Cyclohexane Derivatives Research Articles

Selective Hydrogenation and Hydrodeoxygenation of Aromatic Ketones to Cyclohexane Derivatives Using a Rh@SILP Catalyst.

Rhodium nanoparticles immobilized on an acid‐free triphenylphosphonium‐based supported ionic liquid phase (Rh@SILP(Ph3‐P‐NTf2)) enabled the selective hydrogenation and hydrodeoxygenation of aromatic ketones. The flexible molecular approach used to assemble the individual catalyst components (SiO2, ionic liquid, nanoparticles) led to outstanding catalytic properties. In particular, intimate contact between the nanoparticles and the phosphonium ionic liquid is required for the deoxygenation reactivity. The Rh@SILP(Ph3‐P‐NTf2) catalyst was active for the hydrodeoxygenation of benzylic ketones under mild conditions, and the product distribution for non‐benzylic ketones was controlled with high selectivity between the hydrogenated (alcohol) and hydrodeoxygenated (alkane) products by adjusting the reaction temperature. The versatile Rh@SILP(Ph3‐P‐NTf2) catalyst opens the way to the production of a wide range of high‐value cyclohexane derivatives by the hydrogenation and/or hydrodeoxygenation of Friedel–Crafts acylation products and lignin‐derived aromatic ketones.

Selective Hydrogenation and Hydrodeoxygenation of Aromatic Ketones to Cyclohexane Derivatives Using a Rh@SILP Catalyst

AbstractRhodium nanoparticles immobilized on an acid‐free triphenylphosphonium‐based supported ionic liquid phase (Rh@SILP(Ph3‐P‐NTf2)) enabled the selective hydrogenation and hydrodeoxygenation of aromatic ketones. The flexible molecular approach used to assemble the individual catalyst components (SiO2, ionic liquid, nanoparticles) led to outstanding catalytic properties. In particular, intimate contact between the nanoparticles and the phosphonium ionic liquid is required for the deoxygenation reactivity. The Rh@SILP(Ph3‐P‐NTf2) catalyst was active for the hydrodeoxygenation of benzylic ketones under mild conditions, and the product distribution for non‐benzylic ketones was controlled with high selectivity between the hydrogenated (alcohol) and hydrodeoxygenated (alkane) products by adjusting the reaction temperature. The versatile Rh@SILP(Ph3‐P‐NTf2) catalyst opens the way to the production of a wide range of high‐value cyclohexane derivatives by the hydrogenation and/or hydrodeoxygenation of Friedel–Crafts acylation products and lignin‐derived aromatic ketones.

Simple Perylene Diimide Cyclohexane Derivative With Combined CPL and TPA Properties.

In this work we describe the linear and non-linear (chiro)optical properties of an enantiopure bis-perylenediimide (PDI) cyclohexane derivative. This compound exhibits upconversion based on a two-photon absorption (TPA) process with a cross-section value of 70 GM together with emission of circularly polarized luminescence (CPL), showing a glum in the range of 10−3. This simple structure represents one of the scarce examples of purely organic compounds combining both TPA and CPL responses, together with large values of molar absorptivity and fluorescence quantum yield with emission in the 500–600 nm. Self-assembly induced by introduction of a poor solvent allows for a spectacular shift of the emission into the near-infrared (NIR, 650–750 nm) by formation of well-defined rotationally displaced dimers. Therefore, we are here presenting a versatile platform whose optical properties can be simply tuned by self-assembly or by functionalization of the electron-deficient aromatic core of PDIs.

The Reactivity and Deactivation Mechanism of Ru@C Catalyst over Hydrogenation of Aromatics to Cyclohexane Derivatives

AbstractNano Ru supported on carbon catalysts with different Ru nanoparticle sizes were reported for the aromatics (dioctyl phthalate, xylene, p‐phenylenediamine, cinnamic acid and nitrobenzene) hydrogenation to the corresponding value‐added cyclohexane derivatives. Ru@C–DP prepared by facile deposition‐precipitation strategy, exhibited the smaller Ru nanoparticle (NP) size 2.0 nm, higher Ru dispersion degree (60.2%) and larger Ru specific surface area (220.1 m2⋅gRu−1) than Ru@C‐EG and Ru@C–IM synthesized with ethylene glycol reduction and impregnation method, respectively. Ru@C–DP possessed excellent activity with aromatic conversion ≥ 99% and cyclohexane derivative selectivity ≥ 99%, which was attributed to its smaller Ru NP size, suggesting the presence of a size‐dependent effect. Moreover, compared with the commercial Ru@C–ID catalyst, Ru@C–DP showed remarkable reusability in aromatic hydrogenation. After the several hydrogenation recycles, the catalyst lost some activity mainly account for the pore blocking by reactant/product molecules, part oxidation and aggregation of Ru NPs.

