Alcohol Research Articles

Catalyst-free synthesis of novel α-trifluoromethylated tertiary alcohols bearing azaarenes as potential antifungal agents

Herein, α-trifluoromethylated tertiary alcohols bearing azaarenes were successfully synthesized via the reaction of 2-methyl azaarenes and CF3-substituted 1,3-diols with high yields under catalyst-free, mild conditions. The antifungal activities against Gaeumannomyces graminis var tritici, Rhizoctonia cerealis, Fusarium graminearum, Rhizoctonia solani, Fusarium moniliforme, Sclerotium rolfsii Sacc were investigated. The bioassay results indicated that the antifungal activity against Gaeumannomyces graminis var tritici was obviously better compared to other five fungi and compound 3dd displayed the highest activity, with an EC50 value of 27.73 μg/mL in vitro.

Modular Synthesis of Heterobenzylic Amines via Carbonyl Azinylative Amination

AbstractTransformations enabling the synthesis of α‐alkyl, α′‐2‐azinyl amines by addition of 2‐heteroaryl‐based nucleophiles to in situ‐generated and non‐activated alkyl‐substituted iminium ions are extremely rare. Approaches involving classical 2‐azinyl organometallics, such as the corresponding Grignard reagents, often fail to produce the desired products. Here, we report an operationally straightforward solution to this problem through the development of a multicomponent coupling process wherein a soft 2‐azinyl indium nucleophile, generated in situ from the corresponding 2‐iodo heteroarene and indium powder, adds to an iminium ion that is also formed directly in the reaction. This modular carbonyl azinylative amination (CAzA) displays a broad scope and only a metal reductant is needed to generate a reactive 2‐azinyl nucleophile. Beyond the addition to iminium ions, the 2‐azinyl addition to polyfluoromethyl ketones forms the corresponding tertiary alcohols. Together, the products of these reactions possess a high degree of functionality, are typically challenging to synthesize by other methods, and contain motifs recognized as privileged in the context of pharmaceuticals and agrochemicals.

Chemoselective Synthesis of α-Tertiary Hydroxy Oximes via Photochemical 1,3-Boronate Rearrangement.

Tertiary alcohols with adjacent nucleophilic labile groups are prevalent in bioactive molecules but are challenging to synthesize. Herein we introduce a direct, protecting group-free method to access α-tertiary hydroxy oximes via photochemical 1,3-boronate rearrangement. This reaction delivers high yields (up to 94%) using readily available boronic acids, is scalable to gram quantities, and allows for further derivatization to other nitrogen-containing molecules.

Visible Light‐Switchable Lattice Oxygen Sites for Selective C−H and C(O)−C Bond Electrooxidation

Lattice‐oxygen is highly oxidizable, ideal for electrocatalytic C−H oxidation but insufficient alone for C(O)−C bond cleavage due to the non‐removable nature of lattice sites. Here, we present a visible light‐assisted electrochemical method of in‐situ formulating removable lattice‐oxygen sites in a nickel‐oxyhydroxide (ESE‐NiOOH) electrocatalyst. This catalyst efficiently converts aromatic alcohols and carbonyls with C(O)−C fragments from lignin and plastics into benzoic acids (BAs) with high yields (83–99%). Without light irradiation, ESE‐NiOOH’s intrinsic lattice‐oxygen is non‐removable and inert for C(O)−C bond cleavage. In‐situ characterizations show light‐induced lattice‐oxygen removal and regeneration via OH– refilling. Theoretical calculations identify the nucleophilic oxygen attack on ketone‐derived carbanion as a rate‐determining step, which can be remarkably facilitated by removable lattice‐oxygen to activate α‐C−H bonds. As a proof‐of‐concept, an “electrochemical funnel” strategy is developed for high‐efficiency upgrading aromatic mixtures with C(O)−C moieties into BA with up to 94% yield. This in‐situ removal‐regeneration approach for lattice sites opens an avenue for the tailored design of interfacial electrocatalysts to selectively upcycle waste carbon sources into valuable products.

