Synthesis and Characterization of New Chalcone ...

Synthetic Communications

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Synthesis and Characterization of New Chalcone Derivatives from cis-Bicyclo[3.2.0]hept-2-en-6-one Mustafa Ceylan & Esra Fındık To cite this article: Mustafa Ceylan & Esra Fındık (2009) Synthesis and Characterization of New Chalcone Derivatives from cis-Bicyclo[3.2.0]hept-2-en-6-one, Synthetic Communications, 39:6, 1046-1054, DOI: 10.1080/00397910802474974 To link to this article: http://dx.doi.org/10.1080/00397910802474974

Published online: 25 Feb 2009.

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Synthetic Communications1, 39: 1046–1054, 2009 Copyright # Taylor & Francis Group, LLC ISSN: 0039-7911 print=1532-2432 online DOI: 10.1080/00397910802474974

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Synthesis and Characterization of New Chalcone Derivatives from cis-Bicyclo[3.2.0]hept-2-en-6-one Mustafa Ceylan and Esra Fındık Faculty of Arts and Sciences, Department of Chemistry, Gaziosmanpasa University, Tokat, Turkey

Abstract: A series of chalcone derivatives (3a–k) were prepared via the reaction of cis-bicyclo[3.2.0]hept-2-en-6-one (1) with the respective arylaldehydes (2a–k) and were then characterized by Fourier transform infrared (FT-IR), 1H NMR, 13 C NMR, and elemental analyses. Keywords: cis-Bicyclo[3.2.0]hept-2-en-6-one, condensation

chalcone,

Claisen–Schmidt

a,b-Unsaturated ketones, especially 1,3-diarylprop-2-en-1-ones, commonly known as chalcones, have received considerable attention in medicinal chemistry.[1] Chalcones are natural or synthetic compounds belonging to the flavonoid family,[2] and they are important compounds not only because of their biological properties but also because they serve as important intermediates for the synthesis of a large number of heterocyclic systems.[1] They are also very important as a Michael acceptor in organic syntheses.[3] Moreover, chalcones have been extensively studied[4] for their broad spectrum of biological activities, including bacteriostatic, fungistatic, antiparasitic, cardiovascular, antitumor,[5] anticancer,[6,7] anti-inflammatory,[8,9] antileishmanial,[10] antitubercular,[11] and antifung[12] activities. In fact, the

Received June 25, 2008. Address correspondence to Mustafa Ceylan, Faculty of Arts and Sciences, Department of Chemistry, Gaziosmanpasa University, 60250 Tokat, Turkey. E-mail: [email protected] 1046

New Chalcone Derivatives

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Scheme 1. Synthesis of chalcone derivatives 3a–k.

pharmacological properties of chalcones are due to the presence of both a,b-unsaturation[13] and an aromatic ring. Constant interest in chalcones has resulted in syntheses of new derivatives using both classical[14,15] and combinatorial techniques.[16] In this study, a series of new chalcone-like compounds (3a–k) were synthesized by the reaction of cis-bicyclo[3.2.0]hept-2-en-6-one with appropriately aldehyde derivatives (2a–k). The general synthetic strategy employed to prepare the chalcone derivatives (3a–k) based on Claisen–Schmidt condensation, which was reported previously.[17] As shown in Scheme 1 and Table 1, new chalcone derivatives (3a–k) were prepared by base-catalyzed condensation of cisbicyclo[3.2.0]hept-2-en-6-one with substituted benzaldehydes, furfural, thiophene-2-carbaldehyde, and 1H-pyrrole-2-carbaldehyde in yields of 89–98% (Scheme 1). The structures of all the 11 chalcone derivatives (3a–k) synthesized in this study were established on the basis of infrared (IR), 1H NMR and 13C NMR spectral data, and elemental analyses. 1 H NMR spectrum of all chalcone derivatives show AB system at d ¼ 2.76–2.45 ppm arising from H3 protons, the AB system of H2 and H6 protons at d ¼ 4.50–3.80 ppm, and the signal of b proton at d ¼ 6.80 ppm as singlet. Fourteen lines in 13C NMR chalcone derivative spectrum are in agreement with the proposed structures.