A New Polyoxygenated Cyclohexene From the Rhizomes of Globba pendula Roxb.

A new polyoxygenated cyclohexene, globbanol A (1), 2 other cyclohexene derivatives, crotepoxide (2) and boesenboxide (3), along with a chalcone, 2ʹ- hydroxy-4,4ʹ,6ʹ-trimethoxy-chalcone (4) were isolated from the rhizomes of Globba pendula Roxb. ( Zingiberaceae) of Vietnam. Their structures were elucidated on the basis of extensive analysis of high-resolution electrospray ionization mass spectrometry and NMR spectral data. Absolute configuration of new compound was determined by circular dichroism spectra. All these compounds are first reported from the genus Globba.

Application of the Brook Rearrangement in Tandem with Single Electron Transfer Oxidative and Radical Processes

Merging rearrangement with radical reactions is a largely unexplored field but may hold promise for approaching scaffolds that are inaccessible by other methodology. Here a tandem nucleophilic substitution/Brook rearrangement/single‐electron transfer oxidation/radical oxygenation strategy is presented, through which α,γ‐dioxygenated ε,ζ‐unsaturated amides are efficiently prepared in a single step from enantiomerically enriched allylepoxides and 2‐silylacetamides. The resulting compounds can be easily transformed by persistent radical effect‐based 5‐exo‐trig or 6‐endo‐trig radical cyclization reactions to functionalized carbocycles bearing three or four stereocenters. The stereochemical outcome of the cyclization reactions can predicted by the Beckwith–Houk model. The cyclic compounds can be easily diversified by post‐cyclization modifications. The tandem process can be further extended by an acylation step leading to β‐dicarbonyl enolates, which were also transformed to cyclopentane and cyclohexane derivatives under oxidative conditions.

Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from Uvaria grandiflora

Chromatographic purification of the DCM sub-extract of Uvaria grandiflora led to the isolation and characterization of a new polyoxygenated cyclohexane derivative, grandifloranol (1), together with five known compounds. Among the compounds isolated, zeylenone (3) showed moderate antitubercular activity against Mycobacterium tuberculosis H37Rv with MIC90 value of 51.2 μM and antiproliferative or cytotoxic activity against human myeloid leukaemia (K-562) and HeLa cells with IC50 values of 2.3 and 18.3 μM, respectively.

Oxygenated Cyclohexene Derivatives and Other Constituents from the Roots of Monanthotaxis trichocarpa.

Three new oxygenated cyclohexene derivatives, trichocarpeols A (1), B (2), and C (3), along with nine known secondary metabolites, were isolated from the methanolic root extract of Monanthotaxis trichocarpa. They were identified by NMR spectroscopic and mass spectrometric analyses, and the structure of trichocarpeol A (1) was confirmed by single-crystal X-ray diffraction. Out of the 12 isolated natural products, uvaretin (4) showed activity against the Gram-positive bacterium Bacillus subtilis with a MIC value of 18 μM. None of the isolated metabolites was active against the Gram-negative Escherichia coli at a ∼5 mM (2000 μg/mL) concentration. Whereas 4 showed cytotoxicity at EC50 10.2 μM against the MCF-7 human breast cancer cell line, the other compounds were inactive or not tested.

Chemo- and Regioselective Synthesis of Acyl-Cyclohexenes by a Tandem Acceptorless Dehydrogenation-[1,5]-Hydride Shift Cascade

An atom-economical methodology to access substituted acyl-cyclohexenes from pentamethylacetophenone and 1,5-diols is described. This process is catalyzed by an iridium(I) catalyst in conjunction with a bulky electron rich phosphine ligand (CataCXium A) which favors acceptorless dehydrogenation over conjugate reduction to the corresponding cyclohexane. The reaction produces water and hydrogen gas as the sole byproducts and a wide range of functionalized acyl-cyclohexene products can be synthesized using this method in very high yields. A series of control experiments were carried out, which revealed that the process is initiated by acceptorless dehydrogenation of the diol followed by a redox-neutral cascade process, which is independent of the iridium catalyst. Deuterium labeling studies established that the key step of this cascade involves a novel base-mediated [1,5]-hydride shift. The cyclohexenyl ketone products could readily be cleaved under mildly acidic conditions to access a range of valuable substituted cyclohexene derivatives.

