The metal template effect on O-alkylation of tetrahydroxy[3.1.3.1]metacyclophane with 4-(chloromethyl)pyridine to afford tetrakis- [(4-pyridylmethyl)oxy][3.1.3.1]metacyclophanes and their conformational studies

• Published in: Canadian journal of chemistry Vol. 79; no. 10; pp. 1422 - 1430
• Main Authors: Yamato, Takehiko, Kumamaru, Kenji, Tsuzuki, Hirohisa
• Format: Journal Article
• Language: English
• Published: Ottawa, Canada NRC Research Press 01-10-2001
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v01-115

An attempted O-alkylation of the flexible macrocycle tetrahydroxy[3.1.3.1]metacyclophane (
1
) with 4-(chloromethyl) pyridine (
2a
) in the presence of NaH under THF reflux gave 1,3-di-O-substitution product distal-
3a
as a major product. In contrast, tetraol
1
was O-alkylated with
2a
in the presence of Cs
2
CO
3
to afford a mixture of two conformers of tetra-O-alkylated product
4a
in a ratio of 77:23 (1,4-alternate-
4a
:partial-cone-
4a
) in 95% yield. No formation of the cone conformer in the reaction of the tetraol
1
with
2a
, in comparison with those with 2-(chloromethyl) pyridine (
2b
) or benzyl bromide (
2c
) in the presence of NaH or K
2
CO
3
, which predominantly afforded cone-conformer, might be attributable to the absence of contributions derived from cation–N interactions as well as cation– interactions. The latter effect might be much smaller because of the decreased -density of the pyridine ring compared to that of the benzene ring. The structural characterization of these products in solution as well as solid state is also discussed.Key words: macrocycles, calixarenes, cyclophanes, [3.1.3.1]metacyclophanes, O-alkylation, conformation, crystal structure, cation–N interaction.