Heterocycles from substituted amides. VIII Oxazole derivatives from reaction of isocyanates with 2-isocyanoacetamides

A facile reaction of 2-isocyanoacetamides 1 with reactive aryl and sulfonyl isocyanates is shown to give 5-amino-2-oxazolecarboxamides 3 in a reaction arising from electrophilic attack of isocyanate with the nucleophilic isocyanide carbon. This reaction, perhaps proceeding through an unstable nitrile ylid intermediate reminiscent of the Cornforth rearrangement, is a first example of ring closure via acylation, involving the activated methylene of an organic isocyanide, without recourse to added base. Isomeric 5-amino-4-oxazolecarboxamides 4 are formed when 5-aminooxazoles 2 react with isocyanates. Since 2 has previously been shown to easily form by thermal isomerization of 1 , methods now exist for the preparation of both 5-amino- 2- and 4-oxazolecarboxamides from the single starting material 1 . In contrast, 1 with acyl isocyanates is shown to give a variety of products, including iminooxazolinediones, 5-amino-2-oxazolecarbox-amide 3 and 2 (1) pyrazinones (tentatively identified), depending on the structure of the isocyanates.     

Fabrication,spectroscopic characterization,calf thymus DNA binding investigation,antioxidant and anticancer activities of some antibiotic azomethine Cu(II), Pd(II), Zn(II) and Cr(III) complexes

This study was conducted to prepare novel azomethine chelates of Cu(II), Pd(II), Zn(II) and Cr(III) with tridentate dianionic azomethine OVAP ligand 2‐[(2‐hydroxyphenylimino)methyl]‐6‐methoxyphenol. The prepared compounds were characterized using elemental analyses and spectral, conductivity, magnetic and thermal measurements. The spectroscopic data suggest that the parent azomethine ligand binds to the investigated metal ions through both deprotonated phenol oxygen and azomethine nitrogen atoms, and adopts distorted octahedral geometry in the case of Cr(III) and Cu(II) ions while tetrahedral and square planar geometries for Zn(II) and Pd(II) ions, respectively. In order to confirm the molecular geometry of the investigated azomethine chelator and its complexes, theoretical density functional theory calculations were employed. Correlation between experimental observations and theoretical calculations of geometry optimization results are in a good agreement. Absorption titration was used to explore the interaction of the investigated azomethine metal chelates with calf thymus DNA, and the binding constant as well as Gibbs free energy were evaluated. Viscosity measurements and gel electrophoresis studies suggest intercalative and replacement binding modes of the azomethine metal chelates with calf thymus DNA. Additionally, the antimicrobial activity of the complexes was screened against some pathogenic bacteria and fungi. This biological study shows that the complexes exhibit a marked inhibitory effect compared to the corresponding ligand and standard drug s. Furthermore, the effect of the novel compounds as antioxidants was determined by reduction of 1,1‐diphenyl‐2‐picrylhydrazyl and compared with that of vitamin C. Finally, in vitro cell proliferation via MTT assay was investigated against colon carcinoma cells (HCT‐116), hepatic cellular carcinoma cells (HepG‐2(and breast carcinoma cells (MCF‐7) to calculate the cytotoxicity of the prepared compounds. Cell proliferation is inhibited for all compounds and in a dose‐dependent manner in the sequence of OVAPPd > OVAPCu > OVAPZn > OVAPCr > OVAP azomethine ligand.     

Ring opening reactions of pyromellitic dianhydride for the synthesis of first row transition metal dicarboxylate complexes

The ring opening reaction of pyromellitic dianhydride by methanol is an effective method to prepare first row transition metal dicarboxylate complexes. The reactions of different first row transition metal salts with pyromellitic dianhydride in the presence of nitrogen donating bidentate ligands such as 1,10-phenanthroline and 2,2′-bipyridine gives different compositions depending on the ligand and the metal salts used. For example, the reaction of nickel(II) acetate with pyromellitic dianhydride in the presence of 1,10-phenanthroline results in the formation of a carboxylato bridged nickel(II) metallacycle through the ring opening reaction of pyromellitic dianhydride (PAH) at the 1 and 3-positions, whereas a mononuclear tetra-aqua 2,2′-bipyridine nickel(II) complex is formed in a similar reaction of nickel(II) acetate through ring opening at the 1,4-position of PAH. Mononuclear cobalt(II) dicarboxylate complexes are formed from the ring opening reaction of pyromellitic dianhydride in methanol in the presence of the nitrogen donor ligands 1,10-phenanthroline or 2,2′-bipyridine. Copper(II) chloride on reaction with PAH and 2,2′-bipyridine gives a mononuclear complex via ring opening at the 1 and 4-positions; having chlorides inside and outside the coordination sphere. Whereas, the reaction of copper(II)acetate gives dinuclear copper complexes having a monodentate carboxylato bridge arising from the carboxylato groups at the 1 and 4-positions on the aromatic ring. The crystal structures of all the complexes have been determined.     

