Methyl Cyclohexanone Research Articles

Synthesis and spectral studies of some polysubstituted cyclohexanone oximes; DFT approach for the optimization

A series of t(3)-aryl-r(2), c(4)-bis(isopropoxycarbonyl)-c(5)-hydroxy-t(5)-methyl cyclohexanone oximes 8-14 were synthesized by condensing corresponding cyclohexanones with sodium acetate and hydroxylamine hydrochloride in ethanol solvent. For all synthesized compounds 1H and 13C NMR were recorded in CDCl3. HOMOCOSY, HSQC, HMBC, and NOESY spectra have been recorded for the representative compound in the series using CDCl3 as solvent. The coupling constants for all the compounds were calculated and it suggests that all the synthesized compounds be in normal chair conformation. The orientations of all substituents were at an equatorial position except hydroxy at C-5. All the synthesized cyclohexanone oximes were in E configuration about the C and N double bond. In CDCl3 the hydroxy proton at C-5 prefers to be anti to C(5)-C(6) bond. Long-range coupling was observed between the hydroxy proton at the C-5 and axial methylene proton at C-6 by having a “W” arrangement. The optimized molecular structure of compound 14 has been performed by using the DFT method with a B3LYP/6-311++G(d,p) basis set. The Non-linear optical (NLO) activity of compound 14, the linear polarizability, dipole moment, and first-order hyperpolarizability were derived from molecular polarizability by the theoretical-based calculations. To study the intramolecular charge transfer, bonding (Lewis), and anti-bonding (Non-Lewis) structural calculation was carried out using NBO analysis. The charge transfer occurring within molecule 14 was analyzed from the HOMO-LUMO calculation. The molecular electrostatic potential (MEP) surface shows the active sites present in the molecule.

Synthesis of Ketamine Derivatives by Mannich Reactions

Arylcyclohexylamine Ketamine (HCL) has played an important role in Veterinary and Human Medicine as safe and reliable anesthetic agent but asit produces dysphoria several new derivatives of Ketamine have been synthesized till date. In this Research we have Utilized Mannich reaction to Synthesize The ammonia, primary amine and secondary amine are treated with hydrochloric acid and then added to the formaldehyde. Three novel derivatives were synthesized namely2-(2-chlorophenyl)- 6-[(diethyl amino) methyl]-2-(methylamino) cyclohexanone by RXN:102 Mannich Reaction of Ketamine with Di-ethylamine , rxn 113 2-(2chlorophenyl-6-dinitrophenyl hydrazine-methyl2(methylamino) cyclohexanone by Reaction of Ketamine with Di-nitro Phenyl Hydrazine & Rxn: 601. Mannich Reaction of Ketamine with Piperazine to form (2-chlorophenyl)-2-(methylamino)-6-(piperazine -1-yl) methyl cyclohexanone. Other reactions were also undergone to prepare oxazolidine derivatives of ketamine namely Synthesis of ketamine dioxolane derivative:Ketal and Hemiaminal Formation , Rxn: 103 Reaction of Ketamine with Glycerin [6-(2-chlorophenyl)-6-(methylamino)-1, 4-dioxaspiro [4.5] dec-2-yl] methanol and Rxn: 801 Reaction of Ketamine with Ephedrine N ,3,4-trimethyl-2,6 diphenyl-1oxa-4azaspiro [4.5] decan-6-amine derivative was formed. Thin layer chromatography of the synthesized derivatives was performed by using a solvent system of ethyl acetate and chloroform (50:50) and the RF values were calculated. The solubility test proves that compounds obtained from ketamine are polar in nature. All derivatives show similarity in solubility of ketamine. Although the melting points were not exactly comparable to that of ketamine, the range was not more than 5-10°C. This relatively narrow range of melting points proved that these were pure compounds. NMR spectroscopy was performed on all newly synthesized derivatives of ketamine. The notable ones obtained from reactions i.e. Rxn 102, 113, 103, 601and 801. The results of spectroscopy demonstrate that the compounds obtained were completely new species however they were structurally related to ketamine. These derivatives synthesized and confirmed by NMR technology. The derivatives can potentially be formulated for therapeutical purpose. Despite some limitations which are being considered in current drug design, the derivatives have the potential to develop into chemically modified entities that can play a major role in clinical therapeutics. Additional research studies will potentially help to determine the advanced method for high and sophisticated yield of these derivatives. Moreover, synthesis of ketamine metabolites namely N-demethyl compound and N-demethyl-5,6-dehydro analogues is established. However, further studies and modifications of these compounds will open new ventures of drug design and development of clinical implications in health care system.

