Heteroatom Chemistry
Volume 2019 (2019), Article ID 1459681, 10 pages
https://doi.org/10.1155/2019/1459681

Research Article

An Efficient Selectfluor-Mediated Oxidative Thio- and Selenocyanation of Diversely Substituted Indoles and Carbazoles

Rodrigo Abonia,¹ Luisa F. Gutierrez,1,2 Angela T. Zwarycz,² Sebastián Correa Smits,² and Kenneth K. Laali²

¹Research Group of Heterocyclic Compounds (GICH), Department of Chemistry, Universidad del Valle, A. A. 25360, Cali, Colombia
²Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA

Correspondence should be addressed to Kenneth K. Laali; kenneth.laali@unf.edu

Received 18 October 2018; Accepted 14 November 2018; Published 2 January 2019

Academic Editor: Gianluigi Broggini

Copyright © 2019 Rodrigo Abonia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A facile Selectfluor-mediated oxidative method for direct introduction of SCN and SeCN groups into diversely substituted indoles and carbazoles is described, by employing readily available thiocyanate and selenocyanate salts, and the scope of the method is underscored by providing 24 examples. The feasibility to sequentially introduce SCN followed by SeCN on a carbazole framework and to synthesize the corresponding S-tetrazole and Se-tetrazole derivatives is also demonstrated.

1. Introduction

Selectfluor,1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-octane bis(tetrafluoroborate), also known as F-TEDA-BF₄) is a safe, bench stable, nontoxic, and highly reactive onium dication salt that delivers an equivalent of electrophilic or radical fluorine [1, 2]. For that reason, it is widely used in the synthesis of organofluorine compounds [3–8], but it also serves as a versatile catalyst and mediator in transformations involving oxidizable functional groups [9–13].

Aryl thio- and selenocyanates are versatile intermediates for various sulfur- and selenium-containing compounds that are of synthetic and biological interest [14–26]. Aryl thiocyanates are widely employed as building blocks in the synthesis of diverse sulfides [27, 28], thiocarbamates [29], thionitriles [30], sulfonic acids [31], sulfonyl chlorides [32], thioesters [33], and sulfonyl cyanides [31] and mainly in the synthesis and functionalization of heterocyclic compounds [25, 26, 34–40]. Particularly, selenium-containing organic compounds have recently attracted the interest of the scientific community due to their promising chemopreventive properties in connection with cancer therapy [32, 41–44], and also as antioxidant agents [45, 46].

Owing to the aforementioned chemical versatility and biological activity, functional organic compounds bearing the thiocyanato and selenocyanate derivatives are highly sought after, and over the years a number of strategies and reagents have been utilized to enable the direct introduction of SCN and SeCN moieties into organic motifs. In particular, direct oxidative thiocyanation of C-H bonds have been achieved by using thiocyanate salts in the presence of oxidizing agents such as Mn(OAc)₃ [15], NCS [47], CAN [48], hypervalent iodine reagents [49], DDQ [50], oxone [51], oxygen [52], DEAD [53], and TBHP [22]. In comparison, direct selenocyanation approaches have not been reported under similar oxidative conditions [20–26]. Therefore, developing new and broad-based protocols for direct introduction of SCN and SeCN moieties into organic structures, in particular those motifs that are important for medicinal chemistry as building blocks of pharmaceuticals, continues to be relevant.

In a limited study in 2008, Yadav et al. [54] provided examples of arene thiocyanation by using Selectfluor, but a broader investigation to determine tolerance to a wider range of substituents and to gauge efficacy in selenocyanation remained unexplored.

In connection with previous studies from our laboratory on the use of Selectfluor as a versatile mediator for generation of incipient electrophiles through oxidation [55, 56], we report here a mild and efficient Selectfluor-mediated direct thio- and selenocyanation of C-H bonds (Scheme 1), focusing mainly on diversely substituted indoles 3 and carbazoles 6. Sequential introduction of SCN and SeCN and synthesis of thio- and selenotetrazoles on a carbazole motif are also demonstrated, in preliminary studies using this chemistry.

Scheme 1: Selectfluor-mediated thio- and selenocyanation of diverse heterocyclic substrates 1, 3, and 6.

2. Results and Discussion

Following an initial feasibility study with 2-methylfuran 1 and 2-methylindole 3a (entries 1 and 2, Table 1), we focused on the indole derivatives bearing electron-withdrawing substituents, in particular HCO, F, Br, NO₂, and CN groups.

Table 1: Products resulting from thiocyanation and selenocyanation of diverse furano 1 and indole 3 substrates.

Entry
Substrate
Product
Yield ()

1

51

2

68

3

70

4

72

5

63

6

79

7

92

8

96

9

89

10

67

11

87

12

57

13

66

14

72

15

90

16

72

17

85

18

60

In relation to other studies in our laboratory on the synthesis of heterocyclic curcuminoids and their antitumor properties [57], we were especially interested in the indole backbone bearing isomeric formyl substituents. Fortunately, both thio- and selenocyanation of the isomeric indole-carboxaldehydes 3b-c proved successful with the formyl group remaining intact (entries 3-5, Table 1). All other aforementioned substituents were tolerated and the corresponding SCN and SeCN derivatives were isolated in yields ranging from 96% to 57% (Table 1).

In the next phase of the study, we focused on the carbazole motif 6 (Table 2). Thus, parent carbazole 6a and its N-isopropyl derivative 6b reacted to furnish the corresponding 3-SCN and 3-SeCN derivatives (7-8)a and (7-8)b, respectively, in yields ranging from 87% to 75%. In other studies, the isolated carbazole-SCN derivatives 7a and 7b were successfully selenocyanated to produce the SCN/SeCN disubstituted derivatives 9 and 10, respectively (entries 23-24, Table 2). However, when this transformation was performed in the reverse order by subjecting the carbazole-SeCN derivatives 8a and 8b to thiocyanation conditions the corresponding seleno/thio-bis-adducts 9 and 10 could not be obtained. This is likely due to ease of oxidation of carbazole-SeCN derivative which could prevent further SCN introduction. ⁷⁷Se NMR of the indole-SeCN derivatives fall in a relatively close range irrespective of the nature of the substituents (δ 149-162 ppm). Remarkably though ⁷⁷Se chemical shifts for the carbazole-SeCN compounds 8a and 8b and the disubstituted derivatives 9 and 10 are significantly different (δ 313-317 ppm) (see experimental section and SI file available here).

