Synthesis and structure of large 24-mer and 36-mer oxamate-based macrocycles

2.1 Synthesis

In order to have a suitable precursor to synthesize H₄L¹, 1 was converted to 2, as displayed in Scheme4. The synthesis of 1 was readily achieved by the reaction of two equivalents of 2-nitroaniline with one equivalent of oxalyl chloride in THF to afford 1 as a green-yellow precipitate. The insolubility of 1 prevented its full characterization, cf. Experimental Section. Nevertheless, 1 was subjected to undergo a reduction reaction as described in the Experimental Section to afford 2 as a light-yellow powder in high yield.

Scheme 4:

Principal synthetic strategy to synthesize 1 and 2.

In order to synthesize H₄L¹ starting from 2, we explored several sets of conditions and reagents as dimethyl oxalate, oxalyl chloride or ethoxalyl chloride in different molecular ratios, concentrations and solvents. Unfortunately, all variations did not give rise to the desired product. Additionally, trials to convert 2 into a cyclic product in analogy to a protocol reported recently for 1,4,8,11-tetraazacyclotetradecane-2,3-dione failed [8]. In all cases, the formation of colorless solid materials was observed, which were found to be nearly insoluble in common organic solvents. Most likely, that indicates the formation of oligomeric and polymeric products. In the course of these investigations, it was observed that by following a procedure as described in the Experimental Section a colorless powder can be obtained, which was found to be the novel 24-membered macrocycle H₈L², Scheme cf. 5. According to our procedure, H₈L² can be synthesized with yields reaching 15%. Macrocyclic H₈L² is slightly soluble in DMF and DMSO, allowing its characterization by NMR spectroscopy and even by single-crystal X-ray crystallographic studies, cf. below. Trials to use H₈L² as a potential ligand to form multinuclear Cu^II complexes as reported for macrocycles related to H₈L², cf. [8, 9] for example, failed so far.

Scheme 5:

Principal synthetic strategy to synthesize H₈L², H₁₂L³ and 4 starting with compound 2.

In experiments to expand the size of 24-mer H₈L², compound 2 was treated first with an equimolar amount of ethoxalyl chloride, followed by the addition of one equivalent of oxalyl chloride, cf. Scheme 5 and Experimental Section. Out of such experiments colorless solid materials were isolated, which were nearly insoluble in all common organic solvents. However, sonication of a DMF suspension of such a colorless solid afforded after crystallization the formation of a few crystals, representing the 36-membered macrocycle H₁₂L³, cf. Scheme 5. The molecular and crystal structures of 36-mer H₁₂L³ are illustrated in Figs. 3 and 4, respectively.

In order to have an alternative approach to the desired type VII complex (Scheme 2), compound 2 was treated first with Cu(OAc)₂·H₂O, followed by the addition of NaOH with the aim to afford complex 3, cf. Scheme 5. It was supposed that the addition of oxalyl chloride to 3 could give rise to the type VII complex (Scheme 2) in a final ring-closing synthetic step. However, out of such reactions only binuclear 4, cf. Scheme 5, could be so far isolated as the only pure reaction product obtained after crystallization. The molecular and crystal structures of 4 are illustrated below in Figs. 5 and 6 or 7, respectively.

2.2 Single-crystal X-ray diffraction studies

In the following, the molecular and crystal structures of H₈L², H₁₂L³ and 4, as determined by single-crystal X-ray diffraction, are reported. Crystal data and numbers pertinent to data collection and structure refinement are summarized in Table 1.

2.2.1 Crystallographic characterization of H₈L²

The molecular structure of H₈L² is displayed in Fig. 1, and selected bond lengths and angles are summarized in Table 2. Selected geometrical parameters of inter- and intramolecular hydrogen bonds of H₈L² are given in Table 3. Macrocyclic H₈L² exhibits crystallographically imposed C₂ symmetry, with the C₂ axes passing the center of its cavity. As displayed in Fig. 1, four molecules of DMF interact with H₈L² on its exterior by means of hydrogen bond formation, cf. entries 5–8 in Table 3.

Fig. 1:

Ortep plot (30% probability ellipsoids) of the molecular structure of H₈L². All carbon-bonded hydrogen atoms were omitted for clarity. Additionally, the four DMF molecules which interact with H₈L² by means of hydrogen bonds (indicated by dotted lines) are shown. Symmetry code used to generate “A” labeled atoms: −x+1, y, −z+1/2.

