Visible-Light-Induced, Graphene Oxide-Promoted C3-Chalcogenylation of Indoles Strategy under Transition-Metal-Free Conditions.

An efficient and general method for the synthesis of 3-sulfenylindoles and 3-selenylindoles employing visible-light irradiation with graphene oxide as a promoter at room temperature has been achieved. The reaction features are high yields, simple operation, metal-free and iodine-free conditions, an easy-to-handle oxidant, and gram-scalable synthesis. This simple protocol allows one to access a wide range of 3-arylthioindoles, 3-arylselenylindoles, and even 3-thiocyanatoindoles with good to excellent yields.

1. Introduction

Organosulfur and organoselenium compounds, which possess broad biological and pharmaceutical activities, have been widely employed as important scaffolds for medicinal chemistry (Figure 1) [1,2,3,4,5,6]. Among them, 3-sulfenylindoles and 3-selenylindoles represent important classes of sulfur and selenium-containing compounds having more greater therapeutic values in the treatment of cancer [7,8,9,10,11,12], HIV [13,14,15], tubulin assembly inhibition [16,17], and bacterial diseases [18,19,20,21,22]. In this regard, numerous methods for the straightforward construction of C-S and C-Se bonds have been developed for the synthesis of 3-sulfenylindoles and 3-selenylindoles. Among these various approaches, the most commonly used methods involved the direct sulfenylation and selenation of the indole moieties with various electrophilic sulfur and selenium reagents [23,24,25,26,27,28,29,30,31,32,33,34,35].

Figure 1

Selected examples of biologically active 3-selanyl- and 3-sulfanylindole compounds.

However, these strategies suffer from limitations, such as the need for stoichiometric or super stoichiometric amounts of catalysts, strong acidic or oxidizing reagents, harsh reaction conditions, the complex synthetic process of activated sulfur or selenium reagents, and limited substrate scopes [36,37,38,39,40,41]. Most importantly, these reactions employ arylsulfur or arylselenium reagents such as benzenesulfonyl chlorides [42,43,44,45], N-(thiophenyl)succinimide [46,47], S-phenyl benzenesulfonothioate [48,49], disulfides [50,51,52], benzene-sulfonhydrazide [53,54,55,56], N-phenylselenophthalimide [57], N-phenylselenosuccinimide [58], and diselenides [59,60,61,62,63], generation of stoichiometric byproducts still cannot be avoided under the conditions used. Therefore, the development of green and sustainable synthetic methods is highly desirable under mild conditions so as to avoid the use of external oxidants, transition metal catalysts, or harsh reaction conditions.

In recent years, graphene oxide (GO) [64,65,66,67], which is a readily available and inexpensive material, has historically functioned primarily as a precursor to reduced graphene oxide (rGO) or chemically modified graphene (CMG) materials [68,69], and has generated tremendous excitement due to its potential applications in plastic electronics, solar cells, optical materials, and biosensors [70,71]. In addition, photo-induced organic transformations have emerged as an attractive and suitable approach in recent years [72,73,74,75,76,77,78,79,80,81]. Although GO has been reported as a photocatalyst for hydrogen production from water under UV irradiation [82], the potential application of GO in synthetic photochemistry is still rare [83].

More recently, Wu et al developed a procedure of GO-mediated thiolation of indoles with thiols in water (Scheme 1) [84]. This methodology provided an atom economical and transition-metal and iodine free procedure for the direct synthesis of 3-sulfenylindoles. Subsequently, Kumar and Rathore reported a benign oxidant, photocatalyst and transition-metal-free visible light induced methodology for the construction of carbon-chalcogen (S, Se, Te) bond that enables the 3-chalcogenyl indole (Scheme 1) [29]. However, most of these methods suffer from some drawbacks such as low atom efficiency and limited substrate scope. Recently, we reported a new and efficient method for the C3-chalcogenylation of indolines employing visible-light irradiation and graphene oxide as a promoter at room temperature [85]. However, the reaction substrates are expensive and difficult to obtain for this synthesis method. In continuation of our work on indole chemistry [86,87,88,89,90,91,92] and GO-promoted C-H functionalisation of indoles [93], herein, we wish to report the combination of GO and blue LEDs, which works in synergy to efficiently promote the organo chalcogenylation (S and Se) of indoles in DCE under air atmosphere by using commercially available substrates. The highlight of this work is that GO not only acts as an oxidant, but as a photocatalyst as well.

Scheme 1

C3 chalcogenylation of indoles.

2. Results and Discussion

The GO material used in this investigation was prepared by Hummers oxidation of graphite and subsequent exfoliation, as reported [94,95]. The obtained GO material was characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), visible Raman spectroscopy, and atomic force microscopy (AFM) [96] (see the Supplementary Materials).

To commence our investigation, the reaction of indole 4a with 4-methylbenzenethiol 5a was performed using 40 wt % GO as a promoter under irradiation with sunlight in open air (Table 1). The reaction proceeded and produced the desired coupling product 6a with a 28% yield (entry 1). Different light sources, such as CWF bulb (22 W, λmax = 365 ± 10 nm), green LED (1.0 W, λmax = 530 ± 10 nm), and blue LED (3.0 W, λmax = 425 ± 15 nm), were tested. Blue LED was more effective than other light sources, indicating the higher activity of GO in the presence of high-intensity blue light (entries 2–4). The reaction in the absence of a light source either failed to take place at room temperature (entry 5), or only a trace amount of the target product was formed (entry 17). The solvent also plays an important role in this transformation. DCE (1,2-dichloroethane) was more effective than the other tested solvents, such as THF, DMSO, toluene, DMF, and 1,4-dioxane (entries 6–11). Subsequent efforts were directed toward optimizing the GO loadings (entries 12–16). Whereas 50 wt % GO afforded 87% of the target product, decreasing the loading to 20 wt % GO was found to be sufficient to drive the cross-coupling reaction to quantitative conversion. No product was detected without GO. On the basis of our screening experiments, the best reaction condition is using 50 wt % GO in DCE and irradiation with blue LED in open air at 25 °C for 12 h, which afforded the desired product 6a in high yield (87%, entry 14).

