Benzyl Alcohol Derivatives Research Articles

Synthesis of β-lactams and transformation to β-amino acid ethyl ester derivatives: Theoretical calculations

Because of the important biological properties of β-amino acids in the present work, two new β-amino acid ethyl ester derivatives were synthesized, and their mechanistic occurrence was investigated. The title compounds were synthesized from related tetralone derivatives containing bromine and methoxy groups. Tetralone derivatives were reduced to their benzyl alcohol derivatives with NaBH4, followed by elimination with p-toluenesulfonic acid (pTSA) to give the desired 1,2-dihydronaphthalene derivatives. The reactions of 1,2-dihydronaphthalenes with chlorosulfonyl isocyanate (CSI) afforded β-lactams. β-Amino acids were obtained from the reaction of β-lactams with EtOH in HCl. Computational studies are concerned with synthesizing four-membered lactams (β-lactam) formed by the reaction between 1,2-dihydronaphthalene derivatives and CSI. The mechanism of the formation of compounds has been elucidated using DFT at M06-2X.

Pd(0)/Xantphos-Catalyzed Benzylic C(sp3)-O Arylation of Benzyl Heteroaryl Ethers: Reduction of Pd(II) to Pd(0) by Xantphos.

Herein, we report the synthesis of 1,1-diarylmethanes via palladium-catalyzed benzylic C(sp3)-O arylation of benzyl alcohol derivatives. An efficient, straightforward approach to synthesizing Pd(0)(xantphos)2 was developed through in situ reduction of Pd(II) to Pd(0) with the bidentate tertiary phosphine xantphos, which proved to be a highly active precatalyst in the Suzuki-Miyaura cross-coupling reaction of benzyl heteroaryl ethers.

Designing Cobalt(II) Complex for Chemoselective Synthesis of 2-Aryl-3-Formyl Indoles from Amino Alcohols and Alcohols†.

An air-stable, inexpensive, and isolable cobalt(II) complex (C1) of N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(phenylselanyl)ethan amine (L1) was synthesized and characterized. The complex was used to catalyze a one-pot cascade reaction between 2-(2-aminophenyl)ethanols and benzyl alcohol derivatives. Interestingly, 2-aryl-3-formylindole derivatives were formed instead of N-alkylated or C-3 alkylated indoles. A broad substrate scope can be activated using this protocol with only 5.0 mol % catalyst loading to achieve up to 87 % yield of 2-aryl-3-formylindole derivatives. The mechanistic studies suggested that the reaction proceeds through tandem imine formation followed by cyclization.

Polygonal mesopores microflower catalysts for the catalytic oxidation of 2-nitro-4-methylsulfonyltoluene to 2-nitro-4-methylsulfonylbenzoic acid in a continuous-flow microreactor

The development of efficient systems for the catalytic oxidation of 2-nitro-4-methylsulfonyltoluene (NMST) to 2-nitro-4-methylsulfonyl benzoic acid (NMSBA) with atmospheric air or molecular oxygen in alkaline medium presents a significant challenge for the chemical industry. Here, we report the synthesis of FeOOH/Fe3O4/MOF polygonal mesopores microflower templated from a MIL-88B(Fe) at room temperature, which exposes polygonal mesopores with atomistic edge steps and lattice defects. The obtained FeOOH/Fe3O4/MOF catalyst was adsorbed onto glass beads and then introduced into the microchannel reactor. In the alkaline environment, oxygen was used as oxidant to catalyze the oxidation of NMST to NMSBA, showing impressive performance. This sustainable system utilizes oxygen as a clean oxidant in an inexpensive and environmentally friendly NaOH/methanol mixture. The position and type of substituent critically affect the products. Additionally, this sustainable protocol enabled gram-scale preparation of carboxylic acid and benzyl alcohol derivatives with high chemoselectivities. Finally, the reactions can be conducted in a pressure reactor, which can conserve oxygen and prevent solvent loss. Moreover, compared with the traditional batch reactor, the self-built microchannel reactor can accelerate the reaction rate, shorten the reaction time and enhance the selectivity of catalytic oxidation reactions. This approach contributes to environmental protection and holds potential for industrial applications.

