One-Pot Synthesis of 2,5-Furandicarboxylic Acid from 2-Furoic Acid by a Pd-catalyzed Bromination–Hydroxycarbonylation Tandem Reaction in Acetate Buffer

The one-pot synthesis of 2,5-furandicarboxylic acid from 2-furoic acid with a yield of 57 % was achieved for the first time using a Pd-catalyzed bromination-hydroxycarbonylation tandem reaction in HOAc-NaOAc buffer. This synthetic protocol shows major improvements compared to previously reported methods, such as using biomass-based 2-furoic acid as low-cost raw material, one-pot synthesis without isolation of intermediate products, and no need for an acidification procedure. Experiments indicate that the involved Xantphos-modified Pd-catalyst and the buffer solution play significant promoting roles for each individual reaction whereas Br₂ (as the brominating reagent) had a negative effect on the second hydroxycarbonylation step, while CO was deleterious for the first bromination step. Hence, in this practical one-pot synthesis, Br₂ should be consumed in the first bromination step as fully as possible, and CO is introduced after the first bromination step has been completed.     

扭辫法对糠酸聚合反应机理的研究

应用扭辫分析法(TBA)及IR谱的解析,研究了糠酸在浓硫酸催化下的开环聚合反应机理,探讨了催化剂用量及温度等对聚合反应的影响。结果表明,在浓硫酸存在下,随着温度的升高,糠酸的聚合反应历程为分段的逐步聚合过程;糠酸在210℃以后方可聚合完全;糠酸树脂在350℃以下耐热性良好。     

Lactams—I The synthesis and acid hydrolysis of 4- and 5-substituted 1-benzyl-2-piperidone derivatives

In order to explain the difficulty in hydrolysing the lactam linkage of 1-benzyl-2-oxo-5-ethyl-4-piperidineacetic acid (XIV) under acid conditions, several model compounds such as 1-benzyl-2-piperidone (X), 1-benzyl-5-ethyl-2-piperidone (XI), 1-benzyl-4-ethyl-2-piperidone (XII) and 1-benzyl-2-oxo-4-piperidineacetic add (XIII) were prepared and their hydrolysis in boiling 6N HCl was studied. For each of the lactams, the hydrolysis was found to proceed to an equilibrium as shown in Table 1. Substituents at the 4- and 5-positions of the piperidone ring seemed to favour the ring form in the equilibrium between piperidones (X-XIV) and ω-amino acid hydrochlorides (type XV).     

2-O-Benzylation in D-Gluconamide Derivative Under Basic Conditions with Complete Retention of Stereo-Integrity: Convenient Access to 2-O-benzyl-3,4:5,6- di-O-isopropylidene-D-glucitol and other Differently Protected D-glucitol Derivatives

A new and convenient synthesis of 2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol has been accomplished and has been generalized with the syntheses of differently protected D-glucitols at C-2 position. In the course of our new route to the differently protected D-glucitols at C-2 position, a new D-gluco configured building block, 1-morpholino-(3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide has been achieved.     

Synthesis and physicochemical properties of fac-[Re(CO)3(κ2-N,N-dpkfah)Cl], dpkfah=di-2-pyridyl ketone 2-furoic acid hydrazone: the molecular structure of fac-[Re(CO)3(κ2-N,N-dpkfah)Cl] · acetone

Reaction between [Re(CO)₅Cl] and di-2-pyridyl ketone 2-furoic acid hydrazone (dpkfah) (1) in refluxing toluene gave fac-[Re(CO)₃(κ²-N,N-dpkfah)Cl] (2). Spectroscopic and electrochemical measurements disclosed sensitivity of 2 to its surroundings. ¹H-NMR measurements showed that the amide proton exchanged with solvent protons, and its chemical shift is solvent and temperature dependent, while the chemical shifts of aromatic protons are solvent and temperature independent. Electronic absorption spectra of 2 divulged two intra-ligand charge transfer transitions (ILCT) in protophilic solvents and a single ILCT transition in non-protophilic solvents. Optical measurements on protophilic solutions of 2 established an equilibrium between 2 and its conjugate base, fac-[Re(CO)₃(κ²-N,N-dpkfah-H)Cl]^? (3). Thermo-optical measurements confirmed that the interconversion between 2 and 3 and gave ΔG ^ø values of ?26.48 and 22.99?kJ?mol^?1, respectively, for the protonation of DMF and DMSO by 2. Optosensing measurements showed that [MCl₂] (M?=?Zn, Cd, or Hg) in concentrations as low as 1.00?×?10^?7?mol?L^?1 can be detected and determined using protophilic solutions of 2. Electrochemical measurements showed 2 to be more stable in CH₃CN than DMF. Single-crystal X-ray structural analysis on fac-[Re(CO)₃(κ²-N,N-dpkfah)Cl]?·?acetone (4) obtained from an acetone solution of 2 confirmed the solvent–complex interaction and revealed two symmetry-independent molecules in the asymmetric unit. The extended structure of 4 disclosed parallel stacks connected via a network of classic and non-classic hydrogen bonds.     

