The unanticipated oxidation of a tertiary amine in a tetracyclic glyoxal-cyclam condensate yielding zinc(II) coordinated to a sterically hindered amine oxide

The crystal structure of the first reported glyoxal–tetraazamacrocycle condensate amine oxide is presented. The sterically hindered oxidized amine binds zinc(II) through the oxygen atom in its folded cleft, with an internal hydrogen bond across the cleft between the oxygen and a protonated tertiary nitrogen.

Tertiary amines, like those found in glyoxal-tetraazamacrocycle condensates, are known to oxidize to amine oxides under oxidizing conditions, usually in the presence of hydrogen peroxide or 3-chloroperbenzoic acid (O'Neal et al., 2001;Bernier et al., 2009).These amine oxides can be reduced back to amines in the presence of reducing agents (Hayashi et al., 1959); zinc metal is often involved in the reduction reaction (Emerson & Rees, 1962;Kagami & Motoki, 1978;Jousseaume & Chanson, 1987;Balicki, 1989).In the present case, the tertiary amine was oxidized to the amine oxide in the presence of air, methanol, and zinc(II) chloride.Molecular oxygen is able to oxidize tertiary amines (Bernier et al., 2009), although it is generally inefficient and often is improved by the presence of transition metal ions, which may form metal-oxo catalysts in situ, although unlikely in the present case with zinc(II) (Jain & Sain, 2002;Wang et al., 1999;Imada et al., 2003).Under development in our labs are more efficient ways to make the mono-and diamine oxides of glyoxal-tetraazamacrocycle condensates -at present both hydrogen peroxide and 3chloroperbenzoic acid have shown increased activity over molecular oxygen -and will be reported in due course.
Here, we present the first example of a glyoxal-tetraazamacrocycle condensate that serendipitously oxidized to a mono-amine-oxide during a complexation reaction with zinc(II) chloride.The resulting sterically demanding amine oxide coordinates in a monodentate fashion to a zinc(II) ion concomitantly coordinated to three additional chloro ligands.

Structural commentary
We pioneered the use of glyoxal-tetraazamacrocycle condensates as rigid, bulky, bidentate ligands for transition metal ions (Hubin, McCormick, Busch & Alcock 1998), and have continued our efforts (Hubin et al., 1999(Hubin et al., , 2002;;May et al., 2004, Won et al., 2015) in coordinating various metal-containing species, in this case ZnCl 2 , to these bidentate amines of the glyoxal-cyclam condensate.During the course of the current work, air oxidation of one amine occurred, which produced an amine oxide moiety that subsequently resulted in coordination of [ZnCl 3 ] À in a monodentate fashion.In the majority of the unoxidized amine examples, where two non-adjacent amine nitrogen atoms point into the cleft of the folded ligand, the metal ion coordinates in a bidentate fashion [palladium(II) and copper(II) examples: Hubin, McCormick, Alcock, et al., 1998;Hubin et al., 2002;May et al., 2004;Won et al., 2015].However, in the present case (Fig. 1), the oxygen atom, O1, extends the reach of the amine oxide and renders bidentate coordination unfavorable.Furthermore, the oxygen of the amine oxide moiety is situated in the center of the tetracycle cavity by virtue of the distorted tetrahedral geometry about the atoms participating in the intramolecular N3� � �O1 hydrogen-bonding interaction.In addition, the oxygen atom fills most of this cavity created by the tetracycle, thus the larger than expected N1-O1-Zn1 bond angle [124.84 (9) � , Table 1] is instrumental in minimizing the steric hindrance caused by the bulk of the trichloro zinc unit.An interesting comparison can be drawn to our copper(I) glyoxal-cyclam condensate structure (Hubin et al., 1999).In that case, the low coordination number preferred by copper(I), along with the steric bulk of the ligand, resulted in a copper(I) complex with two cyclamglyoxal ligands coordinated in a linear fashion to the metal.

