Next Article in Journal
Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance
Next Article in Special Issue
The Use of Supported Acidic Ionic Liquids in Organic Synthesis
Previous Article in Journal
Two New Chemical Constituents from the Stem Bark of Garcinia mangostana
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 19
Issue 6
10.3390/molecules19067317
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation

by
Damiano Rocchi
,
Juan F. González
and
J. Carlos Menéndez
*
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, Madrid 28040, Spain
*
Author to whom correspondence should be addressed.
Molecules 2014, 19(6), 7317-7326; https://doi.org/10.3390/molecules19067317
Submission received: 27 March 2014 / Revised: 14 May 2014 / Accepted: 26 May 2014 / Published: 4 June 2014
(This article belongs to the Special Issue Heterogeneous Acid Catalysts)
Browse Figures
Versions Notes

Abstract

:
An environmentally benign, clean and general protocol was developed for the synthesis of aryl and heteroaryl trans-chalcones. This method involved solvent-free reaction conditions under microwave irradiation in the presence of a clay-based catalyst, and afforded the target compounds in good yields and short reaction times. Furthermore, the same conditions allowed the synthesis of symmetrical, diarylmethylene-α,β-unsaturated ketones from aromatic aldehydes and ketones.

1. Introduction

Chalcones (trans-1,3-diaryl-2-propen-1-ones) are a very important class of compounds due to their occurrence in Nature and their interesting and versatile pharmacological properties, as summarized in several reviews [1,2,3,4,5]. These properties include antineoplastic [5,6,7], antimalarial [8], antiviral (HIV) [9,10], antibacterial [4,11,12], antioxidant [12] and anti-inflammatory [4,13] activities, among others. These compounds are also flexible scaffolds for the construction of five- and six-membered rings or their subsequent elaboration into polycyclic systems [14,15]. Chalcones are traditionally accessed by cross-aldol condensations of aryl methyl ketones and aromatic aldehydes in the presence of alkali [16,17,18], a reaction that requires the use of an organic solvent and a highly polluting alkaline base and in most cases needs to be followed by purification by column chromatography, leading again to waste generation in the form of volatile organic solvents and discarded chromatographic stationary phases.
Economic and environmental concerns connected to the practice of organic synthesis have received especial attention in recent years. In this context, a particularly important area is the development of synthetic processes in the absence of solvents [19,20,21,22]. Microwave-assisted organic synthesis (MAOS) has emerged as an efficient and powerful tool in this area [23,24,25,26,27,28] and often leads to simple protocols, short processing times, increased product yields, energy savings [29] and lower costs, thereby enabling environmentally friendly processes [30]. On the other hand, methods based on the use of heterogeneous catalysts are widely used in industrial fine and pharmaceutical chemistry, and play an important role in the current bid for the development of green synthetic processes. In particular, there is much interest in the use of clays as solid acid catalysts because of their desirable properties such as environmental compatibility, non-corrosive and non-toxic nature, low cost and, furthermore, because they often allow very simple isolation procedures. To summarize, heterogeneous catalysis is crucial to chemical technology, and clays in particular are finding increasing applications as catalysts [31,32,33,34].
In this paper, we describe a method that combines the desirable features of both approaches and its application to the preparation of chalcones. The need for this research became apparent in the course of our program on the use of aryl and heteroaryl trans-chalcones in heterocyclic synthesis [35,36,37,38], when we noticed the shortcomings of the currently available protocols for the synthesis of the required starting materials. Thus, we present here our studies on a solvent-free protocol for their synthesis under microwave irradiation conditions in the presence of a montmorillonite clay catalyst, its application to a large number of examples in order to establish its scope and a brief study of its subsequent generalization to other types of substrates.

