X-ray Diffraction Study of Fluorine-Functionalized Thiosemicarbazones and Cyclometallated Compounds ^†

Abstract

In this work, an X-ray diffraction study of fluorine-functionalized thiosemicarbazone ligands and their corresponding cyclometallated compounds is discussed. The results are in agreement with previous characterization by IR spectroscopy, ¹H and ¹⁹F NMR spectroscopy. Suitable crystals were obtained for a thiosemicarbazone ligand and a cyclometallated compound. The crystal structure analyses are in accordance with the proposed structures: a fluorine-functionalized thiosemicarbazone ligand and a cyclometallated compound in which the thiosemicarbazone is a tridentate [C, N, S] ligand. A comparative study of bond distances and angles is shown, providing information about the coordination of the ligand to the metal center.

1. Introduction

In this work, fluorine-thiosemicarbazone ligands were used to synthesize cyclometallated palladium compounds. The fluorine functionality increases their solubility, which is one of the main issues when dealing with this type of species [1,2].

The ligands are widely used in coordination and organometallic chemistry due to the number of different heteroatoms and their versatile coordination to metal centers [3], generating a wide range of compounds. In addition, these ligands are relevant in the biological field; the free ligands themselves possess a certain degree of biological activity [4,5], usually enhanced by coordination to one or more metal atoms [6,7].

Furthermore, cyclometallated compounds are a large family of complexes that contain a chelate ring comprising a coordinated heteroatom–metal bond or a σ carbon–metal bond [8,9]. The metalated atom may be an aromatic [10,11] or alkenyl [12] sp² carbon or an sp³ carbon [13]. Many of these compounds are used in catalysis, and they produce very good results in cross-coupling reactions with carbon–carbon bond formation (Suzuki–Miyaura [14,15] and Mizoroki–Heck [16,17]) and carbon–nitrogen bond formation (Buchwald–Hartwig [18,19]). Likewise, their biological activity has been shown to be quite high, and it has been tested for a huge variety of metals and ligands [20,21,22,23].

2. Results and Discussion

An X-ray diffraction study of a thiosemicarbazone ligand and the ensuing palladium cyclometallated product is discussed (see Scheme 1). The results agree with a previous characterization by IR, ¹H NMR and ¹⁹F NMR spectroscopies [24]. In addition, a structural study and comparison between the two structures were carried out.

2.1. X-ray Diffraction Study

Suitable crystals for compounds were obtained by slow evaporation of a DMSO−acetone (3a) or chloroform (4b) solution, shown in Scheme 2. The X-ray diffraction study showed the proposed structures. The structures were solved by direct methods and refined by full-matrix least-squares on F². Hydrogen atoms were included in calculated positions. Refinement converged at a final R₁ = 0.0302 and wR₂ = 0.0712 (compound 3a) and R₁ = 0.0299 and wR₂ = 0.0625 (compound 4b) with allowance for thermal anisotropy of all non-hydrogen atoms. The structure solution and refinement were carried out using the program OLEX2 [25].

2.1.1. Compound 3a

Compound 3a crystallizes in a monoclinic system, P2₁/n space group. The unit cell contains four molecules of thiosemicarbazone (see Figure 1). Crystal data is shown in Appendix A (

Table A1. Crystal data and structure refinement for 3a.

Identification code	3a
Empirical formula	C11H14FN3S
Formula weight	239.31
Temperature	100(2) K
Wavelength	0.71073 Å
Crystal system	Monoclinic
Space group	P21/n
Unit cell dimensions	a = 5.8663(2) Å, α = 90°
	b = 19.5573(6) Å, β = 105.0047(10)°.
	c = 10.5485(3) Å, γ = 90°.
Volume	1168.96(6) Å3
Z	4
Density (calculated)	1.360 Mg/m3
Absorption coefficient	0.266 mm−1
F(000)	504
Crystal size	0.240 × 0.127 × 0.119 mm3
Theta range for data collection	2.083 to 26.366°.
Index ranges	−6 ≤ h ≤ 7, −24 ≤ k ≤ 24, −13 ≤ l ≤ 13
Reflections collected	32894
Independent reflections	2399 [R(int) = 0.0527]
Completeness to theta = 25.242°	100.0%
Refinement method	Full-matrix least-squares on F2
Data/restraints/parameters	2399/0/147
Goodness-of-fit on F2	1.050
Final R indices [I > 2sigma(I)]	R1 = 0.0302, wR2 = 0.0712
R indices (all data)	R1 = 0.0372, wR2 = 0.0751
Largest diff. peak and hole	0.246 and −0.266 e·Å−3

).

The structure shows thiosemicarbazone in the thionic form, with E conformation [26], probably due to the intramolecular interaction (2.179 Å) between the imine nitrogen and the thioamide proton, shown in Figure 2a.

In addition, intramolecular interaction (2.378 Å) between the fluorine atom and the imine methyl group is observed. Consequently, in Figure 2b, the aromatic ring is turned away from the thiosemicarbazone plane, with a 34.34° deviation.

2.1.2. Compound 4b

Compound 4b crystallizes in a triclinic system, P-1 space group. The unit cell contains two cyclometallated molecules and eight chloroform molecules. Crystal data is shown in Appendix A (

Table A2. Crystal data and structure refinement for 4b.

