5,6,7,8-Tetrafluoro-4-hydroxycoumarin derivatives in reactions with o-phenylenediamine

The reactions of 5,6,7,8-tetrafluoro-4-hydroxycoumarin derivatives with o-phenylenediamine occur with pyrone heterocycle cleavage and formation of substituted benzodiazepin-2-ones. 5,6,7,8-Tetrafluoro-4-hydroxycoumarin affords 4-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-2-one, 3-acetimidoyl-5,6,7,8-tetrafluoro-4-hydroxycoumarin produces 3-(3,4,5,6-tetrafluoro-2-hydroxybenzoyl)-4-methyl-1,2-dihydro-1H-1,5-benzodiazepin-2-one, and 3-acetyl-5,6,7,8-tetrafluoro-4-hydroxycoumarin yields both these heterocycles.     

Reaction of 4-hydroxycoumarin with arylglyoxals and ureas

One-pot condensation of 4-hydroxycoumarin with arylglyoxals and ureas gave 4-aryl-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1H-imidazol-2(3H)-ones. The same compounds may be obtained from aroylbis(4-hydroxy-2-oxo-2H-chromen-3-yl)methanes and urea. The reaction of 4-bromobenzaldehyde with 4-hydroxycoumarin in the presence of urea led to the formation of the corresponding Michael adduct without participation of urea.     

Synthesis of Functionalized Dihydrofurocoumarin Derivatives from 3-Aminoalkyl-4-hydroxycoumarin

Some dihydrofuro-fused coumarin derivatives were synthesized from 3-aminoalkyl-4-hydroxycoumarin via in situ generation of N-ylide. The 3-aminoalkylated 4-hydroxycoumarin derivatives were synthesized from one-pot, three-component reaction of 4-hydroxycoumarin, aryl aldehydes, and secondary amines in ethanol at room temperature. Again, when salicylaldehyde was employed instead of benzaldehyde, interestingly pyranocoumarins were obtained. The reaction protocol can be further explored toward the synthesis of many other heterocyclic fused dihydrofurans.     

4-Hydroxycoumarin/2-hydroxychromone tautomerism: Infrared spectra of 2-13c and 3-D labeled 4-hydroxycoumarin and its anion

Bands with primarily v (C=O) and v (C=O) character in the spectra of 4-hydroxycoumarin and its anion were identified by isotopic substitution with either ¹³C or deuterium. Two bands of each type were found for spectra of 4-hydroxycoumarin in solution in chloroform, dioxane, or dimethylsulfoxide, with v (C=O) at 1704–1733 cm^?1 and ～ 1567 cm^?1. Two bands, at 1618 and 1559 cm^?1, are associated with v (C=C) in the spectrum of crystalline 4-hydroxycoumarin monohydrate, but only a single v (C=O) band at ～ 1655 cm^?1 was observed. Anhydrous 4-hydroxycoumarin has v (C=O) bands at ～ 1700 cm^?1 and a shoulder at ～ 1670 cm^?1. The strong band at 1660 cm^?1 in the spectrum of 4-hydroxycommarin anion in dimethylsulfoxide solution is due to a delocalized v (O = C = O) vibration, whereas the band at 1555 cm^?1 has partial v (C=C) character and involves C(3) but not C(2), supporting a fully delocalized char structure for the anion. No evidence for the existence of the 2-hydroxychromone tautomer was found, except in the case of anhydrous 4-hydroxycoumarin in the solid state.     

Synthesis of 4-aminopolymethoxycoumarins from 4-hydroxycoumarin triflates

4-Aminocoumarins were synthesized in high yields by the reaction of 4-hydroxycoumarin trifluoromethanesulfonates with amines. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1583–1588, September, 2006.     

Reaction of 4-hydroxycoumarin with 2-acetyloxiranes

The reaction of 4-hydroxycoumarin with 2-acetyloxiranes in dimethylformamide in the presence of triethylamine gave 2,3-dihydro-4H-furo[3,2-c]chromen-4-ones which were converted into 4H-furo[3,2-c]-chromen-4-one derivatives as a result of dehydration or fragmentation.     

Synthesis of zwitterionic 4-hydroxycoumarin derivatives through a unique reaction of 4-hydroxycoumarins with p- benzoquinone and pyridine

[reaction: see text] A unique reaction of 4-hydroxycoumarins with p-benzoquinone and pyridine was found, and through the reaction, six zwitterionic 4-hydroxycoumarin derivatives were synthesized. The structures of these compounds were determined by IR, MS(ESI), 1H NMR, 13C NMR, and single-crystal X-ray diffraction studies.     

A convergent paired electrochemical synthesis of new heterocyclic compounds. Reaction of benzoquinones with 3-Amino-4-hydroxycoumarin

Electrochemical oxidation of catechols (1) has been studied in the presence of cathodically generated 3-amino-4-hydroxycoumarin (3a) as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-benzoquinones derived from catechols (1) participate in Michael addition reaction with 3-amino-4-hydroxycoumarin (3a) to form the corresponding new heterocyclic compounds (7) (oxidized form of coumestan derivatives). The electrochemical process consists of a multi-step including (a) cathodic reduction of 4-hydroxy-3-nitrocoumarin (3) to 3-amino-4-hydroxycoumarin (3a), (b) anodic oxidation of catechols (1) to related o-benzoquinone (2), (c) the Michael addition reaction of 3-amino-4-hydroxycoumarin (3a) to o-benzoquinone (2), and (d) anodic oxidation of formed adduct. The paired electrochemical synthesis of compounds 7a and 7b has been successfully performed in a one-pot process at carbon rods as working and counter electrodes in an undivided cell.     

