Coumarins, microwave-assisted

For the synthesis of coumarins, the Pechmann reaction [145] is one of the most popular synthetic routes. As the reaction is conventionally carried out at high temperature, two microwave-assisted versions have been recently described. Besson and co-workers described the cyclocondensation of different m-amino phenols 226 with /1-ketoesters 227 on graphite/montmorillonite KIO support (Scheme 83). The use of graphite was crucial in the development of the reaction conditions. In fact, microwave irradiation of the reagents using different conditions gave poor results in terms of yields and purity. The optimized conditions, using a monomode microwave system, employed... 

A modified Pechmann microwave-assisted reaction has been reported using an electron-rich phenol 229 and an a,/l-unsaturated acid in order to obtain coumarins without a substituent in position 4 [147]. Even in this case, the use of an acid solid catalyst (the support) was needed. Best results were obtained with Dowex or Amberhte-15 at 120 °C for 15 min (Scheme 84). 

De la Hoz et al. have studied the microwave-assisted synthesis of substituted coumarins by the condensation of phenol, 1,3-dihydroxybenzene/l,3,5-trihydroxy-benzene and propynoic/propenoic acids55. The examples illustrate that the application of heterogeneous supported catalysts can eliminate the production of acidic waste streams, associated with conventional Lewis acid catalysts. This synthetic approach constitutes an interesting alternative to the Pechman reaction (Scheme 3.34). 

Synthesis of the benzopyran ring has also been performed by microwave-assisted copper-catalysed cross coupling of an aryl iodide with terminal alkynes, in the presence of copper(I) iodide/triphenylphosphine (Scheme 3.35)56. An alternative approach involving microwave heating of mixtures of salicylaldehyde and various derivatives of ethyl acetate in the presence of piperidine has enabled rapid Knoevenagel synthesis of coumarin derivatives (Scheme 3.35)57. 

Solventless, Microwave-Assisted Synthesis of Coumarins via a Tandem Knoevenagel Condensation and an Intramolecular Nucleophilic Acyl Substitution... 

A method for microwave-assisted transesterifications has been published [74]. The microwave-mediated derivatization of poly(styrene-co-allyl alcohol) was investigated as key step in the polymer-assisted synthesis of heterocycles. The procedure was applied to several j8-ketoesters and multigram quantities of products were obtained when neat mixtures of the reagents in open vessels were exposed to micro-wave irradiation in a domestic microwave oven. The soluble supports obtained were used for preparation of a variety of bicyclic heterocycles, for example pyrazo-lopyridinediones or coumarins. 

Scheme 12 Microwave-assisted synthesis of saiicyiaidehydes and coumarins.

Martino E, Ramaiola I, Urbano M, Bracco F, Collina S (2006) Microwave-assisted extraction of coumarin and related compounds from Melilotus officinalis (L.) Pallas as an alternative to Soxhlet emd ultrasound-assisted extraction. J Chromatogr A 1125(2) 147-151 Mashkovskii MD (1953) The pharmacology of tropacin. Farmeikol Toksikol (5) 3-8 (in Russian)... 

Coumarin-3-carboxyHc acids are of great pharmaceutical importance due to their wide range of biological activities. Genovese and coworkers have reported a new microwave-assisted solvent-free protocol for the synthesis of coumarin-3-carboxyHc acids 78 by reacting 2-hydroxybenzaldehydes or 2-hydroxyacetophenones 76 and Meldrum s acid 77 in the presence of... 

Hassan, V, Abbas, S. 2005. An efficient procedure for the synthesis of coumarin derivatives using TiCl4 as catalyst under solvent-free conditions. Tetrahedron Lett. 46 3501-3503. Helavi, B. V, Solabannavar, S. B., Salunkhe, R. S., Mane, R. B. 2003. Microwave-assisted solventless Pechmann condensation. J. Chem. Res. 5 279-280. 

Microwave-assisted High-temperature Metalation of Weakly Activated Aromatics and Heteroaromatics. Over the last few decades, microwave irradiation has been used to accelerate numerous organic reactions, including metalations. Organozinc reagents of the type RZnX possess a good thermal stability and tolerate functional groups, even at elevated temperatures. The direct zincation of coumarin requires 7 days at room temperature to achieve 85% conversion. However, under microwave irradiation, the zincation was achieved in over 90% yield (80 °C, 1 h) (eq 7). ... 

Several coumarins starting from appropriate phenolic compounds have been synthesized in a microwave-assisted reaction using trifluoroacetic acid, which acts as an acidic reagent and a reaction medium. Alternatively, polymer-supported sulfonic acid Amberlyst-15 could also be utilized to assist the formation of coumarins. The usage of a particularly built microwave synthesizer with liquid handling tools rendered the automated synthesis of a coumarin library achievable (07CHE151). 

Zhang, Y. Zou, B. Wang, K. Microwave-assisted synthesis of 4-methyl-coumarin derivatives. Huaxue Shiji 2010, 32, 787-789, 831. 

Valizadeh, H. Shockravi, A. Gholipur, H. Microwave assisted synthesis of coumarins via potassium carbonate catalyzed Knoevenagel condensation in l-n-butyl-3-methylimidazolium bromide ioiuc liquid. J. Heterocycl. Chem. 2007,44, 867-870. 

Bogdal, D. Stepien, L Sanetra, J. Gondek, E. Microwave-assisted synthesis and copolymerization of photo- and electroluminescent methacrylates containing carbazole and coumarin pendant groups. 

Sinhamahapatra et al. (2011) reported that the microwave-assisted synthesis is the most appropriate method for synthesis of coumarins as it provides improved yield in very less time. Mesoporous zirconium phosphate (m-ZrP) is used as a solid acid catalyst for the synthesis of coumarins via Pechmann condensation reaction. Among the substituted phenols, m-amino phenol is more reactive and 100% yield was obtained in very short time at low temperature due to the presence of ring activating amine group in meta position. The m-ZrP is also active towards phenols for the synthesis of 4-methyl coumarin, where only 57% yield was obtained in conventional heating method. 

Hydroxy-3-methoxyphenyl)-3-[4-(coumarin-3-yl)-thiazole-2-yl]-2-isoxa-zoline was synthesized using 2-N-(4-hydroxy-3-methoxyphenylchalconyl)-amino-4-(coumarin-3-yl)-thiazole and hydroxylamine hydrochloride by both the conventional and microwave-assisted method. The conventional method requires about 6-9 h, while microwave irradiation method requires only 2.5-3.5 min and yield is also high (Desai and Desai, 2008). 

---