Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4-oxadiazole-5-thiol derivatives. 1. Synthesis and characterization

Kaniz Rubab¹, Muhammad A Abbasi¹ , Aziz-ur-Rehman ¹, Sabahat Z Siddiqui¹, Muhammad N Akhtar²

¹Department of Chemistry, Government College University, Lahore-54000, Pakistan; ²Faculty of Industrial Sciences & Technology, University Malaysia Pahang, Leburaya TunRazak, Kuantan Pahang, Malaysia.

For correspondence:- Muhammad Abbasi Email: abbasi@gcu.edu.pk Tel:+9242111000010

Accepted: 21 April 2016 Published: 31 July 2016

Citation: Rubab K, Abbasi MA, A, Siddiqui SZ, Akhtar MN. S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4-oxadiazole-5-thiol derivatives. 1. Synthesis and characterization. Trop J Pharm Res 2016; 15(7):1515-1524 doi: 10.4314/tjpr.v15i7.23

© 2016 The authors.
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Abstract

Purpose: To synthesize and characterize S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives.

Methods: 2-(1H-indol-3-yl)acetic acid (1) was reacted with absolute ethanol and catalytic amount of sulfuric acid to form ethyl 2-(1H-indol-3-yl)acetate (2) which was transformed to 2-(1H-indol-3-yl)acetohydrazide (3) by refluxing with hydrazine hydrate in methanol. Ring closure reaction of 3 with carbon disulfide and ethanolic potassium hydroxide yielded 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (4) which was finally treated with alkyl/aralkyl halides (5a-u) in DMF and NaH to yield S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u). Structural elucidation was done by IR, 1H-NMR and EI-MS techniques

Results: 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (4) was synthesized as the parent molecule and was characterized by IR and the spectrum showed peaks resonating at (cm^-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) and 1527 (Ar C=C ); 1H-NMR spectrum showed signals at δ 11.00 (s, 1H, NH-1E7;), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7'), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6 Hz, 1H, H-5'), 7.00 (t, J = 7.6 Hz, 1H, H-6') and 4.20 (s, 2H, CH2-10E7;). EI-MS presented different fragments peaks at m/z 233 (C₁₁H₉N₃OS)^H9;+ [M+2]⁺, 231 (C₁₁H₉N₃OS)^H9;+ [M]⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)^H9;+, 130 (C₉H₈N)⁺. The derivatives (6a-6u) were prepared and characterized accordingly.

Conclusion: S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u) were successfully synthesized.

Keywords: 2-(1H-indole-3-ylmethyl)-1,3,4-oxadiazole-5-thiol, S-alkylated/aralkylated derivatives, Synthesis, Characterization, 1H-NMR and EI-MS

Introduction

The synthesis and analysis of chemical and biological behaviors of 2, 5-disubstituted-1,3,4-oxadiazole-2-thiol derivatives have gained substantive importance in the past few decades for biological, medical and agricultural reasons [1-5]. Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acyl hydrazides and acids can be done by acid activation with CDI, followed by coupling with the required acyl hydrazide and dehydration in the same pot with CBr₄ and Ph₃P [6]. The appropriate aromatic acids are transformed to corresponding oxadiazoles through their hydrazides [7,8]. Substitution of alkyl/aralkyl halides can be done at 1, 3, 4-oxadiazole-2-thiol, to study structure-activity relationship [9].

Indole derivatives display a wide range of biological activities. 2-(1H-indol-3-yl) acetic acid is a plant growth hormone. It is obtained naturally from diets rich in vegetable stems and is synthesized from tryptophan, which is also used for the hormones serotonin and melatonin, the anti-inﬂammatory drug indomethacin, the psychotropic drug LSD and the anti-tumor agent vinblastine [10,11]. In continuation of our ongoing research efforts [12,13], we report herein the synthesis of alkylated/aralkylated 2-[1H-indol-3-ylmethyl]-1,3,4-oxadiazole-5-thiols (6a-u) which might be employed for pharmacological evaluation in search of new drug candidates.

Methods

Materials and instruments

Alkyl halides were purchased from Sigma Aldrich and Alfa Aesar, while 3-indoleacetic acid and hydrated hydrazine were from DAE Jung. All solvents were obtained through local supplier and used after distillation. Thin layer chromatography (TLC) was carried out on pre-coated silica gel G-25-UV₂₅₄ plates, run in different ratios of EtOAc and n-hexane and visualized at UV 254 nm. Melting points of synthesized compounds were recorded on Griffin and George melting point apparatus by open capillary tube and were uncorrected; IR spectra, was recorded in KBr pellet method on a Jasco-320-A spectrometer (Germany) in cm^-1; ¹H-NMR spectra were recorded in DMSO on a Bruker spectrometer (USA) at 300, 400 & 500 MHz with chemical shifts in ppm; and EIMS spectra were recorded on a JMS-HX-110 spectrometer with a data system.

Synthesis

Ethyl 2-(1H-indol-3-yl)acetate (2): 2-(1H-indol-3-yl)acetic acid (20.0 g; 0.11 mol; 1) in absolute ethanol (60 mL) and catalytic amount of concentrated sulfuric acid (10 mL; 0.18 mol) were put into a round bottomed flask and refluxed for 8 h. The flask contents were then neutralized with 25 mL of 10 % Na₂CO₃ solution. The product was isolated by solvent extraction with chloroform.

