Improved ultrasound-induced synthesis of 1,5-diaryl-1,4-pentadien-3-ones

Chen Guofeng, Li Jitai, Duan Huiyun, Li Tongshuang
(College of Chemistry and Environmental Science, Hebei University; Key Laboratory of Analytical Science and Technology, Hebei Province, Baoding 071002,   China)

Received Nov. 4, 2003; Supported by Educational Ministry of China and Natural Science Foundation of Hebei Province (203107), China.

Abstract Synthesis of 1,5-diaryl-1,4-pentadien-3-ones from acetone or benzalacetone with aromatic aldehydes is carried out in excellent yields with potassium hydroxide as catalyst under ultrasound irradiation.
Keywords dibenzalacetone; Claisen-Schmidt condensation; ultrasound.

1 INTRODUCTION
The 1,5-diaryl-1,4-pentadien-3-ones are used as precursors to potentially bioactive pyrimidine derivatives ^[1], intermediates of spiro prostaglandin analog which might act as a mediator in many physiological activities^[2] and optically active poly(g-ketosulfide)s^[3]. Preparation of 1,5-diaryl-1,4-pentadien-3-ones is usually completed via Claisen-Schmidt condensation between acetone and aromatic aldehydes using conventional stirring or heating method ^[4-6]. However, there were some shortcoming in terms of long reaction time or low yield. Gupta et al. have reported that the preparation of 1,5-diaryl-1,4-pentadien-3-ones catalyzed by sodium hydroxide under microwave gave good yield^[7]. Further there are no reports to our knowledge about the use of ultrasound-induce the condensation between acetone or benzalacetone with aromatic aldehydes.
    Ultrasound has been used more and more frequently in organic synthesis in recent three decades^[8]. Compared with traditional methods, this method is more convenient and easily controlled.A great many of organic reactions can be carried in higher yields, shorter reaction time or milder conditions under ultrasound irradiation. Recently, our laboratory has reported the Claisen-Schmidt condensation of furfural with cycloalkanones catalyzed by NaOH under ultrasound irradiation, and the results are better than that under conventional heating condition ^[9]. In continuation of broad programme being pursued in our laboratory on ultrasound-induced organic reactions, herein we wish to report a facile sonochemical synthesis of 1,5-diaryl-1,4-pentadien-3-ones catalyzed by aqueous potassium hydroxide. 