MOF-808 as a Highly Active Catalyst for the Diastereoselective Reduction of Substituted Cyclohexanones.

Zr-containing MOF-808 is an excellent heterogeneous catalyst for the diastereoselective Meerwein–Ponndorf–Verley reduction of substituted cyclohexanones. The presence of substituents at the 2 or 3 position of the cyclohexanone ring strongly drives the reaction towards the formation of one of the two possible isomers. For 3-methyl cyclohexanone, the available space inside the MOF pores allows the formation of the bulkier transition state leading to the thermodynamically stable 3-cis-cyclohexanol. For 2-methyl cyclohexanone, the reaction rate is much slower and the final diastereoselectivity depends on the size of the alcohol used. Finally, reduction of 2-phenyl cyclohexanone is considerable faster over MOF-808 than for any other catalyst reported so far. The large size of the phenyl favors the selective formation (up to 94% selectivity) of the cis-alcohol, which goes through a less hindered transition state.

Binary mixtures of 2-methyl cyclohexanone with various functional groups (Thermodynamic and acoustic properties)

In the binary mixtures of 2-methylcyclohexanone with various functional groups (3-methyl aniline, 4-methoxy benzyl alcohol, 4-hydroxy benzoic acid and isobutyric acid) the densities, and speeds of sound including those of pure liquids, were measured over the entire composition range at different temperatures (303.15, 308.15 and 313.15) K and atmospheric pressure 0.1 MPa. Using these experimentally determined data, the excess values of molar volume, isentropic compressibility of the studied binary mixtures and partial molar volumes, partial molar isentropic compressibilities of these pure components at infinite dilution were calculated. The results are discussed both in terms of free volume and proton donor–acceptor interactions between the unlike molecules.

Acoustic, volumetric and FTIR study of binary liquid mixtures of 2-methyl cyclohexanone with amides

Densities, speeds of sound, and viscosities at various temperatures were determined for the systems: 2-methylcyclohexanone (2-MCYH) + formamide (F), N-methylformamide (NMF) and N, N-dimethylformamide (DMF). From the experimental results, Excess molar volume VmE, Excess isentropic compressibility κsE, deviation in viscosity Δη and excess Gibbs energy of activation of viscous flow G*E, Excess partial molar properties at infinite dilution V¯m,1°E, V¯m,2°E, K¯s,m,1°E and K¯s,m,2°E were calculated. There is evidence of complex formation between unlike molecules. FT-IR properties have been carried out to study the specific interaction, such as the formation of the hydrogen bond between unlike molecules in the binary liquid mixtures, a good agreement is observed among the excess parameters and FT-IR spectroscopic properties.

Intermolecular interaction studies of binary liquid mixtures of 2-methyl cyclohexanone with o-anisidine/m-anisidine/p-anisidine in terms of thermo-acoustic parameters at different temperatures

In this present investigation, the thermo-acoustic fundamental parameters such as density (ρ) and speed of sound (U) were measured experimentally for the anisidine isomers (2-methoxy aniline, 3-methoxy aniline and 4-methoxy aniline) with solvent agent such as 2-methyl cyclohexanone in various concentrations within temperatures from 303.15 to 313.15K (5K interval) at ambient atmospheric pressure. From these experimentally determined values, various thermo-acoustic parameters of excess isentropic compressibility, K and excess molar volume, V are calculated. The calculated excess functions were correlated with reduced Redlich-Kister polynomial equation and results are analyzed in terms of structural molecular interactions between component molecules. Moreover, calibration of the partial molar volume's and partial isentropic compressibility’s of components shows strong interaction in 2-methyl cyclohexanone + 4-methoxy aniline than any other composites. In addition to the FTIR characteristic spectrum of all combinations at different concentrations gives the more promising features such as interaction behavior that helps our analysis to guide the interactions of individual bonding strength of the molecules.

