Secondary Alcohols Research Articles

Mechanistic Insights into the Appel Reaction Mediated by a Poly-Phosphamide Material as a Heterogeneous Catalyst.

Due to notable thermochemical stability, polyphosphamides are often regarded as flame retardants, while molecular phosphamides can serve as versatile Lewis base to catalyze diverse organic transformations. Being chemically analogous to phosphine oxide, phosphamide can also be considered as a mediator for the phosphine-mediated reaction. Herein, an amorphous polymeric material consisting of phosphamide (-NH-P(O)) in the repeating unit (POP) has been prepared via condensation of tris(2-aminoethyl)amine (TREN) and phenyl phosphinic dichloride (PPDC). The POP is isolated as a metal-free and pure organic material which is made of a strong covalent bond and the phosphamide unit is deployed in the organic framework. The presence of phosphamide in the repeating unit of the isolated amorphous POP material can be confirmed by 31P CPMAS NMR, FTIR, and Raman studies. The core-level N 2p and P 2p X-ray photoelectron spectra are in accordance with the presence of tertiary amine nitrogen attached to carbon and secondary amine nitrogen attached to phosphorus. Elemental analyses have depicted approximately 19.7% of phosphorus content in the material, which is being utilized to study the catalytic Appel reaction with 76% conversion of alcohol to a corresponding halide and TON of 462. Quasi in situ Raman study has identified that amino phosphine formed via in situ reduction of the phosphamide unit of the POP catalyzes the halogenation of primary and secondary alcohols with wide substrate scope and functional group tolerance. Kinetic studies have established a first-order dependence with respect to alcohol, while deuterium labeling experiments emphasize that the deprotonation of alcohol is the rate-limiting step. High thermal stability of the material, scope of easy catalyst recyclability, and a cumulative TON of 1386 have led the POP as an emerging pure organic material to be explored further for other phosphine-mediated organocatalysis.

Base-controlled NHC-Ru-catalyzed transfer hydrogenation and α-methylation/transfer hydrogenation of ketones using methanol

Herein, we report the NHC-Ru catalyst system that realizes the chemo-selective transformation of ketones with methanol. By simply changing the base, a broad range of structurally diverse ketones, could be selectively and efficiently converted to the corresponding β-methylated secondary alcohols or secondary alcohols. Remarkably, this catalytic system was very effective for the synthesis of bio-related molecules and deuterated alcohols, as well as the three-component coupling between methyl ketones, primary alcohols, and methanol. The reaction mechanism was further revealed by experiment and DFT mechanistic investigations.

Selective control of secondary alcohols upgrading using Ir-catalyzed cross-coupling strategy

Selective control of secondary alcohols upgrading using Ir-catalyzed cross-coupling strategy

Enzymatic approach to the synthesis of chiral intermediate of Rodatristat ethyl

Ketoreductases are widely explored for the reduction of prochiral ketones for the preparation of chiral alcohols. Though, the chiral Ir(III) catalyst has been used for the asymmetric reduction of keto intermediate of Rodatristat ethyl, an enzymatic approach for its preparation has not yet been reported. In this regard, we report, for the first time the preparation of enantiopure secondary alcohols (R-3) and (S-3) from 1-(5-chloro-[1,1’-biphenyl]-2-yl)-2,2,2-trifluoroenthan-1-one (2) using commercially available ketoreductases at 30 °C in the presence of 125 mM sodium phosphate buffer pH 6 over 24 h. This enzymatic approach provides the (R)-3 and (S)-3 chiral alcohols in >99% enantiomeric excess (ee) with >99% conversion using KRED-244 and KRED-101 respectively. Furthermore, the KRED-244 and KRED-101 enzymes have been successfully immobilized with sodium alginate, which makes them recyclable and reusable in subsequent reactions. The reusability experiments were carried out over 15 cycles without any apparent loss of activity even after 10 cycles. It is a sustainable approach to the synthesis of enantiopure intermediates of rodatristat ethyl, contributing to the advancement of green chemistry.