2. Results and Discussion

We started our study by examining the model cross aldol condensation reaction between acetophenone (1a) and benzaldehyde (2a) at a relatively large scale (8.6 mmol) in the presence of montmorillonite KSF (MKSF). The choice of catalyst was based on literature precedent for the thermal cross-condensation of acetophenone and benzaldehyde in the presence of clay although we were concerned about its generality, since the scope of this literature method was quite narrow [39]. Thus, we set out to optimize conditions for this model reaction by varying the following experimental parameters: temperature, time, stoichiometry, and amount of clay. In order to study the influence of temperature, an equimolecular mixture of 1a and 2a with 0.3 g/mol of the clay catalyst was irradiated under focused microwave for 1 hour. When the reaction mixture was heated at 100 °C or 120 °C, poor conversions were observed (Table 1, entries 1 and 2), but a further increase in the reaction temperature to 150 °C afforded chalcone 3a in a very good 88% yield (Table 1, entry 3). The next parameter that we investigated was the amount of catalyst, and to this end we performed the reaction with an equimolecular mixture of 1a and 2a, for 1 hour at 150 °C, in the presence of MKSF 0.06, 0.12, 0.24 and 0.30 gram of clay per mol of 1a. These experiments led us to select 0.24 g/mol as the optimal clay/substrate ratio (Table 1, entries 5 to 8). Under these conditions, reaction times below 1 h (entries 9 and 10) proved to be detrimental to conversion and were therefore avoided in further experiments. We also observed that an increase of the 1a/2a ratio led to decreased yield (Table 1, entry 11). When the reaction was carried out in a multigram scale, an increase in the temperature was required in order to obtain chalcone 3a in a good yield (Table 1, entry 12). Finally, in order to compare the performance of microwave irradiation versus conventional heating, the reaction was performed at 150 °C in an oil bath using the optimal 1a/2a ratio and amount of clay. In this experiment, a very long reaction time (20 h) was needed for the reaction to achieve completion, and 3a was isolated in a poor 16% yield, together with many unidentified by-products (Table 1, entry 13). To summarize these experiments, it can be concluded that focused microwave irradiation has a highly beneficial effect on the reaction, both in terms of yields and reaction times.
Table
Table 1. Optimization of the synthesis of model chalcone 3a. Molecules 19 07317 i001
Table 1. Optimization of the synthesis of model chalcone 3a. Molecules 19 07317 i001
Entry1a/2aT (°C)TimeKSF/substrate ratio (g/mol)Yield (%) a
11/1100 °C60 min0.308
21/1120 °C60 min0.3023
31/1150 °C60 min0.3088
41/1160 °C60 min0.3088
51/1150 °C60 min0.065
61/1150 °C60 min0.1281
71/1150 °C60 min0.2497
81/1150 °C60 min0.3088
91/1150 °C40 min0.2474
101/1150 °C20 min0.2450
112/1150 °C60 min0.2486
121/1160 °C60 min0.2478 b
131/1150 °C20 h0.2916 c
a Isolated yields, when the reaction was performed under microwave irradiation at 0.86 mmol scale, except where noted otherwise; b Isolated yields, when the reaction was performed under microwave irradiation in a 30 mmol scale; c Isolated yield under reflux conditions.
The substrate scope of the cross aldol condensation reaction in the presence of the MKSF clay catalyst was explored with a variety of substituted acetophenone substrates containing either electron donating or electron withdrawing groups, with the results shown in Scheme 1 and Table 2. As expected, the presence of electron-releasing substituents in the acetophenone component, which acts as the nucleophile, is slightly beneficial to yield (compare, for instance, the yields in entries 1, 10, 19, 23 and 26). The reaction was not sensitive to steric hindrance in the aldehyde, since it tolerates well the presence of ortho substituents (compare the yields in entries 4–5, 7–9 and 15–16). Generally speaking, the substituents at the aromatic ring of the aldehyde component did not have a significant influence in the yield, but it is remarkable that some of the best results corresponded to reactions with methoxybenzaldehyde derivatives (entries 2, 11, 15, 20), in spite of the fact that the electron-releasing nature of the methoxy substituent should lead to a lower reactivity as electrophiles.