Manganese‐Catalyzed α‐Alkylation of Sulfones using Alcohols via a Hydrogen‐Borrowing Strategy: Synthesis of Branched Sulfones

AbstractHerein, we report an efficient and sustainable manganese‐catalyzed α‐C−H bond alkylation methodology to synthesize branched sulfones via a hydrogen borrowing pathway. The air‐stable and phosphine‐free Mn‐catalyst, (NNN)Mn(II)Cl2 was synthesized by using an earth‐abundant, commercially available, and inexpensive precursor MnCl2.4H2O, and a stable NNN pincer i. e. [N‐((benzimidazole‐2‐yl)methyl)quinoline‐8‐amine] ligand system. Taking benzyl phenyl sulfones as substrates, and benzyl alcohol derivatives as alkylating agents, a range of branched sulfones were synthesized in 40–82 % isolated yields using (NNN)Mn(II)Cl2 complex as the catalyst under open‐air conditions. Control experiments and deuterium incorporation studies have also been conducted to investigate the possible reaction mechanism and to provide evidence for the hydrogen borrowing pathway.

Silver‐doped rutile TiO2 nanotubes synthesis. First insights into selective photo‐oxidation of benzyl alcohol derivatives under visible light

AbstractThe synergistic effect between rutile TiO2 nanotubes and silver nanoparticles on the surface was studied. For that purpose, rutile TiO2 nanotubes were elaborated by a hydrothermal method, doped with silver by a wetness impregnation approach and fully characterized. The as synthesized material showed an improved photocatalytic activity, compared with bare rutile nanotubes, which was correlated to the changes in the optical, structural, and textural properties associated with the variation of silver amount. The photocatalytic activity of the as‐prepared catalysts was evaluated into the oxidation of different benzyl alcohol derivatives under visible light.

Highly efficient magnetically separable SrFe12O19 for photo-assisted oxidation of benzylic alcohol derivatives under visible light

The selective oxidation of the Cα−OH group of benzylic alcohols is a crucial process for the conversion of lignin into useful products. In this study, we describe the synthesis and characterization of magnetic strontium hexaferrite, SrFe12O19. The SrFe12O19 nano-powder was produced through coprecipitation at a pH level of 10. The catalyst has been studied using various methods such as X-ray diffraction (XRD), scanning electron microscopy (SEM) combined with energy-dispersive X-ray analysis (EDX), UV–vis diffuse reflectance spectroscopy (DRS), and magnetic field dependence measurements. The study aimed to evaluate the photocatalytic performance of SrFe12O19 in selective oxidation of benzylic alcohols and degradation of methylene blue under visible light. Additionally, the magnetic properties of the catalyst were also investigated. Magnetic properties were also investigated. M-SrFe12O19 with a band near 2 eV, showed excellent photocatalytic degradation performance at ca. 90% of MB under visible light. The photocatalytic degradation activity was evaluated for three cycles, and the results demonstrate that it maintains its photodegradation potency, with significant photo-degradation conversion of 89%, 87%, and 84%. The experiment clearly demonstrated that the reaction kinetics followed a pseudo-first order. The oxidation of benzyl alcohol (BzOH) was successfully carried out over SrFe12O19 in the presence of hydrogen peroxide, a highly effective green oxidant, under visible light. Notably, the experiment results showed a maximum conversion of BzOH, reaching approximately 70%, with absolute selectivity towards benzaldehyde (BzCHO). Furthermore, the yield of aldehyde increases according to the Hammett constant, with the highest yield being obtained for 2-hydroxybenzaldehyde (σ = −0.37). The synthesized M-SrFe12O19 material shows potential as an eco-friendly method for lignin valorization.

