C3-Borylated Indolines

“…However, 5-fluoroindoline 10 and chloro-substituted indolines 11−13 were formed in good yields and regioselectivities. Additionally, electron-rich 5-and 6-methoxyindoles underwent dearomatization in excellent yields (product [15][16], though 6-methoxyindoline 16 formed in diminished regioselectivity (7:1 rr). This observation can perhaps be attributed to destabilization of the forming benzylic alkyl- [Ni] complex in the transition state by electron donation from the methoxy substituent, resulting in higher rates of formation of the other regioisomer.…”

“…Reaction with the arylbromide electrophile would form arylboration product V or VI . A significant challenge in the development of this intermolecular dearomatization could be overcoming the energy of aromaticity, ∼18.7 kcal/mol, at a rate faster than Miyaura borylation. Additionally, controlling the regioselectivity of the migratory insertion event was identified as an opportunity to access both regioisomers of the product ( V or VI ).…”