Table 2:

Selected bond lengths (Å) and angles (deg) of H₈L².^a

Bond lengths
C1–O1		1.220(2)		N2–C2		1.340(2)		C3–O3		1.222(2)		N4–C16		1.418(2)
C1–N1		1.345(2)		C5–C10		1.393(2)		C3–N3		1.345(2)		N4–C4		1.343(2)
N1–C5		1.425(2)		C2–O2		1.219(2)		N3–C11		1.419(2)		C4–O4		1.217(2)
N2–C10		1.421(2)		C2–C3		1.542(2)		C11–C16		1.403(2)		C4–O1A		1.543(2)
Bonds angles
O1–C1–N1		126.4(2)		N1–C5–C10		120.0 (2)		C2–C3–O3		121.8(2)		C16–N4–C4		122.1(1)
O1–C1–C4A		121.8(1)		C5–C10–N2		120.7(1)		O3–C3–N3		126.4(2)		N4–C4–O4		126.1(2)
C1A–C4–O4		120.9(2)		C10–N2–C2		122.1(1)		C3–N3–C11		123.4(2)		C1A–C4–N4		113.0(1)
C1–N1–C5		123.4(1)		N2–C2–O2		126.0 (2)		N3–C11–C16		120.1 (1)		C1A–C4–O4		120.9(2)
N1–C1–C4A		111.8(1)		N2–C2–C3		113.1(2)		C11–C16–N4		120.5 (1)		C16–N4–C4		122.1(1)

1. ^aSymmetry transformations used to generate equivalent atoms “A”: −x+1, y, −z+1/2.

Table 3:

Selected bond lengths (Å) and angles (deg) of intra- and intermolecular hydrogen bonds of H₈L².

Entry	D–H···Aa	D–H	H···A	D···A	D–H···A
			Intramolecular
1	N1–H1···O4A	0.91(2)	2.25(2)	2.680(2)	108(2)
2	N2–H2···O3	0.92(2)	2.36(2)	2.721(2)	104(2)
3	N3–H3···O2	0.91(2)	2.28(2)	2.678(2)	106(2)
4	N4–H4···O1A	0.91(2)	2.37(2)	2.722(2)	103(2)
			Intermolecularb
5	N1–H1···O5	0.92(2)	2.04(2)	2.890(2)	153(2)
6	N2–H2···O5	0.92(2)	2.01(2)	2.865(2)	155(2)
7	N3–H3···O6	0.91(2)	2.06(2)	2.901(2)	153(2)
8	N4–H4···O6	0.91(2)	1.95(2)	2.812(2)	157(2)

1. ^aSymmetry code: −x+1, y, −z+1/2.

2. ^bIntermolecular hydrogen bonds refer to those between H₈L² and DMF molecules.

The observed configuration of H₈L² seems to be fixed by several intramolecular hydrogen bonds between its N–H and C=O groups, cf. Fig. 1 and entries 1–4 in Table 3. Noticeably, none of the N–H or C=O groups are oriented into the cavity of H₈L². The analysis of the crystal structure revealed that no further intermolecular interactions are observed for H₈L². As described in the Experimental Section, there seems to be an Et₂O molecule inside the cavity of H₈L² and located along the crystallographic C₂ axes, although it could not be refined reliably.

Keeping the potential presence of one Et₂O inside the cavity of H₈L² in mind, the geometry of the cavity itself can be described as approximately quadratic as, for example, the distances N1···N4 and N3···N2A amount to 7.56 Å. In order to visualize the cavity further, we show in Fig. 2 two additional perspective views together with the indication of the geometrical centroid of H₈L². The atoms O1–O4 are located in the range from 4.293 to 4.312 Å away from the centroid, while the ranges of the nitrogen atoms N1–N4 and of the carbon atoms C1–C4 are 4.111–4.239 Å and 3.908–3.950 Å, respectively. The shortest distance between symmetry-related atoms of H₈L² is observed for C3···C3A with 7.722 Å.

Fig. 2:

Ortep plot (30% probability ellipsoids) of the molecular structure of the 24-mer macrocycle H₈L² in two different perspective views including its geometrical centroids of the atoms O1–O4, N1–N4 and their symmetry generated equivalents. All carbon-bonded hydrogen atoms are omitted for clarity. Dotted lines are used to symbolize formal bonds of O and N atoms to the geometrical centroid. Symmetry code used to generate “A” labeled atoms: −x+1, y, −z+1/2. Left: top view; right: side view.

Attempts to complex H₈L² in MeOH with varying amounts of Cu(NO₃)₂·6H₂O, CuCl₂·2H₂O or CuSO₄·5H₂O and NaOH or [ⁿBu₄N]OH and to isolate from these reaction mixtures the hypothetic Cu^II complexes such as, for example, [Cu₂(H₄L²)] failed so far.

