American Chemical Society
jo2c02733_si_003.mp4 (4.12 MB)

14- and 17-Membered Macrocycles Containing Amide, Amino, and Carbamate Groups in The Monocyclic Skeleton: An Accidental Byproduct Obtained from a Residue after Separation

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posted on 2023-05-15, 16:07 authored by Hiroki Horita, Izumi Sato, Huiyeong Ju, Eunji Lee, Mari Ikeda, Shunsuke Kuwahara, Yoichi Habata
A 14-membered cyclic compound (3) containing amide, amino, and carbamate groups, which was serendipitously obtained in the oily residue after the separation of 4-benzyl-1,4,7,10-tetraazacyldododecane-2,6-dione (2a) and 4,16-dibenzyl-1,4,7,10,13,16,19,22-octaazacyclo-tetracosane-2,6,14,18-tetraone (2b), is reported. The structure of 3 is formally a CO2 insertion between positions 3 and 4 of the 12-membered ring in 2a. The CO2 insertion was confirmed in the synthesis of diethyl 2,2′-(benzylazanediyl)diacetate (1) by the reaction of benzylamine with ethyl bromoacetate using K2CO3 as the base. In addition, the selective synthesis of 3 and ethyl N-benzyl-N-((2-ethoxy-2-oxoethoxy)carbonyl)glycinate (5) and their kinetic behavior are reported. The reaction of 5 with triethylenetetramine afforded a 17-membered macrocycle (7), which was obtained in an 18% yield. Compounds 6 and 8 were prepared from 3 and 7 by introducing benzyl groups to improve their solubility in organic solvents. Titration experiments using 1H NMR showed that both 6 and 8 exhibit Li+ selectivity.