An efficient synthesis of imidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxides by a one-pot, three-component reaction in water
- Jabbar Khalafy
,Nasser EtivandandNeda Khalillou
Abstract
An improved synthesis of 2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-aryl-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide derivatives4a–k via the reaction of aryl glyoxal monohydrates1a–k, quinoline-2,4-diol2 and 2-amino-[1,3,4]thiadiazole(3) in the presence of Et3N/sulfamic acid in H2O is described. This green protocol is characterized by the use of the readily available catalyst and reactants, short reaction times, operational simplicity and high yields of products. The structures of all compounds were characterized by1H NMR,13C NMR and Fourier-transform infrared (FT-IR) spectral data and microanalyses.
Introduction
Fused heterocyclic compounds containing nitrogen atoms are an important class of natural and synthetic products [1], [2], [3], [4], [5], [6], [7], [8]. The bicyclic imidazo[2,1-b][1,3,4]thiadiazole system, composed of imidazole and 1,3,4-thiadiazole moieties [9], is present in natural products [10] including alkaloids [11] and in pharmaceuticals [12]. Applications in oncology [13], infectiology [14], cardiovascular diseases [15] or central nervous system neurodegenerative diseases [16] have been reported. Imidazo[2,1-b][1], [3], [4]thiadiazoles exhibit biological activities including antibacterial [17], antifungal [18], antitubercular [19], anti-inflammatory [20] and anticancer [21] properties. Some drugs of this class are displayed inFigure 1.
![Figure 1 Drugs containing an imidazo[2,1-b][1,3,4]thiadiazole unit.](/image.pl?url=https%3a%2f%2fdoi.org%2fdocument%2fdoi%2f10.1515%2fhc-2018-0117%2fasset%2fgraphic%2fj_hc-2018-0117_fig_001.jpg&f=jpg&w=240)
Drugs containing an imidazo[2,1-b][1,3,4]thiadiazole unit.
The outstanding potential of one-pot multicomponent reactions (MCRs) is the synthesis without separating intermediate species, purification or swapping the solvent [22], [23], [24]. In addition, such reactions often are characterized by extraordinary chemo- and regioselectivity [25], [26]. Accordingly, industrial and academic researchers have increasingly focused on the development of MCRs [27]. The use of water as a green solvent for the synthesis of heterocyclic compounds is also one of the goals of the chemists [28], [29]. Unfortunately, imidazo[2,1-b][1,3,4]thiadiazoles have been synthesized by using reactions in organic solvents [30], [31], [32], [33], [34], [35], [36].
Results and discussion
In continuation of our efforts on synthesis of new heterocyclic compounds by using MCRs [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], herein we report the efficient synthesis of 5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-aryl-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxides4a–k by a one-pot three-component reaction (TCR) of aryl glyoxal monohydrates1a–k, quinoline-2,4-diol2 and 5-ethyl-1,3,4-thiadiazol-2-amine3 in water under reflux conditions. The synthesized new compounds are interesting from the biological and pharmaceutical points of view (Scheme 1). The starting aryl glyoxal monohydrates containing electron-donating and electron-withdrawing substituents were prepared by oxidation of the corresponding acetophenones with SeO2 in H2O/dioxane under reflux conditions [48]. This work started with the examination of a one-pot TCR using aryl glyoxal monohydrate1a (1.00 mmol), quinoline-2,4-diol2 (1.00 mmol) and 5-ethyl-1,3,4-thiadiazol-2-amine3 (1.00 mmol). First, this model reaction was attempted in the absence of any catalyst in different organic solvents, but no product formation was observed after 24 h of stirring under reflux. In a similar way, in the presence of basic catalysts such as K2CO3, 1,4-diazabicyclo[2.2.2]octane (DABCO) and Et3N in organic solvents, no product was formed even after 18 h at elevated temperatures. The use of acidic catalysts includingL-proline, InCl3, FeCl3 and ZnO in organic solvents also failed to produce the desired product4a. Finally, in the presence of sulfamic acid as a catalyst in water under reflux, the desired product4a was obtained in a 27% yield. It was found that under the optimized conditions the reaction leading to4a is best conducted in water under reflux in the presence of the catalyst composed of sulfamic acid (25 mol%) and triethylamine (TEA, 10 mol%). Under these conditions, the desired product4a was synthesized in an 87% yield after 3 h of reflux. The yield of4a was 40% for the reaction conducted at room temperature for 24 h. The reaction mixture was alkaline (pH=8) after addition of TEA, became acidic (pH=3) after addition of sulfamic acid and remained acidic during heating for 3 h.