Visible Light-Switchable Lattice Oxygen Sites for Selective C-H and C(O)-C Bond Electrooxidation.

Lattice-oxygen is highly oxidizable, ideal for electrocatalytic C-H oxidation but insufficient alone for C(O)-C bond cleavage due to the non-removable nature of lattice sites. Here, we present a visible light-assisted electrochemical method of in-situ formulating removable lattice-oxygen sites in a nickel-oxyhydroxide (ESE-NiOOH) electrocatalyst. This catalyst efficiently converts aromatic alcohols and carbonyls with C(O)-C fragments from lignin and plastics into benzoic acids (BAs) with high yields (83-99%). Without light irradiation, ESE-NiOOH's intrinsic lattice-oxygen is non-removable and inert for C(O)-C bond cleavage. In-situ characterizations show light-induced lattice-oxygen removal and regeneration via OH- refilling. Theoretical calculations identify the nucleophilic oxygen attack on ketone-derived carbanion as a rate-determining step, which can be remarkably facilitated by removable lattice-oxygen to activate α-C-H bonds. As a proof-of-concept, an "electrochemical funnel" strategy is developed for high-efficiency upgrading aromatic mixtures with C(O)-C moieties into BA with up to 94% yield. This in-situ removal-regeneration approach for lattice sites opens an avenue for the tailored design of interfacial electrocatalysts to selectively upcycle waste carbon sources into valuable products.

Leveraging Natural Product-Inspired Antifungals to Investigate the Mechanism of Action of Peniciaculin A.

Ubiquinone mimics known as quinone outside inhibitors (QoIs) are one of the most prominent fungicides used to protect crops in the agricultural industry. Due to chemotype similarities with known QoIs, peniciaculin A, a triaryl natural product, was proposed to exhibit similar broad spectrum antifungal activity against phytopathogens. Instability of the tertiary alcohol and phenol motif, however, prompted exploration of the antifungal properties of simplified analogues to probe possible overlap in mechanism of action between the natural product and QoIs. Peniciaculin A inspired analogues mimicking known QoI scaffolds displayed broad spectrum antifungal activity while those containing scaffolds dissimilar to QoIs possessed negligible bioactivity. These activity profiles suggest peniciaculin A is likely acting as a QoI.

Pyridine-Catalyzed Chemoselective Four-Component Cascade Reaction of Aromatic Aldehydes, Malononitrile/Cyanoacetates, MBH Carbonates, and Alcohols.

An efficient pyridine-catalyzed chemoselective four-component cascade reaction of aromatic aldehydes, malononitrile/cyanoacetates, Morita-Baylis-Hillman (MBH) carbonates, and alcohols has been established. This one-pot reaction progressed in an unusual reaction with solvent participation via a Knoevenagel condensation/oxa-Michael addition/SN2' substitution sequence. This method allowed for facile access to an array of functionalized chain alkylbenzenes and dihydroquinolinones bearing one all-carbon quaternary center in moderate to excellent yields. It is worth noting that the configuration of the all-carbon quaternary center could be modulated by changing only the electron-withdrawing groups via a tandem reduction/cyclization reaction.

Catalytic Appel Reaction Accessing the Mesoporous Substructure of a Robust and Heterogeneous Polyphosphamide