2.2.2 Crystallographic characterization of H₁₂L³

As described in Scheme 5 and the Experimental Section, the successive treatment of 2 with ethoxalyl and oxalyl chloride resulted in the formation of a colorless solid, which was nearly insoluble in all organic solvents. This indicates that the solid represents polyamide(s) with long chain lengths. Assuming that this solid might contain soluble parts, a small amount of it was taken up in large excess of DMF and treated as described below. Out of such DMF dispersions, and unfortunately in just one occasion so far, a very small number of crystals could be separated. Their crystallographic characterization revealed unambiguously the formation of the 36-mer macrocycle H₁₂L³. The molecular structure of H₁₂L³ is displayed in Fig. 3, and selected bond lengths and angles are summarized in Table 4. Selected geometrical parameters of inter- and intramolecular hydrogen bonds of H₁₂L³ are given in Table 5.

Fig. 3:

Ortep plot (20% probability ellipsoids) of the molecular structure of H₁₂L³. All carbon-bonded hydrogen atoms and interstitial solvent molecules are omitted for clarity. Of the disordered atoms only one atomic position is shown. Dotted lines refer to intermolecular hydrogen bonds by which three DMF molecules interact with H₁₂L³ and to intramolecular hydrogen bonds, respectively.

Table 4:

Selected bond lengths (Å) and angles (deg) of H₁₂L³.

Bond lengths
C1–O1		1.227(2)		C19–C24		1.401(3)		C6–C7		1.541(2)		C37–C42		1.399(2)
C1–C12		1.541(2)		C24–N4		1.432(2)		C7–O7		1.225(2)		N10–C42		1.414(2)
C1–N1		1.337(2)		N4–C4		1.334(2)		N7–C7		1.338(2)		N10–C10		1.336(2)
N1–C13		1.416(2)		C4–O4		1.233(2)		N7–C31		1.424(2)		C10–O10		1.226(2)
C13–C18		1.397(3)		C4–C5		1.226(2)		C31–C36		1.395(3)		C10–C11		1.541(2)
N2–C18		1.425(2)		C5–O5		1.226(2)		N8–C36		1.416(2)		C11–O11		1.222(2)
N2–C2		1.337(2)		N5–C5		1.336(2)		N8–C8		1.340(2)		N11–C11		1.345(2)
C2–O2		1.228(2)		N5–C25		1.418(2)		C8–O8		1.340(2)		N11–C43		1.409(2)
C2–C3		1.535(2)		C25–C30		1.399(2)		C8–C9		1.538(2)		C43–C48		1.396(3)
C3–O3		1.219(2)		N6–C30		1.413(2)		C9–O9		1.228(2)		N12–C48		1.430(2)
C3–N3		1.348(2)		N6–C6		1.341(2)		N9–C9		1.336(2)		N12–C12		1.340(2)
N3–C19		1.416(2)		C6–O6		1.221(2)		N9–C37		1.424(2)		C12–O12		1.224(2)
Bond angles
O1–C1–N1		126.5(2)		C2–C3–N3		111.0(1)		C30–N6–C6		125.0 (2)		C8–C9–N9		113.9(2)
O1–C1–C12		121.7(2)		O3–C3–N3		128.4(2)		N6–C6–O6		127.2 (2)		O9–C9–N9		125.8(2)
N1–C1–C12		111.8(2)		N3–C19–C24		120.2(2)		N6–C6–C7		112.2(2)		N9–C37–C42		120.9(2)
C1–N1–C13		125.3(2)		C19–C24–N4		124.9(2)		O7–C7–N7		126.2(2)		N10–C10–O10		127.0 (2)
N1–C13–C18		121.4(2)		N4–C4–O4		126.7(2)		N7–C31–C36		119.6(2)		N10–C10–C11		111.6(2)
C13–C18–N2		123.3(2)		N4–C4–O5		113.3(2)		C13–C36–N8		120.6(2)		O10–C10–C11		121.3(2)
N2–C2–O2		126.7(2)		O4–C4–C5		120.1(2)		C36–N8–C8		124.7(2)		O11–C11–N11		127.5(2)
N2–C2–C3		112.2(2)		C4–C5–O5		121.4(2)		N8–C8–O8		127.1(2)		N11–C43–C48		118.3(2)
O2–C2–C3		121.1(2)		O5–C5–N5		126.3(2)		N8–C8–C9		122.1(2)		N12–C12–O12		125.9(2)
C2–C3–O3		120.7(2)		N5–C25–C30		123.4(2)		C8–C9–O9		120.3(2)		O12–C12–C1		113.9(2)

Table 5:

Selected bond lengths (A) and angles (deg) of intra- and intermolecular hydrogen bonds of H₁₂L³.