EXPERIMENTAL Instruments Melting points of the compounds were measured using an Electrothermal 9100 apparatus. IR spectrums (KBr or liquid) were taken by a Jasco FT=IR-430 IR spectrophotometer. 1H and 13C NMR spectra were recorded using a Brucker Avance III instrument using tetramethylsilane (TMS, d 0.00) for 1H NMR and CDCl3 (d 77.0) for 13C NMR spectroscopy as internal reference standards; J values were given in hertz. The multiplicities of the signals in the 1H NMR spectra are abbreviated by s (singlet), d (doublet), t (triplet), q (quarted), m (multiplet), br (broad),

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M. Ceylan and E. Fındık

Table 1. Synthesized new chalcone derivatives


Entry

Ketones

Ar

Products

Isolated yield (%)

1

1

Ph

95

2

1

4-BrPh

97

3

1

4-ClPh

98

4

1

4-CH3OPh

95

5

1

4-CH3Ph

93

6

1

3-CH3Ph

91

7

1

3-ClPh

93

8

1

3-BrPh

94

9

1

Thienyl

95

(Continued )


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Table 1. Continued


Entry

Ketones

Ar

Products

Isolated yield (%)

10

1

Furyl

92

11

1

Pyrrol

89

and combinations thereof. Elemental analyses were obtained from a LECO CHNS 932 elemental analyzer. Reagent Bicyclo[3.2.0]hept-2-en-6-one and aldehyde derivatives were commercial products with the highest reagent grade.

General Procedure for Synthesis (3a–k) A solution of NaOH (2.3 mmol) in water was added to a vigorously stirring solution of the mixture of cis-bicyclo[3.2.0]hept-2-en-6-one (2.3 mmol) and benzaldehyde derivative (2.3 mmol) in ethanol (10 ml). The resultant solution was then stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc, neutralized with HCl solution (10%), and then washed with water. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated. Solid compounds were recrystallized in EtOAc=n-hexane (1:9).

Data 7-Benzylidenebicyclo[3.2.0]hept-2-en-6-one (3a) Viscous oil, bp 188–190 C=760 torr; 1H NMR (400 MHz, CDCl3) d ¼ 7.56– 7.55 (m, 2H, ArH), 7.38–7.37 (m, 3H, ArH), 6.83 (s, 1H), 6.01–5.99 (m, 1H), 5.83–5.82 (m, 1H), 4.36 (m, 1H), 3.88–3.85 (m, 1H), 2.78–2.76 (m, 1H), 2.58–2.44 (m, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.7,

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149.41, 134.25, 133.27, 129.99, 129.88 (2C), 129.0 (2C), 128.86, 124.17, 60.56, 49.68, 34.84. IR (liquid): 3419, 3237, 3054, 2916, 2851, 1742, 1640, 1448, 1241, 1162, 1101, 1089, 895, 751, 674, 625, 466, 413. Anal. calcd. for C14H12O:C, 85.68; H, 6.16, Found: C, 85.48; H, 5.96.


7-(4-Brombenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3b) Yellowish crystals, mp 95–97 C. 1H NMR (400 MHz, CDCl3): d ¼ 7.52 (d, J ¼ 8.4 Hz, 2H), 7.42 (d, J ¼ 8.4 Hz, 2H), 6.77 (s, 1H), 5.98–5.96 (m, 1H), 5.87–5.86 (m, 1H), 4.35–4.34 (m, 1H), 3.92–3.88 (m,1H), 2.78 (bd, J ¼ 17.6 Hz, 1H), 2.58 (dd, J ¼ 17.6, 10.4 Hz, 1H). 13CNMR (100 MHz, CDCl3): d ¼ 203.61, 149.91, 133.68, 133.16, 132.25 (2 C), 131.13 (2 C), 128.36, 124.34, 122.88, 60.84, 49.61, 34.77. IR (KBr): 3444, 3057, 301, 2918, 2899, 1736, 1636, 1484, 1399, 1154, 1069, 906, 811, 717, 533, 472. Anal. calcd. for C14H11BrO: C, 61.11; H, 4.03, Found: C, 60.98; H, 4.16.

7-(4-Chlorobenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3c) Yellowish crystals, mp 92–94 C. 1H NMR (400 MHz, CDCl3): d ¼ 7.51 (d, J ¼ 8.4 Hz, 2H), 7.38 (d, J ¼ 8.4 Hz, 2H), 6.80 (d, J ¼ 2 Hz, 1H), 6.00–5.97 (m, 1H), 5.89–5.87 (m, 1H), 4.37–4.36 (m, 1H), 3.90 (ddd, J ¼ 9, 7, 2 Hz, 1H), 2.82–2.75 (m, 1H), 2.63–2.55 (m, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.59, 149.79, 135.95, 133.66, 132.76, 130.93 (2 C), 129.30 (2 C), 128.40, 122.81, 60.82, 49.58, 34.75. IR (KBr): 3414, 3057, 3010, 2965, 2902, 2848, 1736, 1636, 1404, 1234, 1076, 897, 814, 720, 535, 474, 406. Anal. calcd. for C14H11ClO: C, 72.89; H, 4.81, Found: C, 72.68; H, 4.49.