2 EXPERIMENTAL
Liquid aldehydes were purified by distillation prior to use. Melting points were uncorrected. IR spectra were recorded on a Bio-Rad FTS-40 spectrometer (KBr). ¹H NMR spectra were measured on Bruker AM-400S (400 MHz) spectrometer using TMS as internal standard and CDCl₃ as solvent. Mass spectra were determined on a VG-7070E spectrometer (EI, 70eV). Sonication was performed in a Shanghai Branson-CQX ultrasonic cleaner with a frequency of 25 kHz and a nominal power 500W. The reaction flask was located in the maximum energy area in the cleaner and addition or removal of water was used to control the temperature of the water bath.
    General procedure for the synthesis of 1,5-diaryl-1,4-pentadien-3-ones: A Pyrex flask (50 mL) was added 95% ethanol (4 mL), acetone or benzalacetone (2 mmol), aromatic aldehyde (4 mmol or 2 mmol) and 1.25 mol/L aqueous potassium hydroxide (4 mL). The mixture was irradiated in the water bath of an ultrasonic cleaner at the temperature for the period as indicated in Table 1 (Sonication was continued until aromatic aldehyde was disappeared indicated by TLC). After a period time of cooling in an ice-water bath, the precipitate was isolated by suction filtration, washed with ice-cooled 95% ethanol, cool water to neutral, dried. In most cases, the crude products are reasonably pure. The authenticity of the products was established by comparing their melting points with the literature and the data of IR, MS and ¹H NMR spectra.
    4d: yellow platelets from ethanol；n_max (KBr)：3045, 3000, 1655, 1622, 1588, 1438, 1400, 1333, 1188, 1088, 977, 822 cm^-1； d_H (400 MHz)：7.05 (2H, d, J=16 Hz, Ar-CH=CH-), 7.41 (4H, d, J=8.4 Hz, H_b), 7.57 (4H, d, J=8.4 Hz , H_a ), 7.71 (2H, d, J=16 Hz, Ar-CH=CH-) ppm；m/z (%)：304 (M+2, 10), 302 (M⁺,15), 267 (10), 204 (10), 165 (87), 139 (100), 101 (80), 75(85), 51(70).
    4e: yellow platelets from ethanol；n_max (KBr)：3045, 3000, 1655, 1600, 1466, 1411, 1316, 1188, 1077, 983, 877, 800 cm^-1； d_H (400 MHz)： 7.08 (2H, d, J=16 Hz, Ar-CH=CH-), 7.36-7.51 (6H, m, H_a, H_b, H_c), 7.63 (2H, s, H_e), 7.69 (2H, d, J=16 Hz, Ar-CH=CH-) ppm；m/z (%)：304 (M+2, 33), 302 (M⁺,50), 267 (60), 239 (18), 204 (30), 165 (54), 137 (42), 101 (100), 75(64), 63(14), 51(35).
    4h: yellow platelets from ethanol；n_max (KBr)：3057, 3000, 1655, 1588, 1466, 1333, 1177, 1100, 977, 822, 777 cm^-1； d_H (400 MHz): 7.05 (2H, d, J=16 Hz, Ar-CH=CH-), 7.33 (2H, dd, J₁=2.0Hz, J₂=8.4Hz, H_b), 7.50 (2H, d, J=2.0 Hz H_d), 7.68 (2H, d, J=8.4 Hz, H_a), 8.07 (2H, d, J=16 Hz, Ar-CH=CH-) ppm；m/z (%)：374 (M+4, 10), 372 (M+2, 20), 370 (M⁺,15), 337 (100), 272 (12), 236 (11), 199 (21), 171 (30), 136 (66), 99 (57), 75(40), 51(70).
    4i: white platelets from ethanol；n_max (KBr)：3079, 1688, 1633, 1600,1522, 1255, 1111, 988, 877, 822, 744 cm^-1； d_H (400 MHz)：7.59 (2H, d, J=16 Hz, Ar-CH=CH- ), 7.78 (2H, t, J=8.0Hz H_b) 7.98 (2H, d, J=16 Hz, Ar-CH=CH-), 8.27-8.31 (4H, m, H_a, H_c ), 8.65 (2H, s, H_e) ppm；m/z (%)：324 (M⁺, 30), 307(20), 277 (10), 176 (55), 129 (25), 102 (100), 76 (40), 51(40).
    5b: yellow platelets from ethanol；n_max (KBr)：3050, 3022, 2909, 1644, 1622, 1577, 1444, 1333, 1166, 1088, 933, 811, 744 cm^-1； d_H (400 MHz)：2.42 (3H, s, -CH₃), 7.07 (1H, d, J=16 Hz, Ar-CH=CH- ), 7.11 (1H, d, J=16 Hz, Ph-CH=CH-), 7.25 (2H, d, J=8.0 Hz, H_b, H_d), 7.44-7.65 (5H, m, Ph-H), 7.55 (2H, d, J=8.0 Hz, H_a, H_e), 7.75 (1H, d, J=16 Hz, Ar-CH=CH-), 7.78 (1H, d, J=16 Hz, Ph-CH=CH-) ppm; m/z (%)：248 (M⁺,100), 233 (90), 219 (15), 205 (42), 191 (10), 170 (10), 145 (50), 131 (50), 128 (42), 115 (72), 103(92), 91 (98), 77 (95), 51 (62).
    5c: yellow platelets from ethanol；n_max (KBr)：3045, 2954,, 2800, 1666, 1622, 1600, 1555, 1511, 1411, 1344, 1255, 1166, 1100, 988, 811, 755 cm^-1； d_H (400 MHz)：3.88 (3H, s, -CH₃O), 6.96 (2H, d, J=8.8 Hz, H_b, H_d), 6.99 (1H, d, J=16 Hz, Ar-CH=CH- ), 7.11 (1H, d, J=16 Hz, Ph-CH=CH-), 7.43-7.65 (5H, m, Ph-H), 7.60 (2H, d, J=8.8 Hz, H_a, H_e), 7.74 (1H, d, J=16 Hz, Ar-CH=CH-), 7.75 (1H, d, J=16 Hz, Ph-CH=CH-) ppm；m/z (%)：264 (M⁺, 68), 249 (10), 233 (20), 205 (15), 161 (35), 131 (40), 108 (50), 103 (80), 77 (100), 51 (42).
    5d: yellow platelets from ethanol；n_max (KBr)：3045, 3022, 1655, 1622, 1588, 1488, 1333, 1188, 1088, 977, 811, 755, 688 cm^-1； d_H (400 MHz)：7.08 (1H, d, J=16 Hz, Ph-CH=CH- ), 7.09 (1H, d, J=16 Hz, Ar-CH=CH-), 7.39 (2H, d, J=9.6Hz, H_b, H_d), 7.42-7.64 (5H, m, Ph-H), 7.57 (2H, d, J=8.4Hz, H_a, H_e), 7.71 (1H, d, J=16 Hz, Ph-CH=CH-), 7.76 (1H, d, J=16 Hz, Ar-CH=CH-) ppm；m/z (%)：270 (M+2, 34), 268 (M⁺,100), 233 (12), 205 (12), 165 (11), 131 (20), 103 (24), 77 (30), 51 (18).
    5e: yellow platelets from ethanol；n_max (KBr)：3057, 3023, 1650, 1622, 1583, 1455, 1333, 1200, 1078, 922, 867, 788, 755 cm^-1； d_H (400 MHz)： 7.08 (1H, d, J=16 Hz, Ph-CH=CH- ), 7.11 (1H, d, J=16Hz, Ar-CH=CH-), 7.33-7.64 (9H, m, Ar-H, Ph-H), 7.69 (1H, d, J=16Hz, Ph-CH=CH-), 7.77 (1H, d, J=16Hz, Ar-CH=CH-) ppm；m/z (%)：270 (M+2, 21), 268 (M⁺,62), 233 (18), 205 (20), 165 (25), 131 (48), 103 (80), 77 (100), 51 (57).

