Imino Compounds Research Articles

Asymmetric Hydrogenation of α-Amino Esters into Optically Active β-Amino Alcohols through Dynamic Kinetic Resolution Catalyzed by Ruthenabicyclic Complexes.

Racemic α-substituted α-amino esters were hydrogenated into enantioenriched β-amino alcohols through dynamic kinetic resolution with chiral ruthenabicyclic complexes. The reaction was carried out with a substrate/catalyst molar ratio of 200-1000 under 15 atm of H2 at 25 °C to afford a variety of β-substituted β-aminoethanols in up to 96% ee (24 examples). The mechanistic studies including deuteration experiments suggested that the reaction proceeds with 1,2-hydride migration of the α-amino acetalate intermediate into the α-hydroxy imine followed by the continuous reduction of the imino compound, affording the amino alcohol product.

Synthesis and antidiabetic activity of novel triazole derivatives containing amino acids

AbstractNew series of triazole derivatives coupled with amino acids 1a‐h were obtained via multicomponent reaction of 2‐hydroxy benzaldehyde or 2‐hydroxy acetophenone with thiosemicarbazide and different amino acids. The obtained compounds were reacted with p‐toluinesulfonyl chloride 2 to give the corresponding sulfonamides 3a‐h. Compound 1b was allowed to react with different aromatic aldehydes or cyclic ketone under alkaline conditions to afford the expected imino compounds 4a‐d and 6a‐c, respectively. These compounds were allowed to react with ethyl glycolate to yield the expected thiazolidinone derivatives 5a‐d or 7a‐c, respectively. Structures of the newly synthesized compounds were found to be in accordance with their elemental analyses and spectral data. The obtained compounds exhibited very prominent in vitro and in vivo antihyperglycemic effect at a dose of 40 mg/kg body weight compared to the standard drug gliclazide and control. The antidiabetic effect was investigated using oral glucose tolerance test in normal and non‐insulin‐dependent diabetes mellitus (NIDDM) in STZ‐rat model. Compounds 3a‐h, 5b, 5c, 5d, 7a, 7b, and 7c showed significant activity in lowering blood glucose (more than 80%) compared to the NIDDM control.

Development of Asymmetric Reactions Catalyzed by Ruthenium Complexes with Two Kinds of Ligands

Abstract Two types of chiral Ru(II) complexes, each with two kinds of ligands, have been designed and utilized as catalysts for several asymmetric reactions under appropriate conditions. The first type, the diphosphine/diamine–Ru(II)-type complexes, were found to catalyze the hydrogenation of a variety of simple and functionalized ketones as well as imino compounds with high activity and enantioselectivity. The double asymmetric hydrogenation of α,β-unsaturated ketones into the chiral saturated alcohols was achieved by using the dual catalyst system, which reversibly forms two catalytic species. The asymmetric isomerization of primary allylic alcohols into the optically active aldehydes with almost perfect enantioselectivity was realized with this type of catalyst. The second type, the amino acid/diphosphine–Ru(II)-type complexes combined with Li compounds, exhibited excellent catalyst performance in the asymmetric cyanosilylation of aldehydes as well as simple and functionalized ketones. The isolated Ru·Li bimetallic complexes were suitable for the asymmetric hydrocyanation of aldehydes. This combined system was applicable to the asymmetric conjugate hydrocyanation of α,β-unsaturated ketones and carboxylic acid derivatives, and the Strecker-type reaction of the π-isoelectronic N-alkoxycarbonyl aldimines. This account describes the concept underlying the design of these catalysts, and the catalyst performance in the asymmetric reactions.

Dual-mode cross-coupling on aromatic imino compounds by dihydridoruthenium catalysts

In the catalytic cross-coupling reaction of ketimines, derived from 1-acetonaphthone or acetophenone derivatives and benzylamine, with trialkoxyvinylsilanes RuH2(PPh3)4 or RuH2(CO)(PPh3)3 catalyst caused the selective alkenylation and alkylation on each aromatic ring of the ketimines separately (i.e. dual-mode coupling). Alkenylation occurred at the ortho-position(s) of the benzyl unit and alkylation occurred at the ortho-position(s) of 1-arylethylidene moiety of the substrates. By the stoichiometric reaction of N-1-(4-methylphenyl)ethylidene-4-methylbenzylamine with RuH2(CO)(PPh3)3 in the presence of three equivalents of vinylsilane, a novel ruthenium bismetallacylclic complex with two ruthenium-carbon bonds was isolated. This (C,N,C)-bismetallacycle complex was converted to the alkenylated complex by the reaction with two equiv. of vinylsilane. These observations indicate that the dual-mode coupling proceeds in a sequence of alkenylation followed by alkylation via intermediary bismetallacyclic complex formation.

