Ketimine Derivatives Research Articles

Development of Silica‐Immobilized Material as Heterogeneous Hydrogen Bond Donor (HBD) Catalyst: Synthesis of Cyclic Carbonates from CO2 and Epoxides

AbstractComposite silica materials have been developed by hydrothermal method and utilized as heterogeneous Hydrogen Bond Donor (HBD) catalysts, where the functionalized ketimine derivatives have been immobilized on the solid support. Such functional materials have been found to be efficient catalysts for the synthesis of cyclic carbonates through the installation of CO2 with epoxides. Characterization of these materials was systematically done using various spectroscopic and imaging techniques to confirm the presence of organic compounds on the silica surface. These composite materials exhibited significantly higher catalytic activity as compared to the other homogeneous methods. Additionally, this synthetic process was extremely convenient in terms of all the external parameters such as, solvent free condition at ambient reaction temperature with normal pressure of CO2, very low catalyst loading with proper regeneration and reusability of the catalyst. These facets have definitely made this technique greener and more sustainable.

Experimental and computational study on the spectroscopic and colorimetric copper sensing behaviour of three ketimine derivatives

Three imine based colorimetric copper sensors were successfully synthesized and their copper sensing behaviours characterized via absorption spectroscopy and rationalized by density functional theoretical (DFT) calculations. All three compounds interact strongly with copper in non-aqueous and semi- aqueous media, as indicated by the exergonic nature of this process: ΔGbinding = ∼ -28 kJ mol−1, which leads to a visible colour change; a process controlled by entropic effects in combination with the relative hardness of the binding sites. These compounds allow selective detection of copper at concentrations as low as 0.16 ppm with linear ranges of 1–5 ppm and quantification limits as low as 0.52 ppm. Whereas, only zinc leads to reduced accuracy for 2-[1-(2-hydroxyphenyl)ethylideneamino]phenol, at equimolar levels, for the other derivatives, hard-soft interactions allow significant interference from various metals, present at such a concentration. Overall, these compounds represent a viable starting point for the development of cheap colorimetric copper sensors.

Enantioselective synthesis of 3-hydroxy- and 3-amino-3-alkynyl-2-oxindoles by the dimethylzinc-mediated addition of terminal alkynes to isatins and isatin-derived ketimines.

A common protocol for enantioselective alkynylation of isatins and isatin-derived ketimines using terminal alkynes and Me2Zn in the presence of a catalytic amount of a chiral perhydro-1,3-benzoxazine with moderate to excellent enantioselectivity under mild reaction conditions is described. The additions to ketimines present a novel approach to chiral amines being derivatives of oxindoles. The reaction is broad in scope with respect to aryl- and alkyl-substituted terminal alkynes and isatin derivatives. In isatins, the alkynylation occurs at the Si face of the carbonyl group, whereas in the ketimine derivatives it occurs at the Re face of the imine.

Direct access to spirooxindole dihydropyrrole fused pyrazolones and bis-spiropyrazolone derivatives

A highly regio- and diastereo-selective [3 + 2] annulation of Morita–Baylis–Hillman carbonates of isatins/pyrazolones with pyrazolone derived ketimines has been developed to access spiroheterocycles. The protocol worked effectively to construct spirooxindole dihydropyrrole fused pyrazolone and bis-spiropyrazolone dihydropyrrole derivatives bearing two vicinal quaternary spirocentres in good to excellent yields with very high diastereoselectivities under mild catalytic condition at room temperature. The protocol proved to be efficient with diverse MBH carbonates and ketimine derivatives. The method has successfully demonstrated the utility of DMAP as the commercially viable catalyst for this transformation.

Visible light-promoted CO2 fixation with imines to synthesize diaryl \u03b1-amino acids

Light-mediated transformations with CO2 have recently attracted great attention, with the focus on CO2 incorporation into C–C double and triple bonds, organohalides and amines. Herein is demonstrated visible light -mediated umpolung imine reactivity capable of engaging CO2 to afford α-amino acid derivatives. By employing benzophenone ketimine derivatives, CO2 fixation by hydrocarboxylation of C=N double bonds is achieved. Good to excellent yields of a broad range of α,α–disubstituted α-amino acid derivatives are obtained under mild conditions (rt, atmospheric pressure of CO2, visible light). A procedure that avoids tedious chromatographic purification and uses sustainable sunlight is developed to highlight the simplicity of this method.