AbstractPolyphosphamides are normally good flame retardants. Herein a mesoporous polyphosphamide (p‐PPA) with an accessible average pore diameter of <10 nm and a surface area of 1.773 m2/g has been synthesized via condensation of 1,3‐diamino benzene (DAB) and phenyl phosphinic dichloride (PPDC). 31P, 13C CP‐MAS solid‐state NMR, Raman, and X‐ray photoelectron spectroscopic (XPS) characterizations confirm the presence of ‐{PV(O)‐NH}‐ in the repeating unit of the p‐PPA that is further used as a catalytic mediator to perform the Appel reaction i. e., conversion of alcohols to halides with a broad substrate scope and high TON (561). The heterogeneity of p‐PPA allows easy recovery of organic halides and recycling of the catalyst many times. Mesoporous p‐PPA has further given a scope to perform shape‐selective conversion of primary alcohols with linear alkyl chain (1‐dodecanol) while a low conversion for the bulky secondary (cyclo‐hexanol) and tertiary alcohol (tert‐butanol) is observed. Perhaps, the phosphamide units present inside the porous channel are non‐preferable sites for bulkier alcohols, as evident from the competitive experiments. A comparatively less catalytic conversion obtained with an analogous non‐porous n‐PPA, made of tris(2‐aminoethyl)amine (TREN) linker, highlights the role of porosity in p‐PPA to enhance the accessibility of numerous ‐{PV(O)‐NH}‐ reactive units to increase the TON.

Magnetic Ru nanocatalysts for green solvent-free oxidation reactions of aromatic alcohols

A kind of magnetic hybrid organic-inorganic nanoparticles containing Ru metal (Fe3O4@SiO2-FPBA-Ru) was prepared. It was spherical with the characteristic lattice fringe of ruthenium atom. The size was in the range of 5–15 nm and it contained 0.30 mmol/g Ru. Its saturation magnetization value was 15.95 emu/g, which could be easily and efficiently recovered from solution through an external magnet. It was also stable below 240°C and hot filtration experiment proved Ru wasn't leaked from Fe3O4@SiO2-FPBA-Ru in 70°C oxidation reaction. It could be recovered and reused at least 7 cycles. The low amount of Fe3O4@SiO2-FPBA-Ru (75 mmol%) could convert the 99 % of 1-phenylethanol to acetophenone under solvent-free system, which verified its green and environment-friendly properties. The yield was exceed that of homogeneous (RuCl3, 85 %). Beside this, the TON (5181), TOF (7430 h−1) in oxidation of 1-phenylethanol and high conversion yields for a series of oxidation reactions of aromatic secondary alcohols proved the high catalytic ability of Fe3O4@SiO2-FPBA-Ru. These laid a foundation for its industrial applications.

Friedel–crafts alkylations of indoles, furans, and thiophenes with arylmethyl acetates promoted by trimethylsilyl trifluoromethanesulfonate

Various indoles undergo Friedel–Crafts alkylation at the 3-position when treated with secondary arylmethyl acetates in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine. Tertiary benzylic alcohols are also effective alkylating agents, undergoing TMSOTf-promoted activation to yield alkylated indoles that feature quaternary centers. A related study shows that benzofuran reacts under similar conditions to yield 2-alkylated benzofurans when treated with similar alkylating agents, and the reaction has been extended to include other representative heteroarenes. Yields for these Friedel–Crafts alkylation products range from 43%–99% over a wide range of substrate combinations.

Catalyst-Free Dearomative Allylboration of Ketones with Benzo[b]thiophenylmethyl Boronic Acids.

A novel approach to the dearomative allylboration of ketones with benzo[b]thiophenylmethyl boronic acids has been developed. By leveraging the inherent reactivity of the boronic acid unit, this process occurs under mild reaction conditions without the need for a catalyst, leading to the efficient formation of homoallylic tertiary alcohols accompanied by the construction of three-dimensional sulfur-containing alicyclic scaffolds in high yields with excellent stereoselectivities.

Catalytic Generation of Benzyl Anions from Aryl Ketones Utilizing [1,2]-Phospha-Brook Rearrangement and Their Application to Synthesis of Tertiary Benzylic Alcohols.

A synthetic method of tertiary alcohols was developed based on the formal umpolung addition of aryl ketones with electrophiles utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The addition reaction of α-hydroxyphosphonates, derived from alkyl aryl- and diaryl ketones, with electrophiles such as phenyl vinyl sulfone, afforded phosphates having a tertiary alkyl group, which were readily convertible to the corresponding tertiary benzylic alcohols. This operationally simple protocol provides efficient complementary access to tertiary alcohols that are difficult to synthesize by conventional methods.