Addition de cyano-2 aziridines,ylures dázomethine potentiels aux isocyanates

The addition of azomethine ylids resulting from the thermal ring opening of the corresponding 2-cyanoaziridines on methyl and phenyl isocyanates occured exclusively at the CN double bond. Only one orientation of the addition was observed and a mixture or diastereoisomeric imidazolidones was obtained in each case. On the basis of X ray structure of one diastereoisomer the stereochemistry of the other imidazolidones was established by NMR considering the long range coupling constants values between H₂ and H₅ (J_cis < J_trans). The reaction of sodium methylate with the imidazolones led to imidates resulting from a nucleophilic addition on the nitrile fonction on the C₂ carbon atom of the heterocycles. These irnidates are easily hydrolyzed to the corresponding esters. If the reaction was carried out in the presence of oxygen the CHCN group was transformed into CO group via the oxidation of the C₂ carbanion.     

Generation and metathesis of azomethine imines in reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with het(aryl)methylidenemalononitriles

A new metathesis reaction of azomethine imines is found. Catalytic or thermal diaziridine ring opening of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes leads to azomethine imines reacting further with het(aryl)methylidenemalononitriles to give in situ new azomethine imines inaccessible by common synthetic methods. New azomethine imines are detected as pyrazolines formed via a 1,4-H shift and trapped by the [3+2] cycloaddition with various dipolarophiles to yield 1,5-diazabicyclo[3.3.0]octane derivatives bearing pharmacophoric heterocycles, e.g. furan, nitrofuran, thiophene, and indole. The best results are achieved in the Et₂O·BF₃-catalyzed reactions in ionic liquids.     

N,N'-bis(substituted phenyl)-1,2,4,5-benzenetetracarboxylic-1,2:4,5-diimides

The preparation of N,N'-bis(substituted phenyl)-1,2,4,5-benzenetetracarboxylic-1,2:4,5-di-imides by the reaction of 1,2,4,5-benzenetetracarboxylic-1,2:4,5-dianhydride ( 1 ) with aryl-amines and with aryl isocyanates is described. Correlations are made between the properties of these diimides and the nature and position of the substituents in the phenyl ring. The condensation of dianhydride 1 with diisocyanates yields polymers varying from soft elastomers to tough films, depending upon the amount of imide structure in the polymer chain.     

Lanthanoid isopropoxide as a novel initiator for anionic polymerization of isocyanates

Lanthanum isopropoxide was found to serve as a novel anionic initiator for the polymerization of hexyl isocyanate affording poly(hexyl isocyanate) with very high molecular weight (M _n > 10⁶) under appropriate conditions. Other lanthanoid alkoxides, such as samarium, ytterbium and yttrium isopropoxides, also brought about the polymerization of hexyl isocyanate. Butyl, isobutyl, octyl and m-tolyl isocyanates also underwent the polymerization reaction to form the corresponding polymers by using lanthanum isopropoxide as initiator, while polymerizations of tert-butyl and cyclohexyl isocyanates with lanthanum isopropoxide did not occur under identical conditions.     

Thermolysis of dimethyl <Emphasis Type="Italic">cis</Emphasis>- and <Emphasis Type="Italic">trans</Emphasis>-1 pthalimidoaziridine-2,3-dicarboxylates in the presence of dipolarophiles

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory. The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the concerted addition mechanism.     

[1,3,5]Triazino[1,2-a] azepines: A new ring system

The reaction of 2-pyrrolidino-1-aza-1-cycloheptene with aryl isocyanates leads, via 1,4-dipolar cycloaddition, to 1,3-diaryl-10a-pyrrolidinoperhydro[1,3,5]triazino[1,2-a]azepine-2,4-diones. The reaction provides a facile route to the novel [1,3,5]triazino[1,2-a]azepine ring system.     

