Equilibria and kinetics for pH-dependent axial ligation of ethylester and methylester(aquo)cobaloximes with aromatic and aliphatic N-donor ligands and a molecular mechanistic study of the Co-C bond

Equilibrium constants are determined for the reaction of ethylester and methyl ester (aquo) cobaloximes with histamine, histidine, glycine and ethyl glycine ester as a function of pH at 25°C, using spectrophotometric technique. The functional dependence of pK _a on the substitution rate of H₂O varies with the pK _a of the incoming ligand, establishing the existence of nucleophilic participation of the ligand in the transition state. This data is interpreted with the help of kinetic data where dissociation kinetic reactions were also studied as a function of pH. Binding and kinetic data were correlated based on the basicity, steric hindrance of the entering ligand and HSAB principle. To compare the rate constants of the entering ligands pH-independent second-order rate constants were calculated. The effect of incoming ligand on Co-C bond is studied using molecular mechanics     

Equilibria and kinetics for pH-dependent axial ligation of bromomethyl(aquo)cobaloxime by aliphatic amine ligands

Kinetics and equilibria of axial ligation of bromomethyl(aquo) cobaloxime by a series of straight chain primary amines (methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine), cycloamines (cyclopentylamine, cyclohexylamine, cycloheptylamine) and secondary amines (N,N-dimethylamine, N,N-diethylamine) have been measured as functions of pH by spectrophotometric technique in aqueous solution, ionic strength 1 M (KCl) at 25°C. The rate of substitution of H₂O varies with the pKa of incoming ligand, thus establishing nucleophilic participation of the ligand in the transition state. Binding and kinetic data are interpreted based on the basicity and steric influence of the entering ligand. To compare the rate constants of the entering ligands, pH independent second-order rate constants (k _on ) are calculated.     

Equilibrium and kinetic studies on ligand substitution reactions of chloromethyl(aquo)cobaloxime with aromatic and aliphatic N-donor ligands

Equilibria and kinetics of the reactions of chloromethyl(aquo)cobaloxime with histamine, histidine, glycine and ethyl glycine ester were studied as a function of pH at 25°C, 10 M ionic strength (KCl) by spectrophotometric techniques. Comparison of equilibrium constants and rate constants tells that the order isK _Hisdn >K _Hiamn >K _Gly >K _EtGlyest. The rate of substitution of H₂O varies with the pKa of the incoming ligand and nucleophilic participation of the ligand in the transition state. The rate constants and equilibrium constants are correlated to the hardness and softness of the ligands and the Co(III) of cobaloxime.     

Coenzyme B12 model studies: An HSAB approach to the equilibria and kinetics of axial ligation of alkyl(aquo)-cobaloximes by imidazole and cyanide

Kinetics and equilibria of the axial ligation of alkyl(aquo)cobaloximes by imidazole and cyanide have been measured spectrophotometrically in aqueous solutions of ionic strength 1.0 M at 25°C as a function of pH. Comparison of K_IMD and K_CN- of CH₃, C₂H₅ and BrCH₂cobaloximes indicates that their stability is in the order BrCH₂>CH₃>C₂H₂. As the electron-withdrawing capacity of the alkyl grouptrans to water increases, the electron density of the cobalt(III) decreases and thus it becomes a stronger Lewis acid and binds more strongly to imidazole and cyanide. The association and dissociation rate constants are better correlated to the relative softness of the ligand showing that cyanide binds 30 times faster than imidazole. These complexes are isolated and are characterized by IR and¹H NMR spectra.     

A trans influence study in propyl (aquo)cobaloxime by imidazoles and amino acids

Substitution reactions of propyl cobaloxime with imidazole, substituted imidazoles, histidine, histamine, glycine and ethyl glycine ester are carried out as a function of pH. Trends in the formation constants are explained based on the steric hindrance, extent of π-bonding and Σ-donor capacity of the incoming ligand. Molecular mechanics is used to theoretically determine the bond length and bond strain values by MM2 parametrization and these are correlated with the experimental data.     

Stability of Copper(II), Nickel(II) and Zinc(II) Binary and Ternary Complexes of Histidine,Histamine and Glycine in Aqueous Solution

The binary and mixed-ligand complexes formed between ligands (histidine (His), histamine (Him) and glycine (Gly)) and some transition metals (Cu(II), Ni(II) and Zn(II)) were studied potentiometrically in aqueous solution at (25.0 ± 0.1) C and I = 0.10 M KCl in order to determine the protonation constants of the free ligands and stability constants of binary and ternary complexes. The complexation model for each system has been established by the software program BEST from the potentiometric data. The most probable binding mode for each binary species of histidine and for all mixed species was also discussed based upon derived equilibrium constants and stability constants related to the binary species. The ambidentate nature of the histidine ligand, i.e. the ability to coordinate histamine-like, imidazolepropionic acid-like and glycine-like modes was indicated from the results obtained. The stability of ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters, log K, log X and ₁₁₁₀. The concentration distributions of various species formed in solution were also evaluated. In terms of the nature of metal ion, the complex stability follows the trend Cu(II) > Ni(II) > Zn(II), which is in agreement with the Irving-Williams order of metal ions. Thus, the results obtained were compared and evaluated with those in the literature.     