Identification code	4b
Empirical formula	C64H52Cl12F4N12Pd4S4
Formula weight	2044.41
Temperature	100(2) K
Wavelength	0.71073 Å
Crystal system	Triclinic
Space group	P-1
Unit cell dimensions	a = 13.6814(4) Å, α = 87.1620(10)°
	b = 15.1512(4) Å, β = 79.4790(10)°
	c = 19.9092(5) Å, γ = 64.1110(10)°
Volume	3648.25(17) Å3
Z	2
Density (calculated)	1.861 Mg/m3
Absorption coefficient	1.585 mm−1
F(000)	2016
Crystal size	0.180 × 0.160 × 0.070 mm3
Theta range for data collection	2.082 to 28.342°.
Index ranges	−18 ≤ h ≤ 18, −20 ≤ k ≤ 20, −26 ≤ l ≤ 26
Reflections collected	112138
Independent reflections	18195 [R(int) = 0.0390]
Completeness to theta = 25.242°	99.9%
Refinement method	Full-matrix least-squares on F2
Data/restraints/parameters	18195/0/1020
Goodness-of-fit on F2	1.049
Final R indices [I>2sigma(I)]	R1 = 0.0299, wR2 = 0.0625
R indices (all data)	R1 = 0.0390, wR2 = 0.0666
Largest diff. peak and hole	2.352 and −1.613 e·Å−3

).

The thiosemicarbazone acts as a tridentate ligand (see Figure 3a), generating two five-membered chelate rings, and the compound shows a tetranuclear structure in Figure 3b, with the ligands assuming an antiparallel arrangement and being perpendicular to each other.

In one of the monomers, the palladium center (Pd1) is surrounded by the ortho aromatic carbon of the phenyl ring (C5), the imine nitrogen (N1) and two sulfur atoms (S1 and S2) exhibiting two different bonds with palladium: Pd−S_chelate (S1) and Pd−S_bridging (S2).

As in the thiosemicarbazone ligand, an intramolecular interaction of ca. 2.5 Å (Figure 4) is observed between the fluorine atom and the imine methyl group. In this case, the aromatic ring is unable to rotate due to metallation, so the methyl group displays an eclipsed conformation.

2.1.3. Comparison between Bond Distances (Å) and Angles (°)

A comparative study of bond distances (

Table 1. Comparison between bonds in compounds 3a and 4b.

Bond	3a/Å	4b/Å
N(1)-C(7)	1.2870(18)	1.304(3)
C(9)-N(2)	1.3677(18)	1.297(3)
C(9)-S(1)	1.6816(14)	1.807(3)
C(9)-N(3)	1.3297(18)	1.361(3)
C(5)-C(6)	1.399(2)	1.424(4)

) and angles (

Table 2. Comparison between angles in compounds 3a and 4b.

Angle	3a/°	4b/°
C(5)-C(6)-C(7)	121.14(12)	116.3(2)
N(1)-N(2)-C(9)	117.90(11)	114.1(2)
N(2)-C(9)-S(1)	119.57(11)	125.16(19)
N(2)-C(9)-N(3)	115.62(12)	120.6(2)
N(3)-C(9)-S(1)	124.81(11)	114.08(18)

) between the thiosemicarbazone ligand 3a and the cyclometallated compound 4b was carried out.

The N(1)-C(7) and C(5)-C(6) bonds are somewhat longer in the cyclometallated compound due to the back-bonding of the palladium metal to the N(1) and the C(5) atoms, respectively.

The C(9)-N(2) and C(9)-S(1) bond differences are because of metallation; since it occurs in the thiolic form of the thiosemicarbazone, tautomerization of the C(9)=S(1) double bond is thus needed.

The C(9)-N(3) bond is slightly longer, probably due to the tautomerization of the thionic bond and the coordination of the sulfur atom.

The N(2)-C(9)-S(1), N(2)-C(9)-N(3) and N(3)-C(9)-S(1) angles change upon going to the cyclometallated compound due to the tautomerization and the coordination of the sulfur atom to palladium.

The C(5)-C(6)-C(7) and N(1)-N(2)-C(9) are smaller due to the formation of the five-membered chelate ring upon cyclometallation.

2.1.4. Palladium Bonds and Angles in Compound 4b

The bond distances with palladium are in accordance with those found in similar complexes [27,28,29] and angles with a square-planar geometry of the metal center (see

Table 3. Distance bonds (Å) and angles (°) around palladium metal center.

Bond	/Å	Angle	/°
Pd(1)-N(1)	1.996(2)	N(1)-Pd(1)-C(5)	81.24(9)
Pd(1)-C(5)	2.003(2)	N(1)-Pd(1)-S(1)	83.31(6)
Pd(1)-S(2)	2.3060(6)	C(5)-Pd(1)-S(2)	94.39(8)
Pd(1)-S(1)	2.3729(6)	S(2)-Pd(1)-S(1)	100.81(2)
		N(1)-Pd(1)-S(2)	174.68(6)
		C(5)-Pd(1)-S(1)	164.07(8)

).

3. Conclusions

• X-ray structural analysis was carried out for a thiosemicarbazone ligand and its cyclometallated palladium derivative.
• A comparative study allowed the determination of variations in bond distances and angles in the structure of the ligand after the cyclometallation process.
• The metal atom displays the typical square-planar geometry for palladium.