Table 2: Products resulting from thiocyanation and selenocyanation of the carbazole motif 6.

Entry
Substrate
Product
Yield ()

19

87

20

75

21

81

22

86

23

43

24

16

Finally, by employing the chemistry we reported previously for the synthesis of tetrazoles using Cu-Zn alloy nanopowder [58], in an exploratory study we subjected the carbazole-SCN 7b and carbazole-SeCN 8b derivatives to the reaction conditions shown in Scheme 2 and successfully obtained the first examples of thio- and selenotetrazoles (11b and 12b, respectively), on a carbazole motif 6. Observation of line broadening at room temperature in the proton NMR spectra of the corresponding tetrazoles 11-12 (SI file) is indicative of a rapid 2H- to 1H-tetrazole tautomerization.

Scheme 2: Cu-Zn alloy-mediated synthesis of tetrazole derivatives 11b and 12b from thio- and selenocyanates 7b and 8b, respectively.

3. Conclusions

In summary, a practical and easy to perform method for oxidative thio- and selenocyanation of diversely substituted indoles 3 as well as carbazoles 6 employing Selectfluor is presented. The feasibility to sequentially introduce the SCN followed by SeCN on a carbazole motif 6 is also demonstrated, and first examples of carbazole-S-tetrazole and carbazole-Se-tetrazole derivatives (11b and 12b, respectively) are provided.

4. Experimental

4.1. General Experimental Information

The reagents employed were high-purity commercial samples and were used without further purification. Column chromatography was performed on silica gel (32–63 particle size). Melting points were measured with a MEL-TEMP apparatus and are uncorrected. Multinuclear NMR spectra (¹H, ¹³C, ¹⁹F, and ⁷⁷Se) were recorded on a Varian INOVA 500 instrument. ¹⁹F and ⁷⁷Se NMR spectra were externally referenced (relative to CFCl₃ and Me₂Se) as set by the instrument and verified by comparison with known reference samples. Some ¹H and ¹³C NMR spectra were recorded on a Bruker Avance 400 instrument. HRMS analyses were performed on a Finnigan Quantum ultra-AM in electrospray mode using methanol as solvent. Other HRMS spectra were recorded on a Waters Micromass AutoSpec-Ultima spectrometer (equipped with a direct inlet probe) operating at 70 eV. Additional mass spectra were run on a Shimadzu-GCMS 2010-DI-2010 spectrometer (equipped with a direct inlet probe) operating at 70 eV.

4.2. General Procedure for the Thiocyanate and Selenocyanate Products 2, 4, 5, and 7-10

For a solution of ammonium thiocyanate (107 mg, 1.5 equiv.) or potassium selenocyanate (203 mg, 1.5 equiv.) and Selectfluor® (500 mg, 1.5 equiv.) in MeCN (10 mL), the appropriated substrate 1, 3, 6, 7a, or 7b (1 equiv.) was added and the mixture was stirred at room temperature under inert atmosphere for 2h. After completion (monitored by TLC), the reaction mixture was concentrated under reduced pressure, and water was added. The aqueous solution was extracted with ethyl acetate, and the combined organic extracts were dried with anhydrous Na₂SO₄. After removal of the solvent, the crude products were purified by column chromatography using hexane: ethyl acetate (7:3) as eluent.

4.2.1. 2-Methyl-5-thiocyanatofuran (2)

Yellow oil, Rf 0.71 (15% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 6.79 (d, 1H, J = 3.3 Hz), 6.12 - 6.13 (m, 1H), 2.38 (s, 3H, CH₃) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 159.4, 127.7, 123.4, 109.2, 108.8 (SCN), 14.1 (CH₃) ppm.

4.2.2. 2-Methyl-3-thiocyanato-1H-indole (4a)

Beige solid, mp 96-99°C, Rf 0.62 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.49 (bs, 1H, NH), 7.71 - 7.69 (m, 1H), 7.34 - 7.32 (m, 1H), 7.29 - 7.23 (m, 2H), 2.56 (s, 3H, CH₃) ppm. ¹³C NMR (CDCl³, 125 MHz): δ 141.9, 135.1, 128.7, 123.0, 121.6, 118.2, 111.9, 111.2, 89.2 (SCN), 12.1 (CH₃) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₀H₉N₂S: 189.04864; found: 189.04207.

4.2.3. 3-Thiocyanato-1H-indole-4-carbaldehyde (4b)

Beige solid, mp 169-171°C, Rf 0.31 (30% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.50 (bs, 1H, NH), 10.85 (s, 1H, CHO), 8.06 (d, 1H, J = 3.5 Hz), 7.93 (dd, 1H, J = 8.0, 1.0 Hz), 7.87 (dd, 1H, J = 7.5, 1.0 Hz), 7.47 (t, 1H, J = 8.0 Hz) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 190.6, 138.5, 134.1, 129.3, 124.9, 122.8, 119.1, 119.0, 112.0, 92.3 (SCN) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₀H₇N₂OS: 203.02791; found: 203.02448.

4.2.4. 3-Thiocyanato-1H-indole-5-carbaldehyde (4c)

White solid, mp 174-175°C, Rf 0.22 (30% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.52 (bs, 1H, NH), 10.19 (s, 1H, CHO), 8.38 (d, 1H, J = 0.7 Hz), 8.11 (d, 1H, J = 2.8 Hz), 7.88 (dd, 1H, J = 8.5, 1.5 Hz), 7.76 (d, 1H, J = 8.5 Hz) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 191.6, 140.1, 134.7, 131.3, 127.8, 122.9, 122.6, 113.5, 110.9, 93.3 (SCN) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₀H₇N₂OS: 203.02791; found: 203.02432.

4.2.5. 3-Selenocyanato-1H-indole-5-carbaldehyde (5c)

Orange-brown solid, mp > 150°C decomposes, Rf 0.22 (30% EtOAc in hexane). ¹H NMR (DMSO-d₆, 500 MHz): δ 12.30 (bs, 1H, NH), 10.10 (s, 1H, CHO), 8.21 (d, 1H, J = 1.0 Hz), 8.04 (d, 1H, J = 3.0 Hz), 7.77 (dd, 1H, J = 8.0, 2.0 Hz), 7.66 (d, 1H, J = 8.5 Hz) ppm. ¹³C NMR (DMSO-d₆, 125 MHz): δ 193.2, 140.2, 135.9, 130.6, 129.1, 124.1, 122.8, 113.7, 105.0, 92.4 (SeCN) ppm. ⁷⁷Se NMR (DMSO-d₆, 95 MHz): δ 162.1 (s) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₀H₇N₂OSe: 250.97236; found: 250.95178.

