Home Eelectrosynthesis of benzothiazole derivatives via C–H thiolation
Article Open Access

Eelectrosynthesis of benzothiazole derivatives via C–H thiolation

  • Reza Ahdenov , Ali Asghar Mohammadi EMAIL logo , Somayeh Makarem , Salman Taheri and Hoda Mollabagher
Published/Copyright: May 10, 2022
Download Article (PDF)
Heterocyclic Communications
From the journal Heterocyclic Communications Volume 28 Issue 1

Abstract

Benzothiazole derivatives are essential intermediates in synthesizing a wide variety of medical and pharmaceutical compounds, and there is a great demand for a simple and efficient method to synthesize benzothiazoles under mild reaction conditions. Organic electrosynthesis as an energy-efficient process represents an environmentally benign and safer method than traditional methods for organic synthesis. Herein, we present bromine-free and straightforward synthesis of 2-amino benzothiazole derivatives via the reaction of aniline derivatives and ammonium thiocyanate using electrosynthesis in the presence of sodium bromide both as an electrolyte and as a brominating agent at room temperature in isopropyl alcohol (i-PrOH) as a solvent. The reaction of ammonium thiocyanate via C–H thiolation routes, using various aniline derivatives, resulted in a simple, green, and bromine-free synthesis of 2-amino benzothiazole in moderate to good yields under mild reaction conditions. Riluzole drug can be produced using the same procedure in moderate yields.

Graphical abstract

Keywords: benzothiazole; electrosynthesis; C–H thiolation; green chemistry; Riluzole

1 Introduction

Economic and green synthesis of biologically active heterocycles has become a trending research topic in green chemistry [1,2,3,4,5]. Benzo[d]thiazole derivatives are a vital class of organic compounds in the pharmaceutical industry for the treatment of some diseases like epilepsy [6] and tuberculosis [7] and are applied as anticonvulsant [8,9], analgesic [10], anti-diabetic [11], anticancer [12], and antiviral agent [13]. Examples of the clinically approved benzothiazole-based compounds are Halethazole (antibacterial) [14], Thioflavin-T (amyloid imaging agent) [15], Dimazole (antifungal) [16], Ethoxzolamide (treatment of glaucoma) [17], Phortress (antitumor) [18], Riluzole (antidepressant) [19], Flutemetamol (radiopharmaceutical) [20], and Frentizole (immunosuppressive) [21] (Figure 1).

Figure 1 Benzo[d]thiazole-based compounds in the pharmaceutical industry.
Figure 1

Benzo[d]thiazole-based compounds in the pharmaceutical industry.

2-Aminobenzothiazoles were synthesized in the early 1900s by cyclization of arylthiourea in the presence of liquid bromine as an oxidant for the first time [22]. The reaction was carried out at room temperature to produce 2-aminobenzothiazole in good yields in the presence of liquid bromine, which is highly corrosive and toxic and difficult to handle on a laboratory scale. Therefore, discovering new reaction conditions for the synthesis of aminobenzothiazole using bromine-free methods is an ongoing challenge for researchers in modern organic synthesis. In this context, one pot for the synthesis of aminobenzothiazole has been widely investigated recently [23,24,25].

Electro-organic synthesis was first reported in 1834, and so far, it is known as a powerful and safe tool in organic synthesis [26]. Electrosynthesis is a huge topic in the field of electrochemistry and also has industrial applications. Organic electrosynthesis used alternative tools for multicomponent reactions in synthesizing heterocyclic compounds and redox processes. As a result, toxic, elusive, and hazardous oxidants are replaced with a safe and environmentally friendly reagent for electrochemical synthesis of the organic compound via C–H or C–X (X = heteroatoms) bond formations [27,28,29]. Furthermore, electrosynthesis of the substituted benzothiazoles [30,31,32] has also been reported in the literature. For instance, Tabaković et al. reported the first electrochemical synthesis of benzothiazole in 1979 using tetraethylammonium perchlorate in the divided cell at a constant current with acetonitrile as a solvent [33]. Their strategy requires the use of a divided cell and high potential and received little attention. Qian et al. demonstrated the electrosynthesis of benzothiazoles from N-arylthioamides [32] using 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as a radical catalyst. Mechanistic studies have suggested that the thioamide substrate is oxidized through the electrochemically generated cationic TEMPO [32].

2 Results and discussion

Earlier studies in our laboratories dealt with the electrosynthesis of heterocyclic compounds such as 3-hydroxy-3-(1H-indol-3-yl) indolin-2-one derivatives [34], 2-amino-pyranes [35], phthalazines [36], and spirocyclopropane derivatives [5]. Herein, we report a simple and efficient synthesis of a variety of 2-aminothiazole derivatives through an electrochemical-mediated approach by using NaBr both as an electrolyte and as a bromination source as relatively non-toxic and inexpensive reagents. These oxidative cyclizations have been achieved using iron-based catalysts [37], visible light, oxygen and palladium–ruthenium [38], and platinum cathode [32,39,40,41] (Figure 2). The major disadvantages of these methods are their high cost of process and deposition of a remarkable quantity of metal and, consequently, a relatively high metal waste production [42,43].