Entry	D–H···Aa	D–H	H···A	D···A	D–H···A
			Intramolecular
1	N1–H1···O2	0.92(3)	1.88(3)	2.658(2)	142(2)
2	N1–H1···O12	0.92(3)	2.24(2)	2.660(2)	107(2)
3	N2–H2···O3	0.86(2)	2.34(2)	2.726(2)	107(2)
4	N3–H3···O2	0.88(2)	2.33(2)	2.716(2)	106(2)
5	N3–H3···O4	0.88(2)	1.92(2)	2.701(2)	147(2)
6	N4–H4···O5	0.91(3)	2.26(2)	2.717(2)	111(2)
7	N5–H5···O4	0.80(2)	2.27(2)	2.677(2)	112(2)
8	N5–H5···O12	0.80(2)	2.17(2)	2.940(2)	160(2)
9	N6–H6···O5	0.84(2)	2.04(2)	2.733(2)	140(2)
10	N6–H6···O7	0.84(2)	2.32(2)	2.702(2)	108(2)
11	N7–H7···O6	0.83(3)	2.31(2)	2.693(2)	109(2)
12	N8–H8···O7	0.87(2)	2.05(2)	2.750(2)	136(2)
13	N8–H8···O9	0.87(2)	2.21(2)	2.645(2)	110(2)
14	N9–H9···O8	0.84(2)	2.40(2)	2.738(2)	105(2)
15	N10–H10···O9	0.82(2)	2.12(2)	2.787(2)	138(2)
16	N10–H10···O11	0.82(2)	2.26(2)	2.677(2)	112(2)
17	N11–H11···O10	0.84(2)	2.28(2)	2.683(2)	110(2)
18	N11–H11···N12	0.84(2)	2.46(2)	2.797(2)	105(2)
19	N12–H12···O1	0.81(3)	2.43(2)	2.737(2)	104(2)
			Intermolecularb
20	N4–H4···O1D	0.91(3)	2.02(3)	2.856(2)	153(2)
21	N12–H12···O2D	0.81(3)	2.04(3)	2.854(2)	166(2)
22	N9–H9···O3D	0.84(2)	2.05(3)	2.822(2)	154(2)
23c	N7A–H7A···O8	0.83(3)	2.18(3)	2.928(2)	150(2)
24c	N2–H2···O1B	0.86(2)	2.15(3)	2.964(2)	157(2)

1. ^aFor disordered atoms only one hydrogen bond is given.

2. ^bIntermolecular hydrogen bonds refer to those between H₁₂L³ and DMF molecules as well as to those between individual molecules of H₁₂L³.

3. ^cSymmetry codes: “A”=1−x, 1−y, −z; “B”=−x, 2−y, 1−z.

In contrast to H₈L² the larger macrocycle H₁₂L³ does not form a cavity in the solid state, cf. Fig. 3. This could be attributed to the larger number of acidic N–H acceptors and basic C=O acceptors of H₁₂L³ compared to H₈L² to form intramolecular hydrogen bonds or the higher flexibility of H₁₂L³. On the other hand, both Et₂O and DMF as solvents for the crystallization of H₁₂L³ might not represent suitable molecules for encapsulation by this large 36-mer cyclic polyamide. Nevertheless and as observed for H₈L², H₁₂L³ is also involved in several intermolecular hydrogen bonds with DMF molecules as well as several intramolecular ones. Especially the latter are regarded to fix the observed configuration of H₁₂L³, cf. Fig. 3 and Table 5, as discussed for H₈L². Interestingly, macrocycle H₁₂L³ forms chains in the solid state due to formation of intermolecular hydrogen bonds, cf. Fig. 4 and entries 23 and 24 in Table 5.

Fig. 4:

Ortep plot (30% probability ellipsoids) of a selected part of one of the chains formed by H₁₂L³ in the solid state due to intermolecular hydrogen bonds, indicated by dotted bonds. Symmetry codes: “A”=1−x, 1−y, −z; “B”=−x, 2−y, 1−z.

2.2.3 Crystallographic characterization of 4

The molecular structure of binuclear 4 is displayed in Fig. 5, and selected bond lengths and angles are summarized in Table 6. The complex exhibits crystallographically imposed inversion symmetry, with the inversion center located in the middle of the bond between atoms C7 and C7A, cf. Fig. 5.

Fig. 5:

Ortep (50% probability ellipsoids) of the molecular structure of 4. Symmetry code used to generate “A” labeled atoms: −x, −y+1, −z. Disordered water molecules which interact with 4 by means of hydrogen bond formation are omitted for clarity.

