- Email: [email protected]
Microwave-assisted aldol condensation of benzil with ketones
Available online at www.sciencedirect.com
Chinese Chemical Letters 20 (2009) 401–403 www.elsevier.com/locate/cclet
Microwave-assisted aldol condensation of benzil with ketones Katayoun Marjani a, Maryam Asgari a, Akram Ashouri a, Gholam Hossein Mahdavinia b, Hossien Abbastabar Ahangar a,* b
a Faculty of Chemistry, Tarbiat Moallem University, P.O. Box 15614, Tehran, Iran Department of Chemistry, Islamic Azad University-Marvdasht Branch, Marvdasht, Iran
Received 9 September 2008
Abstract Under microwave irradiation, the corresponding hydroxycyclopentenones were prepared in high yields by the cross-aldol reactions of benzil with various ketones. When the reactions were performed in various solvents under classical heating for a long time, they produced the products in relatively low yields. # 2008 Hossien Abbastabar Ahangar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Benzil; Microwave irradiation; Cross-aldol reaction; Hydroxycyclopentenones
Cyclopentenones are of interest for their anti tumor and anti diabetic [1], pesticide and bactericide [2] properties. They have also been used in commercial goods as labeling materials for their photochemical properties [3]. Substituted cyclopentenones are used for incorporation in fine fragrances, cosmetics, toiletries and related applications [4] In addition, the cyclopentenone moiety is a very useful building block for the synthesis of other biologically active compounds composed of five membered units, due to the versatility of the a,b-unsaturated carbonyl functionality. Among a variety of approaches for preparation of cyclopentenones, such as Pauson-Khand reaction [5–7], Nazarove cyclization [8] and Rautenstrauch rearrangement [9], aldol condensation of a-diketones with acetone derivatives is a simple and inexpensive method for preparation of cyclopentenone derivatives. This method is flexible, as there are several simple routes available for the preparation of a-diketones [10,11]. The recent development in so called ‘‘green chemistry’’ shows that alternative methods of carrying out chemical transformation can minimize the environmental harmfulness of classical reactions. One of the most popular and interesting approach in this field is employing the microwaves energy for conducting many chemical transformations [12,13]. The interaction of the matter with such kinds of electromagnetic waves results in higher speed of heating [14], much shorter reaction time and very often the higher selectivity of desired products. The acceleration of reactions by microwave exposure results from material-wave interactions leading to thermal effects (which may be easily estimated by temperature measurements) and specific (non purely thermal) effects [15]. Here, we report on a facile aldol condensation protocol using benzil and different ketones with a dramatic reduction of reaction time for synthesis of hydroxycyclopentenones derivatives (Scheme 1).
* Corresponding author. E-mail address: [email protected] (H.A. Ahangar). 1001-8417/$ – see front matter # 2008 Hossien Abbastabar Ahangar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.12.036
402
K. Marjani et al. / Chinese Chemical Letters 20 (2009) 401–403
Scheme 1.
Table 1 Microwave-assisted aldol condensation. Entry
G
R
R0
R00
Product
Time (min)
Yield (%) a
mp (8C)
Lit. Mp (8C)
1 2 3 4 5 6 7 8
H H H H H Br Br Br
H CH3 H CH3 C6H5 H CH3 H
H H CH3 H H H H CH3
H H CH3 CH3 H H H CH3
1a 1b 1c 1d 1e 1f 1g 1h
2 8 4 6 8 4 6 8
90 80 98 82 87 97 85 85
147–148 114–116 180–182 134–136 166–167 239–241 167–169 197–199
149 [17] 116–118 181 [16] 129–130 165 [19] 239–241 167–169 197–199
a
[16] [18] [20] [20] [20]
Isolated yield.