3 RESULTS AND DISCUSSION
As shown in Table 1, several aromatic aldehydes including benzaldehyde, p-chlorbenzaldehyde, m-chlorbenzaldehyde and cinnamic aldehyde underwent clean and remarkably fast condensation with acetone or benzalacetone under this procedure. The dramatic improvement observed is with regard to reaction time and yields of the products. Many reactions are completed within a period of 20 minutes. For example, in the classical reaction catalyzed by sodium hydroxide in absolute ethanol, the products (4c) and (4f) were obtained in 90% and 91% yield by stirring at room temperature for 10 h respectively ^[6], whereas the present procedure results in 89% and 86% yield respectively at 25-30 ^oC within 60 min. In the classical reaction catalyzed by the same catalyst in 95% EtOH, compounds (4a, 4b, 4c and 4g) were obtained with 50-60%, 50-60%, 40-50% and 40-60% yields ^[4]. While, the present method gave the compounds(4a, 4b, 4c and 4g) in 97%, 92%, 89% and 90% yields respectively. We also did the experiment catalyzed by potassium hydroxide in the absence of ultrasound, the condensation of benzaldehyde (1) with acetone (2) was carried out in 86% (4a) yield using stirring at r.t. within 150 min. Sonication of benzaldehyde (1) with acetone (2) gave 97% (4a) yield only for 15 min. It is apparent that the condensation of aromatic aldehydes with acetone or benzalacetone can be finished in shorter reaction time and obtained in good yields under ultrasound irradiation.
    It is noteworthy that no corresponding products can be obtained when the substrates are p-hydroxybenzaldehyde, vanillin, p-dimethylaminobenzaldehyde, salicylaldehyde, p-aminobenzaldehyde and acetophenone in these experiments.
   
Table 1. Preparation of 1,5-diaryl-1,4-pentadien-3-one catalyzed by aqueous KOH in 95%EtOH under ultrasound irradiation.

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