*Article* **1,3,4-Thiadiazole-Containing Azo Dyes: Synthesis, Spectroscopic Properties and Molecular Structure**

**Agnieszka Kudelko 1,\* , Monika Olesiejuk <sup>1</sup> , Marcin Luczynski <sup>1</sup> , Marcin Swiatkowski <sup>2</sup> , Tomasz Sieranski <sup>2</sup> and Rafal Kruszynski <sup>2</sup>**


Academic Editors: Jorge Bañuelos Prieto and Ugo Caruso Received: 10 June 2020; Accepted: 13 June 2020; Published: 18 June 2020

**Abstract:** Three series of azo dyes derived from 2-amino-5-aryl-1,3,4-thiadiazoles and aniline, *N,N*-dimethylaniline and phenol were synthesized in high yields by a conventional diazotization-coupling sequence. The chemical structures of the prepared compounds were confirmed by <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, IR, UV-Vis spectroscopy, mass spectrometry and elemental analysis. In addition, the X-ray single crystal structure of a representative azo dye was presented. For explicit determination of the influence of a substituent on radiation absorption in UV-Vis range, time-dependent density functional theory calculations were performed.

**Keywords:** heterocycles; 2-arylazo-5-aryl-1,3,4-thiadiazoles; azo-coupling reactions; crystal structure

#### **1. Introduction**

Thiadiazoles are five-membered heterocyclic arrangements which are rarely found in nature. Nitrogen, sulfur and carbon atoms can be arranged in several different ways in such a ring, which gives rise to several isomers: 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole and 1,3,4-thiadiazole [1,2]. Of these four isomers, derivatives of 1,3,4-thiadiazole seem to be the most popular among scientists. Many compounds containing such a scaffold exhibit a broad spectrum of biologic interactions and have been shown to have antifungal [3,4], antimicrobial [5], anti-inflammatory [6] and anticancer activities [7]. As well as other industrial applications, it is worth mentioning their use as viscosity stabilizers in rubber processing [8], additives for the production of lithium battery electrodes [9], dyes [10] and optoelectronic materials [11]. There are also reports of the applications of 1,3,4-thiadiazole derivatives, in particular 2,5-dimercapto-1,3,4-thiadiazoles, as lubricants [12].

Azo dyes, characterized by the presence of azo moiety (N=N) in their structure, are the most essential group of disperse dyes [13]. They have found a broad application mainly in dyestuff industry, but also in food, cosmetics and pharmaceuticals production. Generally azo dyes exhibit excellent coloring properties and offer vivid colors, starting from yellows, through oranges, reds and ending up in blues. One of the subgroups of this family are conjugated 1,3,4-thiadiazoles containing an azo group (N=N) in their structure. Such heterocyclic azo disperse dyes have received attention from the scientific community due to their brightness, clarity and affinity to various fibers [14,15]. The most common methodology to introduce this type of group into a final azo compound is a two-step transformation through appropriate diazonium salts [16]. The latter are usually produced from the reaction of primary aromatic amines with nitrites in the presence of strong mineral acids at

low temperatures. Due to the extreme instability of diazonium salts [17], they are used immediately after their formation in coupling reactions with phenols or amines, substituted with electron-donating groups. Other methods used to prepare azo dyes include the condensation of nitro compounds with amines [18], reduction of nitro compounds [19,20], oxidation of amines [21,22] or condensation of nitroso compounds with amines [23]. In contrast to typical aromatic amines, diazotization and subsequent coupling of 1,3,4-thiadiazole-2-amine derivatives is rarely described in the literature [24–26], although thiadiazoles contain an important thiazole chromophoric core in their structure. This may be due to the presence of an additional electronegative nitrogen atom, which decreases the basicity of the external amino group and reduces its reactivity.

