Ethyl Chloroformate Research Articles

An easy and sensitive assay for acetohydroxyacid synthases based on the simultaneous detection of substrates and products in a single step.

Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) catalyzes the first step in the synthesis of the branched-chain amino acids valine, leucine, and isoleucine, pathways being present in plants and microorganisms, but not in animals. Thus, AHAS is an important target for numerous herbicides and, more recently, for the development of antimicrobial agents. The need to develop new and optimized herbicides and pharmaceuticals requires a detailed understanding of the biochemistry of AHAS. AHAS transfers an activated two-carbon moiety derived from pyruvate to either pyruvate or 2-oxobutyrate as acceptor substrates, forming 2-acetolactate or 2-acetohydroxy-2-butyrate, respectively. Various methods have been described in the literature to biochemically characterize AHAS with respect to substrate preferences, substrate specificity, or kinetic parameters. However, the simultaneous detection and quantification of substrates and unstable products of the AHAS-catalyzed reaction have always been a challenge. Using AHAS isoform II from Escherichia coli, we have developed a sensitive assay for AHAS-catalyzed reactions that uses derivatization with ethyl chloroformate to stabilize and volatilize all reactants in the aqueous solution and detect them by gas chromatography coupled to flame ionization detection or mass spectrometry. This assay allows us to characterize the product formation in reactions in single and dual substrate reactions and the substrate specificity of AHAS, and to reinterpret previous biochemical observations. This assay is not limited to the AHAS-catalyzed reactions, but should be applicable to studies of many metabolic pathways.

Green Synthesis and Biological Evaluation of Substituted 1,3,4-Oxadiazoles Through Ethyl Chloroformate and 2-Amino-5-Nitrothiazole

Green Synthesis and Biological Evaluation of Substituted 1,3,4-Oxadiazoles Through Ethyl Chloroformate and 2-Amino-5-Nitrothiazole

3-Ethoxycarbonyl-1,4-benzodioxin-2-carboxylic Acid

3-Ethoxycarbonyl-1,4-benzodioxin-2-carboxylic acid, a novel 2,3-disubstituted benzodioxin, was prepared from readily available 1,4-benzodioxin-2-carboxylic acid by lithiation at C(3) and a reaction with the electrophile ethyl chloroformate. The analytical characterization of the product was performed via IR, 1H-NMR, 13C-NMR, HRMS, and HPLC-UV. Due to the unsymmetrically disubstituted unsaturation, the obtained monoester of 1,4-benzodioxin-2,3-dicarboxylic acid is a building block of great potential in the synthesis of a variety of compounds containing the benzodioxin or benzodioxane scaffold.

On the fate of protonated chloroformates in the gas phase: a competition between forming HCl and chloroformic acid.

Chloroformates are prevalent in the atmosphere due to their utilization as fuel additives and industrial solvents. These species may undergo interactions with atmospheric water resulting in protonated chloroformates. This study delves into the gas-phase dissociation of these protonated species. Tandem mass spectrometry was employed to scrutinize the unimolecular dissociation of protonated methyl (1), ethyl (2), neopentyl (3), and phenyl chloroformate (4). Notably, 1 and 4 exhibited HCl loss, yielding CH3OCO+ and C6H5OCO+, respectively, with 1 additionally generating neutral methanol and ClCO+. 4 additionally loses CO and CO2. In contrast, 2 and 3 each only exhibit a single fragmentation channel, with 2 losing C2H4 to generate protonated chloroformic acid and 3 generating protonated 2-methylbutene by losing neutral chloroformic acid. Density functional theory at the B3LYP/6-311+G(d,p) level of theory was employed to explore minimum energy reaction pathways for each ion, and CBS-QB3 single-point energy calculations were added to provide reliable energetics. The Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of the rate constants for selected competing processes were carried out to link theory and experiment. One common unimolecular process observed was the 1,3-H shift of the proton from the carbonyl oxygen to the ester oxygen before dissociation.

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis.