Coenzyme B12 model studies: Equilibrium constants for the pH-dependent axial ligation of benzyl(aquo)cobaloxime by various N- and S-donor ligands

Equilibria of the axial ligation of benzyl(aquo)cobaloximes by imidazole, 1-methyl imidazole, histidine, histamine, glycine, ethyl glycine ester, thiourea and urea have been spectrophotometrically measured in aqueous solutions of ionic strength 1.0M (KCl) at 25°C as a function of pH. The equilibrium constants are in the order CN⁻> 1-methyl imidazole > imidazole > histidine > histamine>glycine>ethyl glycine ester > thiourea > urea. The order of stability of benzyl(ligand)cobaloxime is explained based on the basicity of the ligand, Co(III) →>L dπ- pπback bonding and soft-soft and soft-hard interaction. Imidazole, substituted imidazoles, histidine and histamine form more stable complexes than glycine, ethyl glycine ester in contrast to the basicity of the ligands. Benzyl(ligand)cobaloximes were isolated and characterized by elemental analysis, IR and¹H NMR spectra.     

C(2)-Functionalization of 1-substituted imidazoles with cyanoacetylenes and aromatic or heteroaromatic aldehydes

Substituted imidazoles (substituents are Me, Et, i-Bu, n-Hexyl, (CH₂)₂S-Bu-n, Ph, Bn) react smoothly (room temperature, without catalyst and solvent) with cyanoacetylenes (3-phenyl-2-propynenitrile and 4-(1-butoxyethoxy)-4-methyl-2-pentynenitrile) and aromatic or heteroaromatic aldehydes (benzaldehyde, 4-CN-benzaldehyde, pyridine-3-aldehyde) to give 3-(2-imidazolyl)-3-aryl-2-acylpropanenitriles, a hitherto unknown family of functionalized imidazole derivatives, in up to 62% yield. This three-component manifold represents a novel C(2)-functionalization of the imidazole nucleus involving zwitterionic, carbene and enol ether intermediates. Unlike the analogous reaction with aliphatic aldehydes, which gives enol ethers, in this case the latter undergo the further rearrangement to 3-(2-imidazolyl)-3-aryl-2-acylpropanenitriles.     

Equilibrium constants and kinetics of carbon monoxide insertion in alkyl complexes of ruthenium(II)

The equilibrium constants of the reaction of cis, trans-[Ru(CO)₂(PMe₃)₂(CH₃)I] (Mc) with carbon monoxide to give cis, trans[Ru(CO)₂(PMe₃)₂ (COMe)i] (Ac) and trans, trans[Ru(CO)₂(PMe₃)₂(COMe)I] (At) were measured at various temperatures in toluene. The thermodynamic parameters are compared with those obtained for the isoelectronic complexes of iron, and the trend is discussed. The kinetics of the carbonylation reaction of Mc, as well as those of the inverse decarbonylation reaction of At were measured. The kinetics of the carbonylation of the new complex trans, trans-[Ru(CO)₂(PMe₃)₂(CH₃)I] (Mt) were also investigated. All the results afford further support to the previously proposed CO insertion mechanism occurring via methyl migration. The comparison of these kinetic results with those of isoelectronic complexes of iron indicates that ruthenium is more reactive than iron, which is reflected by its greater aptitude to act as catalyst in many processes.     

Synthesis, characterization and antitumor activity study of some cyclometalated organoplatinum(II) complexes containing aromatic N-donor ligands

A general approach has been designed to synthesize some mononuclear and binuclear cyclometalated platinum(II) complexes, containing aromatic N-donor ligands with the presence of one Cl⁻trans to carbon. In this way, cyclometalated platinum(II) complex [Pt(C^N)Cl(dmso)], 1, C^N = N(1),C(2′)-chelated, deprotonated 2-phenylpyridine and dmso = dimethylsulfoxide, was used as a precursor to react with imidazole derivatives (1-methylimidazole, 2a, imidazole, 2b,), monodentate pyridine derivatives (4-methylpyridine, 2c, pyridine, 2d,) and bidentate pyridine derivative (4,4′-bipyridine, 3 and 4,). Synthesized complexes were fully characterized by using multinuclear NMR spectroscopy (¹H, ¹³C{¹H} and ¹⁹⁵Pt), correlation NMR spectroscopy (¹H-¹H COSY, ¹³C{¹H}-¹H Heteronuclear Multiple Quantum Correlation, HMQC, Heteronuclear Multiple Bond Correlation, HMBC, ¹⁵N-¹H HETCOR), elemental analysis, X-ray crystallography and ESI-Mass spectrometry. Antitumor effects of mononuclear cyclometalated platinum(II) complexes 2a, 2c, 2d and 3 were determined on Jurkat, K562, and Raji cell lines and results showed reasonable cytotoxicities.     