Molecules 19 07317 g001 550
Scheme 1. Clay-promoted synthesis of chalcones under microwave irradiation.
Scheme 1. Clay-promoted synthesis of chalcones under microwave irradiation.
Molecules 19 07317 g001
Table
Table 2. Scope and yields in the synthesis of chalcones 3.
Table 2. Scope and yields in the synthesis of chalcones 3.
EntryAr1Ar2CompoundYield (%) a
1C6H5C6H53a97
2C6H54-MeOC6H43b85
3C6H54-MeC6H43c55
4C6H54-ClC6H43d74
5C6H52-ClC6H43e77
6C6H54-BrC6H43f69
7C6H52-NO2C6H43g51
8C6H53-NO2C6H43h44
9C6H54-NO2C6H43i43 (57) b
104-MeOC6H4C6H53j91
114-MeOC6H44-MeOC6H43k83
124-MeOC6H44-BrC6H43l73
134-MeC6H4C6H53m95
144-MeOC6H44-NO2C6H43n55
154-MeC6H42-MeOC6H43o93
164-MeC6H44-MeC6H43p77
174-MeC6H44-BrC6H43q76
184-MeC6H42-NO2C6H43r66
194-ClC6H4C6H53s54
204-ClC6H43-OMeC6H43t78
214-ClC6H44-BrC6H43u64
224-ClC6H42-NO2C6H43v48
234-BrC6H4C6H53w60
244-BrC6H44-BrC6H43x86
254-BrC6H44-NO2C6H43y49
264-NO2C6H4C6H53z65 c
274-NO2C6H44-OMeC6H43aa64 c
284-NO2C6H44-MeC6H43ab77 c
294-NO2C6H44-BrC6H43ac68 c
304-NO2C6H44-NO2C6H43ad60 c
31C6H5 Molecules 19 07317 i0023ae57
32C6H5 Molecules 19 07317 i0033af63
334-MeC6H4 Molecules 19 07317 i0043ag54
344-MeC6H4 Molecules 19 07317 i0033ah64
354-BrC6H4 Molecules 19 07317 i0043ai48
36C6H5 Molecules 19 07317 i0053aj85
37 Molecules 19 07317 i005C6H53ak60
38 Molecules 19 07317 i005 Molecules 19 07317 i0053al97
39 Molecules 19 07317 i0052-NO2C6H43am45
40 Molecules 19 07317 i006C6H53an54
41C6H5 Molecules 19 07317 i0063ao78
42 Molecules 19 07317 i006 Molecules 19 07317 i0063ap92
a General reaction conditions: A mixture of aldehyde 2 (0.86 mmol), ketone 1 (0.86 mmol) and MKSF (200 mg) in a sealed tube, was heated under microwave irradiation at 150 °C for 1 h; b Reaction conditions for the reaction proceeding in 57% yield: 170 °C, 3 h; c Reaction conditions for entries 26–30: A mixture of aldehyde 2 (0.86 mmol), ketone 1 (0.86 mmol) and MKSF (200 mg) in a sealed tube, was heated under microwave irradiation at 170 °C for 3 h.
Since the catalytic affect of the clay can be attributed to the Lewis acid activity of its metallic centers (Scheme 2a), the good reactivity of the methoxy derivatives can be explained by accepting that coordination of the oxygen atom in the OMe group with cationic centers in the clay attenuates its electron-releasing effect (Scheme 2b) [40]. Another special case was that of nitrobenzaldehyde derivatives which, again unexpectedly, gave relatively low yields (entries 7, 8, 9, 13, 18, 22, 25, 30–35). In this case, we propose that the lower reactivity is due to an increased activation energy associated to stabilizing interactions of the aldehyde with the clay by coordinating two of the cationic centers (Scheme 2c). In agreement to this explanation, we found an increase in yield from 43% to 57% for the case of compound 3i when changing the conditions from 150 °C, 1 h to 170 °C, 3 h (enthy 9). Unfortunately, higher temperatures could not be used because they led to the decomposition of p-nitrobenzaldehyde. Finally, in order to demonstrate the wide application of this methodology, the reaction was carried out with selected examples of heteroaromatic aldehydes and ketones, to give good yields of compounds 3aj to 3ap (entries 36–42).
Molecules 19 07317 g002 550
Scheme 2. Explanation proposed for the observed substituent effects on yield.
Scheme 2. Explanation proposed for the observed substituent effects on yield.
Molecules 19 07317 g002
In order to further demonstrate the generality of this methodology, the pseudo three-component, double aldol reactions of representative aliphatic ketones with two equivalents of benzaldehyde were briefly examined under the optimal microwave conditions previously developed, leading to compounds 5–7 in good to excellent yields. Also, one example of a Knoevenagel reaction was carried out, affording compound 8 [41] in an excellent 92% yield (Scheme 3).
Molecules 19 07317 g003 550
Scheme 3. Additional examples showing the generality of the clay-promoted condensations.
Scheme 3. Additional examples showing the generality of the clay-promoted condensations.
Molecules 19 07317 g003