Regioselective synthesis of 4- and 7-alkoxyindoles from 2,3-dihalophenols: application to the preparation of indole inhibitors of phospholipase A2

An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been developed from commercially available starting materials such as 3-halophenols and 3-chloroanisole. Directed ortho-metalation followed by two palladium-catalyzed processes, a Sonogashira coupling and a tandem amination/cyclization reaction, allows the synthesis of regiochemically pure 4- and 7-substituted indoles. This strategy has been successfully applied to the preparation of 2-[3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yloxy]acetic acid (LY315920), a known inhibitor of phospholipase A2.     

A direct RP-HPLC method for the determination of furanic aldehydes and acids in honey

In this study 5-hydroxymethyl-2-furaldehyde (HMF), 2-furaldehyde, 3-furaldehyde, 2-furoic acid and 3-furoic acid are contemporarily determined in honey using a swift and direct RP-HPLC approach. The validation protocol was performed in terms of detection and quantification limits, precision (by repeatability and reproducibility), linearity and accuracy (by recovery tests); the acceptability of the precision and accuracy results was positively verified using Horwitz's model and AOAC guidelines, respectively. The method was tested on 18 honey samples of different ages, and botanical and geographical origin. HMF and 2-furaldehyde correlated highly with the age of the samples, whereas no correlation was observed with regards to 2-furaldehyde and 2-furoic acid. Hypotheses relating to the formation of minority furanic compounds are also proposed.     

A convenient preparation of 2-thioxo-4(3H)-quinazolinones

A simple method is described for the preparation of 3-aryl-2-thioxo-4(3H)-quinazolinones (4) by the reaction of anthranilic acids and ammonium or triethylammonium N-aryl-dithiocarbamates in ethanol. The method is also applicable to the preparation of 3-ethyl-2-thioxo-4(3H)-quinazolinone.     

Mononuclear to Polynuclear UIV Structural Units: Effects of Reaction Conditions on U-Furoate Phase Formation

Uranium(IV) complexation by 2-furoic acid (2-FA) was examined to better understand the effects of ligand identity and reaction conditions on species formation and stability. Five compounds were isolated: [UCl₂(2-FA)₂(H₂O)₂]_n ( 1 ), [U₄Cl₁₀O₂(THF)₆(2-FA)₂] ⋅ 2 THF ( 2 ), [U₆O₄(OH)₄(H₂O)₃(2-FA)₁₂] ⋅ 7 THF ⋅ H₂O ( 3 ), [U₆O₄(OH)₄(H₂O)₂(2-FA)₁₂] ⋅ 8.76 H₂O ( 4 ), and [U₃₈Cl₄₂O₅₄(OH)₂(H₂O)₂₀] ⋅ m H₂O ⋅ n THF ( 5 ). The structures were determined by single-crystal X-ray diffraction and further characterized by Raman, IR, and optical absorption spectroscopy. The thermal stability and magnetic behavior of the compounds were also examined. Variations in the synthetic conditions led to notable differences in the structural units observed in the solid state. At low H₂O/THF ratios, a tetranuclear oxo-bridged [U₄O₂] core was isolated. Aging of this solution resulted in the formation a U₃₈ oxo cluster capped by chloro and water ligands. However, at increasing water concentrations only hexanuclear units were observed. In all cases, at temperatures of 100–120 °C, UO₂ nanoparticles formed.     

Fluorophotometric Determination of Glucuronic Acid Using the Fluorescence-Reaction with N-Benzyl-2-Naphthylamine

Abstract

First, the fluorescence-reactions between glucuronic acid (D-glucuronolactone) as an uronic acid and N-benzyl-2-naphthylamine(NBNA) or N-benzyl-1-naphthylamine(NB-1-NA) as a secondary naphthylamine were systematically investigated in acetic acid medium. Secondly, NBNA-glucuronic acid fluorescence-product that has a maximum emission wavelength(Em) at 508 nm with excitation wavelength(Ex) at 468 nm was used for a selective assay of glucuronic acid; the calibration curve was linear in the range from 5 ng/ml to 2.0 μg/ml glucuronic acid, and the recovery test in normal urine was satisfactory (98.4–102.5%).     