Separation and Resolution of Methylcyclohexanones by Enclathration with Deoxycholic Acid

Deoxycholic acid (DCA) includes all the isomers of methylcyclohexanones (MCH). Competition experiments showed that the preference is 2MCH > 3MCH > 4MCH confirmed by crystal structure analysis, NMR, and thermal analysis. DCA resolves 2MCH, enclathrating the S-conformer, whereas 3MCH remains unresolved. However, in competition experiments of rac-2MCH/rac-3MCH, both guests are resolved yielding S-conformers, suggesting that 2MCH has a templating effect on the final structures. The activation energies of desolvation of the clathrates with 2MCH and 3MCH are similar (∼74 kJ/mol) but significantly lower for 4MCH (∼48 kJ/mol).

Studies on synthesis of environment-friendly products for paint and coating applications

ABSTRACTIn the study, environment-friendly products, such as ketonic resins were prepared by self-polymerisation of ketonic monomers in the presence of a base catalyst using a high-pressure batch reactor. The cross-polymerisation reactions of ketonic monomers were also examined in the work. The effects of reaction parameters, such as reaction time, temperature, catalyst concentration and monomer concentration on physico-chemical properties of the product, such as physical state, hydroxyl value, iodine value, acid value, viscosity, average molecular weight, solubility, softening temperature and thermal stability have been studied. From the results, it was observed that the polymerisation reactions with methylcyclohexanone (MCH) or cyclopentanone (CP) monomers offered high viscous liquid resins. However, addition of small proportion (5–10 wt%) of MCH or CP along with cyclohexanone (CH) can play a significant role in obtaining a better quality product. It was also observed that CH and MCH monomers offered white colour resins, whereas CP monomer offered brown colour resins. The in-house-developed resins are thermally stable up to a temperature of around 180°C. From the overall investigation, it can be concluded that the in-house-developed ketonic resin products can be a suitable substitute of alkyd, ketone−aldehyde or phenol−aldehyde resins for paint and coating applications.

Baeyer–Villiger Oxidation of Cyclohexanone by Hydrogen Peroxide with Fe3O4@GO as Catalyst Under Solvent Free Conditions

An efficient magnetic nanocomposite catalyst (Fe3O4@GO) was synthesized and utilized as a sustainable and convenient catalyst for Baeyer–Villiger oxidation. The catalyst was characterized by XRD, FT-IR, TEM, SEM, XPS, Raman and VSM. Under solvent free conditions, hydrogen peroxide as green oxidant, Fe3O4@GO showed an efficient catalytic activity and excellent selectivity for Baeyer–Villiger oxidation at room temperature. Conversion of 2-methyl cyclohexanone and selectivity of e-heptanlactone were 84% and 94%, respectively. The catalyst can be magnetically reused and recycled for several runs without any significant loss in efficiency and selectivity. An efficient magnetic nanocomposite catalyst (Fe3O4@GO) was synthesized to show high catalytic activity and excellent selectivity for the Baeyer–Villiger oxidation under solvent free conditions with hydrogen peroxide.

