Phenyl Benzoate Research Articles

Zeolite Catalysts for Phenol Benzoylation with Benzoic Acid: Exploring the Synthesis of Hydroxybenzophenones

In this paper, we report on the reaction of phenol benzoylation with benzoic acid, which was carried out in the absence of solvent. The aim of this reaction is the synthesis of hydroxybenzophenones, which are important intermediates for the chemical industry. H-beta zeolites offered superior performance compared to H-Y, with a remarkably high conversion of phenol and high yields to the desired compounds, when using a stoichiometric amount of benzoic acid. It was found that the reaction mechanism did not include the intramolecular Fries rearrangement of the primary product phenyl benzoate, but indeed, the bimolecular reaction between phenyl benzoate and phenol mainly contributed to the formation of hydroxybenzophenones. The product distribution was greatly affected by the presence of Lewis-type acid sites in H-beta; it was suggested that the interaction between the aromatic ring and the electrophilic Al3+ species led to the preferred formation of o-hydroxybenzophenone, because of the decreased charge density on the C atom at the para position of the phenolic ring. H-Y zeolites were efficient than H-beta in phenyl benzoate transformation into hydroxybenzophenones.

Remoldable Crosslinked Liquid-Crystalline Polysiloxane with Side Chain Mesogens Based on Exchangeable Crosslinks

Crosslinked liquid-crystalline polymers (CLCPs) show unique behavior of deforming macroscopically when stimulated with heat, electricity and light. However, they cannot be remolded and reshaped once prepared. Here, we designed crosslinked polysiloxane with side chain mesogens that contain exchangeable crosslinking points based on transesterification between phenyl benzoates and hydroxy groups. After the formation of a polymer network, a base catalyst was introduced into the CLCP. When heated at 80°C, a piece of the CLCP was reshaped into a film and separate pieces of the CLCP were fused together, indicating that the CLCP is remoldable.

Acylation of piperidine and morpholine with phenyl benzoates in the mixtures water-2-propanol and water-dioxane

Kinetics of acylation of piperidine and morpholine with 4-nitro- and 2,6-dinitrophenyl benzoates was studied in binary systems water-2-propanol and water-dioxane. Structural and energy characteristics of solvate complexes of morpholine and piperidine with the components of the mixed solvents were calculated. Kinetic regularities of acylation are considered from the viewpoint of specific solvation of amines.

A first continuous 4-aminoantipyrine (4-AAP)-based screening system for directed esterase evolution.

Esterases hydrolyze ester bonds with an often high stereoselectivity as well as regioselectivity and are therefore industrially employed in the synthesis of pharmaceuticals, in food processing, and in laundry detergents. Continuous screening systems based on p-nitrophenyl- (e.g., p-nitrophenyl acetate) or umbelliferyl-esters are commonly used in directed esterase evolution campaigns. Ongoing challenges in directed esterase evolution are screening formats which offer a broad substrate spectrum, especially for complex aromatic substrates. In this report, a novel continuous high throughput screening system for indirect monitoring of esterolytic activity was developed and validated by detection of phenols employing phenyl benzoate as substrate and p-nitrobenzyl esterase (pNBEBL from Bacillus licheniformis) as catalyst. The released phenol directly reacts with 4-aminoantipyrine yielding the red compound 1,5-dimethyl-4-(4-oxo-cyclohexa-2,5-dienylidenamino)-2-phenyl-1,2-dihydro-pyrazol-3-one. In this continuous B. licheniformis esterase activity detection system (cBLE-4AAP), the product formation is followed through an increase in absorbance at 509 nm. The cBLE-4AAP screening system was optimized in 96-well microtiter plate format in respect to standard deviation (5 %), linear detection range (15 to 250 μM), lower detection limit (15 μM), and pH (7.4 to 10.4). The cBLE-4AAP screening system was validated by screening a random epPCR pNBEBL mutagenesis library (2000 clones) for improved esterase activity at elevated temperatures. Finally, the variant T3 (Ser378Pro) was identified which nearly retains its specific activity at room temperature (WT 1036 U/mg and T3 929 U/mg) and shows compared to WT a 4.7-fold improved residual activity after thermal treatment (30 min incubation at 69.4 °C; WT 170 U/mg to T3 804 U/mg).