Synthesis and Reactions of Pyrido[2,1‐a]isoquinolin‐4‐yl Formimidate Derivatives and Antimicrobial Activities of Isolated Products

Treatment of arylidene malononitriles 2A–C with 1‐cyanomethylisoquinoline 1 afforded 4‐amino‐2‐arylpyrido[2,1‐a]isoquinoline‐1,3‐dicarbonitrile derivatives 5A–C, which converted to formimidates 6A–C via reaction with triethylorthoformate. Treatment of the latter compounds with hydrazine hydrate gave the corresponding amino–imino compounds 7A–C, which underwent Dimroth rearrangement to afford 13‐aryl‐1‐hydrazinylpyrimido[5′,4′:5,6]pyrido[2,1‐a]isoquinoline‐12‐carbonitrile 8A–C. The latter reacted with aldehyde to give 9a–i. Oxidative cyclization of the latter compounds 9a–i gave [1,2,4]triazolo[4″,3″:1′,6′]‐pyrimido[5′,4′:5,6]pyrido[2,1‐a]isoquinolines 10a,d,g. Such compounds isomerized to the thermodynamically more stable isomers [1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:5,6]‐pyrido[2,1‐a]isoquinolines 11a,d,g. Antimicrobial activities for some compounds were studied.

Chemical and Antioxidant Properties of Betalains.

Betalains are vacuolar pigments composed of a nitrogenous core structure, betalamic acid. Betalamic acid condenses with imino compounds (cyclo-DOPA/its glucosyl derivates) or amino acids/derivates to form violet betacyanins and yellow betaxanthins. These pigments have gained the curiosity of scientific researchers in recent decades. Their importance was increased not only by market orientation toward natural colorants and antioxidants but also by their safety and health promoting properties. To date, about 78 betalains have been identified from plants of about 17 families. In this review, all of the identified pigments are presented, followed by a comprehensive discussion of their structure-activity relationship.

Stereodynamics and edge-to-face CH-π aromatic interactions in imino compounds containing heterocyclic rings.

By comparison with close contact interactions between benzene rings there is a paucity of experimental data available for attractive interactions involving aromatic heterocyclic rings, especially for small molecules in solution. Herein we describe aromatic heterocyclic and carbocyclic edge-to face interactions and conformational stereodynamics of N-1,2-diphenylethyl imines bearing a phenyl group and either a 2-pyridyl, 3-pyridyl, 2-thiophene or 2-furanyl moiety on the imino carbon. X-ray crystal structures have been determined for two compounds. Slow rotation about the phenyl-imino bond in the E-isomers and around the heterocycle-imino bond in the Z-isomers of the pyridyl compounds was observed at low temperatures by NMR. Abnormally large shielding of one ortho hydrogen indicates that both the imino phenyl and heterocycle rings can engage in an edge-to-face interaction with the N-terminal phenyl moiety in the appropriate isomer. Some rotational barriers around the phenyl-imino and heterocycle-imino bonds were measured.

Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols.

Catalytic asymmetric hydrogenation of ketones through the "metal-ligand cooperative mechanism" has been improved in terms of the efficiency, stereoselectivity, and scope of substrates by varying the arrangement of the catalyst structure and reaction conditions. Imino compounds are also smoothly converted to the optically active amines with appropriate catalysts. This type of catalyst exhibits excellent performance on the asymmetric isomerization of primary allylic alcohols into the optically active aldehydes. This personal account describes recent progress on these topics.

Plant Betalains: Safety, Antioxidant Activity, Clinical Efficacy, and Bioavailability.