Solvent-free oxidation of alcohols by a heterogeneous Fe3O4@SiO2-DTPA-Ru nanocatalyst

A novel magnetic heterogeneous ruthenium catalyst (Fe3O4@SiO2-DTPA-Ru) was prepared by using magnetic silicon spheres as support, ethylenediaminepentaacetic acid (DTPA) as functional ligands, ruthenium chloride as catalyst precursor. The results obtained after a series of characterizations showed that the catalyst Fe3O4@SiO2-DTPA-Ru was 5–15 nm in size with a 0.205 nm lattice and contained 0.31 mmol Ru/g catalyst. It also had a good thermal stability under 232°C which was verified by thermal filtration method. Besides, the saturation magnetic intensity was as high as 20.54 emu/g. The catalyst Fe3O4@SiO2-DTPA-Ru was applied for the first time into thirteen oxidation reactions of aromatic alcohols and showed good catalytic activity even the yields of eleven aromatic alcohols were all over 90%. In catalyzing 1-phenylethanol to acetophenone, its TOF and TON were 9677 h−1 and 6991, respectively. The Fe3O4@SiO2-DTPA-Ru catalyst could still maintain good reusability and catalytic performance after 15 cycles of 1-phenylethanol oxidation, which was superior to many reported catalysts and had great potential in future industrial production.

FTIR and GC-MS analyses of raw materials produced from food wastes used in synthesis of biofilms

The present study carried out the GC-MS and FTIR analyses of raw materials (ripe plantain peel powder, cassava starch, glycerol, acetic acid (vinegar) and eggshell powder) produced from food wastes that are used in production of biofilm. The GC-MS results revealed the presence of pentadecane, bis (2-methylpropyl) ester and benzoic acid, 3-(2-Hydroxy-6-methylphenyl)-4(3H)-quinazolinone). The FTIR analysis revealed 17 peaks for glycerol, 16 peaks for vinegar, 15 peaks for cassava starch, 16 peaks for eggshell; representing the functional groups of ether, ethene, amine, carboxylic acid, nitriles, methylene cyclic ester, primary, secondary and tertiary alcohols common to hydrocarbons. The presence of carboxylic acid was important for enhancing the mechanical and chemical properties of biofilms thereby making them viable alternatives to petroleum-based plastics. Amines contributed to the flexibility, strength, and thermal degradation resistance of biofilms, thus aiding in their biodegradability. In conclusion, the study showed that the raw materials possessed biological activities and their functional groups indicated that the raw materials are safe to humans and the environment.

Synthesis of plantain peel powder-based biofilm

The present study investigated the use of ripe plantain peel powder, crude glycerol, vinegar, egg shell powder and cassava starch as source raw materials for producing plantain peel-based biodegradable biofilm (P-BF). The synthesized biofilm was characterized by chemical test (FTIR, GC-MS, morphology test, water absorption property, biodegradation test, solubility test and swelling test) and mechanical test (ultimate tensile test, flexural, hardness test, % elongation and thermogravimetric analysis). Results showed successful production of P-BF. A non-plantain bioplastic (NP-BF) served as control. The FTIR analysis showed eight functional groups; ether, ethene, amine, carboxylic acid, nitriles, methylene, cyclic ester, primary, secondary and tertiary alcohols common to hydrocarbons. The biodegradation test showed the P-BF degraded at the same pace as NP-BF which degraded on the 6th day of the test. The mechanical test showed P-BF had higher thermal stability and water absorption property compared to the NP-BF. However, P-BF showed lower ultimate tensile test, flexural, hardness test, percentage elongation compared to the NP-BF. Morphology test showed that there was uneven distribution of constituents materials in P-BF compared to the NP-BF which affected its mechanical properties. In conclusion, the study successfully produced plantain peel-based biodegradable biofilm with good mechanical properties, biodegradability, thermal stability, fair water absorption property.

