Manganese(III) Acetate Mediated Synthesis of 3-Arylsulfenylindoles and Evaluation of Their Antibacterial Activity

Among the most important heterocyclic units indole nucleus has received major attention as a key structural building block due to their medicinal and pharmaceutical applications.¹ Further 3-thioindole motifs are very common in various drugs for the treatment of heart disease,² allergies,³ these are also utilized in the field of organic nonlinear optical materials.⁴ The following compounds such as MK-886 (III) is having antitumor activity,⁵ L-737,126 (VII) is identified as a potent anti-HIV agent,⁶ the 3-(arylsulfenyl)indole is able to inhibit human breast cancer cell growth,⁷ vasoconstrictor tinazoline (I) is 4,5-dihydro-2- (3-indolyl) mercaptoimidazole known as a nasal decongestant⁸ and acting as an alpha-adrenergic blocking drug (Figure 1).

Figure 1: Biologically active thioindole derivatives and indole-benzimidazoles Click here to View figure

It is planned to synthesize analogues of tinazoline by replacing the imidazole moiety with benzimidazole because compounds containing benzimidazole have numerous biological activities, for example antitumor⁹ and antiparasitic¹⁰. Although compounds containing both indole-benzimidazoles are known to show diuretic acitivity¹¹ but their complete study is unexplored and hence this work targets to synthesize Compounds containing both indole-benzimidazoles (or benzothiazole ) through C-S bond.

Recently, various methods are reported for the 3-arylthiolation of indoles using the various sulfenylating agents such as buntesalts,¹² disulfides,¹³sulfenyl halides,¹⁴ and N-thioarylphthalimides.¹⁵ Reagents such as Vanadium oxyacetylacetonate,¹⁶ AlCl₃¹⁷,Selectfluor¹⁸, NCS¹⁹,  oxone²⁰, FeF₃²¹, (bis(trifluoroacetoxy)iodo benzene)²²,  Cu²³ and  Iodine²⁴, and CeCl₃³⁰  have been reported under different conditions. Particularly substrates substituted benzimidazolethiol and benzothiazolethiol were unexplored in the 3-arylthiolation. Therefore, the development of a simple, convenient and general methodology for the sulfenylation of indoles utilizing a stable and readily available reagent would extend the scope of this reaction and further applications of 3-arylsulfenyl indole products.

Although Mn(OAc)₃ is a good single-electron oxidant, selective,  mild oxidant and commercially available.  Use of Mn(III)acetate  in  C-C bond construction between carbon centered radical with olefins²⁵ and arenes²⁶ was well investigated. But its applications are limited mostly in the field of sulfur-centered free radicals generating from thiols.²⁷ The main advantage in the selection of this reagent is its moderate reactivity thereby is envisioned higher selectivity in the thioarylation.

Table 1: Screening of the Optimal Conditionsa   Click here to View table

 

Table 2: reaction of various indoles with different thiols using Mn (OAc)3. Click here to View table

 

Material and Methods

Initially we conducted reaction between 1H-indole and 1H-benzoimidazole thiol using Mn(OAc)₃and tried to optimize the reaction conditions (Table 1). In the beginning, this reaction is conducted under solvent free conditions followed by preferred solvents such as water and Ethanol. But good results were not observed in the reaction. Then reaction is examined with toluene, acetonitrile, THF, DMF and acetic acid²⁸. Among the different solvents surveyed, better yield was observed with Acetic acid and moderate yield in DMF. Acetic acid is the solvent of choice, because it has a good solubility for Mn(OAc)₃ and also giving higher yields in addition to that it degrades rapidly to harmless substances in the environment.

