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Article

5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-Furan-2yl-4H [1,2,4] triazole-3-thiol and Their Thiol-Thione Tautomerism

by
M. Koparır
*,
A. Çetin
and
A. Cansız
Department of Chemistry, Faculty of Science, Fırat University, 23119, Elazıg, Turkey
*
Author to whom correspondence should be addressed.
Molecules 2005, 10(2), 475-480; https://doi.org/10.3390/10020475
Submission received: 30 June 2004 / Revised: 15 July 2004 / Accepted: 1 August 2004 / Published: 28 February 2005
Browse Figure
Versions Notes

Abstract

:
5-Furan-2-yl[1,3,4]oxadiazole-2-thiol (Ia) and 5-furan-2-yl-4H-[1,2,4]- triazole-3-thiol (Ib) were synthesized from furan-2-carboxylic acid hydrazide. Mannich bases and methyl derivatives were then prepared. The structures of the synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra. Their thiol-thione tautomeric equilibrium is described.

Introduction

Triazoles and their derivatives have been proven to be effective bactericides, pesticides and fungicides [1,2,3] Further, some findings that the 1,2,3-triazole nucleus is associated with diverse pharmacological activities such as analgesic, antiasthematic, diuretic, antihypertensive and antiinflammatory properties have made them important chemotherapeutic agents [4,5,6,7]. Derivatives of 1,3,4-oxadiazole are also known to have a broad spectrum of biological activities [8,9,10]. Acyl hydrazides have been in general use as the starting materials in some 1,2,4-triazole and 1,3,4-oxadiazole syntheses [11,12]. In addition there are some studies on electronic structures and thiol-thione tautomeric equilibrium of heterocyclic thione derivatives [13,14,15].
In the present study 5-furan-2-yl[1,3,4]oxadiazole-2-thiol (Ia) and 5-furan-2-yl-4H[1,2,4]-triazole-3-thiol (Ib) and some of their derivatives were synthesized. Compound Ia was synthesized by the ring closure reaction of furan-2-carboxylic acid hydrazide with carbon disulfide. A series of Mannich bases of 5-furan-2-yl[1,3,4]oxadiazole-2-thiol (IIIa-g) were then synthesized by the reaction of Ia with suitably substituted amines and formaldehyde in ethanol. 5-Furan-2-yl-4H[1,2,4]triazole-3-thiol (Ib) was prepared by the reaction of the appropriate 2-furoyl thiosemicarbazide and potassium hydroxide in ethanol for 3 h under reflux, followed by acidification with acetic acid. The 2-furoyl thiosemicarbazide employed in these reactions was obtained by refluxing the corresponding furan-2-carboxylic acid hydrazide with ammonium thiocynate in presence of aq. hydrochloric acid for 3 h. IIa and IIb were obtained from reaction of Ia and Ib with CH3I in an alkaline medium. These synthetic reactions are summarized in Scheme 1.
Molecules 10 00475 g001 550
Scheme 1.
Scheme 1.
Molecules 10 00475 g001

Results and Discussion

The characterization data of compounds Ia and Ib are given in the Experimental section and that of the other compounds synthesized is summarized in Table 1. All the newly synthesized compounds gave satisfactory analyses for the proposed structures, which were confirmed on the basis of their IR and 1H-NMR spectral data. The IR spectra of these compounds showed moderately strong bands around 3100-3360 cm-1, 1600-1650 cm-1 and 1250-1270 cm-1, characteristic of the NH, C=N and C=S groups, respectively. In the 1H-NMR spectra, a characteristic signal due to the –N-CH2-N- protons appeared at 5.00-6.05. The signal due to the NH protons appeared at 5.50-5.52. The signals due to the aromatic protons appeared as multiplets at 6.50-8.40.
We have observed that extensive thiol-thione tautomerism exists in compounds Ia and Ib. In the 1H-NMR the signal of the SH protons were recorded, although they were very weak and also the ready synthesis of the Mannich bases IIa, IIIa-g, IIb and Ib [16] from Ia and Ib confirmed the tautomerism. It has been reported that the crystal structures of Ia- and Ib-like compounds correspond to the thione form [17,18,19], but the reaction conditions for the synthesis of IIa prove that Ia can be in the thiol form too. Finally, the crystal structures of Ia and Ib [17,18] corresponded to the thione form, but they showed thiol-thione tautomerism in solution.