Figure 2 Methods used for the synthesis of benzothiazoles.
Figure 2

Methods used for the synthesis of benzothiazoles.

Interestingly, it was found that sodium bromide, both as an electrolyte and as a brominating agent, gives outstanding results. The reaction between aniline derivatives 1(a–j) and ammonium thiocyanate (2) was investigated in detail under electrosynthesis reaction conditions, and a series of 2-aminobenzothiazole products 7(a–j) were designed and synthesized in moderate and good yields.

The model reaction was carried out with aniline reacting with ammonium thiocyanate (2) in the presence of NaBr (50 mol%) in isopropanol (i-PrOH) under a constant current at room temperature in a one-pot mode. The formation of 2-aminobenzothiazole derivatives 7a was observed at moderate yields (Table 1, Entry 1). After various trials, it was observed that one-pot reaction conditions did not work very well for this protocol, and benzothiazole formation was not satisfactory. According to the previous reports [43,44], it was found that the reaction works best under two steps. First, phenylthiourea derivatives 3(a–j) were synthesized from the reaction of anilines 1(a–j) and ammonium thiocyanate (2) (Table 1). All the anilines 1(a–j) containing electron-donating and electron-withdrawing groups produced corresponding phenylthiourea 3(a–j) derivatives in moderate to good isolated yields (Table 1).

Table 1

Reaction condensation of amines 1(a–j) with ammonium thiocyanate 2 for preparation of phenylthiourea (3a–j) derivatives

Entry Producta R M.P. (oC) M.P. (oC) [Lit.] Yield (%)b
1 3a H 151–153 127–128 [44] 94
2 3b 4-Cl 175 174–178 [45] 92
3 3c 4-Br 186 217–219 [46] 89
4 3d 4-Me 179 127–129 [47] 84
5 3e 4-I 180 206–208 [48] 87
6 3f 4-MeO 207 160–162 [49] 82
7 3g 2-Me 148 135–137 [50] 89
8 3h 2-Br 132 134–135 [51] 85
9 3i 4-CF3 124 119–122 [52] 87
10 3j 4-OCF3 135 118 [53] 79

aFor all reactions, aniline derivatives (1.0 mmol), ammonium thiocyanate 2 (1.0 mmol), and solvent (15 mL) were added at room temperature, and the solution was heated at 70°C for 15 min.

bIsolated yields based on aniline.

The optimization of reaction conditions was carried out via cyclization of phenylthiourea (3a–j) derivatives to 2-aminobenzothiazoles 7(a–j) in various reaction conditions. The results are shown in Table 2. The model reaction was optimized under a constant current of 40 mA in i-PrOH at an undivided cell, while sodium bromide was an electrolyte and a brominating agent at room temperature. Completion of the reaction within 3 h was monitored using thin-layer chromatography (TLC). A number of electrolytes (NaBr and NaCl), solvents (EtOH and i-PrOH), and currents (0.1, 0.2, 0.3, 0.4, and 0.5 A) were also screened (Table 2, Entries 1–13), it has been found that NaBr, i-PrOH, and current of 0.4 A at room temperature promote the reaction for preparation of benzothiazole derivatives (Table 2, Entry 10).

Table 2

Comparing the effect of different solvents, electrolyte, and currents on the reaction of 1-phenylthiourea 3a with NaBr and NaCl as an electrolyte

Entry Current (A) Electrolyte Solvent Time (h) Yield (%)a
1 0.5 NaCl (50%) i-PrOH 3 —
2 0.1 NaBr (50%) i-PrOH 1 20
3 0.1 NaBr (50%) EtOH 1 —
4 0.1 NaBr (50%) i-PrOH 2 28
5 0.1 NaBr (50%) i-PrOH 3 35
6 0.1 NaBr (50%) i-PrOH 4 34
7 0.1 NaCl (50%) i-PrOH 3 —
8 0.2 NaBr (50%) i-PrOH 3 55
9 0.3 NaBr (50%) i-PrOH 3 61
10 0.4 NaBr (50%) i-PrOH 3 74
11 0.5 NaBr (50%) i-PrOH 3 68
12 0.4 NaBr (50%) i-PrOH 2 52
13 0.4 NaBr (70%) i-PrOH 3 65

aIsolated yields based on aniline.

Encouraged by the successful results, we attempted to extend the scope of this procedure to various phenylthiourea derivatives 3(a–j), leading to the generation of corresponding 2-aminobenzothiazoles 7(a–j). In all cases, phenylthiourea substituted with either electron-donating or electron-withdrawing groups underwent a satisfactory reaction and gave the products in moderate to good yields (Table 3). All the aminobenzothiazoles were characterized by their melting points (MPs) and comparison of their nuclear magnetic resonance spectra with those of authentic samples.

