Ammonium Oxathioamidate

Abstract

Ammonium oxathioamidate (1) was synthesised by the reaction between O-ethyl-thioxamate (oxalic acid-1-amide-2-O-ethyl ester) and ammonium hydrogen carbonate in water solution. Compound 1 was fully characterised by both microanalytical (elemental analysis, melting point determination) and spectroscopic means (FT-IR and NMR spectroscopy). Crystals suitable for single-crystal X-ray diffraction were isolated by slow evaporation of an ethanol solution of the compound. The analysis of the crystal packing reveals the prominent role exerted by intermolecular hydrogen bonding (HB) and chalcogen bonding (ChB) interactions.

1. Introduction

Salts and esters deriving from oxamic acid, H₂NC(O)C(O)OH, represent a class of compounds that has found applications in fields spanning from organic synthesis [1,2] to medicine [3,4]. In recent years, salts of N-substituted oxamates, such as ammonium N-phenyloxamate [5] and N-(pyridyn-2-ylmethyl)oxamate [6], were investigated as conservation agents for carbonate stone substrates, which are of interest in the field of cultural heritage [7]. In addition, the structural features of several N,N′-diamides of oxalic acid (oxalamides) with both alkyl [8,9] and aryl [10,11] substituents have been investigated. In fact, N-substituted and N,N′-disubstituted oxamates display extended solid-state networks based on hydrogen bonds (HBs) [12,13] that render such compounds of interest in both crystal [14,15] and protein [16] engineering or as organic gelators [17,18].

Surprisingly, while vicinal dithioxamides, the completely sulphurated congeners of oxalamides, have been extensively reported in the literature [19,20,21,22,23,24], monothioxamates, displaying a single thiocarbonyl group, have been investigated to a much lesser extent. To the best of our knowledge, only a few monothioxamates have been characterised crystallographically in the form of salts (1 example, CSD refcode ZOKSOH) [25], coordination compounds (7 examples, refcodes: GAYZEL, GAYZIP, TACYUR, WIFSEJ, WIFSIN, WIFSOT, and ZIRMAO), or—more frequently—O-esters (10 examples: BOZLAD, DIFWOF, DIFVUL, DIFXAS, DIFXEW, JIRTIO, LEDROE, LEDRUK, LEDSAR, and PILZUG).

We describe here the synthesis and the spectroscopic and structural characterisation of ammonium oxathioamidate (1).

2. Results and Discussion

Following a modification of the synthetic procedure adopted for the synthesis of the ammonium salts of N-substituted oxamates [5,6], the synthesis of ammonium oxathioamidate was directly achieved by hydrolysis of O-ethyl-thioxamate (oxalic acid-1-amide-2-O-ethyl ester) with ammonium hydrogen carbonate in water solution (Scheme 1).

Compound 1 was fully characterised by various means, including elemental analysis, melting point determination, FT-IR, and ¹H-NMR spectroscopy. The FT-IR spectrum of compound 1 (Figure S1) closely resembles that previously published for the corresponding potassium salt H₂NC(S)C(O)OK, whose vibrational features were assigned based on the spectra recorded at different temperatures (−190 and 24 °C) and the comparison with the spectrum of the deuterated species D₂NC(S)C(O)OK [25]. In the FT-IR spectrum of compound 1, the peak corresponding to the stretching mode of the N–H bond of the oxamide anion falls at 3318 cm⁻¹ (3367 cm⁻¹ for the reported potassium salt) [25] and partially overlaps with a broad band centred at 3145 cm⁻¹ due to the combination of the stretching modes of the ammonium counterion. A broad structured band can be envisaged in the range 1790–1520 cm⁻¹. This, in agreement with the assignment by Hereygers [25], can be attributed to the combined modes of the carbonyl stretching and the bending modes of the amino group. The strong band at 1400 cm⁻¹ can be analogously considered to have a large C–N stretching characteristic. Finally, the peak at 798 cm⁻¹ can be assigned to the C–C vibration. The ¹H-NMR spectrum recorded in DMSO-d₆ clearly shows the two broad singlets attributed to the protons of the ammino group at 9.04 and 9.25 ppm, respectively, while the broad signal corresponding to the ammonium protons can be detected at 7.3 ppm.

