Table of Contents Author Guidelines Submit a Manuscript
Journal of Chemistry
Volume 2015, Article ID 382381, 8 pages
http://dx.doi.org/10.1155/2015/382381
Research Article

Synthesis and Characterization of Novel Thieno-Fused Bicyclic Compounds through New Enaminone Containing Thieno[2,3-b]pyridine Scaffold

1Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
2Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt
3Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
4Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
5Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
6Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Al-Mukarramah 21955, Saudi Arabia

Received 6 October 2015; Accepted 2 November 2015

Academic Editor: Josefina Pons

Copyright © 2015 Yahia Nasser Mabkhot et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

New substituted thieno-fused bicyclic compounds named (1H-pyrazol-3-yl)thieno[2,3-b]pyridin-4(7H)-one derivatives (4a,b), 2-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (5), phenylthieno[2,3-b]pyridin-4(7H)-one derivatives (6ac, 7ac, and 8), and 3-(3-methyl-4-oxo-7-phenyl-4,7-dihydrothieno[2,3-b]pyridin-2-yl)-3-oxopropyl 4-chlorobenzoate (9) were synthesized by reacting the new enaminone (3) with different reagents. The chemical structure of the new molecules was determined by means of different spectroscopic methods such as NMR, IR, MS spectrometry, and by CHN analyses. The molecular structure of the 1,1′-(3-methyl-5-(phenylamino)thiophene-2,4-diyl)diethanone (2) was successfully solved by X-ray single crystal.

1. Introduction

E naminones are a precursor for the synthesis of heterocycles which have been devoted in the last decade. These synthons were reacted with several nucleophilic and electrophilic reagents to construct new heterocyclic systems of pharmaceutical targets such as pyrazolo[3,4-d]pyrimidin-4-one, pyrazolo[1,5-a]pyrimidine derivatives [1], pyrido[2,3-d] [1,2,4]triazolino[4,3-a]pyrimidin-4-one, pyridino[2,3-d]pyrimidin-4-one, and pyrido[2,3-d] [1,2,4]triazolino[4,5-a]pyrimidin-5-one [2]. Thieno-fused bicyclic compounds incorporate pyrimidine, pyrazoles, benzo[4,5]imidazo[1,2-a]pyrimidine and [1,2,4]triazolo[1,5-a]pyrimidine rings [3], isoquinoline [4], and natural products and their analogues [5, 6].

Additionally, the thieno[2,3-b]pyridine core structure and its substituents are scaffold possessing potential biological activities including estrogenic, antihypertensive anti-inflammatory, antiviral, anticancer, and antimicrobial activities [715]; indeed, many substituted thieno[2,3-b]pyridine building blocks were synthesized and recognized for the selectivity of these bioisosteres of the antibacterial quinolones such as ofloxacin, ciprofloxacin, and norfloxacin [16, 17]. In continuation of our interest in the chemistry of thieno-fused bicyclic compounds [1821] to develop new library of pharmaceutical targets we started from new enaminone 3 as precursor for synthesis of new thieno-fused bicyclic compounds containing thieno[2,3-b]pyridine core.

2. Experimental Section

2.1. General

All the chemical products were purchased from various suppliers, including Sigma-Aldrich and Fluka, and were used without further purification, unless otherwise stated. All melting points were measured on a Gallenkamp melting point apparatus in open glass capillaries and are uncorrected. IR spectra were recorded as KBr pellets on a Nicolet 6700 FT-IR spectrophotometer. The NMR spectra were recorded on a Varian Mercury Jeol-400 NMR spectrometer. 1HNMR (400 MHz) and 13C-NMR (100 MHz) were run in deuterated dimethyl sulphoxide (DMSO-d6). Chemical shifts () are referred to in ppm while J-coupling constants were represented in Hz. Mass spectra were recorded on a Jeol of JMS-600 H. Elemental analysis was carried out on Elmer 2400 Elemental Analyzer, CHN mode.

1,1-(3-Methyl-5-(phenylamino)thiophene-2,4-diyl)diethanone (2). In a round bottom flask (100 mL) acetylacetone (10 mL, 100 mmol) was dissolved in DMF (45 mL); then the reaction mixture was kept at RT for 5 mins; subsequently, phenyl isocyanate (13.5 mL, 100 mmol) was added and stirred for further 30 mins. the reaction mixture was then cooled by using ice bath, and chloroacetone (9.25 mL, 100 mmol) was added and stirred for 15 mins. The reaction mixture was allowed to warm to rt and continued stirring for 30 mins. The precipitated product was filtered off and washed by H2O and dried. The crude product was purified by crystallization from glacial acetic acid to afford the pure compound in yellow crystals.