In continuation of our study on the synthesis and versatile applications of conjugated 1,3,4-thiadiazole derivatives [27–29], we attempted to synthesize and characterize the structural features of a new series of 2-phenylazo-1,3,4-thiadiazoles, functionalized with aryl substituents directly on the heterocyclic ring. Such systems combining the 1,3,4-thiadiazole ring with other aromatic compounds through an azo linker may find potential industrial applications, not only as classical synthetic dyes and pigments, laser dyes and monomers for the production of OLEDs, but also in medicine and agriculture due to the presence of a toxophoric N–C–S moiety [30].

#### **2. Results and Discussion**

## *2.1. Synthesis*

The starting reagents in the synthesis of 1,3,4-thiadiazole-containing azo dyes were commercially available aromatic carboxylic acids substituted at position 4 with electron-donating or withdrawing groups (**1a**–**e**, Scheme 1). They were heated with thionyl chloride SOCl<sup>2</sup> and the resulting crude acid chlorides were transformed into derivatives of 2-benzoylhydrazinecarbothioamide (**2a**–**e**) in a two-phase water–toluene solvent system in the presence of base (NaHCO3). The resulting acyclic intermediates underwent cyclization in concentrated sulfuric acid to give the desired 2-amino-5-aryl-1,3,4-thiadiazoles (**3a**–**e**). The next stages in the few-step reaction sequence were the diazotization of 2-amino-1,3,4-thiadiazole derivatives (**3a**–**e**) and the subsequent coupling of the diazonium salts formed from aniline, *N,N*-dimethylaniline and phenol (Scheme 1). Diazotization involved the reaction of a primary heteroaromatic amine (**3a**–**e**) with a nitrosating agent (nitrosyl cation) generated in situ from sodium nitrite and concentrated sulfuric acid at low temperatures. Reactions were performed in a mixture of glacial acetic acid and propionic acid in order to improve the solubility of the starting thiadiazoles. An excess of nitrous acid in the post-reaction mixture was detected with potassium iodide–starch study and eliminated by adding urea. The resulting colored diazonium salts were then used directly without purification in the coupling sequence with aromatic amines: aniline (G=NH2) and *N,N*-dimethylaniline (G=NMe2) and with phenol (G=OH). Due to the limited stability of diazonium salts, the transformations were carried out at low temperatures (0–5 ◦C) and the final products were precipitated from solution by adding base (Na2CO3) after reagents were combined. The reactions resulted in the formation of three series of 2-arylazo-5-aryl-1,3,4-thiadiazole dyes in various yields (**4a**–**e**, **5a**–**e**, **6a**–**e**, Scheme 1). The highest yields were obtained from the transformations involving phenol (**6a**–**e**, 75–91%, Scheme 1), while the reactions using *N,N*-dimethylaniline (**5a**–**e**, 56–69%, Scheme 1) and aniline (**4a**–**e**, 51–81%, Scheme 1) produced lower yields. Such situation may be caused by partial deactivation of anilines in acidic media. Generally, 1,3,4-thiadiazole-containing azo dyes are high-melting solids (melting point range 169–293 ◦C) and are insoluble in both water and hydrocarbons (hexane, toluene). They are highly soluble in DMSO, acetone and methanol. It is worth noting that among the synthesized derivatives, 12 are new compounds not yet described in the literature.

– – – – – – – **Scheme 1.** Preparation of 2-amino-1,3,4-thiadiazole precursors (**3a**–**e**) and synthesis of 2-arylazo-5-aryl-1,3,4-thiadiazole dyes (**4a**–**e**, **5a**–**e**, **6a**–**e**). Reaction conditions: (i) toluene, reflux, 5–15 h; (ii) toluene, NaHCO<sup>3</sup> , H2O, rt, 24 h; (iii) conc. H2SO<sup>4</sup> , 24 h and then aqueous NH<sup>3</sup> ; (iv) NaNO<sup>2</sup> , conc. H2SO<sup>4</sup> , AcOH/EtCOOH, 0–5 ◦C; (v) H2O, 0–5 ◦C and then Na2CO<sup>3</sup> .