Table 1

Optimization of the reaction conditions .

Entry	GO (wt %) b	Light Source	Solvent	Yield (%) c
1	40	Sunlight	CH3CN	28
2	40	22 W CWF bulb	CH3CN	22
3	40	1W Green LED	CH3CN	7
4	40	3W blue LED	CH3CN	61
5	40	No light	CH3CN	0
6	40	3W blue LED	THF	5
7	40	3W blue LED	DMSO	7
8	40	3W blue LED	Toluene	34
9	40	3W blue LED	DCE	78
10	40	3W blue LED	DMF	0
11	40	3W blue LED	1,4-Dioxane	0
12	20	3W blue LED	DCE	67
13	30	3W blue LED	DCE	72
14	50	3W blue LED	DCE	87
15	60	3W blue LED	DCE	85
16	0	3W blue LED	DCE	0
17	50	No light	DCE	<5

Reaction conditions: 4a (0.3 mmol), 5a (0.36 mmol), and solvent (1 mL), for 12 h at rt under open air. With respect to the substrate 4a. Isolated yield.

With the best experimental conditions for the synthesis of 6a in hand, we first evaluated the efficiency of different substituted indoles 4 while keeping 4-methylbenzenethiol 5a constant. Under the optimized conditions, the desired products 6aa-6ma could be efficiently obtained in good to excellent yields (Table 2). Various substituted indoles 4, i.e., electrondonating (EDG, R = Me, OMe, OBn) and electron-withdrawing (EWG, R = Cl, I, CN, CO2CH3) groups successfully afforded the corresponding 3-sulfenylindoles and had no significant effect on the reactivity and the regioselectivity of reactions. In general, the EDG were better than the EWG. Furthermore, the introduction of various groups at the N-1, C-2, -3, -4, -5, -6, or -7 position of the indoles all proceeded with 5a under standard reaction conditions. Exceptions to this are 4-methylindole and methyl-4-indolecarboxylate, showing moderate sulfenylation yields (6ha and 6ia), probably due to the steric hindrance effect (entries 8 and 9). Interestingly, introducing a methyl group at the C-3-position of the indole afforded the 2-sulfenylindole product 6ma in 84% yield.

Table 2

Scope of indoles .

Entry	R1	R2	R3	Product	Yield (%) b
1	H	H	H	6aa	87
2	5-I	H	H	6ba	83
3	5-CH3	H	H	6ca	89
4	5-CN	H	H	6da	78
5	6-OCH3	H	H	6ea	90
6	7-Cl	H	H	6fa	80
7	7-OBn	H	H	6ga	83
8	4-CH3	H	H	6ha	71
9	4-CO2CH3	H	H	6ia	67
10	H	H	2-CH3	6ja	86
11	H	CH3	H	6ka	86
12	5-CH3	H	2-CH3	6la	82
13 c	H	H	3-CH3	6ma	84

Reaction conditions: 4 (0.3 mmol), 5a (0.36 mmol), GO (50 wt %) with respect to the substrate 4a, and DCE (1 mL), for 12 h at rt under open air. Isolated yield. 3-Methyl-2-(p-tolylthio)-1H- indole (6ma) was obtained.

Next, a diverse array of arylthiols were employed as substrates to explore the scope of this reaction (Table 3). These substrates also showed high reactivity in this transformation. All reactions proceeded smoothly when the thiophenol was bearing, regardless of electron-donating groups (Me and OMe) or electron-withdrawing groups (Cl, Br, and NO2) on the phenyl ring; the 3-sulfenylindoles were obtained in good to excellent yields.

Table 3

Scope of thiols .

Entry	R	Product	Yield (%) b
1	4-ClPh	6ab	86
2	4-BrPh	6ac	88
3	4-OCH3Ph	6ad	83
4	4-C2H5Ph	6ae	80
5	2,4-dimethylphenyl	6af	82
6	4-NO2Ph	6ag	91
7	Naphthalen-2-yl	6ah	78
8 c	4-OCH3Ph	6ai	78
9 d	4-CH3	6aj	76

Reaction conditions: 4a (0.3 mmol), 5 (0.36 mmol), GO (50 wt %) with respect to the substrate 4a, and DCE (1 mL), for 12 h at rt under open air. Isolated yield. 5-Methoxy-3-((4-methoxyphenyl)thio)-1H-indole (6ai) was obtained. 3-(p-Tolylthio)-1H-pyrrolo[3,2-b]pyridine (6aj) was obtained.

The success in using aryl thiols encouraged us to examine the reaction of indole 4a with various heterocyclic thiols including benzo[d]thiazole-2-thiol, 1-methyl-1H-imidazole-2-thiol, 1,3,4-thiadiazole-2-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, 1-methyl-1H-tetrazole-5-thiol, and the results are summarized in Scheme 2. In general, the desired products were formed in moderate to excellent yields under the standard reaction conditions.

Scheme 2

Heterocyclic thiols and potassium thiocyanate used as C3 sulfenylation of indoles.

Organothiocyanates are valuable synthetic intermediates which can be easily transformed into an array of organosulfur molecules [97,98,99]. Under the optimized conditions, we sustained our studies by treating indoles or 1H-pyrrolo[2,3-b]pyridine with KSCN under the standard reaction conditions, and the corresponding thiocyanated product 7a–f were obtained with 43–85% yields (Scheme 2). The results have shown that electronegativities of substituents play a major role in governing the reactivity of the substrates. Electron-donating substitutents show better results than electron-withdrawing substitutents in this transformation.

The developed protocol can also be applied for the preparation of 3-selenyl-indoles using various indole derivatives 4 and diphenyl diselenide 8. In general, the desired products 9 were formed in good to excellent yields in 8 h (Scheme 3), which was more efficient than the generation of 3-sulfenylindoles with regard to the yields and reaction times.