![Scheme 1 Synthesis of imidazo[2,1-b][1,3,4]thiadiazoles 4a–k via the one-pot TCRs.](/image.pl?url=https%3a%2f%2fdoi.org%2fdocument%2fdoi%2f10.1515%2fhc-2018-0117%2fasset%2fgraphic%2fj_hc-2018-0117_scheme_001.jpg&f=jpg&w=240)
Synthesis of imidazo[2,1-b][1,3,4]thiadiazoles4a–k via the one-pot TCRs.
In order to assess the scope of the reaction, a series of aryl glyoxal monohydrates1b–k were allowed to react with 2,4-quinolinediol2 and 5-ethyl-1,3,4-thiadiazol-2-amine3 under the optimized conditions. In all cases, the expected imidazo[2,1-b][1,3,4]thiazoles4b–k were obtained in high yields (Scheme 1).
The given structures of all synthesized imidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide derivatives4a–k were confirmed by analysis of their1H NMR,13C NMR and Fourier-transform infrared (FT-IR) spectral data and microanalyses. In the1H NMR spectra, a sharp singlet atδ 11.20–11.30 can be attributed to the O-H group. The N-H group of the dihydroimidazole moiety shows as a doublet or a broad singlet atδ 8.98–9.82. The protons of aromatic rings appear aroundδ 6.70–8.20. The C-H absorption of the dihydroimidazole resonates as a doublet or a broad singlet at aroundδ 6.72–8.31 due to coupling with N-H. Upon addition of D2O, the N-H absorption disappears and the C-H signals are converted to a sharp singlet due to decoupling.
A mechanism for the synthesis of compounds4a–k is suggested inScheme 2. The first steps are trimethylamine-mediated conversion of the aryl glyoxal monohydrates1a–k to the aryl glyoxals by dehydration and ionization of quinoline-2,4-diol2 to its enolate ion. The Knoevenagel condensation between the two reactants mentioned leads to the formation of an intermediate productA. The regioselective Michael addition of 5-ethyl-1,3,4-thiadiazol-2-amine3 toA in the presence of sulfamic acid leads to the formation of an intermediate productB, which is subsequently converted to the observed hydroxides4a–k by intramolecular condensation, followed by keto-enol tautomerization (Scheme 2).
![Scheme 2 Proposed mechanism for the synthesis of imidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxides 4a–k.](/image.pl?url=https%3a%2f%2fdoi.org%2fdocument%2fdoi%2f10.1515%2fhc-2018-0117%2fasset%2fgraphic%2fj_hc-2018-0117_scheme_002.jpg&f=jpg&w=240)
Proposed mechanism for the synthesis of imidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxides4a–k.
Conclusions
A green, efficient method for the synthesis of imidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide compounds4a–k, via a one-pot TCR of aryl glyoxals, quinoline-2,4-diol and 5-ethyl-1,3,4-thiadiazol-2-amine in the presence of TEA (10 mol%)/sulfamic acid (25 mol%) in water was developed. The simple work-up, operational simplicity, regioselectivity and high yields are the main advantages of this protocol.
