Facile Access to Mono-Cinchona Alkaloid-Derived Ligands

Abstract

Two facile accesses to mono-cinchona alkaloid-derived ligands, by conventional heating conditions and solvent-free microwave irradiation, are described. 1,4-Dichlorophthalazine (PHAL) or 3,6-dichloropyridazine (PYDZ) reacted with quinine (QN), cinchonine (CN), or cinchonidine (CND) by using CaH₂ as acid-bonding reagent in DMF at 90–100°C to provide mono-cinchona alkaloid-derived ligands 2a–f (87–95%) in 1.5 h. However, the coupling reactions were performed under solvent-free microwave conditions to yield 2a–f (64–89%) within 15 min.

Keywords:

• CaH₂
• 1,4-dichlorophthalazine
• 3,6-dichloropyridazine
• microwave irradiation
• mono-cinchona alkaloid-derived ligands

ACKNOWLEDGMENT

We thank the National Science Foundation of China (NSFC 20672141) for financial support of this work.

Notes

^a Isolated yield based on PHAL or PYDZ.

^a QN (1.0 mmol), PHAL (0.5 mmol), K₂CO₃ (2.0 mmol), and TBAB (10 mol%) were used unless otherwise noted.

^b Isolated yield based on 1,4-dichlorophthalazine (PHAL).

^c Bis-QN ligand [(QN)₂ PHAL] was obtained in 13% yield.

^d The ratio of QN and PHAL is 1:1.

^e The ratio of QN and PHAL is 3:1; bis-QN ligand [(QN)₂ PHAL] was obtained in 67% yield.

^a The ratio of cinchona alkaloids and PHAL or PRDZ is 1:1.

^b Isolated yield based on PHAL or PYDZ.