The reductive repair of 1, 3-dhnethylthymine bromohydrin into 1, 3-dimethylthymine by 1, 5-dihydro-5-deazaflavin or 1, 4-dihydroquinoline

The reductive conversion of 1, 3-dimethylthymine bromohydrin into 1, 3-dimethylthymine by 10-ethyl-3-methyl-1, 5-dihydro-5-deazaflavin or 1-benzyl-3-carbamoyl-1, 4-dihydroquinoline has been achieved in the presence of trifluoroacetic acid.     

3-acylamino furans

3-Acylaminofurans are readily prepared from 3-furoic acid. Their Diels Alder reactions and electrophilic substitutions at C-2 have been investigated.     

Synthesis of certain metabolites and analogs of vitamin B6 and their ring-chain tautomerism

Pyridoxol and pyridoxal on benzylation with dimethylphenylbenzylammonium hydroxide (“leucotrope”) gave 3-O-benzylpyridoxol (IV) and 3-O-benzylpyridoxal (V), respectively. As a possible mechanism of this reaction an ion pair intermediate has been postulated. Oxidation of IV and V with chromic oxide-pyridine-acetic acid complex gave 3-O-benzyl-4-pyridoxic acid lactone (VI), which could also be obtained by benzylation of 4-pyridoxic acid. Treatment of VI with dimethylamine gave 2-methyl-3-benzyloxy-5-hydroxymethylpyridine-4-N,N-dimethylcarbox-amide (X) which oxidized to form the 5-formyl derivative (XI). The latter on hydrolysis yielded the metabolite, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylic acid (I). When reacted with liquid ammonia, VI gave 3-O-benzyl-4-pyridoxamide (VII) which was then oxidized to give 2-methyl-3-benzyloxypyridine-4,5-dicarboxylic acid cyclicimide(IX). Acid hydrolysis of IX gave another metabolite, 2-methyl-3-hydroxypyridine-4,5-dicarboxylic acid (XIII), which could also be obtained by oxidizing XI with potassium permanganate in water to yield 2-methyl-3-benzyloxy-5-carboxypyridine-4-N,N-dimethylcarboxamide (XII) and subsequent hydrolysis with hydrochloric acid. A positional isomer of I, 2-methyl-3-hydroxy-4-formylpyridine-5-carboxylic acid (XVII) was synthesized starting from 3-O-benzyl-5-pyridoxic acid lactone (XIV) following similar reaction sequences used for the preparation of I. Ring-chain tautomerism has been studied in I, XVII, opianic acid (XVIII), phthalaldehydic acid (XIX) and (2-carboxy-4,5-dimethoxy)-phenylacetaldehyde (XX) in different solvents by nmr and in the solid state by ir spectroscopy. A direct and reliable differentiation between the open form (aldehyde proton in low field) and the ring form (lactol proton in the intermediate field) has been obtained by nmr spectroscopy. In sodium deuteroxide and pyridine-d₅ the open chain form existed exclusively (except for homolog (XX) which is in cyclic form in pyridine-d₅), whereas in 18% hydrogen chloride in deuterium oxide all the compounds are completely in the cyclic form. In hexafluoroacetone hydrate-d₂, XVIII, XIX, and XX exist in the cyclic form whereas I is in the open form. In DMS0-d₆ both cyclic and open-chain forms have been observed in XVIII, XIX and XX. Definite peak assignment for the two forms could not be made in I due to broadening or superimposition with C₆-H. The metabolite I, isometabolite (XVII) and opianic acid (XVIII) form cyclic acetyl derivatives which give a sharp lactol peak. In the solid state XVIII, XIX are in the cyclic form and I and XX in the open-chain form as observed by ir spectroscopy.     

Regioselective synthesis of 3-aryl-5-(1H-indole-3-carbonyl)-4-hydroxyfuroic acids as potential insulin receptor activators

3-Methoxy-4-aryl-furan-2,5-dicarboxylic acid (8) is selectively converted into its C-5 methylester (6) by treatment with methyl chloroformate followed by decarboxylation in one flask. Acylation of the resulting half ester with a 7-substituted indole was performed under mild conditions to afford 3-aryl-5-(1H-indole-3-carbonyl)-4-methoxy-2-furoic acid (11). The synthetic utility of the resulting furoic acids as a skeleton in the synthesis of potential insulin receptor activators is established.     