Yield: 95%; m.p. 115°C; IR (): 1492, 1602–1646 (C=O), 3415 (NH); 1H-NMR (DMSO-d6): δ 2.85 (s, 3H, CH3), 3.38 (s, 6H, 2CH3), 5.85 (s, 1H, NH), 7.63–7.84 (m, 5H, C6H5); 13C-NMR: δ, 16.08 (CH3), 40, 46 (COCH3), 120.19, 122.46, 130.55, (Ar-C), 137.04 (CH3COC), 140.95 (Ar-C-N), 142.34 (CH3-C); MS m/z (%): 274 [M+, 100]; Anal. calcd. for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12; S, 11.73; Found: C, 65.92; H, 5.55; N, 5.10; S, 11.70.

2-(3-(Dimethylamino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (3). A mixture of 1,1′-(3-methyl-5-(phenylamino)thiophene-2,4-diyl)diethanone 2 (1.37 g, 0.5 mmol) and DMF-DMA (1.19 mL, 0.01 mol) was refluxed in m-xylene (15 mL) for 3 h. After cooling, the resulting solid product was collected by filtration to give the desired product 3 used for the next step without any further purification.

Yellow crystal; Yield: 63%; m.p. 235°C; IR (): 1593 (C=C), 1613–1640 (C=O).; 1H-NMR (DMSO-d6): δ, 2.85 (s, 3H, CH3), 3.16 (s, 6H, N(CH3)2), 5.36 (d, 1H, ) 5.39 (d, 1H, ), 6.14 (d, 1H, ) 6.16 (d, 1H, ), 7.63–7.68 (m, 5H, C6H5); 13C-NMR: δ, 16.12 (-CH3), 45.15 (-N=(CH3)2), 94.03 (-CH=CH-N=), 153.15 (-), 126.35, 128.58, 130.55 (Ph), 142.35 (-C-CH3), 115.14 (-), 154.45 (-), 154.54 (=CNS), 176.49, 180.51 (C=O); MS m/z (%): 325 [M+, 30%]; Anal. calcd. for C18H17N2O2S: C, 67.43; H, 5.36; N, 8.28; S, 9.47; Found: C, 67.45; H, 5.40; N, 8.31; S, 9.50.

2.2. General Procedure for the Preparation of Compounds 4a,b

Compounds 4a,b were prepared using the following general procedure.

Compound 3 (0.131 g, 0.5 mmol) was added to hydrazine hydrate (2 mL, 63 mmol) or phenylhydrazine (1 mL, 10 mmol) (to make compounds 4a,b, resp.). The mixture of compound 3 and the appropriate hydrazine was refluxed until compound 3 is completely dissolved, followed by addition of the mixed solvent EtOH/DMF. The reaction mixture was then refluxed for 6-7 h and the product was filtered after cooling. The desired product was obtained in a pure form by recrystallization from MeOH. Using the general procedure, the following compounds were prepared.

3-Methyl-7-phenyl-2-(1H-pyrazol-3-yl)thieno[2,3-b]pyridin-4(7H)-one (4a). Red crystal; Yield: 67%; m.p. 285°C; IR (): 1616 (C=N), 1637 (C=O), 3477 (NH); MS m/z (%): 322 [M+, 30%]; Anal. calcd. for C18H16N3OS: C, 66.43; H, 4.26; N, 13.67; S, 10.43; Found: C, 66.41; H, 4.25; N, 13.66; S, 10.41.