Enantioselective Organocatalytic Mannich Reaction and Fluorination Sequence of Pyrazolones to Isatin‐derived Ketimines

An efficient asymmetric synthesis of oxindole‐pyrazolone adducts via organocatalytic Mannich reaction of 1‐phenyl‐1H‐pyrazol‐5(4H)‐ones with ketimine derivatives derived from isatins, followed by sequential electrophilic fluorination, has been developed. This approach offers a facile way to prepare chiral 3‐amino‐3‐(4‐fluoropyrazol‐4‐yl)‐substituted oxindole derivatives with a wide range of functional group tolerance.

Chirality Transfer in Rhodium(I)-Catalyzed [3 + 2]-Cycloaddition of Vinyl Aziridines and Oxime Ethers: Atom-Economical Synthesis of Chiral Imidazolidines.

A highly efficient and stereoselective synthesis of enantioenriched imidazolidines by rhodium-catalyzed intermolecular [3 + 2] cycloaddition reaction of chiral vinyl aziridines and oxime ethers has been successfully developed. Notably, both aldoximes and ketoximes are suitable substrates to afford the corresponding chiral imidazolidines in high yields with good stereoselectivity. This transformation represents an unprecedented example that utilizes ketimine derivatives as an aza-[2C]-component in cycloadditions of vinyl aziridines.

Benzothiazoline: versatile hydrogen donor for organocatalytic transfer hydrogenation.

CONSPECTUS: The asymmetric reduction of ketimines is an important method for the preparation of amines in optically pure form. Inspired by the biological system using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation of ketimines to furnish amines with high to excellent enantioselectivities. We focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric acid catalyzed transfer hydrogenation reaction of ketimines for the following reasons: (1) benzothiazoline is readily prepared just by mixing 2-aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability) and enantioselectivity would be controlled by tuning the 2-substituent of benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under inert atmosphere without conceivable decomposition. Both the 2-position of benzothiazoline and the 3,3'-position of phosphoric acid are tunable in order to achieve excellent enantioselectivity. Benzothiazoline proved to be useful hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation reaction of ketimine derivatives to afford the corresponding amines with high to excellent enantioselectivities by tuning the 2-substituent of benzothiazoline. Ketimines derived from acetophenone, propiophenone, α-keto ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be suitable substrates. Benzothiazoline could be generated in situ starting from 2-aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral phosphoric acid and successfully worked in the sequential transfer hydrogenation reaction. The reductive amination of dialkyl ketones also proceeded with high enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of α-deuterated amines with excellent enantioselectivities. The kinetic isotope effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D-benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond is the rate-determining step in the transfer hydrogenation reaction. Benzothiazoline yielded products with higher enantioselectivity in the transfer hydrogenation reaction of ketimines, particularly ketimines derived from propiophenone derivatives, than Hantzsch ester. DFT study elucidated the mechanism, as well as the difference in selectivity, between benzothiazoline and Hantzsch ester. The chiral phosphoric acid activates ketimines and benzothiazoline by means of the Brønsted acidic site (proton) and the Brønsted basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer reaction.

Hypervalent iodine-mediated synthesis of benzoxazoles and benzimidazoles via an oxidative rearrangement

A Beckmann-type rearrangement of o-hydroxy and o-aminoaryl N–H ketimines has been developed to prepare benzoxazoles and N-Ts benzimidazoles, respectively. The ketimine derivatives were easily prepared by condensation of ammonia with the corresponding ketones and (diacetoxyiodo)benzene was found to act as an efficient oxidant to trigger the [1,2]-aryl migration towards the formation of the desired heterocycles. Depending on the substitution pattern, the results revealed another mechanistic pathway through which benzisoxazoles or 1H-indazoles could be formed. The Beckmann-type rearrangement strategy was applied to the synthesis of benzimidazole-containing biorelevant targets such as chlormidazole and clemizole.

ChemInform Abstract: Chiral Phosphoric‐Acid‐Catalyzed Transfer Hydrogenation of Ethyl Ketimine Derivatives by Using Benzothiazoline.

AbstractIt is demonstrated that asymmetric hydrogenation of ketimines can be advantageously achieved with benzothiazoline as hydrogen donor in the presence of a chiral BINOL derived phosphonic acid as catalyst.

Chiral phosphoric-acid-catalyzed transfer hydrogenation of ethyl ketimine derivatives by using benzothiazoline.

Chiral phosphoric acid catalyzed transfer hydrogenation of ketimines derived from propiophenone derivatives and reductive amination of alkyl ethyl ketone derivatives were extensively examined in the presence of two representative hydrogen donors. The excellent enantioselective transfer hydrogenation was achieved by use of benzothiazoline as a hydrogen donor. The theoretical studies elucidated that the unsymmetrical structure of benzothiazoline plays an important role in high enantioselective hydrogenation.