Exploring the Intricacies and Functionalities of Galactose Oxidase: Structural Nuances, Catalytic Behaviors, and Prospects in Bio-electrocatalysis

Galactose Oxidase, also known as GOase, is an enzyme found mostly in Fusarium graminearum, Dactylium dendroides, and Gibberella fujikuroi. GOase, containing copper, serves catalytic functions in oxidizing substrates and primary alcohols such as d-galactose, benzyl alcohol derivatives, and dihydroxyacetone. The catalytic property of galactose oxidase that differentiates it from other enzymes is its cofactor consisting of a Cu (II)-bound Cys-Tyr* radical. The cofactor is vital for enabling regioselective oxidation. The application of galactose oxidase (GOase) covers several fields such as enzymatic synthesis, biosensors development, and processes of diagnosis.
 Galactose oxidase (GOase) was discovered to have a crystallographic structure by X-ray diffraction, which revealed an active site containing copper ions displaying relatively square pyramidal geometry. There are three unique structural and functional domains of the enzyme GOase. The domains include Tyr495 and a covalent bond between Cys228 and Tyr272 serving as equatorial and axial ligands, respectively. The mechanism of catalysis covers three different oxidation states, which include the active state containing Cu (II)-radical, the intermediate state containing Cu (II)-tyrosine, and the Cu(I)-tyrosine state. The cycle of catalysis that has been posited comprises several phases which are: (i) substrate binding, (ii) the transfer of proton (iii) the transfer of hydrogen atom, and (iv) subsequent oxidation steps. These phases eventually yield the synthesis of aldehyde and hydrogen peroxide.
 Galactose oxidase’s (GOase) mechanism of catalysis has been studied thoroughly via extensive research focusing on explaining the ping-pong mechanism that occurs in both oxidative and reductive half-reactions. The processes of activating and reactivating galactose (GOase) involve the transfer of electrons in which horseradish peroxidase (HRP) serves as an activator. The electrochemical investigations provide evidence of the electrochemical activation and reactivation of GOase in the presence of mediators.
 This comprehensive review enhances the comprehension of the structural complexities, catalytic mechanisms, and bio-electrocatalytic potential of GOase, thereby establishing a basis for future investigations and developments in technology.

Meta-C-H functionalization of phenylethyl and benzylic alcohol derivatives via Pd/NBE relay catalysis.

The transition metal-catalyzed meta-C-H functionalization of alcohols and their hydroxylamine derivatives remains underdeveloped. Herein, we report an efficient meta-C-H arylation of both phenylethyl and benzylic alcohols and their hydroxylamine derivatives using a readily removable oxime ether directing group. Using electronically activated 2-carbomethoxynorbornene as the transient mediator and 3-trifluoromethyl-2-pyridone as the enabling ligand, this reaction features a broad substrate scope and good functional group tolerance. More importantly, with this oxime-directed meta-C-H functionalization, this method provides a dual approach for efficient access to both meta-substituted alcohols and hydroxylamines using two sets of simple deprotection conditions. This protocol leads to the efficient synthesis of bioactive compounds possessing promising reactivities for the treatment of pulmonary fibrosis.

Synthesis, Antibacterial Activity and Molecular Modelling of Benzyl Acetate Derivatives

Benzyl alcohol derivatives are known for their antibacterial efficacy. In this work five known benzyl acetate derivatives were synthesized by the acetylation of their corresponding benzyl alcohol derivatives and their structures confirmed using 1H, 13C NMR and FTIR spectroscopic techniques. The synthesized compounds were tested for antibacterial activity against Staphylococcus aureus and Shigella spp using disc diffusion method. Also the activity of amoxicillin disc (0.5 g/L ) was measured as a positive control. Furthermore, the drug-likeness as well as the interactions of the compounds against the active site of E. coli carbonic anhydrase which share >98% similarity to that of S. spp were studied using molecular modelling method. The antibacterial activity showed that all the five compounds 3a-e inhibited the two organisms at 100 µg/ml compared to the positive control. The largest inhibition zones of Staphylococcus aureus and Shigella spp were found to be 16.5 mm and 17.5 mm for compound 3d and 3e, respectively. Molecular modelling predicted the compounds to be water soluble, highly absorbed through GI tract, not Pgp substrates and not CYP3A4 inhibitors. Molecular docking studies showed that the compounds showed affinity to E. coli carbonic anhydrase active site, blocking access to the Zn2+ cofactor.

Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives.

ConspectusNickel-catalyzed reactions of alkyl alcohol derivatives leverage the high prevalence of hydroxyl groups in natural products, medicinal agents, and synthetic intermediates to provide access to C(sp3)-rich frameworks. This Account describes our laboratory's development of stereospecific and stereoconvergent C-C bond forming reactions employing C(sp3)-O and C(sp3)-N electrophiles. In the context of development of new transformations, we also define fundamental characteristics of the nickel catalysts.Part I details the nickel-catalyzed cross-coupling reactions developed by our group which hinges on stereospecific formation of stable π-benzyl intermediates. Acyclic and cyclic ethers, esters, carbamates, lactones, and sulfonamides undergo Kumada-, Suzuki-, and Negishi-type coupling reactions to produce enantioenriched products with high fidelity of stereochemical information. We describe extension to include ring-opening reactions of saturated heterocycles to afford acyclic 1,3-fragments in high diastereomeric ratios. We also describe our advances in stereospecific nickel-catalyzed cross-electrophile coupling reactions. Tethered C-O and C-X electrophiles proved fruitful for construction of a variety of carbocyclic frameworks. We report an intramolecular cross-electrophile coupling of benzylic pivalates with aryl bromides for the synthesis of indanes and tetralins. We found that 4-halotetrahydropyrans and 4-halopiperidines readily undergo stereospecific ring contraction to afford substituted cyclopropanes. Mechanistic investigations are consistent with closed-shell intermediates, a Ni(0)/Ni(II) cycle, and an intramolecular SN2-type reaction of a key organonickel intermediate to form the cyclopropane. Building toward more complex cascade reactions, we have demonstrated that 2-alkynyl piperidines incorporate MeMgI in a dicarbofunctionalization of the alkyne to afford highly substituted vinyl cyclopropanes.In Part II we present our development of stereoconvergent reactions of alkyl alcohol derivatives. In order to expand the utility of the intramolecular XEC reaction, we sought to employ unactivated alkyl electrophiles. Specifically, alkyl dimesylates engage in intramolecular XEC reactions to form alkyl cyclopropanes. In contrast to our previous work, these reactions proceed through open-shell intermediates and favor stereoconvergent formation of the trans-cyclopropane. Enantioselective aldol reactions can be employed in syntheses of 1,3-diols which furnish enantioenriched cyclopropanes in high ee. Experimental and computational evidence reveals that MeMgI mediates formation of alkyl iodides in situ. The coupling reaction initiates with halogen atom abstraction at the secondary alkyl iodide. The alkyl Ni(II) complex then proceeds through a stereospecific SN2-type ring closure to form cyclopropane. In an effort to increase functional group compatibility in the synthesis of cyclopropanes from alkyl dimesylates we developed a zinc-mediated reaction of 1,3-dimesylates prepared from medicinal analogues. In challenging nickel-catalyzed intramolecular cross-electrophile coupling we were also able to show that vicinal carbocycles can be prepared under similar conditions, affording vicinal cyclopentyl-cyclopropyl motifs in high yield.In Part III we discuss our recent findings on the role of ligand identity in catalyst selectivity for stereospecific vs stereoablative mechanisms for oxidative addition. We demonstrate multivariable control of mechanism, where the choice of substrate and ligand work together to promote open- or closed-shell intermediates. In divergent reactions of 4-halotetrahydropyrans we observe distinct ligand preference for reactions at the C(sp3)-O center or the C(sp3)-Cl center. These findings are the source of continued investigations in our laboratory.