Table 3

Intramolecular cyclization reaction of phenylthiourea 3(a–j) for preparation of 2-aminobenzothiazoles 7(a–j)

Producta R M.P. (oC) M.P. (oC) [Lit.] Yield (%)b
7a H 127 127–128 [44] 74
7b 4-Cl 173–177 175–179 [45] 77
7c 4-Br 219–221 217–219 [46] 75
7d 4-Me 126–128 127–129 [47] 70
7e 4-I 207–209 206–208 [48] 72
7f 4-MeO 159–162 160–162 [49] 71
7g 2-Me 133–135 135–137 [50] 73
7h 2-Br 137–139 134–135 [51] 68
7i 4-CF3 117–118 119–122 [52] 64
c 7j 4-OCF3 120–122 118 [53] 77
  1. a

    All reactions were run with phenylthiourea 3(a–j) (1mmol) and 0.05g (0.5mmol) of NaBr in 15mL of i-PrOH, current 0.4 A in an undivided cell equipped with an iron cathode (5cm2) and a graphite (5cm2) anode at room temperature. bIsolated yields based on aniline

  2. c

    7j is Riluzole.

A plausible mechanism for electrosynthesis of the 2-aminobenzothiazoles 7(a–j) is outlined in Scheme 1. Accordingly, on the cathode surface, isopropanol deprotonation causes the formation of an alkoxide anion. The subsequent reaction between the alkoxide anion and phenylthiourea (3a–j) gives a phenylthiourea anion (4a–j). On the anode surface, NaBr oxidation leads to the formation of Br2, and then, phenylthiourea anion (4a–j) undergoes bromination to afford ((bromothio)(imino)methyl)(phenyl)amide (5a–j), subsequently leading to a cascade of intramolecular cyclizations (6a–j). Finally, the product (7a–j) is formed by intramolecular protonation and rearrangement of intermediate (6a–j) (Scheme 1).

Scheme 1 Proposed mechanism for the synthesis of benzothiazole derivatives via electrochemical C–H thiolation.
Scheme 1

Proposed mechanism for the synthesis of benzothiazole derivatives via electrochemical C–H thiolation.

3 Conclusion

In summary, we have developed a green and straightforward electro-organic synthesis of benzothiazole scaffolds as a promising technique in the presence of NaBr both as an oxidant and as an electrolyte through electrocyclization of phenylthiourea derivatives 3(a–j) in good yields. This electrosynthesis procedure employs simple equipment, low-cost electrode, and low-toxic oxidant. Omitting liquid bromine as an oxidant and replacing sodium bromide are the main advantages of this procedure. The method allowed us to synthesize a Riluzole drug in moderate yields under green reaction conditions without harmful solvents and reagents.

4 Experimental

All reagents and solvents are commercially available and were purchased and used without further purification. Products were confirmed using 1H NMR spectroscopy. The reactions are monitored using TLC on silica gel with ultraviolet light as detecting agents. MPs were recorded in open capillary tubes and were measured using an electrothermal 9200 apparatus. 1H NMR spectra were determined using a Bruker 500, with DMSO-d 6 as a solvent.

4.1 General procedure for the preparation of phenylthiourea (3a-j)

A mixture of ammonium thiocyanate (2) (1 equiv.) in acetic acid (5 mL) at room temperature was prepared, aniline (1 equiv.) was added, and the solution was heated at 70°C for 15 min. Reaction progress was monitored using TLC. After completion of the reaction, the reaction mixture was poured into cold water, the precipitate was filtered, and the pH of the system was adjusted with NH3 (30%). The product was purified and recrystallized in ethanol, yielding 94% M.P. 151–153°C.

4.2 General procedure for the preparation of 2-aminobenzothiazoles 7(a–j)

A mixture of phenylthiourea (3a–j) (1 mmol) and NaBr (0.5 mmol) in i-PrOH (15 mL) was magnetically stirred and electrolyzed in an undivided cell equipped with an iron cathode (5 cm2) and graphite (5 cm2) anode at room temperature under a constant current of 0.4 A. After the completion of the reaction (monitored using TLC and ethyl acetate/n-hexane ratio of 2:1), the solvent was evaporated under reduced pressure to give the crude product. Then, the crude product was purified using flash column chromatography (hexane–ethyl acetate ratio of 4:1).

4.3 Benzo[d]thiazol-2-amine (7a)

Yield: 235 mg (74%); white solid; M.P.: 127°C (Lit. [44] 127–128°C); 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 7.21 (s, 1H, Ar-H), 7.24–7.27 (d, 2H, Ar-H), 7.56 (s, 1H, Ar-H), 7.63 (s, 2H, NH2).

4.4 6-Chlorobenzo[d]thiazol-2-amine (7b)

Yield: 244 mg (77%); white yellow solid; M.P.: 192–194°C (Lit. [45] 173–177°C); (500 MHz, DMSO-d 6) δ (ppm) 7.20 (d, J = 8.6 Hz, 1H, Ar-H), 7.29 (d, J = 8.6 Hz, 1H, Ar-H), 7.60 (br.s, 2H, NH2), 7.76 (d, J = 2.3 Hz, 2H, Ar-H).

4.5 6-Bromobenzo[d]thiazol-2-amine (7c)

Yield: 238 mg (75%); white yellow solid; M.P.: 219–221°C (Lit. [46] 217–219°C); (500 MHz, DMSO-d 6) δ (ppm) 7.24 (d, J = 10.1 Hz, 1H, Ar-H), 7.32–7.34 (m, 1H, Ar-H), 7.64 (br.s, 2H, NH2), 7.88 (d, J = 3 Hz, 1H, Ar-H).