Results and Discussion

The optimized condition for regeoselectivesulfenylation reaction of indoles consists of using Indole (1.0equiv.), thiol (1.0 equiv.), reagent (2 equiv.) in acetic acid at 80⁰C for 2hours (Table-1, entry 2).With this optimized reaction condition, the scope of the reaction is extended by taking into account various thiols with indole derivatives. As shown in the Table 2, unsubstituted indole with thiol yielded with the required products (85- 90%, entries 1-3),indoles with electron-donating methyl group (88-92%; Table entries 4,5,6,13 & 14) resulted  higher yields in comparison to those having electron-withdrawing groups(72-76%; Table 2, entries 10-12). The reaction is tolerant to bromo substituent on the aromatic ring of indole, and the corresponding target products were obtained in good yields (80-84%; Table 2, entries 7-9). Compounds 2a, 3a,5a, 6a,8a, 9a, 11a and 12a, are existing as a mixture of tautomers.²⁹

Plausible Mechanism

Scheme 2: Mechanism in volved in the arylthiolation of ln doles Click here to View scheme

 

A plausible mechanism^27c  is proposed involving ligand-exchange pathway for the reaction of indole with 1H-benzo[d]imidazole-2-thiol (1b) shown in the Scheme-2. The ligand exchange between Mn(OAc)3 and 1H-benzo[d]imidazole-2-thiol produces the intermediate (IIA), whichgets oxidized to the sulphur centered free radical (IIIA), and then attacks the electron-rich site of indole  i.e. the 3ʹ-position to yield radical (IVA). Subsequently, Mn(OAc)3 oxidizes radical (IVA) to cation (VA) , and finally loses a proton affording 3-arylthiol product (1).

Experimental Section

Chemistry

Melting points were determined in open capillaries and are uncorrected. IR spectra (KBr) were recorded on a Jasco, FT / IR–4100 spectrophotometer. Mass spectras were recorded on Shimadzu, LC-2010EV. 1H NMR and 13C NMR spectra were recorded on JEOL 400MHz and Brukar Avance 300 MHz spectrometer. TMS was used as internal reference. All the analysis data obtained at Sapala Organics Private Limited, Hyderabad.

Materials and Methods

Manganese(III) acetate mono hydrate used for these reactions was purchased from Aldrich. All the other  solvents and raw materials were purchased from common suppliers. Reactions were monitored by thin-layer chromatography (TLC) on silica gel plates (60A˚; Aldrich), visualized under 254 nm ultraviolet Light. Column chromatography separations were performed using silica gel (70–230 mesh) obtained from the Aldrich Company. The solvents used for elution varied depending on the compound and included either one or a combination of hexane and ethylacetate. All reactions were conducted under a nitrogen atmosphere unless otherwise noted.

Typical experimental procedure for the synthesis of Compounds 1-14.

Manganese triacetate (2 mmol) is added portion wise to a pre dissolved solution of Indole (1mmol) and benzimidazolethiol (1mmol) in acetic acid (10mL) at room temperature under Nitrogen atmosphere. The reaction mixture is stirred at 80⁰C for 2hr. After completion of reaction, as monitored by T.L.C analysis, the reaction mixture was quenched by the addition of water 20ml. The organic compounds are extracted with ethyl acetate (3x20ml). The combined layers are dried over anh.Na₂SO₄. The required product is purified by column Chromatography, eluted with 8% methanol in DCM to get the product. The product is confirmed by ¹H, ¹³C, NMR, IR and mass.

2-(1H-indol-3-ylthio)-1H-benzo[d]imidazole (Compound 1)

 90% Yield; m.p. 221⁰C; R_f= 0.750 (Hexane:Ethyl acetate, 60:40, v/v);¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 8.32 – 8.43 (3 H, m), 8.52 (1 H, t, J=7.44 Hz), 8.66 (2 H, br s), 8.79 (1 H, d, J=8.1 Hz), 8.83 – 8.86 (1 H, m), 9.21 (1 H, d, J=3.1 Hz), 13.13 (2 H, br s); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 95.6, 112.3, 118.1, 120.2, 121.2, 121.2, 122.1, 128.8, 133.0, 136.6, 150.9; IR: 3381cm^-1 (N-H); ESI-Mass: m/z 266[M^{. +}+1 peak]; Mol. Formula:C₁₅H₁₁N₃S;

2-(1H-indol-3-ylthio)-6-(difluoromethoxy)-1H-benzo[d]imidazole &   2-(1H-indol-3-ylthio)-5-(difluoromethoxy)-1H-benzo[d]imidazole (Compound 2 as tautomeric mixture of 2a and 2a’)