Generally, without microwave irradiation, the reaction of benzil with ketones took a long time to complete, for example we observed that the yield of product for the reaction of benzil and butanone was only 63% after 17 days at room temperature [16], while under microwave irradiation it was 80% after 8 min. The powdered KOH, benzil and ketone were ground together with a mortar and pestle. When irradiated in a microwave oven, the mixture burnt due to the tendency of KOH to absorb the microwave energy. On the other hand, a mixture of KOH in ethanol, benzil, and ketone was irradiated by microwave. It was observed that ethanol evaporated and the reaction was not complete. Therefore, the mixture of benzil, ketone and a solution of KOH in ethanol was irradiated in a water bath inside the microwave oven for the indicated times (Table 1). The air used for cooling the magnetron ventilates the microwave cavity, thus preventing ethanol from reaching explosive concentration and we did not encounter any accident during these studies. Consequently, using microwave irradiation in the aldol condensation reaction, not only shortens the reaction time, but also increases yields. 1. Experimental The microwave oven used for this work was ETHOS-MR (800 W, 180 8C) at 2450 MHz. Melting points were determined on an Electrothermal 9100 and are uncorrected. IR spectra were recorded on a PerkinElmer FT-IR 240-C Spectrophotometer (KBr). 1H NMR spectra were recorded on a varian 500 MHz spectrometer in acetone-d6 using TMS as an internal reference. Products were identified by comparison of melting points and spectroscopic data with those reported. General procedure for microwave-assisted synthesis of 1a–1h In a test tube, powdered benzil (0.1 g, 0.5 mmol) was mixed with acetone (0.1 mL, 1 mmol) and potassium hydroxide in ethanol (0.3 mL, 5%). Then, the mixture was placed in a water bath inside a microwave oven (800 W), and irradiated for the indicated times (Table 1). After that, it was washed with water to give the product. The additional
K. Marjani et al. / Chinese Chemical Letters 20 (2009) 401–403
403
examples are summarized in Table 1. All the products are known and were confirmed by comparing their melting point and IR, 1H NMR spectral data with those reported. Acknowledgment We are grateful to Tarbiat Moallem University Research Council for partial support of this work. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]
L. Akella, R. Vince, Tetrahedron 52 (1996) 8407. D. Takashi, O. Kumiko, Y. Hidetoshi, M. Kunimutsu, Jpn. Kokai Tokkyo Koho Jp 06 145 (1994) 172. H.G. Heller, M.J. Vincent, U.S Patent 5,916,943 (1999). J. Levorse, R.A. Weiss, B.D. Newirth, U.S Patent 714,169,9B1 (2006). P.L. Pauson, Tetrahedron 41 (1985) 5855. O. Geis, H.G. Schmalz, Angew. Chem. Int. Ed. 37 (1998) 911. Y.K. Chung, Coordin. Chem. Rev. 188 (1999) 297. E.A. Uhrich, W.A. Batson, M.A. Tius, Synthesis (2006) 2139. X. Shi, D.J. Gorin, F.D. Toste, J. Am. Chem. Soc. 127 (2005) 5802. A. Giraud, O. Provot, J.F. Peyrat, M. Alami, J.D. Brion, Tetrahedron 62 (2006) 7667. J. Estager, J.M. Leveque, R. Turgis, M. Draye, Tetrahedron Lett. 48 (2007) 755. R.A. Abramovitch, Org. Prep. Proc. Int. 23 (1991) 683. A. Loupy, Microwaves in Organic Synthesis, Wiley-VCH, Weinheim, 2002. C. Gabriel, S. Gabriel, E. Grant, B.S.J. Halstead, D. Mingos, Chem. Soc. Rev. 27 (1997) 213. P. Lidstorm, J. Tierney, B. Wathey, J. Westman, Tetrahedron 57 (2001) 9225. F.R. Japp, J. Knox, J. Chem. Soc. 87 (1905) 673. W. Brown, J. Am. Chem. Soc. 80 (1958) 202. T.J. Clark, J. Org. Chem. 3 (1938) 1749. W. Dilthey, G. Hurtig, Chem. Ber. 67 (1934) 2004. K. Marjani, M. Mousavi, A. Ashouri, O. Arazi, S. Bourghani, M. Asgari, J. Chem. Res. 5189 (2008) 398.
