S1

Supplementary Information

Selenium Dioxide-promoted Selective Synthesis of Mono- and Bis-sulfenylindoles Samuel Thurow,a Filipe Penteado,a Gelson Perin,a Diego Alves,a Claudio Santi,b Bonifacio Monti,b Carl H. Schiesser,*c Thiago Barcellosd and Eder J. Lenardão*a

a Laboratory of Clean Organic Synthesis - LASOL – Universidade Federal de Pelotas - UFPel - P.O. Box 354, 96010-900, Pelotas, RS - Brazil. E-mail: lenardao@ufpel.edu.br (EJL)b Department of Pharmaceutical Sciences - University of Perugia - Via del Liceo, 1, Perugia (PG), Italy.c Seleno Therapeutics Pty. Ltd, Brighton East, Victoria, 3187, Australia. E-mail: carl@selenotherapeutics.com.d Laboratory of Biotechnology of Natural and Synthetic Products - Universidade de Caxias do Sul - UCS, Caxias do Sul, RS - Brazil.

Table of Contents

General Information ................................................................................................................................................S2

Table S1. Preliminary studies on the preparation of 3aa ........................................................................................S2

Figure S1: Reaction time studies for the preparation of 3aa...................................................................................S3

Table S2: Studies on the solvent effect during the formation of mono-sulfenylindole 3aa ....................................S3

Control Experiments ................................................................................................................................................S3

Procedure #1 .......................................................................................................................................................S3

Procedure #2 .......................................................................................................................................................S4

Procedure #3 .......................................................................................................................................................S4

Procedure #4 .......................................................................................................................................................S4

Procedure #5 .......................................................................................................................................................S4

Procedure #6 .......................................................................................................................................................S4

Procedure #7 .......................................................................................................................................................S4

Mechanistic studies through monitoring short-live intermediates by HRMS..........................................................S5

General Procedure for the Synthesis of the 3-(thioaryl)-1H-indoles 3 ....................................................................S7

General Procedure for the Synthesis of the 2,3-bis(thioaryl)-1H-indoles 4.............................................................S7

Supporting Information References ......................................................................................................................S12

Selected Spectra ....................................................................................................................................................S13

Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2018

S2

General Information

The reactions were monitored by TLC on Merk silica gel (60 F254) visualized with UV light or with 5% of vanillin in 10% H2SO4 with heating. Merck silica gel (particle size 0.040-0.063 mm) was used for flash chromatography. 1H NMR spectra were obtained at 400 MHz on a Bruker DPX 400 spectrometer. The spectra were recorded in CDCl3. Chemical shifts are reported in ppm, referenced against tetramethylsilane (TMS) as the internal standard. 1H coupling patterns are described as singlet (s), doublet (d), triplet (t) and multiplet (m). Coupling constants (J) are reported in Hz. 13C NMR spectra were obtained at 100 MHz on the above-mentioned instrument. The chemical shifts are reported in ppm, referenced to the solvent peak (CDCl3). Low-resolution mass spectra were obtained on a Shimadzu GC-MS-QP2010 mass spectrometer. GC analyses were performed using a RESTEC RTX-5MS capillary column (30m, 0.25 mm id, 0.25 µm film thickness) using products dissolved in ethyl acetate under the following conditions: Injected sample volume, 1.0 µL; flow rate, 54.1 mL/min; initial inlet temperature, 40 oC ramped to 72 oC at 10 oC/min followed by a 5 oC/min ramp to 100 oC (held for 10 min) and 10 oC/min to 280 oC and held for 20 min (total run time: 56.8 min). High-resolution mass spectra were obtained on a Bruker Daltonics micrOTOF-Q II instrument equipped with an ESI and APCI source operating in both positive and negative modes. The samples were dissolved in HPLC-grade acetonitrile and injected into the APCI source by means of a syringe pump at a flow rate of 5.0 µL/min. The Compass 1.3 for micrOTOF-Q II software (Bruker daltonics, USA) was used for data acquisition, processing, and isotopic simulations.

Table S1. Preliminary studies on the preparation of 3aa.a

NH N

H

SPh

NH

SPh

SPhPhSSPhI2, oxidant

glycerol100 °C

1a 2a 3aa 4aa

+ +

aReaction conditions: A mixture of 1a (0.5 mmol), 2a (0.3mmol), SeO2 (20 mol%, 0.011 g), I2 (10 mol%, 0.0076 g), and glycerol (1.0 mL) was stirred at 100 oC and the reaction progress was followed by TLC. cConversion values obtained by GC-MS. c0.01 mL of a 30% w/w H2O2 aqueous solution was added (0.1 mmol). d1.0 mL of 30% w/w aqueous H2O2 solution (10 mmol) was added without additional solvent. e1.0 equiv. (0.055 g) with respect to indole 1a. f0.6 mmol of 2a (1.2 equiv) was added. g0.6 mmol of 2a (2.4 equiv.) was added. hBr2 was used as catalyst in replacement to I2.

Entry Oxidant (20 mol%) I2(mol%) Time(h) % of 3aab % of 4aab

1 - 10 24 57 -2 - - 24 19 -3c H2O2 10 3 76 244d H2O2 10 3 traces -5 SeO2 10 1 84 -6e SeO2 10 1 52 487e,f SeO2 10 1 - 1008g SeO2 10 1 100 -9 SeO2 10h 3 25 -

S3

NH

PhSSPh

SeO2 (30 mol%)I2 (10 mol%)

Glycerol100 °C

NH

SPh

1a 2a 3aa

+

0 2 4 6 8 10 12 14 16 18 200

20

40

60

80

100

Time (min)

Conv

. (%

)

Figure S1: Reaction time studies for the preparation of 3aa. Blue line (♦): 1a, red line (■): 3aa. [1a (0.5mmol), 2a (0.3 mmol), SeO2 (30 mol%, 0.016 g), I2 (10 mol%, 0.0076 g) and glycerol (1.0 mL)].

Table S2: Studies on the solvent effect during the formation of mono-sulfenylindole 3aa.

NH

I2 (10 mol%), SeO2 (30 mol%)

Solvent (1.0 mL), 100 ºC

1a 2aonly product

+ PhSSPhNH

SPh

3aa

Entry Solvent Time for 100% of conversion to 3aaa

1 Glycerol 4 min2 H2O 4 min3 PEG-400 1 h4 DMF 12 min5 THFb 24 h

a Conversion values obtained by GC-MS. b A sealed vial was used.

