Synthesis of Macrocyclic Tetraamido-N Ligands

Gordon-Wylie etaU US Patent 6,011,152 (January 4, 2000) Assignee Carnegie Mellon University Utility Ligands for Oxidizing Complexes 

The product from Stepl (10 mmol) was dissolved in 50 ml pyridine and 1,2-benzene diamine (10 mol) added. The mixture was heated to 55 °C, PCI3 (20 mmol) quickly added, and the mixture heated to 110-115 °C 48 hours. Thereafter, the contents were acidified with HCl to a final pH 2. The mixture was stirred with 300 ml CH2CI2 3 hours, extracted twice with 150 ml CH2CI2, and dried. The combined organics were washed with twice 100 ml 0.1 M HCl and then dilute Na2C03. Solvents were removed and the crude product re-crystallized in 95% ethyl alcohol. H- and C-NMR and IR data supplied for products. 

Tetramethyl diethyl, (I), and dicyclohexyl diethyl, (II), macrolinkers were also prepared in 60-65% and 70-75% yields, respectively, by the author. 

Another ring closure method entails converting the macrolinker intermediate into the corresponding di-oxazolone by refluxing with isobutyryl chloride and then reacting with 1,2-diamine-4-acetamide dihydrobromide as illustrated in Eq. 1 and discussed by the author. 

Non-aromatic macrocycles were also prepared by the author for ring sizes 12, (III), 13, (VI), and 14, (V), respectively. 

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