Experimental
All chemicals were obtained from Arcos and Merck companies and were used without further purification. Melting points were determined on a Philip Harris C4954718 apparatus and are uncorrected. The progress of the reactions were monitored by thin layer chromatography (TLC) on Merck’s silica gel plates. Infrared spectra were recorded on a Thermo Nicolet Nexus 670 FT-IR instrument using KBr discs.1H and13C NMR spectra were recorded on a Bruker Advance AQS 300 MHz spectrometer in DMSO-d6 at 300 MHz and 75.5 MHz, respectively.
General procedure for the synthesis of 2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-aryl-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxides 4a–k
A suspension of quinoline-2,4-diol2 (0.161 g, 1.00 mmol) and TEA (10 mol%) in water (5 mL) was stirred under reflux for 10 min to make a solution. Aryl glyoxal1a–k (1.00 mmol), 5-ethyl-1,3,4-thiadiazol-2-amine3 (0.129 g, 1.00 mmol) and sulfamic acid (25 mol%) were added to the solution and the mixture was stirred under reflux for the period of time indicated below. The progress of the reaction was monitored by TLC eluting with chloroform/methanol (10:1). After completion of the reaction, the residue of the product4a–k was filtered and washed with water.
2-Ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-phenyl-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4a)
Yield 87%; white solid; mp 196–197°C; reaction time 3 h; IR: νmax 3297, 2940, 2845, 1690, 1648, 1606, 1508, 1441, 1390, 1272, 748 cm−1;1H NMR:δ 11.24 (s, 1H, exchanged by D2O addition, OH), 9.06 (bd, 1H,J=7 Hz, exchanged by D2O addition, NH), 7.96 (d,J=8 Hz, 1H, Ar), 7.72 (d,J=8 Hz, 2H, Ar), 7.46 (t,J=7 Hz, 2H, Ar), 7.35 (t,J=7.5 Hz, 2H, Ar), 7.17 (d,J=8 Hz, 1H, Ar), 7.13 (d,J=8 Hz, 1H, Ar), 6.32 (d,J=7 Hz, 1H, converted to a singlet by D2O addition, CH), 2.82 (q,J=7.5 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 194.2, 169.0, 162.3, 162.0, 161.2, 138.8, 136.0, 132.5, 129.5, 129.1, 127.57, 126.9, 125.3, 122.8, 121.0, 116.4, 111.0, 25.1, 23.5. Anal. Calcd for C21H18N4O3S: C, 62.06; H, 4.46; N, 13.78. Found: C, 62.40; H, 4.41; N, 14.13.
2-Ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-(4-methoxyphenyl)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4b)
Yield 91%; white solid; mp 210–211°C; reaction time 2 h; IR: νmax 3310, 2942, 2842, 1664, 1606, 1545, 1505, 1442, 1391, 1252, 1171, 752 cm−1;1H NMR:δ 11.22 (s, 1H, exchanged by D2O addition, OH), 8.99 (d, 1H,J=5 Hz, exchanged by D2O addition, NH), 7.96 (d,J=7.5 Hz, 2H, Ar), 7.46 (t,J=9 Hz, 1H, Ar), 7.20–7.13 (m, 2H, Ar), 6.90 (d,J=9 Hz, 2H, Ar), 6.24 (d,J=5 Hz, converted to a singlet by D2O addition, 1H, CH), 3.73 (s, 3H, OCH3), 2.82 (q, 3H,J=7.5 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 192.5, 168.9, 163.1, 162.3, 161.9, 161.8, 138.8, 131.4, 129.1, 128.4, 125.3, 122.8, 120.9, 116.51, 114.8, 112.9, 111.3, 56.8, 25.0, 23.5. Anal. Calcd for C22H20N4O4S: C, 60.54; H, 4.62; N, 12.84. Found: C, 60.76; H, 4.53; N, 12.75.