3. Experimental Section

3.1. General Information

Melting points were measured in open capillary tubes and are uncorrected. A CEM Discover focused microwave synthesizer with a maximum microwave power level of 400 W and microwave frequency of 2,444 MHz was employed. The 1H-NMR and 13C-NMR spectra were recorded on a Bruker (Avance) 250 MHz NMR instrument maintained by the CAI de Resonancia Magnética, Universidad Complutense, using unless indicated otherwise CDCl3 as solvent and the residual CHCl3 as reference. Chemical shifts are given in parts per million (δ scale) and the coupling constants are given in Hertz. Silica gel-G plates (Merck) were used for TLC analysis. Elemental analyses were measured by the CAI de Microanálisis Elemental, Universidad Complutense, on a Leco 932 CHNS analyser. IR spectra were recorded on a Perkin Elmer Paragon 1000 FT IR instrument (neat samples on a NaCl window). Montmorillonite KSF (product number 28,153-0) was purchased from Sigma-Aldrich (Madrid, Spain) and used as received. This particular clay has 20–25 μm particle size and a surface area of 20–40 m2/g.

3.2. General Procedure for Cross Aldol Condensations

A mixture of the suitable aldehyde (1.0 mmol), acetophenone (1.0 mmol) and clay catalyst (240 mg) was warmed at 150 °C in a sealed tube under microwave irradiation, for 1 h. In the reactions involving solid starting materials, they were thoroughly mixed by grinding in a mortar before irradiation. The reaction mixture was diluted with hot ethanol (20 mL), the catalyst was filtered off, the solvent was evaporated and the residue was purified by crystallization (EtOH) for solid chalcones (compounds 3a–3d, 3f–3m, 3p–3ar) or by column chromatography (silica gel, ethyl acetate/hexanes) for oily chalcones (compounds 3e, 3o), to afford the pure final products. All yields were calculated from isolated products. Characterization data for previously unknown compounds are given below. For full characterization data, see the Supporting Information.
(E)-3-(5-Bromo-2-nitrophenyl)-1-(p-tolyl)-2-propen-1-one (3ag). White solid (54%). M.p. 164–166 °C. IR νmax (KBr): 1663, 1598, 1520 cm−1. 1H-NMR δ: 8.08 (1H, d, J = 15.7 Hz), 8.00–7.83 (4H, m), 7.68 (1H, dd, J = 9.0, 2.8 Hz), 7.32 (3H, m), 2.45 (3H, s). 13C-NMR δ: 189.6, 147.2, 144.5, 138.5, 134.8, 133.6, 133.3, 132.3, 129.7, 129.1, 128.6, 128.3, 126.7, 21.9. Anal. Calcd. for C16H12BrNO3: C, 55.51; H, 3.49; N, 4.05. Found: C, 55.28; H, 3.21 N, 3.95.
(E)-3-(4,5-Dimethoxy-2-nitrophenyl)-1-(p-tolyl)-2-propen-1-one (3ah). White solid (64%). M.p. 180–182 °C. 1H-NMR δ 8.20 (d, J = 15.7 Hz, 1H), 7.97–7.91 (m, 2H), 7.67 (s, 1H), 7.36–7.29 (m, 2H), 7.20 (d, J = 15.7 Hz, 1H), 7.07 (s, 1H), 4.06 (s, 3H), 4.01 (s, 3H), 2.45 (s, 3H). 13C-NMR δ 190.8, 153.3, 150.0, 144.0, 141.4, 141.1, 135.0, 129.5, 129.1, 126.7, 126.2, 110.2, 108.1, 56.7, 56.6, 21.8. Anal. Calcd. for C18H17NO5: C, 66.05; H, 5.23; N, 4.28. Found: C, 59.93; H, 5.09; N, 4.15.
(E)-3-(5-Bromo-2-nitrophenyl)-1-(4-bromophenyl)-2-propen-1-one (3ai). White solid (48%). M.p. 191–193 °C. 1H-NMR, DMSO-d6) δ: 8.49 (1H, d, J = 2.7 Hz), 8.16 (2H, d, J = 9.0 Hz), 8.05 (1H, d, J = 9.0 Hz), 7.98 (2H, d, J = 3.8 Hz), 7.92 (1H, dd, J = 9.0, 2.7 Hz), 7.82 (2H, d, J = 9.0 Hz). 13C-NMR (63 MHz, DMSO-d6) δ: 13C-NMR (63 MHz, DMSO) δ 188.0, 147.8, 137.7, 135.9, 133.7, 132.0, 131.8, 130.9, 127.9, 127.6, 126.9, 126.8. Anal. Calcd. for C15H9Br2NO3: C, 43.83; H, 2.21; N, 3.41. Found: C, 43.57; H, 2.39; N, 3.17.