Scheme 3

Synthesis of 3-selenylindoles. Reaction conditions: 4 (0.3 mmol), 8 (0.36 mmol), GO (50 wt %), and DCE (1 mL), for 8 h at rt under open air. Isolated yield.

In order to demonstrate the effectiveness of this new strategy, a gram scale reaction was performed under the standard conditions. 10 mmol indole 4a and 12 mmol 4-methylbenzenethiol 5a were subjected to the reaction in the presence of GO (468 mg, 40 wt %) in 50 mL DCE at room temperature. After 12 h, the desired product 6a was obtained in 84% yield, which demonstrated the practical application of this protocol to prepare 3-sulfenylindoles on a gram-scale (Scheme 4). To our delight, when the amount of GO was reduced to 40 wt %, the yield was not affected to any observable extent.

Scheme 4

Scale-up reaction between 4a and 5a.

To gain some insight into the mechanism of this reaction, some control experiments were conducted as shown in Scheme 5. Because the visible-light-induced, GO-promoted cross-coupling reaction was performed under open air, the role of O2 in this reaction was explored. Initially, When the optimal reaction was performed under an oxygen atmosphere instead of open air, there was no effect on the yield, but a faster conversion of the starting material to the reaction product was observed, indicating that O2 could be involved in the reaction pathway. Similarly, when the reaction was carried out under an argon atmosphere, no major effect was observed, indicating that the reaction follows a different route in an argon environment.

Scheme 5

Control experiments.

Then, radical trapping experiments were conducted by adding butylated hydroxytoluene (BHT) or 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) into the standard conditions of 4a and 5a. Experimental results show that these reaction were completely inhibited, indicating the involvement of radical species in the transformation.

On the basis of our control experiments and several other reports from the literature [29,85,100,101,102], we proposed two plausible mechanisms for this reaction in argon and in oxygen environments as shown in Scheme 6. Graphene oxide might act as a radical initiator [29]. Under an argon atmosphere (path A), promoted by the functional groups on the surface of GO, 5-methylbenzenethiol transformed into phenylthiophenol radical 10. Next, the thioyl radical 10 interacted with 4a to produce the radical intermediate 11. After that, 11 was oxidized to the intermediate 12. Finally, deprotonation of intermediate 12 led to the formation of product 6a. GO probably plays a crucial role during the process of oxidation and deprotonation.

Scheme 6

The proposed mechanism for the reaction.

In 2012, Loh et al suggested that the edge sites with unpaired electrons in GO constitute the active catalytic sites and afford enhanced kinetics for the trapping and activation of molecular oxygen by a sequence of electron transport and reduction to superoxide radical [103,104]. Thus, in the case of an oxygen atmosphere (path B), the anion radical of O2 (O2•−), which is produced through a SET from unpaired electrons in GO, would abstract a proton from 12, which would generate the desired product 6a and perhydroxyl radical (HO2•). The transfer of H• from 5a to HO2• would generate 10 and H2O2.

3. Materials and Methods

3.1. General Information

Unless otherwise specified, commercial reagents and solvents were used without further purification. Commercially available chemicals were purchased from Leyan (Shanghai, China) and used without any further purification. 1H and 13C NMR spectra were recorded on a Bruker spectrometer at 400 and 100 MHz, respectively. The chemical shifts were given in parts per million relative to CDCl3 (7.26 ppm for 1H) and CDCl3 (77.0 ppm for 13C. Peak multiplicities were reported as follows: s, singlet; d, doublet; t, triplet; m, multiplet; br. s, broad singlet and J, coupling constant (Hz). Mass spectra were recorded with Bruker Dalton Esquire 3000 plus LC-MS apparatus. Elemental analyses are expressed as percentage values. HRFABMS spectra were recorded on a FTMS apparatus. Silica gel (300–400 mesh) was used for flash column chromatography, eluting (unless otherwise stated) with an ethyl acetate/petroleum ether (PE) (60–90 °C) mixture.

3.2. General Procedure of the Products

In a 10 mL Schlenk tube, indole (0.3 mmol), GO (17.6 mg), and thiol (0.36 mmol) were stirred in DCE (1 mL) for 12 h at room temperature under an air atmosphere irradiated by blue LEDs. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc/PE = 1:10) to yield the corresponding product 6.

3-(p-Tolylthio)-1H-indole (6aa). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.37 (s, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.46 (d, J = 2.6 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.26 (dt, J = 1.0, 8.1 Hz, 1H, Ar-H), 7.18 (t, J = 7.1 Hz, 1H), 7.05 (d, J = 8.3 Hz, 2H), 6.99 (d, J = 8.3 Hz, 2H), 2.26 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 136.5, 135.5, 134.7, 130.4, 129.5, 129.1, 126.3, 123.0, 120.8, 119.7, 111.5, 103.6, 20.8. MS (ESI): 240 (M + H+, 100). These assignments matched with those previously published [27].

5-Iodo-3-(p-tolylthio)-1H-indole (6ba). Brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.51 (s, 1H, NH), 7.99 (d, J = 1.5 Hz, 1H, Ar-H), 7.53 (dd, J = 8.5, 1.5 Hz, 1H, Ar-H), 7.43 (d, J = 1.5 Hz, 1H, Ar-H), 7.21 (d, J = 8.5 Hz, 1H, Ar-H), 7.06–7.01 (m, 4H, Ar-H), 2.29 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 135.6, 135.1, 134.9, 131.7, 131.4, 131.3, 129.6, 128.4, 126.3, 113.6, 102.8, 84.6, 20.9. MS (ESI): 366 (M + H+, 100). These assignments matched with those previously published [105].

5-Methyl-3-(p-tolylthio)-1H-indole (6ca). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.19 (s, 1H, NH), 7.55 (d, J = 0.7 Hz, 1H, Ar-H), 7.40 (d, J = 2.6 Hz, 1H, Ar-H), 7.34 (d, J = 8.2 Hz, 1H, Ar-H), 7.21–7.13 (m, 3H, Ar-H), 7.08 (d, J = 8.2 Hz, 2H, Ar-H), 2.52 (s, 3H, CH3), 2.36 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 135.9, 134.9, 134.7, 130.94, 130.4, 129.7, 129.5, 126.2, 124.7, 119.2, 111.5, 102.4, 21.6, 21.0. MS (ESI): 254 (M + H+, 100). These assignments matched with those previously published [105].