4.6 6-Methylbenzo[d]thiazol-2-amine (7d)

Yield: 222 mg (70%); white yellow solid; M.P.: 126–128°C (Lit. [47] 127–129°C); yield (70%); (500 MHz, DMSO-d 6) δ (ppm) 2.29 (s, 3H, CH3), 7.22–7.25 (m, 1H, Ar-H), 7.47 (d, J = 8.1 Hz, 1H, Ar-H), 7.74 (br.s, 2H, NH2), 7.94 (m, 1H, Ar-H).

4.7 6-Iodobenzo[d]thiazol-2-amine (7e)

Yield: 228 mg (72%); white yellow solid; M.P.: 207–209°C (Lit. [48] 206–208°C); (500 MHz, DMSO-d 6) δ (ppm) 7.28 (d, J = 8.7 Hz, 1H, Ar-H), 7.42 (d, J = 8.3 Hz, 1H, Ar-H), 7.85 (br.s, 2H, NH2), 8.12 (s, 1H, Ar-H).

4.8 6-Methoxybenzo[d]thiazol-2-amine (7f)

Yield: 225 mg (71%); white; M.P.: 159–162°C (Lit. [49] 160–162°C); (500 MHz, DMSO-d 6) δ (ppm) 3.68 (s, 3H, CH3), 6.79 (d, J = 7 Hz, 1H, Ar-H), 7.15 (s, 2H, NH2), 7.22–7.23 (m, 1H, Ar-H), 7.27–7.29 (m, 1H, Ar-H).

4.9 4-Methylbenzo[d]thiazol-2-amine (7g)

Yield: 231 mg (73%); white; M.P.: 133–135°C (Lit. [50] 135–137°C); (500 MHz, DMSO-d 6) δ (ppm) 2.32 (s, 3H, CH3), 7.12–7.15 (m, 1H, Ar-H), 7.27–7.29 (m, 1H, Ar-H), 7.24 (br.s, 2H, NH2), 7.54 (m, 1H, Ar-H).

4.10 4-Bromobenzo[d]thiazol-2-amine (7h)

Yield: 216 mg (68%); white; M.P.: 137–139°C (Lit. [51] 134–135°C); (500 MHz, DMSO-d 6) δ (ppm) 6.93 (t, J = 7.7 Hz, 1H, Ar-H), 7.32 (s, 2H, NH2), 7.43 (s, 1H, Ar-H), 7.62 (d, J = 7.7 Hz, 1H, Ar-H).

4.11 6-(Trifluoromethyl)benzo[d]thiazol-2-amine (7i)

Yield: 203 mg (64%); white; M.P.: 117–118°C (Lit. [52] 119–122°C); (500 MHz, DMSO-d 6) δ (ppm) 6.28 (s, 2H, NH2), 7.51–7.53 (m, 2H, Ar-H), 7.81–7.83 (m, 1H, Ar-H).

4.12 6-(Trifluoromethoxy)benzo[d]thiazol-2-amine(7j)

Yield: 244 mg (77%); white yellow solid; M.P.: 120–122°C (Lit. [53] 118°C) (500 MHz, DMSO-d 6) δ (ppm) 7.17 (d, 1H, J = 8.7 Hz, Ar-H), 7.37 (d, J = 8.6 Hz, 1H, Ar-H), 7.73 (br.s, 2H, NH2), 7.77 (m, 1H, Ar-H).

Acknowledgments

The authors gratefully acknowledge the financial support of the Chemistry and Chemical Engineering Research Center of Iran.

  1. Funding information: The study was funded by the Chemistry and Chemical Engineering Research Center of Iran.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

[1] Mohammadi AA, Taheri S, Amini A, Ahdenov R. Synthesis of some new triamide derivatives via Ugi five-component reaction in aqueous solution. Mol Divers. 2018;22:999–1006.10.1007/s11030-018-9846-zSearch in Google Scholar PubMed

[2] Mohammadi AA, Taheri S, Ghaderi P, Ahdenov R, Azizian H, Mohammadi-Khanaposhtani M, et al. Synthesis of the new tri-amide derivatives as novel α-glucosidase inhibitors by Ugi four-component reaction. J Mol Struct. 2021;1227:129531.10.1016/j.molstruc.2020.129531Search in Google Scholar

[3] Kratena N, Pfeffer S, Enev VS, Gmeiner G, Gärtner P. Synthesis of human long-term metabolites of dehydrochloromethyltestosterone and oxymesterone. Steroids. 2020;164:108716.10.1016/j.steroids.2020.108716Search in Google Scholar PubMed

[4] Štanfel U, Slapšak D, Grošelj U, Požgan F, Štefane B, Svete J. Synthesis of 6, 7-Dihydro-1H, 5H-pyrazolo [1, 2-a] pyrazoles by azomethine imine-alkyne cycloadditions using immobilized Cu (II)-catalysts. Molecules. 2021;26:400.10.3390/molecules26020400Search in Google Scholar PubMed PubMed Central