Preparation and spectral characterization of new macrocyclic Ni(II) and Co(II) complexes derived from 1,4- bis (2-carboxyaldehydephenoxy)butane and various diamines

Six new macrocyclic complexes were synthesized by the template effect from reaction of 1,4-bis(2-carboxyaldehydephenoxy)butane, Ni(NO₃)₂ · 6H₂O or Co(NO₃)₂ · 6H₂O and various diamines. The metal-to-ligand ratios of Ni(II) or Co(II) metal complexes were found to be 1 : 1. Coordination of the Schiff base to Ni(II) and Co(II) through the two nitrogen and two oxygen atom (ONNO) are expected to reduce the electron density in the azomethine link and hydroxyl group. The Ni(II) and Co(II) complexes are proposed to be tetrahedral and are 1 : 2 electrolytes as shown by their molar conductivities (Λ_M) in DMF (dimethyl formamide) at 10^?3 M. The structures are proposed from elemental analysis, FT-IR, UV-VIS, magnetic susceptibility measurements, molar conductivity measurements, and mass spectra.     

Optimum conditions for the synthesis of linear polylactic acid‐based urethanes

The reactions of polylactic acid (PLA) oligomers and isocyanates (4,4′‐diphenylmethane diisocyanate and toluene diisocyanate) are reported. The effects of the reaction conditions, that is, the reaction time, reaction temperature, molar ratios, isocyanates, and catalyst, on the number‐average molecular weight (M_n ) are demonstrated. The optimum reaction conditions are determined by the synthesis of relatively high M_n PLA‐based linear polyurethanes. The structure of the polymer samples was investigated with dynamic light scattering, ¹H NMR, IR, and matrix‐assisted laser‐desorption ionization time‐of‐flight mass spectroscopy (MALDI‐TOF MS). © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2925–2933, 2000     

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

The ruthenium(II)‐catalyzed C?H functionalization of (hetero)aryl azomethine imines with allylic acetals is described. The initial formation of allylidene(methyl)oxoniums from allylic acetals could trigger C(sp²)?H allylation, and subsequent endo‐type [3+2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones. The utility of this method is showcased by the late‐stage functionalization of bioactive molecules such as estrone and celecoxib. Combined experimental and computational investigations elucidate a plausible mechanism of this new tandem reaction. Notably, the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.     

(2S,3R,4S,5R)‐Diethyl 2‐(10,10‐dimethyl‐3,3‐dioxo‐3λ6‐thia‐4‐azatricyclo[5.2.1.01,5]decan‐4‐ylcarbonyl)‐5‐phenylpyrrolidine‐3,4‐dicarboxylate: a novel isomorphous‐by‐addition compound

The title compound, C₂₇H₃₆N₂O₇S, (I), is isomorphous by addition with the dimethyl ester analogue [Garner, Dogan, Youngs, Kennedy, Protasiewicz & Zaniewski (2001). Tetrahedron, 57 , 71–85], (II), by replacing two methyl ester H atoms with two methyl groups. With the exception of the conformation of one of the ester groups, the molecules are almost superimposable. Likewise, apart from a slightly larger c axis in (I), few differences in the cell packing of (I) and (II) are found, with both dominated by the same C—H...O hydrogen bonds. Full synthetic and spectroscopic details of (I) are given. The molecular synthesis is important as an example of chiral auxiliary‐assisted 1,3‐dipolar cycloaddition of an azomethine ylid.     

Synthesis of 2,3‐Disubstituted Quinolines via Ketenimine or Carbodiimide Intermediates

Cyclopenta[b]quinolines and cyclohexa[b]quinolines were prepared via the reactions of α‐diazo ketones with N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and N‐(2‐cyclobutylidenemethylphenyl) phosphanimine, respectively. The reaction proceeds in a cascade involving ketenimine formation, 6 π‐electron ring closure, and 1,3‐alkyl shift. A similar approach was developed for the synthesis of dihydropyrrolo‐[2,3‐b]quinolines from N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and isocyanates.     

