Cycloaliphatic Ketones Research Articles

Electrochemical oxo-functionalization of cyclic alkanes and alkenes using nitrate and oxygen

Direct functionalization of C(sp3)–H bonds allows rapid access to valuable products, starting from simple petrochemicals. However, the chemical transformation of non-activated methylene groups remains challenging for organic synthesis. Here, we report a general electrochemical method for the oxidation of C(sp3)–H and C(sp2)–H bonds, in which cyclic alkanes and (cyclic) olefins are converted into cycloaliphatic ketones as well as aliphatic (di)carboxylic acids. This resource-friendly method is based on nitrate salts in a dual role as anodic mediator and supporting electrolyte, which can be recovered and recycled. Reducing molecular oxygen as a cathodic counter reaction leads to efficient convergent use of both electrode reactions. By avoiding transition metals and chemical oxidizers, this protocol represents a sustainable oxo-functionalization method, leading to a valuable contribution for the sustainable conversion of petrochemical feedstocks into synthetically usable fine chemicals and commodities.

The mechanism of one-pot assembly of tetracyclic derivatives of frontalin from cycloaliphatic ketones and acetylene in KOH/DMSO medium: A quantum-chemical study

Abstract The mechanism of one-pot assembly of tetracyclic derivatives of frontalin from cycloaliphatic ketones and acetylene, in superbasic KOH/DMSO medium has been investigated using the quantum-chemical B2PLYP/6-311+G∗∗//B3LYP/6-31+G∗ approach. It is demonstrated that the diastereomeric composition of tetracyclic frontalins is determined at the stage of ethynylation of the intermediate 1,5-diketone, and the violation of the diastereoselectivity of the assembly is associated with comparable activation barriers and rates of ethynylation reaction for different diastereomers. It is shown that the reactions of ethynylation of cyclohexanone and subsequent O-vinylation of propargyl alcohol, which compete with the cascade assembly of tetracyclic frontalins, are thermodynamically and kinetically less favorable.

The selective reductive amination of aliphatic aldehydes and cycloaliphatic ketones with tetragonal zirconium dioxide as the heterogeneous catalyst

A selective reductive amination of aliphatic aldehydes and cycloaliphatic ketones is achieved with tetragonal zirconium dioxide (t-ZrO2) as the catalyst. With N, N-dimethyl formamide (DMF) as the solvent, low-molecular-weight amine source and reductant, a more than 99 % yield of N, N-dimethylpentan-1-amine or N, N-dimethyl cyclohexanamine was obtained when n-pentanal or cyclohexanone was used as the substrate. Particularly, the crystallographic structures exhibit a significant effect on catalytic performance where the tetragonal crystalline was preferable to monoclinic one during the reductive amination reaction. In addition, the recycling experiments of catalysts indicate that t-ZrO2 still kept a high catalytic activity even after being reused five times. From the result of DFT calculations, it is concluded that the crystalline of zirconium dioxide is closely related to the charge transferring rate between the catalyst and the adsorbed reactant. Finally, based on the experiment phenomena and simulation result, a possible reaction mechanism is proposed for the reductive amination of cyclohexanone.

Thermodynamics and isomerism of products and intermediates of a one-pot superbase-promoted assembly of tetracyclic frontalin derivatives: A quantum chemical study

Tetracyclic frontalin derivatives are used as precursors of drugs for the therapy and prevention of HIV infections and cancer, as well as antibiotics with a wide spectrum of antibacterial action. A recently proposed method of the preparation of tetracyclic frontalin derivatives from two cycloaliphatic ketone molecules and two acetylene molecules in a superbasic catalytic system KOH/DMSO has opened up an elegant and direct approach to the design of these classes of biologically active compounds. In this work, we carried out a quantum-chemical study of isomerism and thermodynamic stability of intermediates and product of the reaction underlying the aforementioned approach. Particular attention was paid to the issues of diastereomerism and violation of diastereoselectivity of the reaction when replacing alkylaromatic or dialkyl ketones by cycloaliphatic ketones in the reactions with acetylene. Based on the results we propose a possible reason for the experimentally observed formation of a mixture of diastereomers of 14,16-dioxatetracyclohexadecane in the cascade assembly of two cyclohexanone molecules and two acetylene molecules. It is shown that the observed ratio of the 14,16-dioxatetracyclohexadecane diastereomers correlates with the equilibrium ratio of cascade assembly intermediates, the semiketal anion diastereomers.