[5] Mohammadi AA, Makarem S, Ahdenov R, Notash NA. Green pseudo-multicomponent synthesis of some new spirocyclopropane derivatives via electro-catalyzed reaction. Mol Divers. 2020;24:763–70.10.1007/s11030-019-09979-8Search in Google Scholar PubMed

[6] Mishra CB, Kumari S, Tiwari M. Thiazole: A promising heterocycle for the development of potent CNS active agents. Eur J Med Chem. 2015;92:1–34.10.1016/j.ejmech.2014.12.031Search in Google Scholar PubMed

[7] Samala G, Devi PB, Saxena S, Meda N, Yogeeswari P, Sriram D. Design, synthesis and biological evaluation of imidazo [2, 1-b] thiazole and benzo[d]imidazo [2, 1-b] thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors. Bioorg Med Chem. 2016;24:1298–307.10.1016/j.bmc.2016.01.059Search in Google Scholar PubMed

[8] Tripathi RKP, Ayyannan SR. Anticonvulsant activity, organotypic hippocampal neuroprotection assay and in-silico sodium channel blocking potential of 2-amino-6-nitrobenzothiazole derived semicarbazones. Biomed Pharmacother. 2017;95:1451–60.10.1016/j.biopha.2017.09.070Search in Google Scholar PubMed

[9] Ahmadi A, Khalili M, Mohammadinoude MK, Nahri-Niknafs B. Synthesis and Analgesic Properties of Lidocaine Derivatives with Substituted Aminobenzothiazoles. Comb Chem High Throughput Screen. 2016;19:507–12.10.2174/1386207319666160517115310Search in Google Scholar PubMed

[10] Westaway SM, Thompson M, Rami HK, Stemp G, Trouw LS, Mitchell DJ, et al. Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1. Bioorg Med Chem Lett. 2008;18:5609–13.10.1016/j.bmcl.2008.08.105Search in Google Scholar PubMed

[11] Bhutani R, Pathak DP, Kapoor G, Husain A, Kant R, Iqbal MA. Synthesis, molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their anti-diabetic activity through in vivo model. Bioorg Chem. 2018;77:6–15.10.1016/j.bioorg.2017.12.037Search in Google Scholar PubMed

[12] Uremis N, Uremis MM, Tolun FI, Ceylan M, Doganer A, Kurt AH. Synthesis of 2-substituted benzothiazole derivatives and their in vitro anticancer effects and antioxidant activities against pancreatic cancer cells. Anticancer Res. 2017;37:6381–9.10.21873/anticanres.12091Search in Google Scholar

[13] Sharma PC, Sinhmar A, Sharma A, Rajak H, Pathak DP. Medicinal significance of benzothiazole scaffold: an insight view. J Enzyme Inhib Med Chem. 2013;28:240–66.10.3109/14756366.2012.720572Search in Google Scholar PubMed

[14] Chu FC, Leung WK, Tsang PC, Chow TW, Samaranayake LP. Identification of cultivable microorganisms from root canals with apical periodontitis following two-visit endodontic treatment with antibiotics/steroid or calcium hydroxide dressings. J Endod. 2006;32:17–23.10.1016/j.joen.2005.10.014Search in Google Scholar PubMed

[15] Ma L, Yang S, Ma Y, Chen Y, Wang Z, James TD, et al. Benzothiazolium Derivative-Capped Silica Nanocomposites for β-Amyloid Imaging In Vivo. Anal Chem. 2021;93:12617–27.10.1021/acs.analchem.1c02289Search in Google Scholar PubMed PubMed Central

[16] Zhao S, Zhao L, Zhang X, Liu C, Hao C, Xie H, et al. Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents. Eur J Med Chem. 2016;123:514–22.10.1016/j.ejmech.2016.07.067Search in Google Scholar PubMed

[17] Ribeiro A, Sosnik A, Chiappetta DA, Veiga F, Concheiro A, Alvarez-Lorenzo C. Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy. J R Soc Interface. 2012;9:2059–69.10.1098/rsif.2012.0102Search in Google Scholar PubMed PubMed Central

[18] Mortimer CG, Wells G, Crochard J-P, Stone EL, Bradshaw TD, Stevens MF, et al. Antitumor benzothiazoles. 26. 2-(3, 4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J Med Chem. 2006;49:179–85.10.1021/jm050942kSearch in Google Scholar PubMed

[19] Wilkinson ST, Kiselycznyk C, Banasr M, Webler RD, Haile C, Mathew SJ. Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression. J Affect Disord. 2018;241:514–8.10.1016/j.jad.2018.08.075Search in Google Scholar PubMed PubMed Central

[20] Taylor NJ, Emer E, Preshlock S, Schedler M, Tredwell M, Verhoog S, et al. Derisking the Cu-mediated 18F-fluorination of heterocyclic positron emission tomography radioligands. J Am Chem Soc. 2017;139:8267–76.10.1021/jacs.7b03131Search in Google Scholar PubMed

