Alcoholic Hydroxy Groups Research Articles

Ring-closing C–O/C–O metathesis of ethers with primary aliphatic alcohols

In canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C–O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C–O/O–H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a Re2O7 mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available Re2O7 through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C–O/C–O σ-bond metathesis. Due to the preference for the activation of alcohol rather than ether, this intramolecular transetherification reaction is therefore suitable for substrates bearing multiple ether moieties, unparalleled by any previous methods.

Molecular insights into dissolution of lignin bunch in ionic liquid-water mixture for enhanced biomass conversion

Globally, the shift towards lignocellulosic biorefinery has opened avenues for valorizing lignin, a majorly accumulated recalcitrant by-product. A targeted lignin processing by ionic liquid-cosolvent mixtures can be an effective biomass conversion strategy. An understanding of lignin-ionic liquid dissolution can enable in designing a significant lignin processing technique to synthesis lignin-based renewable products. Here, we explored the molecular interaction during the dissolution of lignin containing five guaiacyl decamer chains in various (1-Ethyl-3-Methylimidazolium Acetate) EmimOAc-water mixtures using molecular dynamics simulation. The analysis showed that in only water, lignin formed a compact aggregate. Nevertheless, in 50%, 80%, and 100% EmimOAc-water, lignin underwent a segregated chain disentanglement with widespread dynamic motion. A detailed multifaceted analysis of Emim+, OAc− and water distribution on the polar and non-polar sites of lignin units was illustrated. An effective lignin dissolution was observed for 50% and 80% EmimOAc-water systems. The OAc− distribution was stronger around lignin's alkyl chains and alcoholic hydroxy groups. The Emim+ tails significantly impacted the benzene ring, whereas Emim+ heads were distributed around methoxy and hydroxy groups. Altogether, this study explores the lignin dissolution at atomistic level in EmimOAc-water mixtures; these understanding could serve as a cornerstone for engineering new ionic liquid-mediated lignin biorefinery.

Direct substitution of the hydroxy group of alcohols with N-nucleophiles mediated by the substoichiometric amount of Selectfluor™ F-TEDA-BF4 as a precatalyst under mild reaction conditions

Selectfluor™ F-TEDA-BF4 was introduced, tested, and applied as an efficient, metal-free, and environmentally benign precatalyst for direct cross-coupling of various alcohols with N-nucleophiles under mild reaction conditions enhancing the green chemical profiles of these transformations. The scale-up procedure was achieved with an almost quantitative yield, confirming the presented method's synthetic applicability and potential for industrial application.

Transition-Metal-Free O-Arylation of Alcohols and Phenols with S-Arylphenothiaziniums.

Herein, we report the transition-metal-free O-arylation of alcohols and phenols with S-arylphenothiaziniums, which can be easily synthesized from boronic acids. Aryl substituents derived from arylboronic acids were selectively introduced into the hydroxy groups in alcohols and phenols, and a variety of aryl ethers were synthesized. This selectivity is supported by theoretical calculations.

Direct benzylation of amines with benzylic alcohols catalyzed by palladium/phosphine-borane catalyst system

Direct catalytic benzylation of amines with benzylic alcohols to give benzylamines has been newly developed by using palladium/phosphine-borane catalyst system. In this catalytic reaction, the linking between both phosphine and borane moieties in the ligand is very important. Hydroxy group of benzylic alcohols is activated by Lewis acidic borane to form a benzylpalladium intermediate which is attacked by amines to give benzylamine products.

Investigation of phase II metabolism of 11-hydroxy-\u0394-9-tetrahydrocannabinol and metabolite verification by chemical synthesis of 11-hydroxy-\u0394-9-tetrahydrocannabinol-glucuronide