Betalains are accepted food additives derived from vacuoles of plants belonging to about 17 families in the order Caryophyllales. These pigments are composed of a nitrogenous core structure, betalamic acid [4-(2-oxoethylidene)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid]. Betalamic acid condenses with imino compounds (cyclo-DOPA and/or its glucosyl derivatives) or amines and/or their derivatives to form violet betacyanins (for example, betanin) and yellow betaxanthins (for example, indicaxanthin), respectively. Till date, structures of 75 betalains have been elucidated from plants under the order Caryophyllales. The extracted betalains are safe to consume and they act as micronutrients in the body. In vitro studies to highlight radical-scavenging activity, cell culture studies to assess cytotoxicity and absorption of betalains, and proven clinical efficacies are compiled in this review. The literature on biological activity has not been analyzed for a synthesis of safety, clinical efficacy, and bioavailability to arrive at the concentrations required for the purported health benefits. Most betalains are under-utilized in pharmaceutical and cosmetic preparations due to poor stability and lack of scientific reports highlighting their superior tinctorial strength including flourescence, water solubility, and functional value alongside their bioavailability. This is the first comprehensive review on the dietary safety, biological activity and bioavailability of betalains. Based on this review, for future debate and input from health professionals, a human daily intake of betanin and indicaxanthin can be proposed at 100 and 50 mg, respectively.

ChemInform Abstract: Control of Asymmetry in the Radical Addition Approach to Chiral Amine Synthesis

AbstractReview: 66 refs.

Reaction of pentafluoropyridine with oxime nucleophiles via SNAr reactions for preparation of new p-substituted tetrafluoropyridyl derivatives

A new and improved preparation of perfluoropyridin-4-yloxy imino compounds from pentafluoropyridine is described. Pentafluoropyridine was used as the starting material for the preparation of a range of pyridine derivatives that bear mono-substituent. The nucleophilic substitution of pentafluoropyridine with oximes occurs at the 4-position of pyridine ring by the oxygen site of oxime. Therefore, in this work, we wish to report an efficient synthetic route of the oxime-containing perfluoroheteroaromatic systems for the first time. .

Imino(phenoxide) compounds of magnesium: Synthesis, structural characterization, and polymerization studies

ABSTRACTA plethora of magnesium compounds containing imino(phenoxide) (1–4) and bis(imino)phenoxide (5–10) ligand backbone have been synthesized via the reaction of diethyl magnesium with two equivalent of the corresponding ligand. These compounds were completely characterized by different spectroscopic techniques and elemental analyses. The monomeric nature of the magnesium complexes 3, 5, 6, 9, and 10 were further confirmed by single crystal X‐ray diffraction studies. The magnesium centers posses distorted trigonal bipyramidal geometry. The controlled hydrolysis compound Mg7O8 (C22H28NO2)6 (11) was adequately characterized using 1H, 13C NMR, ESI‐MS, and the biscubane structure was further confirmed by single crystal X‐ray diffraction studies. The Mg7O8 core is deeply embedded with the ligand periphery. These compounds (1–10) were found to be active towards the bulk ring opening polymerization (ROP) of lactides, yielding polymers with high number average molecular weight (Mn) and controlled molecular weight distributions (MWDs). In addition, these compounds have been shown to be highly active toward the copolymerization of carbon dioxide with cyclohexene oxide and styrene oxide. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1474–1491

Utility of Styrylpyrazoloformimidate in the Synthesis of Fused Heterocyclic Compounds

Refluxing of (E)-5-amino-1-phenyl-3-styryl-1H-pyrazole-4-carbonitrile 2 with triethylor-thoformate in acetic anhydride afforded the corresponding formimidate 3. Treatment of 3 with hydrazine hydrate in ethanol afforded amino imino compound 4. Reaction of 4 with diethyl dicarbonate at reflux gave (E)-7-phenyl-9-styryl-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine 7. Refluxing of 4 with hydrazine hydrate afforded (E)-4-hydrazinyl-1-phenyl-3-styryl-1H-pyrazolo[3,4-d] pyrimidine 8. Treatment of the latter compound 8 with aldehydes in boiling ethanol in the presence of acetic acid afforded the corresponding hydrazone 10. Oxidative cyclization of the hydrazone 10 led to the formation of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 11. The latter products re-arranged to pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines 13. The structures of the new products were established on the basis of elemental analysis and spectral data.

ChemInform Abstract: Organomanganese‐Mediated Radical Reactions

AbstractReview: 141 refs.

Facile Synthesis and Characterization of New 2,3-Disubstituted Benzimidazole Derivatives

Benzimidazoles are known to represent a class of medicinally important compounds which are extensively used as antibacterial agents. Hence, a series of five 2-substitutedbenzimidazole precursors (1a-e) were synthesized via [4 + 1] condensation and imino compound (1f) by simple condensation in the presence of Conc. HCl as catalyst. Synthetic modification of N-1 position was achieved in order to obtain new 5-chloro-2,4-dinitrophenyl bearing 1,2-disubstituted benzimidazole 2a-e and 2f, and 3-chlorobenzyl bearing 1,2-disubstituted benzimidazole 3a-e and 3f in good to excellent yields using a facile approach. The chemical structures of all synthesized compounds were confirmed using spectroscopic means such as UV-visible, IR, Mass spectra, 1H and 13C NMR as well as C, H, N elemental analytical data.