Evaluation of substituted methyl cyclohexanone hybrids for anti-tubercular, anti-bacterial and anti-fungal activity: Facile syntheses under catalysis by ionic liquids

An library of unresolved racemic Mannich bases incorporating two stereogenic carbon centers was evaluated for antibacterial activity against clinically isolated Gram-positive bacteria i.e. Staphylococcus aureus, Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and for antifungal activity against Candida albicans strains. Additionally, the susceptibility of microorganisms to Mannich bases prompted us to evaluate the potential for anti-tubercular activity against clinically isolated Mycobacterium tuberculosis and virulent H37Rv strains. All compounds showed potent activity against M. tuberculosis strains at MIC ranging from 50μg/mL to 6.25μg/mL of concentration. Facile one pot Mannich type syntheses of rac-(2S)-2-[(R)-[(4-substituted phenyl){[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone derivatives were achieved by reactions of various 2-amino-4-aryl-thiazoles, appropriately substituted aromatic aldehydes and cyclohexanone in Bronsted acidic quaternary ammonium sulfated ionic liquids serving as dual solvents and catalysts.

Asymmetric hydrogenation of prochiral and kinetic resolution of chiral cyclohexanone derivatives with Pd catalysts

This paper focuses on the investigation of the role of catalytic and molecular factors determining the optical yield in the enantioselective hydrogenation of C=C double bonds in prochiral unsaturated ketones and in the kinetic resolution of racemates of chiral cyclic ketones with proline mediated reductive alkylation. The hydrogenation of two unsaturated methyl cyclohexenones, and the kinetic resolution of two saturated methyl cyclohexanones with proline were studied with different Pd catalysts. The aim was to find out the effects of catalyst modifiers and chiral auxiliary, beside that of the structure and the degree of substitution of the substrates on the stereochemical outcome and yield of these reactions.

Ultrasonic Studies on Molecular Interactions in Binary Mixtures of N-Methyl Aniline with Methyl Isobutylketone, +3-Pentanone, and +Cycloalkanones at 303.15 K

Densities, ρ, viscosities, η, and ultrasonic sound velocities u of pure methyl isobutylketone, diethylketone, cyclopentanone, cyclohexanone, 2-methyl cyclohexanone and those of their binary mixtures with N-methyl aniline were measured at 303.15 K over the entire composition range. These experimental data have been used to calculate the excess volume (V E), deviation in ultrasonic sound velocity (∆u), isentropic compressibility (κ s), intermolecular free length (L f), excess intermolecular free length ( L_{text{f}}^{text{E}} ), acoustic impedance (Z), excess isentropic compressibility ( kappa_S^{text{E}} ), deviation in viscosity (∆η) and excess Gibbs energy of activation of viscous flow (G *E). The viscosity data have been correlated using three equations proposed by Grunberg and Nissan, Katti and Chaudhri, and Hind et al. The excess/deviations have been fitted by Redlich–Kister equation and the results are discussed in terms of molecular interactions present in these mixtures.

Reengineered carbonyl reductase for reducing methyl-substituted cyclohexanones

The carbonyl reductase from Candida parapsilosis (CPCR2) is a versatile biocatalyst for the production of optically pure alcohols from ketones. Prochiral ketones like 2-methyl cyclohexanone are, however, only poorly accepted, despite CPCR2's large substrate spectrum. The substrate spectrum of CPCR2 was investigated by selecting five amino positions (55, 92, 118, 119 and 262) and exploring them by single site-saturation mutagenesis. Screening of CPCR2 libraries with poor (14 compounds) and well-accepted (2 compounds) substrates showed that only position 55 and position 119 showed an influence on activity. Saturation of positions 92, 118 and 262 yielded only wild-type sequences for the two well-accepted substrates and no variant converted one of the 14 other compounds. Only the variant (L119M) showed a significantly improved activity (7-fold on 2-methyl cyclohexanone; vmax = 33.6 U/mg, Km = 9.7 mmol/l). The L119M substitution exhibited also significantly increased activity toward reduction of 3-methyl (>2-fold), 4-methyl (>5-fold) and non-substituted cyclohexanone (>4-fold). After docking 2-methyl cyclohexanone into the substrate-binding pocket of a CPCR2 homology model, we hypothesized that the flexible side chain of M119 provides more space for 2-methyl cyclohexanone than branched L119. This report represents the first study on CPCR2 engineering and provides first insights how to redesign CPCR2 toward a broadened substrate spectrum.