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11)) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score (S, kcal/mol) ranged between -8.23 (for compound 5), -8.12 (for compound 3) and -8.03 (for compound 9) to -6.01 (for compound 8). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds (5, 3, and 9) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (ΔE) of compounds 5, 3, and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Nickel(I)-catalysed multicomponent reductive hydrocarbonylation of alkenes: A theoretical study of mechanism, regio-, enantio-, and chemoselectivity

In the present study, theoretical calculations were performed to gain a deeper understanding of the nickel-catalysed multicomponent reductive hydrocarbonylation of alkenes using ethyl chloroformate as the CO source and hydrosilane as the hydride source. The computations show Ni(I) species acts as the active catalyst entering the catalytic cycle. The calculated mechanism corroborates the experimental mechanistic proposals on the elementary steps. Nonetheless, the sequence of elementary steps and the oxidation state of the nickel center are different from the experimental proposal. The calculations reproduced quite well the experimentally observed regio- and enantioselectivity. The distortion/interaction analysis and frontier molecular orbital theory confirm that the interaction energy determines the regioselectivity. The high S-enantioselectivity arises from the stronger C–H/π interactions in the S-configuration compared to those in the R-type enantiomer. One of the biggest challenges faced by multicomponent reactions is competing side-reactions. To explore the reaction's chemoselectivity, we calculated the formation mechanisms of five potential by-products and analyzed the driving force behind the formation of the desired product.

A Simple and Efficient Approach for the Synthesis of Aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one Derivatives

AbstractIn this work, a series of 4-aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one derivatives is synthesized through nucleophilic intramolecular cyclization reactions of ethyl 2-(2,2,2-trifluoro-1-(arylimino)ethyl)hydrazine-1-carboxylate intermediates, which are themselves prepared in high yields via reactions of ethyl chloroformate and N-aryl-2,2,2-trifluoroacetimidoyl chloride derivatives. Some of the merits of the reported procedure are an operationally simple and concise method, the ready availability of starting materials, excellent product yields, no formation of harmful by-products and easy purification of the products.

Rapid indirect separation of glutamine enantiomers by micellar electrokinetic chromatography. Analysis of dietary supplements.

Glutamine is the most abundant free proteinogenic α-amino acid. It is naturally produced in the organism and acts as a precursor for the synthesis of different biologically important molecules (such as proteins or nucleotides). However, under stressful conditions, the organism is unable to produce it in enough amounts to function properly. Thus, glutamine (Gln)-based supplements have become increasingly popular over the last decade. Since legal regulations establish that amino acid-based dietary supplements must contain only the L-enantiomer and not the racemate, adequate chiral methodologies are required to achieve their quality control. In this work, an analytical methodology based on the use of micellar electrokinetic chromatography is proposed for the rapid enantiomeric determination of DL-Gln in dietary supplements. Using (+)-1-(9-fluorenyl)-ethyl chloroformate as a derivatizing agent and ammonium perfluorooctanoate as separation medium, the Gln diastereoisomers formed under optimal conditions were separated in 8min with a resolution of 2.8. The analytical characteristics of the method were evaluated in terms of linearity, precision, accuracy, and limits of detection/quantitation, and they were found appropriate for the analysis of L-Gln-based dietary supplements.

Stability and reactivity of alkylidene dihydropyridines.

Alkylidene dihydropyridines (ADHPs) are electron-rich nucleophilic intermediates that can be readily prepared by dearomatization of 4-alkylpyridines using chloroformate reagents and mild base. Their stability and reactivity can be tuned with the chloroformate reagent used as evidenced by NMR chemical shifts and oxidation potentials. ADHPs prepared with ethyl, allyl and trichloroethyl chloroformate undergo decomposition under an oxygen atmosphere at different rates (ethyl > allyl > trichloroethyl), predominantly to the corresponding 4-acylpyridine. The ADHPs derived from benzyl chloroformate are stable towards oxidation, and those derived from phenyl chloroformate hydrolyze readily.

