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A Novel Approach to the Evaluation of the Importance of Steric and Electronic Effects in S N Ar Reactions: A Computational, Thermodynamic and 1 H and 13 C NMR Study of “Meisenheimer‐Type” Adducts in the Benzo[ b ]thiophene Series
Author(s) -
Consiglio Giovanni,
Cosimelli Barbara,
Guernelli Susanna,
Lanza Camilla Zaira,
Sancassan Fernando,
Spinelli Domenico,
Stenta Marco
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000725
Subject(s) - chemistry , steric effects , thiophene , adduct , nucleophile , electronic effect , equilibrium constant , reaction rate constant , methoxide , chemical shift , nuclear magnetic resonance spectroscopy , stability constants of complexes , medicinal chemistry , computational chemistry , methanol , stereochemistry , organic chemistry , kinetics , catalysis , physics , quantum mechanics , aqueous solution
The synthetically useful nucleophilic attack on nitrobenzo[ b ]thiophenes, a starting point for ring‐opening/ring‐closure pathways to different heterocyclic systems, has been investigated in detail. 3‐Nitrobenzo[ b ]thiophene ( 9 ) and 2‐nitrobenzo[ b ]thiophene ( 10 ) react with sodium methoxide in either DMSO or methanol to give the relevant “Meisenheimer‐type” adducts 9′ and 10′ , identified by NMR spectroscopy. A UV study indicated that the equilibrium constants for the formation of 9′ at 293 K are 10.1 and 40 700 L mol –1 in methanol and in DMSO, respectively. Competition reactions showed that the stability constant of 10′ is lower than that of 9′ : accordingly, DFT [B3LYP/6‐31+G(d,p)] calculations indicate that the formation of 9′ is thermodynamically more favoured than that of 10′ both in the gas phase and in DMSO. The reason for the opposite sequence in the stability constants previously found for the corresponding gem ‐dimethoxy Meisenheimer adducts 7′ and 8′ was therefore investigated in depth and appears to be a consequence of different steric interactions in the starting compounds, 2‐methoxy‐3‐nitro‐( 7 ) and 3‐methoxy‐2‐nitrobenzo[ b ]thiophene ( 8 ), respectively. A study of 13 C NMR chemical shift changes accompanying the formation of adducts 9′ and 10′ confirms that the formation of the adduct exhibiting the larger stability constant is accompanied by a smaller π electron density redistribution, as we have previously found in other cases all governed by electronic effects. The opposite behaviour is observed in the formation of the gem ‐dimethoxy adducts 7′ and 8′ , which is a consequence of the predominance of steric effects. Further outcomes of more general interest deal with the aromatic character of benzo[ b ]thiophenes. NMR spectroscopic data and calculated bond lengths show that in the studied reactions the benzene ring, unlike the thiophene one, is scarcely affected by methoxide addition, retaining its nearly “full” aromatic character. Benzocondensation increases the stability constants of σ‐adducts mainly because of a marked reduction in the aromatic character of the thiophene ring in the substrates.