3-Methyl-7-phenyl-2-(1-phenyl-1H-pyrazol-3-yl)thieno[2,3-b]pyridin-4(7H)-one (4b). Green crystal; Yield: 68%; m.p. 275°C; IR (): 1602 (C=N), 1640 (C=O); 1H-NMR (DMSO-d6): δ, 2.29 (s, 3H, CH3), 6.14–6.16 (d, 1H, ), 6.72–6.74 (d, 1H, ), 7.63–7.65 (d, 1H, ), 7.67–7.78 (d, 1H, ), 7.61–7.69 (m, 5H, C6H5); 13C-NMR: δ, 15.09 (CH3), 113.23 (), 119.70, 126.31, 129.49 (Ar-C), 130.49 (-C-CH3), 130.93 (N-CHCS), 131.04 (-C-S), 140.39 (C-CO), 142.42 (Ar-C-N), 145.95 (), 175.74 (C=O); MS m/z (%): 307 [M+, 30%]; Anal. calcd. for C17H13N3OS: C, 72.04; H, 4.47; N, 10.96; S, 8.36; Found: C, 72.04; H, 4.49; N, 11.0; S, 8.37.

2-([1,2,4]Triazolo[1,5-a]pyrimidin-7-yl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (5). It is a mixture of 3 (0.131 g, 0.5 mmol) and 3-amine-1H-1,2,4-triazole (0.042 g, 0.5 mmol) in dioxane. Catalytic amount of TEA (triethyl amine) and ZnCl2 was added into the reaction mixture. The reaction mixture was then refluxed for 6 h and the product was filtered after cooling.

Yellow crystal; Yield: 72%; m.p. >300°C; IR (): 1618 (C=N), 1634 (C=O); MS m/z (%): 359 [M+, 30%]; Anal. calcd. for C19H13N5OS: C, 63.50; H, 3.65; N, 19.49; S, 8.92; Found: C, 63.51; H, 3.65; N, 19.50; S, 8.93.

2.3. General Procedure for the Preparation of Compounds 6ac

Compounds 6ac were prepared using the following general procedure.

Compound 3 (0.131 g, 0.5 mmol) was added to ethane-1,2-diamine (0.03 g, 0.5 mmol), propane-1,3-diamine (0.04 g, 0.5 mmol), or hexane-1,2-diamine (0.06 g, 0.5 mmol) (to make compounds 6ac, resp.) in AcOH (0.1 mmol) as solvent and NH4OAc (0.1 mmol) as catalyst. The reaction mixture was then refluxed for 3 h and the product was filtered after cooling. The desired product was obtained in a pure form by recrystallization from EtOH. Using the general procedure, the following compounds were prepared.

2-(3-((2-Aminoethyl)amino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (6a). Yellow powder; Yield: 62%; m.p. 142°C; IR (): 1593 (C=C), 1616–1637 (2C=O), 2931 (CH2), 3238 (NH2) 3415 (NH); 1H-NMR (DMSO-d6): δ 2.63 (s, 3H, CH3), 2.93 (q, 2H, CH2NH), 3.48 (m, 2H, CH2NH2), 6.16 (s, 2H, NH2), 5.24–5.40 (d, 1H, ), 5.83–5.91 (d, 1H, ), 7.02–7.00 (m, 1H, ), 7.08–7.20 (d, 1H, ), 7.64–7.67 (m, 5H, C6H5); 13C-NMR: δ 115.20 (CH2NH2), 115.52 (CH2-CH=CH), 129.31, 130.91, 130.94, 143.28, (Ar-C), 131.04 (), 137.45 (=CCO), 141.62 (S-CCO), 142.31 (-C-CH3), 143.28 (Ar-C-N), 153.19 (), 155.15 (), 155.74 (), 176.48 (C=O); MS m/z (%): 353 [M+, 30%]; Anal. calcd. for C18H14N2O2S: C, 64.57; H, 5.42; N, 11.89; S, 9.07; Found: C, 64.56; H, 5.40; N, 11.91; S, 9.10.

2-(3-((3-Aminopropyl)amino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (6b). Yellow powder; Yield: 64%; m.p. 145°C; IR (): 1593 (C=C), 1616–1637 (2C=O), 2931 (CH2), 3238 (NH2) 3415 (NH); 1H-NMR (DMSO-d6): δ 2.74 (s, 3H, CH3), 3.16 (t, 2H, NH2), 1.30–2.95 (m, 6H, CH2), 6.08–6.20 (m, 1H, ), 6.17–6.20 (d, 1H, ), 7.64–7.43 (d, 1H, ), 9.90–7.80 (d, 1H, ), 7.62–7.72 (m, 5H, C6H5); 13C-NMR: δ, 13.93 (CH3), 28.50 (-CH2), 33.00 (-CH2NH2), 69.92 (-CH2-NH) 114.60 (), 126.36, 129.18, 130.13 (Ar-C), 131.06 (), 136.05 (=CCO), 139.77(-C-CH3), 142.57 (), 151.40 (), 175.74 (C=O); MS m/z (%): 367 [M+, 30%]; Anal. calcd. for C28H26N2O2S2: C, 65.37; H, 5.76; N, 11.44; S, 8.72; Found: C, 65.35; H, 5.77; N, 11.45; S, 8.74.