Table 6:

Selected bond lengths (Å) and angles (deg) of 4^a.

Bond lengths
Cu1–N1		2.017(3)		N1–C1		1.454(4)		N2–C7A		1.310(4)
Cu1–N2		1.921(3)		N2–C6		1.454(4)		C7–C7A		1.539(5)
Cu1–O1		2.0032(2)		O1–C7		1.260(3)		C1–C6		1.406(4)
Cu1−O2		1.945(2)		–		–		–		–
Bond angles
N1–Cu1–N2		83.92(10)		N1–Cu1–O1		167.19(10)		N2–Cu1−O2		177.98(9)
N1–Cu1–O2		97.86(10)		N2–Cu1–O1		83.94(9)		O1–Cu1–O2		94.35(9)

1. ^aSymmetry transformations used to generate equivalent atoms “A”: −x, −y+1, −z.

Each Cu^II ion of 4 is coordinated by one deprotonated amido and one neutral N donor atom as well as an oxygen atom of the bapoxH₄²⁻ ligand. Each Cu^II is coordinated furthermore by an O donor atom of an acetate ligand to give rise to a planar-quadratic CuN₂O₂ coordination unit. The planarity of the CuN₂O₂ coordination unit of the binuclear {Cu₂(bapoxH_4]}²⁺ complex fragments including the O2/O2A donor atoms of the acetate ligands is revealed by the calculation of a mean plane of all atoms. The root-mean-square deviation from planarity amounts to just 0.051 Å, whereby the smallest and highest deviation from planarity are observed for C7/C7A (0.004(2) Å) and N1/N1A (0.127(2) Å), respectively. Furthermore, the planarity of the CuN₂O₂ coordination units can be revealed by the sum of cis bond angles around Cu1 of 360.1(2)°.

The binuclear complex 4 has similar structural features as a closely related binuclear Cu^II Schiff-base complex reported by Opozda et al. [10], although the Schiff base corresponds to a tetraanionic ligand. However, in contrast to this report binuclear units of 4 interact with each other in the solid state to form layers. The layers are composed of chains due to the formation of dispersion interactions between individual complexes of 4, oriented along the crystallographic c axes, cf. Figs. 6 and 7.

Fig. 6:

Ortep plot (30% probability ellipsoids) of a selected part of one of the chains formed by 4 in the solid state due to intermolecular dispersion interactions. All carbon-bonded hydrogen atoms and the water molecules are omitted for clarity. The signs ∢ (angle) refer to interplanar angles and d gives the distance between π-stacked aromatic rings. Atoms belonging to either green- or red-colored areas exhibit at least one intermolecular distance to one atom of the opposite colored area of <3.6 Å. Symmetry codes: “A”=−x, −y+1, −z; “C”=x, y, z−1; “D”=x, y, z+1.

Fig. 7:

Ortep plot (30% probability ellipsoids) of a selected part of one of the layers formed by 4 in the solid state due to intermolecular dispersion and hydrogen bond interaction in two different views. All carbon-bonded hydrogen atoms and the water molecules are omitted for clarity. Dotted lines denote intermolecular hydrogen bonds. Dispersion interactions are not indicated. Left: side view, illustrating details of the intermolecular hydrogen bonds including atom labeling. Symmetry codes: “A”=−x, −y+1, −z; “C”=x, y, z−1; “D”=x, y, z+1; “E”=2−x, y−1/2, 5/2−z; “F”=2−x, y−1/2, 3/2−z; “G”=2−x, y−1/2, 1/2−z; “H”=2−x, y+1/2, 3/2−z. Right: top view, illustrating the arrangement of the layers along the crystallographic b axes by hydrogen bonds and along the crystallographic c axes by dispersion interactions.

These chains interact with each other by the formation of intermolecular hydrogen bonds. Selected structural parameters of the hydrogen bonds are given in Table 7, while Fig. 7 displays a part of one of the layers with emphasis on the illustration of observed hydrogen bond formation.

Table 7:

Selected bond lengths (Å) and angles (deg) of intermolecular hydrogen bonds of 3^a.

Entry	D–H···A	D–H	H···A	D···A	D–H···A
1	N1–H1···O3I	0.92(3)	2.00(3)	2.884(3)	161(3)
2	N1J–H2J···O1W	0.91(3)	2.24(3)	2.970(7)	137(2)
3	N1J–H2J···O1W	0.96(4)	1.93(4)	2.875(10)	166(4)
4	O1W–H3···O2	0.96(4)	2.36(4)	2.866(9)	113(3)

1. ^aSymmetry codes: I=1−x, 1−y, 1−z; J=x, 3/2−y, 1/2−z.