4.2.6. 1-Butyl-3-thiocyanato-1H-indole (4d)

Yellow oil, Rf 0.74 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 7.85 - 7.83 (m, 2H), 7.44 - 7.42 (m, 2H), 7.39 - 7.32 (m, 2H), 4.11 (t, 2H, J = 7.2 Hz, CH₂), 1.86 - 1.80 (m, 2H, CH₂), 1.40 - 1.32 (m, 2H, CH₂), 0.98 (t, 3H, J = 7.4 Hz, CH₃) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 136.6, 134.2, 128.6, 123.3, 121.5, 119.0, 112.0, 110.5, 89.7 (SCN), 46.8 (CH₂), 32.0 (CH₂), 20.1 (CH₂), 13.7 (CH₃) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₃H₁₅N₂S: 231.09559; found: 231.10324.

4.2.7. 1-Butyl-3-selenocyanato-1H-indole (5d)

Yellow oil, Rf 0.74 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 7.78 - 7.75 (m, 1H), 7.45 (s, 1H), 7.41 - 7.43 (m, 2H), 7.36 - 7.30 (m, 2H), 4.16 (t, 2H, J = 7.2 Hz, CH₂), 1.89 - 1.83 (m, 2H, CH₂), 1.40 - 1.35 (m, 2H, CH₂), 0.97 (t, 3H, J = 7.4 Hz, CH₃) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 136.5, 135.0, 129.6, 123.1, 121.4, 120.0, 110.2, 101.8, 87.2 (SeCN), 46.8 (CH₂), 32.1 (CH₂), 20.1 (CH₂), 13.6 (CH₃) ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ 149.6 (s) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₃H₁₅N₂Se: 279.04004; found: 279.04199.

4.2.8. 5-Bromo-3-thiocyanato-1H-indole (4e)

White solid, mp 133-136°C, Rf 0.35 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.8 (bs, 1H, NH), 7.92 (d, 1H, J = 1.2 Hz), 7.52 (d, 1H, J = 1.4 Hz), 7.39 (dd, 1H, J = 8.6, 1.9 Hz), 7.30 (d, 1H, J = 9.4 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 134.6, 132.1, 129.3, 127.0, 121.4, 115.4, 113.6, 111.6, 92.0 (SCN) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₉H₆BrN₂S: 252.94351/254.94146; found: 252.93964/254.93404.

4.2.9. 5-Bromo-3-selenocyanato-1H-indole (5e)

Beige solid, mp 155-157°C, Rf 0.35 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.7 (bs, 1H, NH), 7.90 (d, 1H, J = 1.7 Hz), 7.56 (d, 1H, J = 2.7 Hz), 7.42 (dd, 1H, J = 8.6, 1.8 Hz), 7.33 (d, 1H, J = 9.0 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 134.7, 132.8, 130.5, 127.0, 122.4, 115.4, 113.3, 101.3, 89.4 (SeCN) ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ 151.9 (s) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₉H₆BrN₂Se: 300.88796/302.88591; found 300.88208/302.87494.

4.2.10. 5-Fluoro-3-thiocyanato-1H-indole (4f)

Off-white solid, mp 108-110°C, Rf 0.51 (40% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.2 (br. s, 1H, NH), 7.99 (d, 1H, J = 2.5 Hz), 7.61 (dd, 1H, J = 8.5, 4.5 Hz), 7.45 (dd, 1H, J = 9.0, 2.5 Hz), 7.12 (td, 1H, J = 9.0, 3.0 Hz) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 158.8 (d, ¹JCF = 236.6 Hz), 134.4 (d, JCF = 20 Hz), 133.3, 128.6 (d, JCF = 10.5 Hz), 114.1 (d, JCF = 10.5 Hz), 111.6 (d, JCF = 25.7 Hz), 111.1, 102.9 (d, JCF = 25 Hz), 91.0 (d, ⁴JCF = 4.7 Hz) ppm. ¹⁹F NMR (acetone-d₆, 470 MHz): δ -123.2 (m) ppm. HRMS (ESI): m/z [M+H]⁺ calcd for C₉H₆N₂FS: 193.02357; found: 193.01202.

4.2.11. 5-Fluoro-3-selenocyanato-1H-indole (5f)

Light-brown solid, mp 109-111°C, Rf 0.33 (40% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.13 (s, 1H, br, NH), 7.93 (d, 1H, J = 2.5 Hz), 7.59 (dd, 1H, J = 8.7, 4.5 Hz), 7.38 (dd, 1H, J = 9.5, 2.5 Hz), 7.10 (dt, 1H, J = 9.0, 3.0 Hz). ¹³C NMR (acetone-d₆, 125 MHz): δ 157.7 (d, ¹JCF = 236.6 Hz), 134.8 (d, JCF = 20.0 Hz), 133.2, 129.8 (d, JCF = 10.5 Hz), 113.8 (d, JCF = 5.6 Hz), 111.3 (d, JCF = 26.6 Hz), 103.8 (d, JCF = 24.7 Hz), 101.5, 89.0 ppm. ¹⁹F NMR (acetone-d₆, 470 MHz): δ -123.68 (m) ppm. ⁷⁷Se NMR (acetone-d₆, 95 MHz): δ 149.7 (s). HRMS (ESI): m/z [M+H]⁺ calcd for C₉H₆N₂FSe: 240.96802; found: 240.95600.

4.2.12. 1-Butyl-5-fluoro-3-thiocyanato-1H-indole (4g)

Yellow oil, Rf 0.26 (10% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 7.48 (s, 1H), 7.44 (dd, 1H, J = 8.2, 2.5 Hz), 7.33 (dd, 1H, J = 9.0, 4.0 Hz), 7.08 (dt, 1H, J = 8.7, 2.5 Hz), 4.14 (t, 2H, J = 7.0 Hz), 1.84 (m, 2H), 1.36 (m, 2H), 0.97 (t, 3H, J = 7.5 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 158.9 (d, ¹JCF = 238.3 Hz), 135.4, 133.0, 129.4 (d, ³JCF = 10.5 Hz), 112.0 (d, ²JCF = 25.0 Hz), 111.5 (d, JCF = 12.5 Hz), 111.4, 104.3 (d, ²JCF = 24.8 Hz), 89.9 (d, ⁴JCF = 4.7 Hz), 32.0, 20.1, 13.6 ppm. ¹⁹F NMR (CDCl₃, 470 MHz): δ -121.36 (m) ppm. HRMS (ESI): m/z [M+H]⁺ calcd for C₁₃H₁₄N₂FS: 249.08617; found: 249.07428.