Analysis of D-amino acids secreted from murine islets of Langerhans using Marfey’s reagent and reversed phase LC-MS/MS

D-amino acids (D-AAs) are important signaling molecules due to their ability to bind ionotropic N-methyl-D-aspartate receptors. D-serine (D-Ser), D-alanine (D-Ala), and D-aspartate (D-Asp) have been found individually in the endocrine portion of the pancreas, the islets of Langerhans, and/or their secretions. However, there has been no report of a comprehensive assessment of D-AAs in islet secretions. To evaluate the release of these compounds, the effectiveness of both 1-(9-fluorenyl)-ethyl chloroformate (FLEC reagent) and 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (Marfey’s reagent, MR) in separation of D/L-AA enantiomeric pairs in islet-specific buffers were evaluated. MR-derivatized D/L AAs showed greater than baseline resolution (Rs ≥ 1.5) of 13 enantiomeric pairs when using a non-linear gradient and an acidic mobile phase system, while FLEC-derivatized AAs exhibited limited resolution on both biphenyl and C18 columns. The optimized MR method yielded highly reproducible separations with retention times less than 1% RSD. Excellent linearity between the analyte concentrations and response (R2 > 0.98) were obtained, with less than 15% RSD for all analyte responses. Most analytes had an LOD at or below 100 nM, except for L-Ala (200 nM). The optimized MR method was used to quantify D-AAs in secretions of 150 murine islets after incubation in 3- and 20-mM glucose. In response to both solutions, D-Ser and D-glutamine were tentatively identified via comparison of retention time and quantifier-to-qualifer ion ratios with standards, and from spiking experiments. Both were secreted in low quantities which did not differ significantly in either low (D-Ser: 44 ± 2 fmol islet-1h−1; D-Gln: 300 ± 100 fmol islet-1h−1) or high (D-Ser: 23 ± 1 fmol islet-1h−1; D-Gln: 120 ± 50 fmol islet-1h−1) glucose across 3 biological replicates. The method developed is robust and can be applied to further examine the release of D-AAs and their potential roles in islet physiology.

Efficient Approach for the Synthesis of Aryl Vinyl Ketones and Its Synthetic Application to Mimosifoliol with DFT and Autodocking Studies.

An efficient and elegant method was developed for the preparation of substituted phenyl vinyl ketones using low-cost and commercially available ethyl chloroformate and diisopropylethylamine as reagents. This methodology was also applied to the synthesis of natural products such as mimosifoliol and quinolines. Frontier molecular orbital (FMO) studies on mimosifoliol were carried out to understand its chemical reactivity. Electron localization function (ELF) and localized orbital locator (LOL) analysis gave information about localized and delocalized electrons. Reduced density gradient (RDG) analysis gave information on steric, van der Waals, and hydrogen-bonding interactions. Molecular electrostatic potential (MEP) and Fukui functions gave information about nucleophilic and electrophilic attack. Nonlinear optical (NLO) analysis represented the mimosifoliol good NLO material. Molecular docking showed that the mimosifoliol compound had effectively inhibited the aspulvinone dimethylallyltransferase enzyme.

Synthesis and Anticancer Activity of Novel Chromene Derivatives, Chromeno[2,3-d][1,3]Oxazines, and Chromeno[2,3-d]Pyrimidines.

Several chromene derivatives have a wide variety of biological and pharmacological activity. They had anticancer activity, antimicrobial activity, antituberculosis activity, anticonvulsant activity, antidiabetic activity, antichlolinesterase activity, and inhibitor of monoamine oxidase activity. The above-mentioned activities directed us to synthesize novel chromene derivatives, chromeno[2,3-d][1,3]oxazines, and chromeno[2,3-d]pyrimidines. The starting material was 2- amino-8-(2-chlorobenzylidene)-4-(2-chlorophenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. Several novel chromene derivatives had been synthesized. Compound 1 reacted with carbon disulfide, and ethyl chloroformate to afford chromene derivatives 2, 3. Chromene derivative 3 reacted with hydrazine dydrate to give compound 4. Chromene derivative 1 reacted with acetic acid and sulphuric acid to produce compounds 5, and 6. Amino derivative 5 reacted with chloroacyl derivative to afford compounds 7a-c which cycalized in dry xylene to afford compounds 8a-c. Chromene derivative 8a reacted with hydroxyl amine to afford compound 9. The structures of novel synthesized chromene derivatives had been confirmed using mass spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Most of the prepared compounds were screened against liver cancer cell lines (HepG-2), human colon cancer cell lines (HT-29), and breast adenocarcinoma cell lines (MCF-7). Chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. The rest of the tested compounds had anticancer activity against human colon cancer cell lines (HT-29) lower than that of the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Several chromene derivatives had been synthesized and their structures had been confirmed using different spectroscopic techniques. Some of the chromene derivatives that were screened against different cancer cell lines showed promising anticancer activity higher than the reference standard drug. For example, chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Chromene derivative 6 had anticancer activity against breast adenocarcinoma cell lines (MCF-7) higher than the standard drug.