2-(3-((4-Aminobutyl)amino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (6c). Yellow powder; Yield: 67%; m.p. 282°C; IR (): 1593 (C=C), 1616–1637 (2C=O), 2931 (CH2), 3238 (NH2) 3415 (NH); 1H-NMR (DMSO-d6): δ 2.74 (s, 3H, CH3), 1.15–2.87 (m, 6H, CH2), 3.80 (t, 2H, NH2), 6.18 (q, 1H, ), 6.19 (d, 1H, ), 6.20 (d, 1H, ), 6.20 (d, 1H, ), 7.58–7.67 (m, 5H, C6H5); 13C-NMR: δ 13.93 (CH3), 28.50 (-CH2), 33.00 (-CH2NH2), 69.92 (-CH2-NH) 114.60 (), 126.36, 129.18, 130.13 (Ar-C), 131.06 (), 136.05 (=CCO), 139.77(-C-CH3), 142.57 (), 151.40 (), 175.74 (C=O); MS m/z (%): 409 [M+, 30%]; Anal. calcd. for C23H24N2O2S: C, 66.12; H, 6.08; N, 11.01; S, 8.40; Found: C, 66.12; H, 6.11; N, 11.04; S, 8.41.

2.4. General Procedure for the Preparation of Compounds 7ac

Compounds 7ac were prepared using the following general procedure.

Compound 3 (0.131 g, 0.5 mmol) was added to 4-chloroaniline (0.06 g, 0.5 mmol), 4-methoxyaniline (0.06 g, 0.5 mmol), or p-toluidine (0.05 g, 0.5 mmol) (to make compounds 6ac, resp.) in dioxane as solvent and TEA (triethyl amine) (0.1 mmol) as catalyst. The reaction mixture was then refluxed for 4 h and the product was filtered after cooling. The desired product was obtained in a pure form by recrystallization from EtOH.

2-(3-((4Chlorohphenyl)amino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (7a). Yellow powder; Yield: 58%; m.p. >300°C; IR (): 1578 (C=C), 1636 (C=O), 3415 (NH); 1H-NMR (DMSO-d6): δ 2.49 (s, 3H, CH3), 5.21 (d, 1H, NH), 6.51–6.53 (d, 1H, ), 6.55–6.57 (d, 1H, ), 6.97 (d, 1H, ), 6.97–6.99 (t, 1H, ), 7.01–7.03 (t, 1H, ), 7.78–7.82 (m, 4H, C6H4); 13C-NMR: δ 115.70, 119.21, 129.03 (Ar-C), 148.25 (Ar-C-N); MS m/z (%): 420.5 [M+, 30%]; Anal. calcd. for C23H15ClN2O2S: C, 65.63; H, 4.07; Cl, 8.42; N, 6.66; S, 7.62.; Found: C, 65.64; H, 4.09; Cl, 8.40; N, 6.67; S, 7.63.

2-(3-((4-Methoxyphenyl)amino)acryloyl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (7b). Yellow powder; Yield: 47%; m.p. >300°C; IR (): 1578 (C=C), 1636 (C=O), 3415 (NH); 1H-NMR (DMSO-d6): δ, 2.50 (s, 3H, CH3), 3.61 (s, 3H, OCH3), 4.62 (d, 1H, NH), 6.50–6.52 (d, 1H, ), 6.62–6.65 (d, 1H, ), 6.95–6.98 (t, 1H, ), 7.69–7.82 (t, 1H, ), 7.78–7.82 (m, 9H, C6H4); 13C-NMR: δ, 56.00 (OCH3), 115.02, 115.57 (Ar-C), 142.76 (SCCO), 151.24 (Ar-C-N). MS m/z (%): 417 [M+, 30%]; Anal. calcd. for C24H18N2O3S: C, 69.21; H, 4.84; N, 6.73; S, 7.70.; Found: C, 69.20; H, 4.84; N, 6.74; S, 7.70.