Mesoporous MCM-41@SnPr-Kryf.23-Mn a versatile and reusable nanocatalyst for the oxidation of primary and secondary alcohols in the presence of hydrogen peroxide as oxidant

Mesoporous MCM-41@SnPr-Kryf.23-Mn a versatile and reusable nanocatalyst for the oxidation of primary and secondary alcohols in the presence of hydrogen peroxide as oxidant

An unexpected side reaction in the transformation of an alcohol to an amine facilitated by triflic anhydride-pyridine

Two N-triflyl-4-vinyl-1,4-dihydropyridines 3 and 4 were identified as isomeric impurities in the mother liquor of a 3-step “telescopic” transformation of a secondary alcohol 1 to an amine 2 facilitated by triflic anhydride-pyridine. The vinyl ether moiety of impurities 3 and 4 was readily hydrolyzed under acidic condition to form a keto-alcohol product 5 where four chiral centers were established on a cyclopentane ring. Another keto-alcohol impurity 6 was also isolated from the same mother liquor and identified as a hydrolysis product of the putative vinyl ether intermediate V in support of postulating a plausible mechanism for such an unexpected side reaction. The unexpected finding of the vinyl ether intermediate V could be derivatized with electrophiles besides N-triflylpyridinium to form a variety of compounds with four chiral centers established on a cyclopentane ring.

Syntheses and characterizations of two-dimensional heteronuclear tetracyanonickelate(II) complexes with 4-ethylpyridine and investigation of the catalytic activity of [Cd(4epy)2Ni(µ-CN)4

Three new 2D heteronuclear tetracyanonickelate(II) complexes with 4-ethylpyridine (4epy), [Cu(4epy)2Ni(µ-CN)4]n (1), [Zn(4epy)2Ni(µ-CN)4]n (2) and [Cd(4epy)2Ni(µ-CN)4]n (3), were synthesized and characterized by vibrational (FT-IR and Raman) spectroscopy, elemental and thermal analyses, single crystal (SC-XRD) and powder X-ray diffraction (PXRD) techniques. The single crystal X-ray analysis reveals that each metal ion (Cu(II), Zn(II), and Cd(II)) is coordinated by two nitrogen atoms from 4epy ligands and four nitrogen atoms from cyanide ligands and Ni(II) ions are coordinated by four carbon atoms from cyanide ligands showing a distorted octahedral and square planar coordination geometries, respectively. The most outstanding features of the complexes are the weak intermolecular C–H⋅⋅⋅Ni interactions between the Ni(II) ion and hydrogen atom of the ethyl group of the 4epy ligand. Adjacent 2D structures are further combined by these C–H⋅⋅⋅Ni interactions, generating a 3D network. The heterogeneous catalytic activity of 3 was investigated for oxidation of some primary and secondary aliphatic or aromatic alcohols; no acid formation was observed in some aromatic alcohols after 24 h and 100% aldehyde selectivity was determined.

Screening and identification of differential-expressed RNAs in thrombin-induced in vitro model of intracerebral hemorrhage.

Survival of olfactory mucosal mesenchymal stem cells (OM-MSCs) remains the low level in the cerebral microenvironment during intracerebral hemorrhage (ICH). This article aims to reveal the differential expression profile of ICH-stimulated OM-MSCs based on whole transcriptome sequence analysis. OM-MSCs were isolated from 6-week C57BL/6 mice. Morphology and surface markers of OM-MSCs were investigated by light microscope and flow cytometry, respectively. OM-MSCs were incubated with 20 U/mL thrombin for 24h to mimic ICH-induced injury in vitro. Total RNA was extracted for whole transcriptome sequencing and qPCR. OM-MSCs were characterized by negative for CD45 and CD34, and positive for CD44, CD90 and CD29. Thrombin led to decrease in cell viability and increase in senescence and apoptosis in OM-MSCs. In total, 736 lncRNAs (upregulated: 393; downregulated: 343), 21 miRNAs (upregulated: 7; downregulated: 14) and 807 mRNAs (upregulated: 422; downregulated: 385) were identified. GO and KEGG pathways were enriched in protein heterodimerization activity, trans-synaptic signaling, membrane pathway, alcohol metabolic process, organic hydroxy compound biosynthesis process, secondary alcohol metabolic process, alcoholism, neutrophil extracellular trap formation, systemic lupus erythematosus, metabolic process, steroid biosynthesis and drug metabolism-cytochrome P450. 200 lncRNA-miRNA-mRNA were predicted in thrombin-induced OM-MSCs. Based on qPCR, we validated COMMD1B, MOAP1, lncRNA CAPN15, lncRNA ALDH1L2, miR-3473b and miR-1964-3p were upregulated in thrombin-stimulated OM-MSCs, and GM20431, lncRNA GAPDH and miR-122b-3p were downregulated. Our findings provide novel understanding for thrombin-induced injury in OM-MSCs. Differently-expressed RNAs can be the targets of improving therapeutic application of OM-MSCs.

