Synthesis of tetra- and octahydroxanthene derivatives by the condensation of dimedone with aromatic aldehydes

The reaction of dimedone with salicyl and 2-hydroxy-1-naphthoyl aldehydes gave derivatives of tetrahydroxanthene and tetrahydrobenzo[a]xanthene and not aldimedone as occurs in condensations with other aldehydes. Derivatives of decahydroacridine were obtained by reaction of the tetrahydroxanthene derivatives with methyl-and ethylamine. Tetrahydro- and octahydroxanthene derivatives were obtained from the reaction of acetylsalicylaldehyde with dimedone in acetic anhydride. The structures of the ketoenol forms of the products containing a-ketoenol unit were determined by¹H and¹³C NMR spectroscopy, and the mechanism of their interconversion is discussed.Institute of Bioorganic Chemistry, Belarus Academy of Science, Minsk, 220141. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 742–753, June, 1996. Original article submitted February 22, 1996.     

以淀粉溶液为催化剂一锅三组分法合成四氢苯并[b]吡喃和3,4-二氢吡喃并[c]苯并吡喃衍生物(英文)

Tetrahydrobenzo[b]pyran and 3,4-dihydropyrano[c]chromene derivatives were synthesized via a one-pot three-component condensation of aromatic aldehydes with malononitrile and dimedone or 4-hydroxycoumarin in excellent yields in the presence of starch solution as a highly efficient homogenous catalyst.The use of a nontoxic and biodegradable catalyst,simple work-up procedure,and short reaction time are advantages of this method.     

Design and synthesis of novel α-substituted phosphonic acids catalyzed by nano zinc oxide

A series of α-substituted phosphonic acids were synthesized by a reaction between dimedone, aromatic aldehydes, and triethylphosphite in ethanolic solution under reflux conditions and using nano zinc oxide as a catalyst. Their structures were determined by Infrared, carbon, hydrogen, nitrogen, and sulfur analysis, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR.     

以淀粉溶液为催化剂锅三组分法合成四氢苯并[b]吡喃和3,4-二氢吡喃并[c]苯并吡喃衍生物简

Tetrahydrobenzo[b]pyran and 3,4-dihydropyrano[c]chromene derivatives were synthesized via a one-pot three-component condensation of aromatic aldehydes with malononitrile and dimedone or 4-hydroxycoumarin in excellent yields in the presence of starch solution as a highly efficient homogenous catalyst. The use of a nontoxic and biodegradable catalyst, simple work-up procedure, and short reaction time are advantages of this method.     

Determination of aldehydes in fish by high-performance liquid chromatography

A new analytical method to determine trace volatile aldehydes isolated from the headspace of fish meat at room temperature by high-performance liquid chromatography (HPLC) in the form of 2,4-dinitrophenylhydrazone (DNPHo) derivatives has been developed. Aliquots (50 g) of the fish purée were introduced into a 500-mL glass recipient and were purged with N2 for 40 min through two SEP-PAK C18 cartridges (connected in series) coated with an acid solution of 2,4-dinitrophenylhydrazine. The cartridges were then eluted with acetonitrile (2 mL) and the 2,4-DNPHo formed was quantitated by HPLC-UV analysis using a Zorbax C18 column. The isolated compounds from the dynamic headspace sampling of four kinds of fish species were saturated aldehydes, formaldehyde, acetaldehyde, propanal, butanal, pentanal, and hexanal. Under optimized conditions the detection limits of the HPLC method were in the range of 0.75 nmol/g (formaldehyde) to 2.19 nmol/g (hexanal). The calibration curves were linear in the concentration range from 1.3 nmol/mL to 12.5 nmol/mL. Propanal and acetaldehyde were the major carbonyl compounds identified (ranging from 3.9 nmol/g and 10 nmol/g). This study has revealed the widespread occurrence of formaldehyde, acetaldehyde, propanal, butanal, pentanal, and hexanal in fish meat.     

A facile electrochemical method for synthesis of new benzofuran derivatives

Electrooxidation of 3-substituted catechols has been studied in the presence of dimedone in aqueous solution, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols participate in Michael addition reactions with dimedone to form the corresponding benzofuran derivatives (6a-c). We propose a mechanism for the electrode process. The efficient electrochemical synthesis of 6a-c has been performed at carbon rod electrodes in an undivided cell using a constant current.     

Oxazolidinone/enamine ratios in the reactions of α-silyloxy and α-alkoxy aldehydes with proline

α-Silyloxy and α-alkoxy aldehydes (propanal derivatives 1–4), when treated with proline in DMSO-d₆, give oxazolidinones rather than enamines. In fact, the relative trend is much stronger than that of all other carbonyl compounds examined, including simple aldehydes, α-branched aldehydes, α-(alkylthio)aldehydes, and standard ketones. For 1–4, the high prevalence of oxazolidinones prevents or delays the partial racemization of the α-stereocenters.     