3-Methyl-7-phenyl-2-(3-(p-tolylamino)acryloyl)thieno[2,3-b]pyridin-4(7H)-one (7c). Gray powder; Yield: 59%; m.p. 250°C; IR (): 1578 (C=C), 1636 (C=O), 3415 (NH); 1H-NMR (DMSO-d6): δ 1.28–3.37 (s, 6H, CH3), 4.29 (d, 1H, NH), 4.26–4.28 (d, 1H, ), 4.29–4.31 (d, 1H, ), 6.90 (t, 1H, ), 7.00–7.05 (t, 1H, ), 7.78–7.826.98-7.12 (m, 4H, C6H4). 13C-NMR: δ 14.66 (CH3), 114.06, 115.11, 122.96, (Ar-C), 114.06 (), 129.77 (), 143.23 (SCCO), 143.23 (Ar-C-N), 159.92 (S-C-N); MS m/z (%): 400 [M+, 30%]; Anal. calcd. for C24H18N2O2S: C, 71.98; H, 5.03; N, 6.99; S, 8.01.; Found: C, 72.00; H, 5.01; N, 7.00; S, 8.00.

2-(Benzo[4,5]imidazo[1,2-a]pyrimidin-4-yl)-3-methyl-7-phenylthino[2,3-b]pyridin-4(7H)-one (8). It is a mixture of 3 (0.131 g, 0.5 mmol) and 2-aminobenzimidazole (0.07 g, 0.5 mmol) in EtOH as solvent and TEA (triethyl amine)/ZnCl2 as catalyst. The reaction mixture was then refluxed for 8 h and the product was filtered after cooling. The desired product was obtained in a pure form.

Red crystal, Yield: 62%; m.p. 210°C; IR (): 1588 (C=N), 1628 (C=O); 1H-NMR (DMSO-d6): δ 2.75 (s, 3H, CH3), 5.48–5.51 (d, 1H, ), 6.24–6.26 (d, 1H, ), 7.10–7.27 (t, 1H, ), 7.87–8.02 (t, 1H, ),7.71–7.79 (m, 9H, C6H5). 13C-NMR: δ, 15.47 (CH3), 114.83 (), 121.17, 125.80, 126.16, 130.19, 130.58, 140.62, 142.50 (Ar-C), 125.80 (), 126.16 (), 130.68 (S-C=CH3), 162.50 (N-C=N(pyrazole)), 162.21 (), 162.50 (N-C=CCH3), 176.50 (S-C-N), 189.64 (C=O). MS m/z (%): 422 [M+, 30%]; Anal. calcd. for C25H19N4OS: C, 65.88; H, 4.07; N, 16.17; S, 9.25; Found: C, 65.85; H, 4.06; N, 16.18; S, 9.25.

3-(3-Methyl-4-oxo-7-phenyl-4,7-dihydrothieno[2,3-b]pyridin-2-yl)-3-oxoprop-1-en-1-yl 4-chlorobenzoate (9). It is a mixture of 3 (0.131 g, 0.5 mmol) and 4-chlorobenzoic acid (0.08 g, 0.5 mmol) in dioxane as solvent and TEA (triethyl amine) (0.1 mmol) as catalyst. The reaction mixture was then refluxed for 4 h and the product was filtered after cooling. The desired product was obtained in a pure form by recrystallization from EtOH.

Yellow powder, Yield: 67%; m.p. 265°C; IR (): 1594 (C=C), 1610–1630 (3C=O). 1H-NMR (DMSO-d6): δ 3.12 (s, 3H, CH3), 5.36–5.39 (d, 1H, ), 6.15–6.17 (d, 1H, ), 7.66–7.68 (t, 1H, ), 7.70-7.80 (t, 1H, ), 7.66–7.68 (m, 5H, C6H5); 13C-NMR: δ, 16.11 (CH3), 115.13 (), 126.33 (), 128.58, 130.54, 130.95, 132.60, 137.24 (Ar-C), 141.03 (S-CCO), 142.34 (-C-CH3), 153.16 (), 154.52 (S-C-N), 176.51 (COO), 180.51 (C=O); MS m/z (%): 444 [M+, 30%]; Anal. calcd. for C24H14ClNO4S: C, 64.36; H, 3.15; Cl, 7.91; N, 3.13; S, 7.16; Found: C, 64.37; H, 3.14; Cl, 7.91; N, 3.15; S, 7.18.