3-(p-Tolylthio)-1H-indole-5-carbonitrile (6da). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.20 (s, 1H, NH), 7.99 (d, J = 1.6 Hz, 1H, Ar-H), 7.81 (s, 1H, Ar-H), 7.66 (d, J = 8.4 Hz, 1H, Ar-H), 7.53 (d, J = 8.4 Hz, 1H, Ar-H), 7.04 (d, J = 8.0 Hz, 2H, Ar-H), 6.99 (d, J = 8.0 Hz, 2H, Ar-H), 2.20 (s, 3H, CH3). 13C NMR (101 MHz, DMSO-d): δ 139.1, 135.3, 135.2, 134.9, 130.1, 129.0, 126.9, 125.4, 124.1, 120.7, 114.3, 102.8, 102.5, 20.9. MS (ESI): 265 (M + H+, 100). These assignments matched with those previously published [106].

6-Methoxy-3-(p-tolylthio)-1H-indole (6ea). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H, NH), 7.51 (d, J = 8.6 Hz, 1H, Ar-H), 7.34 (d, J = 2.2 Hz, 1H, Ar-H), 7.08 (d, J = 8.2 Hz, 2H, Ar-H), 7.02 (d, J = 8.2 Hz, 2H, Ar-H), 6.90 (d, J = 2.2 Hz, 1H, Ar-H), 6.86 (dd, J = 8.6, 2.2 Hz, 1H, Ar-H), 3.87 (s, 3H, OCH3), 2.29 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 157.2, 137.3, 135.6, 134.7, 129.5, 129.3, 126.3, 123.3, 120.3, 110.8, 103.4, 95.2, 55.7, 20.9. MS (ESI): 270 (M + H+, 100). These assignments matched with those previously published [106].

7-(Benzyloxy)-3-(p-tolylthio)-1H-indole (6ga). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.71 (s, 1H, NH), 7.52 (d, J = 7.1 Hz, 2H, Ar-H), 7.49–7.40 (m, 4H, Ar-H), 7.27 (d, J = 8.4 Hz, 1H, Ar-H), 7.09 (t, J = 7.8 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 2H, Ar-H), 7.01 (d, J = 8.0 Hz, 2H, Ar-H), 6.81 (d, J = 7.8 Hz, 1H, Ar-H), 5.24 (s, 2H, OCH2), 2.28 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 145.6, 136.9, 135.7, 134.6, 130.8, 130.1, 129.5, 128.7, 128.3, 128.0, 127.2, 126.3, 121.2, 112.6, 104.0, 103.7, 70.4, 20.9. MS (ESI): 346 (M + H+, 100). Anal calcd for C22H19NOS: C, 76.49; H, 5.54; N, 4.05; S, 9.28. Found C, 76.35; H, 5.47; N, 4.33; S, 8.95.

4-Methyl-3-(p-tolylthio)-1H-indole (6ha). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H, NH), 7.43 (d, J = 2.6 Hz, 1H, Ar-H), 7.29 (d, J = 8.1 Hz, 1H, Ar-H), 7.17 (t, J = 8.1 Hz, 1H, Ar-H), 7.06–6.98 (m, 4H, Ar-H), 6.92 (d, J = 7.1 Hz, 1H), 2.70 (s, 3H, CH3), 2.29 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 137.9, 137.0, 134.3, 132.2, 131.7, 129.6, 127.0, 125.5, 123.1, 122.4, 109.4, 102.9, 20.9, 18.7. MS (ESI): 254 (M + H+, 100). These assignments matched with those previously published [106].

Methyl 3-(p-tolylthio)-1H-indole-4-carboxylate (6ia). Brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 9.19 (s, 1H, NH), 7.51 (d, J = 2.6 Hz, 1H, Ar-H), 7.49 (d, J = 1.0 Hz, 1H, Ar-H), 7.38 (d, J = 2.6 Hz, 1H, Ar-H), 7.24 (t, J = 7.8 Hz, 1H, Ar-H), 6.98 (s, 4H, Ar-H), 3.68 (s, 3H), 2.30 (d, J = 37.7 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 169.6, 137.6, 136.4, 134.6, 133.4, 129.4, 126.2, 125.4, 125.3, 122.1, 122.0, 115.1, 103.1, 51.9, 20.8. MS (ESI): 298 (M + H+, 100). Anal calcd for C17H15NO2S: C, 68.66; H, 5.08; N, 4.71; S, 10.78. Found C, 68.80; H, 5.26; N, 4.64; S, 10.57.

2-Methyl-3-(p-tolylthio)-1H-indole (6ja). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.26 (s, 1H, NH), 7.58 (d, J = 7.8 Hz, 1H, Ar-H), 7.36 (dt, J = 1.0, 7.8 Hz, 1H, Ar-H), 7.22 (dt, J = 1,0, 7.8 Hz, 1H, Ar-H), 7.15 (dt, J = 1.0, 7.8 Hz, 1H, Ar-H), 6.99 (s, 4H, Ar-H), 2.54 (s, 3H, CH3), 2.27 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 141.0, 135.7, 135.5, 134.4, 130.4, 129.5, 125.8, 122.1, 120.7, 119.0, 110.7, 99.9, 20.9, 12.2. MS (ESI): 254 (M + H+, 100). These assignments matched with those previously published [106].

1-Methyl-3-(p-tolylthio)-1H-indole (6ka). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 8.2 Hz, 1H, Ar-H), 7.45 (d, J = 8.2 Hz, 1H, Ar-H), 7.39 (dt, J = 1.0, 7.0 Hz, 1H, Ar-H), 7.37 (s, 1H, Ar-H), 7.28 (dt, J = 1.0, 7.0 Hz, 1H, Ar-H), 7.15 (d, J = 8.2 Hz, 2H, Ar-H), 7.07 (d, J = 8.2 Hz, 1H, Ar-H), 3.86 (s, 3H, NCH3), 2.35 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 137.6, 136.1, 134.9, 134.6, 123.0, 129.6, 126.3, 126.2, 122.6, 120.5, 119.8, 109.8, 101.3, 33.1, 21.0. MS (ESI): 254 (M + H+, 100). These assignments matched with those previously published [105].