Control of asymmetry in the radical addition approach to chiral amine synthesis.

The state-of-the-science in asymmetric free radical additions to imino compounds is presented, beginning with an overview of methods involving stereocontrol by various chiral auxiliary approaches. Chiral N-acylhydrazones are discussed with respect to their use as radical acceptors for Mn-mediated intermolecular additions, from design to scope surveys to applications to biologically active targets. A variety of aldehydes and ketones serve as viable precursors for the chiral hydrazones, and a variety of alkyl iodides may be employed as radical precursors, as discussed in a critical review of the functional group compatibility of the reaction. Applications to amino acid and alkaloid synthesis are presented to illustrate the synthetic potential of these versatile stereocontrolled carbon-carbon bond construction reactions. Asymmetric catalysis is discussed, from seminal work on the stereocontrol of radical addition to imino compounds by non-covalent interactions with stoichiometric amounts of catalysts, to more recent examples demonstrating catalyst turnover.

ChemInform Abstract: Asymmetric Methods for Radical Addition to Imino Compounds

AbstractReview: 143 refs.

Buchwald–Hartwig C–N cross coupling reactions catalyzed by a pseudo-pincer Pd(II) compound

The reaction of the imino compound [C 6H 4-1-(OH)-3-(CH NC 6H 2-2,4,6-Me 3)] ( 1) with [Pd(COD)Cl 2] affords in good yields the cyclometalated product ▪ ( 2), both species being unequivocally identified by single crystal X-ray structure analysis. Careful analysis of both structures in the solid state reveals the presence of important hydrogen bond interactions, leading in the case of the Pd(II) derivative to the formation of a pseudo-pincer/non-covalent pincer compound ▪ ( 2). The catalytic activity of this species was examined in Buchwald–Hartwig C–N cross coupling of morpholine with a series of p-substituted bromo-benzenes.

A discussion on the solid state organization of 4-pyridyl imino compounds and on the co-crystallization between their molecular precursors

The synthesis and the crystal structures of several 4-pyridyl imino compounds are reported. Their solid-state organization is based on head-to-tail chains sustained by O–H⋯N hydrogen bonds; the supramolecular arrangement is analysed by means of the Hirshfeld surfaces and of the corresponding 2D-fingerprint plots. The co-crystallization between 4-aminobenzyl alcohol and 4-acetylpyridine is analysed, correlating reactivity trends and structural characters. In this context, the single crystal X-ray diffraction analyses of 4-aminobenzyl alcohol and 3,5-diphenyl-4-hydroxyaniline are also reported.

Quantitative Scale for the Extent of Conjugation of Carbonyl Groups: “Carbonylicity” Percentage as a Chemical Driving Force

Despite the carbonyl group being one of the most pervasive chemical building blocks in natural, synthetic, and industrial processes, its exact description in terms of precise quantification of the degree of carbonyl conjugation has yet to be determined. The present work suggests a novel yet simple method for quantifying the conjugation in general carbonyl groups (such as ketones, aldehydes, carboxylic acids and their respective halogenides, amides, etc.) on a linear scale, defined as the "carbonylicity scale". This was achieved by use of the computed enthalpy of hydrogenation (DeltaH(H2)) of the > C=O group in the compounds examined. In the present conceptual work, the DeltaH(H2) value for formate ion is used to define complete conjugated character (carbonylicity = +100%), while formaldehyde represents complete absence of conjugation (carbonylicity = 0%). The component DeltaH(H2) values were computed at differing levels of theory, providing a nearly "method-independent" measure of carbonylicity computationally. A total of 49 common carbonyl compounds were used as accuracy scoring criteria of the methodology. For the compounds examined, correlations have been made between the computed carbonylicity percentage and the > C=O proton affinities, IR frequencies, and their reactivity values in a nucleophilic addition reaction. Selected chemical reactions were also studied to illustrate the utility of carbonylicity scale. Examples herein include demonstrating that change in the carbonylicity value represents a thermodynamic driving force in acylation reactions. The definition was extended to substituted thiocarbonyl and imino compounds.