Convenient, efficient synthesis of amide-thioethers in ionic liquids

Article abstract of DOI:10.1080/00397911.2010.523490

An improved method for the synthesis of carboxamide ligands containing thioether donor sites is described. This replaces the pyridine as the reaction medium used in the classical method by tetrabutylammonium bromide. The desired products, 1,4-bis[o-(R-2-c

Full text of DOI:10.1080/00397911.2010.523490

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Convenient, Efficient Synthesis of
Amide-Thioethers in Ionic Liquids
Soraia Meghdadi a , Valiollah Mirkhani a & Peter C. Ford b
a Department of Chemistry , University of Isfahan , Isfahan , Iran
b Department of Chemistry and Biochemistry , University of
California , Santa Barbara , California , USA
Accepted author version posted online: 26 Jul 2011.Published
online: 14 Sep 2011.
To cite this article: Soraia Meghdadi , Valiollah Mirkhani & Peter C. Ford (2012) Convenient,
Efficient Synthesis of Amide-Thioethers in Ionic Liquids, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:2, 246-250, DOI:
10.1080/00397911.2010.523490
To link to this article: http://dx.doi.org/10.1080/00397911.2010.523490
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Synthetic Communications1, 42: 246–250, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.523490
CONVENIENT, EFFICIENT SYNTHESIS OF
AMIDE-THIOETHERS IN IONIC LIQUIDS
Soraia Meghdadi,1 Valiollah Mirkhani,1 and Peter C. Ford2
1Department of Chemistry, University of Isfahan, Isfahan, Iran
2Department of Chemistry and Biochemistry, University of California, Santa
Barbara, California, USA
GRAPHICAL ABSTRACT
Abstract An improved method for the synthesis of carboxamide ligands containing
thioether donor sites is described. This replaces the pyridine as the reaction medium used
in the classical method by tetrabutylammonium bromide. The desired products,
1,4-bis[o-(R-2-carboxamidophenyl)]-1,4-dithiobutane, R ¼ quinoline (1), furan (2),
thiophene (3), pyridine (4), and pyrazine (5), were obtained in good yields and shorter
reaction times.
Keywords Amide-thioethers; environmentally friendly conditions; ionic liquid; synthesis
INTRODUCTION
The transition-metal coordination chemistry of flexible hybrid N,S-donor ligands
in designing new molecular architectures[1,2] and in bioinorganic chemistry[3–5] has been
the focus of growing attention.[6–9] Many of these efforts have been devoted to the
design and synthesis of new caboxamide ligands, and the standard preparation method
uses pyridine as the solvent.[10–15] Drawbacks of this method include modest yields as
well as potential health hazards resulting from the pyridine solvent. Thus, preparation
Received June 29, 2010.
Address correspondence to Soraia Meghdadi, Department of Chemistry, Isfahan University of
Technology, Hezar jerib, Isfahan 84156-83111, Iran. E-mail: smeghdad@cc.iut.ac.ir
246

SYNTHESIS OF AMIDE-THIOETHERS
247
Scheme 1. Synthesis of amide-thioethers in ionic liquid, TBAB, as reaction medium.
of differently functionalized carboxamide ligands under green conditions with shorter
reaction time and better yield would be highly desirable for a range of applications. In
this context, we have recently developed a benign and efficient method for the synthesis
of these ligands using tetrabutylammonium bromide (TBAB) as the reaction medium,
eliminating the necessity to use pyridine as solvent.[16]
Described here is an extension of this technique to new carboxamide ligands
that incorporate thioether donor sites. We report the synthesis of three new ligands
(1–3), plus two previously reported ones (4 and 5),[3] from the appropriate precursors
using TBAB as the reaction medium (Scheme 1).
RESULTS AND DISCUSSION
Our goal was to apply the newly developed method of synthesis that we used
for carboxamides[16] to the production of amide-thioethers in the ionic liquid,
TBAB. We demonstrate here that the coupling between the diamine thioether
and carboxylic acid occurs under benign conditions with moderate to excellent
yields, when pyridine is replaced by TBAB as the reaction medium (Scheme 1).
To optimize the reaction conditions, the reaction temperature, period of heating,
and amount of TBAB were examined. Interestingly, the reaction time was reduced
from 5 h in the established method[3] to 1 h in the new method and better yields
were obtained in most cases.
=
The spectral analysis showed infrared (IR) bands for NꢀH and C O groups in
1
their respective regions, listed in the Experimental section. The H NMR spectra
display resonances for the amidic NꢀH’s, aromatic ring protons, and aliphatic
protons in the 9.21–11.47, 6.55–9.45, and 2.90–3.16 regions respectively. The mass
spectral data and elemental analyses are in excellent agreement with the molecular
weight of the amide-thioeters prepared by this method.

