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2,4,6-trihydroxytoluene (methylphloroglucinol) is a promising reagent in organic synthesis, after development out getting it from 2,4,6-trinitrotoluene. We previously synthesized of derivatives of 5,7-dihydroxy-2H-1-benzopyran-2-ones by the interaction of 2,4,6-trihydroxytoluene and 2,4,6 -trihydroxy-3-methylbenzoic acid with polyfunctional carbonyl compounds. The first time, a detailed analysis of the electronic absorption and fluorescence spectra of derivatives of 5,7-dihydroxy-2H-1-benzopyran-2-ones is carried out. In the electronic absorption spectra of the studied compounds, the absorption in the long-wavelength region of the spectrum is determined by electronic transitions with intramolecular charge carry. The possibility of controlling the bathochromic or hypsochromic shift of the long-wavelength absorption band by introducing substituents of various electronic nature into the molecule has been revealed. It was shown that some of the studied compounds have pronounced luminescence in the blue-green region of the spectrum (390–508 nm) with a quantum yield of 9–40%. The highest quantum yield (38%) was achieved when the 5,7-dihydroxy-2H-1-benzopyran-2-one carboxyl group was introduced into position 6. The bromination of this compound leads to a decrease in the quantum yield to 9.5 % The introduction into the 3 position of 5,7-dihydroxy-4,8-dimethylchromen-2-one phenyl substituted fragment along with O-acylation leads to a sharp decrease in the quantum yield. It is concluded that the studied objects are promising as basic structures for the search for new biosensors.

In present study, a novel class of 3,7-disubstituted 2H-1-benzopyran-2-one derivatives (3xa-3zc) bearing a basic ether side chain at C-7 and a substituted phenyl ring at C-3 of the coumarin ring is synthesized. These compounds have been evaluated for antimicrobial (antibacterial/antifungal) activities. Some of the compounds viz. 3xc, 3xe, 3xf, 3yb, 3yc and 3yf have shown significant antifungal activities against selective strains. Compounds 3xe, 3yb and 3yc with the MIC values of 1.56 μg/mL displayed better antifungal activity than fluconazole against Trichophyton mentagrophytes

Tricyclic benzopyrans are medicinally important biologically active compounds. Synthesis of a series of tricyclic benzopyrans derivatives via N-Heterocyclic carbene (NHC) catalyzed annulation of enals to α-methylidenetetralones/chromanones is described. This reaction afforded the benzopyrans in high yield with aromatic as well as aliphatic enals.

Proceeding from 2,4,6-trihydroxytoluene (methylphloroglucinol) dihydroxy-2H-1-benzopyran-2-ones were prepared, and also their bromo and acyl derivatives. The structure of compounds synthesized was established, and their potential pharmacokinetic properties were estimated by means of computer simulation.

The reactivity of 4-(1-butoxyvinyl)-2H-chromen-2-one (1) and (E)-4-(2-butoxyvinyl)-2H-chromen-2-one (2) as diene in thermal Diels–Alder cycloaddition reactions with several electron-poor dienophiles is reported. Among several dienophiles used in this study 1,4-benzoquinone afforded cycloadducts 11-butoxy-1H-naphtho[1,2-c]chromene-1,4,5-trione (3e) and 1H-naphtho[1,2-c]chromene-1,4,5-trione (4g) that showed Cdc25 phosphatase-inhibition activity at low micromolar values, with both compounds more effective against Cdc25 A and Cdc25 C isoforms.

An efficient one-pot synthesis of 3-[(4,5-dihydro-1H-pyrrol-3-yl)carbonyl]-2H-chromen-2-one (=3-[(4,5-dihydro-1H-pyrrol-3yl)carbonyl]-2H-1-benzopyran-2-one) derivatives 4 by a four-component reaction of a salicylaldehyde 1, 4-hydroxy-6-methyl-2H-pyran-2-one, a benzylamine 2, and a diaroylacetylene (=1,4-diarylbut-2-yne-1,4-dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H-1-benzopyran-2-one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, 1H- and 13C-NMR, and EI-MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).

6-Alkenyl, alkynyl, and aryl-3,4-dihydrocoumarins have been prepared from 6-bromo-3,4-dihydrocoumarin via palladium catalysed coupling reactions. 6-Carboalkoxy- and 6-keto-3,4-dihydrocoumarins have been obtained via palladium-catalysed carbonylations of 6-bromo- and 6-iodo-3,4-dihydrocoumarins respectively.

A novel straightforward synthesis of 3-(1H-tetrazol-5-yl)coumarins (=3-(1H-tetrazol-5-yl)-2H-1-benzopyran-2-ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3-dipolar cycloaddition of substituted salicylaldehydes (=2-hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H2O is reported (Scheme 1 and Table 2). This general protocol provides a wide variety of 3-(1H-tetrazol-5-yl)coumarins in good yields under mild reaction conditions.