Indium‐Promoted Diastereo‐ and Regioselective Propargylation of Chiral Sulfinylimines

AbstractThe reaction of different chiral imines 3 derived from aldehydes or ketones with the silylated propargyl bromide 4b under sonication in the presence of indium metal led mainly or exclusively to the formation of protected homopropargylamines 5 in a diastereoselective manner. Of special interest are the ketimine derivatives because the new stereocenter has a quaternary configuration. The selective deprotection of the two protecting groups, the silicon and sulfinyl moieties, was easily achieved by conventional methodologies.

Hybrid NCS palladium pincer complexes of thiophosphorylated benzaldimines and their ketimine analogs

A series of novel hybrid pincer ligands bearing thiophosphoryl and imino groups as donating arms was obtained by the condensation of 3-diphenylthiophosphorylbenzaldehyde with RNH2 (R = Ph, tBu) to afford aldimine derivatives 2a, b or by the reaction of lithiated 3-(thiophosphoryl)bromobenzene with an appropriate substituted lactam yielding their ketimine analogs 2c–e with 5–7-membered azacycloalkene moieties. The direct cyclopalladation of the ligands with (PhCN)2PdCl2 in MeCN under reflux led to κ3-NCS pincer complexes 3b–e with two five-membered fused metallacycles, isolated in low to moderate yields (12–53%); their structures were confirmed by multinuclear NMR and X-ray diffraction study. The palladacycles demonstrated high activity as (pre)catalysts for the Suzuki cross-coupling of phenylboronic acid with aryl bromides, which was found to increase in the series 3e ∼ 3d <3c< 3b, i.e. passing from ketimine derivatives 3d, e with larger azacycloalkene to their analog with smaller five-membered cyclic imine moiety and further to benzaldimine complex 3b. The tendency observed was explained by the controlled release of Pd(0) catalytically active species in the case of less sterically hindered complexes.

Synthesis of the ketimine of chitosan and 4,6-diacetylresorcinol, and study of the catalase-like activity of its copper chelate

In this study, a new chitosan derivative (ketimine) was synthesized by condensation of chitosan with 4,6-diacetylresorcinol (DAR) at heterogeneous medium. The ketimine derivative of chitosan (DAR-chitosan) was characterized by elemental (C, H, N), spectral (DR-UV–vis and FT-IR spectroscopy), structural (powder XRD), and morphological (SEM) analyses. The degree of substitution (DS) of DAR-chitosan was evaluated by elemental analysis and 13C CP-MAS NMR spectroscopy and found to be around 12%. The copper (II) metal complex of DAR-chitosan was prepared and characterized by FT-IR, DR-UV–vis and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Thermal behaviors of the synthesized compounds were investigated by DSC and TG-DTG-DTA analysis. The catalytic activity of copper (II) complex of chitosan derivative (DAR-chitosan-Cu) was investigated on hydrogen peroxide decomposition. The copper chelate showed high efficiency (over 80%) towards the decomposition of hydrogen peroxide as heterogeneous catalyst.

Synthesis, Electronic Structure, and Catalytic Activity of Reduced Bis(aldimino)pyridine Iron Compounds: Experimental Evidence for Ligand Participation

The two-electron reduction chemistry of the aryl-substituted bis(aldimino)pyridine iron dibromide, ((iPr)PDAI)FeBr(2) ((iPr)PDAI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N═CH)(2)C(5)H(3)N), was explored with the goal of generating catalytically active iron compounds and comparing the electronic structure of the resulting compounds to the more well studied ketimine derivatives. Reduction of ((iPr)PDAI)FeBr(2) with excess 0.5% Na(Hg) in toluene solution under an N(2) atmosphere furnished the η(6)-arene complex, ((iPr)PDAI)Fe(η(6)-C(7)H(8)) rather than a dinitrogen derivative. Over time in pentane or diethyl ether solution, ((iPr)PDAI)Fe(η(6)-C(7)H(8)) underwent loss of arene and furnished the dimeric iron compound, [((iPr)PDAI)Fe](2). Crystallographic characterization established a diiron compound bridged through an η(2)-π interaction with an imine arm on an adjacent chelate. Superconducting quantum interference device (SQUID) magnetometry established two high spin ferrous centers each coupled to a triplet dianionic bis(aldimino)pyridine chelate. The data were modeled with two strongly antiferromagnetically coupled, high spin iron(II) centers each with an S = 1 [PDAI](2-) chelate. Two electron reduction of ((iPr)PDAI)FeBr(2) in the presence of 1,3-butadiene furnished ((iPr)PDAI)Fe(η(4)-C(4)H(6)), which serves as a precatalyst for olefin hydrogenation with modest turnover frequencies and catalyst lifetimes. Substitution of the trans-coordinated 1,3-butadiene ligand was accomplished with carbon monoxide and N,N-4-dimethylaminopyridine (DMAP) and furnished ((iPr)PDAI)Fe(CO)(2) and ((iPr)PDAI)Fe(DMAP), respectively. The molecular and electronic structures of these compounds were established by X-ray diffraction, NMR and Mössbauer spectroscopy, and the results compared to the previously studied ketimine variants.

