Synthesis, NMR spectroscopy, and crystal structure of [9](N6,9)-6-aminopurinophane

Abstract

[9](N6,9)-6-Aminopurinophane, 9, was synthesized by Mitsunobu coupling of 9-azidononanol, 5, and 6-chloropurine, 6. Reduction of the azide allowed for intramolecular nucleophilic displacement of chloride by the resultant amine and cyclization to the cyclophane. Variable temperature proton NMR showed the presence of two conformers below −25 °C separated by an activation barrier having a ΔGc≠ = 50.2 ± 2.5 kJ mol−1. The conformers arose from partial rotation about the C6—N6 bond, with the anti conformation assigned to the major isomer, 9a, and the syn conformation to the minor, 9b. The crystal structure of the [9](N6,9)-6-aminopurinophane, C14H21N5, was determined at 173 K. The crystals are monoclinic, of space group P21/n, with a = 16.941(3) Å, b = 8.512(2) Å, c = 19.300(2) Å, β = 95.90(1)°, V = 2769(1) Å3,Dc = 1.24 g cm−3 Dm = 1.27 g cm−3, for Z = 8, λ(CuKα) = 1.540598 Å. R1 = 0.0364, R2 = 0.0395 for 2846 reflections, ((R1) = 0.0319, R2 = 0.0365 for 2556 reflections with 1 > 2.5σ(I)). The purine ring shows small but significant distortions from planarity. The N(1)—C(6)—N(6)—C(1′) fragment adopts an anti conformation, which is twisted by approximately 35° from the plane of the purine ring, and the exocyclic 6-nitrogen is partially pyramidalized. Such pyramidalization is consistent with the Bader–Wiberg theory of barriers to rotation about bonds.