2-(1H-indol-3-yl)acetohydrazide (3): Ethyl 2-(1H-indol-3-yl) acetate (19.0 mL; 2) and 80 % hydrazine hydrate (25 mL) in 30 mL methanol were put into a round bottomed flask. The reaction mixture was stirred for 3 h at room temperature and the resultant acid hydrazide was obtained by distilling methanol from the reaction mixture.

2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (4): 2-(1H-indol-3-yl) acetohydrazide (20.0 g, 0.11 mol; 3) and absolute ethanol (30 mL) were put into a round bottom flask. Carbon disulfide (14.0 mL, 22 mol) was then added to the solution, followed by addition of potassium hydroxide (6.3 g, 0.11 mol). The mixture was refluxed for 6 h. and then diluted with distilled water (50 mL) and acidified with dilute hydrochloric acid to pH 2-3. The precipitate thus formed was filtered, washed with water and re-crystallized in ethanol.

S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1, 3, 4-oxadiazole-5-thiols (6a-u): 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (0.20 g; 0.001 mol; 4) as a nucleophile in N,N-dimethyl formamide was placed in a round bottom flask followed by addition of sodium hydride (0.002 g, 0.1 mmol) to the reaction mixture, which was then stirred for about half an hour at room temperature. The electrophiles, alkyl/aralkyl halides (5a-5u), were added in stoichiometric amounts and stirred for 8 h. After completion of reaction, the derivatives (6a-6u) were obtained as precipitates by addition of distilled water or by solvent extraction depending on the nature of the product.

Results

The S-substituted derivatives (6a-6u) of 2-(1H-indol-3-yl-methyl)-1,3,4-oxadiazole-5-thiol (4) were synthesized by the protocol sketched in Scheme 1 and the different S-substituted alkyl/aralkyl groups are listed in while the spectral and mass fragmentation patterns are shown in -4. The spectral characterizations of the compounds are provided below.

2-(1H-indol-3-yl)acetate (2): Brownish liquid, Yield: 85 %; Molecular formula: C₁₂H₁₃NO₂; Molecular weight: 203 gmol^-1; IR (KBr) v_max: 3315 (N-H), 2930 (Ar-H), 1624 (C=O ), 1531 (Ar. C=C ); ¹H-NMR (400 MHz, DMSO-d₆): δ 10.9 (s, 1H, NH-1ʹ), 7.48 ( br.d, J = 8.0 Hz, 1H, H-4'), 7.34 (br.d, J = 8.0 Hz, 1H, H-7'), 7.23 (br.s, 1H, H-2'), 7.06 (t, J = 7.6 Hz, 1H, H-5'), 6.97 (t, J = 7.6 Hz, 1H, H-6'),4.16 (q, J= 7.2, 2H, -OCH₂CH₃), 3.71 (s, 2H, CH₂-10ʹ),1.17 (t, J = 7.2 Hz, 3H, -OCH₂CH₃). EIMS: m/z 203 (C₁₂H₁₃NO₂)˙⁺ [M]⁺, 158 (C₁₀H₈NO)⁺, 130 (C₉H₈N)⁺, 73 (C₃H₅O₂)⁺.

2-(1H-indol-3-yl)acetohydrazide (3): Brownish crystals; Yield: 89 %; M.P. 113 °C; Molecular formula: C₁₀H₁₁N₃O; Molecular weight: 189 gmol^-1; IR (KBr) v_max: 3310 (N-H), 2930 (Ar-H), 1630 (C=O ), 1529 (Ar. C=C ); ¹H-NMR (400 MHz, DMSO-d₆): δ 10.8 (s, 1H, NH-1ʹ),9.08 (s, 1H, NHNH₂)_, 7.55 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.31 (br.d, J = 8.0 Hz, 1H, H-7'), 7.16 (br.s, 1H, H-2'), 7.04 (t, J = 7.2 Hz, 1H, H-5'), 6.95 (t, J = 7.6 Hz, 1H, H-6'), 4.16 ( s,1H, NHNH₂) 3.43 (s, 2H, CH₂-10ʹ). EIMS: m/z 203 (C₁₀H₁₁N₃O)˙⁺ [M]⁺, 158 (C₁₀H₈NO)⁺, 130 (C₉H₈N)⁺, 59 (C₃H₅O₂)⁺.

2-(1H-indol-3-yl-methyl)-1,3,4-oxadiazole-5-thiol (4): Dark brown powder; Yield: 76 %; M.P. 125 °C; Molecular formula: C₁₁H₉N₃OS; Molecular weight: 231 gmol^-1; IR (KBr) v_max: 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ), 1527 (Ar C=C ) ; ¹H-NMR (400 MHz, DMSO-d₆ ): δ 11.0 (s, 1H, NH-1ʹ), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7'), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6 Hz, 1H, H-5'), 7.00 (t, J = 7.6 Hz, 1H, H-6'), 4.20 (s, 2H, CH₂-10ʹ). EIMS: m/z 233 (C₁₁H₉N₃OS)˙⁺ [M+2]⁺, 231 (C₁₁H₉N₃OS)˙⁺ [M]⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺.

