Study of the Influence of a Solvent on the Crystal Structure of an Ethyl-Substituted Bisthiosemicarbazone Ligand ^†

Abstract

A potentially dianionic symmetric bisthiosemicarbazone ligand H₂L^Et has been prepared by a condensation reaction between two equivalents of 4-N-ethyl-3-thiosemicarbazide and one equivalent of 4,4′-methylenebis(acetophenone). The crystal structures obtained from solvents with different donor abilities were studied. The recrystallization of H₂L^Et from methanol and dimethylsulfoxide enables the isolation of single crystals suitable for the X-ray diffraction studies of [H₂L^Et] 1 and [H₂L^Et]·CH₃SOCH₃ 2, respectively. This study shows that the solvent does not affect the macrostructure but influences the microstructure of the ethyl-substituted bisthiosemicarbazone ligand H₂L^Et.

1. Introduction

To date, a vast family of thiosemicarbazone ligands has been synthesized because of their high versatility in coordination chemistry and their interesting properties related to biomedical and pharmacological activities [1,2]. These ligands can be easily obtained by a condensation reaction between an appropriate carbonyl compound and a thiosemicarbazide [3], giving rise to the formation of an imine bond and the liberation of a water molecule.

In the case of thiosemicarbazone ligands, the influence of different factors such as the presence of metal ions [4], the pH of the medium [5] or the solvent [6], among others, can lead to a desulfurization process, giving rise to the loss of the sulfur atom. Having this in mind, in this work, we decided to study the influence of the recrystallization solvent on the desulfurization process and the concomitant modification of the macrostructure of the bisthiosemicarbazone ligand H₂L^Et. For this reason, we have again prepared the ethyl-substituted bisthiosemicarbazone published [7] and recrystallized it in solvents with different donor abilities.

2. Experimental Section

2.1. Reactants and Solvents

All solvents, 4,4′-methylenebis(acetophenone) and 4-N-ethyl-3-thiosemicarbazide are commercially available ant they were used without further purification.

2.2. Preparation of the Bisthiosemicarbazone Ligand H₂L^Et

The [N₂S₂] bisthiosemicarbazone ligand H₂L^Et was obtained by means of a condensation reaction between two equivalents of 4-N-ethyl-3-thiosemicarbazide and one equivalent of 4,4′-methylenebis(acetophenone) using absolute ethanol as a solvent (ca. 50 mL) and p-toluensulfonic acid as a catalyst [7]. The recrystallization of H₂L^Et from dimethylsulfoxide yielded yellow needle-shaped crystals that were suitable for monocristal X-ray-crystallographic studies.

2.3. Crystallographic Data

[H₂L^Et]·CH₃SOCH₃ 2: C₂₃H₃₀N₆S₂·C₂H₆OS, MW: 532.78; crystal dimensions: 0.53 × 0.14 × 0.1; monoclinic; P2₁/c; a = 17.8816(15); b = 14.0286(11); c = 10.9880(9) Å; α = 90; β = 91.617(3); γ = 90°; V = 2755.3(4) ų; Z = 4; μ = 0.30 mm⁻¹; measured reflexions = 21262678; independent reflexions [R_int] = 5642 [0.040]; R = 0.048; wR = 0.131.

3. Results and Discussion

The ethyl-substituted bisthiosemicarbazone ligand H₂L^Et was prepared by means of a condensation reaction between 4-N-ethyl-3-thiosemicarbazide and 4,4′-methylenebis(acetophenone), as previously reported [7].

The recrystallization of H₂L^Et from methanol allows discrete molecules of H₂L^Et 1 to be isolated [7]. In the ligand, both thiosemicarbazone arms adopt an E configuration with respect to the imine bonds and an anti conformation, with the two thiosemicarbazone arms facing different sides.

With the aim of exploring if the solvent of recrystallization influences in the macro- and microstructure of the ligand H₂L^Et, we used dimethylsulfoxide to recrystallize the solid obtained from the synthesis. The recrystallization of the ligand solid in dimethylsulfoxide allowed us to obtain yellow needle-shaped crystals suitable for X-ray diffraction studies. The crystal structure of [H₂L^Et]·CH₃SOCH₃ 2 is shown in Figure 1.

Compound [H₂L^Et]·CH₃SOCH₃ 2 (Figure 1) crystallize solvated by one molecule of dimethylsulfoxide. The crystal structure consists of discrete molecules in which both thiosemicarbazone arms adopt an E configuration with respect to the imine bonds and an anti configuration with the two thiosemicarbazone arms oriented on opposite sides, similar to the previously published ethyl-substituted bisthiosemicarbazone ligand crystal structure obtained using methanol as a solvent [7]. The main C=N, N-N and C-S bond distances and angles given in

Table 1. Selected bond lengths (Å) for [H₂L^Et]·CH₃SOCH₃ 2.

Main Bond Distances (Å)
C3—S1	1.685 (2)	C21—S2	1.387 (3)
C5—N3	1.290 (3)	C22—N8	1.288 (4)
N2—N3	1.381 (3)	N4—N7	1.383 (3)

are very similar to H₂L^Et 1 being in the expected range for thiosemicarbazone ligands and need no further discussion [7].

However, the comparison of 1 and 2 shows that there are some differences related to the hydrogen bonds established in the crystal lattice.

In the case of H₂L^Et 1, moderate intermolecular hydrogen bonds are observed between the thioamidic sulfur atom of one of the ligand arms and one of the thioamidic NH groups of the adjacent unit ligand, connecting the molecules along the crystal lattice. Also, intramolecular hydrogen bonds between the iminic nitrogen and the thioamidic nitrogen atom of one branch are observed [7].

On the other hand, in the case of H₂L^Et·CH₃SOCH₃ 2, the ligand establishes a moderate intermolecular hydrogen bond between the thioamidic nitrogen atom of one of their branches and the oxygen atom of the solvation dimethylsulfoxide molecule. Also, a weak intermolecular hydrogen bond exists between one methyl group of the dimethylsulfoxide molecule and the hydrazidic nitrogen of another ligand unit (Figure 2). However, in this case there are no intramolecular hydrogen bonds.

4. Conclusions

The recrystallization of the ethyl-substituted bisthiosemicarbazone ligand H₂L^Et in methanol [7] and in dimethylsulfoxide allowed to explore the influence of solvents with different donor abilities in the structure of the compound. It is clear from the crystal data obtained that the solvents used do not have an influence on the macrostructure of the bisthiosemicarbazone compound, confirming that there is no evidence of a desulfurization process. However, the solvent affects the microstructure showing a higher number of hydrogen bonds in the case of the crystal structure obtained in methanol, H₂L^Et 1, compared with the crystal structure obtained in dimethylsulfoxide, H₂L^Et·CH₃SOCH₃ 2.