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The synthesis of phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2- c ]chromenes 4 is accomplished via cyclocondensation of 4-oxo-4 H -chromen-3-carbaldehydes 1 with appropriately substituted acetic acids 2 under mild conditions. Further treatment of 4 with alcohol or water led to 5-alkoxy- and 5-hydroxy-2 H ,5 H -pyrano[3,2- c ]chromen-2-ones 5 and 6 , respectively. Acid and thermal catalysed rearrangement of 4 – 6 gave 5-hydroxypyrano[2,3- b ]chromen-2(10a H )-ones 7 and their subsequent substitution led to 5-alkoxyderivatives 8 . Reaction of 4 with amides led to 5-acylamino or 5-phenylsulfonamino substituted 2 H ,5 H -pyrano[3,2- c ]chromen-2-ones 9 . Reactions were performed under heating or microwave irradiation.

The reaction of 4-oxo-4H-chromen-3-carbaldehydes with coumarin-4-acetic acids under the Perkin conditions follows an interesting pathway that involves aldol reaction and subsequent intramolecular lactonization to afford 2-oxo-2H,5H-pyrano[3,2-c]chromene skeleton. In contrast to chromone-3-carbaldehydes, the same reaction with chromone-2-carbaldehydes yielded only the aldol condensation product. The reaction was performed under thermal and microwave conditions. The reactivity of 2-oxo-2H,5H-pyrano[3,2-c]chromenes in water, alcohol and acetic acid was described.

One-pot and facile preparations of 6-(2-hydroxy-5-R-benzoyl)-4-methyl-2-R1- pyrazolo[3,4-b]pyridines 4a-o are described, using the reaction of 3-formyl chromones 1 with 5-amino-1-R1-pyrazoles 2. An enamine-intermediate 2-ethyloxy-6-R-3-(3-methyl-1- phenylpyrazol-5-ylaminomethylene)chroman-4-one 3 was isolated at lower temperatures. Acyloxy-derivatives 5 of compounds 4 were obtained by acylation with acid chlorides or acid anhydrides. Coumarins 6 substituted at the 3- and 4-positions were prepared from the pyrazolo[3,4-b]pyridines 4 by condensation reactions and hydrazones 7 were formed from their reaction with 2,4-dinitrophenyl hydrazine. Reactions under microwave irradiation proceeded significantly faster and with high yields.

This review presents a survey of the condensations of 3-formylchromone with various active methylene and methyl compounds, e.g. malonic or barbituric acid derivatives, five-membered heterocycles, etc. The utilisation of the condensation products for the synthesis of different heterocyclic systems, which is based on the ability of the gamma-pyrone ring to be opened by the nucleophilic attack is also reviewed. Finally, the applications of microwave irradiation as an unconventional method of reaction activation in the synthesis of condensation products is described and the biological activity of some chromone derivatives is noted.

2-Alkoxy-3-(arylaminomethylene)chroman-4-ones and 3-(aryliminomethyl)chromones were prepared by acid catalyzed reaction of 3-formylchromones with aromatic amino carboxylic acids in alcoholic reaction media. The results of the kinetic study have confirmed that 3-(aryliminomethyl)chromones are formed from 2-alkoxy-3-(arylaminomethylene)chroman-4-ones. The dependence of the reaction rate on reactant structure, the reaction media and the concentration of catalyst has been studied. In contrast to the alcoholic media reaction, the same reaction in dry aprotic reaction media yielded only 2-hydroxy-3-(arylaminomethylene)chroman-4-ones. No 3-(aryliminomethyl)chromones were isolated in that case.

The hereditary bleaching test on Euglena gracilis was used for detecting extranuclear mutations. The highest bleaching activity (induction of the chloroplast-free mutants) was shown by the 6- R -3-formylchromones. On the other hand, bleaching-inactive 6- R -3-formylchromone acylhydrazones (derived from gallic and salicylic acids), added at sufficient concentrations in the case of chloroplast mutagenesis in E. gracilis , act as a potent antimutagen. This effect appeared to be a unique feature of chromone derivatives, but was dependent on the type of mutagen. These substances were very effective against the bleaching activity of acridine orange, and were less effective against N -methyl- N ′-nitro- N -nitrosoguanidine. The genotoxic effects of these mutagens was reduced, especially during the first stages of induction of this specific cytoplasmic mutation. The experimental study of mutagenicity and antimutagenicty of 3-formylchromone hydrazones was reinforced by data obtained by the semi-empirical AM1 method and lipophilicity values.

The synthesis of eight hydroxy- and 2-oxopyranochromone-3-carboxaldehydes 3, 5 and their reactions with 2-hydroxyaniline, 2,4-dinitrophenylhydrazine and 2-benzothiazolylhydrazine were investigated. Products were confirmed by IR, NMR spectral and elemental analysis data. The semi-empirical AM1 quantum-chemical method has been used to study optimal geometries and heats of formation of synthesized 3-formylchromones.

The synthesis of the biologically active novel systems derived from reaction of 3-formylchromones with three types of amino derivatives, 6-R2-2-aminobenzothiazoles, 6-amino-2-R3-thiobenzothiazoles and hydrazide derivatives (derived from cyanoacetic, isonicotine, salicylic and gallic acids) was carried out. The structures of the prepared compounds have been proved by elemental analysis, 1H NMR and IR spectra. Antimicrobial activity was studied against the following microorganisms — bacteria G+ (Staphylococcus aureus 29 58 , Bacillus subtilis 18 66 ), G− (Escherichia coli 326 71 , Pseudomonas aeruginosa); yeasts; Candida albicans, Saccharomyces cerevisiae; moulds; Microsporum gypseum, Aspergillus niger, Scopulariopsis brevicaulis; and against typical and atypical mycobacteria: Mycobacterium tuberculosis (H37Rv), Mycobacterium kansasii (PFG 8), Mycobacterium avium (My 80 72 ), Mycobacterium fortuitum (1021). The hereditary bleaching effect on the plastid system of Euglena gracilis, a unique phenomenon of the biological activity of chromone derivatives, is reported. The bleaching test on E. gracilis is used for detecting extranuclear mutations.

The semiempirical PM3 method has been used to study possible reaction paths of the condensation of 3-formylchromones with amides and triazoles. Optimal geometries of intermediates 7, products 8 and all other putative reaction intermediates were obtained. Pertinent transition states, TS I for the dehydratation to carbocation 13, and TS II for amidoalkylation, were located. The semiempirical PM3 method was also used for the calculation of the heats of formation and optimal structures of 4-chromanones 10 and 4-chromones 11. Several compounds of these types have been prepared. Their structures were proved by elemental analysis and 1H-NMR spectra.

Cesium acetate was found to be the best catalyst for the synthesis of 3-benzylidenephthalide from phthalic anhydride and phenylacetic acid. Reasonable to good yields of different 3-arylmethylenephthalides were isolated from the microwave Gabriel synthesis, even when phenylthio- and 2-(3-)thienyl- acetic acids were used as the starting material.