88% Yield; m.p. 209-211⁰C ⁰C; R_f= 0.77 (Hexane: Ethyl acetate, 60:40, v/v); ¹H NMR (400MHz, DMSO-d₆,25°C) δ 6.90-6.93 (m, 1H), 7.05-7.36(m , 4H), 7.45 -7.52 (d, J = 7.8 Hz, 4H), 7.91 (1 H, d, J = 2.3 Hz), 11.82 (br s, 1H);  ¹³C NMR (100MHz, DMSO-d₆) δ  95.2, 112.3, 113.6, 116.8, 118.0, 120.3, 122.2, 128.7, 133.2, 136.6, 145.7, 202.3; IR: 3411cm^-1 (N-H); ESI-Mass: m/z 332 [M^{. +}+1 peak]. Mol. Formula: C₁₆H₁₁F₂N₃OS

2-(1H-indol-3-ylthio)-6-methoxy-1H-benzo[d]imidazole & 2-(1H-indol-3-ylthio)-5-methoxy-1H-benzo[d]imidazole (compound 3 as tautomeric mixture of 3a and 3a’)

85% Yield; m.p. 219-221⁰C ⁰C; R_f= 0.77 (Hexane: Ethyl acetate, 60:40, v/v);¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 3.71 (s, 3H), 6.68 (dd, J= 8.6, 2.3 Hz, 1H), 6.86 (br s, 1H), 7.07 – 7.11(m, 1H), 7.15 – 7.29 (m, 2H), 7.47 (br d, J = 7.82 Hz, 1H), 7.51 (d, J = 7.83 Hz, 1H), 7.87 (d, J = 2.35 Hz, 1H), 11.78 (br s, 2H); ¹³C NMR(100 MHz, DMSO-d₆) δ ppm 55.3, 96.1, 110.3, 112.2, 118.1, 120.1, 122.1, 128.8, 132.8, 136.6, 155.1; IR: 3363cm^-1 (N-H); ESI-Mass: m/z 296[M^{. +}+1 peak]; Mol. Formula: C₁₆H₁₃N₃OS

2-(7-methyl-1H-indol-3-ylthio)-1H-benzo[d]imidazole (compound 4)

83% yield; m.p. 183⁰C; Rf= 0.49 (Hexane: Ethyl acetate, 70:30, v/v); ¹H NMR(300 MHz, DMSO-d₆, 27°C) δ ppm 2.55 (3 H, s), 6.98 – 7.06 (4 H, m), 7.22 – 7.29 (2 H, m), 7.40 – 7.43 (1 H, m), 7.90 (1 H, d, J=2.7 Hz), 11.77 (1H, s),  – 11.83 (1 H, s); ¹H NMR (300 MHz, CDCl3, 27°C) δ ppm 2.56 (3 H, s), 7.03 – 7.19 (6 H, m), 7.47 – 7.52 (2 H, m), 8.38 (1 H, bs); ¹³C NMR (500 MHz, DMSO-d₆) δ ppm 97.5, 115.5, 118.0, 118.0,  121.5, 121.9, 123.0, 123.9, 126.1, 127.7, 133.5, 154.0, 171.4; ESI-Mass: m/z 280 [M^.++1 peak]; Mol. Formula: C₁₆H₁₃N₃S

2-(7-methyl-1H-indol-3-ylthio)-6-methoxy-1H-benzo[d]imidazole & 2-(7-methyl-1H-indol-3-ylthio)-5-methoxy-1H-benzo[d]imidazole (compound 5 as tautomeric mixture of 5a and 5a’)

90% yield;  m.p. 183⁰C; Rf= 0.6 (Hexane: Ethyl acetate, 70:30, v/v);¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 2.45 (6 H, s), 3.30(6 H, s), 3.66(6 H, s), 3.77(6 H, s), 6.45(1 H, d, J=2 Hz), 6.57(1 H, d, J=2 Hz), 6.57(1 H, d, J=2 Hz), 6.74-6.79 (2H, m),6.83-6.87 (2H, m), 6.97-7.01 (5H, m), 7.16 (1H, d, J=8.8Hz), 7.42-7.47 (2H, m); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 16.7, 55.6, 55.6, 94.7, 94.7, 99.5, 99.7, 109.9, 110.2, 110.3, 110.9, 118.0, 118.1, 119.6, 120.8, 120.9, 122.5, 122.5, 124.9, 126.4, 126.4, 128.2, 128.4, 128.5, 131.6, 134.0, 134.1, 135.1, 156.1, 156.6, 170.1; IR: 3410cm^-1 (N-H); ESI-Mass: m/z 310 [M^{. +}+1 peak]; Mol. Formula: C₁₇H₁₅N₃OS