Merging Radical Brook Rearrangement and 1,5‐Hydrogen Atom Transfer: Facile Synthesis of Ketone‐Containing ɑ‐Fluoroalkyl Alcohols

AbstractHerein, we report a cascade process that is initiated by radical Brook rearrangement and promoted by 1,5‐hydrogen atom transfer. A series of α‐fluoroalkyl alkyl secondary alcohols were synthesized with unactivated terminal olefins and α‐fluoroalkyl‐α‐silyl methanols. The strategy features mild reaction conditions and broad substrate scope. The diversified down‐stream transformations demonstrated the synthetic potential of the reaction.

Phenotypic Diversity in Leaf Cuticular Waxes in Brassica carinata Accessions.

Brassica carinata has received considerable attention as a renewable biofuel crop for semi-arid zones due to its high oil content and polyunsaturated fatty acids contents. It is important to develop new drought-resistant cultivars of B. carinata production to expand its areas into more arid regions. The accumulation of leaf cuticular wax on plant surfaces is one mechanism that reduces non-stomatal water loss, thus increasing drought resistance in plants. To explore phenotypic variations in cuticular wax in B. carinata, leaf waxes were extracted and quantified from a diversity panel consisting of 315 accessions. The results indicate that the accessions have a wide range of total leaf wax content (289-1356 µg dm-2), wax classes, and their components. The C29 and C31 homologues of alkanes, C29 ketone homologue, C29 secondary alcohol, and C30 aldehyde were the most abundant leaf waxes extracted from B. carinata accessions. The high heritability values of these waxes point to the positive selection for high wax content during early generations of future B. carinata breeding programs. Positive correlation coefficients, combined with the effects of these waxes on leaf wax content accumulation, suggest that modifying specific wax content could increase the total wax content and enhance cuticle composition. The identified leaf wax content and compositions in B. carinata will lead to the future discovery of wax biosynthetic pathways, the dissection of its genetic regulatory networks, the identification of candidate genes controlling production of these waxes, and thus, develop and release new B. carinata drought-tolerant cultivars.

Mechanistic Insights into a Co(II)-Coordinated "Free" Metal Site of 2D Zinc-Based MOFs for β-Alkylation of Secondary Alcohols with Primary Alcohols.

Through in-depth study of the properties and reaction mechanisms of catalysts, it is possible to better optimize catalytic systems and improve reaction efficiency and selectivity. This remains one of the challenges in the field of catalysis. Therefore, the research and design of catalysts play crucial roles in understanding and optimizing catalytic reaction mechanisms. A robust 2D zinc-based MOFs (Zn-HA) supported Co(II) ion catalyst (Zn-HA@Co) has been designed and synthesized via a coordination-assisted strategy for β-alkylation of secondary alcohols with primary alcohols. The characterization demonstrated that the anchoring of Co(II) on Zn-HA via coordination could efficiently enhance the Co(II) ion dispersity and interaction between Co(II) and Zn-HA MOFs. Importantly, the density functional theory results have provided mechanistic insights into the energy of the HOMO and LUMO of the Zn-HA@Co catalyst as well as the energy change of the entire process after interacting with the reactants and the specific energy changes of each orbital. The synthesized Zn-HA@Co MOFs effectively lower the energy barrier of the catalytic reaction process. We expect that our research and design of catalysts will serve as valuable guideline for understanding and optimizing catalytic reaction mechanisms.

Transition-Metal-Catalyzed C-C Bond Formation from C-C Activation.