Atmospheric degradation of chloroacetoacetates by Cl atoms: Reactivity, products and mechanism in coastal and industrialized areas

Kinetic studies of the reaction of Cl atoms with ethyl 2-chloroacetoacetate, CH3C(O)CHClC(O)OCH2CH3, (k1) and methyl 2-chloroacetoacetate, CH3C(O)CHClC(O)OCH3, (k2) have been developed for the first time using SPME/GC-FID and in situ FTIR spectroscopy at (298 ± 2) K and 1000 mbar in glass atmospheric chambers. Relative rate coefficients obtained by Fourier Transform Infrared Spectroscopy (FTIR) using different reference compounds, were the following (in cm3.molecule−1.s−1): kE2CAA-FTIR= (2.41 ± 0.57) × 10−10 and kM2CAA-FTIR= (2.16 ± 0.85) × 10−10. Similar and reproducible values were obtained using Gas Chromatography equipped with Flame Ionization Detection coupled with Solid Phase Micro Extraction (SPME), kE2CAA-GC-FID = (2.54 ± 0.81) × 10−10 and kM2CAA-GC-FID = (2.34 ± 0.87) × 10−10 all values in units of cm3.molecule−1.s−1. In addition, product studies were performed in similar conditions to the kinetic experiments to identify the reaction products and postulate their tropospheric degradation mechanisms. The reaction of Cl atoms with saturated esters initiates via H-atom abstraction from the alkyl groups of the molecule. Formyl chloride, chloroacetone, and acetyl chloride were positively identified as reaction products by FTIR. On the other hand, acetyl chloride, 1,1,1-trichloropropan-2-one, 1,1-dichloropropan-2-one, 1-chloropropan-2-one, ethyl chloroformate, and methyl chloroformate were identified by the GC-MS technique. Structure–Activity Relationship (SAR), calculations were also performed to estimate the more favorable reactions pathways in agreement with the products observed. The atmospheric implications of these reactions were assessed by the estimation of the residence times of the chloroesters studied as following: τCl-E2CAA = 1.47 days, and τCl-M2CAA = 1.57 days. Additionally, the possible impact of the emission of chloro acetoacetates in rain acidification was evaluated from the moderate Acidification Potentials (AP), 0.19, and 0.21 obtained for E2CAA and M2CAA, respectively.

Synthesis of nalbuphine and investigation of several mixtures of nalbuphine with other drugs for BALB/c mice anesthesia

AbstractIn this research, the conversion of thebaine into oxycodone was achieved using oxidizing reagents, with a yield of 80%. Subsequently, oxycodone was converted into oxymorphone in the presence of an acidic environment, resulting in a yield of 55%. The synthesized oxymorphone was then de‐methylated using ethyl chloroformate to obtain the intermediate noroxymorphone. The latter was further transformed into nalbuphone using cyclobutyl methyl bromide reagent, with a yield of 82%. Finally, nalbuphone was converted into nalbuphine using a reducing reagent, with a yield of 75%. The identification of all intermediates was ensured through the use of NMR, FT‐IR, Mass, and HPLC spectroscopy. The chemical transformations were primarily associated with the formation of noroxymorphone, which served as a crucial intermediate in the synthesis of nalbuphin. Additionally, the effects of three drugs, namely azaperone, medetomidine, and nalbuphine, were investigated on BALB/c mice. The results showed that the best formulation for short‐term anesthesia of mice was a combination of the three drugs, each at a concentration of 1 mg/kg of body weight.