Synthesis and Anti‐influenza Virus Activity of Novel bis(4H‐chromene‐3‐carbonitrile) Derivatives

An efficient and convenient method for the synthesis of bis(4H‐chromene‐3‐carbonitrile) derivatives by one‐pot, multicomponent reaction of bis‐aldehydes, malononitrile, and dimedone in the presence of a catalytic amount of piperidine is reported. Bis(2‐benzylidene‐1H‐indene)‐1,3‐(2H )‐dione derivatives were obtained as the main products as a result of reaction of the bis(arylidenemalononitriles) with indandione. The anti‐influenza H5N1 virus activities of the newly prepared bis‐chromene derivatives are also investigated.     

Synthesis of Spiro Dihydrofurans and 1,8-Dioxo-xanthenes via DABCO Catalyzed Tandem Reaction of Aldehyde with Cyclohexane-1,3-dione and Dimedone

The 1,4-diazabicyclo[2.2.2]octane(DABCO) catalyzed reaction of cyclohexane-1,3-dione or dimedone with various aldehydes in acetonitrile resulted in the polysubstituted tetraketones, spiro dihydrofurans or 1,8-dioxo-xanthenes derivatives as main products respectively according to the structure of reactants and reaction conditions.     

Detection of low molecular weight aldehydes in aqueous solution by membrane introduction mass spectrometry

Membrane introduction mass spectrometry (MIMS) is used to detect low molecular weight aldehydes in aqueous solutions. The best sensitivity was obtained by aqueous phase derivatization of aldehydes with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBOA) and electron capture detection. This negative chemical ionization mass spectrometry procedure allowed the measurement of C(1)C(6) aldehydes at low concentrations in mixtures. The characteristic ion signals in the mass spectrum of the mixture were verified by examining the full mass spectra and product ion MS/MS spectra of the derivatives of individual aldehydes. A reaction scheme is proposed to explain the fragmentation pattern of the molecular anions (M(-.)) of the derivatives. The processes observed include loss of HF to form (MHF)(-.) ions which then competitively fragment by elimination of H(R)CN and NO(.) to produce ions of m/z 178 and (M-50)(-.), respectively. Multiple reaction monitoring was applied to establish the lower limits of detection. Formaldehyde could be detected without preconcentration at 1 ppb with S/N = 3/1. The detection limits of acetaldehyde, propanal and butanal were found to be 10 ppb and that of pentanal and hexanal were found to be 20 ppb. Response curves vs. concentration are linear in the ppb range. This method is not as readily applicable to the corresponding ketones.     

Synthesis of a novel tetracationic acidic organic salt based on DABCO and its applications as catalyst in the Knoevenagel condensation reactions in water

Synthesis of a novel tetracationic acidic organic salt based on DABCO containing two sulfonic acid groups in the skeleton and four hydrogensulfate groups as counterion is described. Its catalytic efficiency in the Knoevenagel condensation of aldehydes with active cyclic methylene compounds in water is investigated. While 2,2'-(phenylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) derivatives were obtained in 40–98% isolated yields in the reaction of aldehydes with dimedone, the corresponding Knoevenagel adducts were provided in 85–95% yields using 1,3-dimethylbarbituric acid. In addition, a DABCO-based polycationic organic salt polymer was prepared and characterized for the first time.     

Headspace single-drop microextraction with in-drop derivatization for aldehyde analysis

A new technique, headspace single-drop microextraction (HS-SDME) with in-drop derivatization, was developed. Its feasibility was demonstrated by analysis of the model compounds, aldehydes in water. A hanging microliter drop of solvent containing the derivatization agent of O-2,3,4,5,6-(pentaflurobenzyl)hydroxylamine hydrochloride (PFBHA) was shown to be an excellent extraction, concentration, and derivatization medium for headspace analysis of aldehydes by GC-MS. Using the microdrop solvent with PFBHA, acetaldehyde, propanal, butanal, hexanal, and heptanal in water were headspace extracted and simultaneously derivatized. The formed oximes in the microdrop were analyzed by GC-MS. HS-SDME and in-drop derivatization parameters (extraction solvent, extraction temperature, extraction time, stirring rate microdrop volume, and the headspace volume) and the method validations (linearity, precision, detection limit, and recovery) were studied. Compared to liquid-liquid extraction and solid-phase microextraction, HS-SDME with in-drop derivatization is a simple, rapid, convenient, and inexpensive sample technique.     