248
S. MEGHDADI, V. MIRKHANI, AND P. C. FORD
EXPERIMENTAL
Materials
All solvents and chemicals were purchased from Merck and Aldrich (Grade
Pro Analysis). 1,2-Di(o-aminophenylthio)ethane (DAPTE) was prepared using the
reported procedure.[2] 1H NMR spectra were recorded on a Bruker Avance 500
(500-MHz) spectrometer. Infrared (IR) spectra were obtained with a ATI Mattson
Research Series II Fourier transform (FT)–IR spectrophotometer. The mass spectra
were recorded using a Waters micromass Q-TOF-2 spectrometer in positive-ion
mode. Elemental analyses were performed using a CE440 elemental analyzer.
General Procedures
A dried, 25-mL, round-bottom flask was charged with triphenylphosphite
(TPP) (10 mmol, 3.10 g), tetrabutylammonium bromide (TBAB) (5 mmol, 1.61 g),
the appropriate carboxylic acid (10 mmol), and DAPTE (5 mmol, 1.38 g). The flask
was placed in an oil bath, and the reaction mixture was heated until a homogeneous
solution was formed. The solution was stirred for 1 h at 120 ꢁC. The viscous slurry
was treated with 10 ml methanol, and the resulting solid was filtered off, washed with
cold ethanol, and dried in vacuo.
Selected Data
1,4-Bis[o-(quinoline-2-carboxamidophenyl)]-1,4-dithiobutane (1). White
1
solid (yield: 91%). IR (KBr, cmꢀ1) 3297 (N-H), 1685 (C O). H NMR (500 MHz,
=
CDCl3): d (ppm from TMS): 11.47 (s, 2H, amide NH), 8.67(d, 2H, ArH), 8.14
(d, 2H, ArH), 8.10 (d, 2H, ArH), 7.92 (d, 2H, ArH), 7.78 (d, 2H, ArH), 7.63
(t, 2H, ArH), 7.59 (d, 2H, ArH), 7.55 (m, 2H, ArH), 7.40 (t, 2H, ArH), 7.03
(t, 2H, ArH), 3.16 (s, 4H, SCH2). ESI-MS: m=z ¼ 609.14 [M þ Na]þ. Anal. calcd.
for C34H26N4O2S2: C, 69.60; H, 4.47; N, 9.55. Found: C, 69.10; H, 4.40; N, 9.52.
1,4-Bis[o-(furan-2-carboxamidophenyl)]-1,4-dithiobutane (2). White solid
1
(yield: 60%). IR (KBr, cmꢀ1) 3343 (N-H), 1682 (C O). H NMR (500 MHz, CDCl3):
=
d (ppm from TMS): 9.50 (s, 2H, amide NH), 8.56 (d, 2H, ArH), 7.50 (m, 4H, ArH),
7.40 (t, 2H, ArH), 7.24 (d, 2H, ArH), 7.06 (t, 2H, ArH), 6.55 (t, 2H, ArH), 2.91
(s, 4H, SCH2). ESI-MS: m=z ¼ 487.09 [M þ Na]þ. Anal. calcd. for C24H20N2O4S2:
C, 62.05; H, 4.34; N, 6.03. Found: C, 61.50; H, 4.25; N, 6.12.
1,4-Bis[o-(thiophene-2-carboxamidophenyl)]-1,4-dithiobutane (3). White
1
solid (yield: 50%). IR (KBr, cmꢀ1) 3315 (N-H), 1650 (C O). H NMR (500 MHz,
=
CDCl3): d (ppm from TMS): 9.21 (s, 2H, amide NH), 8.52 (d, 2H, ArH), 7.67
(d, 2H, ArH), 7.54 (d, 2H, ArH), 7.49 (d, 2H, ArH), 7.41 (t, 2H, ArH), 7.13 (t,
2H, ArH), 7.07 (t, 2H, ArH), 2.90 (s, 4H, SCH2). ESI-MS: m=z ¼ 519.04 [M þ Na]þ.
Anal. calcd. for C24H20N2O2S4: C, 58.04; H, 4.06; N, 5.64. Found: C, 57.60; H, 3.94;
N, 5.69.
1,4-Bis[o-(pyridine-2-carboxamidophenyl)]-1,4-dithiobutane (4). White
1
solid (yield: 90%). IR (KBr, cmꢀ1) 3287 (N-H), 1690 (C O). H NMR (500 MHz,
=