2.3 Ion-binding properties of H₈L²

According to the single-crystal X-ray diffraction analysis, the diameter of the cavity of macrocycle H₈L² is 7.5 Å. Thus, we suggested that H₈L² is a suitable macrocycle for binding spherical anions and cations. According to the 55% solution established by Mecozzi and Rebek Jr. [11], the volumes of species should be maximum, about 120 ų. Because of this, anions as the halides with spherical volumes of 11, 25, 31 and 44 ų for F⁻, Cl⁻, Br⁻ and I⁻ [12], respectively, or cations as Li⁺ (1 ų), Na⁺ (4 ų) and K⁺ (10 ų) [12] could be expected to be even multiple coordinated by the 24-mer macrocycle H₈L². We have conducted the binding experiments only with H₈L² because only this macrocycle was sufficiently soluble in DMSO (concentration of 10⁻⁵ M). The dilution experiments followed nicely the Lambert Beer law, which verified that there was no aggregate formation of the macrocycle in DMSO solution (Experimental Section). To determine the binding properties, we measured the UV/Vis spectrum of the macrocycle and followed its changes during the addition of cations or anions. For testing cation-binding properties, H₈L² was titrated with the salts LiBF₄, NaBF₄, KBF₄ and [ⁿBu₄N]BF₄. From this series, only Na⁺, K⁺ and [ⁿBu₄N]BF₄ induced changes in the UV/Vis spectrum of the macrocycle, although relatively small (ΔA=0.01, after the addition of 10 equiv.). Thus, we concluded that cations were not bound to the macrocycle and the small changes are attributable to the binding of the [BF₄]⁻ anion. For testing anion-binding properties, we used [ⁿBu₄N]BF₄, [ⁿBu₄N]Cl, [ⁿBu₄N]Br and [ⁿBu₄N]I. For chloride, bromide and iodide significant changes in UV/Vis spectra were observed, which led to calculated binding constants of 4500±120 M⁻¹, 22300±800 M⁻¹ and 12500±200 M⁻¹, respectively. Thus, H₈L² appeared to be selective for bromide and iodide anions, as it was expected from the volume assessment. This result led us to conclude that the cavity of the macrocycle in DMSO solution should be smaller than that observed in the solid state.

4.1 General methods and materials

All chemicals were purchased from commercial sources and used as received without further purification. The solvents were purified and dried according to standard procedures [13]. NMR spectra were recorded at room temperature with a Bruker AvanceIII 500 Ultra Shield Spectrometer (¹H at 500.300 MHz and ¹³C{¹H} at 125.813 MHz) in the Fourier transform mode. Chemical shifts are reported in δ (ppm) vs. SiMe₄ with the solvent signal as the reference ([D₆]DMSO: ¹H NMR, δ=2.50; and ¹³C{¹H}NMR, δ=39.52). FT-IR spectra were recorded in the range of 400–4000 cm⁻¹ on a Perkin-Elmer Spectrum 1000 FT-IR spectrophotometer in the form of KBr pressed pellets. Elemental analysis for C, H and N was performed on a Thermo FlashAE 1112 series. High-resolution mass spectra were recorded with a Bruker Daltonik micro-TOF-QII spectrometer.

4.2 UV/Vis anion recognition studies

The stock solutions of the macrocycle H₈L² were made up in DMSO with a final concentration of 10⁻⁵ M. Stock solutions of the guests were prepared by dissolving 10–100 equivalents of the [ⁿBu₄N]⁺ salt of the anion in question into 1 or 2 mL of the stock solution of the host. Serial dilutions of the solution containing the guest were performed so as to provide 20–25 equiv. of the guest relative to the host. UV/Vis spectroscopic data were then collected and combined to produce plots that showed the changes in host spectral features as a function of changes in the concentration of guest. The data were imported into the program HyperSpec and fitted by using all wavelengths recorded to obtain a binding constant [14].

4.3 X-ray crystallography

Data of H₈L², H₁₂L³ and 4 were collected with an Oxford Gemini S diffractometer. The structures were solved by direct methods and refined by full-matrix least-squares procedures on F² [15]. All non-hydrogen atoms were refined anisotropically. All carbon-bonded hydrogen atoms were refined using a riding model. The position of oxygen- and nitrogen-bonded hydrogen atoms was taken from difference Fourier maps and these hydrogen atoms were refined isotropically with appropriate DFIX and DANG restraints.

