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Effect of Microwave Irradiation on Condensation of 6-Substituted 3-Formylchromones with Some Five-membered Heterocyclic Compounds

R. Gasparová, M. Lácová^* and D. Loos^*

Table 1. Continued.

^* The upper data of yield and reaction time (t_r) are given for the condensation in microwave oven, the lower data for the classic condensation.
Table 2. IR Spectral Data of Synthesized Compounds

Table 2 Continued

^a[nu](CO)_pyr, ^b[nu](CO)_het
Table 3. ¹H NMR spectra data of prepared compounds

Table 3. Continued

Table 3. Continued

Results and Discussion
2-Acetamido-1-methyl-5-[(6-R-4-oxo-4H-benzopyran-3-yl)methylidene]-4,5-dihydroimidazol-4-ones Va - Vf were obtained by condensations of Ia - If with creatinine II were carried out in acetic anhydride, both under classical and microwave irradiation conditions.
Although the yields in both methods were almost the same (46 - 84 %), reactions in microwave oven were considerably shorter (Table 1).
When boric acid instead of potassium acetate was used as a catalyst and reaction was carried out in dimethyl sulfoxide, 2-imino-1-methyl-5-[(6-R-4-oxo-4H-[1]-benzopyran-3-yl) methylidene]imidazolidin-4-ones VIa - VIe were obtained in 67 - 98 % yields.
A convenient synthesis of 1-metyl-4-oxo-5-[(6-R-4-oxo-4H-[1]-benzopyran-3-yl)methylidene]-4,5-dihydroimidazol-2-carbamoic acids VII was realized by reaction of creatinine II with ethylchloroformate in N, N - dimethylformamide with subsequent addition of aldehyde I. The hydrolyzed products VIIa - VIIe with 69 - 71 % yields were obtained by both classical and microwave irradiation methods, respectively. Compounds VII resulted from utilization of condensing water in the process of hydrolysis, because carbamoic acids VII have been created in all our experiments, also in case of anhydrous conditions. In the ¹H NMR spectra of compounds VII did not occur signals for ethyloxygroup.
Condensations of I with thiohydantoin III were carried out in acetic anhydride in the presence of potassium acetate. The difference of reaction times between these two condensation methods was also evident although the yields of 2-thioxo-5-[(6-R-4-oxo-4H-[1]-benzopyran-3-yl) methylidene]imidazolidin-4-ones VIIIa -VIIIe were comparable (59 - 96%).
Reactions of I with 3-ethylrhodanine IV in microwave oven lead to arising of 2-thioxo-5-[(6-R-4-oxo-4H-benzopyran-3-yl)methylidene]thiazolidin-4-ones IXa and IXb in 67 - 70 % yields.
All condensation products are stable solid compounds, rather insoluble in common solvents, with high melting points. For their difficult solubility in DMSO we had to make their ¹H NMR spectra measured at elevated temperature.
We tried to hydrolyze some of prepared compounds in diluted mineral acids, but use of concentrated hydrochloric acid was successful only by case of 4 hrs. reflux. Thus were isolated compounds X with both opened heterocycles (yields 47 - 56 %). On the base of ¹H NMR -, ¹³C NMR - spectra and elemental analysis we could propose the structure of compounds X, which contain guanidinyl, carboxyl and enolic groups. Compounds X can be regarded as a mixtures of isomers with a very fast tautomeric equilibrium both enolic and oxo groups. The assumption of fast tautomeric equilibrium is supported by the high data for shift signals of C-9 in ¹³C NMR spectra.
We attempted to realize Diels - Alder reactions with various dienophiles, using e.g. maleinanhydride, diethyl butindioate and tetracyanoethylene classic as well as microwave irradiation - focused procedures. Only heating a mixture of Vb in toluene with surplus of maleinanhydride at 40 ^oC over 15 hrs. was successful and was formed out spiroheterocyclic aducts XI (yield 64 %). The using of microwave irradiation for Diels - Alder experiments was unsuccessful.
Summary
The synthesis of different types of 3-substituted 4H-4-oxobenzopyranes was realized under focused microwave irradiation as well as by a classic method.
The beneficial effect of microwave irradiation on aldol condensation of 3-formylchromones with 2-imino-1-methylimidazolidine-4-one (creatine), 2-thioxoimidazolidine-4-one (thiohydantoin) and 2-etyl-2-thioxothiazolidin-4-one (3-ethylrodanine) in different reaction media is described. Our results showed that the effect of microwave irradiation on studied reactions caused the shortening of reaction time, smoothly increased the yields. The subsequent product reaction with some nucleophiles are discussed. The structures of products has been prooved by elemental analysis, IR - and ¹H NMR - spectra.
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Acknowledgments. The authors' thanks are due to Dr. K. Gáplovská for elemental analyses. Mgr. I. Prokes for measurement of proton NMR spectra and Dr. A. Perjéssy for IR spectra measurement, members of Faculty of Natural Sciences, Comenius University, Bratislava. Financial support for this research by the Slovak Grant Agency is gratefully acknowledged, Grant No. 1/5085/98.