Search Results (46)

Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against Staphylococcus aureus and Escherichia coli, obtaining preliminary and promising results. Full article

Polyols derived from poly(vinyl alcohol) (PVA) have not been reported before. The hydroxyalkylation of PVA with oxiranes leads to powdered or gum-like products that are not miscible with isocyanates and therefore useless as sources of polyurethane foams. Glycidol and ethylene carbonates were used to dissolve and convert PVA into liquid polyol. The physical properties of the PVA-derived polyol, such as the density, viscosity, and surface tension, were determined. The polyol was then used to obtain rigid polyurethane foams (PUFs). Foaming conditions were optimized, and the apparent density, volume water uptake, dimensional stability, heat conductance coefficient, pore size, thermal resistance, compressive strength, and glass transition temperature of the obtained PUFs were determined. The properties of the obtained PUFs were similar to those of classic rigid PUFs, but the thermal resistance of the former is better. Specifically, PVA-derived PUFs are thermally resistant at temperatures of up to 150 °C. Furthermore, they are ecologically safe; in standard soil conditions, 54.6% or 100% biodegradation of the foams in cube and powder form, respectively, was observed, as measured by BOD after 28 days of storage. Full article

One of the current challenges in organic synthesis is the direct alkylation of heterocyclic systems with a minimal impact on the environment. In this report, 4-substituted hydroxyalkyl quinolines were obtained by treating quinoline with different alkyl carboxylic acids in the presence of catalytic amounts of an iron (III) chloride–phenanthroline complex. The reaction was mediated by blue LED light under acidic conditions as a cleaner alternative to conventional heating, reducing the use of harmful substances. Full article

Oxazoles are important five-membered heterocycles that contain both nitrogen and oxygen atoms. Due to their wide range of biological activities, many oxazoles demonstrate potential for extensive application in various fields, including medicinal chemistry. Trifluoromethyl carbinol, an important pharmacophore, contains both trifluoromethyl and hydroxyl groups and is common in molecules with important biological activities. Constructing oxazoles that contain a trifluoromethyl carbinol unit is undoubtedly important and valuable for expanding the chemical space in drug discovery. In this study, a simple and efficient method was developed for the synthesis of oxazoles containing a CF₃-substituted alcohol unit via the tandem cycloisomerization/hydroxyalkylation of N-propargylamides with trifluoropyruvates through a rational Lewis acid catalytic mechanism. This Zn(OTf)₂-catalyzed synthetic protocol is operationally simple and provides a series of oxazoles in moderate to good yields. The protocol demonstrates broad substrate scope, high functional group tolerance, and high atom economy and can achieve gram-level reactions, indicating the strong possibility of its practical application. Full article

The aim of this study is to prepare new cellulose derivatives that show good feasibility and processability. Accordingly, in this study, we demonstrate Michael addition to hydroxyalkyl acrylates, that is, 2-hydroxyethyl and 4-hydroxybutyl acrylates (HEA and HBA, respectively), to synthesize amorphous cellulose derivatives under alkaline conditions. The reactions were carried out in the presence of LiOH in ionic liquid (1-butyl-2,3-dimethylimidazolium chloride)/N,N-dimethylformamide (DMF) solvents at room temperature or 50 °C for 1 h. The Fourier transform infrared and ¹H nuclear magnetic resonance (NMR) measurements of the products supported the progress of Michael addition; however, the degrees of substitution (DS) were not high (0.3–0.6 for HEA and 0.6 for HBA). The powder X-ray diffraction analysis of the products indicated their amorphous nature. The cellulosic Michael adduct from HEA with DS = 0.6 was swollen with high polar organic liquids, such as DMF. In addition to swelling with these liquids, the cellulosic Michael adduct from HBA was soluble in dimethyl sulfoxide (DMSO), leading to its ¹H NMR analysis in DMSO-d₆. This adduct was found to form a cast film with flexible properties from its DMSO solutions. Furthermore, films containing an ionic liquid, 1-butyl-3-methylimidazolium chloride, showed thermoplasticity. The Michael addition approach to hydroxyalkyl acrylates is quite effective to totally reduce crystallinity, leading to good feasibility and processability in cellulosic materials, even with low DS. In addition, the present thermoplastic films will be applied in practical, bio-based, and eco-friendly fields. Full article