Enthalpies of formation, bond dissociation energies, and molecular structures of the n-aldehydes (acetaldehyde, propanal, butanal, pentanal, hexanal, and heptanal) and their radicals

Aldehydes are important intermediates and products in a variety of combustion and gas-phase oxidation processes, such as in low-temperature combustion, in the atmosphere, and in interstellar media. Despite their importance, the enthalpies of formation and bond dissociation energies (BDEs) for the aldehydes are not accurately known. We have determined enthalpies of formation for acetaldehyde, propanal, and butanal from thermodynamic cycles, using experimentally measured reaction and formation enthalpies. All enthalpy values used for reference molecules and reactions were first verified to be accurate to within around 1 kcal mol-1 using high-level ab initio calculations. Enthalpies of formation were found to be -39.72 +/- 0.16 kcal mol-1 for acetaldehyde, -45.18 +/- 1.1 kcal mol-1 for propanal, and -49.27 +/- 0.16 kcal mol-1 for butanal. Enthalpies of formation for these three aldehydes, as well as for pentanal, hexanal, and heptanal, were calculated using the G3, G3B3, and CBS-APNO theoretical methods, in conjunction with bond-isodesmic work reactions. On the basis of the results of our thermodynamic cycles, theoretical calculations using isodesmic work reactions, and existing experimental measurements, we suggest that the best available formation enthalpies for the aldehydes acetaldehyde, propanal, butanal, pentanal, hexanal, and heptanal are -39.72, -45.18, -50.0, -54.61, -59.37, and -64.2 kcal mol-1, respectively. Our calculations also identify that the literature enthalpy of formation of crotonaldehyde is in error by as much as 1 kcal mol-1, and we suggest a value of -25.1 kcal mol-1, which we calculate using isodesmic work reactions. Bond energies for each of the bonds in the aldehydes up to pentanal were calculated at the CBS-APNO level. Analysis of the BDEs reveals the R-CH(2)CH=O to be the weakest bond in all aldehydes larger than acetaldehyde, due to formation of the resonantly stabilized vinoxy radical (vinyloxy radical/formyl methyl radical). It is proposed that the vinoxy radical as well as the more commonly considered formyl and acetyl radicals are important products of aldehyde combustion and oxidation, and the reaction pathways of the vinoxy, formyl, and acetyl radicals are discussed. Group additivity values for the carbon-oxygen-hydrogen groups common to the aldehydes are also determined. Internal rotor profiles and electrostatic potential surfaces are used to study the dipole induced dipole-dipole interaction in the synperiplanar conformation of propanal. It is proposed that the loss of this dipole-dipole interaction in RC(.-)HCH(2)CH=O radicals causes a ca. 1-2 kcal mol-1 decrease in the aldehyde C-H and C-C bond energies corresponding to RC(.-)HCH(2)CH=O radical formation.     

A novel three-component method for the synthesis of triazolo[1,2-a]indazole-triones

An efficient synthesis of triazolo[1,2-a]indazole-1,3,8-trione derivatives based on the three-component condensation of urazole, dimedone and aromatic aldehydes under solvent-free conditions is described.     

Simple derivatization of aldehydes with D-cysteine and their determination in beverages by liquid chromatography-tandem mass spectrometry

We describe a simple derivatization method to determine aldehydes. This method is based on derivatization with D-cysteine and consecutive liquid chromatography-tandem mass spectrometry (LC-MS/MS). The optimum derivatization conditions of aldehydes with D-cysteine were 10 min at 50°C and pH 7.0. The formed alkyl thiazolidine-4-carboxylic acid derivatives were directly injected in LC-MS/MS. In the established condition, the method was used to detect eight aldehydes in beverages. The limit of detection (LOD) and limit of quantification (LOQ) of the aldehydes were 0.2-1.9 μg L(-1) and 0.7-6.0 μg L(-1) and the relative standard deviation was less than 2.0% at concentrations of 0.1 mg L(-1) and 1.0 mg L(-1) with the exception of octanal. All the beverage samples had detectable levels of methanal (0.033-0.145 mg L(-1)), ethanal (0.085-2.12 mg L(-1)), propanal (ND to 0.250 mg L(-1)), butanal (ND to 0.003 mg L(-1)), pentanal (ND to 0.471 mg L(-1)), hexanal (ND to 0.805 mg L(-1)), heptanal (0.019-3.91 mg L(-1)) and octanal (0.029-0.118 mg L(-1)).     

Bakers’ yeast catalyzed synthesis of polyhydroquinoline derivatives via an unsymmetrical Hantzsch reaction

Bakers’ yeast efficiently catalyzes the unsymmetrical Hantzsch reaction through a four-component coupling of aldehydes, β-ketoesters, dimedone and ammonium acetate to form polyhydroquinoline derivatives in good to excellent yields.     

Production of aliphatic aldehydes on peroxidation of various types of lipids.