3-({5-[(2-Bromoethyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6a): Light brown amorphous solid; Yield: 81 %; M.P. 146 °C; Molecular formula: C₁₃H₁₂N₃OSBr; Molecular weight: 338 gmol^-1; IR (KBr): v_max 3226 (N-H), 2910 (C-H Ar), 1484 (C=N), 1476 (C=C Ar), 840 (C-N) and 810 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 7.8 Hz, 1H, H-4'), 7.35 (br.d, J = 7.8 Hz, 1H, H-7'), 7.31 (br.s, 1H, H-2'), 7.09 (t, J = 6.9 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.13 (s, 2H, CH₂-10ʹ), 3.22-3.25 (m-overlapped, 4H, CH₂-1'' & CH₂-2''); EIMS: m/z 341 (C₁₃H₁₂N₃OSBr)˙⁺ [M+4]⁺, 339 (C₁₃H₁₂N₃OSBr)˙⁺ [M+2]⁺, 337 (C₁₃H₁₂N₃OSBr)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈NO)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 158 (C₆H₄Br+2)⁺, 156 (C₆H₄Br)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 110 (C₂H₄Br)⁺,108 (C₂H₄Br)⁺.

3-({5-[(2-Chloroethyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6b): Light brown amorphous solid; Yield: 85 %; M.P. 208 °C; Molecular formula: C₁₃H₁₂N₃OSCl; Molecular weight: 293.5 gmol^-1; IR (KBr): v_max: 3221 (N-H), 2919 (C-H Ar), 1484 (C=N), 1470 (C=C Ar), 843 (C-N) and 814 (C-S); ¹H-NMR (500 MHz, DMSO-d₆ ): δ 10.99 (s, 1H, NH-1ʹ), 7.51 (br.d, J = 8.0 Hz, 1H, H-4'), 7.38 (br.d, J = 8.0 Hz, 1H, H-7'), 7.33 (br.s, 1H, H-2'), 7.10 (t, J = 8.0 Hz, 1H, H-5'), 7.00 (t, J = 8.0 Hz, 1H, H-6'), 4.34 (s, 2H, CH₂-10ʹ), 3.91 (t, 2H, J = 7.0 Hz, CH₂-2''), 3.56 (t, 2H, J = 7.0 Hz, CH₂-1''); EIMS: m/z 297 (C₁₃H₁₂N₃OSCl)˙⁺ [M+4]⁺, 295 (C₁₃H₁₂N₃OSCl)˙⁺ [M+2]⁺, 293 (C₁₃H₁₂N₃OSCl)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130(C₉H₈N)⁺, 65 (C₂H₄Cl+2)⁺, 63 (C₂H₄Cl)⁺.

3-{[5-(Propylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6c): Brown amorphous solid; Yield: 70 %; M.P. 103°C; Molecular formula: C₁₄H₁₅N₃OS; Molecular weight: 273 gmol^-1; IR (KBr): v_max: 3225 (N-H), 2932 (C-H Ar), 1479 (C=N), 1474 (C=C Ar), 840 (C-N) and 816 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 7.6 Hz, 1H, H-4'), 7.35 (br.d, J = 7.6 Hz, 1H, H-7'), 7.31 (br.s, 1H, H-2'), 7.09 (t, J = 6.8 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.16 (s, 2H, CH₂-10'), 3.84 (t, J = 7.6 Hz, 2H, CH₂-1''), 1.64 (sex, J = 7.2 Hz, 2H, CH₂-2''), 1.05 (t, J = 7.2 Hz, 3H, CH₃-3''); EIMS: m/z 275 (C₁₄H₁₅N₃OS)˙⁺ [M+2]⁺, 273 (C₁₄H₁₅N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺,43(C₃H₇)⁺.

3-{[5-(iso-Propylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6d): Light brown amorphous solid; Yield: 75 %; M.P. 78 °C; Molecular formula: C₁₄H₁₅N₃OS; Molecular weight: 273 gmol^-1; IR (KBr): v_max: 3225 (N-H), 2928 (C-H Ar), 1478 (C=N), 1470 (C=C Ar), 845 (C-N) and 809 (C-S); ¹H-NMR (500 MHz, DMSO-d₆ ): δ 11.02 (s, 1H, NH-1ʹ), 7.50 (br. d, J = 8.0 Hz, 1H, H-4'), 7.37 (br. d, J = 8.0 Hz, 1H, H-7'), 7.33 (br. s, 1H, H-2'), 7.10 (t, J = 7.0 Hz, 1H, H-5'), 7.00 (t, J = 7.5 Hz, 1H, H-6'), 4.78 (s, 2H, CH₂-10ʹ), 3.76-3.71 (m, 1H, CH-1''), 1.36 (d, J = 6.0 Hz, 6H, CH₃-2'' & CH₃-3''); EIMS: m/z 275 (C₁₄H₁₅N₃OS)˙⁺ [M+2]⁺, 273 (C₂₀H₁₉N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231( C₁₄H₁₅N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 43 (C₃H₇)⁺.

3-{[5-(sec-Butylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6e): Dark brown sticky solid; Yield: 73 %; Molecular formula: C₁₅H₁₇N₃OS; Molecular weight: 287 gmol^-1; IR (KBr): v_max: 3220 (N-H), 2930 (C-H Ar), 1485 (C=N), 1472 (C=C Ar), 838 (C-N) and 814 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br. d, J = 7.6 Hz, 1H, H-4'), 7.35 (br. d, J = 8.0 Hz, 1H, H-7'), 7.31 (br. s, 1H, H-2'), 7.09 (t, J = 6.8 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.43 (s, 2H, CH₂-10ʹ), 4.25-4.21 (m, 1H, H-1"), 1.01 (d, J = 6.8 Hz, 3H, CH₃-4"), 0.90-0.85 (m, 2H, H-2"), 0.74 (t, J = 7.2 Hz, 3H, CH₃-3"). EIMS: m/z 289 (C₁₅H₁₇N₃OS)˙⁺ [M+2]⁺, 287 (C₁₅H₁₇N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 58 (C₄H₉)⁺, 43 (C₃H₆)˙⁺.