Control Experiments

Procedure #1

Indole (1a) (0.5 mmol, 0.058 g), SeO2 (0.5 mmol, 0.055 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred for 20 h at 100 °C (oil bath), after which the reaction mixture poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

S4

Procedure #2

Indole (1a) (0.5 mmol, 0.058 g), SeO2 (0.5 mmol, 0.055 g), molecular iodine (10 mol%, 0.05 mmol, 0.0127), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred at 100 °C (oil bath) and followed by TLC. After 15 min, the reaction mixture poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

Procedure #3

3,3'-Di-indolyl selenide (5) (0.25 mmol, 0.0778 g), the diorganyl disulfide 2a (0.3 mmol, 0.0655 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred at 100 °C (oil bath) and followed by TLC. After 1 h, the reaction mixture poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

Procedure #4

Diphenyl disulfide (2a) (0.3 mmol, 0.0655g), indole 1a (0.5 mmol, 0,0586 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred at 100 °C (oil bath) and followed by TLC. After 24 h, the reaction mixture poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

Procedure #5

Diphenyl disulfide (2a) (0.3 mmol, 0.0655g), indole 1a (0.5 mmol, 0,0586 g), SeO2 (30 mol%, 0.015 mmol, 0.0166 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred under argon at 100 °C (oil bath). After 4 min, the reaction mixture was poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

Procedure #6

Diphenyl disulfide (2a) (0.3 mmol, 0.0655g), indole 1a (0.5 mmol, 0,0586 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred under argon on at 100 °C (oil bath). After 24 h, the reaction mixture was poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

Procedure #7

Diphenyl disulfide (2a) (0.3 mmol, 0.0655g), indole 1a (0.5 mmol, 0,0586 g), I2 (0.3 mmol, 0.0761 g), and glycerol (1.0 mL) were added to a round-bottomed flask. The resulting solution was stirred at 100 °C (oil bath). After 4 min, the reaction mixture was poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was then analyzed by GC-MS.

S5

Mechanistic studies through monitoring short-live intermediates by HRMS

For mechanistic studies, the short-live intermediates were analyzed by HRMS. Aliquots which were sampled directly from the reaction experiments and immediately dissolved in MeOH and injected into the ESI or APCI source at a constant flow rate of 3.0 µL/min. The presence of the selenium atom in the intermediates was confirmed its characteristic isotope pattern, which comprises six stable and abundant isotopes. Peaks attributed to intermediates were better detected using the APCI source.

Experimental procedure: Diphenyl disulfide (2a) (0.3 mmol, 0.0655g), indole 1a (0.5 mmol, 0,0586 g), SeO2 (30 mol%, 0.015 mmol, 0.0166 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and water* (1.0 mL), In a 20 mL vial were added respectively. The resulting solution was stirred at 100 °C (oil bath). After 2 min, a 50 µL aliquot was removed with an infusion syringe and immediately dissolved in MeOH and injected into the ESI source. The recorded spectra and expanded regions, including simulated peaks, are displayed below.

*water was used instead glycerol because glycerol self-polymerizes to generate a large number of peaks.

Figure S2. Expanded region between m/z 100 and 450 of the HRMS spectrum (APCI source) obtained from Experiment #1.

Figure S3. Expanded region of the experiment #1 spectra (Figure S2) showing the peak with m/z of 195.9647 attributed to intermediate II (A), and the simulated m/z and isotope pattern for the molecular formula C8H5NSe [M+H]+ (B).

(A)

(B)

N

Se

Hintermediate IIC8H6NSe [M+H]+

Calculated m/z 195.9660

S6

Figure S4. Expanded region of the experiment #1 spectra (Figure S2) showing the peak with m/z of 313.0213 attributed to intermediate 5 (A), and the simulated m/z and isotope pattern for the molecular formula C16H13N2Se [M+H]+ (B).

Figure S5. Expanded region of the experiment #1 spectra (Figure S2) showing the peak with m/z of 421.0256 attributed to intermediate I (A), and the simulated m/z and isotope pattern for the molecular formula C22H17N2SSe [M+H]+ (B).

Figure S6. Expanded region of the experiment #1 spectra (Figure S2) showing the peak with m/z of 226.00671 corresponding to the product 3aa (A), and the simulated m/z and isotope pattern for the molecular formula C14H11NSe [M+H]+ (B).

NH2

S

3aaC14H11NSe [M+H]+

Calculated m/z 195.9660

(A)

(B)

(A)

(B)

(A)

(B)

N NH

Se

Hintermediate 5

C16H13N2Se [M+H]+

Calculated m/z 313.0239

N

Se

NH

PhS

Hintermediate I

C22H17N2SSe [M+H]+

Calculated m/z 421.0272

S7

General Procedure for the Synthesis of the 3-(Thioaryl)-1H-indoles 3

The diorganyl disulfide 2a-j (0.3 mmol), indole 1a-c (0.5 mmol), SeO2 (30 mol%, 0.15 mmol, 0.0166 g), I2 (10 mol%, 0.03 mmol, 0.0076 g), and glycerol (1 mL) were added to a round-bottomed flask. The resulting solution was stirred at 100 °C (oil bath) for the time indicated in Table 2, after which the reaction mixture was poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by silica-gel chromatography column with hexane/ethyl acetate as the eluent.

General Procedure for the Synthesis of the 2,3-bis(thioaryl)-1H-indoles 4

The diorganyl disulfide 2a-g (0.6 mmol), indole 1a-c (0.5 mmol), SeO2 (60 mol%, 0.3 mmol, 0.0333 g), I2 (10 mol%, 0.06 mmol, 0.0152 g), and glycerol (1 mL) were added to a round-bottomed flask. The resulting mixture was stirred at 100 °C (oil bath) for the time indicated in Table 4, after which the reaction mixture was poured into water (20 mL), extracted with ethyl acetate (3 x 10 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by silica-gel chromatography column with hexane/ethyl acetate as the eluent.

NH

S

3-(Phenylthio)-1H-indole (3aa):1 Yield: 0.191 g (85%); Brown solid; mp 149-151 °C (Lit.1: 150-151 °C). 1H NMR (400 MHz, CDCl3) δ 11.02 (s, 1H), 7.55 - 7.41 (m, 3H), 7.17 (t, J = 7.4 Hz, 1H), 7.14 - 7.02 (m, 5H), 6.99 (t, J = 7.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 138.7, 136.0, 130.6, 128.1, 127.6, 124.7, 123.6, 121.3, 119.2, 117.9, 111.2, 99.6. MS (relativeintensity) m/z: 225 (100), 193 (19), 148 (9), 121 (8), 89 (4), 77 (13), 63 (3).

NH

S

3-(p-Tolylthio)-1H-indole (3ab):1 Yield: 0.0905 g (76%); Beige solid; mp 124-126 °C (Lit.1: 123-124°C). 1H NMR (400 MHz, CDCl3) δ8.11 (bs, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.29 - 7.22 (m, 2H), 7.16 - 7.10 (m, 1H), 7.04 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.1 Hz, 2H), 2.13 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 136.4, 135.4, 134.7, 130.4, 129.5, 129.1, 126.3, 122.9, 120.8, 119.6, 111.5, 103.5, 20.7. MS (relative intensity) m/z: 239 (100), 223 (23), 148 (11), 121 (13), 117 (5), 77 (21), 65 (10).