Synthesis of 5-polyfluoroalkyl-4-( p -tolyl-sulfonyl)pyrazoles and 4-polyfluoroalkyl-5-( p -tolylsulfonyl)pyrimidines from 1-dimethylamino-2-( p -tolylsulfonyl)-polyfluoro-1-alken-3-ones

1-Dimethylamino-2-(p-tolylsulfonyl)polyfluoro-1-alken-3-ones were obtained from hydrates of 3,3,3-trifluoro-1-(p-tolylsulfonyl)-2-propanone and 3,3,4,4,5,5-hexafluoro-1-(p-tolylsulfonyl)-2-pentanone under conditions of the Vilsmeier-Haack-Arnold reaction. The analogous reaction of 3,3-difluoro-1-(p-tolylsulfonyl)-2-propanone hydrate leads to 3-chloro-1-dimethylamino-4,4-difluoro-2-(p-tolylsulfonyl)-1,3-butadiene. The feasibility of using 1-dimethylamino-2-(p-tolylsulfonyl)-polyfluoro-1-alken-3-ones in reactions with nitrogen binucleophiles has been demonstrated for the regioselective synthesis of pyrazoles and pyrimidines. The structure of 1-phenyl-4-(p-tolylsulfonyl)-5-trifluoromethyl-1H-pyrazole was confirmed by X-ray diffraction structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1052–1058, July, 2007.     

An efficient aerobic oxidation for p -xylene to p -toluic acid catalyzed by cobalt (II) hydroxamates with benzo-15-crown-5

Cobalt (II) hydroxamates with the benzo-15-crown-5 (B15C5) pendant have been synthesized and characterized. These complexes were successfully employed to the oxidation of p-xylene to p-toluic acid with air at 110°C under normal atmospheric pressure. The effects of the B15C5 pendant, the length of chain bonding of B15C5 in these complexes and the addition of alkali metal ions on the oxidation for p-xylene are also investigated by the comparison with the crown-free analogue.     

Reaction of azole heterocycles with tris(dimethylamino)borane, a new method for the construction of tripodal borate-centred ligands

Reaction of 2-mercapto-1-methylimidazole (methimazole) with tris(dimethylamino)borane, B(NMe2)3, provides the tetrahedral dimethylamine adduct of tris(methimazolyl)borane, [(Me2HN)B(methimazolyl)3]. By contrast, imidazole, 2-methylimidazole, 2-chloroimidazole and benzimidazole provide the homoleptic tetra-azolyl systems H[B(azolyl)4], and the same product is obtained even when a substoichiometric quantity of the heterocyle is employed. The change in reaction outcome is correlated with the variation of basic pKa for the heterocycles. A simple acid-base reaction with elimination of HNMe2 is proposed for the reaction with the weakly basic, but more strongly acidic, methimazole. However, for the more strongly basic imidazoles, initial coordination of the heterocycle imine nitrogen to the weakly Lewis acidic boron centre in B(NMe2)3 to form the tetrahedral adduct [(azole)B(NMe2)3] is proposed. The greater availability of the NMe2 lone pairs in this species results in increased basicity and a rapid reaction with further heterocycle to provide the observed H[B(azolyl)4] products. For 2-nitroimidazole, the low basicity (and increased N-H acidity) results in the formation of [(HNMe2)B(2-nitroimidazolyl)3] on reaction with B(NMe2)3, analogous to the product formed with methimazole. Both [(HNMe2)B(methimazolyl)3] and H[B(benzimidazolyl)4] have been structurally characterised by single crystal X-ray crystallography. This chemistry has been exploited to provide a new synthesis of borate-centred tripod ligands, whereby N-methylimidazole is used to activate B(NMe2)3 to reaction with methimazole to form the new ligand [(N-methylimidazole)B(methimazolyl)3] in good yield and a complex of this ligand with Ru(II) has been structurally characterised.     

