Hydrogen-bond-driven electrophilic activation for selectivity control: scope and limitations of fluorous alcohol-promoted selective formation of 1,2-disubstituted benzimidazoles and mechanistic insight for rationale of selectivity.
Hydrogen-bond-driven electrophilic activation for selectivity control during competitive formation of 1,2-disubstituted and 2-substituted benzimidazoles from o-phenylenediamine and aldehydes is reported. The fluorous alcohols trifluoroethanol and hexafluoro-2-propanol efficiently promote the cyclocondensation of o-phenylenediamine with aldehydes to afford selectively the 1,2-disubstituted benzimidazoles at rt in short times. A mechanistic insight is invoked by NMR, mass spectrometry, and chemical studies to rationalize the selectivity. The ability of the fluorous alcohols in promoting the reaction and controlling the selectivity can be envisaged from their better hydrogen bond donor (HBD) abilities compared to that of the other organic solvents as well as of water. Due to the better HBD values, the fluorous alcohols efficiently promote the initial bisimine formation by electrophilic activation of the aldehyde carbonyl. Subsequently the hydrogen-bond-mediated activation of the in situ-formed bisimine triggers the rearrangement via 1,3-hydride shift to form the 1,2-disubstituted benzimidazoles.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar 160 062, Punjab, India.
Rajesh
R
Chebolu
Damodara N
DN
Kommi
Dinesh
D
Kumar
Narendra
N
Bollineni
Asit K
AK
Chakraborti
D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D002384:Catalysis; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry
D000438:Alcohols; D000447:Aldehydes; D001562:Benzimidazoles; D006845:Hydrocarbons, Fluorinated; D012997:Solvents