Cyclodehydration of N-(Aminoalkyl)benzamides under Mild Conditions with a Hendrickson Reagent Analogue

Abstract

Methods for the cyclodehydration of N-(aminoalkyl)benzamides are few and employ harsh reaction conditions. We have found that the easily prepared phosphonium anhydrides 1 (Hendrickson reagent) or 2 can be used for cyclodehydration of N-(aminoalkyl)benzamides under very mild conditions (room temperature) to produce five-, six-, and seven-membered cyclic amidines. Good yields are obtained by employing a temporary trityl group protection strategy. Cyclic analogue 2 can be used when the product cyclic amidine is organic-soluble, thus producing water-soluble byproducts.

Supramolecular gels for the remediation of reactive organophosphorus compounds

“…35 The proposed formation of compounds 7 and 8 through elimination and intramolecular cyclisation has previously been suggested by Loughlin and coworkers. 36 The incorporation of DCP into the reaction mechanism shows this system has potential to act as a novel selective remediation method for reactive organophosphonate compounds including CWAs and pesticides.…”

Synthesis, screening and docking of small heterocycles as Glycogen Phosphorylase inhibitors

“…Illustrative examples of small heterocyclic compounds typically not reported against GP, such as oxazolines 1-3 [41], dihydro-1,3-oxazine 4 [41], tetrahydro-1,3-oxazepine 5 [41], thiazolines 6-7 [41], tetrahydropyrimidines 8-11 [40], tetrahydrodiazepine 12 [40], hexahydro-1H-benzimidazole 13 [40], and morpholines (scaffold for mimetics of EKL) 14- at the AMP, purine and indole binding sites revealed interesting interactions with HGLP. Overall the heterocyclic ring of each compound favours pi stacking in between the rings of TYR613 and PHE285, with approximately 8Å separating the rings of these two residues.…”

“…Samples of compounds 1-13 were synthesised as reported elsewhere [40,41]. 1L5Q) [7] at the indole binding site was also used in Surflex-Dock.…”

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

“…In 2013, Loughlin and co-workers demonstrated the cyclization of N-(aminoalkyl)benzamides 61a promoted by Hendrickson's reagent to give five-, six-, and seven-membered cyclic amidines 61b (Scheme 61). 105 It is worth mentioning that this synthetic protocol utilized mild reaction conditions (room temperature), while traditional methods required elevated temperatures to construct cyclic amidines. 106 A bulky temporary trityl protecting group on the terminal amine in 61a improved the product yields significantly by efficiently preventing its reaction with Hendrickson's reagent.…”