3. Results and Discussion

Novel thieno-fused bicyclic compounds 4a,b, 5, 6ac, 7ac, 8, and 9 were synthesized as shown in Schemes 2 and 3 starting from the new enaminone 3 (Scheme 1). The new synthesized molecules 1–9 were characterized by CHN analyses, NMR, and MS spectral data.

Scheme 1: Synthesis of compound 3.
Scheme 2: Synthesis of compounds 4a,b and 5.
Scheme 3: Synthesis of compounds 69.

The starting intermediate 2 needed for this research proposal was synthesized by reported method by Mabkhot et al. [22]. The new enaminone 3 was synthesized via the reaction of acetyl thiophene 2 with DMF-DMA in xylene as solvent as shown in Scheme 1. The final product 3 was presumably formed as a result of intramolecular conjugate addition of the nucleophilic nitrogen onto the further end of the double bond (β-carbon) of the intermediate bis-enaminone with elimination of a dimethylamine molecule resulting in formation of Michael product 3 as depicted in Scheme 1.

The IR spectrum of the new enaminone 3 has shown an absorption band at 1613–1640 cm−1 ascribed to the carbonyl group ν(C=O) and an abruption band at 1593 cm−1 ascribed to the alkene group ν(C=C).

1H-NMR spectrum of the new enaminone 3 exhibited a singlet at δ 2.85 and 3.15 ppm, due to the methyl of the N(CH3)2 groups. In addition, two doublets for the CH=CH protons at 5.36 ( Hz) and 5.39 ( Hz) were observed. On the other hand, two doublets for the CH=CH protons at 6.14 ( Hz) and 6.16 ( Hz) due to pyridinone ring in addition to a multiplet at δ 7.63–7.68 belong to phenyl ring protons. 13C-NMR spectrum agrees well with the suggested structure and showed the following signals: δ16.12 (-CH3), 45.15 (-N=(CH3)2), 94.03 (-CH=CH-N=), 153.15 (-), 126.35, 128.58, 130.55 (Ph), 142.35 (-C-CH3), 115.14 (-), 154.45 (-), 154.54 (=CNS), and 176.49, 180.51 (2C=O). The GC-MS showed the molecular ion [M]+ at m/z 325 corresponding to the molecular formula C18H17N2O2S.

3.1. X-Ray Crystal Structure of 2

The compound, C15H15NO2S, CCDC: 141975, crystallizes in triclinic, P-1 system with the following unit cell = 10.3859 (3) Å, = 13.8790 (6) Å, = 18.8006 (6) Å, = 86.920 (1)°, = 82.081 (1)°, and = 79.233 (1)°. The unit cell contains four molecules. The molecule consists of tetrasubstituted thiophene ring, in the C3 and C5 two acetyl groups with different orientation. On the other hand, C4 has methyl group and C6 has amine derivative (Figure 1). In the crystal packing the molecules linked via five nonclassical hydrogen bonds were shown in Figure 2 and Table 3. The selected data collection, handling, and bond lengths and angles for the crystal were shown in Tables 1 and 2, respectively [23, 24].

Table 1
Table 2: Bond lengths and bond angles of compound 2 (, °).
Table 3: Hydrogen-bond geometry for compound 2 (, °).
Figure 1: ORTEP of the synthesized compound 2.
Figure 2: Molecular packing of the synthesized compound 2.

Having the new enaminone 3 available in our hands encourage us to use it for the synthesis of the thieno-fused bicyclic compounds. Compounds 4a,b were synthesized by refluxing a mixture of enaminone 3 and N-nucleophile, for example, hydrazine analogous and subsequently heated under reflux in EtOH/DMF as solvent. (Scheme 2). The IR spectrum of the synthesized molecules exhibited absorption bands at 3416, 1640, and 1602 cm−1 due to ν(N-H), ν(C=O), and ν(C=N), respectively.

Next, enaminone 3 reacted with 3-amino-1H-1,2,4-triazole in dioxane in the presence of TEA (triethyl amine) and ZnCl2 as catalyst to afford the final product 2-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-3-methyl-7-phenylthieno[2,3-b]pyridin-4(7H)-one (5). The suggested chemical structure agreed with experimental spectral data.