(−)-Δ-9-tetrahydrocannabinol ((−)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (−)-11-hydroxy-Δ-9-tetrahydrocannabinol ((−)-11-OH-Δ-9-THC), which is psychoactive, and to (−)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((−)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (−)-Δ-9-tetrahydrocannabinol-glucuronide ((−)-Δ-9-THC-Glc) and (−)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((−)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (−)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((−)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding—alcoholic and/or phenolic—remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (−)-11-OH-Δ-9-THC-Glc in vitro as well as in vivo and to identify the glucuronide by chemically synthesis of a reference standard. For in vitro analysis, pooled human S9 liver fraction was incubated with (−)-Δ-9-THC. Resulting metabolites were detected by high-performance liquid chromatography system coupled to a high-resolution mass spectrometer (HPLC-HRMS) with heated electrospray ionization (HESI) in positive and negative full scan mode. Five different chromatographic peaks of OH-Δ-9-THC-Glc have been detected in HESI positive and negative mode, respectively. The experiment set up according to Wen et al. indicates the two main metabolites being an alcoholic and a phenolic glucuronide metabolite. In vivo analysis of urine (n = 10) and serum (n = 10) samples from cannabis users confirmed these two main metabolites. Thus, OH-Δ-9-THC is glucuronidated at either the phenolic or the alcoholic hydroxy group. A double glucuronidation was not observed. The alcoholic (−)-11-OH-Δ-9-THC-Glc was successfully chemically synthesized and identified the main alcoholic glucuronide in vitro and in vivo. (−)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.

Theoretical study of selective hydrogenolysis of methyl vinyl carbinol over Au-Ni bimetallic catalyst: Toward constructing a working hypothesis for the role of dichloroethane solvent and perimeter sites

Au-Ni bimetallic nanoparticles catalyze the hydrogenolysis of the hydroxy group of benzylic alcohols by activating H2 with dichloroethane solvent. To propose a working hypothesis for their reaction mechanism, we performed theoretical calculations for the hydroxylation of methyl vinyl carbinol over the Au1Ni19 cluster. The results showed that there’re two reaction cycles, depending on the presence of HCl. Firstly, the solvent acted as a sacrificial reagent to produce the carbocation intermediate, while HCl was produced in other reaction. It was found that the presence of the exposed Au site played an important role for producing HCl and subsequent hydrogenolysis.

A Bond-Weakening Borinate Catalyst that Improves the Scope of the Photoredox α-C–H Alkylation of Alcohols

The development of catalyst-controlled, site-selective C(sp3)–H functionalization reactions is currently a major challenge in organic synthesis. In this paper, a novel bond-weakening catalyst that recognizes the hydroxy group of alcohols through formation of a borate is described. An electron-deficient borinic acid–ethanolamine complex enhances the chemical yield of the α-C–H alkylation of alcohols when used in conjunction with a photoredox catalyst and a hydrogen atom transfer catalyst under irradiation with visible light. This ternary hybrid catalyst system can, for example, be applied to functional-group-enriched­ peptides.

Calculation of the Isobaric Heat Capacities of the Liquid and Solid Phase of Organic Compounds at 298.15K by Means of the Group-Additivity Method.

The calculation of the isobaric heat capacities of the liquid and solid phase of molecules at 298.15 K is presented, applying a universal computer algorithm based on the atom-groups additivity method, using refined atom groups. The atom groups are defined as the molecules’ constituting atoms and their immediate neighbourhood. In addition, the hydroxy group of alcohols are further subdivided to take account of the different intermolecular interactions of primary, secondary, and tertiary alcohols. The evaluation of the groups’ contributions has been carried out by solving a matrix of simultaneous linear equations by means of the iterative Gauss–Seidel balancing calculus using experimental data from literature. Plausibility has been tested immediately after each fitting calculation using a 10-fold cross-validation procedure. For the heat capacity of liquids, the respective goodness of fit of the direct (r2) and the cross-validation calculations (q2) of 0.998 and 0.9975, and the respective standard deviations of 8.24 and 9.19 J/mol/K, together with a mean absolute percentage deviation (MAPD) of 2.66%, based on the experimental data of 1111 compounds, proves the excellent predictive applicability of the present method. The statistical values for the heat capacity of solids are only slightly inferior: for r2 and q2, the respective values are 0.9915 and 0.9874, the respective standard deviations are 12.21 and 14.23 J/mol/K, and the MAPD is 4.74%, based on 734 solids. The predicted heat capacities for a series of liquid and solid compounds have been directly compared to those received by a complementary method based on the "true" molecular volume and their deviations have been elucidated.