New entry to the enantioselective formation of substituted cyclohexenes bearing an all-carbon quaternary stereogenic center.

Enantioselective formation of cyclohexene derivatives bearing an all-carbon quaternary stereogenic center is described. The racemic cyclohexenes are readily transformed to chiral substituted cyclohexenes in good yield with excellent enantioselectivity and diastereoselectivity by a palladium-mediated deracemization. The resulting products are promising synthetic intermediates of biologically active natural products. This protocol provides us with a new entry to the concise and scalable synthesis of multifunctionalized compounds.

Synthesis of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines

Chalcones are famous compounds due to their mild reaction and acceptable yield, in addition to their pure products. The synthesized compounds in this study were prepared by two steps: step 1. Includes the reaction of chalcone and ethylacetoacetate to produce the previously prepared compound (cyclohexene derivative). Step 2. Includes the reaction of the last one with different primary amines to produce new compound by ring closure reaction. The identification of products based on IR, 13C-NMR How to Cite this Article Pubmed Style Mohammad HJ, Salih II, Mahmood RT. of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. SRP. 2020; 11(9): 124-129. doi:10.31838/srp.2020.9.21 Web Style Mohammad HJ, Salih II, Mahmood RT. of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. http://www.sysrevpharm.org/?mno=1826 [Access: March 29, 2021]. doi:10.31838/srp.2020.9.21 AMA (American Medical Association) Style Mohammad HJ, Salih II, Mahmood RT. of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. SRP. 2020; 11(9): 124-129. doi:10.31838/srp.2020.9.21 Vancouver/ICMJE Style Mohammad HJ, Salih II, Mahmood RT. of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. SRP. (2020), [cited March 29, 2021]; 11(9): 124-129. doi:10.31838/srp.2020.9.21 Harvard Style Mohammad, H. J., Salih, . I. I. & Mahmood, . R. T. (2020) of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. SRP, 11 (9), 124-129. doi:10.31838/srp.2020.9.21 Turabian Style Mohammad, Hamid J., Israa I. Salih, and Rabeah T. Mahmood. 2020. of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Reviews in Pharmacy, 11 (9), 124-129. doi:10.31838/srp.2020.9.21 Chicago Style Mohammad, Hamid J., Israa I. Salih, and Rabeah T. Mahmood. Synthesis of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. Systematic Reviews in Pharmacy 11 (2020), 124-129. doi:10.31838/srp.2020.9.21 MLA (The Modern Language Association) Style Mohammad, Hamid J., Israa I. Salih, and Rabeah T. Mahmood. Synthesis of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Amines. Systematic Reviews in Pharmacy 11.9 (2020), 124-129. Print. doi:10.31838/srp.2020.9.21 APA (American Psychological Association) Style Mohammad, H. J., Salih, . I. I. & Mahmood, . R. T. (2020) of Heterocyclic Nitrogen Compounds using Cyclohexene Derivative with Various Primary Reviews in Pharmacy, 11 (9), 124-129. doi:10.31838/srp.2020.9.21

Fluxional nature in cyclohexane and cyclopentane: spherical conformational landscape model revisited