Improved conditions for the synthesis of tertiary fluorides using a KF/H2SO4 combination

In this paper, we report the deoxyfluorination of tertiary alcohol using a simple combination of potassium fluoride and sulfuric acid. These cheap and widely available reagents allow for the synthesis of tertiary fluorides in good to excellent yields. Extension of the reaction to other functional groups such as alkenes, acetates and ethers have also been studied.

Therapeutic intervention of vitamin B12 in mitigating chronic alcoholism induced alterations in adult zebrafish (Danio rerio): a holistic in vivo approach

Background Chronic alcoholism refers to the unpleasant symptoms directly resulting from excessive drinking. Increased alcohol metabolites and an unbalanced oxidative state are likely to blame for the reported effects under these circumstances. According to preclinical and clinical research, vitamin B12 can act on several organ systems with demonstrated neuroprotective, antioxidant, and glutamate modulating properties. Objective This research sought to examine the ameliorative effects of vitamin B12 (VtB12) in persistent alcohol (AlOH) exposed adult zebrafish with the help of following parameters like the anxiety related behavior test, Oxidative stress, and antioxidant assays, histological and immunofluorescence analysis. Methods Zebrafish pretreated with 0.40% AlOH (v/v) for 120 min (+AlOH) or not (−AlOH), were exposed for 6 h to home tank water (−VtB12) or to 59 µg-VtB12/kg-fish food (+VtB12) to analyze anxiety behavior in the geotaxis (novel tank) test as well as the oxidative brain damage in the adult zebrafish. Results Adult zebrafish exposed to chronic AlOH showed a decrease in the distance travelled, average and mobility speed, and increased the average frozen time, the explored area, and total no. of the site explored in the trapezoid tank. AlOH exposure also resulted in oxidative damage, enhanced lipid peroxidation, advanced oxidative protein products, decreased enzymatic and non-enzymatic antioxidant activities, and enhanced reactive oxygen species generation. Additionally, VtB12 supplementation improved neurogenesis, evident in increased Nissl cell numbers and NeuN expression in the brain. Conclusion Chronic alcoholism may be effect on the brain cells as well as on the neuro-behavior of zebrafish. This research demonstrated that VtB12 shows promise as a neuroprotective agent against chronic alcoholism induced alterations in zebrafish’s brain.

Development of a Stable Lyophilized Cyclophosphamide Monohydrate Formulation Using Non-Aqueous Solvents.

To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55°C with annealing step at -22°C by which the reconstitution time was significantly reduced. The drying was performed at below - 25°C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.

Isothiourea-Catalysed Acylative Kinetic Resolution of Tertiary Pyrazolone Alcohols.

The development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea-catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)-, C(4)- and C(5)-, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically >100) at generally low catalyst loadings (1 mol%). The application of this KR method to tertiary alcohols derived from a natural product (geraniol), alongside pharmaceutically relevant drug compounds (indomethacin, gemfibrozil and probenecid), with high efficiency (s > 100) is also described. The KR process is readily amenable to scale up, with effective resolution on a 50 g (0.22 mol) scale demonstrated. The key structural motif leading to excellent selectivity in this KR process has been probed through computation, with an NC=O•••isothiouronium interaction observed within the favoured transition state. Similarly, the effect of C(5)-aryl substitution that leads to reduced experimental selectivity is probed, with a competitive π-isothiouronium interaction identified as leading to reduced selectivity.

TsOH-catalyzed dehydroxylative cross-coupling of alcohols with phenols: rapid access to propofol derivatives.

Modification of the parent structure of molecules often alters their physicochemical properties and biological activities. Herein, a practical, efficient, and highly regioselective C-H alkylation of phenols with alcohols via dehydroxylative cross-coupling was developed to produce para-alkylated phenols with excellent regioselectivities and yields, using which propofol derivatives were rapidly synthesized. This process is performed under mild and simple conditions and is well-compatible with a variety of alcohols (secondary and tertiary benzylic alcohols as well as allyl alcohols) as alkylated agents. In addition, high aryl ether derivatives were also obtained using this catalytic system.