NH

SO

3-((4-Methoxyphenyl)thio)-1H-indole (3ac):1 Yield: 0.1036 g (84%); Brown solid; mp 111-113°C (Lit.1: 112-114 °C). 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.57 – 7.46 (m, 1H), 7.32 – 7.20 (m, 2H), 7.14 (t, J = 8.0 Hz, 1H), 7.08 – 6.96 (m, 3H), 6.64 (d, J = 8.8 Hz, 2H), 3.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 157.8, 136.4, 130.0, 129.5,

S8

129.00, 128.6, 122.9, 120.7, 119.6, 114.5, 111.5, 104.6, 55.3. MS (relative intensity) m/z: 255 (100), 240 (42), 223 (16), 148 (6), 139 (4), 89 (4), 77(10), 63 (6).

NH

SF

3-((4-Fluorophenyl)thio)-1H-indole (3ad):1 Yield: 0.086 g (71%); Beige solid; mp 134-137 °C (Lit.1: 133-134 °C). 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1H), 7.63 (dd, J = 7.9, 1.1 Hz, 1H), 7.47 (d, J = 2.6 Hz, 1H), 7.44 (dt, J = 8.2, 0.9 Hz, 1H), 7.32 - 7.25 (m, 1H), 7.23 - 7.17 (m, 1H), 7.15 - 7.08 (m, 2H), 6.93 - 6.85 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 160.9 (d, J1(C-F) = 244.1 Hz), 136.5, 134.0 (d, J4(C-F) = 3.0 Hz), 130.5, 128.8, 127.9 (d, J3(C-F) = 7.9 Hz), 123.1, 120.9, 119.5, 115.7 (d, J2(C-F) = 22.0 Hz), 111.6, 103.3. MS (relative intensity) m/z: 243 (100), 211 (29), 183 (11), 148 (15), 121 (17), 89 (7), 77 (16), 63 (6), 45 (9).

NH

SCl

3-((4-Chlorophenyl)thio)-1H-indole (3ae):1 Yield: 0.086 g (67%); Yellow solid; mp 135-137 °C (Lit.1: 134-135 °C). 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.63 (dd, J = 7.8, 0.9 Hz, 1H), 7.49 (d, J = 2.6 Hz, 1H), 7.47 (dt, J = 8.2, 0.9 Hz, 1H), 7.35 - 7.30 (m, 1H), 7.25 - 7.20 (m, 1H), 7.18 - 7.14 (m, 2H), 7.11 - 7.02 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 137.8, 136.4, 130.7, 130.5, 128.7, 128.7, 127.1, 123.2, 121.0, 119.4, 111.6, 102.3. MS (relative intensity) m/z: 259 (100), 224 (66), 148 (23), 121 (19), 111 (32), 77 (31), 63 (12), 45 (17).

NH

SBr

3-((4-Bromophenyl)thio)-1H-indole (3af):2 Yield: 0.0345 g (23%); Orange solid; mp 141-144 °C(Lit.2: 144-146 °C). 1H NMR (400 MHz, CDCl3) δ 10.91 (s, 1H), 7.50 - 7.42 (m, 3H), 7.25 - 7.14 (m, 3H), 7.07 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 138.5, 136.3, 131.0, 130.7, 128.1, 126.6, 121.7, 119.6, 118.1, 117.1, 111.5, 99.4. MS (relative intensity) m/z: 305 (75), 224 (100), 148 (34), 89 (15), 77 (41), 45 (23).

NH

S

H2N

2-((1H-Indol-3-yl)thio)aniline (3ag):2 Yield: 0.0797 g (66%); Black solid; mp 94-97 °C (Lit.2: 93-94 °C). 1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.35 - 7.28 (m, 2H), 7.28 - 7.21 (m, 2H), 7.21 – 7.15 (m, 1H), 7.04 (td, J = 7.9, 1.5 Hz, 1H), 6.70 (dd, J = 8.0, 1.3 Hz, 1H), 6.65 (td, J = 7.5, 1.3 Hz, 1H), 4.19 (s, 2H). 13C NMR

S9

(100 MHz, CDCl3) δ 145.6, 136.3, 131.9, 129.0, 128.7, 128.0, 122.8, 120.8, 120.6, 119.3, 118.9, 115.4, 111.5, 104.1. MS (relative intensity) m/z: 240 (100), 223 (16), 148 (8), 117(71), 90 (14), 77 (12), 45 (5).

NH

S OH

2-((1H-Indol-3-yl)thio)ethanol (3ah): Yield: 0.140 g (93%); Yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.78 - 7.72 (m, 1H), 7.36 - 7.31 (m, 1H), 7.29 - 7.14 (m, 3H), 3.62 (t, J = 5.9 Hz, 2H), 2.85 (t, J = 5.9 Hz, 2H), 2.31 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 136.4, 129.9, 129.2, 122.8, 120.6, 119.1, 111.6, 104.1, 60.5, 39.1. MS (relative intensity) m/z: 302 (92), 282 (13), 145 (12), 78 (100), 51 (56). HRMS (APCI-TOF) m/z: calculated for C10H11NOS [M+H]+ 194.0634, found 194.0634.

NH

S

3-(Benzylthio)-1H-indole (3ai):2 Yield: 0.100 g (84%); Orange solid; mp 79-81 °C (Lit.2: 84-85 °C). 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.69 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 7.4 Hz, 1H), 7.23 - 7.13 (m, 5H), 7.06 - 7.042 (m, 2H), 6.91 (d, J = 2.6 Hz, 1H), 3.84 (s, 2H). 13C NMR (100 MHz, CDCl3) δ138.9, 136.1, 129.8, 129.1, 128.9, 128.1, 126.7, 122.5, 120.4, 119.2, 111.4, 105.0, 40.9. MS (relative intensity) m/z: 239 (78), 206 (18), 148 (100), 121 (10), 104 (8), 91 (92), 77 (16).

NH

S

O

3-((Furan-2-ylmethyl)thio)-1H-indole (3aj): Yield: 0.072 g (31%); Brown solid; mp 77-79 °C. 1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.31 - 7.24 (m, 2H), 7.22 - 7.12 (m, 2H), 7.07 (d, J = 2.5 Hz, 1H), 6.26 - 6.09 (m, 1H), 5.86 (d, J = 3.1 Hz, 1H), 3.85 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 152.1, 141.8, 136.3, 130.0, 129.3, 122.7, 120.5, 119.3, 111.4, 110.3, 107.6, 105.5, 33.5. MS (relative intensity) m/z: 229 (16), 196 (10), 148 (29), 121 (8), 81 (100), 77 (16), 53 (11). HRMS (APCI-TOF) m/z: calculated for C13H11NOS 230.0634 [M+H]+, found 230.0634.