Spherical conformational landscape model was revisited to include yet another class of cyclic compounds; the derivatives of cyclohexane. The updated model is not only capable of explaining Raman spectral features in fluxional cyclopentane but is also capable of revealing similarities between cyclopentane and cyclohexane derivatives for the first time. At the heart of the model lies the aspect of B/T ring coordinates (B/T conformational platform) that represents different levels of puckering (q). DFT-ωb97xd/6-311 + G* computations confirmed by MP2/aug cc-pVTZ computations were used to fully investigate 16 different derivatives of both cyclohexane and cyclopentane. Intrinsic reaction coordinate, IRC, computations were performed to gain insight into patterned inter-platform pathways connecting ring coordinates. These pathways revealed the coupling strength between bent/boat, B, and twist, T, ring coordinates. The coupling is found to be stronger for cyclopentane compared to cyclohexane. Some spectral features in the overlap region near 1400 cm−1 show promising signs on spin–spin relaxation, T2, mechanism. The work opens up an avenue for conformational studies of medium-sized rings. Also, ongoing studies to unravel potential relationships between conformational flexibility and bioactivity of cyclic compounds are underway. Conformationally mobile cyclic carbonic skeletons like cis-Octahydropentalenes are occurring in a number of natural products. A complete conformational analysis of cis-Octahydropentalenes reveals how some natural products populate their bioactive form. The pattern successfully explains the bioactive conformation in (+)-epi-goniofufrone and Hirsutic acid, both of which are natural products with potent bioactivity. Analysis like these are illustrative of how nature can use some special scaffolds to achieve maximal bioactivity, which in turn would fuel research in drug design.

Toll-like receptor 4 inhibition prevents autoimmune diabetes in NOD mice

TLR4 is a transmembrane receptor of the innate immune system that recognizes LPS from gram-negative bacteria. Its stimulation induces pro-inflammatory responses and modulates adaptive immunity. Our aim is to determine the role of TLR4 in the activation and proliferation of T lymphocytes in the onset of autoimmune diabetes, using the non-obese diabetic (NOD) mouse model. Antigen-specific activation and proliferation of diabetogenic T cells were assessed in vitro by Carboxyfluorescein succinimidyl ester (CFSE) dilution, in presence of vehicle or CLI-095, a cyclohexene derivative that inhibits TLR4 signaling. NOD mice were treated with vehicle or CLI-095 and sacrificed either before or after the onset of autoimmune diabetes. T lymphocyte activation and proliferation were evaluated in treated and control mice. Insulitis was analyzed by histology and diabetes incidence was determined in treated and control mice. Our results demonstrate that TLR4 blockade decreases CD4+ T lymphocyte activation and auto-antigen-specific proliferation both in vitro and in vivo, decreases the infiltrative insulitis and finally prevents the onset of spontaneous diabetes. Taken together, our data demonstrate that TLR4 signaling contributes to the development and maintenance of autoimmune diabetes. The immunomodulatory effect of CLI-095 could be part of a preventive strategy targeting patients at risk for type 1 diabetes.

Reductive Cycloisomerization of Diynes by Supported Palladium Catalysts and Subsequent [4+2] Cycloaddition for One‐Pot Synthesis of Cyclohexenes

AbstractAbstract: Supported Pd nanoparticles catalyzed the reductive cycloisomerization of diynes to give 1,3‐dienes, and subsequent intermolecular [4+2] cycloaddition with dienophiles led to cyclohexene derivatives. Various diynes and dienophiles participated in the one‐pot reaction to give the corresponding products in good to high yields. Al2O3‐supported Pd catalysts were highly tolerant toward air and reusable.

Catalytic Living Ring Opening Metathesis Polymerisation: The Importance of Ring Strain in Chain Transfer Agents.

A recently developed catalytic living ring opening metathesis polymerisation (ROMP) was investigated using a series of reversible chain transfer agents (CTA) carrying either cyclopentene or cyclohexene rings, differing only in ring strain. All cyclopentene derivatives examined showed significantly faster reaction rates than the corresponding cyclohexene derivatives. This resulted in lower molecular weight dispersities and better control of the molecular weight for the cyclopentene compared to the cyclohexene CTAs. Both Grubbs' second and third generation catalysts could be employed in catalytic living ROMP using cyclopentene CTA derivatives. The kinetics of different CTAs were studied, block copolymers were synthesised and residual ruthenium quantified by ICP-OES. All polymers were fully characterised by NMR, GPC and MALDI-ToF mass spectrometry. The new cyclopentene CTAs are readily synthesised in a few straightforward steps and provide faster reaction kinetics than all previously reported reversible CTAs.