2-Ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-(3-methoxyphenyl)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4c)
Yield 93%; white solid; mp 197–198°C; reaction time 2.5 h; IR: νmax 3321, 2950, 2843, 1692, 1648, 1606, 1503, 1442, 1388, 1275, 1033, 754 cm−1;1H NMR:δ 11.27 (s, 1H, exchanged by D2O addition, OH), 8.98 (bd, 1H,J=5 Hz, exchanged by D2O addition, NH), 7.95 (d,J=8 Hz, 1H, Ar), 7.47 (t,J=8 Hz, 1H, Ar), 7.31–7.10 (m, 2H, Ar), 7.03 (d,J=8 Hz, 1H, Ar), 6.32 (d,J=5 Hz, 1H, CH), 3.73 (s, 3H, OCH3), 2.82 (q,J=7.5 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 193.9, 168.9, 162.4, 159.8, 143.6, 138.7, 137.6, 135.4, 131.2, 129.3, 125.3, 124.0, 122.9, 122.1, 121.3, 121.0, 116.4, 111.0, 104.1, 56.5, 25.1, 23.5. Anal. Calcd for C22H20N4O4S: C, 60.54; H, 4.62; N, 12.84. Found: C, 60.34; H, 4.62; N, 12.56.
6-(3,4-Dimethoxyphenyl)-2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4d)
Yield 90%; white solid; mp 198–199°C; reaction time 2 h; IR: νmax 3343, 3283, 2962, 1691, 1630, 1512, 1453, 1407, 1260, 1161, 1018, 760 cm−1;1H NMR:δ 11.26 (s, 1H, exchanged by D2O addition, OH), 8.92 (bs, 1H, exchanged by D2O addition, NH), 7.96 (d,J=7.5 Hz, 1H, Ar), 7.47 (t,J=7.5 Hz, 1H, Ar), 7.35 (s, 2H, Ar), 7.30–7.23 (m, 2H, Ar), 6.92 (d,J=9 Hz, 1H, Ar), 6.29 (d,J=4 Hz,1H, CH), 3.73 (s, 3H, OCH3), 3.67 (s, 3H, OCH3), 2.82 (q,J=7 Hz, 2H, CH2), 1.21 (t,J=7 Hz, 3H, CH3);13C NMR:δ 192.4, 168.9, 162.4, 161.7, 161.2, 153.0, 148.4, 138.8, 132.7, 130.5, 128.2, 128.1, 125.2, 125.2, 123.0, 122.9, 121.0, 116.4, 111.3, 57.5, 56.7, 25.1, 23.5. Anal. Calcd for C23H22N4O5S: C, 59.22; H, 4.75; N, 12.01. Found: C, 59.36; H, 4.71; N, 12.11.
2-Ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-(p-tolyl)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4e)
Yield 89%; white solid; mp 215–216°C; reaction time 2 h; IR: νmax 3320, 2948, 2845, 1650, 1608, 1538, 1503, 1440, 1387, 1273, 725 cm−1;1H NMR:δ 11.20 (s, 1H, exchanged by D2O addition, OH), 9.02 (m, 1H, exchanged by D2O addition, NH), 7.95 (d,J=7.5 Hz, 1H, Ar), 7.62 (d,J=7.5 Hz, 2H, Ar), 7.46 (t,J=7.5 Hz, 1H, Ar), 7.20 (t,J=7.5 Hz, 4H, Ar), 6.27 (d, 1H,J=5.7 Hz exchanged to singlet by D2O addition, CH), 2.82 (q,J=7.5 Hz, 2H, CH2), 2.24 (s, 3H, CH3), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 193.7, 169.0, 162.3, 161.9, 143.2, 138.8, 133.3, 130.0, 129.2, 128.2, 127.0, 125.3, 122.8, 121.0, 116.5, 114.6, 111.2, 25.1, 23.5. Anal. Calcd for C22H20N4O3S: C, 62.84; H, 4.79; N, 13.32. Found: C, 62.75; H, 4.83; N, 13.50.