Compound 1 was recrystallised by slow evaporation of a concentrated ethanol solution of the compound, affording crystals suitable for single-crystal X-ray diffraction analysis. The compound crystallises in the monoclinic space group P2₁/c (Tables S1 and S2). The oxathioamidate anion is completely planar, the thioamide moiety lying on the same plane as the carboxylate group (Figure 1). The latter features two near-identical C–O distances [1.2451(15) and 1.2563(14) Å], with an O–C–O angle of 125.85(11)°. These distances, as well as the C–C, C=S, and C–N distances [1.5474(15), 1.6667(12), and 1.3100(15) Å, respectively], are very close to those described for the same anion in the potassium salt [C–C, 1.517(6); C–O: 1.252(6), 1.257(6); C=S, 1.653(5); C–N, 1.329(7) Å] [25]. The planarity of the anion closely recalls that observed for the oxamate anions, attributed to the delocalisation of the lone pair (LP) of electrons of the nitrogen atom on the C(O)NH₂ amide moiety, as confirmed by the Second-Order Perturbation Theory Analysis of the Fock Matrix in the NBO Basis [7,26].

The crystal packing of compound 1 (

Table 1. Intermolecular interactions of compound 1.

Interaction		dD–H/S (Å)	dH/S∙∙∙A (Å)	dD∙∙∙A (Å)	αD–H/S···A (°)
a	N4–H4A···O1 i	0.92(2)	1.98(2)	2.8854(15)	166.1(17)
b	N4–H4B···O2 ii	0.88(2)	2.06(2)	2.9246(15)	164.9(16)
c	N4–H4C···O2	0.90(2)	2.01(2)	2.8712(16)	158.4(17)
d	N4–H4D···S3 iii	0.88(2)	2.65(2)	3.4214(13)	146.1(16)
e	N2 iii–H2B iii ···O2	0.877(17)	1.974(17)	2.8428(14)	170.9(14)
f	N2 iv–H2A iv ···O1	0.872(17)	2.172(17)	2.9395(14)	146.6(14)
g	C2–S3···S3 ii	1.667(1)	3.5833(7)	5.233(1)	169.92(5)

Symmetry operations: ⁱ = +x, +y, −1+z; ⁱⁱ = +x, 3/2−y, −1/2+z; ⁱⁱⁱ = −1+x, +y, +z; ^iv = 1−x, 1−y, 2−z.

and Tables S1–S3) is governed by N–H···O and N–H···S HB interactions [27]. Three protons of the ammonium cation (H4A, H4B, and H4C in Figure 2A) interact with the carboxylate groups of three different symmetry-related oxathioamidate anions by linear or slightly bent N–H···O hydrogen bonds (Table 1; interactions a–c in Figure 2A). The H4D proton forms a further HB with the sulphur atom of a fourth anion (interaction d in Figure 2A; Table 1). Additionally, two HBs are formed between the amido group of an oxathioamidate and the oxygen atoms of carboxylates of adjacent anions (Table 1; interactions e and f in Figure 2A).

The negatively charged (Table S3) sulphur atom S3 is in turn involved in C–S···S interactions arranged to form zig-zag 1D chains running along the [001] direction (interaction g in Figure 2B). The S···S distances (3.5833(7) Å), close to the sum of the relevant van der Waals radii, classify this interaction as a very weak chalcogen bond (ChB; Table 1) [28,29,30], whose geometry reflects the topology of the molecular electrostatic potential (MEP, Figure S2). The length of the S···S distance suggests this interaction to be mainly electrostatic in nature, the contribution from orbital mixing, and in particular from the interaction of the lone pair of electrons on the HOMO of one unit to the LUMO+1 of another (Figure S3) being necessarily minor.

According to the graph set notation, several motifs, formed through N–H···O hydrogen bonds (HBs), can be identified in the crystal structure of compound 1: ${\mathrm{R}}_2^2\left(8\right)$ and ${\mathrm{R}}_4^4\left(12\right)$ motifs defined by interacting oxathioamidate anions (shown in violet and light blue in Figure 3, respectively); ${\mathrm{R}}_4^3\left(10\right)$ involving two ammonium ions and two carboxylates (depicted in brown in Figure 3); and a larger ${\mathrm{R}}_6^4\left(18\right)$ motif aroused from additional interacting amino moieties (shown in green in Figure 3). Additionally, the combination of N–H···O and N–H···S HBs gave rise to ${\mathrm{R}}_3^2\left(8\right)$ and ${\mathrm{R}}_5^5\left(18\right)$ motifs that are depicted in yellow and red in Figure 3, respectively.