Synthesis and Self‐Aggregation of Chlorophyll‐a Derivatives with Ethynylene and Phenylene Groups Inserted Between the Hydroxymethyl Group and the Chlorin π‐Skeleton

AbstractChlorophyll(Chl)‐a derivatives containing some rigid linkers in the C3‐substituent, inserted between a hydroxymethyl group and a zinc 131‐oxo‐chlorin moiety, were synthesized as models of bacteriochlorophyll‐c/d/e molecules in the main light‐harvesting antennae (chlorosomes) of photosynthetic green bacteria. These model compounds were synthesized from a C3‐ethynylated Chl‐a derivative via several coupling reactions, and the lengths of the linkers were controlled by ethynylene and p‐phenylene groups. In less polar organic solvents or an aqueous micellar solution, some derivatives self‐aggregated in a J‐type fashion similar to that observed in natural chlorosomes, which was confirmed with UV/Vis absorption and CD spectroscopies. Their self‐aggregation abilities were dependent on the length of the inserted linkers and the conformation of the propargylic/benzylic alcoholic hydroxy groups.

HYDROGEN SULFIDE IN NUCLEOPHILIC SUBSTITUTION REACTIONS OF HYDROXY GROUPS IN AROMATIC ALCOHOLS

Most methods of obtaining aromatic thiols are based on nucleophilic substitution reactions at halogen derivatives of aromatic hydrocarbons when used as nucleophilic reagents sodium thiolate, thiourea or potassium xanthate at high temperatures, pressure and in the presence of catalysts. The direct reaction of nucleophilic substitution of OH-groups in the phenols, pyrocatechol and benzyl alcohol to the HS-group in conditions of one-electron reducrion of hydrogen sulfide in acetonitrile and pyridinium ionic liquid was investigated for the first time. The proposed reactions proceed at room temperature and atmospheric pressure. The use of "green" solvent - ionic liquid - reduces the syntheses time in а half, improves ecological safety friendliness of the process and reduces the consumption of reagents. The main positive feature of these studies is not only ecological safety of reactions of nucleophilic substitution (due to the lack of harmful byproducts), but the use of electrochemical reactions in ionic liquid media, that is very relevant in modern science in terms of new environmental technologies development.
 For citation:
 Okhlobystina A.V., Okhlobystin A.O., Berberova N.T., Burmistrova D.A. Hydrogen sulfide in nucleophilic substitution reactions of hydroxy groups in aromatic alcohols. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2018. V. 61. N 9-10. P. 36-41
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Vinylogous Nucleophilic Substitution of the Hydroxy Group in Diarylmethanols with 3‐Propenyl‐2‐silyloxyindoles: Towards the Synthesis of α‐Alkylidene‐δ‐diaryl‐2‐oxindoles

AbstractWe report herein a highly stereoselective method for the indium triflate‐catalyzed vinylogous substitution of the hydroxy group of diarylmethyl alcohols with 3‐alkenyl‐2‐silyloxyindoles, which affords broadly substituted α‐alkylidene‐δ‐diaryl‐2‐oxindole products with high efficiency and complete γ‐site and Z‐selectivity. The reaction displays very wide substrate scopes for both the reactants, benzhydryl alcohols and 3‐alkenyl‐2‐silyloxyindoles. The utility of the substituted adducts is shown by their conversion to other useful derivatives.magnified image

In vitro stereospecific hydration activities of the 3-vinyl group of chlorophyll derivatives by BchF and BchV enzymes involved in bacteriochlorophyll c biosynthesis of green sulfur bacteria.

The photosynthetic green sulfur bacterium Chlorobaculum (Cba.) tepidum produces bacteriochlorophyll (BChl) c pigments bearing a chiral 1-hydroxyethyl group at the 3-position, which self-aggregate to construct main light-harvesting antenna complexes, chlorosomes. The secondary alcoholic hydroxy group is requisite for chlorosomal aggregation and biosynthesized by hydrating the 3-vinyl group of their precursors. Using recombinant proteins of Cba. tepidum BchF and BchV, we examined in vitro enzymatic hydration of some 3-vinyl-chlorophyll derivatives. Both the enzymes catalyzed stereoselective hydration of zinc 3-vinyl-8-ethyl-12-methyl-bacteriopheophorbide c or d to the zinc 31 R-bacteriopheophorbide c or d homolog, respectively, with a slight amount of the 31 S-epimric species. A similar R-stereoselectivity was observed in the BchF-hydration of zinc 3-vinyl-8-ethyl- and propyl-12-ethyl-bacteriopheophorbides c, while their BchV-hydration gave a relatively larger amount of the 31 S-epimers. The in vitro stereoselective hydration confirmed the in vivo production of the S-epimeric species by BchV. The enzymatic hydration for the above 8-propylated substrate proceeded more slowly than that for the 8-ethylated, and the 8-isobutylated substrate was no longer hydrated. Based on these results, biosynthetic pathways of BChl c homologs and epimers are proposed.