2-Ethyl-6-(4-hydroxy-3-methoxyphenyl)-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4f)
Yield 94%; white solid; mp 221–222°C; reaction time 3 h; IR: νmax 3074, 2946, 2932, 1634, 1605, 1511, 1399, 1289, 1183, 1029, 769 cm−1;1H NMR:δ 11.26 (s, 1H, exchanged by D2O addition, OH), 9.82 (bd, 1H,J=7 Hz exchanged by D2O addition, NH), 8.87 (s, 1H, exchanged by D2O addition, OH), 7.95 (d,J=8. Hz, 1H, Ar), 7.48 (t,J=7.5 Hz, 1H, Ar), 7.34 (s, 1H, Ar), 7.26 (d,J=8 Hz, 1H, Ar), 7.19 (d,J=7.5 Hz, 2H, Ar) 6.70 (d,J=8 Hz, 1H, Ar), 6.26 (bd,J=7 Hz, 1H, converted to a singlet by D2O addition, CH), 3.79 (s, 3H, OCH3), 2.82 (q,J=7 Hz, 2H, CH2), 1.21 (t,J=7 Hz, 3H, CH3);13C NMR:δ 192.2, 168.9, 165.8, 162.4, 161.5, 151.7, 147.3, 138.7, 132.7, 130.5, 127.0, 125.1, 123.5, 122.9, 121.5, 121.0, 116.4, 113.0, 111.4, 56.6, 25.0, 23.5. Anal. Calcd for C22H20N4O5S: C, 58.40; H, 4.46; N, 12.38. Found: C, 58.23; H, 4.62; N, 12.13.
6-(4-Chlorophenyl)-2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4g)
Yield 89%; white solid; mp 217–218°C; reaction time 2 h; IR: νmax 3307, 2951, 2855, 1689, 1648, 1605, 1502, 1390, 1268, 1094, 754 cm−1;1H NMR:δ 11.25 (s, 1H, exchanged by D2O addition, OH), 9.07 (m, 1H,J=6 Hz, exchanged by D2O addition, NH), 7.96 (d,J=8 Hz, 1H, Ar), 7.73–7.68 (m, 2H, Ar), 7.47–7.40 (m, 3H, Ar), 7.21–7.12 (m, 2H, Ar), 6.32 (m, 1H, CH), 2.82 (q,J=7.5 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 193.4, 169.0, 162.3, 161.3, 138.8, 137.7, 134.8, 131.0, 129.8, 128.7, 127.7, 125.4, 122.9, 121.1, 116.5, 114.6, 110.8, 25.0, 23.5. Anal. Calcd for C21H17ClN4O3S: C, 57.21; H, 3.89; N, 12.71. Found: C, 57.24; H, 3.85; N, 12.57.
6-(4-Bromophenyl)-2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4h)
Yield 87%; white solid; mp 217–218°C; reaction time 2.5 h; IR: νmax 3312, 2955, 2860, 1690, 1646, 1606, 1502, 1452, 1388, 1271, 1067, 756 cm−1;1H NMR:δ 11.26 (s, 1H, exchanged by D2O addition, OH), 9.09 (d, 1H,J=6 Hz exchanged by D2O addition, NH), 7.95 (d,J=8 Hz, 1H, Ar), 7.63 (d,J=8 Hz, 2H, Ar), 7.58 (d,J=8 Hz, 2H, Ar), 7.47 (t,J=7 Hz, 1H, Ar), 7.16 (t,J=8 Hz, 2H, Ar), 6.32 (m, 1H, converted to a singlet by D2O addition, CH), 2.83 (q,J=7 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 193.6, 169.0, 162.3, 143.5, 138.8, 135.1, 132.8, 131.0, 128.9, 126.8, 125.4, 124.0, 122.9, 121.0, 116.5, 110.7, 104.1, 25.0, 23.5. Anal. Calcd for C21H17BrN4O3S: C, 51.97; H, 3.53; N, 11.54. Found: C, 52.05; H, 3.47; N, 11.32.