Light-induced reduction of aryl ketones and aldehydes via Meerwein-Ponndorf-Verley-type reaction with isopropanol under Mild reaction conditions

In the realm of green chemistry, the quest for increasingly eco-friendly and economically viable methods for the transformation of aldehydes and ketones into alcohols assumes critical importance. In the present study, we introduce an innovative approach that enables the direct and light-induced reduction of aldehydes and ketones to alcohols. This method harnesses isopropanol, serving the dual role of both the reaction solvent and reducing agent, in conjunction with t-BuOK. This operationally straightforward, light-promoted strategy follows the Meerwein-Ponndorf-Verley reduction pathway and demonstrates remarkable efficacy in the synthesis of diverse benzylic alcohol derivatives.

Exploring Benzyl Alcohol Derivatives and Related Compounds in the Cleaning of Oil Paintings

ABSTRACT This study examines five benzyl alcohol derivatives and three chemically similar compounds and compares them against benzyl alcohol in gelled emulsions for the removal of overpaint during cleaning of oil paintings. Comparative cleaning tests using xanthan gels, Pemulen® TR-2 gels, and neat solvent were made on overpaint on fragments of a seventeenth-century test painting. This approach demonstrated that molecular changes to a benzyl alcohol core resulted in enhanced control during the cleaning process. In some cases a benzyl alcohol derivative enabled selective removal of non-original material, when benzyl alcohol appeared to affect the original paint. Select derivatives were also tested in an area of overpaint on a sixteenth-century oil on panel painting by Jan van Scorel in the Rijksmuseum Collection through modifying the chemical activity of benzyl alcohol. Finally, two GC-MS-based methods were used to monitor benzyl alcohol retention and possible oxidation in paint layers post-treatment.

Visible-Light-Photoexcited Palladium-Catalyzed Silylmethylation of Benzyl Alcohol Derivatives

AbstractAn intramolecular C–H silylmethylation of benzylic alcohol derivatives catalyzed by a visible-light-photoexcited palladium complex was developed. Irradiation of the palladium complex with blue LEDs resulted in efficient activation of a C–I bond, and subsequent intramolecular radical arylation afforded siloxacycle products. Selective protonation or oxidation of the C–Si bond of the cyclized materials afforded ortho-methylated and ortho-hydroxymethylated derivatives of the benzylic alcohol derivatives.

Microwave-Assisted Synthesis of E-Aldimines, N-Heterocycles, and H2 by Dehydrogenative Coupling of Benzyl Alcohol and Aniline Derivatives Using CoCl2 as a Catalyst.

The acceptorless dehydrogenative coupling (ADC) between alcohols and amines to produce imines has been achieved mostly by employing precious-metal-based complexes or complexes of earth-abundant metal ions with sensitive and complicated ligand systems as catalysts mostly under harsh reaction conditions. Methodologies using readily available earth-abundant metal salts as catalysts without the requirement of ligand, oxidant, or any external additives are not explored. We report an unprecedented microwave-assisted CoCl2-catalyzed acceptorless dehydrogenative coupling of benzyl alcohol and amine for the synthesis of E-aldimines, N-heterocycles, and H2 under mild condition, without any complicated exogenous ligand template, oxidant, or other additives. This environmentally benign methodology exhibits broad substrate scope (43 including 7 new products) with fair functional-group tolerance on the aniline ring. Detection of metal-associated intermediate by gas chromatography (GC) and HRMS, H2 detection by GC, and kinetic isotope effect reveal the mechanism of this CoCl2-catalyzed reaction to be via ADC. Furthermore, kinetic experiments and Hammett analysis with variation in the nature of substituents over the aniline ring reveal the insight into the reaction mechanism with different substituents.

