Sulfur Bridged Multidentate Ligands Based on (Bi)pyridyl-(Bi)-1,3,4-Thiadiazolyl Conjugates

Abstract

The synthesis of a series of mixed (bi)pyridyl/(bi)1,3,4-thiadiazolyl ligands, derived from the condensation of 2-mercapto-5-methylthio-1,3,4-thiadiazole or 5-mercapto-5'-methylthio-2,2'-bi-1,3,4-thiadiazole with 2,6-bis(chloromethyl)pyridine or 6,6’-bis(chloromethyl)-2,2’-bipyridine (compounds L₁–L₄), and of 2,5-dimercapto-1,3,4-thiadiazole or 5,5'-dimercapto-2,2'-di-1,3,4-thiadiazole with picolyl chloride hydrochloride or 6-chloromethyl-6'-methyl-2,2'-bipyridine (compounds L₅–L₈) in the presence of triethylamine is described. All new compounds have been characterized by FAB (+) spectrometry and NMR spectroscopy. ¹³C-NMR spectra are crucial to firmly establish the thiol structure of the title ligands.

Introduction

It is well known that luminescent and redox active polypyridine-type metal complexes are playing a key role as molecular components in the development of supramolecular species capable of harvesting solar energy and transforming light information at the molecular level [1]. Most of such supramolecular species are based on ruthenium (II) and osmium (II) tris-bidentate and/or bis-terdentate (poly)pyridyl building blocks [1d, 2]. On the other hand, a few examples have been reported in the literature regarding the use of (poly)-1,3,4-thiadiazole ligands in the complexation of Ru (II) and/or Os (II) ions [3]. To the best of our knowledge, there is only one paper dealing with the preparation of Ru (II) tris-chelate complexes of thiadiazole derivatives, which show luminescence properties not only at 77 K, but even at room temperature [4]. Following our interest in the field of luminescent polypyridine ruthenium (II), osmium (II) and iridium (III) complexes [5], we now report the synthesis and characterization of eight new mixed (bi)pyridyl/(bi)-1,3,4-thiadiazolyl ligands L₁–L₈ (vide infra, Scheme 1 and Scheme 2) with the aim of studying the photochemical properties of their complexes with transition metals.

Scheme 1.

Scheme 2.

Results and Discussion

Pivotal intermediate 5-mercapto-5'-methylthio-2,2'-bi-1,3,4-thiadiazole (2), required for the synthesis of ligands L₂ and L₄ was obtained by selective methylation of 5,5'-dimercapto-2,2'-bi-1,3,4-thiadiazole (6) with dimethyl sulfate (1 equiv.) under basic conditions (NaOH) (Scheme 1).

The reaction produced a mixture of mono-(methylthio) derivative 2 (26%) and bis-(methylthio) derivative (30%), which were easily separated by exploiting their different solubility in the reaction medium (see Experimental). From the ¹³C-NMR spectrum in deuterated tetrachloroethane (TCE), only the thione form of 2 (C=S resonance at δ 188.7 ppm) was detected.

Reaction of 2-mercapto-5-methylthio-1,3,4-thiadiazole (1) with 0.5 equiv. of 2,6-bis(chloromethyl)-pyridine (3) or 6,6'-bis(chloromethyl)-2,2'-bipyridine (4) in dry N,N-dimethylformamide (DMF) at 90°C in the presence of triethylamine (TEA, 1 equiv) afforded ligands L₁ and L₃ , respectively, in high yield. Ligands L₂ and L₄ were obtained in a similar way by reacting 5-mercapto-5'-methylthio-2,2'-bi-1,3,4-thiadiazole (2) with 3 or 4, respectively, in a 2 : 1 molar ratio, as shown in Scheme 1.

The ligands L₅–L₈ were synthesized using the same strategy as above, namely by condensation of 2,5-dimercapto-1,3,4-thiadiazole (5) or 5,5'-dimercapto-2,2'-bi-1,3,4-thiadiazole (6) with picolyl chloride hydrochloride (7) or 6-chloromethyl-6'-methyl-2,2'-bipyridine (8) (Scheme 2). All the compounds where characterized by elemental analysis, FAB (+) mass spectrometry, and NMR spectroscopy. The FAB (+) mass spectra of L₁–L₈ display prominent molecular ion peaks, and fragmentation patterns in accord with those described for (bi)-1,3,4-thiadiazole sulfur derivatives [6].

Table I reports the results of a complete ¹H-NMR analysis of ligands L₁–L₈. Assignments were aided by the use of 2D homonuclear chemical shift correlated ¹H-NMR (COSY) [7]. The bipyridyl moieties of ligands L₃ and L₄ show the expected pattern for a 6,6' disubstituted 2,2'-bipyridine system, i.e. a doublet-triplet-doublet sequence. On the other hand, a doubling of these signals is observed when the substituents in the 6,6'-positions of the bipyridyl moiety are different, as in L₆ and L₈. The downfield resonances of the protons in the 3,3'-positions (δ in the range 8.16–8.37 ppm, Table I) are suggestive of an anti disposition of the bipyridyl units [8].