2,5-Dimethyl-3-(p-tolylthio)-1H-indole (6la). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H, NH), 7.46 (s, 1H, Ar-H), 7.25 (d, J = 8.2 Hz, 1H, Ar-H), 7.10 (dd, J = 8.2, 1.2 Hz, 1H, Ar-H), 7.46 (s, 4H, Ar-H), 2.51 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.34 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 141.3, 136.0, 134.3, 133.8, 130.7, 130.1, 129.6, 125.7, 123.7, 118.7, 110.5, 99.0, 21.5, 20.9, 12.1. MS (ESI): 268 (M + H+, 100). These assignments matched with those previously published [106].

3-Methyl-2-(p-tolylthio)-1H-indole (6ma). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H, NH), 7.71 (d, J = 7.9 Hz, 1H, Ar-H), 7.33 (d, J = 3.6 Hz, 2H, Ar-H), 7.26 (m, 1H, Ar-H), 7.12 (d, J = 8.3 Hz, 2H, Ar-H), 7.09 (d, J = 8.3 Hz, 2H, Ar-H), 2.51 (s, 3H, CH3), 2.38 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 136.9, 135.9, 133.5, 130.0, 128.6, 127.1, 123.4, 122.3, 119.7, 119.5, 119.4, 111.0, 21.0, 9.6. MS (ESI): 254 (M + H+, 100). These assignments matched with those previously published [106].

3-((4-Chlorophenyl)thio)-1H-indole (6ab). Light yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.47 (s, 1H, NH), 7.58 (d, J = 8.0 Hz, 1H, Ar-H), 7.49 (d, J = 2.6 Hz, 1H, Ar-H), 7.45 (d, J = 8.2 Hz, 1H, Ar-H), 7.29 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.18 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.12 (d, J = 8.7 Hz, 2H, Ar-H), 7.02 (d, J = 8.7 Hz, 2H, Ar-H). 13C NMR (101 MHz, CDCl3): δ 137.8, 136.5, 130.6, 130.5, 128.7, 128.6, 127.1, 123.1, 121.0, 119.4, 111.6, 102.4. MS (ESI): 260 (M + H+, 30), 262 (M + H+, 100). These assignments matched with those previously published [105].

3-((4-Bromophenyl)thio)-1H-indole (6ac). Brown amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.76 (s, 1H, NH), 7.80 (d, J = 2.7 Hz, 1H, Ar-H), 7.51 (d, J = 8.1 Hz, 1H, Ar-H), 7.41–7.35 (m, 3H, Ar-H), 7.20 (dt, J = 1.1, 8.1 Hz, 1H, Ar-H), 7.08 (dt, J = 1.1, 8.1 Hz, 1H, Ar-H), 6.96 (dt, J = 2.7, 8.6 Hz, 2H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 139.5, 137.3, 133.1, 132.1, 128.9, 127.7, 122.7, 120.7, 118.6, 118.0, 112.9, 99.1. MS (ESI): 304 (M + H+, 100), 306 (M + H+, 100). These assignments matched with those previously published [105].

3-((4-Methoxyphenyl)thio)-1H-indole (6ad). Brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.38 (s, 1H, NH), 7.63 (d, J = 8.0 Hz, 1H, Ar-H), 7.46 (d, J = 2.6 Hz, 1H, Ar-H), 7.41 (d, J = 8.0 Hz, 1H, Ar-H), 7.25 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.17 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.13 (d, J = 8.9 Hz, 2H, Ar-H), 6.74 (d, J = 8.9 Hz, 2H, Ar-H), 3.73 (s, 3H, OCH3). 13C NMR (101 MHz, CDCl3): δ 157.8, 136.5, 123.0, 129.5, 129.0, 128.6, 122.9, 120.8, 119.7, 114.5, 111.5, 104.7, 55.3. MS (ESI): 256 (M + H+, 100). These assignments matched with those previously published [27].

3-((4-Ethylphenyl)thio)-1H-indole (6ae). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.34 (s, 1H, NH), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.45 (d, J = 2.3 Hz, 1H, Ar-H), 7.44 (d, J = 8.0 Hz, 1H, Ar-H), 7.32 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.23 (t, J = 7.5 Hz, 1H, Ar-H), 7.13 (d, J = 8.2 Hz, 2H, Ar-H), 7.06 (d, J = 8.2 Hz, 2H, Ar-H), 2.61 (q, J = 7.6 Hz, 2H, CH2), 1.23 (t, J = 7.6 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 141.3, 136.5, 135.9, 130.7, 129.2, 128.5, 126.3, 123.1, 120.9, 119.7, 111.8, 103.2, 28.4, 15.7. MS (ESI): 254 (M + H+, 100). Anal calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.53; S, 12.65. Found C, 75.59; H, 5.63; N, 5.71; S, 12.32.

3-((2,4-Dimethylphenyl)thio)-1H-indole (6af). Tawny amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H, NH), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.45 (d, J = 8.0 Hz, 1H, Ar-H), 7.41 (d, J = 2.6 Hz, 1H, Ar-H), 7.36 (t, J = 7.7 Hz, 1H, Ar-H), 7.27 (t, J = 7.7 Hz, 1H, Ar-H), 7.09 (s, 1H, Ar-H), 6.83 (d, J = 8.0 Hz, 1H, Ar-H), 6.78 (d, J = 8.0 Hz, 1H, Ar-H), 2.59 (s, 3H, CH3), 2.34 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 136.6, 134.7, 134.6, 134.4, 130.9, 130.5, 129.3, 127.1, 126.1, 123.0, 120.8, 119.7, 111.6, 103.0, 20.7, 19.9. MS (ESI): 254 (M + H+, 100). Anal calcd for C16H15NS: C, 75.85; H, 5.97; N, 5.53; S, 12.65. Found C, 76.04; H, 5.83; N, 5.66; S, 12.35.