7-(4-Methoxybenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3d) Yellowish crystals, mp 82–84 C. 1H NMR (400 MHz, CDCl3): d ¼ 7.53 (d, J ¼ 8.6 Hz, 2H), 6.93 (d, J ¼ 8.6 Hz, 2H), 6.82 (s, 1H), 6.03–6.02 (m, 1H), 5.85–5.83 (m, 1H), 4.33–4.32 (m, 1H), 3.89–3.86 (m, 1H), 3.83 (s, 3H, -OCH3), 2.76 (bd, J ¼ 17.6 Hz, 1H), 2.55 (dd, J ¼ 17.6, 10.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.7, 161.7, 147.06, 133.12, 131.65 (2C), 129.03, 126.89, 124.21, 114.55 (2C), 60.4, 55.39, 49.35, 34.50. IR (KBr): 3417, 3081, 3041, 2967, 2927, 2853, 1736, 1597, 1510, 1307, 1257, 1175, 1023, 824, 708, 544, 493, 406. Anal. calcd. for C15H14O2: C, 79.62; H, 6.24, Found: C, 79.44; H, 6.02.


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7-(4-Methylbenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3e) Viscous oil, bp 217–219 C=760 torr; 1H NMR (400 MHz, CDCl3): d ¼ 7.44 (d, J ¼ 8 Hz, 1H), 7.18 (d, J ¼ 8 Hz, 1H), 6.80 (s, 1H), 6.01– 5.99 (m, 1H), 5.81–5.79 (m, 1H), 4.31–4.30 (m, 1H), 3.83 (dt, J ¼ 7.2, 2 Hz, 1H), 2.70 (dd, J ¼ 17.2, 2 Hz, 1H), 2.53 (ddd, J ¼ 17.2, 10.2, 2 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 203.72, 148.42, 140.49, 133.10, 131.71, 129.93 (2 C), 129.78 (2 C), 128.78, 124.33, 60.51, 49.57, 34.61, 21.53. IR (liquid): 3406, 3050, 3026, 2918, 2852, 1739, 1637, 1617, 1511, 1236, 1160, 1109, 1078, 907, 811, 704, 603, 469. Anal. calcd. for C15H14O: C, 85.68; H, 6.71, Found: C, 85.38; H, 6.34. 7-(3-Methylbenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3f) Viscous oil, bp 213–215 C=760 torr; 1H NMR (400 MHz, CDCl3): d ¼ 7.37 (d, J ¼ 7.6 Hz, 1H), 7.39 (s, 1H), 7.26 (t, J ¼ 7.6 Hz, 1H), 7.16 (d, J ¼ 7.6 Hz, 1H), 6.78 (s, 1H), 6.0–5.98 (m, 1H), 5.81–5.79 (m, 1H), 4.32–4.31 (m, 1H), 3.82 (dt, J ¼ 8, 1.6 Hz, 1H), 2.74 (bd, J ¼ 17.2 Hz, 1H), 2.53 (ddd, J ¼ 17.2, 10.4, 1.6 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 203.65, 149.21, 138.58, 134.19, 133.14, 130.88, 130.85, 128.96, 128.88, 126.82, 124.38, 60.58, 49.70, 34.67, 21.39. IR (liquid): 3236, 3051, 2949, 2918, 2852, 1745, 1637, 1443, 1288, 1244, 1076, 893, 784, 706, 508, 458. Anal. calcd. for C15H14O: C, 85.68; H, 6.71, Found: C, 85.54; H, 6.67. 7-(3-Chlorobenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3g) Viscous oil, bp 220–221 C=760 torr; 1H NMR (400 MHz, CDCl3): d ¼ 7.48 (s, 1H), 7.42–7.39 (m, 1H), 7.30–7.29 (m, 2H), 6.72 (s, 1H), 5.96–5.94 (m, 1H), 5.84–5.83 (m, 1H), 4.33–4.32 (m, 1H), 3.87 (dt, J ¼ 8.6, 1.2 Hz, 1H), 2.74 (bd, J ¼ 17.6 Hz, 1H), 2.55 (ddd, J ¼ 17.6, 10.4, 1.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.64, 150.50, 136.03, 134.87, 133.67, 130.22, 129.82, 129.43, 128.38, 127.86, 122.76, 60.87, 49.66, 34.83. IR (liquid): 3423, 3056, 2920, 2852, 1744, 1639, 1563, 1428, 1242, 1160, 1080, 915, 784, 684, 540, 435. Anal. calcd. for C14H11ClO: C, 72.89; H, 4.81, Found: C, 72.61; H, 4.64. 7-(3-Brombenzylidene)bicyclo[3.2.0]hept-2-en-6-one (3h) Viscous oil, bp 205–207 C=760 torr;1HNMR (400 MHz, CDCl3): d ¼ 7.65 (s, 1H), 7.46 (d, J ¼ 7.6 Hz, 1H), 7.29–7.21 (m, 2H), 6.71