N

S

1-Methyl-3-(phenylthio)-1H-indole (3ba):1 Yield: 0.076 g (64%); Yellow solid; mp 83-85 °C (Lit.1: 85-87 °C). 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.29 - 7.22 (m, 2H), 7.17 - 7.05 (m, 5H), 7.03 - 6.97 (m, 1H), 3.74 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.6, 137.5, 135.0, 129.8, 128.6, 125.7, 124.6, 122.5, 120.4, 119.7, 109.7, 100.5, 33.0. MS (relative intensity) m/z: 239 (100), 224 (18), 162 (10), 128 (4), 91 (2), 77 (13).

S10

NH

SBr

5-Bromo-3-(phenylthio)-1H-indole (3ca):1 Yield: 0.075 g (52%); White solid; mp 121-123°C (Lit.1: 121-123 °C). 1H NMR (400 MHz, CDCl3) δ 8.39 (bs, 1H), 7.74 (d, J = 1.8 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.32 (dd,J = 8.6, 1.8 Hz, 1H), 7.27 - 7.22 (m, 1H), 7.16 (dd, J = 8.1, 6.9 Hz, 2H), 7.10 - 7.03 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 138.7, 135.1, 131.8, 130.9, 128.8, 126.1, 125.9, 125.0, 122.2, 114.4, 113.1, 102.8. MS (relative intensity) m/z: 305 (100), 224 (91), 191 (21), 165 (9), 88 (4), 77 (9).

NH

S

S

2,3-Bis(phenylthio)-1H-indole (4aa):3 Yield: 0.1421 g (85%); Yellow oil. 1H NMR (400 MHz, CDCl3) δ 10.45 (s, 1H), 7.55 (s, 1H), 7.37 (s, 1H), 7.31 - 6.92 (m, 12H). 13C NMR (100 MHz, CDCl3) δ 138.1, 137.3, 135.4, 132.5, 129.6, 128.9, 128.4, 128.4, 126.3, 126.2, 124.7, 123.3, 120.5, 119.4, 111.6, 108.9. MS (relative intensity) m/z: 333 (54), 254 (3), 224 (100), 197 (4), 146 (5), 121 (6), 77 (8).

NH

S

S

2,3-Bis(p-tolylthio)-1H-indole (4ab):3 Yield: 0.135 g (75%); Orange oil. 1H NMR (400 MHz, CDCl3) δ 8.28 (bs, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.32 - 7.23 (m, 4H), 7.22 - 7.16 (m, 1H), 7.15 - 7.06 (m, 4H), 7.02 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 137.6, 136.7, 134.8, 134.4, 130.5, 130.2, 130.1, 130.1, 129.4, 127.0, 123.4, 121.0, 119.7, 110.9, 108.5, 20.9, 20.8. MS (relative intensity) m/z: 361 (67), 238 (100), 223 (86), 205 (16), 121 (5), 91 (7), 65 (10), 40 (6). HRMS (APCI-TOF) m/z: calculated for C22H18NS2 [M + H]+ 362.1032, found 362.1032.

NH

S

S

O

O

2,3-Bis((4-methoxyphenyl)thio)-1H-indole (4ac):4Yield: 0.086 g (44%); Yellow solid; mp 127-130 °C.(Lit.4: 134-137 °C). 1H NMR (400 MHz, CDCl3) δ 8.20 (bs, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.30 - 7.13 (m, 5H), 6.85 (d, J = 8.8 Hz, 2H), 6.79 - 6.73 (m, 2H), 3.81 (s, 3H), 3.76 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 159.8,

S11

157.9, 136.6, 135.5, 133.5, 130.2, 129.3, 128.6, 123.5, 123.2, 121.0, 119.4, 115.1, 114.5, 110.8, 108.0, 55.4, 55.3. MS (relative intensity) m/z: 393 (45), 254 (100), 223 (60), 210 (19), 139 (10), 77 (6).

NH

S

S

F

F

2,3-Bis((4-fluorophenyl)thio)-1H-indole (4ad):3 Yield: 0.113 g (62%); Brown oil. 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.26 - 7.11 (m, 4H), 7.06 (t, J = 7.3 Hz, 1H), 7.02 - 6.92 (m, 2H), 6.83 (t, J = 8.6 Hz, 2H), 6.74 (t, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ = 162.2 (, J1(C-F) = 248.2 Hz), 161.0 (d, J1(C-F) = 244.8 Hz), 136.7, 133.7, 132.8 (d, J4(C-F) = 3.2 Hz), 132.2 (d, J3(C-F) = 8.3 Hz), 129.8, 129.1 (d, J4(C-F) = 3.3 Hz), 128.7 (d, J3(C-F) = 7.9 Hz), 124.0, 121.3, 119.7, 116.5 (d, J2(C-F) = 22.2 Hz), 115.7 (d, J2(C-F) = 22.1 Hz), 111.2, 109.5. MS (relative intensity) m/z: 369 (52), 272 (3), 242 (100), 146 (7), 120 (8), 102 (8), 75 (7), 45 (2). HRMS (APCI-TOF) m/z: calculated for C20H13F2NS2[M + H]+ 370.0530, found 370.0530.

NH

S

S

Cl

Cl

2,3-Bis((4-chlorophenyl)thio)-1H-indole (4ae): Yield: 0.0782 g (39%); Yellow solid; mp 68-72 °C. 1H NMR (400 MHz, CDCl3) δ 8.36 (bs, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.23 - 7.14 (m, 1H), 7.13 - 6.96 (m, 7H), 6.90 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 136.8, 136.4, 133.4, 132.9, 132.8, 131.0, 130.7, 129.7, 129.4, 128.8, 127.9, 124.3, 121.5, 119.8, 111.3, 109.6. MS (relative intensity) m/z: 401 (19), 258 (19), 223 (100), 178 (4), 120 (6), 102 (6), 75 (7), 69 (3). HRMS (APCI-TOF) m/z: calculated for C20H13Cl2NS2 [M + H]+ 401.9940, found 401.9940.

NH

S

S

Br

Br

2,3-Bis((4-bromophenyl)thio)-1H-indole (4af): Yield: 0.130 g (53%); Beige solid; mp 109-112 °C. 1H NMR (400 MHz, CDCl3) δ 8.45 (bs, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.42 - 7.16 (m, 7H), 7.08 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 137.1, 136.8, 133.6, 132.6, 132.4, 131.7, 130.8, 129.7, 128.2, 124.3, 121.6, 121.3, 119.9, 118.9, 111.3, 109.6. MS (relative intensity) m/z: 491 (3), 303 (3), 255 (4), 223 (100), 146 (4), 120 (4), 76 (5). HRMS (APCI-TOF) m/z: calculated for C20H13Br2NS2 [M + H]+ 491.8906, found 491.8908.

