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Palladium‐catalyzed cyclization of 2‐alkynyl‐ N ‐ethanoyl anilines to indoles: synthesis, structural, spectroscopic, and mechanistic study
Author(s) -
Hoque Mohammad Mazharol,
Halim Mohammad A.,
Sarwar Mohammed G.,
Khan Md. Wahab
Publication year - 2015
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3477
Subject(s) - chemistry , palladium , density functional theory , catalysis , solvation , homo/lumo , acetonitrile , indole test , photochemistry , solvent effects , computational chemistry , nucleophile , molecular orbital , medicinal chemistry , solvent , molecule , organic chemistry
This study reports a facial regio‐selective synthesis of 2‐alkyl‐ N ‐ethanoyl indoles from substituted‐ N ‐ethanoyl anilines employing palladium (II) chloride, which acts as a cyclization catalyst. The mechanistic trait of palladium‐based cyclization is also explored by employing density functional theory. In a two‐step mechanism, the palladium, which attaches to the ethylene carbons, promotes the proton transfer and cyclization . The gas‐phase barrier height of the first transition state is 37 kcal/mol, indicating the rate‐determining step of this reaction. Incorporating acetonitrile through the solvation model on density solvation model reduces the barrier height to 31 kcal/mol. In the presence of solvent, the electron‐releasing (–CH 3 ) group has a greater influence on the reduction of the barrier height compared with the electron‐withdrawing group (–Cl). These results further confirm that solvent plays an important role on palladium‐catalyzed proton transfer and cyclization . For unveiling structural, spectroscopic, and photophysical properties, experimental and computational studies are also performed. Thermodynamic analysis discloses that these reactions are exothermic. The highest occupied molecular orbitallowest unoccupied molecular orbital gap (4.9–5.0 eV) confirms that these compounds are more chemically reactive than indole. The calculated UV–Vis spectra by time‐dependent density functional theory exhibit strong peaks at 290, 246, and 232 nm, in good agreement with the experimental results. Moreover, experimental and computed 1 H and 13 C NMR chemical shifts of the indole derivatives are well correlated. Copyright © 2015 John Wiley & Sons, Ltd.