3-((4-Nitrophenyl)thio)-1H-indole (6ag). Reddish brown amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.86 (s, 1H, NH), 8.02 (d, J = 9.0 Hz, 2H, Ar-H), 7.55 (t, J = 7.7 Hz, 1H, Ar-H), 7.54 (d, J = 2.6 Hz, 1H, Ar-H), 7.53 (d, J = 8.1 Hz, 1H, Ar-H), 7.34 (t, J = 8.1 Hz, 1H, Ar-H), 7.22 (t, J = 7.7 Hz, 1H, Ar-H), 7.15 (d, J = 9.0 Hz, 2H, Ar-H). 13C NMR (101 MHz, CDCl3): δ 150.0, 144.9, 136.7, 131.4, 128.5, 125.2, 123.9, 123.5, 121.4, 119.2, 112.1, 100.1. MS (ESI): 271 (M + H+, 100). These assignments matched with those previously published [107].

3-(Naphthalen-2-ylthio)-1H-indole (6ah). Reddish brown amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.74 (s, 1H, NH), 7.83 (d, J = 2.5 Hz, 1H, Ar-H), 7.77 (d, J = 8.6 Hz, 1H, Ar-H), 7.73 (d, J = 8.7 Hz, 1H, Ar-H), 7.61 (d, J = 7.5 Hz, 1H, Ar-H), 7.50 (d, J = 2.6 Hz, 1H, Ar-H), 7.48 (s, 1H, Ar-H), 7.40–7.33 (m, 3H, Ar-H), 7.20 (dd, J = 2.6 Hz, 1H, Ar-H), 7.17 (t, J = 2.6 Hz, 1H, Ar-H), 7.03 (t, J = 7.5 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 137.3, 137.2, 133.7, 133.0, 131.3, 129.1, 128.8, 128.1, 127.1, 127.0, 125.7, 124.9, 123.3, 122.6, 120.6, 118.8, 112.9, 99.8. MS (ESI): 276 (M + H+, 100). These assignments matched with those previously published [106].

5-Methoxy-3-((4-methoxyphenyl)thio)-1H-indole (6ai). Red amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.42 (s, 1H, NH), 7.40 (d, J = 2.6 Hz, 1H, Ar-H), 7.28 (d, J = 8.8 Hz, 1H, Ar-H), 7.17 (dt, J = 2.6, 8.8 Hz, 2H, Ar-H), 7.13 (d, J = 2.4 Hz, 1H, Ar-H), 6.95 (dd, J = 8.8, 2.4 Hz, 1H, Ar-H), 6.80 (dt, J = 2.6, 8.8 Hz, 2H, Ar-H), 3.84 (s, 3H, OCH3), 3.76 (s, 3H, OCH3). 13C NMR (101 MHz, CDCl3): δ 157.8, 155.0, 131.5, 131.0, 129.9, 129.8, 128.3, 114.6, 113.4, 112.5, 103.7, 104.0, 55.9, 55.4. MS (ESI): 286 (M + H+, 100). These assignments matched with those previously published [108].

3-(p-Tolylthio)-1H-pyrrolo[3,2-b]pyridine (6aj). Light yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.86 (s, 1H, NH), 8.36 (d, J = 4.0 Hz, 1H, Ar-H), 8.00 (d, J = 2.6 Hz, 1H, Ar-H), 7.86 (d, J = 8.1 Hz, 1H, Ar-H), 7.19 (dd, J = 8.1, 4.5 Hz, 1H, Ar-H), 7.00 (d, J = 7.2 Hz, 2H, Ar-H), 6.96 (d, J = 7.2 Hz, 2H, Ar-H), 2.19 (s, 3H, CH3). 13C NMR (101 MHz, DMSO-d): δ 146.0, 143.8, 136.2, 135.9, 134.5, 129.8, 129.7, 126.5, 120.0, 117.7, 101.6, 20.9. MS (ESI): 241 (M + H+, 100). Anal calcd for C14H12N2S: C, 69.97; H, 5.03; N, 11.66; S, 13.34. Found C, 70.21; H, 5.37; N, 11.31; S, 13.15.

2-((1H-indol-3-yl)thio)benzo[d]thiazole (6ak). Brown amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.03 (s, 1H, NH), 8.04 (d, J = 2.8 Hz, 1H, Ar-H), 7.82 (dd, J = 2.8, 1.8 Hz, 1H, Ar-H), 7.80 (dd, J = 2.1, 1.0 Hz, 1H, Ar-H), 7.57 (d, J = 7.8 Hz, 1H, Ar-H), 7.56 (d, J = 7.8 Hz, 1H, Ar-H), 7.41 (dt, J = 1.2, 8.4 Hz, 1H, Ar-H), 7.30–7.23 (m, 2H, Ar-H), 7.15 (dt, J = 1.0, 7.1 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 173.8, 154.6, 137.2, 135.4, 134.4, 128.4, 126.6, 124.4, 123.1, 122.1, 121.6, 121.3, 118.5, 113.1, 97.7. MS (ESI): 283 (M + H+, 100). These assignments matched with those previously published [101].

3-((1-Methyl-1H-imidazol-2-yl)thio)-1H-indole (6al). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.51 (s, 1H, NH), 7.69 (s, 1H, Ar-H), 7.60 (d, J = 7.6 Hz, 1H, Ar-H), 7.39 (d, J = 7.6 Hz, 1H, Ar-H), 7.16 (s, 1H, Ar-H), 7.10 (t, J = 7.1 Hz, 1H, Ar-H), 7.04 (t, J = 7.1 Hz, 1H, Ar-H), 6.85 (s, 1H, Ar-H), 3.66 (s, 3H, CH3). 13C NMR (101 MHz, DMSO-d): δ 140.0, 136.7, 131.0, 128.9, 128.5, 124.0, 122.4, 120.3, 119.1, 112.5, 100.6, 34.0. MS (ESI): 230 (M + H+, 100). Anal calcd for C12H11N3S: C, 62.86; H, 4.84; N, 18.33; S, 13.98. Found C, 63.10; H, 5.07; N, 18.05; S, 13.61.