S12

N

S

S

1-Methyl-2,3-bis(phenylthio)-1H-indole (4ba): Yield: 0.171 g (99%); Beige solid. mp 92-94°C. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 1H), 7.47 - 7.37 (m, 2H), 7.29 - 7.14 (m, 8H), 7.14 - 7.07 (m, 3H), 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3) 138.4 (2C), 135.8, 134.2, 129.1, 128.6, 127.3, 126.5, 126.1, 124.9, 123.9, 121.0, 120.3, 111.0, 110.1, 31.0. MS (relative intensity) m/z: 347 (100), 238 (92), 223 (83), 205 (5), 165 (4), 121 (4), 77 (11). HRMS (APCI-TOF) m/z: calculated for C21H17S2N1 [M]+ 347.0802, found: 347.0801.

NH

S

SBr

5-Bromo-2,3-bis(phenylthio)-1H-indole (4ca): Yield: 0.1589 g (77%); Brown solid; mp 151-152 °C. 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.36 (d, J = 8.6 Hz, 1H), 7.28 (dd, J = 8.6, 1.9 Hz, 2H), 7.25 - 7.09 (m, 7H), 7.07 - 6.96 (m, 3H). Missing one signal, N-H. 13C NMR (100 MHz, CDCl3) δ 136.6, 134.9, 133.7, 133.3, 129.8, 127.8, 127.4, 127.1, 125.3, 124.6, 123.7, 119.9, 112.5, 112.3, 106.0. MS (relative intensity) m/z: 413 (23), 303 (4), 255 (5), 223 (100), 207 (10), 119 (4), 77 (5). HRMS (APCI-TOF) m/z: calculated for C20H14BrNS2 [M + H]+ 411.9825, found 411.9824.

Supporting Information References

1 X. Fang, R. Tang, P. Zhong, J. Li, Synthesis, 2009, 4183.2 W. Ge, Y. Wei, Green Chem., 2012, 14, 2066.3 H. Zhang, X. Bao, Y. Song, J. Qu, B. Wang, Tetrahedron, 2015, 71, 8885.4 C. D. Prasad, S. Kumar, M. Sattar, A. Adhikary, S. Kumar, Org. Biomol. Chem., 2013, 11, 8036.

S13

Selected Spectra

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

1.03

5.04

1.11

3.00

0.90

6.97

6.99

7.00

7.04

7.06

7.08

7.10

7.12

7.15

7.17

7.19

7.44

7.46

7.48

7.48

7.50

7.52

11.0

2

6.906.957.007.057.107.157.207.257.307.357.407.457.507.55f1 (ppm)

1.03

5.04

1.11

3.00

6.97

6.99

7.00

7.04

7.06

7.08

7.10

7.12

7.15

7.17

7.19

7.44

7.46

7.48

7.48

7.50

7.52

1H NMR (400 MHz, CDCl3/DMSO) spectrum of 3-(p-tolylthio)-1H-indole (3aa)

-20-100102030405060708090100110120130140150160170180190200210f1 (ppm)

99.6

111.

211

7.9

119.

212

1.3

123.

612

4.7

127.

612

8.1

130.

613

6.0

138.

7

110115120125130135140f1 (ppm)

111.

2

117.

911

9.2

121.

312

3.6

124.

7

127.

612

8.1

130.

6

136.

0

138.

7

13C NMR (100 MHz, CDCl3/DMSO) spectrum of 3-(p-tolylthio)-1H-indole (3aa)

NH

S

3aa

NH

S

3aa

S14

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

2.87

1.89

1.84

1.08

1.09

1.99

1.00

0.83

2.13

6.85

6.87

6.93

6.95

7.02

7.04

7.06

7.10

7.12

7.14

7.16

7.25

7.27

7.51

7.53

8.11

6.46.56.66.76.86.97.07.17.27.37.47.57.67.7f1 (ppm)

1.89

1.84

1.08

1.09

1.99

1.00

6.85

6.87

6.93

6.95

7.02

7.04

7.06

7.10

7.12

7.14

7.16

7.25

7.27

7.51

7.53

1H NMR (400 MHz, CDCl3) spectrum of3-(p-tolylthio)-1H-indole (3ab)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.8

103.

511

1.5

119.

612

0.8

122.

912

6.3

129.

112

9.5

130.

413

4.7

135.

413

6.4

118120122124126128130132134136138f1 (ppm)

119.

612

0.8

122.

9

126.

3

129.

112

9.5

130.

4

134.

713

5.4

136.

4

13C NMR (100 MHz, CDCl3) spectrum of3-(p-tolylthio)-1H-indole (3ab)

NH

S

3ab

NH

S

3ab

S15

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

3.00

2.00

3.39

1.10

2.08

1.01

0.72

3.75

6.75

6.77

7.16

7.18

7.20

7.25

7.27

7.29

7.35

7.37

7.39

7.41

7.43

7.43

7.62

7.64

7.66

7.68

8.32

6.46.56.66.76.86.97.07.17.27.37.47.57.67.7f1 (ppm)

2.00

3.39

1.10

2.08

1.01

6.62

6.65

7.03

7.05

7.07

7.12

7.14

7.16

7.22

7.24

7.26

7.28

7.30

7.31

7.49

7.51

7.53

7.55

1H NMR (400 MHz, CDCl3) spectrum of 3-((4-methoxyphenyl)thio)-1H-indole (3ac)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

55.3

0

104.

6311

1.49

114.

5011

9.59

120.

7212

2.89

128.

6112

8.99

129.

5212

9.96

136.

45

157.

80

115120125130135140f1 (ppm)

111.

49

114.

50

119.

5912

0.72

122.

89

128.

6112

8.99

129.

5212

9.96

136.

45

13C NMR (100 MHz, CDCl3) spectrum of 3-((4-methoxyphenyl)thio)-1H-indole (3ac)

NH

S

3ac

O

NH

S

3ac

O

S16

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

2.07

2.05

1.05

1.16

1.02

0.98

1.00

0.88

5.30

6.86

6.87

6.89

6.91

6.92

7.09

7.10

7.11

7.14

7.14

7.18

7.20

7.22

7.27

7.29

7.31

7.42

7.43

7.43

7.44

7.45

7.45

7.47

7.48

7.62

7.62

7.64

7.64

8.38

6.806.856.906.957.007.057.107.157.207.257.307.357.407.457.507.557.607.65f1 (ppm)

2.07

2.05

1.05

1.16

1.02

0.98

1.00

6.86

6.87

6.89

6.91

6.92

7.09

7.10

7.11

7.14

7.14

7.18

7.20

7.22

7.27

7.29

7.31

7.42

7.43

7.43

7.44

7.45

7.45

7.47

7.48

7.62

7.62

7.64

7.64

1H NMR (400 MHz, CDCl3) spectrum of 3-((4-fluorophenyl)thio)-1H-indole (3ad)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

103.

3311

1.61

115.

5911

5.81

119.

4712

0.94

123.

1012

7.83

127.

9112

8.82

130.

4613

3.96

133.

9913

6.46

159.

6616

2.09

133.6133.8134.0134.2f1 (ppm)

133.

9613

3.99

115.0116.0f1 (ppm)

115.

5911

5.81

127.0127.5128.0f1 (ppm)

127.