Chinese Chemical Letters 20 (2009) 401–403 www.elsevier.com/locate/cclet
Microwave-assisted aldol condensation of benzil with ketones Katayoun Marjani a, Maryam Asgari a, Akram Ashouri a, Gholam Hossein Mahdavinia b, Hossien Abbastabar Ahangar a,* b
a Faculty of Chemistry, Tarbiat Moallem University, P.O. Box 15614, Tehran, Iran Department of Chemistry, Islamic Azad University-Marvdasht Branch, Marvdasht, Iran
Received 9 September 2008
Abstract Under microwave irradiation, the corresponding hydroxycyclopentenones were prepared in high yields by the cross-aldol reactions of benzil with various ketones. When the reactions were performed in various solvents under classical heating for a long time, they produced the products in relatively low yields. # 2008 Hossien Abbastabar Ahangar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Benzil; Microwave irradiation; Cross-aldol reaction; Hydroxycyclopentenones
Cyclopentenones are of interest for their anti tumor and anti diabetic [1], pesticide and bactericide [2] properties. They have also been used in commercial goods as labeling materials for their photochemical properties [3]. Substituted cyclopentenones are used for incorporation in fine fragrances, cosmetics, toiletries and related applications [4] In addition, the cyclopentenone moiety is a very useful building block for the synthesis of other biologically active compounds composed of five membered units, due to the versatility of the a,b-unsaturated carbonyl functionality. Among a variety of approaches for preparation of cyclopentenones, such as Pauson-Khand reaction [5–7], Nazarove cyclization [8] and Rautenstrauch rearrangement [9], aldol condensation of a-diketones with acetone derivatives is a simple and inexpensive method for preparation of cyclopentenone derivatives. This method is flexible, as there are several simple routes available for the preparation of a-diketones [10,11]. The recent development in so called ‘‘green chemistry’’ shows that alternative methods of carrying out chemical transformation can minimize the environmental harmfulness of classical reactions. One of the most popular and interesting approach in this field is employing the microwaves energy for conducting many chemical transformations [12,13]. The interaction of the matter with such kinds of electromagnetic waves results in higher speed of heating [14], much shorter reaction time and very often the higher selectivity of desired products. The acceleration of reactions by microwave exposure results from material-wave interactions leading to thermal effects (which may be easily estimated by temperature measurements) and specific (non purely thermal) effects [15]. Here, we report on a facile aldol condensation protocol using benzil and different ketones with a dramatic reduction of reaction time for synthesis of hydroxycyclopentenones derivatives (Scheme 1).
* Corresponding author. E-mail address: [email protected] (H.A. Ahangar). 1001-8417/$ – see front matter # 2008 Hossien Abbastabar Ahangar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.12.036
402
K. Marjani et al. / Chinese Chemical Letters 20 (2009) 401–403
Scheme 1.
Table 1 Microwave-assisted aldol condensation. Entry
G
R
R0
R00
Product
Time (min)
Yield (%) a
mp (8C)
Lit. Mp (8C)
1 2 3 4 5 6 7 8
H H H H H Br Br Br
H CH3 H CH3 C6H5 H CH3 H
H H CH3 H H H H CH3
H H CH3 CH3 H H H CH3
1a 1b 1c 1d 1e 1f 1g 1h
2 8 4 6 8 4 6 8
90 80 98 82 87 97 85 85
147–148 114–116 180–182 134–136 166–167 239–241 167–169 197–199
149 [17] 116–118 181 [16] 129–130 165 [19] 239–241 167–169 197–199
a
[16] [18] [20] [20] [20]
Isolated yield.