Manganese(I)-Pincer Catalyzed α-Alkylation of Sulfones by Alcohols

Sulfones are building blocks in organic synthesis and pharmaceutical chemistry. Direct α-alkylation of sulfones using alcohols with water as the sole byproduct is an efficient and promising method for their structural modifications. However, competitive reactions always exist in this transformation that influences the reaction selectivity. For example, in addition to the desired α-alkylation, Julia-type olefination and α-alkenylation are frequently observed, especially when benzyl alcohol derivatives were used as alkylation reagents. Herein, we report α-alkylation of sulfones using alcohols catalyzed by a pincer complex of earth-abundant manganese. The Mn-PNN-bipyridyl complex exhibited good performance in reaction selectivity. The amount of base also had an important influence on the smooth transformation. Aromatic and aliphatic alcohols are suitable alkylation reagents for sulfones at low metal catalyst loading (0.5 mol %), highlighting the practicality of the developed system.

Se and P dual doped carbon for highly selective oxidation of benzyl alcohol

Metal-free heterogeneous oxidation of alcohols to corresponding aldehydes is a typical green selective oxidation reaction. Rational designing of the metal-free catalyst is highly desired. In the present work, P and Se dual doped carbon catalyst was prepared to achieve a high catalytic efficiency for the selective oxidation of benzyl alcohols to benzaldehyde. The doped P and Se exhibited a synergistic effect for enhancing the titled catalytic performance. The doped P can donate electrons to the adjacent atoms while the doped Se can accept electrons from the adjacent atoms. These interactions accelerated the electron transfer on the carbon surface and consequently enhanced the catalytic activity. Kinetic study revealed that the selectivity was kinetically improved by the doped heteroatoms. The oxidation mechanism investigation indicated that both radical and nonradical routes were involved in the titled reaction. In addition, the dual doped carbon catalyst also showed a good catalytic performance for the various benzyl alcohol derivatives. These finding suggest that the dual doped atoms are promising strategy to improve the catalytic activity and selectivity of the carbon-based metal-free catalysts for the aerobic selective oxidation reactions.

Fabrication of immobilized molybdenum complex on functionalized graphene oxide as a novel catalyst for the synthesis of benzothiazoles

This paper presented a novel amino-modified nano-graphene oxide supported thiophene-2-carbaldehyde Mo-complex (Mo(TC)/GO) catalyst prepared and characterized by FT-IR, SEM, TEM, TGA, EDX, BET, XRD, and N2 adsorption–desorption techniques. The catalyst presented an outstanding performance for synthesizing benzothiazole derivatives through a reaction between benzyl alcohol derivatives and 2-aminothiophenol. The heterogeneous catalyst could be facial separated and reused by filtration without any substantial decline in its catalytic activity even after five runs.

Manganese-Catalyzed Chemoselective Coupling of Secondary Alcohols, Primary Alcohols and Methanol.

Herein, we report a manganese-catalyzed three-component coupling of secondary alcohols, primary alcohols and methanol for the synthesis of β,β-methylated/alkylated secondary alcohols. Using our method, a series of 1-arylethanol, benzyl alcohol derivatives, and methanol undergo sequential coupling efficiently to construct assembled alcohols with high chemoselectivity in moderate to good yields. Mechanistic studies suggest that the reaction proceeds via methylation of a benzylated secondary alcohol intermediate to generate the final product.

Manganese‐Catalyzed Chemoselective Coupling of Secondary Alcohols, Primary Alcohols and Methanol

AbstractHerein, we report a manganese‐catalyzed three‐component coupling of secondary alcohols, primary alcohols and methanol for the synthesis of β,β‐methylated/alkylated secondary alcohols. Using our method, a series of 1‐arylethanol, benzyl alcohol derivatives, and methanol undergo sequential coupling efficiently to construct assembled alcohols with high chemoselectivity in moderate to good yields. Mechanistic studies suggest that the reaction proceeds via methylation of a benzylated secondary alcohol intermediate to generate the final product.