3.2.5. General Procedure for the Synthesis of 2-(4-Hydroxyphenylazo)-5-phenyl-1,3,4-thiadiazole Derivatives (**6a**–**e**)

Sodium nitrite (1.31 g, 0.019 mol) was introduced portion wise into concentrated sulfuric acid (20 mL). The solution was heated to 50 ◦C in a water bath until complete dissolution and then rapidly cooled in an ice/salt bath to 0 ◦C. In the meantime, a solution of the appropriate 2-amino-5-aryl-1,3,4-thiadiazole **3a**–**e** (0.015 mol) in glacial acetic acid (30 mL) and propionic acid (15 mL) was prepared and added dropwise to an agitated solution of sodium nitrite in concentrated sulfuric acid at 0–5 ◦C. Then, the mixture was stirred for 24 h and excess nitrous acid was decomposed by the addition of urea. The resulting diazonium salt solution was slowly introduced into the mixture of phenol (1.41 g, 0.015 mol) in 15 mL of water at 0–5 ◦C. The colored mixture was stirred at room temperature for 24 h and finally neutralized with saturated sodium carbonate solution (75 mL). The solid was filtered off, washed twice with hot water (2 × 25 mL) and dried in air. The crude product (**6a**–**e**) was purified by column chromatography on silica gel (CHCl3/EtOAc, 5:1 *v*/*v*).

*2-(4-Hydroxyphenylazo)-5-phenyl-1,3,4-thiadiazole* (**6a**). The product was obtained as a red solid (3.47 g, 82%); mp 200–202 ◦C (196–198 ◦C [25]); R<sup>f</sup> (CHCl3/EtOAc, 5:1 *v*/*v*) 0.25. IR (ATR) ν: 3060, 1608, 1512 cm−<sup>1</sup> ; Anal. Calcd for C14H10N4OS: C, 59.56; H, 3.57; N, 19.85. Found: C, 59.50; H, 3.52; N, 19.87.

*2-(4-Hydroxyphenylazo)-5-(4-methoxyphenyl)-1,3,4-thiadiazole* (**6b**). The product was obtained as an orange solid (4.26 g, 91%); mp 271–273 ◦C; R<sup>f</sup> (CHCl3/EtOAc, 5:1 *v*/*v*) 0.23. <sup>1</sup>H-NMR (400 MHz, DMSO-d6): δ 3.86 (s, 3H, OCH3), 7.02 (d, 2H, *J* = 9.2 Hz, 2-Ar: H-3, H-5), 7.13 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-3′ , H-5′ ), 7.92 (d, 2H, *J* = 9.2 Hz, 2-Ar: H-2, H-6), 8.03 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-2′ , H-6′ ); <sup>13</sup>C-NMR (100 MHz, DMSO-d6): δ 55.5, 114.9, 116.7, 122.1, 126.8, 129.6, 144.7, 162.2, 164.1, 167.3, 178.4. IR (ATR) ν: 3099, 1601, 1518 cm−<sup>1</sup> ; HRMS calcd for (C15H12N4SO2+H+): 313.0759; found: 313.0755; Anal. Calcd for C15H12N4SO2: C, 57.68; H, 3.87; N, 17.94. Found: C, 57.59; H, 3.85; N, 17.99.

*2-(4-Hydroxyphenylazo)-5-(4-nitrophenyl)-1,3,4-thiadiazole* (**6c**). The product was obtained as a dark brown solid (3.92 g, 80%); mp 258–260 ◦C; R<sup>f</sup> (CHCl3/EtOAc, 5:1 *v*/*v*) 0.35. <sup>1</sup>H-NMR (400 MHz, DMSO-d6): δ 6.97 (d, 2H, *J* = 8.8 Hz, 2-Ar: H-3, H-5), 7.92 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-3′ , H-5′ ), 8.28–8.40 (m, 4H, 2-Ar, 5-Ar: H-2, H-6, H-2′ , H-6′ ); <sup>13</sup>C-NMR (100 MHz, DMSO-d6): δ 117.4, 124.4, 124.6, 127.5, 129.0, 144.7, 157.3, 164.1, 167.4, 179.1. IR (ATR) ν: 3080, 1598, 1515 cm−<sup>1</sup> ; HRMS calcd for (C14H9N5SO<sup>3</sup> + H+): 328.0504; found: 328.0502; Anal. Calcd for C14H9N5SO3: C, 51.37; H, 2.77; N, 21.40. Found: C, 51.50; H, 2.78; N, 21.47.