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(s, 1H), 5.97–5.95 (m, 1H), 5.79–5.76 (m, 1H), 4.34–4.33 (m, 1H), 3.87 (dt, J ¼ 8.4, 1.2 Hz, 1H), 2.75 (d, J ¼ 17.2 Hz, 1H), 2.55 (ddd, J ¼ 17.2, 9.2, 1.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.6, 150.53, 136.32, 133.70, 132.72, 132.42, 130.49, 128.38, 128.24, 123.04, 122.52, 60.90, 49.66, 34.84. IR (liquid): 3486, 3236, 3056, 3016, 2918, 2852, 1742, 1638, 1161, 1074, 910, 781, 616. Anal. calcd. for C14H11BrO: C, 61.11; H, 4.03, Found: C, 61.00; H, 3.87.


7-(Thiophen-2-ylmethylene)bicyclo[3.2.0]hept-2-en-6-one (3i) Yellowish crystals, mp 62–64 C. 1H NMR (400 MHz, CDCl3): d ¼ 7.46 (d, J ¼ 4.4 Hz, 1H), 7.26 (d, J ¼ 3.2 Hz, 1H), 7.08–7.05 (m, 2H), 6.07 (dd, J ¼ 5.4, 2 Hz, 1H), 5.82 (dd, J ¼ 5.4, 2 Hz, 1H), 4.23–4.22 (m, 1H), 3.80 (ddd, J ¼ 8.4, 7, 2 Hz, 1H), 2.72 (bd, J ¼ 17.2 Hz, 1H), 2.50 (ddd, J ¼ 17.2, 10.4, 2 Hz, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 202.88, 147.28, 138.31, 133.23, 132.81, 130.01, 128.69, 128.17, 117.33, 59.82, 49.08, 34.45. IR (KBr): 3417, 3086, 3072, 2945, 2911, 1725, 1619, 1415, 1231, 1107, 1081, 923, 861, 709, 580, 471, 404. Anal. calcd. for C12 H10 OS: C, 71.25; H, 4.98; S, 15.85, Found: C, 70.96; H, 4.76; S, 15.64. 7-(Furan-2-ylmethylene)bicyclo[3.2.0]hept-2-en-6-one (3j) Orange crystals, mp 52–54 C. 1H NMR (400 MHz, CDCl3): d ¼ 7.55 (s, 1H), 6.64–6.63 (m, 2H), 6.48–6.46 (m, 1H), 5.96 (dd, J ¼ 5.2, 2 Hz, 1H), 5.77 (dd, J ¼ 5.2, 2 Hz, 1H), 4.29–4.28 (m, 1H), 3.79 (ddd, J ¼ 8.6, 7, 1.6 Hz, 1H), 2.70 (bd, J ¼ 17.2 Hz, 1H), 2.52 (ddd, J ¼ 17.2, 10.4, 1.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): d ¼ 203.34, 150.96, 146.98, 145.44, 132.27, 130.58, 116.28, 112.53, 111.07, 59.82, 49.34, 34.73. IR (KBr): 3412, 3103, 2956, 2913, 2846, 1728, 1637, 1617, 1474, 1267, 1232, 1133, 754, 702, 594, 466, 414. Anal. calcd. for C12H10O2: C, 77.40; H, 5.41, Found: C, 77.42; H, 5.26. 7-((1H-pyrrol-2-yl)methylene)bicyclo[3.2.0]hept-2-en-6-one (3k) Green crystals, mp 141–144 C. 1H NMR (400 MHz, CDCl3): d ¼ 11.37 (s, 1H, -NH), 7.09–7.08 (d, J ¼ 1.2 Hz, 1H), 6.72–6.69 (m, 2H), 6.25 (s, 1H), 6.06–6.04 (m, 1H), 5.79–5.74 (m, 1H), 4.17 (m, 1H), 3.80–3.75 (m, 1H), 2.53–2.40 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 201.96, 142.83, 132.52, 130.22, 127.49, 124.20, 115.02, 114.14, 111.62, 59.22, 48.42, 33.94. IR (KBr): 3477, 3415, 3241, 3101, 2899, 2838, 1698, 1615, 1430, 1336, 1160, 1029, 984, 891, 741, 613, 418, 406. Anal. calcd. for C12H11NO: C, 77.81; H, 5.99; N, 7.56, Found: C, 77.62; H, 6.15.


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ACKNOWLEDGMENT The authors are indebted to the Gaziosmanpasa University Scientific Research Projects Committee (BAP-2005=30) and the Scientific and Technical Research Council of Turkey (TUBITAK-BI˙DEP) for financial support.


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