2-((1H-indol-3-yl)thio)-1,3,4-thiadiazole (6am). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.98 (s, 1H, NH), 9.29 (s, 1H, Ar-H), 8.00 (d, J = 2.8 Hz, 1H, Ar-H), 7.56 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (d, J = 7.9 Hz, 1H, Ar-H), 7.25 (dt, J = 1.0, 8.0 Hz, 1H, Ar-H), 7.16 (d, J = 7.9 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 173.0, 154.3, 137.2, 133.6, 127.8, 123.2, 121.3, 118.4, 113.2, 98.6. MS (ESI): 234 (M + H+, 100). Anal calcd for C10H7N3S2: C, 51.48; H, 3.02; N, 18.01; S, 27.48. Found C, 51.83; H, 3.39; N, 17.85; S, 27.17.

2-((1H-indol-3-yl)thio)-5-methyl-1,3,4-thiadiazole (6an). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.95 (s, 1H, NH), 7.96 (d, J = 2.7 Hz, 1H, Ar-H), 7.55 (d, J = 2.7 Hz, 1H, Ar-H), 7.53 (d, J = 2.7 Hz, 1H, Ar-H), 7.24 (d, J = 7.5 Hz, 1H, Ar-H), 7.16 (d, J = 7.5 Hz, 1H, Ar-H), 2.50 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 172.4, 165.7, 137.1, 133.5, 128.0, 123.1, 121.3, 118.4, 113.1, 98.8, 15.6. MS (ESI): 248 (M + H+, 100). Anal calcd for C11H9N3S2: C, 53.42; H, 3.67; N, 16.99; S, 25.92. Found C, 53.76; H, 3.92; N, 16.84; S, 25.59.

3-((1-Methyl-1H-tetrazol-5-yl)thio)-1H-indole (6ao). Pink amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.85 (s, 1H, NH), 7.94 (d, J = 2.7 Hz, 1H, Ar-H), 7.54 (d, J = 8.7 Hz, 1H, Ar-H), 7.51 (d, J = 8.7 Hz, 1H, Ar-H), 7.22 (d, J = 7.2 Hz, 1H, Ar-H), 7.13 (d, J = 7.2 Hz, 1H, Ar-H), 4.03 (s, 3H, NCH3). 13C NMR (101 MHz, DMSO-d): δ 153.8, 136.9, 133.5, 128.8, 122.9, 121.0, 118.6, 112.9, 94.5, 34.5. MS (ESI): 232 (M + H+, 100). Anal calcd for C10H9N5S: C, 51.93; H, 3.92; N, 30.28; S, 13.86. Found C, 52.20; H, 4.28; N, 29.91; S, 13.93.

3-Thiocyanato-1H-indole (7a). White amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.76 (s, 1H, NH), 7.83 (dd, J = 5.9, 3.1 Hz, 1H, Ar-H), 7.52 (d, J = 2.8 Hz, 1H, Ar-H), 7.45 (dt, J = 5.9, 3.1 Hz, 1H, Ar-H), 7.35 (t, J = 3.1 Hz, 1H, Ar-H), 7.33 (t, J = 3.1 Hz, 1H, Ar-H). 13C NMR (101 MHz, CDCl3): δ 136.0, 131.0, 127.7, 123.9, 121.9, 118.8, 112.1, 111.9, 92.3. MS (ESI): 175 (M + H+, 100). These assignments matched with those previously published [109].

5-Chloro-3-thiocyanato-1-H-indole (7b). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.20 (s, 1H, NH), 8.05 (s, 1H, Ar-H), 7.66 (s, 1H, Ar-H), 7.55 (d, J = 7.7 Hz, 1H, Ar-H), 7.26 (d, J = 7.7 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 135.3, 135.2, 129.1, 126.4, 123.5, 117.4, 115.0, 112.5, 89.9. MS (ESI): 209 (M + H+, 100), 211 (M + H+, 32). These assignments matched with those previously published [110].

5-Methyl-3-thiocyanato-1-H-indole (7c). White amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.00 (s, 1H, NH), 7.94 (d, J = 2.9 Hz, 1H, Ar-H), 7.35 (d, J = 8.2 Hz, 1H, Ar-H), 7.12 (t, J = 8.2 Hz, 1H, Ar-H), 6.93 (d, J = 7.1 Hz, 1H, Ar-H), 2.85 (s, 3H, CH3). 13C NMR (101 MHz, DMSO-d): δ 137.2, 134.6, 129.9, 125.7, 123.4, 123.0, 114.3, 111.3, 89.8, 19.2. MS (ESI): 189 (M + H+, 100). These assignments matched with those previously published [111].

5-Methoxy-3-thiocyanato-1H-indole (7d). White amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H, NH), 7.67 (d, J = 8.7 Hz, 1H, Ar-H), 7.40 (d, J = 2.7 Hz, 1H, Ar-H), 6.97 (dd, J = 8.7, 2.1 Hz, 1H, Ar-H), 6.90 (d, J = 2.1 Hz, 1H, Ar-H), 3.86 (s, 3H, OCH3). 13C NMR (101 MHz, CDCl3): δ 157.7, 136.9, 129.8, 121.8, 119.5, 112.1, 111.9, 95.2, 92.3, 55.7. MS (ESI): 205 (M + H+, 100). These assignments matched with those previously published [109].

3-Thiocyanato-1-H-indole-5-carbonitrile (7e). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.52 (s, 1H, NH), 8.23 (d, J = 2.6 Hz, 1H, Ar-H), 8.21 (s, 1H, Ar-H), 7.71 (d, J = 8.5 Hz, 1H, Ar-H), 7.64 (dd, J = 8.6, 2.6 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 143.4, 141.1, 132.5, 130.9, 128.6, 125.1, 119.5, 117.2, 108.7, 96.8. MS (ESI): 200 (M + H+, 100). These assignments matched with those previously published [110].

