Suzuki-Miyaura Cross-Coupling Reaction of Dichloro-Heteroaromatics: Synthesis of Functionalized Dinucleophilic Fragments

Abstract

The Suzuki-Miyaura cross-coupling reaction has successfully been applied for the synthesis of 4,4'-[6-(diethylamino)-1,3,5-triazine-2,4-diyl]diphenol (4a), 4,4'-(pyrimidine-4,6-diyl)diphenol (4b), 4,4'-(pyridine-2,6-diyl)diphenol (4c). The reaction of 4,6-dichloro-N,N-diethyl-1,3,5-triazin-2-amine (1a), 4,6-dichloropyrimidine (1b) and 2,6-dichloropyridine (1c) with p-methoxyphenylboronic acid (2) in the presence of palladium catalyst followed by demethylation reaction furnished the desired products in good to excellent yields. To test the reactivity of these nucleophiles, the compound 4a was further reacted with cyanuric chloride to get trimeric fragment (5a). All the compounds were characterized by their physical, spectral ( 1 H and 13 C NMR and Mass) and microanalytical data. These dinucleophilic fragments (4a-4c) having triazine, pyrimidine and pyridine rings, respectively, are excellent future candidates for the construction of large functional hetero-atom bridged macrocycles for diverse applications in host-guest chemistry, supramolecular catalysis, self-assembly and other related fields of supramolecular chemistry in addition to their potential in medicinal chemistry.

Functionalized calix[4]arenes as potential therapeutic agents

“…By virtue of these efforts, recently, the heteroatom-bridged calixhetarenes emerged as a new class of macrocyclic host molecules where heteroatom and heteroaromatic rings were installed instead of methylene bridges and simple aromatic ring, respectively, of conventional calixarene. [91][92][93][94][95] This new type of functionalized calix [4]arenes can easily be accessed by the reaction of dinucleophilic fragment [96] with dielectrophilic fragment [97] in either one-pot fashion or fragment-coupling approach, and by changing the size of these dinucleophilic and dielectrophilic components, the cavity size of these macrocycles can be tuned. Owing to the intrinsic electronic nature of bridging heteroatoms such as nitrogen that can adopt different electronic configurations to form various degrees of conjugation with their adjacent aromatic rings, heteroatom-bridged calix [4](het)arenes exhibit unique cavity structure and molecular recognition properties.…”