4.2.13. 1-Butyl-5-fluoro-3-selenocyanato-1H-indole (5g)

Brown oil, Rf 0.32 (10% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 7.48 (s, 1H), 7.39 (dd, 1H, J = 9.0, 2.5 Hz), 7.33 (dd, 1H, J = 9.2, 4.5 Hz), 7.07 (dt, 1H, J = 8.7, 3.0 Hz), 4.14 (t, 2H, J = 7.5 Hz), 1.85 (m, 2H), 1.36 (m, 2H), 0.97 (t, 3H, J = 7.0 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 158.9 (d, ¹JCF = 237.4 Hz), 136.3, 133.0, 130.4 (d, JCF = 11.3 Hz), 111.8 (d, JCF = 21.6 Hz), 111.3 (d, JCF = 9.5 Hz), 105.0 (d, JCF = 24.7 Hz), 101.58, 87.0 (d, JCF = 4.8 Hz), 47.1, 32.0, 20.1, 13.6 ppm. ¹⁹F NMR (CDCl₃, 470 MHz): δ -121.6 (m) ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ 152.0 (s) ppm. HRMS (ESI): m/z [M+H]⁺ calcd for C₁₃H₁₄N₂FSe: 297.03062; found: 297.02386.

4.2.14. 6-Nitro-3-thiocyanato-1H-indole (4h)

Pale-yellow solid, mp 182-183°C, Rf 0.51 (40% EtOAc in hexane). ¹H NMR (DMSO-d₆, 500 MHz): δ 12.64 (s, 1H, NH), 8.43 (d, 1H, J = 2.0 Hz), 8.37 (d, 1H, J = 3.5 Hz), 8.10 (dd, 1H, J = 9.0, 2.5 Hz), 7.85 (d, 1H, J = 9.0 Hz) ppm. ¹³C NMR (DMSO-d₆, 125 MHz): δ 143.8, 139.4, 135.3, 132.6, 118.9, 116.6, 112.4, 110.0, 92.2 ppm. HRMS (ESI negative ion mode): m/z [M-H]⁻ calcd for C₉H₄O₂N₃S: 218.002442; found: 218.08749.

4.2.15. 6-Nitro-3-selenocyanato-1H-indole (5h)

Pale-yellow solid, mp 183-184°C, Rf 0.51 (40% EtOAc in hexane). ¹H NMR (DMSO-d₆, 500 MHz): δ 12.50 (bs, 1H, NH), 8.43 (dd, 1H, J = 2.1, 0.6 Hz), 8.25 (d, 1H, J = 2.8 Hz), 8.08 (dd, 1H, J = 8.8, 2.1 Hz), 7.76 (dt, 1H, J = 8.8, 0.6 Hz) ppm. ¹³C NMR (DMSO-d₆, 125 MHz): δ 143.4, 139.5, 135.1, 133.9, 119.8, 116.2, 109.6, 105.0, 91.9 (SeCN) ppm. ⁷⁷Se NMR (DMSO-d₆, 95 MHz): δ 160.2 (s) ppm. HRMS (ESI negative ion mode): m/z [M-H]⁻ calcd for C₉H₅N₃O₂Se: 266.95470; found: 266.01712.

4.2.16. 1-Benzyl-6-nitro-3-thiocyanato-1H-indole (4i)

Yellow solid, mp 144-146°C, Rf 0.69 (30% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 8.60 (d, 1H, J = 2.5 Hz), 8.40 (s, 1H), 8.20 (dd, 1H, J = 8.7, 2.0 Hz), 7.96 (d, 1H, J = 8.5 Hz), 7.41-7.31 (m, 5H), 5.77 (s, 2H) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 144.4, 140.9, 136.3, 135.6, 133.1, 129.0, 128.2, 127.5, 119.1, 116.6, 110.7, 108.3, 92.3, 50.7 ppm. HRMS (ESI): m/z [M+H]⁺ calcd for C₁₆H₁₂O₂N₃S: 310.0650; found: 310.0584.

4.2.17. 1-Benzyl-6-nitro-3-selenocyanato-1H-indole (5i)

Yellow solid, mp 153-154°C, Rf 0.59 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.38 (d, 1H, J = 2.0 Hz), 8.21 (dd, 1H, J = 9.0, 2.0 Hz), 7.85 (d, 1H, J = 9.0 Hz), 7.71 (s, 1H) 7.40 - 7.37 (m, 3H), 7.21-7.19 (m, 2H), 5.44 (s, 2H, CH₂) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 144.5, 139.9, 135.5, 134.5, 134.2, 129.4, 128.9, 127.3, 120.4, 117.1, 107.5, 100.7, 89.6, 51.3 ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ 153.7 (s) ppm. HRMS (ESI): m/z [M+H]⁺ calcd for C₁₆H₁₂O₂N₃Se: 358.0095; found: 358.0082.

4.2.18. 3-Thiocyanato-1H-indole-5-carbonitrile (4j)

Beige solid, mp 200°C decomposes, Rf 0.13 (30% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.60 (bs, 1H, NH), 8.23 (dt, 1H, J = 1.5, 0.7 Hz), 8.16 (d, 1H, J = 2.9 Hz), 7.80 (dd, 1H, J = 8.5, 0.8 Hz), 7.64 (dd, 1H, J = 8.5, 1.5 Hz) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 138.5, 135.3, 127.7, 126.0, 123.5, 119.4, 114.1, 110.8, 104.7, 92.6 (SCN) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. For C₁₀H₆N₃S: 200.02824; found: 200.01814.