Experimental

General

Melting points were determined in open capillary tubes on a digital Gallenkamp melting point apparatus and are uncorrected. The IR spectra were recorded in KBr with a Mattson 1000 FT-IR spectrometer. 1H-NMR spectra were recorded on a FX 90 JEOL 90MHz NMR and Varian Gemini 200MHz, spectrometers in CDCl3 + DMSO- d6 with TMS as an internal standard. Elemental analyses were done on a LECO-CHNS-938. Starting chemicals were obtained from Merck or Aldrich.
5-Furan-2-yl[1,3,4]oxadiazole-2-thiol (Ia). A mixture of furan-2-carboxylic acid hydrazide (0.01 mole, 1.26 g), sodium hydroxide (0.01 mole, 0.4 g), carbon disulfide (0.02 mole, 1.2 mL) and absolute ethanol (100 mL) was heated under reflux for 12 h. The excess solvent was removed by vacuum evaporation, and the residue was dissolved in water and acidified with acetic acid. The product was recrystallised from water-ethanol (60-40). Yield 55 %; mp: 135-137 oC; IR, cm-1: 3356 (NH), 1642 (C=N), 1255(C=S); 1H-NMR, ppm: 6.56-7.65 (m, 3H, furyl), 13.70 (s, 1H, SH).
5-Furan-2-yl-4H[1,2,4]triazole-3-thiol (Ib). An equimolar quantity of furan-2-carboxylic acid hydrazide (0.01 mole, 1.26 g), ammonium thiocyanate (0.01 mole, 1.52 g) and hydrocholoric acid (5 mL) in absolute ethanol (50 mL) was refluxed for 4 h. The white solid that appeared on cooling was filtered and the excess solvent was removed by vacuum evaporation. The residue was recrystallised from DMF-ethanol (30-70 v/v) to give 1-(2-furoyl)-3-thiosemicarbazide (Yield 90 %; mp: 233-235 oC). This intermediate (0.01 mole 1.85 g) was refluxed in 10 % sodium hydroxide solution (5 mL) for 3 h. The resulting solution was cooled and filtered. The filtrate was acidified with hydrocholoric acid to pH 5-6. The solid which appeared was filtered, dried and recrystallised from dilute ethanol. Yield 75 %; mp: 295 oC; IR, cm-1: 3356-3155 (NH), 1642 (C=N), 1255(C=S); 1H-NMR, ppm: 13.80 (s, 1H, SH), 6.56-7.65 (m, 3H, furyl), 5.10 (s, 1H, NH).

General Procedure for the Preparation of IIa,b.

A mixture of thione Ia-b (0.005 mole), sodium hydroxide (0.005 mole, 0.2 g), and methyl iodide (0.006 mole, 0.840 g) was stirred in water for 14 h. The resulting thioether solution was removed by vacuum evaporation, and the products collected by filtration, washed with water, dried and recrystallised from a suitable solvent. Spectroscopic and physical data are summarized in Table 1.

General Procedure for the Preparation of IIIa-g.