In addition, compounds 6ac, 7ac, and 8 were synthesized by refluxing a mixture of 3 and aliphatic diamines, aromatic amines, and 2-aminobenzimidazole, respectively (Scheme 3).

Interestingly, enaminone 3 treated with p-chlorobenzoic acid to afford the corresponding ester 9. The IR spectrum is consistent with the expected absorption bands. 1H-NMR spectrum in DMSO-d6 showed singlet at 3.12 related to the CH3 group and two doublets corresponding to the CH=CH protons at δ 5.36 ( Hz) and 5.36 ( Hz) and the pyridinone CH protons at δ 6.15 ( Hz) and 6.16 ( Hz), in addition to a multiplet corresponding to the phenyl rings in the range δ 7.68–7.62. 13C-NMR spectrum is also in agreement with the suggested structure; it showed signals corresponding to the different carbon atoms in the compound as follows: δ 16.11 (CH3), 115.13 (), 126.33 (), 128.58, 130.54, 130.95, 132.60, 137.24 (Ar-C), 141.03 (S-CCO), 142.34 (-C-CH3), 153.16 (), 154.52 (S-C-N), 176.51 (COO), and 180.51 (C=O). GC-MS exhibited the correct molecular ion peak [M]+ at m/z = 449 corresponding to the molecular formula C24H14ClNO4S.

4. Conclusions

In summary, we have succeeded in the synthesis of a number of novel thieno-fused bicyclic compounds via novel enaminone containing thieno[2,3-b]pyridine core by classical method. The structures of the new compounds were confirmed by means of different spectroscopic methods and by elemental analyses. The biological activity of the synthesized product is underway in our laboratory.

Supplementary Material

Supplementary Material will be available online at http://dx.doi.org/10.1155/2015/382381.

Conflict of Interests

The authors have declared that there is no conflict of interests.

Authors’ Contribution

The authors contributed equally to this work.

Acknowledgment

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at king Saud University for funding this research group (no. RG -007-2015).