Rhodium(III) catalyzed oxidation of cyclic ketones by alkaline hexacyanoferrate(III)

The kinetics of the oxidation of 2-methyl cyclohexanone and cycloheptanone with Fe(CN)63− catalyzed by RhCl3 in alkaline medium was investigated at four temperatures. The rate follows direct proportionality with respect to lower concentrations of hexacyanoferrate(III) ion, but tends to become zero order at higher concentrations of the oxidant, while the reaction shows first-order kinetics with respect to hydroxide ion and cyclic ketone concentrations. The rate shows a peculiar nature with respect to RhCl3 concentrations in that it increases with increase in catalyst at low catalyst concentrations but after reaching a maximum, further increase in concentration retards the rate. An increase in the ionic strength of the medium increases the rate, while increase in the Fe(CN)64− concentration decreases the rate.

Formation of hydrates from asymmetric and cyclic ketones in their oxidation by alkaline hexacyanoferrate(III)

Alkaline hexacyanoferrate(III) oxidizes 2-methyl-3-pentanone and 2-methylcyclohexanone quite rapidly. Kinetic data show second-order kinetics with respect to hydroxide ion concentrations indicating the formation of hydrates by ketones in aqueous alkaline medium before their reaction with the oxidant. The rate follows direct proportionality with respect to the concentrations of hexacyanoferrate(III) and ketones. Externally added hexacyanoferrate(II) does not affect the reaction velocity indicating the reduction of oxidant takes place after the rate determining step. Orders with respect to various reactants were confirmed by various methods and the overall rate constant of the reaction was calculated by three different variations. Thermodynamic data suggest that 2-methyl-3-pentanone forms the activated complex more easily compared to 2-methylcyclohexanone. Second-order in [OH−] in the oxidation of 2-methyl-3-pentanone and methyl cyclohexanone by alkaline hexacyanoferrate (III) indicates that oxidation proceeds through the formation of hydrates. Rate constant and thermodynamic parameters at five temperatures were calculated. Mono and dicarboxylic acids were confirmedto be the final oxidation products. Rate law given was— $$ -\frac{\hbox{d}[\hbox{Fe}(\hbox{CN})_{6}]^{3-}}{\hbox{d}t}=k \hbox{K}_{1} \hbox{K}_{2} \frac{[\hbox{S}][\hbox{OH}]^{2}[\hbox{Fe}(\hbox{CN})_{6}]^{3-}} {[\hbox{H}_{2}\hbox{O}]^{2}}$$

The effect of the position of the methyl group on the helical twisting powers of aldol condensation products of methyl cyclohexanones

The four aldol condensation products of methylcyclohexanone isomers and 4-(4-hexyloxybenzoyloxy)benzaldehyde have been prepared. These chiral products were either obtained with high enantiomeric excess or the enantiomers were separated by means of chiral HPLC. In all cases only the E-isomer was obtained. UV irradiation was used to isomerize the E-isomers to the Z-isomers. Comparison of the helical twisting powers (HTP) of the E-isomers revealed that the derivative in which the methyl group is directly next to the double bond exhibits the highest value. Although the other three E-isomers have lower HTP values, they show large HTP changes and reversal of the helical twist sense upon irradiation. Of these compounds, the one derived from the commercially available (R)-3-methylcyclohexanone is an interesting candidate for use as an alternative to compounds derived from menthone for realizing photochemically induced twist changes in twisted nematic and cholesteric materials.