Kinetic Study on Alkaline Hydrolysis of Y‐substituted Phenyl Picolinates: Effects of Modification of Nonleaving Group from Benzoyl to Picolinyl on Reactivity and Reaction Mechanism

Second‐order rate constants (k OH–) for alkaline hydrolysis of Y‐substituted phenyl picolinates (6a–6i) have been measured spectrophotometrically. A linear Brønsted‐type plot is obtained with βlg = −0.34, which is typical for reactions reported previously to proceed through a stepwise mechanism with formation of an addition intermediate being the rate‐determining step (RDS). However, constants result in a much poorer Hammett correlation than constants. Furthermore, the Yukawa‐Tsuno plot exhibits an excellent linear correlation with ρ Y = 0.82 and r = 0.72, indicating that a negative charge develops partially on the O atom of the leaving group in the RDS. Thus, the reactions have been concluded to proceed through a forced concerted mechanism with a highly unstable intermediate 7. Comparison of the current kinetic data with those reported previously for the corresponding reactions of Y‐substituted phenyl benzoates has revealed that modification of the nonleaving group from benzoyl to picolinyl causes not only an increase in reactivity but also a change in the reaction mechanism (i.e., from a stepwise mechanism to a forced concerted pathway).

Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents.

New Mannich base-type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4-allyl-2-methoxy-6-(morpholin-4-ylmethyl) phenyl benzoate (7) and 4-{5-allyl-2-[(4-chlorobenzoyl)oxy]-3-methoxybenzyl}morpholin-4-ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C.glabrata (1.23μm), C.albicans and C.krusei (both 0.63μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.

Interfacing supercritical fluid reaction apparatus with on-line liquid chromatography: Monitoring the progress of a synthetic organic reaction performed in supercritical fluid solution

An interface has been developed that connects a supercritical fluid reaction (SFR) vessel directly on-line to a liquid chromatograph. The combined SFR-LC system has enabled the progress of the esterification reaction between phenol and benzoyl chloride to synthesize phenyl benzoate in supercritical fluid carbon dioxide solution to be dynamically monitored. This was achieved by the periodic SFR-LC analysis of samples directly withdrawn from the esterification reaction mixture. Using the series of SFR-LC analysis results obtained for individual esterification reactions, the reaction progress profile for each esterification reaction was obtained by expressing the measured yield of phenyl benzoate as a function of reaction time. With reaction temperature fixed at 75°C, four sets (n=3) of SFR-LC reaction progress profiles were obtained at four different SFR pressures ranging from 13.79 to 27.58MPa. The maximum SFR yield obtained for phenyl benzoate using a standard set of reactant concentrations was 85.2% (R.S.D. 4.2%) when the reaction was performed at 13.79MPa for 90min. In comparison, a phenyl benzoate yield of less than 0.3% was obtained using the same standard reactant concentrations after 90min reaction time at 75°C using either: heptane, ethyl acetate or acetonitrile as conventional organic reaction solvents.

Phenyl benzoate derivatives with anisotropic molecular structure as stabilizers for formulations based on plasticized polyvinyl chloride

The photo- and thermostabilizing performance of nine phenyl benzoate derivatives with chemically active terminal substituents in formulations based on plasticized polyvinyl chloride was studied. The substituted phenyl benzoates exhibit thermal activity allowing them to withstand without decomposition the temperatures at which the polymeric formulations are processed. The potential stabilizers studied are capable of shielding the polymeric matrix from the most hazardous UV radiation. The plasticized polyvinyl chloride film samples stabilized with anisotropic phenyl benzoates surpass in the thermal stability the samples containing commercial stabilizers and exhibit good physicomechanical characteristics.

Novel antidepressant candidate RO-05 modulated glucocorticoid receptors activation and FKBP5 expression in chronic mild stress model in rats

In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) was investigated in TST (tail suspension test), FST (forced swimming test) and CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the behavioral index, anhedonia and normalized the hyperactivity of HPA (hypothalamic–pituitary–adrenal axis) of CMS rats. We further investigated the possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram of RO-05 chronic administration significantly reversed the increase of mRNA and protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 expression. RO-05 also elevated the expression of BDNF (brain-derived neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated that RO-05 is a promising antidepressant candidate. The possible antidepressant mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF expression.