[21] Mase T, Arima H, Tomioka K, Yamada T, Murase K. Imidazo [2, 1-b] benzothiazoles. 2. New immunosuppressive agents. J Med Chem. 1986;29:386–94.10.1021/jm00153a014Search in Google Scholar PubMed

[22] Hugershoff A. Einwirkung von halogenen auf thioharnstoffe. Ber Dtsch Chem Gese. 1901;34:3130–5.10.1002/cber.190103402286Search in Google Scholar

[23] Afsar SY, Mohammadi Ziarani G, Mollabagher H, Gholamzadeh P, Badiei A, Abolhasani Soorki A. Application of SBA-Pr-SO3H in the synthesis of 2, 3-dihydroquinazoline-4 (1H)-ones: characterization, UV–Vis investigations and DFT studies. J Iran Chem Soc. 2017;14:577–83.10.1007/s13738-016-1006-8Search in Google Scholar

[24] Taheri S, Mohammadi AA, Ahdenov R, Azarlak R, Amini SK, Halvagar MR. A straightforward approach for the synthesis of novel fused thiopyrano [2, 3-b] indole derivatives from the Intramolecular Friedel-Crafts acylation. J Mol Struct. 2020;1208:127854.10.1016/j.molstruc.2020.127854Search in Google Scholar

[25] Mohammadi AA, Ahdenov R, Sooki AA. Design, synthesis and antibacterial evaluation of 2-alkyl-and 2-aryl-3-(phenylamino) quinazolin-4 (3H)-one derivatives. Heterocycl Commun. 2017;23:105–8.10.1515/hc-2016-0201Search in Google Scholar

[26] Pollok D, Waldvogel SR. Electro-organic synthesis–a 21 st century technique. Chem Sci. 2020;11:12386–400.10.1039/D0SC01848ASearch in Google Scholar PubMed PubMed Central

[27] Wang H, Zhang J, Tan J, Xin L, Li Y, Zhang S, et al. Electrosynthesis of trisubstituted 2-oxazolines via dehydrogenative cyclization of β-amino arylketones. Org Lett. 2018;20:2505–8.10.1021/acs.orglett.8b00165Search in Google Scholar PubMed

[28] Xu F, Li Y-J, Huang C, Xu HC. Ruthenium-catalyzed electrochemical dehydrogenative alkyne annulation. ACS Catal. 2018;8:3820–4.10.1021/acscatal.8b00373Search in Google Scholar

[29] Dissanayake DMMM, Vannucci AK. Transition-Metal-Free and Base-Free Electrosynthesis of 1 H-Substituted Benzimidazoles. ACS Sustain Chem Eng. 2018;6:690–5.10.1021/acssuschemeng.7b03029Search in Google Scholar

[30] Folgueiras-Amador AA, Qian XY, Xu HC, Wirth T. Catalyst‐and supporting‐electrolyte‐free electrosynthesis of benzothiazoles and thiazolopyridines in continuous flow. Chem Eur J. 2018;24:487–91.10.1002/chem.201705016Search in Google Scholar PubMed

[31] Lai Y, Ye J, Huang J. Electrochemical Synthesis of Benzazoles from Alcohols and o‐Substituted Anilines with a Catalytic Amount of CoII Salt. Chem Eur J. 2016;22:5425–9.10.1002/chem.201505074Search in Google Scholar PubMed

[32] Qian X-Y, Li S-Q, Song J, Xu HC. TEMPO-catalyzed electrochemical C–H thiolation: synthesis of benzothiazoles and thiazolopyridines from thioamides. ACS Catal. 2017;7:2730–4.10.1021/acscatal.7b00426Search in Google Scholar

[33] Tabaković I, Trkovnik M, Grujić Z. Electrochemical synthesis of heterocyclic compounds. Part 6. The redox behaviour of the formazan–tetrazolium salt system in acetonitrile. J Chem Soc Perkin Trans. 1979;2:166–71.10.1039/P29790000166Search in Google Scholar

[34] Makarem S, Fakhari AR, Mohammadi AA. Electro-organic synthesis of nanosized particles of 3-hydroxy-3-(1 H-indol-3-yl) indolin-2-one derivatives. Mon Chem. 2012;143:1157–60.10.1007/s00706-011-0693-1Search in Google Scholar

[35] Makarem S, Fakhari AR, Mohammadi AA. Electro-organic synthesis of nanosized particles of 2-amino-pyranes. Ind Eng Chem Res. 2012;51:2200–4.10.1021/ie200997bSearch in Google Scholar

[36] Makarem S, Fakhari AR, Mohammadi AA. Electro-organic synthesis: an efficient method for the preparation of nanosized particles of phthalazine derivatives via one-pot multicomponent reactions. Anal Bioanal Chem Res. 2015;2:85–9.Search in Google Scholar

[37] Wang H, Wang L, Shang J, Li X, Wang H, Gui J, et al. Fe-catalysed oxidative C–H functionalization/C–S bond formation. Chem Commun. 2012;48:76–8.10.1039/C1CC16184ASearch in Google Scholar

[38] Cheng Y, Yang J, Qu Y, Li P. Aerobic visible-light photoredox radical C–H functionalization: catalytic synthesis of 2-substituted benzothiazoles. Org Lett. 2012;14:98–101.10.1021/ol2028866Search in Google Scholar PubMed