Non-Statistical Chemical Reactions: The Isomerization over Low Barriers in Methyl and Ethyl Cyclohexanones

At room temperature, methyl cyclohexanone exists in two dominant conformations in which the methyl group is either axial or equatorial to the six membered ring in the chair conformation. In addition to the axial and equatorial conformations, the ethyl cyclohexanones have several ethyl rotor positions. Both theoretical and experimental information indicate that the barriers for axial−equatorial and for the ethyl rotor interconversion are on the order of 4−5 kcal/mol. According to the transition state theory (TST), such low barriers lead to interconversion rates of 109 sec-1. Yet, it has been demonstrated that the room-temperature concentrations are frozen out during the cooling in a pulsed supersonic expansion. This means that vibrational relaxation is much more rapid than interconversion of the various conformations. The analysis of the results indicates that the axial−equatorial or ethyl rotor interconversion rates must be at least 3 orders of magnitude less than predicted by the TST. It is proposed that at the low energies associated with these reactions, most of the vibrational oscillators are in their ground states in which the anharmonic coupling to other modes is minimal. As a result, intramolecular vibrational redistribution (IVR) is insufficient to permit this reaction to proceed at its statistically expected rate. It is also noted that the same reaction in solution phase appears to proceed at the statistical rate which suggests that the participation of the solvent modes enhances IVR.

Some solvents and supporting electrolytes studied for electrochemical measurement at liquid/liquid interface

AbstractSolvents used as the organic phase of electrochemical measurement at liquid‐liquid interfaces, including phenyl isothiocyanate, o‐dichlorobenzene, benzyl cyanide, propiophenone, methyl cyclohexanone, cyclohexanone, and methyl amyl ketone, have been studied. Mixing solvents of different polarities in different ratios gives a number of new solvent systems that are suitable for showing a useful “potential window,” including the mixed‐solvent systems with nitrobenzene plus phenyl isothiocyanate, nitrobenzene plus o‐dichlorobenzene, nitrobenzene plus ketones, and the mixed solvent without nitrobenzene, such as phenyl isothiocyanate plus benzyl cyanide, phenyl isothiocyanate plus benzonitrile, o‐dichlobenzene plus benzyl cyanide, and chlorobenzene plus benzonitrile. Supporting electrolytes such as cetylpyridinium tetraphenylborate, ethyl violet tetraphenylborate, and triheptyl dodecylammonium tetraphenylborate are also introduced as the organic phase in order to extend the potential range in the negative direction.

Stereochemistry of the remote oxidative cyanation of methylcyclohexanones

1. During the oxidative cyanation of 2-, 3-, and 4-methylcyclohexanones in the Na2S2O8-NaCN system the corresponding 4-cyano(methyl)cyclohexanones are formed regiospecifically. 2. The oxidative cyanation of 2- and 3-methylcyclohexanones takes place diastereoselectively with the formation of trans- and cis-4-cyano-2(3)-methylcyclohexanones in a ratio of 1.5∶1 (or 2∶1). The selectivity of cyanation is determined by the bridge structure of the intermediate 4-oxo(methyl)cyclohexyl radicals, which are the precursors of the 4-cyanocyclohexanones.

Photosensitive UV resist of poly(methyl methacrylate) containing a bisazide compound

Poly(methyl methacrylate) (PMMA) doped with a photosensitive aromatic bisazide compound, 2,6-bis(4-azidylbenzylidene)-4- methyl cyclohexanone, was prepared and evaluated as a negative UV resist. Poly(methyl methacrylate) does not have mid-UV sensitivity because it does not absorb UV-light above 250 nm. However, when PMMA is doped with the above bisazide compound, it exhibits mid-UV sensitivity in an exposure range of 15 to 25 mJ/cm 2 (50 times more sensitivity than normally used positive tone PMMA) to give 50% film thickness remaining on the substrate after development. The doping of bisazide had the effect of reversing PMMA from positive tone to negative tone. The resist was successfully applied to contact printings followed by wet development processing using a one-to-one ratio of toluene and xylene as developer. The sensitivity of this PMMA-bisazide resist depends on the bisazide concentration in PMMA solution, and the spatial resolution was determined to be better than 1 μm.