[Pd{2-CH2-5-MeC6H3C(H)NNC(S)NHEt}]3: An unprecedented trinuclear cyclometallated palladium(II) cluster through induced flexibility in the metallated ring

The reaction of 1-(2,5-dimethylbenzylidene)-3-ethylthiosemicarbazone and palladium acetate in acetic acid yields a trinuclear cyclometallated palladium(II) compound. Each thiosemicarbazone ligand is tridentate with the metal bonded to the carbon atom from the 2-methyl group, to the azomethine nitrogen and to the sulfur atom, which bridges to an adjacent palladium center. The crystal structure confirms the presence of a non-planar hexagonal metallated ring plus a central six-membered palladium-sulfur core within the trimer, which also displays a rather deep intramolecular cavity.     

Functionally substituted isoxazoles and isothiazoles: Synthesis,palladium(II) complexes and their catalytic activity

Functionally substituted 5-(p-tolyl)isoxazoles and 4,5-dichloroisothiazoles, whose molecules contain azomethine, amino, carboxyl, and ester moieties in various combinations in the aromatic ring in the position 3 of heterocycle, were synthesized. Synthesis of complexes of Pd(II) with carboxyl derivative of 1,2-azoles was performed. They show high catalytic activity in the Suzuki reaction in aqueous media.     

Stereochemical assignments of 22-isoxazolinylsteroids using circular dichroism

Circular dichroism (CD) spectra of 22-hydroxy- and 22-acetoxy-22-isoxazolinylsteroids were studied. The configuration of the C-5′ center of the heterocycle was established from the sign of the n-π*-transition band of the azomethine chromophore. The band molecular ellipticity was shown to depend on the mutual placement of the isoxazoline ring and the steroid skeleton of the studied compounds. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 495–499, September-October, 2008.     

4‐Substituted 2,3‐Dihydroisoxazoles as Masked Azomethine Ylides: Access to Pyrrole Derivatives by 1,5‐ and 1,7‐Dipolar Electrocyclizations of Enynyl Derivatives

The enynyl‐substituted 2,3‐dihydroisoxazoles (‘isoxazolines') 9 – 14 were prepared by highly (Z)‐selective Peterson olefination reaction from the corresponding carbaldehydes 6 – 8 . On short‐time thermolysis (280 – 406°/10 s) the TMS derivatives 9 – 11 give rise to the annulated pyrrolines 18 – 20 , which, in some cases, suffer CH₄ elimination affording the pyrroles 15 – 17 . In contrast, thermolysis of the terminal alkyne derivatives 12 – 14 leads to the bicyclic compounds 21 – 23 . The reaction pathways are discussed on the basis of the formation of conjugated azomethine ylides as key intermediates, which either undergo a 1,5‐cyclization to 18 – 20 or a 1,7‐ring‐closure affording cycloallene intermediates of type V , which are further transformed into the azepino pyrroles 21 – 23 .     

Study on synthesis,characterizations, and properties of pyridinol-blocked isocyanates and waterborne polyurethane

A series of pyridinol-blocked isophorone isocyanates were synthesized through esterification reaction, Fries rearrangement, and blocking reaction and characterized by ¹H-NMR, ¹³C-NMR, and Fourier transform infrared spectra. Based on the synthesized blocked isocyanates, the blocked waterborne polyurethane (BWPU) was prepared by the self-emulsification method. The deblocking studies revealed that the deblocking temperature reduces with electron-withdrawing and steric hindrance substituents on the ortho position of pyridinol. The stability, molecular weight (M_w), particle size, viscosity, and hydrophilicity of BWPU were studied and compared. The results showed that with an increased amount of blocking agents, molecular weight, particle size, and viscosity decrease and the hydrophilicity increases.     

Azomethine imines of pyrazolidone series and their bis-chelate Ni(II), Zn(II), Cd(II) complexes. Quantum chemical simulation

Prototropic processes in the molecules of azomethine imines with 2-pyrrolylmethylidene fragment were studied by the density functional theory (DFT) method and the most stable by energy isomers with the intramolecular hydrogen bond between the nitrogen atoms of the pyrrole and the pyrazole rings were found. The energy barriers of the reactions of intramolecular proton transfer were estimated. Based on quantum chemical calculations of the molecular structure of azomethine imine bis-chelates ML₂ [M = Ni(II), Zn(II), Cd(II)] with the coordination unit MN₂N₂ the most stable configurations of the complexes were determined.