Three methods of cellulose-derived polyol synthesis were elaborated. The suitable substrates were (hydroxypropyl)cellulose or cellulose, which were hydroxyalkylated in reactions with glycidol and ethylene carbonate in triethylene glycol or in water. The products were characterized by IR, ¹H NMR, and MALDI ToF spectroscopies. For all polyols, IR spectra showed strong bands at 1060 cm⁻¹ from the ether group formed upon the ring opening of GL and EC. The polyol obtained from (hydroxypropyl)cellulose in the triethylene glycol solvent was accompanied by oligomeric products of glycol hydroxyalkylation and oligomeric glycidol. The polyol obtained by the hydroxyalkylation of cellulose with glycidol and ethylene carbonate in the water contained units of hydroxyalkylated cellulose and products of hydroxyalkylation of water. The physical properties of the obtained polyols, like density, viscosity, and surface tension, were determined. The polyols were then used to obtain rigid polyurethane foams. The foams have apparent density, water uptake, and polymerization shrinkage similar to classic rigid PUFs. The foams showed advantageous thermal resistance in comparison with classic ones. After thermal exposure, their compressive strength improved. The biodegradation of the obtained materials was tested by a respirometric method in standard soil conditions by the measurement of biological oxygen demand and also using the cellulases or the enzymes responsible for cellulose degradation. It has been found that polyols are totally biodegradable within one month of exposure, while the foams obtained thereof are at least 50% biodegraded in the same conditions. The enzymatic biodegradation of the PUFs by the action of microbial cellulase was confirmed. Full article

Alkoxyalkylation and hydroxyalkylation methods utilizing oxo-compound derivatives such as aldehydes, acetals or acetylenes and various alcohols or water are widely used tools in preparative organic chemistry to synthesize bioactive compounds, biosensors, supramolecular compounds and petrochemicals. The syntheses of such molecules of broad relevance are facilitated by acid, base or heterogenous catalysis. However, degradation of the N-analogous Mannich bases are reported to yield alkoxyalkyl derivatives via the retro-Mannich reaction. The mutual derivative of all mentioned species are quinone methides, which are reported to form under both alkoxy- and aminoalkylative conditions and via the degradation of the Mannich-products. The aim of this review is to summarize the alkoxyalkylation (most commonly alkoxymethylation) of electron-rich arenes sorted by the methods of alkoxyalkylation (direct or via retro-Mannich reaction) and the substrate arenes, such as phenolic and derived carbocycles, heterocycles and the widely examined indole derivatives. Full article

2-methylfuran is a significant organic chemical raw material which can be produced by hydrolysis, dehydration, and selective hydrogenation of biomass hemicellulose. 2-methylfuran can be converted into value-added chemicals and liquid fuels. This article reviews the latest progress in the synthesis of liquid fuel precursors through hydroxyalkylation/alkylation reactions of 2-methylfuran and biomass-derived carbonyl compounds in recent years. 2-methylfuran reacts with olefins through Diels–Alder reactions to produce chemicals, and 2-methylfuran reacts with anhydrides (or carboxylic acids) to produce acylated products. In the future application of 2-methylfuran, developing high value-added chemicals and high-density liquid fuels are two good research directions. Full article

Previously, we demonstrated the synthesis of a well-defined hydroxyalkyl-functionalized N-heterocyclic carbene (NHC)/Ru(II) complex through the transmetalation reaction between [RuCl₂(p-cymene)]₂ and the corresponding NHC/Ag(I) complex derived from a chiral benzimidazolium salt using the Ag₂O method. In this study, we successfully synthesized [RhX(cod)(NHC)] complexes through a one-pot deprotonation route. The hydroxyalkyl-substituted benzimidazolium salt reacted with [Rh(OH)(cod)]₂ in THF at room temperature, affording the corresponding monodentate NHC/Rh(I) complex in nearly quantitative yield. The rhodium complex was characterized using NMR, HRMS measurement, and elemental analysis. Full article