SYNTHESIS OF AMIDE-THIOETHERS
249
CDCl3): d (ppm from TMS): 11.18 (s, 2H, amide NH), 8.65 (d, 2H, ArH), 8.53
(d, 2H, ArH), 8.23 (d, 2H, ArH), 7.86 (t, 2H, ArH), 7.51 (d, 2H, ArH), 7.40
(m, 4H, ArH), 7.04 (t, 2H, ArH), 3.00 (s, 4H, SCH2). ESI-MS: m=z ¼ 509.12
[M þ Na]þ. Anal. calcd. for C26H22N4O2S2: C, 64.17; H, 4.56; N, 11.51. Found: C,
64.22; H, 4.59; N, 11.46.
1,4-Bis[o-(pyrazine-2-carboxamidophenyl)]-1,4-dithiobutane (5). Pale
yellow solid (yield: 66%). IR (KBr, cmꢀ1) 3295 (N-H), 1686 (C O). 1H NMR
=
(500 MHz, CDCl3): d (ppm from TMS): 10.86 (s, 2H, amide NH), 9.45 (s, 2H,
ArH), 8.78 (d, 2H, ArH), 8.61 (d, 2H, ArH), 8.51 (d, 2H, ArH), 7.51 (d, 2H,
ArH), 7.41 (t, 2H, ArH), 7.07 (t, 2H, ArH), 2.94 (s, 4H, SCH2). ESI-MS:
m=z ¼ 511.10 [M þ Na]þ. Anal. calcd. for C24H20N6O2S2: C, 59.00; H, 4.13; N,
16.50. Found: C, 58.5; H, 4.07; N, 17.20.
SUMMARY
We have described a new and convenient method for the synthesis of five
potentially hexadentate amide-thioether ligands containing thioether donor sites.
To the best of our knowledge, this is the first time that an ionic liquid has been used
as the reaction media for the synthesis of the aforementioned ligands. This relatively
benign method affords good yields and shorter reaction times, and, most important,
replaces the toxic pyridine by TBAB. These advantages open a new avenue in the
synthesis of amide-thioether ligands using more environmentally friendly conditions.
Further application of TBAB in the green and efficient synthesis of other carboxa-
mide ligands is under way in our laboratory.
ACKNOWLEDGMENTS
Partial support of this work by the Isafan University of Technology (IUT)
Research Council is gratefully acknowledged. Also acknowledged is partial support
from the U.S. National Science Foundation Grant NSF-CHE-0749524 to P. C. F.
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