Synthesis and Molecular Structure of 2-(Diphenylphosphano)phenyl Benzoate Borane Adduct

The crystal and molecular structure of 2-(diphenylphosphano)phenyl benzoate borane adduct are reported. The title compound crystallizes from a petroleum ether/ethyl acetate mixture in the triclinic space group P with two molecules in the unit cell. The unit cell parameters are: a = 8.67(1) Å, b = 9.202(1) Å, c = 14.224(2) Å; α = 72.600(7)°, β = 73.577(7)°, γ = 84.349(7)° and V = 1039.5(2) Å3. Bond lengths and angles are typical for this phosphane borane adduct.

Alkenyl-substituted methacrylates as bifunctional monomers in radical polymerization

This paper addresses the radical polymerization of dimethacryloyl monomers with double bonds of different activities. The preferential selective polymerization via methacrylate groups of bifunctional monomers with phenyl, phenyl benzoate, and biphenyl benzoate aromatic “cores” in the presence of less active methacrylamide double bonds is studied. It is shown that the initiated radical polymerization of the dimethacryloyl monomers in dimethylformamide at small conversions makes it possible to prepare soluble polymeric products containing free methacrylamide-methacrylate groups. The molar ratio of these methacrylamide-methacrylate groups depends on reactivity ratios r1 and r2 of the double bonds of different activities in the bifunctional monomers and on the conversions of the monomers.

Crystal structure of 3-({[(morpholin-4-yl)carbono-thio-yl]sulfan-yl}acet-yl)phenyl benzoate.

In the title compound, C20H19NO4S2, the morpholine ring adopts the expected chair conformation. The central phenyl ring makes dihedral angles of 67.97 (4) and 7.74 (3)°, respectively, with the benzoate phenyl ring and the morpholine mean plane. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming zigzag chains along the b-axis direction. C-H⋯π inter-actions link centrosymmetrically related mol-ecules, reinforcing the three-dimensional structure.

In vitro and in vivo characterization of PA01, a novel promising triple reuptake inhibitor

Triple reuptake inhibitors (TRIs) that inhibit the reuptake of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) are being developed as a new class of antidepressants, which is hypothesized to produce more rapid onset and better efficacy than conventional antidepressants in part due to the addition of the DA component. 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)-ethyl]-phenyl benzoate hydrochloride (PA01), a novel compound, potently bound to the human 5-HT, NE, and DA transporters (Ki=105, 644, and 813nM, respectively), and inhibited the reuptake of 5-HT, NE, and DA into recombinant cells (IC50=341, 427, and 753nM, respectively). In vivo, PA01 dose-dependently decreased immobility time in the forced swimming test (FST) in rats, and the tail suspension test (TST) in mice with higher efficacy than desvenlafaxine succinate (DVS), and showed no stimulatory effect on the spontaneous locomotor activity. The anti-immobility effect of PA01 in the TST was significantly prevented by the pretreatment of mice with DL-p-chlorophenylalanine (pCPA, 300mg/kg, an inhibitor of serotonin synthesis), SCH23390 (0.05mg/kg, s.c., dopamine D1 receptor antagonist), and sulpiride (50mg/kg, i.p., dopamine D2 receptor antagonist). PA01 significantly increased head-twitch response induced by 5-hydroxytryptophan (80mg/kg, i.p., a metabolic precursor to serotonin) in rats, potentiated yohimbine (25mg/kg, s.c., a α2-adrenoceptor antagonist) toxicity, and antagonized high dose apomorphine-induced hypothermia in mice. Taken together, these in vitro and in vivo results indicated that PA01 is a novel triple reuptake inhibitor, and exerts an excellent antidepressant activity in the behavioral despair animal models of depression, with more potent antidepressant activity than DVS at the same dose.

Semiconductor clathrates with a periodically modulated topology of a host ferroelectric liquid crystal in thermal, magnetic, and light-wave fields

The characteristics of gallium selenide with a ferroelectric liquid crystal in between its layers are studied. The liquid crystal consists of an achiral smectic (a derivative of phenyl benzoate) and a chiral component. The frequency behavior of the specific impedance, permittivity, and loss tangent at different temperatures, in a magnetic field, and under illumination are found.

ChemInform Abstract: Regioselectivity of the Palladium‐Mediated Intramolecular Coupling Reaction of Highly Oxygenated Phenyl Benzoate Derivatives and Application to the Synthesis of Altertenuol.