IN vitro peroxidation by air, or xanthine-xanthine oxidase (xanthine-XOD) was performed to estimate the production of aliphatic aldehydes from free polyunsaturated fatty acids (PUFA), triglycerides, phospholipids and rat liver microsomes and mitochondria. The aldehyde contents in peroxidized lipids were determined by liquid chromatography and fluorescence detection. In both peroxidation, pentanal, (E)-4-hydroxy-2-nonenal (4-HN), and hexanal were produced from omega-6 PUFA rich lipids and propanal was markedly enhanced by increasing the degree of fatty acid unsaturation. The ratios of 4-HN to hexanal production in xanthine-XOD peroxidation of the omega-6 PUFA rich lipids, and rat liver microsomes and mitochondria were much higher than those in air peroxidation. The ratios (4-HN/hexanal) obtained in microsomes and mitochondria by xanthine-XOD were similar to those in rat liver observed in vitamin E deficient studies. The determination of these aldehydes may be useful to estimate the kinds of fatty acids peroxidized and investigate in vivo lipid peroxidation mechanism.     

One-pot, three-component route to 2H-indazolo[2,1-b]phthalazine-triones

2H-Indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives were synthesized in a simple and efficient method from the three-component condensation reaction of phthalhydrazide, dimedone, and aromatic aldehydes under solvent-free conditions in excellent yields and short reaction times.     

Design,synthesis, molecular docking,and spectral studies of new class of carbazolyl polyhydroquinoline derivatives as promising antibacterial agents with noncytotoxicity towards human mononuclear cells from peripheral blood

In the present study, we report the design and eco-benign synthesis of new class of carbazolyl-1,4-dihydropyridine (1,4-CDHP) and carbazolyl-1,8-dioxodecahydroacridine (CAD) derivatives via a three-component coupling reaction of substituted carbazole aldehydes, ethyl acetoacetate/dimedone, and ammonium acetate under solvent-free conditions at 112°C to 115°C. We also report an efficient one-pot synthesis of new class of carbazolyl polyhydroquinoline (CPQ) derivatives via a four-component coupling reaction of substituted ethyl acetoacetate, dimedone, ammonium acetate, and carbazole aldehydes in acetonitrile/water medium (3:1) at 73°C to 75°C in moderate yields. All the products were thoroughly characterized by ¹H NMR, ¹³C NMR, Fourier transform infrared (FTIR), mass spectral, and CHN analysis. The synthesized heterocyclic compounds were evaluated for their in vitro antibacterial activity against pathogenic strains of both Gram-negative and Gram-positive bacteria. Minimum inhibitory concentration (MIC) of the active compounds was evaluated by macrodilution method. The CPQ derivative ( 8a ) displayed superior antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi with the MIC values of 16.0 to 32.0 μg/mL in comparison with the reference drug. The mechanism of antibacterial action of the CPQ derivatives was investigated via scanning electron microscope (SEM) studies. The molecular docking studies indicate that the CPQ derivative ( 8a ) binds to the cell wall protein of E coli and P aeruginosa by formation of hydrogen bonds with amino acid residues (TYR328 and GLU249) of the bacterial cell wall protein. The 1,4-CDHP, CAD, and CPQ derivatives were either noncytotoxic or exhibited minimal cytotoxicity towards human mononuclear cells from peripheral blood. All the products were evaluated for Lipinski rule of five (RO5) and were found to have good oral bioavailability.     

Quantitative NMR spectroscopy of binary liquid mixtures (aldehyde + alcohol). Part III: (1-decanal or 3-phenylpropanal or 2-chlorobenzaldehyde) + (methanol or ethanol or 1-propanol)

The thermodynamic properties of binary liquid mixtures of (aldehyde + alcohol) are strongly influenced by chemical reactions in particular around and below ambient temperature. In two previous publications the chemical reaction equilibrium was investigated by ¹³C – Fourier transform NMR-spectroscopy at temperatures between 255 K and 295 K for a series of aldehydes (acetaldehyde, 1-propanal, 1-butanal, 1-heptanal) with three alcohols (methanol, ethanol, 1-propanol). Here these investigations are extended to three more aldehydes (1-decanal, 3-phenylpropanal and 2-chlorobenzaldehyde, respectively). The results for the binary systems with decanal or 3-phenylpropanal as the aldehyde in the binary mixture (aldehyde + alcohol) confirm the expectations from the first parts of this series, i.e., that the majority of the constituents of the mixture is present as hemiacetal and the first two poly(oxymethylene) – hemiacetals. The numerical results for the chemical reaction equilibrium constants from the previous investigations can be used to predict quantitatively the speciation in binary systems of ((either 1-decanal or 3-phenylpropanal) + (either methanol or ethanol or 1-propanol)). However the experimental results with 2-chlorobenzaldehyde reveal a different behaviour. In all investigated systems (2-chlorobenzaldehyde + alcohol) the most important reaction product was the corresponding acetal whereas the amounts of hemiacetal were very small. While the amounts of hemiacteal could still be quantified, it was not possible to quantify the amount of any poly(oxymethylene) – hemiacetal.