A mixture of Ia (0.01 mole, 1.56 g) and an alkyl or aryl amine (0.01 mole) was refluxed in ethanol (50 mL) with 36 % formaldehyde (0.02 mole, 1.7 mL) for 3 h. The resulting solid was crystallised from a suitable solvent. Spectroscopic and physical data are summarized in Table 1.
Table
Table 1. Analytical and spectroscopic data for compounds IIa,b and IIIa-g.
Table 1. Analytical and spectroscopic data for compounds IIa,b and IIIa-g.
Comp. No.RXYield, %mp, ºCIR spectrum, υ, cm-11H NMR spectrum, δ, ppm (J, Hz)
IIa O451612982 (CH),1636(C=N), 1260(C=S).6.60-7.60 (m, 3H, furyl), 2.10 (s, 3H, SCH3)
IIb NH501323130(NH), 2982(CH),
1636(C=N),1260(C=S).		6.60-7.50 (m, 3H, furyl), 5.70 (1H, NH), 2.10 (s, 3H, SCH3
IIIa Molecules 10 00475 i001O821332990(CH),1632(C=N)
1270(C=S).		6.56-7.60 (m, 3H, furyl), 5.0 (s, 2H, N-CH2-N)
3.70-3.50 (m, 4H, CH2-O-CH2), 2.70-2.60 (m, CH2-N-CH2).
IIIb Molecules 10 00475 i002O601453320(NH),2970(CH),1630(C=N),1268(C=S).8.24-7.60 (m, 4H, Ar.CH), 6.50-7.60 (m, 3H, furyl), 5.50 (br, 1H, N-CH2-NH), 5.90 (d, J=7 2H, N-CH2-NH), 2.15 (s, 3H, CH3).
IIIc Molecules 10 00475 i003O621483315(NH),2970(CH),1630(C=N),1268(C=S).8.40-7.80 (m, 4H, Ar.CH), 6.50-7.60 (m, 3H, furyl), 5.50 (br, 1H, N-CH2-NH), 5.90 (d, J=7 2H, N-CH2-NH), 3.70 (s, 3H, OCH3).
IIId Molecules 10 00475 i004O501933330(NH), 2982(CH),
1636(C=N),1280(C=S).		8.20-7.80 (m, 7H, Ar.CH), 6.50-7.60 (m, 3H, furyl), 5.52 (br, 1H, N-CH2-NH), 5.85 (d, J=7 2H, N-CH2-NH).
IIIe Molecules 10 00475 i005O401283323(NH), 2982(CH),
1636(C=N),1260(C=S).		8.25-7.90 (m, 5H, Ar.CH), 6.50-7.60 (m, 3H, furyl), 5.52 (br, 2H, -NH), 5.92 (d, J=7 2H, N-CH2-NH), 3.80 (d, J=9 Ar-CH2-NH).
IIIf Molecules 10 00475 i006O701332982(CH),1636(C=N),1265(C=S). 6.50-7.60 (m, 3H, furyl), 5.80 (s, 2H, N-CH2), 2.10-2.80 (m, 10H, CH2).
IIIg Molecules 10 00475 i007O351743315(NH), 2982(CH),
1636(C=N),1270(C=S).		8.40-7.80 (m, 4H, Ar.CH), 6.50-7.60 (m, 3H, furyl), 5.50 (br, 1H, N-CH2-NH), 6.05 (d, J=7 2H, N-CH2-NH).
Comp No.Found, %FormulaCalculated,%
CHNSCHNS
IIa46.153.2915.3317.58C7H6N2O2S46.153.3215.3717.60
IIb46.383.8723.1117.65C7H7N3OS46.403.8923.1917.69
IIIa49.414.8915.7211.98C11H13N3O3S49.434.9015.7212.00
IIIb58.494.5414.6011.13C14H13N3O2S58.524.5614.6211.16
IIIc55.454.3213.8310.55C14H13N3O3S55.434.3213.8510.57
IIId63.133.9913.0010.00C17H13N3O2S63.144.0512.999.92
IIIe58.484.5514.6011.13C14H13N3O2S58.524.5614.6211.16
IIIf54.285.6815.7812.01C12H15N3O2S54.325.7015.8412.08
IIIg48.983.1517.5910.10C13H10N4O4S49.053.1717.6010.07

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MDPI and ACS Style

Koparır, M.; Çetin, A.; Cansız, A. 5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-Furan-2yl-4H [1,2,4] triazole-3-thiol and Their Thiol-Thione Tautomerism. Molecules 2005, 10, 475-480. https://doi.org/10.3390/10020475

AMA Style

Koparır M, Çetin A, Cansız A. 5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-Furan-2yl-4H [1,2,4] triazole-3-thiol and Their Thiol-Thione Tautomerism. Molecules. 2005; 10(2):475-480. https://doi.org/10.3390/10020475

Chicago/Turabian Style

Koparır, M., A. Çetin, and A. Cansız. 2005. "5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-Furan-2yl-4H [1,2,4] triazole-3-thiol and Their Thiol-Thione Tautomerism" Molecules 10, no. 2: 475-480. https://doi.org/10.3390/10020475

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