Designing a Phosphino-Thiosemicarbazone Ligand Capable of Stabilizing Coinage Metal Ions ^†

Abstract

Thiosemicarbazones are interesting organic skeletons due to their great coordinative versatility and their interesting biological and pharmacological properties, as well as their structural diversity. However, the isolation of their monovalent coinage metal complexes, such as Cu(I), Ag(I) and Au(I), is a partially studied field, since co-ligands with soft donor atoms such as phosphines are required. In this context, our research group has been studying a new family of ligands capable of stabilizing coinage complexes without the need for auxiliary co-ligands. To this end, it was decided to incorporate a phosphorus atom into the structure of a thiosemicarbazone kernel. This work presents the design, synthesis and structural characterization of a new phosphino-thiosemicarbazone ligand.

1. Introduction

Among the wide variety of organic skeletons reported to date, thiosemicarbazone ligands must be highlighted due to their interesting biological and pharmacological properties, as well as their structural diversity [1,2,3,4,5]. Nevertheless, in order to obtain their monovalent metal complexes, such as Cu(I) [6], Ag(I) and Au(I) [7,8,9], auxiliary co-ligands incorporating soft donor atoms were needed.

At this point, in the last few years we have designed and prepared a new family of thiosemicarbazone ligands featuring a phosphine unit [10,11,12,13,14]. The phosphine-thiosemicarbazone ligands were capable of stabilizing M(I) complexes without the need for auxiliary co-ligands. For further study, we report herein the design, synthesis and structural characterization of a new phosphino-thiosemicarbazone ligand functionalized with a nitro-phenyl ring (Figure 1).

2. Experimental Section

The new phosphino-thiosemicarbazone ligand HL^PhNO2 has been created by means of an imine condensation reaction (Figure 1). First, 2-diphenylphosphinobenzaldehyde (A) (0.50 g, 1.7 mmol) and 4-(4-Nitrophenyl)thiosemicarbazide (B) (0.72 g, 3.4 mmol) were mixed and dissolved in absolute ethanol. Then, a catalytic amount of p-toluensulfonic acid was added to promote imine bond formation. The reaction mixture was refluxed for 4 h using a Dean−Stark trap to remove the released water. The final white crystalline precipitate was isolated via concentration and filtration and washed with diethyl ether, giving rise to the required HL^PhNO2.

HL^PhNO2: yield 1.498 g, (91%). Elemental analysis, calc. for C₂₆H₂₁N₄O₂PS: C, 64.5; H, 4.4; N, 11.6; S, 6.6. Found: C, 64.3; H, 4.4; N, 11.4; S, 6.3 %. MS ESI+ (m/z): 483.1 [HL-H]-. IR (KBr, cm⁻¹): ν IR (KBr, cm⁻¹): ν(N-H) 3302 (d), ν(C=N + C-N) 1539 (mf), 1514 (f), 1435 (m), ν(NO2) 1333 (mf) ν(C=S) 1111 (m), 748 (m). RMN 1H (300 MHz, DMSO-d6): δ/ppm, 12.30 (s, 1H, -NH), 10.33 (s, 1H, -NH), 8.87 (d, J= 4.9 Hz, 1H), 8.48–6.82 (m, 18H, Ar-H). RMN 13C (126 MHz, DMSO-d6): δ/ppm, 175.24 (C=S), 145.22 (C=N), 143.47–123.76 (C-Ar). RMN 31P (202 MHz, DMSO-d6): δ/ppm, −12.76.

3. Results and Discussion

HL^PhNO2 was characterized using the usual techniques for organic compounds. Analytical data are consistent with the ligand stoichiometry. An IR spectrum shows the bands corresponding to the NH group at 3302 cm⁻¹, to the imine bond at 1539, 1514 and 1435 cm⁻¹ (Figure 2) and to the C=S thioamide group at 1111 and 748 cm−1. MS ESI+ exhibits a peak at 483.1(m/z) consistent with the monodeprotonated ligand molecule. Suitable crystals for X-ray diffraction were also obtained. The crystal structure corresponds with the oxidized HL^PhNO2 ligand, that is shown in Figure 3. The main crystallographic data are summarized in

Table 1. Main crystallographic data for HL^PhNO2.

Crystallographic Data
Formula	C26H21N4O2.30PS
Molecular weight	489.3
Crystal system	Monoclinic
Crystal size/mm	0.70 × 0.11 × 0.03
Volume/Å3	2327.1(3)
Space group	P21/n
Z	4
a/Å	13.7284(8)
b/Å	7.2366(5)
c/Å	23.5622(14)
α/°	90
β/°	96.214(3)
γ/°	90
d/g·cm−3	1.383
μ/mm−1	0.191
F(000)	432
Interval θ/°	2.41–28.13
Measured reflexions	33,552
Independent reflexions [Rint]	5787 [0.0396]
Residues/e·Å−3	0.58 and −0.29
R	0.0392
wR	0.0889

, whereas bond lengths and angles are listed in

Table 2. Selected bond length (Å) and angles (°) for HL^PhNOs2.

Main Bond Distances (Å)
C8-N4	1.271(2)	C10-P1	1.843(1)
N4-N3	1.376(2)	P1-C21	1.823(1)
N3-C7	1.356(2)	C8-C9	1.452(2)
C7-S1	1.683(2)	P1-C15	1.826(2)
N1-O1	1.227(2)	P1-O3	1.377(4)
C7-N2	1.346(2)	C1-N1	1.463(2)
N4-C8	1.271(2)	N1-O2	1.229(2)
Main Bond Angles (°)
C8-N4-N3	117.7(1)	O2-N1-O1	123.6(2)
N4-N3-C7	119.2(1)	C10-P1-C15	101.27(7)
N3-C7-S1	118.7(1)	C21-P1-C10	103.88(7)
N2-C7-N3	114.0(1)	C21-P1-C15	102.48(7)
N2-C7-S1	127.3(1)

. All bond distances and angles are in the order of those found in the literature for thiosemicarbazone and phosphine ligands and do not merit further discussion [10,11,12,13,14].

The asymmetric unit of the HL^PhNO2 ligand consists of a ligand molecule showing an E conformation with respect to the imine group. In addition, the phosphine skeleton and the thiosemicarbazone branch are oriented towards the same side giving rise to a syn conformer (Figure 3).

The HL^PhNO2 ligand crystallized with the oxidized phosphorus atom. This fact causes intramolecular hydrogen bonds to be established (Figure 4) involving the hydrogen in the thioamide position [N2-H2N∙∙∙O1 2.795 Å], which possibly conditions the syn arrangement adopted by the phosphine skeleton and the thiosemicarbazone branch. In addition, intermolecular hydrogen bonds established by the thioamide sulfur and the hydrazide hydrogen atoms allow an interaction between two neighboring ligand molecules [N3-H3N∙∙∙S1 3.461(2) Å].

The HL^PhNO2 structure in the solid state is worthy of analysis for comparative purposes between the free ligand or when it is bound to different metal ions. By observing its arrangement, it should be noted that the O/S donor atoms are oriented in opposite directions. For this reason, a previous conformational rotation would be necessary to achieve both atoms’ coordination to the same metal ion.

4. Conclusions

The new phosphine-thiosemicarbazone ligand HL^PhNO2 has been isolated in high purity and yield. Its crystal structure shows an opposite orientation of oxygen and sulfur donor atoms, which would imply a conformational rotation prior to coordination to the same metal ion.