To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients. Full article

The hydroxyalkyl amination of agarose gels was studied as an approach to improve adsorption of polyphenols and pharmaceuticals from water. Three commercially available agarose gels, Zetarose FlashFlow4, ZetaCell-CL6B and Sepharose 4B were chemically modified using tris-(hydroxymethyl)aminomethane, TRIS, and ethanolamine, EA. The adsorbed amounts of bisphenol A and diclofenac were significantly higher on TRIS- and EA-derivatives compared with the parent gels. Regarding bisphenol A adsorption on TRIS-ZetaCell-CL6B, a maximal adsorption capacity, Q max of 16 μmol/mL gel and an equilibrium dissociation constant K_L of 2.7 × 10⁻⁴ mol/L were observed. Filtration of diclofenac-contaminated water through TRIS-Zetarose FlashFlow 4 resulted in a 10-fold reduction of the pollutant concentration within 64 column volumes of the effluent. The moderate binding affinity of polyphenols to TRIS- and EA-adsorbents facilitates efficient polyphenol desorption and column regeneration. The effects of TRIS- and EA-substituents in agarose gels, can be harnessed for the development of environmental adsorbents, as well as for the preparative separation of polyphenols and pharmaceuticals. We consider the physical shapes and textures of the prospective adsorbents with a particular focus on spongy macroporous cryogels. These innovative materials hold promise for future applications in liquid and air filtration. Full article

Decreasing oil extraction stimulates attempts to use biologically available sources to produce polyols, which are the basic components for obtaining polyurethane foams. Plants are inexhaustible source of oils, sugars, starches, and cellulose. Similar substrates to obtain polyols are chitosans. Commercially available modified chitosans are soluble in water, which gives them the possibility to react with hydroxyalkylating agents. We used a water-soluble chitosan previously to obtain polyols suitable for producing rigid polyurethane foams. Here, we described hydroxyalkylation of a low-molecular-weight chitosan (oligomeric chitosan) with glycidol and ethylene carbonate to obtain polyols. The polyols were isolated and studied in detail by IR, ¹H-NMR, and MALDI–ToF methods. Their properties, such as density, viscosity, surface tension, and hydroxyl numbers, were determined. The progress of the hydroxyalkylation reaction of water-soluble chitosan and chitosan oligomer with glycidol was compared in order to characterize the reactivity and mechanism of the process. We found that the hydroxyalkylation of chitosan with glycidol in glycerol resulted in the formation of a multifunctional product suitable for further conversion to polyurethane foams with favorable properties. The straightforward hydroxyalkylation of chitosan with glycidol was accompanied by the oligomerization of glycidol. The hydroxyalkylation of chitosan with glycidol in the presence of ethylene carbonate was accompanied by minor hydroxyalkylation of chitosan with ethylene carbonate. The chosen polyols were used to obtain rigid polyurethane foams which were characterized by physical parameters such as apparent density, water uptake, dimension stability, heat conductance, compressive strength, and heat resistance at 150 and 175 °C. The properties of polyurethane foams obtained from chitosan-oligomer and water-soluble-chitosan sources were compared. Polyurethane foams obtained from polyols synthesized in the presence of glycerol had advantageous properties such as low thermal conductivity, enhanced thermal resistance, dimensional stability, low water uptake, and high compressive strength, growing remarkably upon thermal exposure. Full article

The 5-(3-hydroxy)phenylmorphan structural class of compounds are unlike the classical morphinans, 4,5-epoxymorphinans, and 6,7-benzomorphans, in that they have an equatorially oriented aromatic ring rather than the axial orientation of that ring found in the classical opioids. This modified and simplified opioid-like structure has been shown to retain antinociceptive activity, depending on its stereochemistry and substituents, and some of them have been found to be much more potent than morphine. A simple C9-hydroxy-5-(3-hydroxy)phenylmorphan enantiomer was found to be about 500 times more potent than morphine in vivo. We have previously examined C9-alkenyl and hydroxyalkyl substituents in the N-phenethyl-5-(3-hydroxy)phenylmorphan class of compounds. Comparable C9-alkyl (methyl through butyl) substituents, with their sets of diastereomers, have not been explored. All these compounds have now been synthesized to determine the effect chain-length and stereochemistry at the C9 position in the molecule might have on their interaction with opioid receptors. We now report the synthesis and in vitro activity of 16 compounds, the C9-methyl, ethyl, propyl, and butyl diastereomers, using the inhibition of forskolin-induced cAMP accumulation assay. Several potent (sub-nanomolar and nanomolar) MOR compounds were found to be selective agonists with varying efficacy. Of greatest interest, a selective MOR antagonist was discovered; it did not display any DOR or KOR agonist activity in vitro, was three times more potent than naltrexone, and was found to antagonize the EC90 of fentanyl at MOR to a greater extent than naltrexone. Full article