3-{[5-(Butylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6f): Brown amorphous solid; Yield: 87 %; M.P. 83 °C; Molecular formula: C₁₅H₁₇N₃OS; Molecular weight: 287 gmol^-1; IR (KBr): v_max: 3220 (N-H), 2925 (C-H Ar), 1480 (C=N), 1477 (C=C Ar), 839 (C-N) and 805 (C-S); ¹H-NMR (500 MHz, DMSO-d₆): δ 11.02 (s, 1H, NH-1ʹ), 7.49 (br. d, J = 8.0 Hz, 1H, H-4'), 7.37 (br.d, J = 8.5 Hz, 1H, H-7'), 7.32 (br.s, 1H, H-2'), 7.09 (t, J = 8.0 Hz, 1H, H-5'), 6.99 (t, J = 7.5 Hz, 1H, H-6'), 4.25 (s, 2H, CH₂-10ʹ), 3.15 (t, J = 7.5 Hz, 2H, CH₂-1''), 1.61 (quint., J = 7.5 Hz, 2H, CH₂-2''), 1.31 (sext, J = 7.0 Hz, 2H, CH₂-3''), 0.84 (t, J = 7.5 Hz, 3H, CH₃-4''). EIMS: m/z 289 (C₁₅H₁₇N₃OS)˙⁺ [M]⁺, 287 (C₁₅H₁₇N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 58 (C₄H₉)⁺, 42 (C₃H₆)˙⁺.

3-{[5-(Pentylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6g): Brown amorphous solid; Yield: 78 %; M.P. 62 °C; Molecular formula: C₁₆H₁₉N₃OS; Molecular weight: 301 gmol^-1; IR (KBr): v_max: 3224 (N-H), 2927 (C-H Ar), 1484 (C=N), 1470 (C=C Ar), 847 (C-N) and 812 (C-S); ¹H-NMR (500 MHz, DMSO-d₆): δ 11.03 (s, 1H, NH-1ʹ), 7.46 (br. d, J = 8.0 Hz, 1H, H-4'), 7.33 (br. d, J = 8.0 Hz, 1H, H-7'), 7.29 (br. s, 1H, H-2'), 7.06 (t, J = 7.0 Hz, 1H, H-5'), 6.96 (t, J = 7.5 Hz, 1H, H-6'), 4.29 (s, 2H, CH₂-10ʹ), 3.11 (t, J = 7.5 Hz, 2H, CH₂-1''), 1.61 (quint., 2H, CH₂-2''), 1.38-1.17 (m, 4H, CH₂-3'', CH₂-4''), 0.79 (t, J = 7.0 Hz, 3H, CH₃-5''); EIMS: m/z m/z 303 (C₁₆H₁₉N₃OS)˙⁺ [M+2]⁺, 301 (C₁₆H₁₉N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈NO)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 71 (C₅H₁₁)⁺, 55(C₄H₇)˙⁺.

3-{[5-(Heptylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6h): Dark brown amorphous solid; Yield: 88 %; M.P. 133 °C; Molecular formula: C₁₈H₂₃N₃OS; Molecular weight: 329 gmol^-1; IR (KBr): v_max: 3225 (N-H), 2931 (C-H Ar), 1480 (C=N), 1475 (C=C Ar), 845 (C-N) and 810 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 7.6 Hz, 1H, H-4'), 7.35 (br.d, J = 7.6 Hz, 1H, H-7'), 7.31 (br.s, 1H, H-2'), 7.09 (t, J = 6.8 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.17 (s, 2H, CH₂-10ʹ),3.67-3.64 (m, 1H, H-1"), 2.02-1.97 (m, 4H, H-2" & H-3"), 1.25-1.18 (m, 6H, H-4" to H-6"), 0.82 (t, J = 7.2 Hz, 3H, CH₃-7"); EIMS: m/z 331 (C₁₈H₂₃N₃OS)˙⁺ [M+2]⁺, 329 (C₁₈H₂₃N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 99 (C₇H₁₄)⁺, 84 (C₆H₁₂)˙⁺, 56 (C₄H₈)˙⁺.

3-{[5-(Allylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6i): Dark brown shiny solid; Yield: 76 %; M.P. 105 °C; Molecular formula: C₁₄H₁₄N₃OS; Molecular weight: 272 gmol^-1; IR (KBr): v_max: 3226 (N-H), 2933 (C-H Ar), 1481 (C=N), 1470 (C=C Ar), 843 (C-N) and 812 (C-S); ¹H-NMR (500 MHz, DMSO-d₆): δ 11.01 (s, 1H, NH-1ʹ), 7.48 (br.d, J = 8.0 Hz, 1H, H-4'), 7.36 (br.d, J = 8.5 Hz, 1H, H-7'), 7.31 (br. s, 1H, H-2'), 7.08 (t, J = 7.5 Hz, 1H, H-5'), 6.98 (t, J = 8.0 Hz, 1H, H-6'), 5.90-5.80 (m, 1H, H-2''), 5.14 (dd, J = 17.0, 1.5 Hz, 1H, H_b-3"), 5.08 (dd, J = 10.0, 0.5 Hz, 1H, H_a-3"), 4.31 (s,2H, CH₂-10ʹ), 3.80 (d, J = 6.9 Hz, 2H, CH₂-1''). EIMS: m/z 274 (C₁₄H₁₄N₃OS)˙⁺ [M+2]⁺, 272 (C₁₄H₁₄N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 41 (C₃H₅)⁺.