3. Materials and Methods

3.1. General Methods

All reagents and solvents were used without further purification. FT-IR measurements were carried out at room temperature on a Thermo-Nicolet 5700 spectrometer on KBr pellets, by using a KBr beam splitter and KBr windows (4000–400 cm⁻¹, resolution 4 cm⁻¹). ¹H-NMR spectra were recorded in DMSO-d₆ at room temperature on a Bruker Avance III HD 600 spectrometer. Chemical shifts are reported in ppm (δ) and are calibrated to the solvent residue. Elemental analysis was performed with a CHNS/O PE 2400 series II elemental analyser (T = 925 °C). Uncorrected melting points were determined in capillaries on a FALC mod. C melting point apparatus. UV–Vis absorption spectra (water solution) were recorded at 25 °C in a quartz cell of 10.00 mm optical path with a Thermo Evolution 300 (190–1100 nm) spectrophotometer. QM calculations were carried out on the oxathioamidate anion at DFT level as described previously [7] by adopting the mPW1PW hybrid functional [31] with a 6-311++g(d,p) basis set including diffuse and polarisation functions.

3.2. X-Ray Diffraction Analysis

Single-crystal X-ray diffraction data for compound 1 were collected at 173 K on a Rigaku XtaLAB P200 diffractometer using a Rigaku FR-X Ultrahigh Brilliance Microfocus RA generator/confocal optics [Mo Kα radiation (λ = 0.71073 Å)]. Intensity data were collected using ω steps accumulating area detector images spanning at least a hemisphere of reciprocal space. Data for compound 1 were collected and processed (including correction for Lorentz, polarisation, and absorption) using CrystalClear [32]. The structure was solved with SHELXT [33] using dual-space methods and refined using SHELXL [34] through cycles of least squares refinement of F². Hydrogen atoms were located from the difference Fourier map, added with isotropic displacement parameters U_iso(H) = 1.2∙U_eq(N), and their positions were refined. All calculations were performed using the CrystalStructure interface [35]. Selected crystallographic data are presented in Table S1.

C₂H₆N₂O₂S (M = 122.15 g/mol): monoclinic space group P2₁/c (no. 14), a = 5.9972(10) Å, b = 13.3982(17) Å, c = 6.3260(10) Å, β = 92.355(4)°, V = 507.88(13) ų, Z = 4, T = 173(2) K, μ(MoKα) = 0.522 mm⁻¹, ρ_calc = 1.597 g/cm³, 6082 reflections measured (6.082° ≤ 2θ ≤ 50.744°), 926 unique (R_int = 0.0577, R_sigma = 0.0246), which were used in all calculations. The final R₁ was 0.0201 (I > 2σ(I)), and wR₂ was 0.0544 (all data).

3.3. Synthesis of Ammonium Oxathioamidate (1)

An aqueous solution (75 mL) of O-ethyl-thiooxamate (3.00 g, 2.25·10⁻² mol) and ammonium hydrogen carbonate (1.70 g, 2.15·10⁻² mol) was stirred at room temperature for 2 h. The solution was filtered, and the solvent was removed under reduced pressure. The resulting yellow solid was washed with CH₂Cl₂ and dried (1.70 g, yield 65%). M.p. = 128 °C dec. Elemental analysis calcd (%) for C₂H₆N₂O₂S: C 19.66%, H 4.95%, N 22.93%; found: C 20.06, H 4.60, N 22.40. FT-IR (KBr, 4000–400 cm⁻¹): 3319 s, 3138 s, 3010 sh, 1601 s, 1446 vs, 1404 vs, 1234 m, 1225 m, 1016 w, 955 m, 868 m, 798 ms, 739 ms, 677 w, 598 m, 490 w, 442 w, 413 mw cm⁻¹. ¹H-NMR (600 MHz, DMSO-d₆) δ: 9.04 (s), 9.25 (s), 7.30 (s, br) ppm. UV–Vis (H₂O) λ (ε): 208 (4600), 272 nm (5600 M⁻¹·cm⁻¹).

4. Conclusions

Ammonium oxathioamidate (1) was synthesised by hydrolysis of O-ethyl-thiooxamate with ammonium hydrogen carbonate and structurally characterised by single-crystal X-ray diffraction and spectroscopic means.

In the crystal packing, hydrogen bonds (HBs) between the ammonium cation and the neighbouring anions and weak chalcogen bonds (ChBs) between the sulphur atoms of the anions were observed. This complex pattern of intermolecular interactions, resulting in an intricate 3D network, can find applications in different fields of crystal engineering.