4. Conclusions

In conclusion, we have developed a solvent-free, inexpensive and fast microwave-assisted method for cross aldol condensations, catalysed by the acidic clay montmorillonite KSF, with a broad scope of application. In comparison to previously reported methods, where strong acids or bases are normally required, the protocol reported here constitutes a user- and environment-friendly alternative that proceeds normally in good to excellent yields.

Supplementary Materials

Supplementary materials can be accessed at: https://www.mdpi.com/1420-3049/19/6/7317/s1.

Acknowledgments

Financial support from Ministerio de Economía y Competitividad (MINECO) is gratefully acknowledged (grant CTQ-2012-33272-BQU).

Author Contributions

D.R., J.F.G. and J.C.M. conceived the research and designed the experiments. D.R. and J.F.G. carried out the experiments. J.F.G. and J.C.M. wrote the paper.

Conflicts of Interest

The authors declare no conflict of interest.

References and Notes

  1. Dimmock, J.R.; Elias, D.W.; Beazely, M.A.; Kandepu, N.M. Bioactivity of chalcones. Curr. Med. Chem. 1999, 6, 1125–1149. [Google Scholar]
  2. Batovska, D.I.; Todorova, I.T. Trends in the utilization of the pharmacological potential of chalcones. Curr. Clin. Pharmacol. 2010, 5, 1–29. [Google Scholar] [CrossRef]
  3. Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem. 2012, 19, 209–225. [Google Scholar] [CrossRef]
  4. Nowakowska, Z. A review of anti-infective and anti-inflammatory chalcones. Eur. J. Med. Chem. 2007, 42, 125–137. [Google Scholar] [CrossRef]
  5. Cabrera, M.; Simoens, M.; Falchi, G.; Lavaggi, M.L.; Piro, O.E.; Castellano, E.E.; Vidal, A.; Azqueta, A.; Monge, A.; López de Ceráin, A.; et al. Synthetic chalcones, flavanones, and flavones as antitumoral agents: Biological evaluation and structure-activity relationships. Bioorg. Med. Chem. 2007, 15, 3356. [Google Scholar] [CrossRef]
  6. Xia, Y.; Yang, Z.Y.; Xia, P.; Bastow, K.F.; Nakanishi, Y.; Lee, K.H. Antitumor agents. Part 202: Novel 2'-amino chalcones: Design, synthesis and biological evaluation. Bioorg. Med. Chem. Lett. 2000, 10, 699–701. [Google Scholar] [CrossRef]
  7. Nam, N.H.; Kim, Y.; You, Y.J.; Hong, D.H.; Kim, H.M.; Ahn, B.Z. Cytotoxic 2',5'-dihydroxychalcones with unexpected antiangiogenic activity. Eur. J. Med. Chem. 2003, 38, 179–187. [Google Scholar] [CrossRef]
  8. Wu, X.; Wilairat, P.; Go, M.L. Antimalarial activity of ferrocenyl chalcones. Bioorg. Med. Chem. Lett. 2002, 12, 2299–2302. [Google Scholar] [CrossRef]
  9. Wu, J.H.; Wang, X.H.; Yi, Y.H.; Lee, K.H. Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Bioorg. Med. Chem. Lett. 2003, 13, 1813–1815. [Google Scholar] [CrossRef]
  10. Hu, G.; Li, X.; Zhang, X.; Li, Y.; Ma, L.; Yang, L.-M.; Liu, G.; Li, W.; Huang, J.; Shen, X.; et al. Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays. J. Med. Chem. 2012, 55, 10108–10117. [Google Scholar] [CrossRef]
  11. Nagwanshi, R.; Bakhru, M.; Jain, S. Comparative antimicrobial activities of chalcones and their photoproducts. Med. Chem. Res. 2012, 21, 1587–1596. [Google Scholar] [CrossRef]
  12. Ahmad, M.R.; Sastry, V.G.; Bano, N.; Anwer, S.; Kumaraswamy, G. Antioxidant and antibacterial activities of some novel chalcone derivatives and their synthesis by conventional and microwave irradiation methods. J. Chem. Pharm. Res. 2011, 3, 710–717. [Google Scholar]