2-Ethyl-6-(4-fluorophenyl)-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4i)
Yield 91%; white solid; mp 197–198°C; reaction time 2 h; IR: νmax 3300, 2932, 2855, 1691, 1647, 1605, 1507, 1448, 1391, 1264, 1233, 752 cm−1;1H NMR:δ 11.25 (s, 1H, exchanged by D2O addition, OH), 9.05 (bs, 1H, exchanged by D2O addition, NH), 7.96 (d,J=7 Hz, 1H, Ar), 7.85–7.66 (m, 2H, Ar), 7.54–7.38 (m, 1H, Ar), 7.30–7.00 (m, 4H, Ar), 6.31 (s, 1H, CH), 2.83 (q,J=7 Hz, 2H, CH2), 1.21 (t,J=7 Hz, 3H, CH3);13C NMR:δ 192.9, 168.9, 162.3, 143.5, 138.8, 135.4, 132.6, 132.0, 129.8, 125.4, 124.0, 122.1, 117.9, 116.5, 114.9, 110.9, 104.2, 25.0, 23.5. Anal. Calcd for C21H17FN4O3S: C, 59.43; H, 4.04; N, 13.20. Found: C, 59.72; H, 3.98; N, 12.97.
2-Ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-6-(4-nitrophenyl)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4j)
Yield 87%; yellow solid; mp 220–221°C; reaction time 3 h; IR: νmax: 3308, 2950, 2857, 1693, 1648, 1607, 1518, 1387, 1353, 1270, 1104, 855 cm−1;1H NMR:δ 11.27 (s, 1H, exchanged by D2O addition, OH), 9.14 (m, 1H, exchanged by D2O addition, NH), 8.20 (d,J=8 Hz, 2H, Ar), 8.07–7.75 (m, 3H, Ar), 7.46 (t,J=8 Hz, 1H, Ar), 7.30–7.00 (m, 2H, Ar), 6.44 (m, 1H, converted to a singlet by D2O addition, CH), 2.83 (q,J=7 Hz, 2H, CH2), 1.21 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 192.5, 168.7, 148.7, 143.8, 142.6, 138.0, 129.0, 126.8, 125.3, 125.1, 124.1, 123.3, 123.2, 122.2, 117.9, 116.0, 104.0, 25.0, 23.6. Anal. Calcd for C21H17N5O5S: C, 55.87; H, 3.80; N, 15.51. Found: C, 55.35; H, 3.74; N, 15.78.
6-([1,1′-Biphenyl]-4-yl)-2-ethyl-5-(2-hydroxy-4-oxoquinolin-3(4H)-ylidene)-5,6-dihydroimidazo[2,1-b][1,3,4]thiadiazol-7-ium hydroxide (4k)
Yield 91%; white solid; mp 198–199°C; reaction time 3 h; IR: νmax 3313, 2954, 2860, 1690, 1646, 1606, 1502, 1451, 1389, 1270, 756 cm−1;1H NMR:δ 11.26 (s, 1H, exchanged by D2O addition, OH), 9.08 (m, 1H, exchanged by D2O addition, NH), 7.98 (d,J=8 Hz, 1H, Ar), 7.82 (d,J=8 Hz, 2H, Ar), 7.68 (d,J=8 Hz, 2H, Ar), 7.65 (d,J=7.5 Hz, 2H, Ar), 7.50–7.30 (m,J=8 Hz, 4H, Ar), 7.16 (t,J=8 Hz, 2H, Ar), 6.35 (m, 1H, converted to a singlet by D2O addition, CH), 2.82 (q,J=7.5 Hz, 2H, CH2), 1.22 (t,J=7.5 Hz, 3H, CH3);13C NMR:δ 193.7, 169.0, 162.4, 144.3, 139.8, 139.2, 134.7, 130.8, 130.3, 129.9, 128.5, 128.4, 127.6, 126.4, 126.3, 125.4, 124.0, 123.1, 122.0, 116.5, 111.0, 25.0, 23.5. Anal. Calcd for C27H22N4O3S: C, 67.20; H, 4.60; N, 11.61. Found: C, 67.11; H, 4.59; N, 11.26.
Acknowledgment
The authors gratefully acknowledge the financial assistance from Urmia University.
References
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