Catalytic Living Ring Opening Metathesis Polymerisation: The Importance of Ring Strain in Chain Transfer Agents

AbstractA recently developed catalytic living ring opening metathesis polymerisation (ROMP) was investigated using a series of reversible chain transfer agents (CTA) carrying either cyclopentene or cyclohexene rings, differing only in ring strain. All cyclopentene derivatives examined showed significantly faster reaction rates than the corresponding cyclohexene derivatives. This resulted in lower molecular weight dispersities and better control of the molecular weight for the cyclopentene compared to the cyclohexene CTAs. Both Grubbs’ second and third generation catalysts could be employed in catalytic living ROMP using cyclopentene CTA derivatives. The kinetics of different CTAs were studied, block copolymers were synthesised and residual ruthenium quantified by ICP‐OES. All polymers were fully characterised by NMR, GPC and MALDI‐ToF mass spectrometry. The new cyclopentene CTAs are readily synthesised in a few straightforward steps and provide faster reaction kinetics than all previously reported reversible CTAs.

Investigation of anaerobic phenanthrene biodegradation by a highly enriched co-culture, PheN9, with nitrate as an electron acceptor

In this study, we developed a highly enriched phenanthrene-degrading co-culture, PheN9, which uses nitrate as an electron acceptor under anaerobic conditions, and the processes mediating biodegradation were proposed. The dominant bacteria populations included Pseudomonas stutzeri (91.7% relative abundance), which shared 98% 16S rRNA-sequence similarity with the naphthalene-degrading, nitrate-reducing strain NAP-3-1, and Candidatus_Kuenenia (2.3% relative abundance), which is a type of anammox bacteria. Enrichment transformed 54% of the added phenanthrene, reduced nitrate, and generated significant amounts of nitrite. Enrichment also result in partial consumption of the produced nitrite by the anammox bacteria. The key initial steps of anaerobic phenanthrene biodegradation by PheN9 were methylation and carboxylation, which were identified for detection of metabolic products, as well as carboxylase and methyltransferase activities. The methylation product was then oxidized to 2-naphthoic acid and then underwent sequential biodegradation steps. Then, ring-system reducing occurred, and the metabolic products were identified as dihydro-, tetrahydro-, hexahydro-, and octahydro-2-phenanthroic acid. Downstream degradation proceeded via a substituted benzene series and cyclohexane derivatives. This study employed anaerobic phenanthrene-biodegradation processes with nitrate as an electron acceptor. These findings can improve our understanding of anaerobic polycyclic aromatic hydrocarbon (PAH) biodegradation processes and guide PAH bioremediation by adding nitrate to anaerobic environments.

Double Thiol-Chiral Brønsted Base Catalysis: Asymmetric Cross Rauhut-Currier Reaction and Sequential [4 + 2] Annulation for Assembly of Different Activated Olefins.

A double catalytic system combining 2-mercaptobenzoic acid and a chiral phase transfer substance was disclosed for the intermolecular cross Rauhut-Currier reaction of 2-cyclopentenone and isatin-based alkylidene malononitriles. The resulting chiral adducts were sequentially assembled with diverse electron-deficient olefins to furnish highly enantioenriched cyclohexane derivatives (up to 96:4 er, >19:1 dr). A similar catalytic system of 2-mercaptobenzoic acid and quinine was further developed for the reaction of 2-cyclopentenone and α-cyano chalcones (up to 96.5:3.5 er).

Electrochemically Induced Diels-Alder Reaction: An Overview.

One of the most important name reactions in organic chemistry, is the Diels-Alder cycloaddition reaction. It is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile to construct a substituted cyclohexene derivative. It is the stereotypical example of a pericyclic reaction with a concerted mechanism. In synthesis, the use of electricity instead of stoichiometric amounts of oxidant or reducing agents is definitely appealing for economic, ecological and selective, reasons. In this review, we try to underscore the combination of the electrosynthesis with Diels-Alder cycloaddition reaction to establish of a powerful synthetic tool which may encourage synthetic organic chemists to use it in the future.

Synthesis of the Madangamine Alkaloid Core by a C-C Bond Activation Cascade.

The diazatricyclic core of the madangamine alkaloids was synthesized from a densely functionalized cyclohexane derivative. An alkene and two cyanoformamide groups are used to form two new rings and a new quaternary stereocenter in a cascade reaction, which involves two Pd-catalyzed C-C bond activation steps. The synthesis of the cascade precursor involves an intramolecular Staudinger reaction of a vicinal diester that gives a [3.2.1]azabicyclooctane derivative, allowing the regioselective introduction of a monosubstituted alkene.