ConspectusC-C single bonds are ubiquitous in organic compounds. The activation and subsequent functionalization of C-C single bonds provide a unique opportunity to synthesize conventionally inaccessible molecules through the rearrangement of carbon skeletons, often with a favorable atom and step economy. However, the C-C bonds are thermodynamically and kinetically inert. Consequently, the activation of C-C bonds is particularly attractive yet challenging in the field of organic chemistry. In the past decade, we sought to develop efficient strategies to carry out transition-metal-catalyzed diverse C-C cleavage/C-C forming reactions and to obtain some insights into the intrinsic reactivities of different C-C bonds. With our efforts, readily available alcohols, carboxylic acids, and ketones served as suitable substrates for the catalytic C-C coupling reactions, which are reviewed in this Account. In 2009, we observed a Ni-catalyzed cross coupling of aryl nitriles with arylboronic esters through C-CN cleavage. Encouraged by these results, we are interested in transition-metal-catalyzed C-C bond activation. Due to their broad availability, we then turned our attention to C-C cleavage of carboxylic acids. Rhodium-catalyzed decarbonylative coupling of carboxylic acids with (hetero)arenes was then achieved through oxidative addition of in situ formed, more reactive mixed anhydrides to Rh(I) without the need for oxidants that are commonly required for the decarboxylative coupling of carboxylic acids. Subsequently, the decarbonylation of more challenging unstrained aryl ketones was realized under Rh catalysis assisted by N-containing directing groups. Following this work, a group exchange of aryl ketones with carboxylic acids was achieved through 2-fold C-C bond cleavage. By employing the chelation strategy, Rh-catalyzed C-C bond activation of secondary benzyl alcohols was also accomplished through β-carbon elimination of the rhodium alcoholate intermediates. The competing oxidation of secondary alcohols to ketones via β-hydrogen elimination of the same intermediates was suppressed as thermodynamically favorable five-membered rhodacycles are formed after β-carbon elimination. Different types of transformations of alcohols, including the Heck-type reaction with alkenes, cross coupling with arylsilanes, and Grignard-type addition with aldehydes or imines, have been achieved, showing the great potential of secondary alcohols in the formation of C-C bonds. These C-C bond-forming reactions are complementary to traditional cross couplings of aryl halides with organometallic reagents. However, these transformations produce small molecules as byproducts. To improve the atom economy, we then investigated C-C bond transformations of strained-ring cyclic compounds. Ni-catalyzed intermolecular cyclization of benzocyclobutenones with alkynes was recently achieved via the uncommon cleavage of the C1-C8 bond by employing a removable blocking strategy. Rh-catalyzed intramolecular annulation of benzocyclobutenols with alkynes was also achieved. In summary, our developments demonstrate the great potential of transition-metal-catalyzed C-C bond activation for the formation of new C-C bonds. To further expand the synthetic utility of C-C bond activation, more efforts are required to expand the substrate scope and to achieve earth-abundant metal-catalyzed transformations.

Stereoselective Synthesis, Pro-resolution, and Anti-inflammatory Actions of RvD5n-3DPA.

The methyl ester of resolvin D5n-3DPA, a lipid mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid, was stereoselectively prepared in 8% yield over 12 steps (longest linear sequence). The key steps for the introduction of the two stereogenic secondary alcohols were an organocatalyzed oxyamination and the Midland Alpine borane reduction. For the assembly of the carbon chain, the Sonogashira cross-coupling reaction and the Takai olefination were utilized. The physical properties, including retention time in liquid chromatography and tandem mass spectra, of the synthetic material were matched against material from human peripheral blood and mouse infectious exudates. Synthetic RvD5n-3DPA, obtained just prior to biological experiments, displayed potent leukocyte-directed activities, upregulating the ability of neutrophils and macrophages to phagocytose bacteria, known as hallmark bioactions of specialized pro-resolving endogenous mediators.

Reverse Micellar Dyeing of Cotton Fabric with Reactive Dye Using Biodegradable Non-Ionic Surfactant as Nanoscale Carrier: An Optimisation Study by One-Factor-at-One-Time Approach.

This study investigates the feasibility of using biodegradable secondary alcohol ethoxylate (SAE) non-ionic surfactant as a building block for the formation of reverse micelles, functioning as reactive dye carriers for the dyeing of cotton fabric in non-aqueous octane medium. Ten dyeing parameters were optimised, by a one-factor-at-a-time approach, namely: (i) effect of colour fixation agent; (ii) surfactant-to-water mole ratio; (iii) surfactant-to-co-surfactant mole ratio; (iv) volume of soda ash; (v) volume of dye; (vi) solvent-to-cotton ratio; (vii) dyeing temperature; (viii) dyeing time; (ix) fixation time; (x) soda-ash-to-cotton ratio. The colour properties, fastness properties and physical properties of SAE-dyed samples were experimentally compared with the conventional water-dyed samples. The optimised condition was found when SAE samples were dyed as follows: (a) 1:20 surfactant-to-water ratio; (b) 1:8 surfactant-to-co-surfactant ratio; (c) 10:1 solvent ratio; (d) 40 min dyeing time; (e) 60 min fixation time; and (f) 70 °C dyeing and fixation temperature. The results showed that SAE-dyed samples have better colour strength, lower reflectance percentage and comparable levelness, fastness and physical properties than that of water-dyed samples. SEM images revealed that the dyed cotton fibres had no severe surface damage caused by an SAE-based reverse micellar dyeing system. The TEM image depicts that the reverse micelle was of nanoscale, spherical-shaped and had a core-shell structure, validating the presence of reverse micelle as a reactive dye carrier and the potential of an SAE-based reverse micellar system for dyeing of cotton fabrics.