2-(7-methyl-1H-indol-3-ylthio)-6-(difluoromethoxy)-1Hbenzo[d]imidazole  & 2-(7-methyl-1H-indol-3-ylthio)-5-(difluoromethoxy)-1H-benzo[d]imidazole  (compound 6 as tautomeric mixture of 6a and 6a’)

89% Yield, m.p. 110⁰C, R_f= 0.77 (Hexane: Ethyl acetate, 60:40, v/v); ¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 2.53 – 2.54 (4 H, m), 6.89 – 6.93 (2 H, m), 6.98 – 7.04 (3 H, m), 7.10 (2 H, s), 7.90 (1 H, d, J=3.1 Hz), 11.67 – 12.07 (2 H, m) ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 16.5, 58.2, 95.5, 113.6, 114.3, 115.6, 116.8, 120.5, 121.6, 122.7, 128.5, 132.9, 136.1, 145.7, 152.7; IR: 3402cm^-1 (N-H); ESI Mass:  m/z 346  [M.++1 peak]; Mol. Formula: C₁₇H₁₃F₂N₃OS

2-(5-bromo-1H-indol-3-ylthio)-1H-benzo[d]imidazole (compound 7)

84% yield, m.p. 268-270⁰C, Rf Value 0.86 (10% methanol in DCM); ¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 7.06 -7.08 (2 H, m), 7.30 – 7.35 (3 H, m), 7.47 – 7.49 (1 H, d , J=8.4), 7.57 (1H, d, J=1.6), 7.93 (1H, d, J=2.8), 11.99 (2H, bs); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 95.2, 113.0, 113.7, 116.8, 114.5, 120.2, 124.8, 130.7, 134.8, 135.4, 145.8; IR: 3392cm^-1 (N-H); ESI-Mass: m/z 344 [M^{. +}+1 peak]; Mol. Formula: C₁₅H₁₀BrN₃S

2-(5-bromo-1H-indol-3-ylthio)-5-(difluoromethoxy)-1H-benzo[d]imidazole & 2-(5-bromo-1H-indol-3-ylthio)-6-(difluoromethoxy)-1H-benzo[d]imidazole (compound 8 as tautomeric mixture of 8a and 8a’)

81% Yield, m.p. 240⁰C, Rf =0.51 (in 10% methanol in DCM); ¹H NMR (400 MHz, DMSO-d₆) δ ppm 6.97(1 H, dt, J=5.8, 2.5 Hz), 7.16 (1 H, s), 7.22(1 H, br s), 7.30 – 7.48(3 H, m), 7.55(1 H, d, J=8.6 Hz), 7.63(1 H, d, J=1.5Hz), 8.02(1 H, d, J=2.3Hz), 11.96 – 12.21(2 H, m); ¹H NMR (400 MHz, CD₃OD) δ ppm 6.69(1H, t, 74.4 Hz), 6.91 (1H, d, J=8.8Hz), 6.93 (5H , d , J= 8.8)¹³C NMR (101 MHz, DMSO-d₆) δ ppm 95.6, 112.9, 114.4, 120.2, 121.3, 124.7, 130.8, 134.6, 135.3, 150.38; IR: 3398cm^-1 (N-H); ESI-Mass: m/z 411 [M.⁺+1 peak]; Mol. Formula: C₁₆H₁₀BrF₂N₃OS

2-(5-bromo-1H-indol-3-ylthio)-5-methoxy-1H-benzo[d]imidazole & 2-(5-bromo-1H-indol-3-ylthio)-6-methoxy-1H-benzo[d]imidazole (compound 9 as tautomeric mixture of 9a and 9a’)