Supramolecular features
Within the asymmetric unit, the ring nitrogen atom, N1, forms a bifurcated hydrogen bond with both the water, O2, and Noxide oxygen, O1, atoms (see Fig. 2, Table 2 for details).One water hydrogen forms a hydrogen bond to one chlorine, Cl1, The molecular structure of (I).Atomic displacement ellipsoids shown at 50% probability with hydrogen atoms shown as spheres of arbitrary radius.
of the standard molecule resulting in an R 2 2 (10) ring (Etter et al., 1990).The remaining water hydrogen atom forms a bifurcated hydrogen bond to a neighboring chlorine, Cl2, related by translation along the a-axis and to a tetracycle nitrogen atom related by the screw-axis parallel to the b-axis.This is true for both components of the disordered water molecule (see below).The overall motif is a di-periodic network (Nespolo, 2019) of hydrogen-bonded molecules parallel to the ab plane.The remaining interactions within the structure (primarily C-H� � �Cl) are van der Waals contacts that direct the packing.

Database survey
We have found only two structural analogues of this zinc(II) coordination sphere -tertiary amine oxide and three chlorides coordinated to tetrahedral zinc(II) (Jasiewicz et al., 2011; refcodes: EWOZOG, EWOZUM).The Jasiewicz complexes utilize a spartein backbone ligand, which naturally form a folded structure with the amine lone pair of electrons pointed either concave or convex to the remainder of the structure.Analogous to our tetraazamacrocycle-glyoxal condensate, this generates either a concave or convex metal binding site.The most direct comparison to our own compound would be the concave isomer [(-)-spartein-16-ium N-1-oxide]trichlorozinc(II).In both this complex and our own, an important non-covalent interaction is the hydrogen bond formed by the oxygen of the amine oxide and the proton located on the nonadjacent nitrogen.The folded nature of the amine oxide functionalized concave backbones allow the zinc atom to fit tightly inside the ligand.Notably, the sparteine compound shows similar average C-N-O bond angles (111.0 � cf 110.68 � ) and a larger N-O-Zn bond angle than our compound [127.4(5) and 124.84 (9) � , respectively].These two angles work in conjunction to determine how far into the cavity the metal atom can approach.The smaller N-O-Zn angle of our tetraazamacrocyclic ligand allows the zinc to sit further into and, ideally, interact more strongly with atoms forming the cavity.

Synthesis and crystallization
The cyclam-glyoxal condensate was prepared according to a literature procedure (Le Baccon et al., 2001): 0.24 g (1 mmol) of cyclam-glyoxal and 0.14 g (1 mmol) of ZnCl 2 were stirred for three days in methanol (20 mL) in the presence of air.A white solid product precipitated and was filtered from the solution on a fine glass frit, and washed with a minimal amount of methanol before being dried under vacuum.X-ray quality colorless block crystals were obtained by ether diffusion into a 2-butanone solution.

Refinement
The structure was solved by dual-space methods (SHELXT; Sheldrick, 2015a) and refinement was routine (SHELXL; Sheldrick, 2015b; Table 3).All non-hydrogen atoms were refined with anisotropic atomic displacement parameters.The water of crystallization exhibited mild positional disorder that was modeled over two equal occupancy sites.Hydrogen atoms on the water and protonated amine nitrogen were initially located in a difference-Fourier map.The amine hydrogen atom was ultimately refined using a riding model.The coordinates of the water hydrogen atoms were allowed to refine, with similarity restraints applied to all four O-H distances.Atomic displacement parameters of these hydrogen atoms were tied to that of the N or O to which they are bonded.All other hydrogen atoms were positioned at geometrically calculated positions with C-H = 0.99 or 1.00 A for methylene and methine carbon atoms respectively; U iso (H) = 1.5 � U eq (O) or 1.2 � U eq (N/C).

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.

Figure 2
Figure 2 Packing diagram of (I) viewed along the c-axis.Hydrogen atoms, except those involved in hydrogen bonding, and one component of the disordered water of crystallization are omitted for clarity.Light-blue dashed lines represent hydrogen-bonding interactions.One layer of molecules is shown for clarity.

Table 3
Experimental details.