3-[(5-(Ethoxycarbonylmethylsulfanyl)-1,3,4-oxadiazole-2-yl)methyl]-1H-indole (6j): Dark brown shiny solid; Yield: 82 %; M.P. 97 °C; Molecular formula: C₁₅H₁₅N₃O₃S; Molecular weight: 317 gmol^-1; IR (KBr): v_max: 3225 (N-H), 2934 (C-H Ar), 1484 (C=N), 1470 (C=C Ar), 840 (C-N) and 814 (C-S); ¹H-NMR (500 MHz, DMSO-d₆): δ 11.04 (s, 1H, NH-1ʹ ), 7.48 (br.d, J = 8.0 Hz, 1H, H-4'), 7.36 (br.d, J = 8.0 Hz, 1H, H-7' ), 7.30 (br.s, 1H, H-2' ), 7.08 (t, J = 7.0 Hz, 1H, H-5'), 6.98 (t, J = 8.0 Hz, 1H, H-6'), 4.31 (s, 2H, CH₂-10ʹ), 4.12 (s, 2H, CH₂-1''' ), 4.04 (q, J = 7.2 Hz, 2H, CH₂-1'' ), 1.11 (t, J = 7.0 Hz, 3H, CH₃-2'' ); EIMS: m/z 319 (C₁₅H₁₅N₃O₃S)˙⁺ [M+2]⁺,317 (C₁₅H₁₅N₃O₃S)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 87 [C₄H₇O₂]⁺, 42 [C₂H₂O]⁺.

3-{[5-(Benzylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6k): Light brown amorphous solid; Yield: 79 %; M.P. 110 °C; Molecular formula: C₁₈H₁₅N₃OS; Molecular weight: 321 gmol^-1; IR (KBr): v_max: 3224 (N-H), 2928 (C-H Ar), 1486 (C=N), 1477 (C=C Ar), 838 (C-N) and 810 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.02 (s, 1H, NH-1ʹ), 7.49 (br.d, J = 8.0 Hz, 1H, H-4'), 7.38 (br.d, J = 8.5 Hz, 1H, H-7'), 7.32 (br.s, 1H, H-2'), 7.28- 7.25 (m, 2H, H-2''& H-6''), 7.24- 7.19 (m, 3H, H-3'' to H-5''), 7.11 (t, J = 8.0 Hz, 1H, H-5'), 7.00 (t, J = 8.0 Hz, 1H, H-6'), 4.35 (s, 2H, CH₂-10'), 4.25 (s, 2H, CH₂-7'' ); EIMS: m/z 323 (C₁₈H₁₅N₃OS)˙⁺ [M+2]⁺, 321 (C₁₈H₁₅N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺,91 (C₇H₇)⁺, 65 (C₅H₅)⁺.

3-({5-[(3-Phenylethyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6l): Dark brown solid; Yield: 80 %; M.P. 75 °C; Molecular formula: C₁₉H₁₇N₃OS; Molecular weight: 335 gmol^-1; IR (KBr): v_max: 3215 (N-H), 2930 (C-H Ar), 1485 (C=N), 1479 (C=C Ar), 846(C-N) and 810 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.49 (br.d, J = 7.6 Hz, 1H, H-4'), 7.36 (br.d, J = 8.0 Hz, 1H, H-7'),7.33 (br.s, 1H, H-2'), 7.26-7.22 (m, 3H, H-3'', H-4'' & H-5''), 7.18-7.12 (m,2H, H-2'' & H-6''), 7.09 (t, J = 7.6 Hz, 1H, H-5'), 6.98 (t, J = 7.6 Hz, 1H, H-6'), 4.32 (s, 2H, CH₂-10'), 3.39 (t, J = 7.2 Hz, 2H, CH₂-8''), 2.95 (t, J = 7.6 Hz, 2H, CH₂-7''); EIMS: m/z 337 (C₁₉H₁₇N₃OS)˙⁺ [M+2]⁺, 335 (C₁₉H₁₇N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺,105 (C₈H₉)⁺, 91 (C₇H₇)⁺, 65 (C₅H₅)⁺.

3-({5-[(3-Phenylpropyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6m): Dark brown shiny powder; Yield: 77 %; M.P. 64 °C; Molecular formula: C₂₀H₁₉N₃OS; Molecular weight: 349 gmol^-1; IR (KBr): v_max: 3225 (N-H), 2927 (C-H Ar), 1484 (C=N), 1476 (C=C Ar), 847 (C-N) and 812 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 7.8 Hz, 1H, H-4'), 7.35 (br.d, J = 7.8 Hz, 1H, H-7'), 7.31 (br.s, 1H, H-2'), 7.27-7.23 (m, 3H, H-3'', H-4'' & H-5''), 7.18-7.12 (m,2H, H-2'' & H-6''),7.08 (t, J = 7.2 Hz, 1H, H-5'), 6.97 (t, J = 6.9 Hz, 1H, H-6'), 4.31 (s, 2H, CH₂-10'), 3.15 (t, J = 7.2 Hz, 2H, CH₂-9''), 2.63 (t, J = 8.1 Hz, 2H, CH₂-7''), 1.94 (quint., J = 7.5 Hz, 2H, CH₂-8''); EIMS: m/z 351 (C₂₀H₁₉N₃OS)˙⁺ [M+2]⁺, 349 (C₂₀H₁₉N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺,119 (C₉H₁₁)⁺, 91 (C₇H₇)⁺, 65 (C₅H₅)⁺.