Substrate‐Tuned Catalysis of the Radical S‐Adenosyl‐L‐Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis

NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.

Substrate-Tuned Catalysis of the RadicalS-Adenosyl-L-Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis

NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5′-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.

Reductive Nucleation of Palladium Nanoparticles on a Cycloolefin Polymer Surface Oxidized with Active Oxygen Species Generated by Vacuum Ultraviolet Excitation

Abstract The ability to reduce palladium (Pd) ions to Pd nanoparticles has been provided on the surface of cycloolefin polymer (COP). The origin of this reductive function is aldehyde and alcoholic hydroxy groups formed by oxidizing the COP surface with active oxygen species, which were generated through the irradiation of atmospheric oxygen and water molecules with vacuum ultraviolet light of 172 nm in wavelength. The Pd nanoparticles successfully served as catalysts for electroless plating.

ChemInform Abstract: Synthesis of Alkyl (4,5‐Dichloroisothiazol‐3‐yl) Ketones and Some of Their Derivatives.

Reactions of 4,5-dichloroisothiazol-3-ylcarbonitrile with methylmagnesium iodide and ethylmagnesium bromide afforded the corresponding alkyl (4,5-dichloroisothiazol-3-yl) ketones. The reaction of (4,5-dichloroisothiazol-3-yl) methyl ketone with morpholine and piperidine provided 5-morpholino-(piperidino)-substituted derivatives, by the action of sodium borohydride in 2-propanol the keto group was reduced to alcoholic hydroxy group. The bromination of (4,5-dichloroisothiazol-3-yl) methyl ketone with elemental bromine gave bromomethyl (4,5-dichloroisothiazol-3-yl) ketone, whose reaction with thiourea resulted in 2-amino-4-(4,5-dichloroisothiazol-3-yl)thiazole.

Synthesis of alkyl (4,5-Dichloroisothiazol-3-yl) ketones and some of their derivatives

Reactions of 4,5-dichloroisothiazol-3-ylcarbonitrile with methylmagnesium iodide and ethylmagnesium bromide afforded the corresponding alkyl (4,5-dichloroisothiazol-3-yl) ketones. The reaction of (4,5-dichloroisothiazol-3-yl) methyl ketone with morpholine and piperidine provided 5-morpholino-(piperidino)-substituted derivatives, by the action of sodium borohydride in 2-propanol the keto group was reduced to alcoholic hydroxy group. The bromination of (4,5-dichloroisothiazol-3-yl) methyl ketone with elemental bromine gave bromomethyl (4,5-dichloroisothiazol-3-yl) ketone, whose reaction with thiourea resulted in 2-amino-4-(4,5-dichloroisothiazol-3-yl)thiazole.

Metal‐binding Sites of N‐Acetylneuraminic Acid

AbstractSialic acid represents a group of thirty derivates of neuraminic acid with various substituents at the amino residue and the alcoholic hydroxy groups. We analysed the behaviour of the tetracoordinated metal ions palladium(II) and silicon(IV) against the most important derivative N‐acetylneuraminic acid (NANA). The molecular structures were assigned by a combined 1H, 13C and 29Si NMR‐spectroscopic approach. Despite the presence of many different functional groups, the coordination chemistry of NANA with PdII follows established rules. Coordination via the N‐acetyl‐group – sterically impossible with PdII – was realised with SiIV.

Reaction of 2-(trifluoromethyl)chromones with pyridoxal: Formation of 1-benzopyranooxepino- and 1-benzopyranopyranopyridines

Pyridoxal undergoes oxa-Michael initiated ring closure with 2-(trifluoromethyl)chromones giving 11a,13-dihydro-6H-1-benzopyrano[3′,2′:6,7]oxepino[3,4-c]pyridin-6-ones and 6H,11aH-1-benzopyrano[3′,2′:5,6]pyrano[2,3-c]pyridin-6-ones. Participation of alcoholic hydroxy group of pyridoxal in the initial oxa-Michael addition leads to the former product and that of the phenyl hydroxy group to the later one.