4.2.19. 3-Thiocyanato-9H-carbazole (7a)

White solid, mp 103-104°C, Rf 0.47 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.35 (bs, 1H, NH), 8.25 (s, 1H), 8.03 (d, 1H, J = 8.0 Hz), 7.55 (dd, 1H, J = 8.5, 2.0 Hz), 7.51 - 7.45 (m, 2H), 7.40 (d, 1H, J = 8.5 Hz), 7.30 (pseudo-dt, 1H, J = 7.2, 1.5 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 140.2, 139.9, 129.6, 127.1, 125.3, 124.8, 122.1, 120.6, 120.4, 112.7, 112.3, 112.1, 111.0 (SCN) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₃H₉N₂S: 225.04864; found: 225.03801.

4.2.20. 3-Selenocyanato-9H-carbazole (8a)

Beige solid, mp 135-137°C, Rf 0.47 (30% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.35 (d, 1H, J = 1.7 Hz), 8.33 (bs, 1H, NH), 8.04 (d, 1H, J = 7.8 Hz), 7.65 (dd, 1H, J = 8.4, 1.7 Hz), 7.50 - 7.45 (m, 2H), 7.38 (d, 1H, J = 8.4 Hz), 7.29 (pseudo-dt, 1H, J = 7.2, 1.5 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 140.1, 139.7, 131.6, 127.4, 127.0, 125.0, 122.2, 120.6, 120.4, 112.4, 111.0, 109.6, 103.0 (SCN) ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ = 317.2 (s) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₃H₉N₂Se: 272.99309; found: 272.96500.

4.2.21. 9-Isopropyl-3-thiocyanato-9H-carbazole (7b)

White solid, mp 124-126°C, Rf 0.58 (15% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 8.53 (d, 1H, J = 2.0 Hz), 8.29 (dd, 1H, J = 7.8, 1.3 Hz), 7.85 (d, 1H, J = 8.8 Hz), 7.76 (d, 1H, J = 8.5 Hz), 7.72 (dd, 1H, J = 8.7, 1.9 Hz), 7.53 (pseudo-dt, 1H, J = 8.4, 1.0 Hz), 7.29 (pseudo-dt, 1H, J = 7.9, 0.9 Hz), 5.22 (sept, 1H, J = 7.0 Hz, CH), 1.73 (s, 3H, CH₃), 1.72 (s, 3H, CH₃) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 140.2, 140.1, 129.3, 126.7, 125.3, 124.7, 122.2, 120.7, 119.7, 112.2, 111.8, 111.4, 110.9 (SCN), 47.0 (CH), 19.9 (CH₃) ppm. HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₆H₁₅N₂S: 267.09559; found: 267.09363.

4.2.22. 9-Isopropyl-3-selenocyanato-9H-carbazole (8b)

Beige solid, mp 161-162°C, Rf 0.58 (15% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 8.60 (t, 1H, J = 1.2 Hz), 8.27 (dd, 1H, J = 7.8, 1.3 Hz), 7.80 (d, 2H, J = 1.2 Hz), 7.75 (d, 1H, J = 8.4), 7.52 (dt, 1H, J = 8.0, 1.3 Hz), 7.28 (dt, 1H, J = 7.9, 1.0 Hz), 5.21 (sept, 1H, J = 7.0 Hz, CH), 1.73 (s, 3H, CH₃), 1.72 (s, 3H, CH₃) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 140.0, 139.9, 131.3, 127.2, 126.5, 124.8, 122.3, 120.6, 119.5, 112.08, 110.8, 109.8, 102.7 (SeCN), 46.9 (CH), 19.9 (CH₃) ppm. ⁷⁷Se NMR (acetone-d₆, 95 MHz): δ 312.9 (s). HRMS (ESI) m/z [M+H]⁺ calcd. for C₁₆H₁₅N₂Se: 315.04004; found: 315.03387.

4.2.23. 3-Selenocyanato-6-thiocyanato-9H-carbazole (9)

Beige solid, mp 150°C decomposes, Rf 0.25 (30% EtOAc in hexane). ¹H NMR (acetone-d₆, 500 MHz): δ 11.09 (bs, 1H, NH), 8.72 (s, 1H), 8.65 (s, 1H), 7.86 (dd, 1H, J = 8.5, 1.8 Hz), 7.74 - 7.78 (m, 2H), 7.71 (d, 1H, J = 8.5 Hz) ppm. ¹³C NMR (acetone-d₆, 125 MHz): δ 141.2, 141.1, 132.6, 130.3, 130.3, 127.8, 125.7, 123.6, 113.4, 113.3, 113.2, 113.1, 111.6, 111.5, 102.7 ppm. ⁷⁷Se NMR (acetone-d₆, 95 MHz): δ 317.3 (s) ppm. EIMS: m/z (%) = 328 (68) [M]+, 284 (30), 271 (24), 249 (57), 57 (65), 43 (100).

4.2.24. 9-Isopropyl-3-selenocyanato-6-thiocyanato-9H-carbazole (10)

Orange yellow solid, mp 126-128°C, Rf 0.44 (40% EtOAc in hexane). ¹H NMR (CDCl₃, 500 MHz): δ 8.43 (d, 1H, J = 2.0 Hz), 8.32 (d, 1H, J = 2.0 Hz), 7.79 (dd, 1H, J = 8.7, 2.0 Hz), 7.68 (dd, 1H, J = 9.0, 2.0 Hz), 7.62 (d, 1H, J = 8.5 Hz), 7.57 (d, 1H, J = 8.9 Hz), 5.00 (sept, 1H, J = 7.0 Hz), 1.72 (d, 6H, J = 6.5 Hz) ppm. ¹³C NMR (CDCl₃, 125 MHz): δ140.6, 140.5, 132.3, 130.1, 127.6, 125.3, 123.9, 123.8, 113.0, 112.3, 112.2, 112.0, 110.4, 102.3, 47.6, 20.8 ppm. ⁷⁷Se NMR (CDCl₃, 95 MHz): δ 317.5 (s). GC-MS: m/z 371 (M+).

4.3. General Procedure for the Synthesis of Tetrazoles (11-12)b

Cu-Zn alloy nanopowder (38 mg) was added to a mixture of the thiocyanate or selenocyanate compound 7b or 8b, respectively (2 mmol), and sodium azide (2.8 mmol) in DMF (6 mL), and the mixture was stirred under ambient conditions for 8h at 90°C. After completion (monitoring by TLC), the resulting mixture was allowed to cool to room temperature and the catalyst was separated by centrifugation and washed with ethyl acetate (three times). After removal of DMF and ethyl acetate under reduced pressure from the resulting centrifugate, it was treated with acetic acid and ethyl acetate with stirring. The organic layer was separated and the aqueous solution left behind was extracted further with ethyl acetate. The combined organic extracts were washed with water and concentrated. Compounds (11-12)b were purified by column chromatography by using chloroform-methanol (20:1).

