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

Truong Hong Hieu; Le Tuan Anh; Anatoly T Soldatenkov; Vasily G Vasil’ev; Victor N Khrustalev

doi:10.1107/S1600536813007241

. 2013 Mar 23;69(Pt 4):o565–o566. doi: 10.1107/S1600536813007241

Ethyl 23-benzyl-8,11,14-trioxa-23,28,29-triazapentacyclo[19.7.1.0^2,7.0^15,20.0^22,27]nonacosa-2,4,6,15(20),16,18,21,26-octaene-26-carboxylate

Truong Hong Hieu ^a,^*, Le Tuan Anh ^a, Anatoly T Soldatenkov ^b, Vasily G Vasil’ev ^b, Victor N Khrustalev ^c

PMCID: PMC3629615 PMID: 23634102

Abstract

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.

Related literature

For general background to the design, synthesis, chemical properties and applications of macrocyclic ligands for coordination chemistry, see: Hiraoka (1982 ▶); Pedersen (1988 ▶); Gokel & Murillo (1996 ▶); Bradshaw & Izatt (1997 ▶). For the crystal structures of related compounds, see: Levov et al. (2006 ▶, 2008 ▶); Komarova et al. (2008 ▶); Anh et al. (2008 ▶, 2012a ▶,b ▶,c ▶); Hieu et al. (2009 ▶, 2011 ▶, 2012a ▶,b ▶); Khieu et al. (2011 ▶); Sokol et al. (2011 ▶).

Experimental

Crystal data

C₃₃H₃₅N₃O₅
M _r = 553.64
Monoclinic,
a = 10.5304 (5) Å
b = 12.6363 (5) Å
c = 10.7246 (5) Å
β = 92.865 (1)°
V = 1425.29 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.30 × 0.24 × 0.21 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.974, T _max = 0.982
18837 measured reflections
8289 independent reflections
6878 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.094
S = 1.00
8289 reflections
377 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Click here for additional data file.^{(37.7KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813007241/cv5393sup1.cif

e-69-0o565-sup1.cif^{(37.7KB, cif)}

Click here for additional data file.^{(405.5KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813007241/cv5393Isup2.hkl

e-69-0o565-Isup2.hkl^{(405.5KB, hkl)}

Click here for additional data file.^{(11.1KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813007241/cv5393Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N24—H24⋯O1′	0.882 (18)	2.015 (18)	2.6928 (16)	132.8 (15)
N25—H25⋯O14	0.882 (18)	2.441 (17)	2.9744 (17)	119.3 (13)
C6—H6⋯O1′ⁱ	0.95	2.42	3.3516 (19)	168
C18—H18⋯O1′ⁱⁱ	0.95	2.42	3.3613 (19)	174

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We thank the National Foundation for Science and Technology Development (NAFOSTED), Hanoi, Vietnam (grant No. 104.02–2012.44) for the financial support of this work.

supplementary crystallographic information

Comment

Design, preparation and applications of macroheterocyclic ligands for coordination, supramolecular and medicinal chemistry draw constant attention of investigators during the last several decades (Hiraoka, 1982; Pedersen,1988; Gokel & Murillo, 1996; Bradshaw & Izatt, 1997). Recently we have developed the effective method of synthesis of azacrown ethers including piperidine (Levov et al., 2006); Anh et al., 2008, 2012a,b), cycloalkanopiperidine (Levov et al. 2008); bispidine (Komarova et al.; Sokol et al.; Hieu et al. 2012a; Anh et al. 2012c); perhydropyrimidine (Hieu et al., 2011) and perhydrotriazine (Hieu et al., 2009, 2012b; Khieu et al., 2011) subunits.

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, C₃₃H₃₅N₃O₅ (I), was unambiguously established by X-ray diffraction study.

The molecule of I comprises a pentacyclic system containing the aza-14-crown-4-ether macrocycle, tetrahydropyrimidine, tetrahydropyridine and two benzene rings (Fig. 2). The aza-14-crown-4-ether ring adopts a bowl conformation. The configuration of the C7—O8—C9—C10 —O11—C12—C13—O14—C15 polyether chain is t–g^(-)–t–t–g⁽⁺⁾–t (t = trans, 180°; g = gauche, ±60°). The dihedral angle between the planes of the benzene rings fused to the aza-14-crown-4-ether moiety is 62.37 (5)°. The central tetrahydropyrimidine ring has an envelope conformation (the C1 carbon atom is out of the plane passed through the other atoms of the ring (r.m.s. deviation = 0.023 Å) by 0.661 (2) Å), which is stabilized by the intramolecular N25—H25···O14 hydrogen bond (Table 1). The terminal tetrahydropyridine ring adopts a distorted chair conformation (the N1' nitrogen and C6' carbon atoms are out of the plane passed through the other atoms of the ring (r.m.s. deviation = 0.012 Å) by -0.245 (3) and 0.431 (3) Å, respectively). The three N24, N25 and N1' nitrogen atoms have the trigonal-pyramidal geometries. The carboxylate substituent (except for the terminal C16' carbon atom) is practically coplanar to the basal C22—C23—C4'—C5' plane of the tetrahydropyridine ring (the O2'—C14'—C4'—C5' dihedral angle is -5.5 (2)°). This disposition is apparently determined by the intramolecular N24—H24···O1' hydrogen bond (Table 1).

The molecule of I possesses an asymmetric center at the C1 carbon atom and crystallizes in the chiral space group P2₁. 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).

Experimental

Ammonium acetate (5.0 g, 65 mmol) was added to a solution of 1,5-bis(2-formylphenoxy)-3-oxapentane (1.57 g, 5.0 mmol) and 1-benzyl-4-ethoxycarbonylpiperidin-3-one (1.48 g, 5.0 mmol) in ethanol (30 ml) – acetic acid (2 ml). The reaction mixture was stirred at 293 K for 3 days. At the end of the reaction, the formed precipitate was filtered off, washed with ethanol and chromatographically purified on the column filled with silica gel. A re-crystallization from hexane:ethylacetate (3:1) mixture gave 0.83 g of light-yellow crystals of I.Yield is 30.0%. M.p. = 373–376 K. IR (KBr), ν/cm^-1: 1599, 1644, 3297, 3374, 3453. ¹H NMR (CDCl₃, 400 MHz, 300 K): δ = 1.29 (t, 3H, J = 7.2 and 6.8, CH₂CH₃), 2.26 and 2.78 (both m, 1H and 3H, correspondingly, NCH₂CH₂), 3.50 and 3.85 (both d, 1H each, J = 13.2 each, NCH₂Ar), 3.73–4.15 (m, 9H, OCH₂CH₂OCH₂CH₂O and CH₂CH₃), 4.83 (s, 1H, N—H25), 6.05 (s, 1H, H1), 6.73 (dd, 2H, J = 7.7 and 1.6, H6 and H16), 6.8 (broad t, 2H, J = 8.9, H4 and H18), 6.97–7.09 (m, 5H, H_arom), 7.28–7.32 (m, 2H, H_arom), 7.47 (dd, 2H, J = 7.6 and 1.6, H3), 7.87 (dd, 2H, J = 7.6 and 1.2, H19), 8.61 (s, 1H, N—H24). Anal. Calcd for C₃₃H₃₅N₃O₅: C, 71.59; H, 6.37; N, 7.59. Found: C, 71.53; H, 6.22; N, 7.37.