8312

7.91

1H NMR (400 MHz, CDCl3) spectrum of 3-((4-fluorophenyl)thio)-1H-indole (3ad)

NH

S

3ad

F

NH

S

3ad

F

S17

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

2.02

2.02

1.06

1.06

1.01

1.01

1.00

0.88

7.05

7.05

7.06

7.07

7.08

7.08

7.14

7.15

7.15

7.17

7.20

7.21

7.22

7.24

7.24

7.30

7.31

7.32

7.33

7.34

7.34

7.45

7.46

7.46

7.47

7.48

7.48

7.49

7.50

7.62

7.62

7.64

7.64

8.42

7.057.107.157.207.257.307.357.407.457.507.557.607.65f1 (ppm)

2.02

2.02

1.06

1.06

1.01

1.01

1.00

7.05

7.05

7.06

7.07

7.08

7.08

7.14

7.15

7.15

7.17

7.20

7.21

7.22

7.24

7.24

7.30

7.31

7.32

7.33

7.34

7.34

7.45

7.46

7.46

7.47

7.48

7.48

7.49

7.50

7.62

7.62

7.64

7.64

1H NMR (400 MHz, CDCl3) spectrum of 3-((4-chlorophenyl)thio)-1H-indole (3ae)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

102.

3411

1.65

119.

4412

1.02

123.

1612

7.07

128.

7112

8.74

130.

5013

0.69

136.

4513

7.77

130.5131.0f1 (ppm)

130.

50

130.

69

128.4128.6128.8129.0f1 (ppm)

128.

7112

8.74

13C NMR (100 MHz, CDCl3) spectrum of 3-((4-chlorophenyl)thio)-1H-indole (3ae)

NH

S

3ae

Cl

NH

S

3ae

Cl

S18

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

2.00

1.13

3.27

3.19

1.09

6.90

6.92

7.05

7.07

7.09

7.16

7.19

7.21

7.44

7.46

7.48

10.9

1

6.86.97.07.17.27.37.47.57.67.7f1 (ppm)

2.00

1.13

3.27

3.19

6.90

6.92

7.05

7.07

7.09

7.16

7.19

7.21

7.44

7.46

7.48

1H NMR (400 MHz, CDCl3/DMSO) spectrum of 3-((4-bromophenyl)thio)-1H-indole (3af)

-20-100102030405060708090100110120130140150160170180190200210f1 (ppm)

99.3

711

1.53

117.

1511

8.12

119.

6412

1.72

126.

5612

8.07

130.

7213

0.98

136.

3013

8.54

120125130135140f1 (ppm)

117.

1511

8.12

119.

6412

1.72

126.

56

128.

07

130.

7213

0.98

136.

30

138.

54

13C NMR (100 MHz, CDCl3/DMSO) spectrum of 3-((4-bromophenyl)thio)-1H-indole (3af)

NH

S

3af

Br

NH

S

3af

Br

S19

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

1.84

1.05

1.00

1.05

1.16

2.21

2.07

1.00

0.93

4.19

6.63

6.63

6.65

6.65

6.67

6.67

6.69

6.69

6.71

6.71

7.02

7.03

7.04

7.04

7.06

7.06

7.16

7.16

7.18

7.20

7.20

7.22

7.23

7.23

7.24

7.25

7.25

7.26

7.26

7.27

7.30

7.31

7.31

7.33

7.70

7.72

8.29

6.56.66.76.86.97.07.17.27.37.47.57.67.77.8f1 (ppm)

1.05

1.00

1.05

1.16

2.21

2.07

1.00

6.65

6.65

6.69

6.69

6.71

6.71

7.04

7.04

7.18

7.20

7.20

7.23

7.23

7.24

7.25

7.25

7.30

7.31

7.31

7.33

7.70

7.72

1H NMR (400 MHz, CDCl3) spectrum of 2-((1H-indol-3-y)thio)aniline (3ag)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

104.

1111

1.54

115.

3711

8.90

119.

3312

0.59

120.

7712

2.78

128.

0012

8.68

129.

0113

1.90

136.

2914

5.56

115120125130f1 (ppm)

115.

37

118.

9011

9.33

120.

5912

0.77

122.

78

128.

0012

8.68

129.

01

131.

90

13C NMR (100 MHz, CDCl3) spectrum of 2-((1H-indol-3-yl)thio)aniline (3ag)

NH

S

3ag

H2N

NH

S

3ag

H2N

S20

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

1.34

2.05

2.05

3.91

1.20

1.00

1.07

2.31

2.83

2.85

2.86

3.61

3.62

3.64

7.15

7.17

7.19

7.20

7.22

7.22

7.24

7.24

7.26

7.27

7.33

7.33

7.34

7.35

7.35

7.74

7.74

7.76

8.44

7.17.27.37.47.77.8f1 (ppm)

3.91

1.20

1.00

7.17

7.19

7.20

7.22

7.22

7.24

7.26

7.27

7.33

7.33

7.34

7.35

7.35

7.74

7.74

7.76

2.62.72.82.93.53.63.73.8f1 (ppm)

2.05

2.05

2.83

2.85

2.86

3.61

3.62

3.64

1H NMR (400 MHz, CDCl3) spectrum of 2-((1H-indol-3-yl)thio)ethanol (3ah)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

39.1

2

60.4

8

104.

1111

1.61

119.

0612

0.62

122.

8112

9.25

129.

8613

6.39

13C NMR (100 MHz, CDCl3) spectrum of 2-((1H-indol-3-yl)thio)ethanol (3ah)

NH

S

3ah

OH

NH

S

3ah

OH

S21

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

2.11

1.00

2.06

5.43

1.03

1.00

0.90

3.84

6.91

6.91

7.04

7.06

7.14

7.17

7.18

7.21

7.22

7.27

7.29

7.68

7.70

7.98

6.76.86.97.07.17.27.37.47.57.67.77.87.98.08.1f1 (ppm)

1.00

2.06

5.43

1.03

1.00

0.90

6.91

6.91

7.04

7.06

7.14

7.17

7.18

7.21

7.22

7.27

7.29

7.68

7.70

7.98

1H NMR (100 MHz, CDCl3) spectrum of 3-(benzylthio)-1H-indole (3ai)

-100102030405060708090100110120130140150160170180190200f1 (ppm)

40.8

9

105.

0111

1.42

119.

1812

0.38

122.

5412

6.68

128.

1412

8.90

129.

1212

9.79

136.

0813

8.94

119120121122123124125126127128129130f1 (ppm)

119.

18

120.

38

122.

54

126.

68

128.

1412

8.90

129.