3-({5-[(2-Chlorobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6n): Dark brown amorphous solid; Yield: 83 %; M.P. 126 °C; Molecular formula: C₁₈H₁₄N₃OSCl; Molecular weight: 355.5 gmol^-1; IR (KBr): v_max: 3230 (N-H), 2929 (C-H Ar), 1480 (C=N), 1472 (C=C Ar), 8441(C-N) and 812 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 8.0 Hz, 1H, H-4'), 7.35 (br.d, J = 7.6 Hz, 1H, H-7'), 7.34 (br.s, 1H, H-2'),7.32 (dd, J = 1.2, 8.0 Hz, 1H, H-3''), 7.29 (br.d, J = 7.6 Hz, 1H, H-6''), 7.16-7.10 (m, 2H, H-4'' & H-5''), 7.08 (t, J = 7.2 Hz, 1H, H-5'), 6.97 (t, J = 6.8 Hz, 1H, H-6'), 4.55 (s, 2H, CH₂-7''), 4.31 (s, 2H, CH₂-10'); EIMS: m/z 359 (C₁₈H₁₄N₃OSCl)˙⁺ [M+4]⁺, 357 (C₁₈H₁₄N₃OSCl)˙⁺ [M+2]⁺, 355 (C₁₈H₁₄N₃OSCl)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 127 (C₇H₆Cl+2)⁺, 125 (C₇H₆Cl)⁺, 101 (C₅H₄Cl+2)⁺, 99 (C₅H₄Cl)⁺, 90 (C₇H₆)⁺, 64 (C₅H₄)⁺.

3-({5-[(3-Chlorobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6o): Dark brown amorphous solid; Yield: 89 %; M.P. 85 °C; Molecular formula: C₁₈H₁₄N₃OSCl; Molecular weight: 355.5 gmol^-1; IR (KBr): v_max: 3219 (N-H), 2926 (C-H Ar), 1477 (C=N), 1478 (C=C Ar), 840(C-N) and 812 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ 11.01 (s, 1H, NH-1ʹ), 7.39 (br.s, 1H, H-2''), 7.36 (br.d, J = 8.6 Hz, 1H, H-4''), 7.35 (br.d, J = 7.5 Hz, 1H, H-6''), 7.33 (br.t, J = 8.1 Hz, 1H, H-5''), 7.31 (br.d, J = 7.8 Hz, 1H, H-4'), 7.30 (br.d, J = 8.1Hz, 1H, H-7'), 7.29 (br.s, 1H, H-2'), 7.11 (t, J = 7.2 Hz, 1H, H-5'), 6.97 (t, J = 7.2 Hz, 1H, H-6'), 4.54 (s, 2H, CH₂-7''), 4.30 (s, 2H, CH₂-10'); EIMS: m/z 359 (C₁₈H₁₄N₃OSCl)˙⁺ [M+4]⁺, 357 (C₁₈H₁₄N₃OSCl)˙⁺ [M+2]⁺, 355 (C₁₈H₁₄N₃OSCl)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 127 (C₇H₆Cl+2)⁺, 125 (C₇H₆Cl)⁺, 101 (C₅H₄Cl+2)⁺, 99 (C₅H₄Cl)⁺, 90 (C₇H₆)⁺, 64 (C₅H₄)⁺.

3-({5-[(4-Chlorobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6p): Brown colored amorphous solid; Yield: 79 %; M.P. 121 °C; Molecular formula: C₁₈H₁₄N₃OSCl; Molecular weight: 355.5 gmol^-1; IR (KBr): v_max: 3215 (N-H), 2928 (C-H Ar), 1480 (C=N), 1470 (C=C Ar), 840(C-N) and 812 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ11.01 (s, 1H, NH-1ʹ), 7.49 (br.d, J = 7.8 Hz, 1H, H-4'), 7.42 (br.d, J = 7.2 Hz, 1H, H-7'), 7.37 (br.d, J = 8.4 Hz, 2H, H-2ʹʹ& H-6ʹʹ), 7.35 (br.s, 1H, H-2'), 7.30 (br.d, J = 8.4 Hz, 2H, H-3'' & H-5''), 7.09 (t, J = 6.9 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.55 (s, 2H, CH₂-7''), 4.31 (s, 2H, CH₂-10'); EIMS: m/z 359 (C₁₈H₁₄N₃OSCl)˙⁺ [M+4]⁺, 357 (C₁₈H₁₄N₃OSCl)˙⁺ [M+2]⁺, 355 (C₁₈H₁₄N₃OSCl)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 127 (C₇H₆Cl+2)⁺, 125 (C₇H₆Cl)⁺, 101 (C₅H₄Cl+2)⁺, 99 (C₅H₄Cl)⁺, 90 (C₇H₆)⁺, 64 (C₅H₄)⁺.