4.3.1. 3-((2H-tetrazol-5-yl)thio)-9-isopropyl-9H-carbazole (11b)

White solid, mp 182 -186°C, Rf 0.31 (5% MeOH in Chloroform). ¹H NMR (DMSO-d₆, 400 MHz): δ 8.50 (br. s, 1H), 8.23 (d, 1H, J = 7.7 Hz), 7.79 (s, 1H), 7.75 (d, 1H, J = 8.4 Hz), 7.63 (br. s, 1H), 7.48 (t, 1H, J = 7.6 Hz), 7.24 (t, 1H, J = 7.3 HZ), 5.19 – 5.12 (m, 1H, CH), 1.65 (br. s, 3H, CH₃), 1.63 (br. s, 3H, CH₃) ppm. ¹³C NMR (DMSO-d₆, 100 MHz): δ 139.9, 139.9, 139.8, 131.4, 126.8, 126.7, 124.1, 122.4, 121.2, 119.7, 117.0, 112.2, 111.2, 46.8 (CH), 20.9 (CH₃) ppm. EIMS: m/z (%) 309 (46) [M]+, 253 (12), 240 (20), 198 (100), 69 (20), 43 (89), 41 (66).

4.3.2. 3-((2H-tetrazol-5-yl)selanyl)-9-isopropyl-9H-carbazole (12b)

White solid, mp 156 - 160°C, Rf 0.53 (5% MeOH in Chloroform). ¹H NMR (CDCl₃, 400 MHz): δ 8.65 (br. s, 1H), 8.14 (d, 1H, J = 7.6 Hz), 7.91 (br. d, 1H, J = 8.4 Hz), 7.65 (d, 1H, J = 7.8 Hz), 7.59 (d, 1H, J = 8.3 Hz), 7.52 (t, 1H, J = 7.6 Hz), 7.28 (t, 1H, J = 7.4 Hz), 5.03 (sep, 1H, J = 7.1 Hz, CH), 1.73 (d, 6H, J = 7.0 Hz, CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ 141.7, 140.0, 140.0, 126.5, 123.9, 123.0, 121.0, 120.9, 119.8, 119.2, 119.2, 110.8, 110.5, 47.2 (CH), 20.8 (CH₃) ppm. EIMS: m/z (%) 496 (37) [M]+, 416 (100), 358 (15), 331 (24), 288 (33), 246 (31), 193 (35), 166 (35), 43(48), 41 (30).

Data Availability

The data used to support the findings of this study are provided in experimental section and in supplementary material. Additional inquiries may be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

Kenneth K. Laali thanks University of North Florida for the outstanding faculty scholarship and presidential professorship awards, faculty scholarship, and UNF Foundation Board grants. Rodrigo Abonia and Luisa F. Gutierrez thank COLCIENCIAS (no. 110665842661) and Universidad del Valle (CI. 71111) for financial support.

Supplementary Materials

Multinuclear NMR spectra of the reported products are gathered in the supplementary file. (Supplementary Materials)

References

P. T. Nyffeler, S. G. Durón, M. D. Burkart, S. P. Vincent, and C.-H. Wong, “Selectfluor: mechanistic insight and applications,” Angewandte Chemie International Edition, vol. 44, no. 2, pp. 192–212, 2004.

R. P. Singh and J. M. Shreeve, “Recent highlights in electrophilic fluorination with 1-chloromethyl-4-fluoro- 1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate),” Accounts of Chemical Research, vol. 37, no. 1, pp. 31–44, 2004.

G. Stavber, M. Zupan, M. Jereb, and S. Stavber, “Selective and effective fluorination of organic compounds in water using selectfluor F-TEDA-BF₄,” Organic Letters, vol. 6, no. 26, pp. 4973–4976, 2004.

A. R. Mazzotti, M. G. Campbell, P. Tang, J. M. Murphy, and T. Ritter, “Palladium(III)-catalyzed fluorination of arylboronic acid derivatives,” Journal of the American Chemical Society, vol. 135, no. 38, pp. 14012–14015, 2013.

D. Cantillo, O. de Frutos, J. A. Rincón, C. Mateos, and C. O. Kappe, “A Continuous-Flow Protocol for Light-Induced Benzylic Fluorinations,” The Journal of Organic Chemistry, vol. 79, no. 17, pp. 8486–8490, 2014.

S. Ventre, F. R. Petronijevic, and D. W. C. MacMillan, “Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis,” Journal of the American Chemical Society, vol. 137, no. 17, pp. 5654–5657, 2015.

Y. Jeong, B. I. Kim, J. K. Lee, and J. S. Ryu, “Direct Synthesis of 4-Fluoroisoxazoles through Gold-Catalyzed Cascade Cyclization–Fluorination of 2-Alkynone O-Methyl Oximes,” The Journal of Organic Chemistry, vol. 79, no. 14, pp. 6444-6445, 2014.

Q. Chen, J. Zeng, X. Yan et al., “Electrophilic Fluorination of Secondary Phosphine Oxides and Its Application to P–O Bond Construction,” The Journal of Organic Chemistry, vol. 81, no. 20, pp. 10043–10048, 2016.

S. Stavber, “Recent Advances in the Application of SelectfluorTMF-TEDA-BF₄ as a Versatile Mediator or Catalyst in Organic Synthesis,” Molecules, vol. 16, no. 8, pp. 6432–6464, 2011.

S. W. Wu and F. Liu, “Synthesis of α-Fluoroketones from Vinyl Azides and Mechanism Interrogation,” Organic Letters, vol. 18, no. 15, pp. 3642–3645, 2016.

N. Ahlsten, A. Bartoszewicz, S. Agrawal, and B. Martín-Matute, “A facile synthesis of α-fluoro ketones catalyzed by [Cp*IrCl₂]₂,” Synthesis, no. 16, pp. 2600–2608, 2011.

Q. Yang, L. L. Mao, B. Yang, and S. D. Yang, “Metal-Free, Efficient Oxyfluorination of Olefins for the Synthesis of α-Fluoroketones,” Organic Letters, vol. 16, no. 13, pp. 3460–3463, 2014.