Table I.

¹H=NMR parameters of ligands L₁–L₈.

Proton	L1	L2	L3	L4	L5	L6	L7	L8
3	7.34 d J = 8.0	7.41 d J = 8.0	8.31 d J = 7.5	8.37 d J = 7.5	7.41 d J = 8.0	7.48 d J = 7.5	8.16 d J = 8.0	8.20 d J = 8.0
4	7.62 t J = 7.5	7.67 t J = 7.8	7.79 dt J = 7.5, 1.5	7.81 t J = 7.5	7.65 dt J = 7.5, 2.0	7.67 dt J = 7.5, 1.0	7.76 t J = 8.0	7.79 t J = 8.0
5	7.34 d J = 8.0	7.41 d J = 8.0	7.44 d J = 8.0	7.49 d J = 7.5	7.20 t J = 6.0	7.22 t J = 7.5	7.39 d J = 7.5	7.45 d J = 8.0
6					8.54 dd J = 3.5, 2.0	8.57 dd J = 4.0, 1.0
3’			8.31 d J = 7.5	8.37 d J = 7.5				8.37 d J = 7.5
4’			7.79 dt J = 7.5, 1.5	7.81 t J = 7.5			7.68 t J = 7.5	7.69 t J = 8.0
5’			7.44 d J = 8.0	7.49 d J = 7.5			7.16 d J = 7.5	7.17 d J = 7.5
CH2	4.57 s	4.72 s	4.69 s	4.83 s	4.58	4.72 s	4.68 s	4.83 s
CH3	2.73 s	2.84 s	2.73 s	2.84 s			2.61 s	2.61 s

Notes: The spectra were obtained in TCE, chemical shifts in ppm, and coupling constants in Hz. Numbering pattern as shown in Scheme 1 and Scheme 2. Abbreviations used: s = singlet, d = doublet, dd = double doublet, t = triplet, dt = double triplet.

It is important to point out, however, that these spectral data alone afforded little assistance in the structural assignment of the products of alkylation of our heterocyclic thiols (1, 2, 5, and 6), because of their aptitude for thiol-thione tautomerism. Since ¹³C-NMR spectroscopy provides a powerful tool for distinguishing between substitution on nitrogen and/or on sulfur [9], we deemed essential the acquisition of the ¹³C-NMR spectra of L₁–L₈ to unambiguously assign their structures. To this end, we assumed the chemical shifts of the quaternary carbons in model compounds 2,5-bis(methylthio)-1,3,4-thiadiazole (δ = 165.5 ppm in CDCl₃) and 3,4-dimethyl-1,3,4-thiadiazolidine-2,5-dithione (δ = 180.3 ppm in CDCl₃) as standards for substitution on sulfur or on nitrogen, respectively [10].

The ¹³C-NMR spectra of ligands L₁–L₈ are gathered in Table II, along with their analytical data. A scrutiny of the Table shows that the resonance(s) of the quaternary carbons of the thiadiazole ring(s) in the range 164.1 ± 6.0 ppm. These values unambiguously prove that the thiols used in this investigation (compounds 1, 2, 5, and 6) have undergone regioselective S-alkylation under basic conditions.

Table II.

Analytical and ¹³C-NMR Spectral Data for the Ligands L₁–L₈.

Lig.	Yield (%) (Cryst. Solv. )	Melting Point (°C)	Molecular Formula	%C Found(Calcd)	%H Found(Calcd)	%N Found(Calcd)	13C NMR
L1	84 (EtOH)	94−95	C13H13N5S6	36.13 (36.17)	3.33 (3.03)	16.04 (16.22)	167.0, 164.0, 155.6, 137.7, 122.1, 39.8, 16.7
L2	63 (DMF)	207−212	C17H13N9S6	33.82 (34.04)	2.22 (2.18)	21.06 (21.02)	170.1, 168.2, 158.8, 158.1, 155.2, 137.8, 123.3, 39.7, 16.7
L3	90 (EtOH-CHCl3)	157−158	C18H16N6S6	42.83 (42.49)	3.06 (3.17)	16.74 (16.52)	166.9, 164.4, 155.2, 154.9, 137.7, 123.1, 120.0, 40.3, 16.7
L4	71 (DMF)	257−258	C22H16N10S8	39.17 (39.03)	2.03 (2.38)	20.92 (20.69)	170.1, 168.6, 158.6, 158.2, 155.2, 154.4, 137.9, 123.2, 120.2, 40.2, 16.7
L5	95 (MeOH-H2O)	80−81	C14H12N4S3	50.91 (50.58)	3.57 (3.64)	16.94 (16.85)	164.9, 155.4, 149.5, 136.9, 123.3, 122.7, 39.9
L6	80 (AcOEt)	163−165	C26H22N6S3	61.01 (60.67)	3.90 (4.31)	16.41 (16.33)	165.4, 157.9, 156.0, 154.8, 154.7, 137.6, 137.0, 123.4, 122.7, 119.9, 118.1, 40.4, 24.6
L7	73 (Dioxane)	159−160	C16H12N6S4	46.52 (46.13)	2.49 (2.90)	19.74 (20.17)	168.3, 158.6, 155.0, 149.6, 136.9, 123.3, 122.8, 39.8
L8	80 Dioxane/DMF	248−250	C28H22N8S4	55.98 (56.16)	3.85 (3.70)	18.92 (18.71)	168.8, 158.6, 157.9, 156.2, 154.7, 154.2, 137.7, 137.0, 123.5, 122.7, 120.0, 118.1, 40.3, 26.6