Mass spectrometric characterization of the isoforms in Escherichia coli recombinant DNA-derived interferon alpha-2b

The isoforms Iso-2, Iso-3, and Iso-4 of Escherichia coli-derived recombinant human interferon alpha-2b (rhIFN α-2b), generated by posttranslational modifications of the protein during fermentation, present a major problem in terms of purification and the yield of the drug substance. We report here the structural characterization of these isoforms by mass spectrometry (MS) methods. An extensive MS study was conducted on Iso-4, which is composed of up to 75% of the in-process IFN, and on the native rhIFN α-2b. The trypsin-digested peptide mixtures generated from the two samples were analyzed by liquid chromatography (LC)–MS, and targeted peptides were further studied by LC–tandem MS (triple quadrupole mass spectrometer), high-resolution MS n (LTQ Orbitrap), and matrix-assisted laser desorption/ionization MS (MALDI–MS). The structure of Iso-4 was elucidated as a novel pyruvic acid ketimine derivative of the N-terminal cysteine (Cys1) of IFN α-2b, where the disulfide bond between Cys1 and Cys98 was fully reduced and the other disulfide bond pair, Cys29-ss-Cys138, was partially reduced. Similarly, Iso-2 was identified as a correctly disulfide-folded rhIFN α-2b with acetylation on Cys1, and Iso-3 was identified as an S-glutathionylated form (Cys98) of partially reduced rhIFN α-2b that was pyruvated on Cys1. Based on the characterization work, a reproducible conversion procedure was successfully implemented to convert Iso-4 to rhIFN α-2b.

RuCl 3(H 2O) n]-catalyzed direct arylations

Catalytic amounts of economically attractive [RuCl 3(H 2O) n ] allow for direct arylations via C–H bond functionalization with aryl bromides under phosphine ligand-free reaction conditions. Thereby, a variety of functionalized (hetero)aryl bromides, bearing either electron-withdrawing or electron-releasing substituents, can be employed for direct arylations of pyridine, oxazoline, pyrazole, or ketimine derivatives as pronucleophiles.

Synthesis and Structural Characterization of a Monofunctionalized Phloroglucin-Derivative: A Precursor for Heterotrinuclear meta-Phenylene Bridged Complexes

As part of our synthetic efforts for new triplesalen derivatives, we reacted 2,4,6-triacetyl- 1,3,5-trihydroxybenzene (1) with excess Cu(ClO4)2 · 6H2O, imidazole, and ethylenediamine. However, not the triple ketimine derivative was formed but the mononuclear CuII complex [LCuII(ImH)]ClO4 · 0.5EtOH · 0.5H2O (HL = 6-(1-(2-aminoethylimino)ethyl)-2,4-diacetyl-1,3,5-trihydroxybenzene) with only one ketimine function. This complex forms a one-dimensional coordination polymer in the solid state through the apical binding of a keto-oxygen atom of one cation to the CuII ion of a neighboring cation. Magnetic measurements reveal the presence of weak antiferromagnetic intra-chain interactions

Polymer-Supported Methyleneaziridines for Multicomponent Reactions

1,3-Disubstituted propanones 4 were prepared by a three-component reaction of 2-methyleneazilizines 1 anchored on the resin with Grignard reagents and electrophiles. Thus, methyleneazilizines 1 reacted with several Grignard reagents in the presence of cupper iodide to form the corresponding metalloenamines 2. The alkylation of metalloenamines 2 with alkyl electrophiles gave ketimine derivatives 3. Filtration and hydrolysis of resin-bound ketimines 3 with pH 4.5 buffer provided the corresponding 1,3-disubstituted propanones 4a-f in 39-81% yields with high purity (91-99%).

Stereoselective Dihydroxylation Reactions of γ‐Amino‐α,β‐unsaturated Esters via Their Aryl Ketimine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.