Polycyclic bridgehead acetals with enol functionality: one-pot assembly from aliphatic ketones and acetylene in KOH/DMSO suspension

Aliphatic and cycloaliphatic ketones undergo selective multi-site cascade C–H functionalization with acetylene in the KOH/DMSO superbase suspension under mild conditions (70–80 °C, 0.5–1.0 h) to afford in one synthetic operation polycyclic bridgehead acetals with enol functionality, [methylene-6,8-dioxabicyclo[3.2.1]octanes] (the isolated yields reach 84%).

Diastereo- and enantioselective reductive amination of cycloaliphatic ketones by preformed chiral palladium complexes

Chiral cycloaliphatic amines were obtained from the direct asymmetric reductive amination of cycloaliphatic ketones using a preformed chiral palladium catalyst.

Transition Metal‐Free Stereoselective α‐Vinylation of Cyclic Ketones with Arylacetylenes in the Superbasic Catalytic Triad Potassium Hydroxide/tert‐Butyl Alcohol/Dimethyl Sulfoxide

AbstractA stereoselective α‐vinylation of cycloaliphatic ketones with arylacetylenes under the transition metal‐free conditions has been developed. The reaction is promoted by the superbasic catalytic triad potassium hydroxide/tert‐butyl alcohol/dimethyl sulfoxide (80–110 °C, 1–2 h) to afford mainly (E)‐β,γ‐ethylenic ketones, their (E)‐α,β‐isomers being minor products, in up to 83% total yield.

Studies on the synthesis and some reactions of (S)-proline hydrazides

A convenient synthesis of (S)-proline hydrazide 2a via the reaction of ethyl (S)-N-benzylprolinate with hydrazine hydrate and subsequent deprotection of (S)-N-benzyl proline hydrazide 5 is described. The latter, in methanolic solution, reacted with aromatic aldehydes as well as with cycloaliphatic ketones at room temperature to give the corresponding hydrazones of type 7 in good yields. The structure of the product with furan-2-carbaldehyde 7b, proving the (E)-configuration of the hydrazone, was established by X-ray crystallography. In the case of the unprotected (S)-proline hydrazide 2a, the analogous reaction with aromatic aldehydes led either to the expected hydrazones 7 or the 1H-pyrrolo[1,2-c]imidazol-1-one derivatives 8, depending on the reaction conditions. The latter were formed via a secondary cyclocondensation of the initially formed 7 with a second molecule of the aldehyde. Whereas the reaction of (S)-N-benzyl proline hydrazide 5 with butyl isocyanate and isothiocyanate gave the corresponding semicarbazide and thiosemicarbazide, respectively, of type 9, the unprotected (S)-proline hydrazide 2a yielded the 1:2 adducts 10. Thiosemicarbazide 9b underwent cyclization reactions under basic (NaOH) and acidic (H2SO4) conditions to yield (S)-prolinyl-substituted 1,2,4-triazole-3-thione 11 and 1,3,4-thiadiazole-2-amine 12, respectively.

Spacer-Dependent Structural and Physicochemical Diversity in Copper(II) Complexes with Salicyloyl Hydrazones: A Monomer and Soluble Polymers

Complexation of copper(II) with a series of heterodonor chelating Schiff bases (LL) of salicylic acid hydrazide and aliphatic or cycloaliphatic ketones affords soluble one-dimensional (1D) metallopolymers containing Schiff bases as bridging ligands. Single-crystal X-ray diffraction results reveal nanometer-sized metallopolymeric wires [Cu(μ-LL)(2)](n) with off-axis linkers and a zigzag geometry. Octahedrally coordinated copper centers, exhibiting a Jahn-Teller distortion, are doubly bridged by two Schiff-base molecules in the μ(2)-η(1),η(2) coordination mode. The use of dibutylketone with long alkyl chains as a component for Schiff base formation leads to a distorted square planar monomeric copper(II) complex [Cu(LL)(2)], as evidenced by its X-ray crystal structure. The compounds are characterized by elemental analyses and IR and UV-vis spectroscopy, as well as magnetic susceptibility and cyclic voltammetry measurements. Electrochemical studies on the complexes reveal an existence of polymeric and monomeric forms in solution and the dependence of Cu(II)/Cu(I) reduction potentials on alkyl groups of salicyloyl hydrazone ligands. Polymeric complexes form conducting films on Pt electrodes upon multicycle potential sweeps.