80% Yield, m.p. 190⁰C, Rf Value 0.47 (in 10% methanol in DCM), ¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 3.70(3H, s), 6.69(1H, dd, J= 8.8Hz, J=2.4Hz), 6.86 (1H, bs), 7.23(1H, d, J=7.2 Hz), 7.3(1H, dd, J=8.4, J=3.2 Hz), 7.47(1H, d, J=7.2 Hz), 7.57 (1H, s), 7.91 (1H, d, J=2.8Hz), 11.82 (1H, s), 11.95(1H, s);  ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 55.3, 95.2, 96.0, 106.0, 110.4, 112.9, 114.4, 120.2, 124.7, 130.7, 134.4, 135.3, 155.1; IR: 3389cm^-1 (N-H); ESI mass: m/z 373[M.⁺+1 peak]; Mol. Formula: C₁₆H₁₂BrN₃OS

methyl 3-(1H-benzo[d]imidazol-2-ylthio)-1H-indole-4-carboxylate (compound 10)

76%Yield, m.p. 240⁰C, Rf Value 0.54(in 10% methanol in DCM); ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.07 – 1.27 (m, 1 H), 3.67-3.95 (m, 4 H), 7.01 – 7.13 (m, 2 H), 7.23 – 7.34 (m, 1 H), 7.40 – 7.50 (m, 1 H), 7.63 (d, J=8.6Hz, 1H), 7.84 (dd, J=8.6, 1.5 Hz, 1H), 8.04 – 8.16 (m, 2H), 11.97 (s, 1H), 12.19 (br s, 1H); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 51.7, 97.4, 110.5, 112.5, 117.4, 120.4, 121.1, 121.5, 121.7, 123.1, 128.5, 135.2, 139.3, 143.9, 150.4, 166.8; IR: 1688cm^-1 (ester, C=O stretching), 1618 (ester, C=O asymm. Str.);ESI Mass: m/z 324 [M^{. +}+1 peak]; Mol. Formula: C₁₇H₁₃N₃O₂S

methyl 3-(5-methoxy-1H-benzo[d]imidazol-2-ylthio)-1H-indole-4-carboxylate & methyl 3-(6-methoxy-1H-benzo[d]imidazol-2-ylthio)-1H-indole-4-carboxylate (compound 11 as tautomeric mixture of 11a and 11a’)

76% Yield, m.p. 220⁰C, Rf Value 0.60(in 10% methanol in DCM); ¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 1.15 – 1.35 (1 H, m), 3.29 (1 H, br s), 3.36 (3 H, br s), 3.70 – 3.90 (7 H, m), 6.71 (1 H, d, J=8.8Hz), 6.87 (1 H, br s), 7.24 (1 H, br d, J=8.6 Hz), 7.62 (1 H, d, J=8.6Hz), 7.84 (1 H, dd, J=8.6, 1.5Hz), 8.04 (1 H, d, J=2.3Hz), 8.16 (1H, s), 12.17 (1H, br s); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 51.7, 55.3, 97.8, 110.4, 112.4, 120.4, 121.7, 123.0, 128.5, 135.0, 139.3, 155.2, 166.8; IR: 1685cm^-1 (ester, C=O symm. str.), 1619 (ester, C=O asymm. Str.) ESI Mass: m/z 354 [M^{. +}+1 peak]; Mol. Formula: C₁₈H₁₅N₃O₃S

methyl 3-(5-(difluoromethoxy)-1H-benzo[d]imidazol-2-ylthio)-1H-indole-4-carboxylate and methyl 3-(6-(difluoromethoxy)-1H-benzo[d]imidazol-2-ylthio)-1H-indole-4-carboxylate (compound 12 as tautomeric mixture of 12a and 12a’)

72% yield, m.p. 205-207⁰C, Rf Value 0.45(in 10% methanol in DCM); ¹H NMR (400 MHz, DMSO-d₆, 25°C) δ ppm 3.74 (1 H, s), 3.78 – 3.86 (3 H, m), 6.93 (1H, br d, J=6.2Hz), 7.11 (1H, s), 7.17 (1H, br s), 7.24 – 7.44 (1H, m), 7.64 (1H, br d, J=8.6Hz), 7.85 (1H, br d, J=7.8Hz), 8.04 – 8.11 (1H, m), 8.11 – 8.17 (1 H, m), 11.99 – 12.27 (2 H, m); ¹³C NMR (101 MHz, DMSO-d₆) δ ppm 51.5, 51.7, 97.0, 112.5, 113.7, 120.3, 121.8, 123.1, 124.8, 128.5, 135.3, 139.3, 145.8, 166.8;  IR: 3312cm^-1 (N-H), 1698 (ester, C=O symm. Str.), 1619 (ester, C=O asymm. Str.); ESI Mass: m/z 390 [M^{. +}+1 peak]; Mol. Formula: C₁₈H₁₃F₂N₃O₃S