Notes: The ¹³C-NMR spectra were obtained in TCE, chemical shifts in ppm.

Conclusions

We have synthesized and characterized a series of polydentate aza/sulfur ligands, based on the (bi)pyridine/(bi)-1,3,4-thiadiazole skeletons, that are potential chelating molecules for the complexation of metal cations such as Ru, Os, and Ir. These complexes, owing to the simultaneous presence of nitrogen and sulfur binding sites, may display new and interesting photophysical properties.

Experimental

General

2-Mercapto-5-methylthio-1,3,4-thiadiazole (1) [11], 2,6-bis(chloromethyl)pyridine (3) [12], 6,6'-bis(chloromethyl)-2,2'-bipyridine (4) [13], 5,5'-dimercapto-2,2'-bi-1,3,4-thiadiazole (6) [14], and 6-chloromethyl-6'-methyl-2,2'-bipyridine (8) [13], were synthesized according to literature procedures. 2,5-Dimercapto-1,3,4-thiadiazole (5), picolyl chloride hydrochloride (7), and anhydrous solvents were purchased from Fluka, and used without further purification. All reactions were conducted under N₂ atmospheres. Melting points were determined on an Electrothermal melting point apparatus and are uncorrected. Elemental analyses were obtained commercially. Unless otherwise stated ¹H- and ¹³C-NMR spectra were performed in deuterated TCE (CDCl₂CDCl₂) with a Varian INOVA 500 instrument, using TMS as an internal standard. The ¹H- and ¹³C-NMR spectra of all compounds synthesized are collected in Table I and Table II. FAB (+) MS spectra were taken on a Kratos MS 50 S double-focusing mass spectrometer equipped with a standard FAB source, using 3-nitrobenzyl alcohol as a matrix.

5-Mercapto-5'-methylthio-2,2'-bi-1,3,4-thiadiazole (2).

To a chilled solution of 5,5'-dimercapto-2,2'-bi-1,3,4-thiadiazole (6, 2.34 g, 10.0 mmol), in aqueous NaOH (0.5 N, 40 mL) was added dropwise dimethyl sulfate (1.26 g, 10 mmol). After stirring for 1 h at room temperature, the solid bis(methylthio) derivative was collected by filtration and recrystallized from MeOH (0.78 g, 30%, mp. 177-178 °C). The filtrate was adjusted to pH 4.0−4.5 by addition of hydrochloric acid, and the precipitate was collected by suction filtration, dried under vacuum and then recrystallized from MeOH to give 0.65 g (26%) of yellow needles: mp 225 °C (dec.); ¹H-NMR δ: 11.16 (bs, 1 H), 2.85 (s, 3 H); ¹³C-NMR δ 188.7, 171.1, 156.4, 151.5, 16.8; FAB (+) MS, m/z 249 [MH]⁺; Anal. Calcd. for C₅H₄N₄S₄: C, 24.18; H, 1.62; N, 22.56. Found: C, 23.96; H, 1.84; N, 22.71.

General Procedure for the Nucleophilic Displacement Reactions: Synthesis of 2,6-Bis[5-methylthio-1,3,4-thiadiazol-2-ylthio)methyl]pyridine (L₁)

A stirred mixture of 2-mercapto-5-methylthio-1,3,4-thiadiazole (0.328 g, 2 mmol), 2,6-bis(chloro-methyl)pyridine (0.176 g, 1 mmol), and Et₃N (0.4 mL) in dry DMF (5 mL) was heated under stirring at 90 °C for 30 min. After cooling, the mixture was diluted with water and the precipitate was collected by filtration, washed with water, and dried. Recrystallization from EtOH provided L₁ as white elongated prisms. Yields, analytical and spectral data of L₁–L₈ are reported in Table I and Table II.