Study of induced hypohalogenation of 1-alkyl(4-methylcyclohex-1-enyl)alkanones, and chemical transformations of the obtained compounds

Induced hydroxyhalogenation of alkyl cyclohexenyl ketones in the systems [MHlg-HX or HHlg]-H2O2 or (NaClO) was performed and the optimal conditions of this reaction were elucidated. It is established that in the system in situ is induced a hypohaloid acid HClO or HBrO is produced that then enters into electrophilic addition at the ring double bond affording hydroxyhalo derivatives of the cycloaliphatic ketones. The alkyl cyclohexenyl ketone chloro(bromo)hydrines and the oxiranes obtained from them are very reactive compounds and can be used as initial compounds for the synthesis of many individual organic compounds

Induced halogenation of alkyl cyclohexenyl ketones involving metal halides, hydrohalogenic acids, and hydrogen peroxide

The induced halogenation and hydroxyhalogenation of alkyl cyclohexenyl ketones in a system [MHlg + HHlg or HHlg]-H2O2 or in NaOCl was performed and optimum reaction conditions were established. Under mild conditions the electrophilic addition of the halogen or the acid occurred at the multiple bond of the ring with the formation of the corresponding dihalo or hydroxyhalo derivatives of cycloaliphatic ketones. From the compounds obtained epoxy- and dioxyketones of aliphatic series were prepared. Chloro(bromo)hydrins of ketones from the alkylcyclohexane series and oxiranes based thereon are reactive compounds and can be employed as synthons in the organic synthesis.

Synthesis of cross‐conjugated polyketones by the crossed‐aldol condensation of cyclic ketones with aromatic dialdehydes

AbstractInsoluble cross‐conjugated polyketones were prepared from terephthalaldehyde and a variety of cycloaliphatic ketones by the crossed‐aldol condensation. Elemental analyses and infrared spectra suggest that the polymeric aldol intermediates were not completely dehydrated. Evidence is also presented that suggests conjugate addition of the base to the α,β‐unsaturated ketone may occur. Soluble cross‐conjugated polyketones were prepared from terephthalaldehyde and 2‐indanone, which contains no beta hydrogens, and from cycloaliphatic ketones and 1,2‐bis(4‐formylphenoxy)ethane, a dialdehyde containing isolated aldehyde groups. It is proposed, therefore, that the lack of solubility in the terephthalaldehyde‐based polyketones arises from crosslinking via enolate anions formed at the beta position of the cyclic ketones, which are delocalized through the carbonyl groups of neighboring backbone repeating units. © 1995 John Wiley & Sons, Inc.

A new and simple synthesis of alkyl, cycloalkyl and aralkyl diselenides from aliphatic or aromatic aldehydes or aliphatic or cycloaliphatic ketones

A new and simple synthesis of alkyl, cycloalkyl and aralkyl diselenides from aliphatic or aromatic aldehydes or aliphatic or cycloaliphatic ketones

Amalgamated aluminium in methylene chloride as reducing agent. A new convenient method for pinacolic reduction of aliphatic and cycloaliphatic ketones.

Amalgamated aluminium in methylene chloride as reducing agent. A new convenient method for pinacolic reduction of aliphatic and cycloaliphatic ketones.

New classes of orally active hormonal derivatives. I. Alkyl androstan-17β-yl and alkyl 19-norandrostan-17β-yl mixed acetals

A series of alkyl steroid- 17β-yl mixed acetals of aliphatic and cyclo-aliphatic ketones have been prepared from several androstane and 19-norandrostane derivatives. By oral administration many of these compounds, which are easily hydrolizable both in vitro and in vivo , have proved to be more potent than methyltestosterone in the usual test for androgenic and myogenic activity.

Ethynylation of cycloaliphatic ketones

1. The ethynylation of cycloaliphatic ketones was studied. With sodium acetylide,3-cyclohexen-1-ylketones condense rather worse than the corresponding cyclohexyl ketones do. 2. In their condensation with lithium acetylide cyclohexyl, 3-cyclohexen-1-yl, and 1-cyclohexen-1-yl ketones form tertiary acetylenic alcohols with equal ease in yields of 70–80%.