References

  1. S. Bondock, W. Fadaly, and M. A. Metwally, “Synthesis and antimicrobial activity of some new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety,” European Journal of Medicinal Chemistry, vol. 45, no. 9, pp. 3692–3701, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. H. M. Hassneen and T. A. Abdallah, “New routes to pyridino[2,3-d]pyrimidin-4-one and pyridino-[2,3-d]triazolino[4,5-a]pyrimidin-5-one derivatives,” Molecules, vol. 8, no. 3, pp. 333–341, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. Y. N. Mabkhot, A. M. Al-Majid, and A. S. Alamary, “Synthesis and chemical characterisation of some new diheteroaryl thienothiophene derivatives,” Molecules, vol. 16, no. 9, pp. 7706–7714, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. K. M. Dawood, A. M. Farag, and Z. E. Kanddeel, “Heterocyclic synthesis via enaminonitriles: one-pot synthesis of some new pyrazole, isoxazole, pyrimidine, pyrazolo [1,5-a]pyrimidine, pyrimido[1,2-a]benzimidazole and pyrido[1,2-a]benzimidazole derivatives,” Journal of Chemical Research, Synopses, no. 2, pp. 88–89, 1999. View at Publisher · View at Google Scholar
  5. L. U. E. Ping and J. V. Greenhill, “Enaminones in heterocyclic synthesis,” Advances in Heterocyclic Chemistry, no. 67, pp. 207–343, 1997. View at Google Scholar · View at Scopus
  6. P. G. Baraldi, A. Barco, S. Benetti, G. P. Pollini, and D. Simoni, “Synthesis of natural products via isoxazoles,” Synthesis, no. 10, pp. 857–869, 1987. View at Google Scholar · View at Scopus
  7. K. Saito, A. Nakao, T. Shinozuka et al., “Discovery and structure-activity relationship of thienopyridine derivatives as bone anabolic agents,” Bioorganic and Medicinal Chemistry, vol. 21, no. 7, pp. 1628–1642, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. L. C. S. Pinheiro, J. C. Borges, C. D. Oliveira et al., “Synthesis of new 4-(phenylamino)thieno[2,3-b]pyridines and derivatives of the novel benzo[b]thieno[3,2-h][1,6]naphthyridine tetracyclic system,” Arkivoc, vol. 2008, no. 14, pp. 77–87, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. A. M. R. Bernardino, L. C. D. S. Pinheiro, C. R. Rodrigues et al., “Design, synthesis, SAR, and biological evaluation of new 4-(phenylamino)thieno[2,3-b]pyridine derivatives,” Bioorganic and Medicinal Chemistry, vol. 14, no. 16, pp. 5765–5770, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. S. A. Al-Trawneh, M. M. El-Abadelah, J. A. Zahra et al., “Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents,” Bioorganic and Medicinal Chemistry, vol. 19, no. 8, pp. 2541–2548, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. J.-P. Wu, R. Fleck, J. Brickwood et al., “The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II,” Bioorganic & Medicinal Chemistry Letters, vol. 19, no. 19, pp. 5547–5551, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. J. W. Lockman, M. D. Reeder, K. Suzuki et al., “Inhibition of eEF2-K by thieno[2,3-b]pyridine analogues,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 7, pp. 2283–2286, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. M. E. Schnute, D. J. Anderson, R. J. Brideau et al., “2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 12, pp. 3349–3353, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Liu, Y. Li, X.-Y. Wang et al., “Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives as potential anti-inflammatory agents,” Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 8, pp. 2349–2352, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. I. Adachi, T. Yamamori, Y. Hiramatsu et al., “Studies on dihydropyridines. III. Synthesis of 4,7-dihydrothieno[2,3-b]-pyridines with vasodilator and antihypertensive activities,” Chemical and Pharmaceutical Bulletin, vol. 36, no. 11, pp. 4389–4402, 1988. View at Publisher · View at Google Scholar · View at Scopus
  16. M. M. El-Abadelah, S. S. Sabri, H. A. Al-Ashqar, P. Mion, J. Bompart, and M. Calas, “Thienopyridinone antibacterials. Part II.1 Synthesis and antibacterial activity of some 2-chloro-7-cyclopropyl-4,7-dihydro-4-oxothieno [2,3-b]pyridine-5-carboxylic acids,” Phosphorus, Sulfur, and Silicon and the Related Elements, vol. 134, no. 1, pp. 21–29, 1998. View at Publisher · View at Google Scholar
  17. E. R. Bacon and S. J. Daun, “Synthesis of 7-ethyl-4,7-dihydro-4-oxo-2-(4-pyridinyl)thieno[2,3-b]pyridine-5-carboxylic acid,” Journal of Heterocyclic Chemistry, vol. 28, no. 8, pp. 1953–1955, 1991. View at Publisher · View at Google Scholar
  18. Y. N. Mabkhoot, “Synthesis and analysis of some bis-heterocyclic compounds containing sulphur,” Molecules, vol. 14, no. 5, pp. 1904–1914, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. N. Mabkhoot, “Synthesis and chemical characterisation of new bis-thieno [2,3-b]thiophene derivatives,” Molecules, vol. 15, no. 5, pp. 3329–3337, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. N. Mabkhot, N. A. E. Kheder, and A. M. Al-Majid, “Facile and convenient synthesis of new thieno[2,3-b]-thiophene derivatives,” Molecules, vol. 15, no. 12, pp. 9418–9426, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. N. Mabkhot, F. D. Aldawsari, S. S. Al-Showiman et al., “Synthesis, bioactivity, molecular docking and POM analyses of novel substituted thieno[2,3-b]thiophenes and related congeners,” Molecules, vol. 20, no. 2, pp. 1824–1841, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. N. Mabkhot, N. N. E. El-sayed, F. Alatibi, A. Barakat, H. A. Ghabbour, and H.-K. Fun, “Synthesis, characterization and X-ray crystal structure of 3-methyl-4-oxo-7-phenyl-4,7-dihydrothieno[2,3-b]pyridine-2-carboxyxlic acid ethyl ester,” Asian Journal of Chemistry, vol. 26, no. 24, pp. 8596–8598, 2014. View at Publisher · View at Google Scholar
  23. G. M. Sheldrick, “A short history of SHELX,” Acta Crystallographica Section A, vol. 64, no. 1, pp. 112–122, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. Brucker, APEX2, SAINT and SADABS, Bruker, Madison, Wis, USA, 2009.