Generally, without microwave irradiation, the reaction of benzil with ketones took a long time to complete, for example we observed that the yield of product for the reaction of benzil and butanone was only 63% after 17 days at room temperature [16], while under microwave irradiation it was 80% after 8 min. The powdered KOH, benzil and ketone were ground together with a mortar and pestle. When irradiated in a microwave oven, the mixture burnt due to the tendency of KOH to absorb the microwave energy. On the other hand, a mixture of KOH in ethanol, benzil, and ketone was irradiated by microwave. It was observed that ethanol evaporated and the reaction was not complete. Therefore, the mixture of benzil, ketone and a solution of KOH in ethanol was irradiated in a water bath inside the microwave oven for the indicated times (Table 1). The air used for cooling the magnetron ventilates the microwave cavity, thus preventing ethanol from reaching explosive concentration and we did not encounter any accident during these studies. Consequently, using microwave irradiation in the aldol condensation reaction, not only shortens the reaction time, but also increases yields. 1. Experimental The microwave oven used for this work was ETHOS-MR (800 W, 180 8C) at 2450 MHz. Melting points were determined on an Electrothermal 9100 and are uncorrected. IR spectra were recorded on a PerkinElmer FT-IR 240-C Spectrophotometer (KBr). 1H NMR spectra were recorded on a varian 500 MHz spectrometer in acetone-d6 using TMS as an internal reference. Products were identified by comparison of melting points and spectroscopic data with those reported. General procedure for microwave-assisted synthesis of 1a–1h In a test tube, powdered benzil (0.1 g, 0.5 mmol) was mixed with acetone (0.1 mL, 1 mmol) and potassium hydroxide in ethanol (0.3 mL, 5%). Then, the mixture was placed in a water bath inside a microwave oven (800 W), and irradiated for the indicated times (Table 1). After that, it was washed with water to give the product. The additional
K. Marjani et al. / Chinese Chemical Letters 20 (2009) 401–403
403
examples are summarized in Table 1. All the products are known and were confirmed by comparing their melting point and IR, 1H NMR spectral data with those reported. Acknowledgment We are grateful to Tarbiat Moallem University Research Council for partial support of this work. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]
L. Akella, R. Vince, Tetrahedron 52 (1996) 8407. D. Takashi, O. Kumiko, Y. Hidetoshi, M. Kunimutsu, Jpn. Kokai Tokkyo Koho Jp 06 145 (1994) 172. H.G. Heller, M.J. Vincent, U.S Patent 5,916,943 (1999). J. Levorse, R.A. Weiss, B.D. Newirth, U.S Patent 714,169,9B1 (2006). P.L. Pauson, Tetrahedron 41 (1985) 5855. O. Geis, H.G. Schmalz, Angew. Chem. Int. Ed. 37 (1998) 911. Y.K. Chung, Coordin. Chem. Rev. 188 (1999) 297. E.A. Uhrich, W.A. Batson, M.A. Tius, Synthesis (2006) 2139. X. Shi, D.J. Gorin, F.D. Toste, J. Am. Chem. Soc. 127 (2005) 5802. A. Giraud, O. Provot, J.F. Peyrat, M. Alami, J.D. Brion, Tetrahedron 62 (2006) 7667. J. Estager, J.M. Leveque, R. Turgis, M. Draye, Tetrahedron Lett. 48 (2007) 755. R.A. Abramovitch, Org. Prep. Proc. Int. 23 (1991) 683. A. Loupy, Microwaves in Organic Synthesis, Wiley-VCH, Weinheim, 2002. C. Gabriel, S. Gabriel, E. Grant, B.S.J. Halstead, D. Mingos, Chem. Soc. Rev. 27 (1997) 213. P. Lidstorm, J. Tierney, B. Wathey, J. Westman, Tetrahedron 57 (2001) 9225. F.R. Japp, J. Knox, J. Chem. Soc. 87 (1905) 673. W. Brown, J. Am. Chem. Soc. 80 (1958) 202. T.J. Clark, J. Org. Chem. 3 (1938) 1749. W. Dilthey, G. Hurtig, Chem. Ber. 67 (1934) 2004. K. Marjani, M. Mousavi, A. Ashouri, O. Arazi, S. Bourghani, M. Asgari, J. Chem. Res. 5189 (2008) 398.