5-Nitro-3-thiocyanato-1-H-indole (7f). Yellow amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 12.63 (s, 1H, NH), 8.51 (d, J = 1.8 Hz, 1H, Ar-H), 8.27 (s, 1H, Ar-H), 8.12 (dd, J = 9.0, 1.8 Hz, 1H, Ar-H), 7.70 (d, J = 9.0 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO-d): δ 142.6, 140.0, 137.5, 127.3, 118.6, 114.8, 114.1, 112.4, 93.6. MS (ESI): 220 (M + H+, 100). These assignments matched with those previously published [110].

4-Methyl-3-thiocyanato-1-H-indole (7g). White amorphous solid. 1H NMR (400 MHz, DMSO-d): δ 11.91 (s, 1H, NH), 7.92 (d, J = 2.9 Hz, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 7.43 (d, J = 8.3 Hz, 1H, Ar-H), 7.10 (dd, J = 8.3, 1.1 Hz, 1H, Ar-H), 2.45 (s, 3H, CH3). 13C NMR (101 MHz, DMSO-d): δ 135.1, 133.5, 130.5, 128.2, 125.0, 117.7, 113.0, 112.8, 89.0, 21.6. MS (ESI): 189 (M + H+, 100). These assignments matched with those previously published [110].

3-Thiocyanato-1H-pyrrolo[2,3-b]pyridine (7h). White amorphous solid. 1H NMR (400 MHz, DMSO): δ 12.62 (s, 1H, NH), 8.40 (d, J = 4.5 Hz, 1H, Ar-H), 8.18 (s, 1H, Ar-H), 8.13 (d, J = 7.8 Hz, 1H, Ar-H), 7.31 (dd, J = 7.8, 4.7 Hz, 1H, Ar-H). 13C NMR (101 MHz, DMSO): δ 148.8, 145.0, 134.4, 127.0, 120.3, 117.8, 112.6, 89.5. MS (ESI): 176 (M + H+, 100). These assignments matched with those previously published [112].

3-(Phenylselanyl)-1H-indole (9a). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.43 (s, 1H, NH), 7.69 (d, J = 7.9 Hz, 1H, Ar-H), 7.49 (d, J = 2.5 Hz, 1H, Ar-H), 7.46 (d, J = 8.2 Hz, 1H, Ar-H), 7.33–7.27 (m, 3H, Ar-H), 7.24–7.12 (m, 4H, Ar-H). 13C NMR (101 MHz, CDCl3): δ 136.4, 133.9, 131.3, 130.0, 129.0, 128.7, 125.6, 123.0, 120.9, 120.4, 111.4, 98.2. MS (ESI): 274 (M + H+, 100). These assignments matched with those previously published [30].

2-Methyl-3-(phenylselanyl)-1H-indole (9b). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.20 (s, 1H, NH), 7.64 (d, J = 7.7 Hz, 1H, Ar-H), 7.36 (d, J = 7.9 Hz, 1H, Ar-H), 7.26 (dd, J = 3.5, 1.4 Hz, 1H, Ar-H), 7.23 (dd, J = 3.5, 1.4 Hz, 2H, Ar-H), 7.20 (d, J = 4.1 Hz, 1H, Ar-H), 7.19–7.12 (m, 3H, Ar-H), 2.56 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 141.0, 135.8, 134.0, 131.3, 129.0, 128.4, 125.5, 122.2, 120.7, 119.8, 110.6, 96.2, 13.2. MS (ESI): 288 (M + H+, 100). These assignments matched with those previously published [113].

5-Methyl-3-(phenylselanyl)-1H-indole (9c). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.30 (s, 1H, NH), 7.51 (d, J = 0.5 Hz, 1H, Ar-H), 7.44 (d, J = 2.5 Hz, 1H, Ar-H), 7.35 (d, J = 8.3 Hz, 1H, Ar-H), 7.31–7.28 (m, 2H, Ar-H), 7.22–7.14 (m, 4H, Ar-H), 2.49 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3): δ 134.7, 134.1, 131.5, 130.4, 130.3, 129.0, 128.6, 125.6, 124.7, 119.9, 111.1, 97.4, 21.5. MS (ESI): 288 (M + H+, 100). These assignments matched with those previously published [32].

5-Methoxy-3-(phenylselanyl)-1H-indole (9d). Yellow amorphous solid. 1H NMR (400 MHz, CDCl3): δ 8.42 (s, 1H, NH), 7.44 (d, J = 2.5 Hz, 1H, Ar-H), 7.33 (d, J = 8.8 Hz, 1H, Ar-H), 7.30 (dd, J = 8.2, 1.5 Hz, 1H, Ar-H), 7.29 (s, 1H, Ar-H), 7.21–7.13 (m, 4H, Ar-H), 6.97 (dd, J = 8.8, 2.5 Hz, 1H, Ar-H), 3.85 (s, 3H, OCH3). 13C NMR (101 MHz, CDCl3): δ 155.1, 134.0, 132.0, 131.4, 130.8, 129.1, 128.5, 125.6, 113.5, 112.4, 101.6, 97.5, 55.9. MS (ESI): 304 (M + H+, 100). These assignments matched with those previously published [113].

4. Conclusions

In summary, we have developed a practical GO-promoted and transition metal-free light induced methodology for the construction of a carbon-chalcogen (S and Se) bond that provides 3-chalcogenyl indoles in good to excellent yields under open air. The key features of this simple and robust protocol are: (1) metal-free and iodine-free conditions; (2) easy-to-handle oxidant; (3) open to the air; (4) atom-economic; (5) performed on a gram-scale; (6) regioselective; and (7) applicable to different sources of organochalcogenides with substituted indoles for this transformation. Moreover, very few methods report the combination of GO and light which works in synergy to efficiently promote the organic reactions [83].