Thermal Claisen rearrangement of 4-allyloxy[1]benzopyran-2-ones in refluxing chlorobenzene gave 3-allyl-4-hydroxy[1]benzopyran-2-ones in 82–90% yield. A number of 3-iodopyrano[3,2-c][1]benzopyran-5(2H)-ones were synthesized in 80–92% yield by the regioselective heterocyclization of 3-allyl-4-hydroxy[1]benzopyran-2-ones with N-iodosuccinimide in acetonitrile at 0–5°C.

Halogen acid-catalysed deprotection and cyclisation of Baylis-Hillman products obtained using O-benzylated salicylaldehyde precursors has been shown to afford 3-(halomethyl)coumarins (3-halomethyl-2H-1-benzopyran-2-ones) chemoselectively and in good yield.

The synthesis of 2H-1-benzopyran-2-ones (coumarins) unsubstituted on the pyranic nucleus was realized by condensation of malic acid and phenols under mild conditions. A short reaction time, improved yields, good purity of the products, and an easy clean experimental protocol are the advantages of this procedure.

7a-Methyl-13,13a-dihydro-7aH-furo[3,2-c: 5,4-f]bis-[1]benzopyran-3-ones (4a-d) are regioselectively synthesised in 65–75% yields by the sequential rearrangements of 6-(4-aryloxybut-2-yn-1-yloxy)[1]benzopyran-2-ones (3a-d) in refluxing N, N-diethylaniline (15 h). However, addition of toluene-4-sulphonic acid in the reaction mixture improved the yield (80–85%) and reduced the reaction time (10 h).

A simple, highly selective transformation of 5,6,7,8-tetrahydro-2H-1-benzopyran-2,5-diones 1–3 and 14 with some phenylhydrazines and heterocyclic hydrazines to 5-hydrazono-2H-1-benzopyran-2-ones 4–12 and 15–16 is described. Under more severe conditions the hydrazonoquinoline derivative 17 was obtained from the benzopyran derivative 3 and Phenylhydrazine.

Substituted 2H-1-benzopyran-2-ones are useful synthons and have potential as biologically active compounds. In order to characterize the transformation of benzopyran-2,5 diones with a heterocyclic hydrazine to 2H-1-quinoline-2,5-diones and 5-hydrazono-2H-1-benzopyran-2-ones we have studied structural parameters of the products using 2D NMR techniques in solution combined with computational tools. Molecular modeling based on experimentally determined NOE distance restraints enabled determination of solution structures of two compounds: N-[1,2,5,6,7,8-hexahydro-1-[(imidazo[1,2-b]pyridazin-6-yl)amino]-7-methyl-2,5-dioxo-3-quinolinyl]benzamide and N-[5,6,7,8-tetrahydro-5-[(imidazo[1,2-b]pyridazin-6-yl)hydrazono]-7-methyl-2-oxo-2H-1-benzopyran-3-yl]benzamide.

An efficient one-pot synthesis of the title benzopyran-2-one derivatives (V) by a four-component reaction is reported.

Reaction of 7,8-dihydroxy-2H-1-benzopyran-2-one, and its 4-methyl derivative, with α-haloketones affords α-pyrano-1,5-benzodioxapines, while 3-chloro-4-methyl-7,8-dihydroxy-2H-1-benzopyran-2-one gives α-pyrano-1,4-benzodioxane. The structures of the compounds were deduced using a combination of 1H nmr, 13C nmr (BB, DEPT), HETCOR, NOESY, and selective INEPT techniques and molecular modeling.

7-Methoxyimino-4-methylchromene-2,8-dione 2 reacts with triarylphosphines 1(a-d) to give the unexpected 7-arylamino-8-hydroxy-4-methyl-2H-[1]-benzopyran-2-ones 7(a-d) and methyl diarylphosphinates 8(a-d) in high yields. The reaction of 2 with trialkylphosphines 1(e,f) as well as with diphenylphosphine 15 leads to the formation of the N-dialkylphosphinoyl derivatives 11, 12, 14 and the N-diphenylphosphinoyl derivative 19, along with compounds 7(e,f). The methylation of compounds 7a, 7f, 11 and 19 is also studied and reaction mechanisms to explain the formation of the products obtained are suggested.

A novel straightforward synthesis of 3-(1H-tetrazol-5-yl)coumarins (=3-(1H-tetrazol-5-yl)-2H-1-benzopyran-2-ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3-dipolar cycloaddition of substituted salicylaldehydes (=2-hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H2O is reported (Scheme 1 and Table 2). This general protocol provides a wide variety of 3-(1H-tetrazol-5-yl)coumarins in good yields under mild reaction conditions.