3-({5-[(2-Bromobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6q): Light brown amorphous solid; Yield: 85 %; M.P. 133 °C; Molecular formula: C₁₈H₁₄N₃OSBr; Molecular weight: 399 gmol^-1; IR (KBr): v_max: 3217 (N-H), 2935 (C-H Ar), 1479 (C=N), 1481 (C=C Ar), 846 (C-N) and 816 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.02 (s, 1H, NH-1ʹ), 7.47 (br.d, J = 7.6 Hz, 1H, H-4'), 7.35 (br.d, J = 7.6 Hz, 1H, H-7'), 7.31 (br.s, 1H, H-2'), 7.29 (dd, J = 1.2, 8.0 Hz, 1H, H-3''), 7.28 (br.d, J = 7.6 Hz, 1H, H-6''), 7.11-7.09 (m, 2H, H-4'' & H-5''), 7.07 (t, J = 7.2 Hz, 1H, H-5'), 6.96 (t, J = 7.6 Hz, 1H, H-6'), 4.55 (s, 2H, CH₂-7''), 4.29 (s, 2H, CH₂-10'); EIMS: m/z 403 (C₁₈H₁₄N₃OSBr)˙⁺ [M+4]⁺, 401 (C₁₈H₁₄N₃OSBr)˙⁺ [M+2]⁺, 399 (C₁₈H₁₄N₃OSBr)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 171 (C₇H₆Br+2)⁺,169 (C₇H₆Br)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 90 (C₇H₆)⁺, 145 (C₅H₄Br+2)⁺,143 (C₅H₄Br)⁺, 64 (C₅H₄)⁺.

3-({5-[(4-Bromobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6r): Light brown amorphous solid; Yield: 86 %; M.P. 130 °C; Molecular formula: C₁₈H₁₄N₃OSBr; Molecular weight: 400 gmol^-1; IR (KBr): v_max: 3215 (N-H), 2927 (C-H Ar), 1484 (C=N), 1478 (C=C Ar), 848(C-N) and 812 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ 11.0 (s, 1H, N-H-1ʹ), 7.45 (br.d, J = 7.8, 1H, H-4'), 7.38-7.36 (m, 3H, H-2ʹʹ, H-6ʹʹ & H-7'), 7.33 (br.s, 1H, H-2'), 7.17 (br.d, J = 8.4 Hz, 2H, H-3'' & H-5''), 7.09 (t, J = 6.9 Hz, 1H, H-5'), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.35 (s, 2H, CH₂-7''), 4.31 (s, 2H, CH₂-10'); EIMS: m/z 403 (C₁₈H₁₄N₃OSBr)˙⁺ [M+4]⁺, 401 (C₁₈H₁₄N₃OSBr)˙⁺ [M+2]⁺, 399 (C₁₈H₁₄N₃OSBr)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 171 (C₇H₆Br+2)⁺,169 (C₇H₆Br)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 90 (C₇H₆)⁺, 145 (C₅H₄Br+2)⁺,143 (C₅H₄Br)⁺, 64 (C₅H₄)⁺.

3-({5-[(4-Fluorobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6s): Brown amorphous solid; Yield: 90 %; M.P. 84 °C; Molecular formula: C₁₈H₁₄N₃OSF; Molecular weight: 339 gmol^-1; IR (KBr): v_max: 3245 (N-H), 2932 (C-H Ar), 1485 (C=N), 1480 (C=C Ar), 850 (C-N) and 825 (C-S); ¹H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, N-H-1ʹ), 7.51 (br.d, J = 7.4 Hz, 1H, H-4'), 7.38 (br.s, 1H, H-7'), 7.37 (dist. dd, J_(a,b&a,¹⁹_F) = 8.8, 5.6 Hz, 2H_b, H-2'' & H-6''),7.35 (br.d, J = 8.0 Hz, 1H, H-2'), 7.09 (t, J = 6.9 Hz, 1H, H-5'), 7.00 (t, J_(b,a&b,¹⁹_F) = 8.8 Hz, 2H_a, H-3'' & H-5''), 6.98 (t, J = 7.2 Hz, 1H, H-6'), 4.55 (s, 2H, CH₂-7''), 4.31 (s, 2H, CH₂-10'); EIMS: m/z 341 (C₁₈H₁₄N₃OSF )˙⁺ [M+2]⁺, 339 (C₁₈H₁₄N₃OSF )˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺, 109 (C₇H₆F)⁺, 90 (C₇H₆)⁺, 83 (C₅H₄F)⁺. 64 (C₅H₄)⁺.

3-({5-[(2-Methylbenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6t): Light brown amorphous solid; Yield: 73 %; M.P. 126 °C; Molecular formula: C₁₉H₁₇N₃OS; Molecular weight: 335 gmol^-1; IR (KBr): v_max: 3245 (N-H), 2930 (C-H Ar), 1480 (C=N), 1470 (C=C Ar), 840 (C-N) and 810 (C-S); 1H-NMR (400 MHz, DMSO-d₆): δ 11.0 (s, 1H, NH-1ʹ), 7.48 ( d, J = 8.0 Hz, 1H, H-4'), 7.36 (d, J = 8.0 Hz, 1H, H-7'), 7.31 ( br.s, 1H, H-2'), 7.14-7.12 (m, 3H, H-3'', H-4'' & H-5''), 7.09 (t, J = 8.0 Hz, 1H, H-5'), 7.00 (t, J = 7.8 Hz, 1H, H-6'),6.97 ( d, J=4.8Hz, 1H, H-6''), 4.41 (s, 2H, CH₂-10'), 4.32 (s, 2H, CH₂-7''), 2.29 (s, 3H, CH₃-2''); EIMS: m/z 337 (C₁₉H₁₇N₃OS)˙⁺ [M+2]⁺, 335 (C₁₉H₁₇N₃OS)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 130 (C₉H₈N)⁺,105 (C₈H₉)⁺, 90 (C₇H)⁺, 79 (C₆H₇)⁺, 64 (C₅H₄)⁺.