  13. Talukdar, J.I.; Kachroo, M.; Razdan, R. Anti-inflammatory activity of some newly synthesized chalcones. Int. J. Pharm. 2013, 3, 728–733. [Google Scholar]
  14. Basnet, A.; Thapa, P.; Karki, R.; Na, Y.; Jahng, Y.; Jeong, B.-S.; Jeong, T.C.; Leec, C.-S.; Lee, E.-S. 2,4,6-Trisubstituted pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure–activity relationship. Bioorg. Med. Chem. 2007, 15, 4351–4359. [Google Scholar] [CrossRef]
  15. Nepal, K.; Singh, G.; Turan, A.; Agarwal, A.; Sapra, S.; Kumar, R.; Banerjee, U.C.; Verma, P.K.; Satti, N.K.; Gupta, M.K.; et al. A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors. Bioorg. Med. Chem. 2011, 19, 1950–1958. [Google Scholar] [CrossRef]
  16. Kurth, E.F. The preparation of the polyhydroxychalcones. J. Am. Chem. Soc. 1939, 81, 861–862. [Google Scholar] [CrossRef]
  17. Smith, H.E.; Paulson, M.C. The preparation of chalcones from hydroxy and methoxy aldehydes and ketones. J. Am. Chem. Soc. 1954, 76, 4486–4487. [Google Scholar] [CrossRef]
  18. Zurd, L.; Horowitz, R.M. Spectral studies on flavonoid compounds. III. Polyhydroxychalcones. J. Org. Chem. 1961, 26, 2561–2563. [Google Scholar] [CrossRef]
  19. Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chem. Rev. 2000, 100, 1025–1074. [Google Scholar] [CrossRef]
  20. Tanaka, K. Solvent-free Organic Synthesis; Wiley-VCH: Weinheim, Germany, 2003. [Google Scholar]
  21. Martins, M.A.P.; Frizzo, C.P.; Moreira, D.N.; Buriol, L.; Machado, P. Solvent-free heterocyclic synthesis. Chem. Rev. 2009, 109, 4140–4182. [Google Scholar]
  22. Zhang, W.; Cue, B.W.; Mack, J.; Muthukrishnan, S. Green Techniques for Organic Synthesis and Medicinal Chemistry; Zhang, W., Cue, B.W., Eds.; Wiley: Chichester, UK, 2012; Chapter 11. [Google Scholar]
  23. Tierney, J.; Lindstrom, P. Microwave Assisted Organic Synthesis; Blackwell: Oxford, UK, 2004. [Google Scholar]
  24. Kappe, C.O. Controlled Microwave Heating in Modern Organic Synthesis. Angew. Chem. Int. Ed. 2004, 43, 6250–6284. [Google Scholar] [CrossRef]
  25. Van der Eycken, E.; Kappe, C.O. (Eds.) Microwave-assisted Synthesis of Heterocycles; Springer Verlag: Berlin, Germany, 2006.
  26. De la Hoz, A.; Díaz-Ortiz, A.; Moreno, A.; Sánchez-Mingallón, A.; Prieto, P.; Carrillo, J.R.; Vázquez, E.; Gómez, M.V.; Herrero, M.A. Microwave-assisted reactions in heterocyclic compounds with applications in medicinal and supramolecular chemistry. Comb. Chem. High Throughput Screen. 2007, 10, 877–902. [Google Scholar] [CrossRef]
  27. Sharma, A.; Appukkuttan, P.; van der Eycken, E. Microwave-assisted synthesis of medium-sized heterocycles. Chem. Commun. 2012, 48, 1623–1637. [Google Scholar]
  28. Zhu, J.; Pallavkar, S.; Chen, M.; Yerra, N.; Luo, Z.; Colorado, H.A.; Lin, H.; Haldolaarachchige, N.; Khasanov, A.; Ho, T.C.; et al. Magnetic carbon nanostructures: Microwave energy-assisted pyrolysis vs. conventional pyrolysis. Chem. Commun. 2013, 49, 258–260. [Google Scholar] [CrossRef]
  29. For a recent example involving experimental measurements of energy consumption for standard and microwave-assisted conditions, see: Prasanna, P.; Balamurugan, K.; Perumal, S.; Menéndez, J.C. A facile, three-component domino protocol for the microwave-assisted synthesis of functionalized naphtho[2,3-b]furan-4,9-diones in water. Green Chem. 2011, 13, 2123–2129. [Google Scholar] [CrossRef]
  30. Strauss, C.R.; Varma, R.S. Microwaves in green and sustainable chemistry. Top. Curr. Chem. 2006, 266, 199–231. [Google Scholar] [CrossRef]