ChemInform Abstract: Regioselectivity of the Palladium‐Mediated Intramolecular Coupling Reaction of Highly Oxygenated Phenyl Benzoate Derivatives and Application to the Synthesis of Altertenuol.

ChemInform Abstract: Synthesis of Nigricanin via Intramolecular Biaryl Coupling Reaction of Functionalized Phenyl Benzoate.

ChemInform Abstract: Synthesis of Nigricanin via Intramolecular Biaryl Coupling Reaction of Functionalized Phenyl Benzoate.

Observation of Transient Alignment-Inversion Walls in Nematics of Phenyl Benzoates in the Presence of a Magnetic Field

Formation of new transient walls by a constant magnetic field at the Fréedericsz critical value has been observed. They are oriented along the initial alignment of the nematic phase of phenyl benzoates and appeared only in relatively thick samples with a thickness between 50 and 100 μm of the cells. The excellent planarity of the liquid crystal orientation is considered to be the most important condition for their presence These magnetic walls are transient as they disappear either after a few seconds for 100 μm thick nematic cells or after parts of a second for thinner (50 μm) nematic cells. Nonregular stable magnetic walls, incorporating disclinations with core, appear immediately after the relaxation of the transient walls, when the planarity of the nematic orientation is not perfect. In thinner nematic cells of 20 μm or less, a Fréedericksz transition has only been observed. The formation of transient magnetic walls can be described by a model taking into account alignment-inversion, twisted along Y regions. The transient walls accompanied by a system of Becke lines relax by going through three-dimensional twist-splay-bend deformations.

C–H···O and C–H···X (X = Cl/Br) hydrogen bond tuned supramolecular assembly: a combined X-ray powder diffraction and Hirshfeld surface analysis

Crystal structures of N-(2-chlorophenyl) acetamide (1) and phenyl (2-bromomethyl) benzoate (2) have been determined from laboratory X-ray powder diffraction data. In addition to intermolecular N–H···O and C–H···O hydrogen bonds, the crystal packing in (1) and (2) exhibits weak C–H···Cl/Br interactions, which facilitate formation of three-dimensional architectures. Hirshfeld surface analysis of compounds (1), (2), and a few related chloro- and bromo-phenyl derivatives retrieved from the CSD indicates that 83–97% of Hirshfeld surface areas in this class of compounds are due to H···H, H···π, H···O, and H···Cl/Br contacts.

Regioselectivity of the Palladium-Mediated Intramolecular Coupling Reaction of Highly Oxygenated Phenyl Benzoate Derivatives and Application to the Synthesis of Altertenuol

Regioselectivity of the Palladium-Mediated Intramolecular Coupling Reaction of Highly Oxygenated Phenyl Benzoate Derivatives and Application to the Synthesis of Altertenuol

Synthesis and anticancer properties of phenyl benzoate derivatives possessing a terminal hydroxyl group.

To assess the cytotoxic effects on A549 human lung cancer cells, we investigated a liquid-crystalline compound possessing a terminal hydroxyl group at concentrations of 0.1-20 μM. The compound, 4-butylphenyl 4-(6-hydroxyhexyloxy)benzoate (2), showed marked cell-growth inhibition at concentrations higher than 5 μM. Cell accumulation in the Sub-G1 phase indicating apoptosis was observed only at the highest concentration. Dynamic light scattering measurements show that the molecules form a spherical nanoparticle with a diameter of 130-170 nm at concentrations of 5-20 μM. We prepared the corresponding dimeric compounds and investigated their anticancer activity. The 1,2-benzene derivative, 1,2-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (4), exhibited cell-growth inhibition without affecting the cell cycle. However, the 1,3-benzene derivative, 1,3-bis[4-(6-hydroxyhexyloxy)benzoyloxy]benzene (5), was found to induce marked cell accumulation in the Sub-G1 phase. Furthermore, we assessed the cytotoxic effects of compounds 2, 4 and 5 on SW480 colon cancer cells and THP1 leukemic cells, as well as on WI-38 normal fibroblast cells. Both compounds 2 and 5 suppressed the growth of the solid cancer cells (A549 and SW480) more strongly compared with that of the hematological cancer cells (THP1). Unexpectedly, they also exhibited a strong cytotoxicity against the normal cells. We discuss the structure-property relationship in the anticancer activity of the mesogenic compounds.