*5-(4-Bromophenyl)-2-(4-hydroxyphenylazo)-1,3,4-thiadiazole* (**6d**). The product was obtained as a brown solid (4.06 g, 75%); mp 263–265 ◦C; R<sup>f</sup> (CHCl3/EtOAc, 5:1 *v*/*v*) 0.33. <sup>1</sup>H-NMR (400 MHz, DMSO-d6): δ 7.03 (d, 2H, J= 9.2 Hz, 2-Ar: H-3, H-5), 7.80 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-3′ , H-5′ ), 7.94 (d, 2H, *J* = 9.2 Hz, 2-Ar: H-2, H-6), 8.03 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-2′ , H-6′ ); <sup>13</sup>C-NMR (100 MHz, DMSO-d6): δ 116.8, 125.5, 127.1, 129.6, 131.7, 132.5, 144.7, 164.4, 166.4, 179.4. IR (ATR) ν: 3047, 1587, 1507 cm−<sup>1</sup> ; HRMS calcd for (C14H9N4SOBr + H+): 360.9759; found: 360.9757; Anal. Calcd for C14H9N4SOBr: C, 46.55; H, 2.51; N, 15.51. Found: C, 46.61; H, 2.50; N, 15.59.

*5-(4-t-Butylphenyl)-2-(4-hydroxyphenylazo)-1,3,4-thiadiazole* (**6e**). The product was obtained as an orange solid (4.06 g, 80%); mp 291–293 ◦C; R<sup>f</sup> (CHCl3/EtOAc, 5:1 *v*/*v*) 0.37. <sup>1</sup>H-NMR (400 MHz, DMSO-d6): δ 1.33 (s, 9H, C(CH3)3), 7.03 (d, 2H, *J* = 9.2 Hz, 2-Ar: H-3; H-5), 7.60 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-3′ , H-5′ ), 7.94 (d, 2H, *J* = 9.2 Hz, 2-Ar: H-2, H-6), 8.01 (d, 2H, *J* = 8.8 Hz, 5-Ar: H-2′ , H-6′ ); <sup>13</sup>C-NMR (100 MHz, DMSO-d6): δ 30.8, 34.8, 116.7, 126.3, 126.9, 127.6, 129.6, 144.8, 155.1, 164.1, 167.5, 178.8. IR (ATR) ν: 3100, 1582, 1507 cm−<sup>1</sup> ; HRMS calcd for (C18H18N4SO + H+): 339.1280; found: 339.1281; Anal. Calcd for C18H18N4SO: C, 63.88; H, 5.36; N, 16.56. Found: C, 63.76; H, 5.39; N, 16.51.

#### **4. Conclusions**

An efficient synthetic strategy for the preparation of new azo dyes using weak heteroaromatic amines containing a 1,3,4-thiadiazole scaffold as the diazo component and aniline, *N,N*-dimethylaniline and phenol as simultaneous coupling precursors, was presented. Three series of azo dyes, the derivatives of 2-phenylazo-5-phenyl-1,3,4-thiadiazole, were obtained in good to excellent yields. The new dyes obtained—demonstrating a broad color spectrum and good solubility in some polar solvents—may serve as potential candidates for the dye industry and will be tested in the near future.

**Supplementary Materials:** Copies of the 1H-NMR, 13C-NMR, UV-Vis and IR spectra of the compounds as well as figures showing the calculated spectra and the contour plots of the most important molecular orbitals are available in the online Supplementary Materials.

**Author Contributions:** A.K., M.O. and M.L. conceived and designed the experiments, performed the experiments and analyzed the data. M.S., T.S. and R.K. performed emission measurements, X-ray structural analysis and time-dependent density functional theory calculations. A.K. wrote the manuscript with the help of M.O. and R.K. All authors read and approved the final manuscript.

**Funding:** The synthetic part of the project was financially supported by the EU under the project RPO WL RPLU.01.02.00-06-1116/16. The crystallographic part was financed by funds allocated by the Ministry of Science and Higher Education to the Institute of General and Ecological Chemistry, Lodz University of Technology in Poland.

**Conflicts of Interest:** The authors declare no conflicts of interest.

## **References**


**Sample Availability:** Samples of the compounds **4a**–**e, 5a**–**e**, **6a**–**e** are available from the authors.

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