GC-MS analysis of eight aminoindanes using three derivatization reagents.

Aminoindanes are a class of novel psychoactive substances (NPSs) that have become more prevalent over the past decade. GC-MS is often utilized for identifying seized drugs and is well regarded for its ability to separate mixtures. However, certain aminoindanes have similar mass spectral data and require specific gas chromatographic stationary phases for separation. Derivatization is an alternative method that can be applied to GC-MS to enhance chromatographic results, providing more selective analysis in seized-drug identification. This study investigates derivatization techniques to provide options for forensic science laboratories in accurately identifying aminoindanes. Three derivatization reagents, N-methyl-bis(trifluoroacetamide) (MBTFA), heptafluorobutyric anhydride (HFBA), and ethyl chloroformate (ECF) were evaluated for the analysis of eight aminoindanes by GC-MS using two common gas chromatographic stationary phases, Rxi®-5Sil MS and Rxi®-1Sil MS. All three derivatization methods successfully isolated eight aminoindanes, including the isomers 4,5-methylenedioxy-2-aminoindane (4,5-MDAI), and 5,6-methylenedioxy-2-aminoindane (5,6-MDAI) that could not be differentiated prior to derivatization. Reduced peak tailing and increased abundance were observed after derivatization for all the compounds, and mass spectra of the derivatives contained individualizing fragment ions that allowed for further characterization of the aminoindanes. This excluded 4,5-MDAI and 5,6-MDAI as they shared the same characteristic ions and were only distinguishable by their retention times. All three derivatization techniques used in this study allow for successful characterization of the aminoindanes and give forensic science laboratories flexibility in their analysis approach when they encounter these compounds.

Synthesis of quercetin functionalized chitosan and determination of antioxidant properties

This paper is dedicated to the synthesis of a copolymer with reducing properties obtained by functionalizing chitosan with quercetin and determining the antioxidant activity of the derivatives obtained depending on the molar mass of the polymer. For this purpose, low molecular weight chitosan was obtained by oxidizing commercial chitosan with hydrogen peroxide and further functionalization with quercetin by the covalent grafting method. The functionalization process was performed through the following steps: functionalization of chitosan with ethyl chloroformate to increase the reactivity of the amine group to the hydroxyl group of quercetin and grafting the quercetin molecule to the synthesized intermediate. The comparative antioxidant properties of the composite obtained by grafting technical chitosan with quercetin and by grafting low molecular weight chitosan were studied by the DPPH (2,2-diphenyl-1-picrylhydrazyl radical) method. The obtained results indicate that a decrease in the molecular weight of chitosan contributed to its grafting with quercetin. As a result, the functionalized polymer composite acquired a higher antioxidant activity and can be successfully used to inhibit the oxidation of various organic substrates in the cosmetic, food and pharmaceutical industries.

Synthesis and X-ray crystallography of new N-, O-acyl pseudoephedrines

N-acylation and O-acylation of pseudoephedrine are studied by using aroyl chlorides and/or ethyl chloroformate as acylating agents. Thus, treatment of pseudoephedrine or its salt with benzoyl or p-nitrobenzoyl chlorides affords the corresponding N- or O-acylated products 2a, b, 3a, b and 4. Also, pseudoephedrine 1 was allowed to react with ethoxymethylenemalononitrile to yield 2-hydroxy-1-methyl-2-phenylethyl](methyl)amino}methylene)malononitrile (5). New oxazolidine derivatives 6a–c were conveniently synthesized in high yields from the reaction of 1 with different bis(methylthio)yledinenitriles. X-ray crystallographic study of 4 revealed that the compound crystallized in orthorhombic system. The structure is stabilized by the intermolecular interactions as well as a network of hydrogen bond contacts, conformed parallel layers.

