Ethyl 23-benzyl-8,11,14-trioxa-23,28,29-triazapentacyclo[19.7.1.02,7.015,20.022,27]nonacosa-2,4,6,15(20),16,18,21,26-octaene-26-carboxylate

The title compound, C33H35N3O5, is the product of the multicomponent condensation of 1-benzyl-4-ethoxycarbonylpiperidin-3-one with 1,5-bis(2-formylphenoxy)-3-oxapentane and ammonium acetate. The molecule comprises a pentacyclic system containing the aza-14-crown-4-ether macrocycle, tetrahydropyrimidine, tetrahydropyridine and two benzene rings. The aza-14-crown-4-ether ring adopts a bowl conformation with a dihedral angle of 62.37 (5)° between the benzene rings. The tetrahydropyrimidine ring has an envelope conformation with the chiral C atom as the flap, whereas the tetrahydropyridine ring adopts a distorted chair conformation. Two amino groups are involved in intramolecular N—H⋯O hydrogen bonds. In the crystal, weak C—H⋯O hydrogen bonds link the molecules into layers parallel to the ab plane.

The title compound, C 33 H 35 N 3 O 5 , is the product of the multicomponent condensation of 1-benzyl-4-ethoxycarbonylpiperidin-3-one with 1,5-bis(2-formylphenoxy)-3-oxapentane and ammonium acetate. The molecule comprises a pentacyclic system containing the aza-14-crown-4-ether macrocycle, tetrahydropyrimidine, tetrahydropyridine and two benzene rings. The aza-14-crown-4-ether ring adopts a bowl conformation with a dihedral angle of 62.37 (5) between the benzene rings. The tetrahydropyrimidine ring has an envelope conformation with the chiral C atom as the flap, whereas the tetrahydropyridine ring adopts a distorted chair conformation. Two amino groups are involved in intramolecular N-HÁ Á ÁO hydrogen bonds. In the crystal, weak C-HÁ Á ÁO hydrogen bonds link the molecules into layers parallel to the ab plane.
In attempts to apply the chemistry for obtaining azacrown ether containing ethoxy-substituted bispidino subunit with two nitrogen atoms in the unsymmetrical positions, we studied the multicomponent condensation of the 1-benzyl-4-ethoxycarbonylpiperidin-3-one (ketone component) with 1,5-bis(2-formylphenoxy)-3-oxapentane (podand) and ammonium acetate. The reaction has proceeded smoothly under mild conditions to give the title compound as an unexpected product ( Fig. 1). The first step of this cascade process appears to be the intermolecular condensation of one aldehyde group of the podand with the activated methylene group of the ketone component. Then the addition of one molecule of ammonia to the keto-group yields its hydroxyl-amino form. Further the second aldehyde group is condensed with the amino group to form the intermediate azacrown ether containing 1,4-azadiene fragment fused to piperidine moiety. The final step is the double Mannich cycloaddition of another molecule of ammonia to the azadiene moiety followed by dehydration to form the product. The structure of the new azacrown system, C 33 H 35 N 3 O 5 (I), was unambiguously established by X-ray diffraction study.
The molecule of I possesses an asymmetric center at the C1 carbon atom and crystallizes in the chiral space group P2 1 .
However, its absolute configuration cannot be objectively determined because the absence of the heavy (Z > 14) atoms within the molecule.
In the crystal, the molecules of I are bound by the weak intermolecular C-H···O hydrogen bonding interactions (Table   1) into layers parallel to ab> plane ( Figure 3).

Refinement
The absolute structure of I cannot be objectively determined by the refinement of Flack parameter because the absence of the heavy (Z > 14) atoms within the molecule.
The hydrogen atoms of the amino groups were localized in the difference-Fourier map and refined isotropically with fixed isotropic displacement parameters [U iso (H) = 1.2U eq (N)]. The other hydrogen atoms were placed in calculated positions with C-H = 0.95-1.00 Å and refined in the riding model with fixed isotropic displacement parameters [U iso (H) = 1.5U eq (C) for the methyl group and 1.2U eq (C) for the other groups].    Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.