W. Zhang, J. Zhang, Y. Liu, and Z. Xu, “A Combination of Copper(0) Powder and Selectfluor Enables Generation of Cationic Copper Species for Mild 1,2-Dicarbonylation of Alkynes,” Synlett, vol. 24, no. 20, pp. 2709–2714, 2013.

R. H. Vekariya and H. D. Patel, “α-thiocyanation of carbonyl compounds: A review,” Synthetic Communications, vol. 47, no. 2, pp. 87–104, 2017.

X.-Q. Pan, M.-Y. Lei, J.-P. Zou, and W. Zhang, “Mn(OAc)₃-promoted regioselective free radical thiocyanation of indoles and anilines,” Tetrahedron Letters, vol. 50, no. 3, pp. 347–349, 2009.

T. B. Mete, T. M. Khopade, and R. G. Bhat, “Transition-metal-free regioselective thiocyanation of phenols, anilines and heterocycles,” Tetrahedron Lett, vol. 58, no. 5, pp. 415–418, 2017.

N. Sun, H. Zhang, W. Mo, B. Hu, Z. Shen, and X. Hu, “Synthesis of Aryl Thiocyanates via Copper-Catalyzed Aerobic Oxidative Cross-Coupling between Arylboronic Acids and KSCN,” Synlett, vol. 24, no. 11, pp. 1443–1447, 2013.

D. S. Bhalerao and K. G. Agamanchi, “Efficient and Novel Method for Thiocyanation of Aromatic and Hetero-aromatic Compounds Using Bromodimethylsulfonium Bromide and Ammonium Thiocyanate,” Synlett, vol. 19, pp. 2952–2956, 2007.

T. Castanheiro, J. Suffert, M. Donnard, and M. Gulea, “Recent advances in the chemistry of organic thiocyanates,” Chemical Society Reviews, vol. 45, no. 3, pp. 494–505, 2016.

Y. Pang, B. An, L. Lou et al., “Design, Synthesis, and Biological Evaluation of Novel Selenium-Containing Isocombretastatins and Phenstatins as Antitumor Agents,” Journal of Medicinal Chemistry, vol. 60, no. 17, pp. 7300–7314, 2017.

K. Sun, Y. Lv, Y. Chen, T. Zhou, Y. Xing, and X. Wang, “A novel metal-free method for the selenocyanation of aromatic ketones to afford α-carbonyl selenocyanates,” Organic & Biomolecular Chemistry, vol. 20, pp. 4249–4478, 2017.

N. Muniraj, J. Dhineshkumar, and K. R. Prabhu, “N-Iodosuccinimide Catalyzed Oxidative Selenocyanation and Thiocyanation of Electron Rich Arenes,” ChemistrySelect, vol. 1, no. 5, pp. 1033–1038, 2016.

P. Maity, B. Paroi, and B. C. Ranu, “Transition-Metal-Free Iodine Catalyzed Selenocayanation of Styrenyl Bromides and an Easy Access to Benzoselenophenes via Intermediacy of Styrenyl Selenocyanate,” Organic Letters, vol. 19, no. 21, pp. 5748–5751, 2017.

S. Redon, A. R. Obah Kosso, J. Broggi, and P. Vanelle, “Easy and efficient selenocyanation of imidazoheterocycles using triselenodicyanide,” Tetrahedron Letters, vol. 58, no. 28, pp. 2771–2773, 2017.

O. Y. Slabko, A. V. Kachanov, and V. A. Kaminskii, “Thio- and Selenocyanation Reactions of Quinone Imines—Derivatives of Pyrido[1,2-a]benzimidazole,” Synthetic Communications, vol. 42, no. 16, pp. 2464–2470, 2012.

J. Chen, T. Wang, T. Wang, A. Lin, H. Yaoa, and J. Xu, “Copper-catalyzed C5-selective thio/selenocyanation of 8-aminoquinolines,” Organic Chemistry Frontiers, vol. 4, no. 1, pp. 130–134, 2017.

F. D. Toste, F. Laronde, and I. W. J. Still, “Thiocyanate as a versatile synthetic unit: Efficient conversion of ArSCN to aryl alkyl sulfides and aryl thioesters,” Tetrahedron Letters, vol. 36, no. 17, pp. 2949–2952, 1995.

T. Billard, B. R. Langlois, and M. Médebielle, “Tetrakis(dimethylamino)ethylene (TDAE) mediated addition of difluoromethyl anions to heteroaryl thiocyanates. A new simple access to heteroaryl-SCF₂R derivatives,” Tetrahedron Letters, vol. 42, no. 20, pp. 3463–3465, 2001.

R. Riemschneider, “Thiocarbamates and Related Compounds. X.1 a New Reaction of Thiocyanates,” Journal of the American Chemical Society, vol. 78, no. 4, pp. 844–847, 1956.

Y. T. Lee, S. Y. Choi, and Y. K. Chung, “Microwave-assisted palladium-catalyzed regioselective cyanothiolation of alkynes with thiocyanates,” Tetrahedron Letters, vol. 48, no. 32, pp. 5673–5677, 2007.

J. M. Blanco, O. Caamaño, F. Fernández, G. Gómez, and C. López, “A useful synthesis of chiral sulfonyl cyanides: (1S,2S,5R)-2-isopropyl-5-methylcyclohexanesulfonyl cyanide,” Tetrahedron: Asymmetry, vol. 3, no. 6, pp. 749–752, 1992.

T. B. Johnson and I. B. Douglass, “The Action of Chlorine on Thiocyanates,” Journal of the American Chemical Society, vol. 61, no. 9, pp. 2548–2550, 1939.

I. Kitagawa, Y. Ueda, T. Kawasaki, and E. Mosettig, “Steroids with functional sulfur groups. III.1 The reaction of some thiocyano steroids,” The Journal of Organic Chemistry, vol. 28, no. 9, pp. 2228–2232, 1963.

W. Fan, Q. Yang, F. Xu, and P. Li, “A visible-light-promoted aerobic metal-free C-3 thiocyanation of indoles,” The Journal of Organic Chemistry, vol. 79, no. 21, pp. 10588–10592, 2014.

D. Yang, K. Yan, W. Wei et al., “Catalyst-Free Regioselective C-3 Thiocyanation of Imidazopyridines,” The Journal of Organic Chemistry, vol. 80, no. 21, pp. 11073–11079, 2015.