Compound H₈L² co-crystallizes with four molecules of DMF and one molecule of Et₂O, of which the DMF molecules could be refined properly. Remaining unrefined electron density peaks were observed in final refinement stages in the cavity of the macrocycle which are attributed to Et₂O. Any trials to refine them to Et₂O packing solvent molecules failed, most likely as the Et₂O molecule is dynamically disordered and is in addition statistically disordered along a crystallographic C₂ (2) axes. Because of this, the routine Squeeze in Platon [16] as a part of the Wingx software [17] was applied to generate a new dataset, to which all data reported here refer. Applying Squeeze resulted in a solvent accessible volume (SAV) of 275 ų per unit cell and an electron count of 85 within the SAV, which corresponds well with the electron count of 84 expected for two molecules of Et₂O. Despite these findings, we continue to refer to that compound as H₈L².

Compound H₁₂L³ co-crystallizes with four DMF molecules and one Et₂O molecule. The Et₂O molecule and one of the four crystallographically independent DMF molecules (O4D, N4D, C10D–C12D) act as pure packing solvents only. The other three DMF molecules interact with H₁₂L³ by means of hydrogen bond formation, as discussed and illustrated above. Despite these findings, we continue to refer to that compound as H₁₂L³. Furthermore, the atoms C11D, C12D and N4D of one DMF molecule were refined disordered with split occupancies of 0.18/0.82. Another DMF molecule with the atoms C4D–C6D, O2D, N2D has been refined disordered with split occupancies of 0.29/0.71.

In case of 4, the centrosymmetric complex did co-crystallize with two molecules of water, of which one is crystallographically independent. This water molecule is disordered and has been refined on two different positions for O1W/O1W′ with occupation factors of 0.69/0.31. The water molecule is involved in hydrogen bonds, as noted in Table 7, although for one hydrogen atom of it, namely H4, no hydrogen bonds are observed. This is attributed to the disorder. The hydrogen bonds of the water molecules are not further illustrated within the article for clarity reason and as they do not convert the described and graphically illustrated layers into a 3D network. Thus, we continue to refer to that compound as 4.

CCDC 1525886 (4), 1525887 (H₈L²) and 1525888 (H₁₂L³) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

4.4 Synthesis of 1

To a solution of 2-nitroaniline (9.66 g, 70 mmol) in THF (150 mL) was added oxalylchloride (3 mL, 35 mmol) dropwise with continuous stirring. The resulting reaction mixture was stirred for further 30 min at room temperature. The green-yellow precipitate was filtered off, washed with THF (2×50 mL) and dried in vacuo. Yield: 10.7 g (92%). – Anal. calcd. (%) for C₁₄H₁₀N₄O₆ (330.25 g mol⁻¹): C 50.92, H 3.05, N 16.96; found C 51.21, H 3.01, N 16.96. – IR: (KBr, cm⁻¹): ν=3293 (s, NH); 2979/2899 (w/w, CH); 1708/1608/1585 (s/m/m, CO); 1512/1339 (s/s, N=O).

The Supplementary Information gives the IR spectra of 1.

NMR spectra could not be recorded due to insolubility of 1 in all common organic solvents.

4.5 Synthesis of 2

To a suspension of 1 (6.6 g, 20 mmol) and 10% Pd/C (1 g) in MeOH, anhydrous ammonium formate (7.5 g, 119 mmol) was added in a single portion. The reaction mixture was stirred for 72 h at 35°C. Next, all solvent was removed and the residue was taken up in THF (500 mL). The resulting mixture was filtered off and the volume of the filtrate was reduced to about 10 mL. The slow addition of H₂O (400 mL) resulted in the formation of a light-yellow compound, which was filtered, washed with H₂O (3×100 mL) and dried in vacuo. Yield: 4.5 g (83%). – Anal. calcd. (%) for C₁₄H₁₄N₄O₂ (270.29 g mol⁻¹): C 62.21, H 5.22, N 20.73; found C 62.23, H 5.21, N 20.67. – IR: (KBr, cm⁻¹): ν=3441 (w, NH); 3368/3245 (m/m, NH₂); 2988/2900 (w/w, CH); 1661/1615 (s/s, CO).– ¹H NMR [(CD₃)₂SO, ppm]: δ=4.99 (s, 4H, H^b,b′), 6.62 (td, 2H, H^6,6′), 6.80 (dd, 2H, H^5,5′), 6.99 (td, 2H, H^4,4′), 7.29 (dd, 2H, H^3,3′), 9.99 (s, 2H,H^a,a′).– ¹³C{¹H} NMR [(CD₃)₂SO, ppm]: δ=116.3 (C^6,6′), 116.4 (C^5,5′), 122.2 (C^7,7′), 125.5 (C^4,4′), 126.7 (C^3,3′), 142.5 (C^2,2′), 158.6 (C^1,1′).