The Chemistry of Hager’s Test for Brucine

The purpose of the article is clear up what is happening in the test tube during the Hager’s test for brucine, that is, throughout the interaction of brucine with manganese dioxide in acidic medium. The paper is a Theoretical Organic Chemistry Study based on the chemical deportment of reagent and substrate, in accordance with the reaction medium. A series of reactions occur during the test: electrophilic attack to double bond, acidolysis of organometallic intermediates, oxidation of secondary alcohol to ketone, acid catalysed hydration, reaction of enol, epoxide formation, ring opening, selective reaction of diol, and ring cleavage of seven-member ring. A yellowish-red to blood-red colour is observed after filtering residual black manganese dioxide. This is due to halochromism, present in acidic medium, since there are no chromogenic groupings.

Enthalpy of Mixing and Liquid Structure for Mixtures of Primary and Secondary Alcohols: Molecular Simulations and COSMO–SAC Calculations

Enthalpy of Mixing and Liquid Structure for Mixtures of Primary and Secondary Alcohols: Molecular Simulations and COSMO–SAC Calculations

Cover Feature: Highly Efficient Base Catalyzed N‐alkylation of Amines with Alcohols and β‐Alkylation of Secondary Alcohols with Primary Alcohols (ChemCatChem 20/2023)

Cover Feature: Highly Efficient Base Catalyzed <i>N</i>‐alkylation of Amines with Alcohols and β‐Alkylation of Secondary Alcohols with Primary Alcohols (ChemCatChem 20/2023)

Deoxyfluorination of 1°, 2°, and 3° Alcohols by Nonbasic O-H Activation and Lewis Acid-Catalyzed Fluoride Shuttling.

A method for deoxyfluorination of aliphatic primary, secondary, and tertiary alcohols is reported, employing a nontrigonal phosphorus triamide for base-free alcohol activation in conjunction with an organic soluble fluoride donor and a triarylborane fluoride shuttling catalyst. Mechanistic experiments are consistent with a reaction that proceeds by the collapse of an oxyphosphonium fluoroborate ion pair with fluoride transfer. The substrate scope complements existing deoxyfluorination methods and enables the preparation of homochiral secondary and tertiary alkylfluorides by stereoinversion of the substrate alcohol.

An improved biocatalyst from Candida antarctica lipase B immobilized on metal organic frameworks for kinetic resolution of chiral secondary alcohols

Immobilization of an enzyme on a solid support is an efficient strategy to enhance its catalytic performance and reusability. Herein, Candida antarctica lipase B (CALB) immobilized on a Materials of Institute Lavoisier framework (MIL-53) to prepare CALB@MIL-53 was investigated. Activity evaluation showed that the specific activity of CALB@MIL-53 (U/mg protein) increased 185.9 % than free CALB. CALB@MIL-53 was employed as a biocatalyst in kinetic resolution of 1-(4-methylphenyl) ethanol (MPE) racemate, achieving an enantiomeric excess of the remaining substrate (ees) of higher than 99 % with substrate conversion (c) of 50.0 % in 12 h. It is found that CALB@MIL-53 has an enhanced tolerance to organic solvents and an enhanced activity compared with the commercial enzyme extract of CALB. Furthermore, CALB@MIL-53 can be steadily reused for three cycles, while the commercialized immobilized CALB (Novozym 435) was disintegrated under identical conditions. The research results indicated the immobilization of CALB on MOFs support showed the huge potential in industrial application.

Structure Confirmation of Dechlorotrichotoxin A through Stereoselective Total Synthesis.

The stereoselective total synthesis of dechlorotrichotoxin A, alongside the synthesis of a 1:1 10E/Z mixture of trichotoxin A, was successfully achieved, commencing from the natural monoterpenoid (-)-citronellal. Key steps in the synthesis involved introducing three alkenes and establishing a stereogenic secondary alcohol center. These transformations were accomplished through olefin cross-metathesis, Tebbe olefination, and enantioselective allylation using a chiral phosphoric acid. A comparison of the spectroscopic data between the synthetic dechlorotrichotoxin A and the reported spectra confirmed that the polyketide isolated from a Smenospongia species corresponds to trichotoxin A rather than dechlorotrichotoxin A.