D. Wu, J. Qiu, P. G. Karmaker, H. Yin, and F.-X. Chen, “N-Thiocyanatosaccharin: A “sweet” electrophilic thiocyanation reagent and the synthetic applications,” The Journal of Organic Chemistry, vol. 83, no. 3, pp. 1576–1583, 2018.

J. S. Yadav, B. V. S. Reddy, S. Shubashree, and K. Sadashiv, “Iodine/MeOH: a novel and efficient reagent system for thiocyanation of aromatics and heteroaromatics,” Tetrahedron Letters, vol. 45, no. 14, pp. 2951–2954, 2004.

L. Wang, C. Wang, W. Liu, Q. Chen, and M. He, “Visible-light-induced aerobic thiocyanation of indoles using reusable TiO₂/MoS₂ nanocomposite photocatalyst,” Tetrahedron Letters, vol. 57, no. 16, pp. 1771–1774, 2016.

X.-Z. Zhang, D.-L. Ge, S.-Y. Chen, and X.-Q. Yu, “A catalyst-free approach to 3-thiocyanato-4H-chromen-4-ones,” RSC Advances, vol. 6, no. 70, pp. 66320–66323, 2016.

C. Wang, Z. Wang, L. Wang, Q. Chen, and M. He, “Catalytic Thiourea Promoted Electrophilic Thiocyanation of Indoles and Aromatic Amines with NCS/NH₄SCN,” Chinese Journal of Chemistry, vol. 34, no. 11, pp. 1081–1085, 2016.

C. Ip, D. J. Lisk, and H. E. Ganther, “Activities of structurally-related lipophilic selenium compounds as cancer chemopreventive agents,” Anticancer Research, vol. 18, no. 6A, pp. 4019–4025, 1998.

Z. Li, L. Carrier, A. Belame et al., “Combination of methylselenocysteine with tamoxifen inhibits MCF-7 breast cancer xenografts in nude mice through elevated apoptosis and reduced angiogenesis,” Breast Cancer Research and Treatment, vol. 118, no. 1, p. 33, 2009.

C. Ip and H. E. Ganther, “Activity of methylated forms of selenium in cancer prevention,” Cancer Research, vol. 50, no. 4, pp. 1206–1211, 1990.

R. Gowda, S. V. Madhunapantula, D. Desai, S. Amin, and G. P. Robertson, “Simultaneous targeting of COX-2 and AKT using selenocoxib-1-GSH to inhibit melanoma,” Molecular Cancer Therapeutics, vol. 12, no. 1, pp. 3–15, 2013.

C. Shen, M. Buck, J. D. E. T. Wilton-Ely, T. Weidner, and M. Zharnikov, “On the importance of purity for the formation of self-assembled monolayers from thiocyanates,” Langmuir, vol. 24, no. 13, pp. 6609–6615, 2008.

S. Shaaban, M. A. Arafat, and W. S. Hamama, “Vistas in the domain of organoselenocyanates,” Arkivoc, vol. 2014, no. 1, pp. 470–505, 2014.

Q. Chen, Y. Lei, Y. Wang et al., “Direct thiocyanation of ketene dithioacetals under transition-metal-free conditions,” Organic Chemistry Frontiers, vol. 4, pp. 369–372, 2017.

V. Nair, T. G. George, L. G. Nair, and S. B. Panicker, “A direct synthesis of aryl thiocyanates using cerium(IV) ammonium nitrate,” Tetrahedron Letters, vol. 40, no. 6, pp. 1195-1196, 1999.

J. S. Yadav, B. V. Subba Reddy, and B. Bala Murali Krishna, “IBX: A novel and versatile oxidant for electrophilic thiocyanation of indoles, pyrrole and arylamines,” Synthesis, no. 23, pp. 3779–3782, 2008.

H. R. Memarian, I. Mohammadpoor-Baltork, and K. Nikoofar, “Ultrasound-assisted thiocyanation of aromatic and heteroaromatic compounds using ammonium thiocyanate and DDQ,” Ultrasonics Sonochemistry, vol. 15, no. 4, pp. 456–462, 2008.

G. Wu, Q. Liu, Y. Shen, W. Wu, and L. Wu, “Regioselective thiocyanation of aromatic and heteroaromatic compounds using ammonium thiocyanate and oxone,” Tetrahedron Letters, vol. 46, no. 35, pp. 5831–5834, 2005.

H. Jiang, W. Yu, X. Tang, J. Li, and W. Wu, “Copper-catalyzed aerobic oxidative regioselective thiocyanation of aromatics and heteroaromatics,” The Journal of Organic Chemistry, vol. 82, no. 18, pp. 9312–9320, 2017.

N. Iranpoor, H. Firouzabadi, D. Khalili, and R. Shahin, “A new application for diethyl azodicarboxylate: Efficient and regioselective thiocyanation of aromatics amines,” Tetrahedron Letters, vol. 51, no. 27, pp. 3508–3510, 2010.

J. S. Yadav, B. V. S. Reddy, and Y. J. Reddy, “1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane Bis(tetrafluoroborate) as Novel and Versatile Reagent for the Rapid Thiocyanation of Indoles, Azaindole, and Carbazole,” Chemistry Letters, vol. 37, no. 6, pp. 652-653, 2008.

K. K. Laali, G. C. Nandi, and S. D. Bunge, “Selectfluor-mediated mild oxidative halogenation and thiocyanation of 1-aryl-allenes with TMSX (X= Cl, Br, I, NCS) and NH₄SCN,” Tetrahedron Letters, vol. 55, no. 15, pp. 2401–2405, 2014.

A. S. Reddy and K. K. Laali, “Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH4SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition,” Beilstein Journal of Organic Chemistry, vol. 11, pp. 1641–1648, 2015.

K. K. Laali, W. J. Greves, A. T. Zwarycz et al., “Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity,” ChemMedChem, vol. 13, no. 18, pp. 1895–1908, 2018.

G. Aridoss and K. K. Laali, “Building heterocyclic systems with RC(OR)2⁺ carbocations in recyclable Bronsted acidic ionic liquids: Facile synthesis of 1‐substituted 1H‐1,2,3,4‐tetrazoles, benzazoles and other ring systems with CH(OEt)₃ and EtC(OEt)₃ in [EtNH₃][NO₃] and [PMIM(SO₃H)][OTf],” Methods in Organic Synthesis, vol. 15, pp. 2827–2835, 2011.