1212

9.79

13C NMR (100 MHz, CDCl3) spectrum 3-(benzylthio)-1H-indole (3ai)

NH

S

3ai

NH

S

3ai

S22

-3-2-1012345678910111213141516f1 (ppm)

2.00

0.98

1.11

1.13

2.41

1.97

1.04

0.99

3.85

5.86

5.87

6.17

6.17

6.18

7.06

7.07

7.13

7.15

7.17

7.17

7.19

7.20

7.27

7.28

7.29

7.66

7.68

8.07

6.97.07.17.27.37.47.57.67.7f1 (ppm)

1.13

2.41

1.97

1.04

7.06

7.07

7.13

7.15

7.17

7.17

7.19

7.20

7.27

7.28

7.29

7.66

7.68

5.85.96.06.16.2f1 (ppm)

0.98

1.11

5.86

5.87

6.17

6.17

6.18

1H NMR (400 MHz, CDCl3) spectrum of 3-((furan-2-ylmethyl)thio)-1H-indole (3aj)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

33.5

3

105.

4710

7.57

110.

3311

1.40

119.

2812

0.51

122.

6712

9.32

129.

9813

6.30

141.

82

152.

09

13C NMR (100 MHz, CDCl3) spectrum of 3-((furan-2-ylmethyl)thio)-1H-indole (3aj)

NH

S

3aj

O

NH

S

3aj

O

S23

-3-2-1012345678910111213141516f1 (ppm)

2.93

1.05

5.52

2.14

1.12

1.00

3.74

6.98

7.00

7.02

7.07

7.09

7.11

7.13

7.15

7.16

7.24

7.25

7.25

7.27

7.31

7.33

7.59

7.61

6.97.07.17.27.37.47.57.6f1 (ppm)

1.05

5.52

2.14

1.12

1.00

6.98

7.00

7.02

7.07

7.09

7.11

7.13

7.15

7.16

7.24

7.25

7.25

7.27

7.31

7.33

7.59

7.61

1H NMR (400 MHz, CDCl3) spectrum of 1-methyl-3-(phenylthio)-1H-indole (3ba)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

32.9

7

100.

55

109.

6711

9.66

120.

4312

2.50

124.

6212

5.75

128.

5912

9.80

134.

9713

7.51

139.

64

13C NMR (100 MHz, CDCl3) spectrum of 1-methyl-3-(phenylthio)-1H-indole (3ba)

N

S

3ba

N

S

3ba

S24

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

3.33

2.28

1.26

1.11

1.06

1.00

0.99

7.04

7.04

7.06

7.08

7.14

7.16

7.16

7.18

7.23

7.24

7.26

7.31

7.31

7.33

7.33

7.42

7.42

7.74

7.75

8.39

7.07.17.27.37.47.57.77.8f1 (ppm)

3.33

2.28

1.26

1.11

1.06

1.00

7.04

7.04

7.06

7.08

7.14

7.16

7.16

7.18

7.23

7.24

7.26

7.31

7.31

7.33

7.33

7.42

7.42

7.74

7.75

1H NMR (400 MHz, CDCl3) spectrum of 5-bromo-3-(phenylthio)-1H-indole (3ca)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

102.

7711

3.06

114.

4412

2.17

125.

0412

5.92

126.

0712

8.80

130.

9513

1.81

135.

0913

8.66

124125126127f1 (ppm)

125.

04

125.

9212

6.07

13C NMR (100 MHz, CDCl3) spectrum of 5-bromo-3-(phenylthio)-1H-indole (3ca)

NH

S

3ca

Br

NH

S

3ca

Br

S25

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

11.8

01.

211.

00

0.84

7.00

7.07

7.17

7.37

7.54

10.4

5

1H NMR (400 MHz, CDCl3) spectrum of 2,3-bis(phenylthio)-1H-indole (4aa)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

108.

8611

1.56

119.

4512

0.55

123.

3412

4.67

126.

1912

6.30

128.

3712

8.39

128.

9012

9.56

132.

5213

5.38

137.

2613

8.15

126.0126.5f1 (ppm)

126.

19

126.

30

128.0128.2128.4128.6128.8f1 (ppm)

128.

3712

8.39

13C NMR (100 MHz, CDCl3) spectrum of 2,3-bis(phenylthio)-1H-indole (4aa)

NH

S

4aa

S

NH

S

4aa

S

S26

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)

3.44

2.91

2.30

4.47

1.20

4.31

1.00

0.92

2.31

2.36

7.01

7.03

7.11

7.14

7.17

7.19

7.20

7.21

7.24

7.26

7.28

7.30

7.65

7.67

8.28

6.97.07.17.27.37.47.57.67.77.8f1 (ppm)

2.30

4.47

1.20

4.31

1.00

7.01

7.03

7.11

7.14

7.17

7.19

7.20

7.21

7.24

7.26

7.28

7.30

7.65

7.67

2.22.32.4f1 (ppm)

3.44

2.91

2.31

2.36

1H NMR (400 MHz, CDCl3) spectrum of 2,3-bis(p-tolylthio)-1H-indole (4ab)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

20.7

920

.95

108.

4711

0.95

119.

6212

0.97

123.

4112

6.96

129.

4113

0.06

130.

1113

0.19

130.

5513

4.43

134.

8213

6.70

137.

59

20.521.021.5129.0129.5130.0130.5131.0f1 (ppm)

20.7

920

.95

129.

41

130.

0613

0.11

130.

1913

0.55

13C NMR (100 MHz, CDCl3) spectrum of 2,3-bis(p-tolylthio)-1H-indole (4ab)

NH

S

4ab

S

NH

S

4ab

S

S27

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.5f1 (ppm)

3.00

2.64

2.10

1.77

5.34

1.84

0.83

0.74

3.76

3.81

6.75

6.78

6.84

6.86

7.16

7.18

7.20

7.22

7.24

7.26

7.29

7.36

7.38

7.62

7.64

8.20

6.57.07.5f1 (ppm)

2.10

1.77

5.34

1.84

0.83

6.75

6.78

6.84

6.86

7.16

7.18

7.20

7.22

7.24

7.26

7.29

7.36

7.38

7.62

7.64

1H NMR(400 MHz, CDCl3) spectrum of 2,3-bis((4-methoxyphenyl)thio)-1H-indole (4ac)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

55.2

755

.35

108.

0411

0.82

114.

4711

5.13

119.

4212

0.96

123.

1712

3.48

128.

5812

9.31

130.

2213

3.54

135.

4813

6.55

157.

9515

9.80

108110112114116118120122124126128130132134136138f1 (ppm)

108.

04

110.

82

114.

4711

5.13

119.

42

120.

96

123.

1712

3.48

128.

5812

9.31

130.

22

133.

54

135.