[39] Inamoto K, Hasegawa C, Kawasaki J, Hiroya K, Doi T. Use of Molecular Oxygen as a Reoxidant in the Synthesis of 2‐Substituted Benzothiazoles via Palladium‐Catalyzed C–H Functionalization/Intramolecular C-S Bond Formation. Adv Synth Catal. 2010;352:2643–55.10.1002/adsc.201000604Search in Google Scholar

[40] Sayyah SM, Azooz RE. Electrosynthesis and characterization of adherent poly (2-aminobenzothiazole) on Pt-electrode from acidic solution. Arab J Chem. 2016;9:S576–86.10.1016/j.arabjc.2011.06.031Search in Google Scholar

[41] Snieckus V, Zhang Y. Continuous-Flow Electrosynthesis of Benzothiazoles and Thiazolopyridines. Synfacts. 2018;14:237.10.1055/s-0037-1609308Search in Google Scholar

[42] Rey V, Soria-Castro SM, Argüello JE, Peñéñory AB. Photochemical cyclization of thioformanilides by chloranil: An approach to 2-substituted benzothiazoles. Tetrahedron Lett. 2009;50:4720–3.10.1016/j.tetlet.2009.06.020Search in Google Scholar

[43] Zhang G, Liu C, Yi H, Meng Q, Bian C, Chen H, et al. External oxidant-free oxidative cross-coupling: a photoredox cobalt-catalyzed aromatic C–H thiolation for constructing C–S bonds. J Am Chem Soc. 2015;137:9273–80.10.1021/jacs.5b05665Search in Google Scholar PubMed

[44] Tezuka N, Shimojo K, Hirano K, Komagawa S, Yoshida K, Wang C, et al. Direct hydroxylation and amination of arenes via deprotonative cupration. J Am Chem Soc. 2016;138:9166–71.10.1021/jacs.6b03855Search in Google Scholar PubMed

[45] Liu H, Jiang X, Gao X, Tian W, Xu C, Wang R, et al. Identification of N-benzothiazolyl-2-benzenesulfonamides as novel ABCA1 expression upregulators. RSC Med Chem. 2020;11:411–8.10.1039/C9MD00556KSearch in Google Scholar

[46] Palkar MB, Patil A, Hampannavar GA, Shaikh MS, Patel HM, Kanhed AM, et al. Design, synthesis and QSAR studies of 2-amino benzo[d]thiazolyl substituted pyrazol-5-ones: novel class of promising antibacterial agents. Med Chem Res. 2017;26:1969–87.10.1007/s00044-017-1898-6Search in Google Scholar

[47] Zhao J, Huang H, Wu W, Chen H, Jiang H. Metal-free synthesis of 2-aminobenzothiazoles via aerobic oxidative cyclization/dehydrogenation of cyclohexanones and thioureas. Org Lett. 2013;15:2604–7.10.1021/ol400773kSearch in Google Scholar PubMed

[48] Patel RV, Kumari P, Rajani DP, Chikhalia KH. Synthesis of coumarin-based 1, 3, 4-oxadiazol-2ylthio-N-phenyl/benzothiazolyl acetamides as antimicrobial and antituberculosis agents. Med Chem Res. 2013;22:195–210.10.1007/s00044-012-0026-xSearch in Google Scholar

[49] Khalili D. Graphene oxide: a promising carbocatalyst for the regioselective thiocyanation of aromatic amines, phenols, anisols and enolizable ketones by hydrogen peroxide/KSCN in water. N J Chem. 2016;40:2547–53.10.1039/C5NJ02314ASearch in Google Scholar

[50] Naeimi H, Heidarnezhad A. Efficient and facile protocol for one-pot synthesis of 2-amino-substituted benzothiazoles catalyzed by nano-BF3/SiO2 under mild conditions. Res Chem Intermed. 2016;42:7855–68.10.1007/s11164-016-2566-zSearch in Google Scholar

[51] Sharma P, Kumar A, Kumari P, Singh J, Kaushik MP. QSAR modeling of synthesized 3-(1, 3-benzothiazol-2-yl) 2-phenyl quinazolin-4 (3 H)-ones as potent antibacterial agents. Med Chem Res. 2012;21:1136–48.10.1007/s00044-011-9626-0Search in Google Scholar

[52] Telvekar VN, Bachhav HM, Bairwa VK. A novel system for the synthesis of 2-aminobenzthiazoles using sodium dichloroiodate. Synlett. 2012;23:2219–22.10.1055/s-0032-1317080Search in Google Scholar

[53] Ghiazza C, Billard T, Dickson C, Tlili A, Gampe CM. Chalcogen OCF3 Isosteres modulate drug properties without introducing inherent liabilities. Chem Med Chem. 2019;14:1586–9.10.1002/cmdc.201900452Search in Google Scholar PubMed

Received: 2021-12-07
Revised: 2022-03-06
Accepted: 2022-03-29
Published Online: 2022-05-10