The Supplementary Information gives the IR, ¹H NMR and ¹³C{¹H} NMR spectra of 2.

4.6 Synthesis of H₈L²

To a solution of 2 (1.00 g, 3.7 mmol) in THF (400 mL) was added a solution of oxalyl chloride (0.32 mL, 3.7 mmol) in THF (50 mL) dropwise over 1 h with continuous stirring with formation of a colorless suspension. After stirring for further 2 h the volume was reduced to about 20 mL and a colorless powder was precipitated by the addition of H₂O (300 mL), which was filtered off, washed thoroughly with H₂O and dried in vacuo. This colorless powder was subjected to a Soxhlet extraction with THF (75 mL) overnight. The solid material remaining was dried in vacuo, and analyzed to be compound H₈L². Yield 0.32 g (13%). – Anal. calcd. (%) for C₃₂H₂₄N₈O₈(648.58 g mol⁻¹): C 59.26 H 3.73, N 17.28; found C 59.09, H 3.83, N 16.95. – IR: ν=3268 (s, NH); 2966/2863 (w/w, CH); 1677/1599 (s/s, CO). – ¹H NMR [(CD₃)₂SO, ppm]: δ=7.32 (dd, 8H, H^4,4′), 7.60 (dd, 8H, H^3,3′),10.70 (s, 8H, NH). – ¹³C{¹H} NMR [(CD₃)₂SO, ppm]: δ=126.2 (C^4,4′), 126.4 (C^3,3′), 130.1 (C^2,2′), 158.7 (C^1,1′). – MS (ESI-TOF, positive, DMSO): m/z=649.1838 [H₈L²+H]⁺.

The Supplementary Information gives the IR, ¹H NMR and ¹³C{¹H} NMR spectra as well as the electrospray ionization-mass spectroscopy (ESI-MS) spectrum of H₈L². Crystals suitable for X-ray crystallographic studies were grown by slow diffusion of Et₂O vapor into a DMF solution of H₈L².

4.7 Successive treatment of 2 with ethoxalyl and oxalyl chloride to afford H₁₂L³

To a solution of 2 (0.30 g, 1.1 mmol) in THF (100 mL) was added a solution of ethoxalyl chloride (0.15 g, 1.1 mmol) in THF (10 mL) dropwise with continuous stirring to form a colorless suspension. The reaction progress was monitored by thin-layer chromatography until the full disappearance of 2 after about 1 h. Next, oxalyl chloride (0.1 mL, 1.1 mmol) dissolved in THF (5 mL) was added to the reaction mixture in situ. After stirring for further 1 h the volume was reduced to about 10 mL and a colorless powder was precipitated by the addition of H₂O (200 mL), which was filtered off, washed with H₂O (2×50 mL) and dried in vacuo. Yield: 90 mg (83%). This colorless powder was checked to be nearly insoluble in all common organic solvent. To approximately 75 mg of the colorless powder was added 5 mL DMF in a conventional test tube. After sonication for 15 min the suspension was left undisturbed for 1 h before the test tube was placed in a Schlenk tube containing Et₂O (about 25 mL) to allow the Et₂O condensate slowly into the DMF suspension. After about 1 week, a few colorless crystals formed beside a large amount of a colorless powder. The crystals were identified to correspond to H₁₂L³; however, due to the small amount of H₁₂L³, only crystallographic studies could be performed.

4.8 Treatment of 2 with Cu(OAc)₂·H₂O to afford 4

To a solution of 2 (0.50 g, 1.85 mmol) in THF (50 mL) an aqueous solution of [Cu(OAc)₂·H₂O] (0.37 g, 1.85 mmol) in (15 mL) H₂O was added dropwise at room temperature. After stirring for 15 min an aqueous solution of NaOH (0.14 g, 3.7 mmol) in (10 mL) H₂O was added dropwise under continuous stirring. After stirring for further 30 min, a solid was formed which was filtered off, washed with H₂O (100 mL) to eliminate NaOAc and then dried in vacuo. Yield of the solid: 0.52 g. Color: light-blue. An elemental analysis of this light-blue powder gave the following results: C 45.81, H 4.40, N 9.26%. These values deviate significantly from the calculated values of 4 with C 42.11, H 3.53, N 10.91. Thus, the obtained light-blue powder does not correspond to pure 4.

The Supplementary Information gives the IR spectra of the light-blue material. So far, all trials to crystallize the light-blue material failed.

The filtrate of the filtration described before was left undisturbed and a few blue crystals suitable for X-ray crystallographic studies were grown after few days by slow evaporation of water. These blue crystals were identified to correspond to complex 4. However, due to the small amount of isolated material, only crystallographic studies could be performed so far.