  31. Varma, R.S. Clay and clay-supported reagents in organic synthesis. Tetrahedron 2002, 58, 1235–1255. [Google Scholar] [CrossRef]
  32. Nagendrappa, G. Organic synthesis using clay and clay-supported catalysts. Appl. Clay Sci. 2011, 53, 106–138. [Google Scholar] [CrossRef]
  33. Kaur, N.; Kishore, D. Montmorillonite: An efficient, heterogeneous and green catalyst for organic synthesis. J. Chem. Pharm. Res. 2012, 4, 991–1015. [Google Scholar]
  34. Sridharan, V.; Menéndez, J.C. Two-step stereocontrolled synthesis of densely functionalized cyclic β-aminoesters containing four stereocenters, based on a new cerium(IV) ammonium nitrate catalyzed sequential three-component reaction. Org. Lett. 2008, 10, 4303–4306. [Google Scholar] [CrossRef]
  35. Tenti, G.; Ramos, M.T.; Menéndez, J.C. One-pot access to a library of structurally diverse nicotinamide derivatives via a three-component formal aza [3+3] cycloaddition. ACS Comb. Sci. 2012, 14, 551–557. [Google Scholar] [CrossRef]
  36. Tenti, G.; Egea, J.; Villarroya, M.; León, R.; Fernández, J.C.; Padín, J.F.; Sridharan, V.; Ramos, M.T.; Menéndez, J.C. Identification of 4,6-diaryl-1,4-dihydropyridines as a new class of neuroprotective agents. Med. Chem. Commun. 2013, 4, 590–594. [Google Scholar] [CrossRef]
  37. Rocchi, D.; González, J.F.; Menéndez, J.C. Microwave-assisted, sequential four-component synthesis of polysubstituted 5,6-dihydroquinazolinones from acyclic precursors and an oxidant-free method for their aromatization under focused microwave irradiation. Green Chem. 2013, 15, 511–517. [Google Scholar]
  38. Tenti, G.; Parada, E.; León, R.; Egea, J.; Martínez-Revelles, S.; Briones, A.M.; Sridharan, V.; López, M.G.; Ramos, M.T.; Menéndez, J.C. New 5-unsubstituted dihydropyridines with improved CaV1.3 selectivity as potential neuroprotective agents against ischemic injury. J. Med. Chem. 2014, 57, 4313–4323. [Google Scholar]
  39. Ballini, R.; Bosica, G.; Maggi, R.; Ricciutelli, M.; Righi, P.; Sartori, G.; Sartorio, R. Clay-catalysed solventless synthesis of trans-chalcones. Green Chem. 2001, 3, 178–180. [Google Scholar] [CrossRef]
  40. Dintzner, M.R.; Little, A.J.; Pacilli, M.; Pileggi, D.J.; Osner, Z.R.; Lyons, T.W. Montmorillonite clay-catalyzed hetero-Diels–Alder reaction of 2,3-dimethyl-1,3-butadiene with benzaldehydes. Tetrahedron Lett. 2007, 48, 1577–1579. [Google Scholar] [CrossRef]
  41. For precedent of a clay-promoted Knoevenagel reaction, see: Martín, R.M.; Ortega, E.; Rojas, M.L.; Vicente, M.A.; Banares, M.A. Ultrasound-activated Knoevenagel condensation of malononitrile with carbonylic compounds catalysed by alkaline-doped saponites. J. Chem. Technol. Biotechnol. 2005, 80, 234–238. [Google Scholar] [CrossRef]
  • Sample Availability: Samples of the compounds described in this paper are available from the authors.

Share and Cite

MDPI and ACS Style

Rocchi, D.; González, J.F.; Menéndez, J.C. Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation. Molecules 2014, 19, 7317-7326. https://doi.org/10.3390/molecules19067317

AMA Style

Rocchi D, González JF, Menéndez JC. Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation. Molecules. 2014; 19(6):7317-7326. https://doi.org/10.3390/molecules19067317

Chicago/Turabian Style

Rocchi, Damiano, Juan F. González, and J. Carlos Menéndez. 2014. "Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation" Molecules 19, no. 6: 7317-7326. https://doi.org/10.3390/molecules19067317

Article Metrics

Back to TopTop