© 2022 Reza Ahdenov et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. Sono and nano: A perfect synergy for eco-compatible Biginelli reaction
  3. Study of the reactivity of aminocyanopyrazoles and evaluation of the mitochondrial reductive function of some products
  4. “Click” assembly of novel dual inhibitors of AChE and MAO-B from pyridoxine derivatives for the treatment of Alzheimer’s disease
  5. Synthesis of 2,2-difluoro-2-arylethylamines as fluorinated analogs of octopamine and noradrenaline
  6. Cyclization of N-acetyl derivative: Novel synthesis – azoles and azines, antimicrobial activities, and computational studies
  7. Two independent and consecutive Michael addition of 1,3-dimethylbarbituric acid to (2,6-diarylidene)cyclohexanone: Flying-bird-shaped 2D-polymeric structure
  8. Ionic liquid-catalyzed synthesis of (1,4-benzoxazin-3-yl) malonate derivatives via cross-dehydrogenative-coupling reactions
  9. Synthesis of novel triiodide ionic liquid based on quaternary ammonium cation and its use as a solvent reagent under mild and solvent-free conditions
  10. Eelectrosynthesis of benzothiazole derivatives via C–H thiolation
  11. Synthesis of fluoro-rich pyrimidine-5-carbonitriles as antitubercular agents against H37Rv receptor
  12. Syntheses, crystal structure, thermal behavior, and anti-tumor activity of three ternary metal complexes with 2-chloro-5-nitrobenzoic acid and heterocyclic compounds
  13. Synthesis of enhanced lipid solubility of indomethacin derivatives for topical formulations
  14. Synthesis of newer substituted chalcone linked 1,2,3-triazole analogs and evaluation of their cytotoxic activities
  15. Novel benzodioxatriaza and dibenzodioxadiazacrown compounds carrying 1,2,4-oxadiazole moiety
  16. Synthesis of rhodium catalysts with amino acid or triazine as a ligand, as well as its polymerization property of phenylacetylene
  17. DABCO-based ionic liquid-promoted synthesis of indeno-benzofurans derivatives: Investigation of antioxidant and antidiabetic activities
  18. Design, synthesis, and biological activity of novel pomalidomide linked with diphenylcarbamide derivatives
  19. Study on effective synthesis of 7-hydroxy-4-substituted coumarins
  20. Review Article
  21. Chemical constituents of plants from the genus Carpesium
  22. Communication
  23. Reactions of 3-amino-1,2,4-triazine with coupling reagents and electrophiles
https://doi.org/10.1515/hc-2022-0008
Keywords for this article
benzothiazole; electrosynthesis; C–H thiolation; green chemistry; Riluzole
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Sono and nano: A perfect synergy for eco-compatible Biginelli reaction
  3. Study of the reactivity of aminocyanopyrazoles and evaluation of the mitochondrial reductive function of some products
  4. “Click” assembly of novel dual inhibitors of AChE and MAO-B from pyridoxine derivatives for the treatment of Alzheimer’s disease
  5. Synthesis of 2,2-difluoro-2-arylethylamines as fluorinated analogs of octopamine and noradrenaline
  6. Cyclization of N-acetyl derivative: Novel synthesis – azoles and azines, antimicrobial activities, and computational studies
  7. Two independent and consecutive Michael addition of 1,3-dimethylbarbituric acid to (2,6-diarylidene)cyclohexanone: Flying-bird-shaped 2D-polymeric structure
  8. Ionic liquid-catalyzed synthesis of (1,4-benzoxazin-3-yl) malonate derivatives via cross-dehydrogenative-coupling reactions
  9. Synthesis of novel triiodide ionic liquid based on quaternary ammonium cation and its use as a solvent reagent under mild and solvent-free conditions
  10. Eelectrosynthesis of benzothiazole derivatives via C–H thiolation
  11. Synthesis of fluoro-rich pyrimidine-5-carbonitriles as antitubercular agents against H37Rv receptor
  12. Syntheses, crystal structure, thermal behavior, and anti-tumor activity of three ternary metal complexes with 2-chloro-5-nitrobenzoic acid and heterocyclic compounds
  13. Synthesis of enhanced lipid solubility of indomethacin derivatives for topical formulations
  14. Synthesis of newer substituted chalcone linked 1,2,3-triazole analogs and evaluation of their cytotoxic activities
  15. Novel benzodioxatriaza and dibenzodioxadiazacrown compounds carrying 1,2,4-oxadiazole moiety
  16. Synthesis of rhodium catalysts with amino acid or triazine as a ligand, as well as its polymerization property of phenylacetylene
  17. DABCO-based ionic liquid-promoted synthesis of indeno-benzofurans derivatives: Investigation of antioxidant and antidiabetic activities
  18. Design, synthesis, and biological activity of novel pomalidomide linked with diphenylcarbamide derivatives
  19. Study on effective synthesis of 7-hydroxy-4-substituted coumarins
  20. Review Article
  21. Chemical constituents of plants from the genus Carpesium
  22. Communication
  23. Reactions of 3-amino-1,2,4-triazine with coupling reagents and electrophiles
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 27.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/hc-2022-0008/html
Scroll to top button