3-({5-[(3-Nitrobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole (6u): Dark brown amorphous solid; Yield: 78 %; M.P. 101 °C; Molecular formula: C₁₈H₁₄N₃OS; Molecular weight: 366 gmol^-1; IR (KBr): v_max: 3240 (N-H), 2931 (C-H Ar), 1480 (C=N), 1475 (C=C Ar), 845 (C-N) and 820 (C-S); ¹H-NMR (300 MHz, DMSO-d₆): δ11.0 (s, 1H, N-H-1ʹ), 8.30 (br.s, 1H, H-2''), 8.08 (d, J = 8.1 Hz, 1H, H-4''), 7.72 (br.d, J = 7.5 Hz, 1H, H-6''), 7.49 (br.d, J = 7.8 Hz, 1H, H-4'), 7.44 (br.t, J = 7.8 Hz, 1H, H-5''), 7.35 (br.d, J = 8.1 Hz, 1H, H-7'), 7.30 (br.s, 1H, H-2'), 7.07 (t, J = 6.9 Hz, 1H, H-5'), 6.96 (t, J = 7.2 Hz, 1H, H-6'), 4.55 (s, 2H, CH₂-7''), 4.29 (s, 2H, CH₂-10'); EIMS: m/z 368 (C₁₈H₁₄N₄O₃S)˙⁺ [M+2]⁺, 366 (C₁₈H₁₄N₄O₃S)˙⁺ [M]⁺, 233 (C₁₁H₉N₃OS+2)⁺, 231 (C₁₁H₉N₃OS)⁺, 198 (C₁₁H₈N₃O)⁺, 172 (C₁₀H₈N₂O)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺, 156 (C₁₀H₈N₂)˙⁺, 136 (C₇H₆NO₂₎⁺ ,130 (C₉H₈N)⁺, 110 (C₆H₄NO₂₎⁺, 64 (C₅H₄)⁺.

Discussion

In Figures 1 and 2, the ¹H-NMR spectra of the compounds 3-{[5-(Allylsulfanyl)-1,3,4-oxadiazol-2-yl]methyl}-1H-indole (6i) and 3-[(5-(Ethoxycarbonylmethylsulfanyl)-1,3,4-oxadiazole-2-yl)methyl]-1H-indole (6j) are provided. The compound 6u was obtained as a dark brown amorphous solid; yield: 78 % and m. p. 101 °C and the molecular formula C₁₈H₁₄N₃OS was ascertained by counting the number of protons in the ¹H-NMR spectrum and EIMS molecular ion peak at m/z 366. Infrared spectrum demonstrated N-H stretching at 3240 cm^-1 and aromatic C-H stretching at 2931 cm^-1. C=N stretching was observed at 1480 cm^-1 and aromatic C=C stretching at1475 cm^-1. C-N gave stretching at 845 cm^-1 and C-S at stretching at 820 cm^-1. In the aromatic region of 1H-NMR spectrum, a broad singlet at δ 8.30 (s,1H, H-2''), two doublets and one triplet at δ 8.08 (d, J = 8.1 Hz, 1H, H-4''), 7.72 (d, J = 7.5 Hz, 1H, H-6'') and 7.44 (t, J = 7.8 Hz, 1H, H-5'') acquiring deshielded position due to the vicinity of an electron withdrawing nitro group which confirmed the substitution of 3-nitrobenzyl group on the parent indole-bearing oxadiazole molecule (4). Another set of two doublets appeared at δ 7.49 (J = 7.8 Hz, 1H, H-4') and 7.35 (J = 8.1 Hz, 1H, H-7') having an integration of one proton each for H-4' & H-7' of the indole moiety. A broad singlet of one proton appeared at δ 7.30 (1H, H-2') of indole moiety. Two triplets resonated at δ 7.07 (J = 6.9 Hz, 1H, H-5') and δ 6.96 (J = 7.2 Hz, 1H, H-6') belonging to phenyl ring of indole moiety. In the aliphatic region, a sharp singlet appeared at δ 4.55, a contributor of two methylene protons at C-7'', which confirms the attachment of 3-Nitrobenzyl group at the thiol position of 1,3,4-oxadizole ring. Another singlet appeared slightly up-field with integration of two protons of C-10' at δ 4.29 (2H, CH₂-10'). EIMS data further supported this structure by revealing base peak at m/z 130 for (C9H8N)⁺ and other major fragments at m/z 231(C₁₁H₉N₃OS)⁺ ,156 (C₁₀H₈N₂)˙⁺, 172 (C₁₀H₈NO)⁺, 170 (C₁₀H₈N₃)⁺, 158 (C₁₀H₈NO)⁺ for indole moiety. Fragments of 3-Nitrobenzyl substituent were observed at m/z 136 (C₇H₆NO₂)⁺, 110 (C₆H₄NO₂)⁺, 64 (C₅H₄)⁺. On the basis of these features, the structure of compound 6u was given as 3-({5-[(3-nitrobenzyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1H-indole. Similarly, the structures of other S-alkylated/aralkylated 2-(1H-indole-3-ylmethyl)-1,3,4-oxadiazole-5-thiols were also characterized by spectroscopic techniques.

Conclusion

All the synthesized compounds (6a-6u) were obtained in good yields and their structures were elucidated by IR, ¹H-NMR, and EI-MS spectral analysis. It is hoped that further studies on possible biological activities of these compounds might produce useful results for the pharmaceutical industries.

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