New method of synthesis of 1,5-benzodiazepin-2-ones from 4-hydroxycoumarin

A new method of synthesis of 1,5-benzodiazepine-2-ones, from 4-hydroxycoumarin and substituted 1,2-phenylenediamines by heating in xylene or acetic acid-ethanol, is reported.     

Synthesis of N-substituted α-aminoacids from 4-hydroxycoumarin

A new series, the N-(methylene-4-oxocoumarinyl)aminoacids were synthesized by condensation of 4-hydroxycoumarin with α-aminoacids in the presence of excess ethyl orthoformate.     

Synthesis and certain conversions of 3-(3,3-dichloroallyl)-4-hydroxycoumarin

A method has been developed for the synthesis of 3-(3,3-dichloroallyl)-4-hydroxycoumarin and 2-thioxo-3-(3,3-dichloroallyl)-4-hydroxy-2H-chromene, and certain conversions of these compounds have been studied. They undergo acid hydrolysis readily, forming (respectively) 3-(4-hydroxy-3-coumarin)- and 3-(2-thioxo-4-hydroxy-2H-chromene-3)propionic acids; these compounds are converted to the corresponding lactones by the action of acetic anhydride.Erevan State University, Erevan 375049. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 48–51, January, 1997.     

Phosphorimetric determination of some 4-methyl-7-hydroxycoumarin derivatives of thin-layer surfaces

Derivatives of 4-methylumbelliferone (4-methyl-7-hydroxycoumarin) are important fluorogenic substrates for the assay of group-specific hydrolases and in enzyme-linked immunoassays. The development of techniques suitable for the low-temperature phosphorimetric detection and determination of such derivatives on thin-layer chromatograms is described.     

The Chemistry of Coumarin Derivatives. Part 5. Unusual course of the reaction of 4-hydroxycoumarin and aliphatic aldehydes

The reaction of 4-hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X-ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3-alkyl-4-hydroxycoumarins.     

Water mediated efficient one-pot synthesis of bis-(4-hydroxycoumarin)methanes

Abstract

Manganous chloride (MnCl₂·4H₂O) has been used as an efficient catalyst for an improved and rapid one-pot synthesis of bis-(4-hydroxycoumarin)methanes in excellent yields using water as a reaction medium. This aqueous mediated reaction of various aromatic and heteroaromatic aldehydes with 4-hydroxycoumarin using catalytic amounts of manganous chloride avoids the use of expensive, corrosive reagents, toxic solvents, and provides operational simplicity.     

Synthesis of 3-(α-naphthylmethyl)-4-hydroxycoumarin and its derivatives

3-(α-Naphthylmethyl)-4-hydroxycoumarin and a series of derivatives are prepared by condensing phenols with diethyl α -naphthylmethylmalonate under the influence of heat.     

Analogs of 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin (warfarin) prepared from substituted salicylic acids

Some derivatives of salicylic acid containing substituents meta to the carboxyl group were used to prepare analogs of the anticoagulant drug warfarin, 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin, containing substituents in either the 6-or 8-position of the courmarin ring. When the substituent was the hydroxyl group, the resulting products are previously identified metabolites of warfarin. The substituted salicylic acid is first acetylated with acetic anhydride, then either converted to the acid chloride and condensed with diethyl malonate in the presence of sodium hydroxide or converted to the mixed anhydride with formic acid and condensed with ethoxymagnesium diethyl malonate to yield, in either case, the corresponding 3-carbethoxy-4-hydroxycoumarin substituted in the 6- or 8-position of the coumarin ring. These compounds readily condense with benzalacetone to form the corresponding substituted warfarin in the presence of 5 mole % tertiary amine catalyst. This method offers an improved route for the synthesis of 8-hydroxywarfarin.     

Reaction of 1,2-diamines with 4-hydroxycoumarin. Synthesis of 1,4-diazepin-5-ones

1,4-diazepin-5-ones were obtained from 4-hydroxycoumarin and substituted 1,2-diamines by heating in 2-methyl-1-propanol.     

Hydrazones derived from thiooxamohydrazides and 3-formyl-4-hydroxycoumarin: synthesis, structures, and fragmentation

Novel hydrazones were obtained from thiooxamohydrazides and 3-3-formyl-4-hydroxycoumarin. According to data from NMR spectroscopy and X-ray diffraction, the coumarin fragment in the compounds obtained exists as 4-hydroxycoumarin or chromane-2,4-dione. When dissolved in dimethyl sulfoxide, these hydrazones undergo fragmentation into derivatives of 1,3,4-thiadiazole and 4-hydroxycoumarin.     

Comparison of a novel thin-layer chromatographic-fluorescence detection method with a spectrofluorometric method for the determination of 7-hydroxycoumarin in human urine.

A novel method for the determination of 7-hydroxycoumarin in human urine which combines thin-layer chromatography (TLC) with fluorescence detection (FD) has been devised. The limit of detection (1 ng/ml) enables determination of 7-hydroxycoumarin after both administration of coumarin and environmental exposure to this fragrance material. When compared to a spectrofluorometric method of analysis, the TLC-FD method proved to be more selective for the analysis of 7-hydroxycoumarin in human urine.     

Synthesis of 4-trifluoromethyl-7-hydroxycoumarin derivatives. Structure of 3-cyano-4-trifluoromethyl-7-acetoxycoumarin

A method was developed for the production of derivatives of 4-trifluoromethyl-7-hydroxycoumarin with electron-withdrawing groups (CN, CF₃CO) at position 3. The structure of 3-cyano-4-trifluoromethyl-7-acetoxycoumarin was proved by x-ray crystallographic investigation. The effect of the substituents on the geometry of the molecule is discussed.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Institute of Biochemistry, Academy of Sciences of Armenia, 375044 Erevan. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 6, pp. 1371–1375, June, 1992.