Synthesis and antibacterial activity of some 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids: Ethers,secondary amines and sulfides as c-7 substituents

A series of 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared from 1-ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 8 . Those derivatives reported contain acyclic and heterocyclic substituents linked to the quinolone C-7 position via O, NH or S. The in vitro antibacterial data of some of these derivatives against 4 Gram positive and 4 Gram negative organisms are reported.     

Ring Opening Reactions of 1,2-Didehydroprolines. Part II. Synthesis of 5-Amino-2,4-dihydroxypentanoic Acids,their 2-Piperidones and Pentanolides [1]

Summary. NMR spectroscopic investigations on 1,2-didehydroproline in alkaline deuterium oxide revealed incorporation of deuterium at position C-3, presumably due to the presence of acyclic 5-amino-2-oxopentanoate in solution. Reduction of this equilibrium mixture with hydride reagents generally yields prolines together with the 2-hydroxy acids. It could be shown that the ratio of the two products depends strongly on the pH. This allowed the optimization of reaction conditions for the preparation of the target compounds (2R,4R)- and (2S,4R)-5-amino-2,4-dihydroxypentanoic acid. In order to separate these isomers and unambiguously assign their respective structures, the (3R,5R)- and (3S,5R)-3,5-dibenzoyloxy-2-piperidones were synthesized as the key intermediates by lactamization and benzoylation. Lactames were also directly transformed to the corresponding lactones.     

Chemical and nuclear magnetic resonance studies of 3,3-diphenyltetrahydrofuran derivatives

Pyrolytic cyclization of a- and β-methadol methiodides afforded cis and trans isomers of 2-ethyl-3,3-diphenyl-5-methyltetrahydrofuran, respectively. Catalytic hydrogenation of 2-ethyli-dene-3,3-diphenyl-5-methyltetrahydrofuran yielded the cis and trans isomers in a 2:1 ratio. The nmr spectra of these and structurally related compounds have been analyzed in terms of a half-chair conformation for 2-ethyl-5-methyl, 2-ethyl, and 5-methyl derivatives. An envelope conformation has been suggested for the compounds containing a double bond at C-2.     

Synthesis of New Fluorinated Derivatives of Quinolinecarboxylic Acids

Ethyl esters of 1-(7-Z-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbamoyl)-5-X-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids (X = H, F; Z = pyrrolidino-, piperidino-, hexamethylenimino-, morpholino-, thiomorpholino-) have been synthesized by the interaction of quinolone-3-carboxylic acid hydrazides with ethyl esters of 3-ethoxy-2-(polyfluorobenzoyl)acrylic acid . It was shown possible to cyclize intramolecularly the esters obtained with the formation of 1,3,4-oxadiazino[6,5,4-i,j]quinoline derivatives.     

New 7-substituted quinolone antibacterial agents. II. The synthesis of 1-ethyl-1,4-dihydro-4-oxo-7-(pyrazolyl,isoxazolyl, and pyrimidinyl)-1,8-naphthyridine and quinolone-3-carboxylic acids

Synthetic methods for the construction of certain aromatic heterocyclic side chains for the quinolone anti-bacterials have been provided. In particular a series of 7-(pyrazol-3 or 4-yl, 4- or 5-isoxazolyl and 4- or 5-pyrimidinyl)-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine and quinoline-3-carboxylic acids have been prepared. All of the heterocycles were prepared from masked 1,3-dicarbonyl derivatives of nalidixic acid ( 9,17 ) or 7-acetyl-1-ethyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acids ( 8 ). These masked 1,3-dicarbonyl derivatives were prepared by the use of t-butoxy-bis-dimethylaminomethane on the activated methyls of 9,19 and 8 . The pyrimidinyl analogs, substituted with a 2-amino or a 2-aminomethyl moiety, were the only derivatives with substantial antibacterial activity.     

Reactions of nitrogen compounds with ruthenium tetroxide. Determination of the absolute configuration of 3-ethylpiperidine

(-)-3-Kthylpiperidine and (R)-(-)-2-ethylglutarie acid have been chemically correlated through N-subslituted α-ethylglutarimides obtained from the oxidation of optically active N-ethyl- and N-benzyl-3-ethylpiperidine with ruthenium tetroxide. The (R)-(-) configuration of (-)-3-ethylpiperidine was confirmed by CD measurements. The selective oxidation of endocyclic methylenes linked to the nitrogen atom was explained in term of different conformational freedom of endo- and exocyclic methylene groups.