Crystal structure of 22,24,25-trimethyl-8,11,14-trioxa-25-azatetracyclo[19.3.1.02,7.015,20]pentacosa-2,4,6,15(20),16,18-hexaen-23-one

Macrocyclic 22,24,25-trimethyl-8,11,14-trioxa-25-azatetracyclo[19.3.1.02,7.015,20]pentacosa-2,4,6,15 (20),16,18-hexaen-23-one obtained by a Petrenko–Kritchenko condensation of 1,5-bis(2-formylphenoxy)-3-oxapentane, pentan-3-one and methylammonium acetate has been studied by X-ray structural analysis.

Recently, we have developed effective methods for the synthesis of azacrown ethers containing -piperidone (Levov et al., 2006Anh et al., 2008Anh et al., , 2012aHieu et al. (2011Hieu et al. ( , 2012a or -arylpyridine (Anh & Soldatenkov, 2016;Tran et al., 2016) subunits. This chemistry allowed us to make systematic studies of the fine structural features of a novel series of azacrown macrocycles using X-ray diffraction. Such data should be of use for the subsequent design of more certain drug-like macroheterocyclic molecules bearing new would-be pharmacophore groups. ISSN 2056-9890 In attempts to apply this chemistry for obtaining azacrown ethers which contain a 1,3,5-trimethyl-substituted -piperidine moiety, we studied the condensation of diethylketone and 1,5bis(2-formylphenoxy)-3-oxapentane in the presence of methylammonium acetate taken both as the nitrogen source and as the template in ethanol/acetic acid solution. The reaction proceeded smoothly to give the expected azacrown title molecule, (I), with 32% yield.
The molecule of (I) possesses four asymmetric centers at the C1, C13, C13A and C1A carbon atoms and can have potentially numerous diastereomers. The crystal of (I) is racemic and consists of enantiomeric pairs with the following relative configuration of the centers: rac-1R*,13S*,13AR*,1AS*.

research communications Figure 3
A portion of the crystal packing of (I) indicating the intermolecularstacking interactions. Dashed lines indicate the intra-and intermolecular C-HÁ Á ÁO hydrogen bonds.

Figure 2
Crystal packing of (I) along the b axis demonstrating the zigzag hydrogen-bonded chains along [100]. Dashed lines indicate the intra-and intermolecular C-HÁ Á ÁO hydrogen bonds.

Refinement
Crystal data, data collection and structure refinement details are summarized in Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2015 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.34 e Å −3 Δρ min = −0.23 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.