All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the 12 diastereomers, 21 (3-((1S,5R,9R)-9-(2-hydroxyethyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol), was a MOR partial agonist with good, but not full, efficacy (E_max = 85%) and subnanomolar potency (EC₅₀ = 0.91 nM) in the cAMP assay. It did not have any KOR agonist activity. This compound was unlike morphine in that it had a limited ventilatory effect in vivo. The activity of 21 could be related to one or more of three well-known theories that attempt to predict a dissociation of the desired analgesia from the undesirable opioid-like side-effects associated with clinically used opioids. In accordance with the theories, 21 was a potent MOR partial agonist, it was highly G-protein biased and did not attract beta-arrestin2, and it was found to have both MOR and DOR agonist activity. All the other diastereomers that were synthesized were either much less potent than 21 or had either too little or too much efficacy for our purposes. It was also noted that a C9-methoxymethyl compound with 1R,5S,9R stereochemistry (41) was more potent than the comparable C9-hydroxymethyl compound 11 (EC₅₀ = 0.65 nM for 41 vs. 2.05 nM for 11). Both 41 and 11 were fully efficacious. Full article

Interaction of [VO(OiPr)₃] with 6-bis(o-hydroxyaryl)pyridine, 2,6-{HOC(Ph)₂CH₂}₂(NC₅H₃), LH₂, afforded [VO(OiPr)L] (1) in good yield. The reaction of LNa₂, generated in-situ from LH₂ and NaH, with [VCl₃(THF)₃] led to the isolation of [VL₂] (2) in which the pyridyl nitrogen atoms are cis; a regioisomer 3∙2THF, in which the pyridyl nitrogen atoms are trans, was isolated when using [VCl₂(TMEDA)₂]. The reaction of the 2,6-bis(o-hydroxyalkyl)pyridine {HOC(iPr)₂CH₂}₂(NC₅H₃), L¹H₂, with [VO(OR)₃] (R = nPr, iPr) led, following work-up, to [VO(OR)L¹] (R = nPr (4), iPr (5)). Use of the bis(methylpyridine)-substituted alcohol (tBu)C(OH)[CH₂(C₅H₃Me-5)]₂, L²H, with [VO(OR)₃] (R = Et, iPr) led to the isolation of [VO(μ-O)(L²)]₂ (6). Complexes 1 to 6 have been screened for their ability to act as pre-catalysts for the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL), and rac-lactide (r-LA) and compared against the known catalyst [Ti(OiPr)₂L] (I). Complexes 1, 4–6 were also screened as catalysts for the polymerization of ethylene (in the presence of dimethylaluminium chloride/ethyltrichloroacetate). For the ROP of ε-CL, in toluene solution, conversions were low to moderate, affording low molecular weight products, whilst as melts, the systems were more active and afforded higher molecular weight polymers. For δ-VL, the systems run as melts afforded good conversions, but in the case of r-LA, all systems as melts exhibited low conversions (<10%) except for 6 (<54%) and I (<39%). In the case of ethylene polymerization, the highest activity (8600 Kg·mol·V⁻¹bar⁻¹h⁻¹) was exhibited by 1 in dichloromethane, affording high molecular weight, linear polyethylene at 70 °C. In the case of 4 and 5, which contain the propyl-bearing chelates, the activities were somewhat lower (≤1500 Kg·mol·V⁻¹bar⁻¹h⁻¹), whilst 6 was found to be inactive. Full article