Sampling chamber with minimal wall surface for simultaneous emission testing of diisocyanates and diamines from polyurethane products

A sampling chamber was developed for emission testing of diisocyanates, methylene diphenyl diisocyanate (MDI), toluene diisocyanate (TDI), and corresponding diamines, methylene diphenyl diamine (MDA), and toluene diamine (TDA) from polyurethane (PU) product surfaces. In addition, a methodology for validation of the sampling chamber was presented, based on the introduction of generated standard atmospheres of the different diisocyanates and diamines to the sampling chamber system. Sampling of diisocyanates and diamines was performed on a circular glass fiber filter (150mm diameter) impregnated with dihexyl amine (DHA) and acetic acid (AA) positioned inside a cylindrical stainless steel sampling chamber. The diisocyanates were immediately derivatized to DHA derivatives, and the amines were derivatized in a subsequent work-up procedure with ethyl chloroformate (ECF). The design of the sampling chamber and the presented methodology allowed for simultaneous sampling and analysis of diisocyanates and diamines of emission from a large surface area with minimal interior wall interaction in the sampling chamber. Performance characteristics of the sampling chamber for different sampling times and air humidity were obtained by determining collected amounts of the diisocyanates and diamines in the different parts of the sampling chamber. The repeatability of the collected amount on the impregnated filters in the sampling chamber was 15% with an overall recovery for 8h of sampling in the range of 61% to 96%. The performance of the sampling chamber was not affected by air humidity (5%-75% RH), and no breakthrough during sampling was observed. LC-MS/MS determinations allowed for emission testing of diisocyanates and diamines on product surfaces as low as 10-30ng m-2 h-1.

Bactericide polymers obtained from nitrofuran and chitosan derivatives

Background: In this study, the synthesis and characterization of chitosan polymeric materials grafted with nitrofuran derivatives – furaceline and isofural in terms of antibacterial properties and prolongation of their action were performed. Material and methods: Synthesis of chitosan analog polymers with maleic anhydride was performed, followed by grafting of nitrofuran derivatives using ethyl chloroformate. The chemical composition of the obtained polymers was confirmed by FT-IR spectroscopy. Antibacterial study has been performed on a wide range of Gram-positive and Gram-negative microorganisms. Results: Chitosan derivatives with a content of 30 mol% of maleic anhydride were obtained. To the analogous polymer ”chitosan maleinized” the medicinal products isofural or furaciline with the help of the ethyl chloroformate were functionalized. By comparative analysis of the IR spectra of the final products with the IR spectra of maleinized chitosan and furacilin or isofuran was demonstrated the individual structure of the polymeric preparations “maleinized chitosan grafted with furacilin“ / “maleinized chitosan grafted with isofural”. The antibacterial substances, isofural and furaciline, among nitrofurans, being grafted with chitosan maleinized, keep their bactericidal activity in the limits of 75-300 μg/mL. The polymeric materials from chitosan maleate grafted with isofural or furacillin in a ratio of 70:30 have a prolonged antibacterial action (observation period 72 hours). Conclusions: It has been found that isofural and furacilin, among nitrofurans, being grafted on chitosan polymeric material, retain their bactericidal activity and possess prolonged antibacterial action.

1,2-Metallate Rearrangement Using Indole Boronate Species to Access 2,3-Diarylindoles and Indolines.

A transition metal-free multicomponent reaction using lithiated indole, boronic ester, pyridine, and ethyl chloroformate was developed to access C2,C3 bis-arylated indoles, which are present in several marketed drugs and bioactive compounds. One-pot access to unsymmetrical C2,C3-diaryl indole from the parent indole remains a huge synthetic challenge. Our group was able to achieve this goal through a transition metal-free 1,2-metalate rearrangement of the indole boronate complex. The reaction of indole boronate species with activated pyridine allows 1,2-migration to access pyridyl-indoleboronate species, which will convert to the corresponding indole upon oxidation and indoline after deborylation. The reaction tolerates substituted pyridines, quinolone, isoquinoline, and more. Both aryl and alkyl boronic esters were accommodated under optimized reaction conditions. Apart from mechanistic studies using 11B-NMR, this methodology has been applied to the gram-scale synthesis of several bioactive compounds.