4813

6.55

13C NMR(100 MHz, CDCl3) spectrum of 2,3-bis((4-methoxyphenyl)thio)-1H-indole (4ac)

NH

S

4ac

S

O

O

NH

S

4ac

S

O

O

S28

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.5f1 (ppm)

2.00

2.01

2.02

1.07

4.15

1.00

0.93

6.72

6.74

6.76

6.81

6.83

6.85

6.97

6.98

6.99

7.00

7.04

7.06

7.08

7.13

7.15

7.17

7.20

7.22

7.47

7.49

8.30

6.46.56.66.76.86.97.07.17.27.37.47.57.67.77.8f1 (ppm)

2.00

2.01

2.02

1.07

4.15

1.00

6.72

6.74

6.76

6.81

6.83

6.85

6.97

6.98

6.99

7.00

7.04

7.06

7.08

7.13

7.15

7.17

7.20

7.22

7.47

7.49

1H NMR (400 MHz, CDCl3) spectrum of 2,3-bis((4-fluorophenyl)thio)-1H-indole (4ad)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

109.

4611

1.19

115.

6311

5.85

116.

3711

6.59

119.

7012

1.34

123.

9612

8.73

128.

8112

9.06

129.

0912

9.82

132.

1613

2.24

132.

8313

2.86

133.

6613

6.73

159.

8716

1.04

162.

3016

3.51

110115120125130135f1 (ppm)

109.

46

111.

19

115.

6311

5.85

116.

3711

6.59

119.

70

121.

34

123.

96

128.

7312

8.81

129.

0612

9.09

129.

8213

2.16

132.

2413

2.83

132.

8613

3.66

136.

73

13C NMR (100 MHz, CDCl3) spectrum of 2,3-bis((4-fluorophenyl)thio)-1H-indole (4ad)

NH

S

4ad

S

F

F

NH

S

4ad

S

F

F

S29

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.5f1 (ppm)

2.03

7.26

1.12

1.03

1.00

0.93

6.89

6.91

6.98

6.99

7.01

7.05

7.06

7.08

7.10

7.10

7.11

7.15

7.17

7.17

7.19

7.19

7.21

7.21

7.24

7.26

7.47

7.49

8.36

6.97.07.17.27.37.47.5f1 (ppm)

2.03

7.26

1.12

1.03

1.00

6.89

6.91

6.99

7.01

7.05

7.06

7.08

7.10

7.10

7.11

7.15

7.17

7.17

7.19

7.19

7.21

7.21

7.24

7.26

7.47

7.49

1H NMR (400 MHz, CDCl3) spectrum of 2,3-bis((4-chlorophenyl)thio)-1H-indole (4ae)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

109.

5711

1.32

119.

8312

1.51

124.

2712

7.86

128.

7912

9.43

129.

7313

0.66

131.

0513

2.78

132.

8813

3.37

136.

4213

6.83

127128129130131132133134135136137138f1 (ppm)

127.

8612

8.79

129.

4312

9.73

130.

6613

1.05

132.

7813

2.88

133.

37

136.

4213

6.83

13C NMR (100 MHz, CDCl3) spectrum of 2,3-bis((4-chlorophenyl)thio)-1H-indole (4ae)

NH

S

4ae

S

Cl

Cl

NH

S

4ae

S

Cl

Cl

S30

-3-2-1012345678910111213141516f1 (ppm)

2.01

1.99

7.34

1.00

0.89

6.93

6.95

7.07

7.09

7.18

7.20

7.24

7.26

7.30

7.33

7.35

7.38

7.58

7.60

8.45

6.97.07.17.27.37.47.57.6f1 (ppm)

2.01

1.99

7.34

1.00

6.93

6.95

7.07

7.09

7.18

7.20

7.24

7.26

7.30

7.33

7.35

7.38

7.58

7.60

1H NMR (400 MHz, CDCl3) spectrum of 2,3-bis((4-bromophenyl)thio)-1H-indole (4af)

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

109.

6011

1.32

118.

8711

9.86

121.

2912

1.56

124.

3212

8.16

129.

7313

0.85

131.

7013

2.36

132.

6313

3.60

136.

8513

7.12

110115120125130135140f1 (ppm)

109.

60

111.

32

118.

8711

9.86

121.

2912

1.56

124.

32

128.

1612

9.73

130.

8513

1.70

132.

3613

2.63

133.

60

136.

8513

7.12

13C NMR (100 MHz, CDCl3) spectrum of 2,3-bis((4-bromophenyl)thio)-1H-indole (4af)

NH

S

4af

S

Br

Br

NH

S

4af

S

Br

Br

S31

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)

2.95

3.07

8.43

1.10

1.05

1.01

3.83

7.06

7.07

7.08

7.09

7.11

7.11

7.14

7.15

7.16

7.17

7.19

7.21

7.24

7.26

7.26

7.37

7.39

7.41

7.42

7.44

7.72

7.74

7.17.27.37.47.57.67.77.8f1 (ppm)

3.07

8.43

1.10

1.05

1.01

7.06

7.07

7.08

7.09

7.11

7.11

7.14

7.15

7.16

7.17

7.19

7.21

7.24

7.26

7.26

7.37

7.39

7.41

7.42

7.44

7.72

7.74

1H NMR (400 MHz, CDCl3) spectrum of 1-methyl-2,3-bis(phenylthio)-1H-indole (4ba)

-100102030405060708090100110120130140150160170180190200f1 (ppm)

31.0

4

110.

1411

1.02

120.

3112

1.02

123.

9312

4.94

126.

1312

6.54

127.

3412

8.59

129.

1213

4.23

135.

7713

8.43

138.

45

138.4138.5138.6f1 (ppm)

138.

4313

8.45

110112114116118120122124126128130132f1 (ppm)

110.

1411

1.02

120.

3112

1.02

123.

9312

4.94

126.

1312

6.54

127.

3412

8.59

129.

12

13C NMR (100 MHz, CDCl3) spectrum of 1-methyl-2,3-bis(phenylthio)-1H-indole (4ba)

N

S

4ba

S

N

S

4ba

S

S32

-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)

3.04

7.12

1.09

1.10

1.00

7.00

7.02

7.03

7.05

7.11

7.13

7.15

7.18

7.19

7.20

7.22

7.24

7.26

7.27

7.28

7.29

7.35

7.37

7.59

6.97.07.17.27.37.47.57.6f1 (ppm)

3.04

7.12

1.09

1.10

1.00

7.00

7.02

7.03

7.05

7.11

7.13

7.15

7.18

7.19

7.20

7.22

7.24

7.26

7.27

7.28

7.29

7.35

7.37

7.59

1H NMR (400 MHz, CDCl3/DMSO) spectrum of 5-bromo-2,3-bis(phenylthio)-1H-indole (4ca)

-20-100102030405060708090100110120130140150160170180190200210f1 (ppm)

106.

0311

2.35

112.

5111

9.90

123.

6912

4.65

125.

2712

7.11

127.

3612

7.79

129.

8513

3.27

133.

7013

4.92

136.

56

112113114122123124125126127128129f1 (ppm)

112.

3511

2.51

123.

69

124.

65

125.

27

127.

1112

7.36

127.

79

13C NMR (100 MHz, CDCl3/DMSO) spectrum of 5-bromo-2,3-bis(phenylthio)-1H-indole (4ca)

NH

S

4ca

SBr

NH

S

4ca

SBr