The toxicity of various hydroxy substituted 2H-1-benzopyran-2-ones (la-c, 2 and 3), ester (la-c, 5 and 6) and hydrazide (7a-c, 8 and 9) derivatives of 2H-l-benzopyranyloxyacetic acids and 2H-l-benzopyranyloxyacetylpiperidines (10a-c, 11 and 12) and corresponding morpholines (13a-c, 14 and 15) was determined against second stage juveniles of root-knot nematode (Meloidogyne javanica) and seed-gall nematode (Anguina tritici). Several of the compounds showed appreciable toxicity against both the tested nematodes. The activity results are discussed in relation to structure of the compounds. In general, the free phenolic compound and derived esters exhibited better toxicity.

Hitherto unreported 2 H -thiopyrano[3,2- c ][1]benzopyran-5-ones 6a – f are synthesized regioselectively in 79–85% yields by the thio-Claisen rearrangement of 4-propargylthio[1]benzopyran-2-ones 5a – f . The substrates 5a – f are synthesized by alkylation of hitherto unreported 4-mercaptocoumarins.

The 15th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural Products Neurodegenerative diseases are becoming prevalent pathologies in developed societies due to increasing average of life expectancy of the population. This fact has encouraged an active research in the development of new drugs, since they may represent an important advance in the treatment of complex diseases such as Alzheimer and Parkinson\'s diseases. Coumarins are a large family of compounds, of both natural and synthetic origin, important because of the pharmacological activities that this compounds display. Therefore, they occupy an important place in the organic and medicinal chemistry realm. In recent years, coumarins have been attracting interest because of their ability of inhibiting some enzymes. The versatility of the Perkin and Knoevenagel reactions has led to a large family of differently substituted compounds. In order to find the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins versus 3-benzoylcoumarins. A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds at different positions of the coumarin moiety. The synthesized compounds were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC50 = 1.35 nM) showed higher inhibitory activity than the R-(-)-deprenyl (IC50 = 19.60 nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study has provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of this coumarin scaffolds Thanks to the Ministerio Español se Sanidad Y Consumo (PS09/00501) and to Xunta de Galicia (PGIDIT09CSA030203PR and 10PXIB203303PR). S.V.R. thanks to Ministerio de Educación y Ciencia for a PhD grant (AP2008-04263). M.J.M. thanks Fundação para a Ciência e Tecnologia for a PhD grant (SFRH/BD/61262/2009).

Acylation of 4-alkoxycarbonyl-3-amino-6-hydroxy-2H-1-benzopyran-2-one derivatives (I) gave under mild conditions the O-substituted derivatives , N,O-disubstituted derivative and N,N-disubstituted derivative . The compound I was transformed with benzoyl chloride under more drastic conditions into a derivative of a new heterocyclic system 2-benzopyrano[3,4-d][1,3]oxazin. The derivatives of 1-benzopyrano[3,4-d]pyrimidine were prepared from I through the corresponding N-heteroarylformamidines and N-heteroarylformamide oximes or by cyclization of thiourea derivative .

Aryllead triacetates are chemoselective and regioseiective reagents for the preparation of 3-aryl-4-hydroxy-1-benzopyran-2-ones in good to excellent yields by C-3 arylation of the preformed 4-hydroxy-1-benzopyran-2-one ring. This approach was applied to the high-yielding synthesis of naturally occurring examples. A radical mechanism was discounted and the mechanism proposed involves the ligand coupling of an intermediate possessing an enolate-to-lead bond to afford arylated products.

The reaction of 3-(1-propanoyloxybenzyl)-2H-1-benzopyran-2-one (2) with the nitriles of 4-dimethylaminobenzoic, 4-diethylaminobenzoic, nicotinic, isonicotinic, and 3-dimethylaminopropionic acid in conc. H2SO4 yields the amides 3a-e. 3a-d were converted into hydrochlorides. Synthese einiger basischer 3-(1-Acylaminobenzyl)-2H-1-benzopyran-2-one Die Umsetzung von 3-(1-Propanoyloxybenzyl)-2H-1-benzopyran-2-on (2) mit Nitrilen der 4-Dimethylaminobenzoe-, 4-Diethylaminobenzoe-, Nicotin-, Isonicotin- und 3-Dimethylaminopropionsaure in konz. H2SO4 lieferte die Amide 3a-e. 3a-d wurden in die Hydrochloride umgewandelt.

7-Methoxyimino-4-methylchromene-2,8-dione 2 reacts with triarylphosphines 1(a-d) to give the unexpected 7-arylamino-8-hydroxy-4-methyl-2H-[1]-benzopyran-2-ones 7(a-d) and methyl diarylphosphinates 8(a-d) in high yields. The reaction of 2 with trialkylphosphines 1(e,f) as well as with diphenylphosphine 15 leads to the formation of the N-dialkylphosphinoyl derivatives 11, 12, 14 and the N-diphenylphosphinoyl derivative 19, along with compounds 7(e,f). The methylation of compounds 7a, 7f, 11 and 19 is also studied and reaction mechanisms to explain the formation of the products obtained are suggested.