Application of Microwave in Organic Synthesis. Dry Synthesis of

Didier Villemin*, Benoit Martin and Nathalie BarEcole Nationale Superieure d'Ingenieurs de Caen (ISMRA) Universite de Caen,UMR 6507,6 Boulevard du Marechal Juin F-14050 Caen Cedex, FranceTel (33) 2 31 45 28 40, Fax (33) 2 31 45 28 77, E-mail: Didier.Villemin@ismra.frReceived: 19 February 1998 / Accepted: 3 March 1998 / Published: 5 March 1998Abstract: 3(2)-Naphthofuranone ( 1) was condensed in the presence of Al 2O3-KF with aromatic aldehydes(4) to give arylidenenaphthofuranones ( 5a-f ) without solvent under focused microwave irradiation.Keywords : Microwaves, organic synthesis, catalysis, dry reaction, furanone, aurone.IntroductionAurones (aurone, sulfuretol, maritimetol, leptosidol,etc.) are natural yellow pigments of plants related toflavonoids [1]. Aurones have a limited occurrence − thefirst aurone was discovered only in 1943 and, because ofthe limited methods of synthesis [1,3], aurones havereceived very limited attention. Analogy with flavonoidssuggests that aurones could have interesting biologicalproperties [2].We have already reported that five-membered ringcompounds with a carbonyl group, like tetronic acid [3a],pyrazolone [3b], thiohydanthoin [3c] or indanone [3d],exhibit a high carbon acidity due to the pseudo-planarstructure. These compounds consequently can becondensed easily with aldehydes in the presence of a solidcatalyst (alumina, clay, Al2O3-KF) without solvent (drycondensation).We report herein the extension of this reaction to thesynthesis of 2-arylmethylene-3(2)-naphthofuranones.Naphthofuranone (1), the homologue of 2-coumaranone(2), can be derived from 2-naphthoxyacetic acid (3), anuseful auxin hormone [4]. We are also interested instudying the biological properties of such 3(2)-naphthofuranones described in older literature [5] butpoorly studied to date.


Introduction
Aurones (aurone, sulfuretol, maritimetol, leptosidol, etc.) are natural yellow pigments of plants related to flavonoids [1].Aurones have a limited occurrence − the first aurone was discovered only in 1943 and, because of the limited methods of synthesis [1,3], aurones have received very limited attention.Analogy with flavonoids suggests that aurones could have interesting biological properties [2].
We have already reported that five-membered ring compounds with a carbonyl group, like tetronic acid [3a], pyrazolone [3b], thiohydanthoin [3c] or indanone [3d], exhibit a high carbon acidity due to the pseudo-planar structure.These compounds consequently can be condensed easily with aldehydes in the presence of a solid catalyst (alumina, clay, Al 2 O 3 -KF) without solvent (dry condensation).
We report herein the extension of this reaction to the synthesis of 2-arylmethylene-3(2)-naphthofuranones.Naphthofuranone (1), the homologue of 2-coumaranone (2), can be derived from 2-naphthoxyacetic acid (3), an useful auxin hormone [4].We are also interested in studying the biological properties of such 3(2)naphthofuranones described in older literature [5] [6] a simple synthesis of aurones by dry condensation of 2coumaranone (2) with arylaldehydes on basic alumina; under these conditions, however, 3(2)-naphthofuranone (1) does not lead to the aurone derivatives.The more basic catalyst potassium fluoride on alumina is necessary in order to obtain condensation products.We have also used focused microwave irradiation [7,8] for increasing the rate of the reaction without solvent.A moderate microwave focused irradiation of microwaves (10 min, 40 W) leads the condensation products (5a-5f) in good yield (57-96%), even with sterically hindered aldehydes such as 2,4,6trimethoxybenzaldehyde (4d).
We have anticipated the possible rearrangement of aurone into flavone.Isomerisation of some aurones into flavones under basic conditions is known [9] and also the competitive formation of aurone and flavone takes place in flavonoid synthesis according to the published reaction conditions [10].We have used 13 C NMR spectroscopy for the determination of the structure of the reaction products.According to the work of Ward et al. [11], significant chemical shift differences on carbon a,b,c, are characteristic of the aurone or flavone structure (table 1).
The chemical shifts of the product 4a are very close to the chemical shifts observed in aurone.For compound 4d, the chemical shifts of carbons a and b correspond to the aurone.Carbon c appears to be more shielded than those described in literature but, in our case, the phenyl group is more hindered than in the literature (table 2).
The condensation of naphthofuranone under our conditions seems to lead to aurones without rearrangement.All the olefinic protons have a chemical shift between 6.95 and 7.2 ppm.The reaction is stereospecific and the Zstereochemistry was assigned by analogy of aurone obtained in the condition with coumaranone.Moreover the Z isomer corresponds to the more stable isomer according to AM1 calculations (see Figure 1).HF= heat of formation (kcal/mol).

Conclusion
3(2)-Naphthofuranone (1) was condensed efficiently and rapidly in the presence of Al 2 O 3 -KF with aromatic aldehydes (4) into Z-arylidene naphthofuranones (5a-f) without solvent under focused microwave irradiation.The method is very simple, safe and convenient.

General
Proton NMR spectra (PMR) in ppm downfield from internal Me 4 Si were recorded on a Brucker AC 250 instrument from a solution in CDCl 3 of the product.Mass spectra were recorded on a Nermag R10.10H spectrometer.Infrared spectra were recorded on Perkin Elmer 684 IR spectrophotometer in KBr with absorptions in cm -1 .Melting point (mp) in °C are uncorrected.AM1 calculations were carried out with HyperChem software [12] on a Silicon Graphics workstation and with Spartan software [13].Satisfactory elemental analytical data have been obtained for all compounds described in this paper.

Synthesis of 2H-naphtho[2,1-b]furan-1-one (1)
2-Naphthoxyacetic acid [3b] (85 mmol, 17.2 g) was heated under reflux for 30 min with thionyl chloride in excess and a drop of dry DMF, in a 250 ml roundbottomed flask equipped with a condenser.The thionyl chloride was distilled off.The acid chloride obtained was slowly added dropwise to AlCl 3 (11.5 g ) in CH 2 Cl 2 (40 ml ) cooled with ice water.The mixture was refluxed for 15 min; then the cake was treated with cold water under a hood.The product was then extracted into ether (4 x 100 ml).The organic layer was dried with magnesium sulphate and filtered on Celite.The solvent was evaporated in vacuum and the product was chromatographed on silica gel (eluent : AcOEt/C 6 H 12 =20/80). Brown

Table 1 .
Comparison of chemical shifts of 4a and literature data.

Table 2 .
Comparison of chemical shifts of 4d and literature data.