Synthesis,complex formation kinetics and thermodynamic study of some acyclic polyamine and N2O2 ligands with copper(II)

The polydentate ligands, 3-(2-aminocyclohexylamino)-2-(2-aminocyclohexyl aminomethyl) propionic acid (L¹ ), 4,7,10-triazatridecanedinitrile trihydrochloride (L² ), and 2,2′-(ethane-1,2-diyl) bis(methylazanediyl) diethanol (L³ ) were prepared and their structures investigated by FT-IR, NMR, and MS. The kinetics of complex formation between Cu(II) and L¹, L², and L³ were investigated in acidic aqueous solutions using the stopped-flow method. The stability constants of the complexes were determined by spectrophotometric titration (T?=?293?K, μ?=?0.1?mol?L^?1 NaClO₄), using a diode array UV-Vis spectrophotometer equipped with peristaltic pump and pH meter. The stability constants for the complexes were CuL^1?>?CuL^2?>?CuL³. Activation enthalpies (ΔH#) of these complexes were 55?kJ?mol^?1 for CuL¹, 61?kJ?mol^?1 for CuL², and 36?kJ?mol^?1 for CuL³, respectively.     

Design and synthesis of enantiopure 1-[1(S)-(2-pyridyl)alkyl]-2(R)-isopropylaziridines, new ligands for asymmetric catalysis

Enantiopure 1-(2-pyridyl)alkyl aziridines were designed as bidentate ligands for asymmetric catalysis. Their synthesis involved the addition of organometallic reagents to the imine prepared from 2-pyridinealdehyde and an enantiopure β-aminoalcohol, followed by cyclisation of the β-aminoalcohol moiety to the aziridine ring. Two such ligands (N–N)* were prepared from (S)-valinol and converted to the complexes (η³-allyl)(N–N)*Pd⁺SbF₆⁻, one of which was characterised by X-ray crystallography. Modest enantioselectivities were achieved in a representative Pd-catalysed allylic substitution reaction.     

1-( p -Fluorophenyl)-2-(2′-pyridyl)ethanol and 1-( p -fluorophenyl)-2-(2′-pyridyl)ethene obtained from the condensation reaction of 2-picoline and p -fluorophenylaldehyde under catalyst-and solvent-free conditions

The novel intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol or 2-[2′-(1-hydroxy-1-(p-fluorophenyl)ethyl]pyridine and the corresponding novel dehydration compound 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene or 2-[p-fluorophenylvinyl]pyridine were obtained from the condensation reaction of p-fluorophenylaldehyde and 2-picoline under catalyst-and solvent-free conditions. The intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol was obtained at 42 h reaction time and temperature of 120°C, respectively. ¹H-NMR, IR spectroscopic data of the 1-(p-fluorophenyl)-2-(2-pyridyl)ethanol clearly showed the presence of the-CH₂-CHOH-group. The compound was obtained as a white powder with m.p. 121–122°C and a yield of 8%. For 1-(p-fluorophenyl)-2-(2-pyridyl)ethene, the reaction conditions were similar, but the reaction temperature was increased to yield the double bond in the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene. At the reaction temperature of 140°C, the compound was a slightly brown powder with a m.p. of 78°C and yield of 18%. ¹H-NMR, IR spectroscopic data for the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene showed the presence of a double bond in trans configuration (-CH=CH-), characteristic of a styrylpyridine.     

Reaction of secondary and tertiary aliphatic halides with aromatic aldehydes mediated by chromium(II): a selective cross-coupling of alkyl and ketyl radicals

Takai-Utimoto reactions with secondary and tertiary aliphatic halides usually failed according to previous reports. Now, significant improvements could be achieved, and especially secondary aliphatic halides can be coupled to aromatic aldehydes in yields of up to >95%. A variety of processes are competing with the desired one, and thus conditions must be adapted to the nature of the aldehyde as well as the aliphatic halide used, as the outcome of these reactions is strongly affected by the putative radical intermediates.     

Complexes of vanadium(III) with aromatic amino acids and l-proline in aqueous solution

The equilibria of the complexation processes of V³⁺ ion with l-phenylalanine, l-tyrosine, l-tryptophan and l-proline in aqueous solution were studied by potentiometric and spectroscopic (UV, Vis, CD) methods. The results indicate that all ligands (except l-tyrosine) form only 1:1 species with vanadium(III) ion in the pH range about 2–5. More complex equilibria were observed in the vanadium(III)–l-tyrosine system. Only in this system relatively stable ML₂ species predominantly exists in the pH range 3–5. The results of spectroscopic measurements indicate that in ML and ML₂ species chelated bounds through O and N atoms appear in all investigated systems. Above pH 5 strong hydrolysis processes of vanadium(III) occurred.     

Synthesis of a new isomer of creatinine and its use in the preparation of the food mutagen 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PHIP)

Base-induced cyclization of N′-cyanomethyl-N′-methylurea gives 1-methyl-4-amino-imidazol-2-one, this in turn is condensed with 3-hydroxy-2-phenylacrolein to yield an imidazo[4,5-b]pyridine which is converted into 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PHIP).