Crystal structure of 9,20-dimethyl-1,8,12,19-tetraazatetracyclo[17.3.1.02,7.013,18]tricosane dihydrate from synchrotron X-ray data

The macrocyclic title compound crystallizes as a dihydrate with a 12-membered inner ring system. Hydrogen bonds involving the lattice water molecules link the components into a three-dimensional network system.


Chemical context
Macrocyclic ligands and their complexes are involved in diverse application fields such as catalysis, enzyme mimics, chemical sensors, purification of waste water, selective metalion recovery and antitumor agents and therapy (Meyer et al., 1998). The family of macrocyclic amines with fourteenmembered inner rings has received attention due to their anti-HIV activity (Liang & Sadler, 2004;Ronconi & Sadler, 2007;Ross et al., 2012). There has also been considerable interest in C-or N-functionalized macrocyclic compounds and their metal complexes because the structural and chemical properties are often quite different from those of the corresponding non-functionalized compounds (Barefield, 2010;Choi et al., 2010). Structural modifications of the macrocycles based on methylene bridging of adjacent nitrogen atoms have been achieved using various methods (Royal et al., 1998;Tripier et al., 2001;Hubin, 2003;Kang et al., 2008).
In the present work, we attempted the reaction of L 1 with one equivalent of formaldehyde and synthesized the title compound, C 21 H 40 N 4 Á2H 2 O, (I). Interestingly, the title compound, containing a six-membered 1,3-diazacyclohexane ring, was the main product of the synthesis, while the compound containing a five-membered 1,3-diazacyclopentane ring did not crystallize. In order to determine the molecular and crystal structure of the title compound, single-crystal X-ray structural determination was performed by using synchrotron data. Fig. 1 shows an ellipsoid plot of the molecular components of compound (I). The asymmetric unit comprises a macrocyclic C 21 H 40 N 4 molecule and two lattice water molecules. The two methyl substituents of the C10 and C20 atoms are on the same side with respect to the macrocyclic plane of the four N atoms (Fig. 1). The cyclohexane rings, together with the 1,3-diazacyclohexane ring and the 1,3-diamino-1-methylpropane moiety, are fused to the 12-membered macrocycle. All sixmembered rings exist in a slightly distorted chair conformation. The N1-C1-C6-N2 and N3-C12-C17-N4 torsion angle displays a gauche conformation. The bond lengths are in the ranges 1.4526 (16)-1.4786 (17) Å and 1.517 (2)-1.5414 (17) Å for the C-N and C-C bonds, respectively. The N1-C20 distance is the longest C-N distance, presumably as a consequence of the methyl group on the C20 atom and the NÁ Á ÁH-O hydrogen bond involving N1. The bond angles within the six-membered 1,3-diazacyclohexane ring, N2-C7-N3, C7-N2-C8, and C7-N3-C10, are 109.89 (10), 109.60 (10), and 108.08 (9) , respectively. All other C-N, C-C, and C-H bond lengths and corresponding angles are in the normal range for such compounds (Royal et al., 1998;Tripier et al., 2001). The intramolecular hydrogen bond between the amine group N4-H1N4 and the tertiary N3 atom lends some rigidity to the 12-membered macropolycycle L 2 ring (Fig. 1).

Figure 2
Crystal packing diagram of (I), viewed perpendicular to the ac plane. H atoms not involved in hydrogen bonds have been omitted. The dashed lines represent N-HÁ Á ÁN (blue), O-HÁ Á ÁO (pink) and O-HÁ Á ÁN (green) hydrogen bonds, respectively.

Figure 1
The asymmetric unit of (I), showing the atom-numbering scheme. Non-H atoms are shown as displacement ellipsoids at the 50% probability level. Hydrogen-bonding interactions are indicated by dashed lines.  (Kang et al., 2008). However, no structure of any other compound with L 2 has been deposited.

Refinement
Crystal data, data collection, and structure refinement details are summarized in Table 2. All C-bound H atoms in the complex were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C-H distances of 0.98-1.00 Å with U iso (H) values of 1.5 and 1.2 U eq of the parent atoms, respectively. N-and O-bound H atoms were assigned based on a difference Fourier map, and were refined with distance restraints of 0.91 (4) and 0.88 (2) Å (using DFIX and DANG commands), respectively, and with U iso (H) values of 1.2U eq of the parent atoms.  Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.042 (4)

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.