2-(7-methyl-1H-indol-3-ylthio)benzo[d]thiazole (Compound 13)

92% Yield,  m.p. 210⁰C, Rf Value 0.80 (10% methanol in DCM) ¹H NMR (300 MHz, DMSO-d₆, 27°C) δ ppm 2.54 (3 H, s), 7.03 (2 H, m), 7.22-7.28 (1H, m), 7.35-7.43 (2H, m), 7.8 (2H, d, J= 8.7Hz), 12.04 (1H, bs);  ¹H NMR (300 MHz, CD₃OD-d₆, 27°C) δ ppm 2.58 (3 H, s), 7.06 – 7.11 (2 H, m), 7.23-7.28 (1H, t, J=7.2Hz), 7.39-7.44 (2H, m), 7.65-7.68 (1H,d, J=8.1Hz), 7.75 -7.78 (2H, m); C¹³NMR (500 MHz, DMSO-d₆, 27°C) 16.5, 97.5, 115.5, 121.02, 121.0, 121.5, 121.9, 123.0, 123.9, 126.1, 127.7, 133.5, 154.0, 173.4; ; IR: 3418cm^-1 (N-H); ESI Mass: m/z 297 [M^{. +}+1 peak]; Mol. Formula: C₁₆H₁₂N₂S₂

2-(7-methyl-1H-indol-3-ylthio)benzoic acid (compound 14)

88% Yield, m.p.143⁰C, Rf Value 0.61(10% methanol in DCM); H¹ NMR (300 MHz, CD3OD, 27°C) δ ppm 2.58 (3H, s), 7.73 – 7.76 (1H, dd, J=0.9Hz, J=6Hz), 6.92-6.98 (2H, m), 7.04 (1H,t, J=6.3), 7.10 (1H, t, J=5.7), 7.98 (1H, d, J=5.7), 7.48 (1H, m), 7.96 (1H, dd, J=6, J=1.2), 11.09 (1H, bs) ESI Mass: m/z 284[M^{. +}+1 peak]; Mol. Formula: C₁₆H₁₃NO₂S

Table 3: Anti-bacterial activity ((Cup-plate Method) Click here to View table

 

Anti-Bacterial Activity

The newly synthesized compounds 1 to 12 are screened for antibacterial activity against gram-positive bacterium (B. subtilis and S. aureus) and Gram-negative bacteria (P. aeruginosa, E. coli and S. typhi). Dimethyl formamide is used as solvent control. The bacterial culture was inoculated on nutrient agar (Merck) (20 mL) and poured into sterilized Petri dishes (99 mm). Media plates were inoculated with liquid cultures homogeneously by spread plate method. All the test compounds were dissolved in dimethyl formamide(DMF) to get different concentration of 100 µL and loaded into the wells of agar plates directly. Plates inoculated with the bacteria were incubated at 37^oC for 24h. All determinations were done in triplicates. Amoxicillin (1mg/mL) were used as standard drugs for antibacterial.

The results for antibacterial activities depicted in Table 3. It reveals most of the compounds (1, 2, 4, 6, 8, 10, 11, and 12) showing good anti-bacterial activity against E.Coli. Incorporation of the ester group in the fourth position of the indole nucleus is favorable to anti-bacterial activity. Whereas the incorporation of Bromo or Methyl group on the indole nucleus is unfavorable to anti-bacterial activity.

Conclusion

A simple, convenient and   inventive protocol for the sulfenylation of indoles using Mn(OAc)₃ reagent was developed. This method offers several advantages such as broad substrate scope, high yields and regioselectivity. The experimental simplicity makes it a valuable and elegant strategy for the synthesis of 3-sulfenyl indoles.

Acknowledgments

We are thankful to the Management of Karpagam University to carry out my research work.

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