Microwave-assisted deformylation of N-aryl formamide by KF on basic Al2O3

The formyl group was successfully removed from N-aryl formamide by KF on a solid support of basic Al₂O₃ in 4-20 min with microwave irradiation. The conditions mimic base-catalyzed hydrolysis of formamide and are compatible with carbamates and t-butyl esters, but not methyl, ethyl, and benzyl esters.     

Evaluation of kinetics parameters for poly(l-lactic acid) hydrolysis under high-pressure steam

In order to evaluate more precise kinetics parameters: rate constant k and E_a values for poly(l-lactic acid) hydrolysis, the reaction was carried out under high-pressure steam in a temperature range of 100-130 °C. Molecular weights of hydrolyzates were calculated by the universal calibration method without being influenced by any weight loss. The changes in molecular weight could be successfully explained according to the auto-catalytic hydrolysis mechanism, clearly indicating the critical point. Resulting k and E_a values were estimated as 8.4 × 10⁻⁵-7.2 × 10⁻⁴ s⁻¹ and 87.2 kJ mol⁻¹ with high R² values, respectively. Moreover, to determine the deviation of the parameter values, influences of four factors on the measurements and calculation: (1) use of number-average molecular weight value alone, (2) use of relative molecular weight based on polystyrene standards, (3) weight loss during the hydrolysis, and (4) selection of reaction mechanism were evaluated quantitatively.     

Synthesis and examination of amine-cyanocarboxyboranes, the boron analogues of α-cyanocarboxylic acids: X-ray structural study of the first lactam containing a boron atom in the lactam ring

The first representatives of chiral boron atom-containing amine-cyanomethoxycarbonyl boranes (A · BH(CN)COOMe) have been synthesized either from the corresponding amine-bromocyanomethoxycarbonylborane complexes with [Bu₄N]CN or from Me₃N · BH(CN)COOMe and an amine in a base-exchange reaction. Acid hydrolyses of methyl esters generated the free acids (A · BH(CN)COOH), which are isoelectronic to the α-cyano carboxylic acids. Their pK_a values and hydrolysis half-lives in acidic medium (that is rate of proton reduction) have been determined. Similarly to the alpha cyano carboxylic acids, the cyano group attached to the boron (in alpha position to the COOH group) increased the acid strength of carboxy boranes with 2.0-2.5 orders of magnitude. Independently from the type of the amine, pK_a values of the amine-cyanocarboxyboranes (6.34-5.82) decrease consistently with the increase of pK_b values of the amines. Hydrolytic decomposition rate of the alkylamine complexes increases with increasing pK_b values of the amines while the opposite was found for pyridine base complexes. When considering both types of the amines, hydrolysis half-lives of the complexes range over several orders of magnitude from 0.005 to 400 h. Based on these observations protonation of the amine nitrogen atom appears to be the rate determining step in the hydrolysis process. With loss of methanol, 2-NH₂-py · BH(CN)COOMe transformed into a five membered lactam derivative. X-ray diffraction revealed that the pyridine ring is coplanar with the five membered lactam ring. In the crystal two molecules are connected in a head to tail arrangement by strong intermolecular H-bonds between N(2)-H and the carbonyl oxygen (O1) with a donor and acceptor distance of 2.867(3) Å. Three new cyanomethoxycarbonylborates having the composition of K[BH_n(CN)_3−nCOOMe] (n = 1, 2) and K[B(OH)(CN)₂COOMe] have also been synthesized and their properties examined.     

Good linear relationship between logarithms of Eigen’s water exchange constants for several divalent metal ions and activation energies of corresponding metal-catalyzed alkoxysilane hydrolysis in ethylene-propylene copolymer system

Catalytic efficiencies of seven divalent metal acetylacetonate complexes [M(acac)₂; M = Cd(II), Co(II), Cu(II), Fe(II), Ni(II), Pb(II), and Zn(II)] with respect to the water-crosslinking kinetics of vinyltrimethoxysilane-grafted ethylene-propylene copolymer (EPR-g-VTMS) were investigated to examine the effects of progressive changes in metal ion using ATR-FTIR spectroscopy. The hydrolysis activation energies of EPR-g-VTMS follows the order: No catalyst ≈ Ni(acac)₂ > Co(acac)₂ > Fe(acac)₂ ≈ Zn(acac)₂ > Cd(acac)₂ ≈ Cu(acac)₂ > Pb(acac)₂. Interestingly, the kinetics results revealed that the plots of hydrolysis activation energies of EPR-g-VTMS containing M(acac)₂ complexes and Eigen’s water exchange constants for corresponding metal ions showed a excellent linear relationship, suggesting that the reaction pathway for the silane water-crosslinking with hydrous M(acac)₂ complex in EPR-g-VTMS system may be similar to that for water exchange of the metal ion in an aqueous system. Based on the knowledge of traditional kinetics studies by Eigen and Wilkins and hybrid sol-gel chemistry, the plausible catalytic mechanism for M(acac)₂ complexes in EPR-g-VTMS system was proposed.     

Study of the in vitro degradation of poly(ethyl glyoxylate)

In vitro degradation of poly(ethyl glyoxylate) (PEtG), a functionalised polyacetal, was investigated. First, the thermodynamic polymerization parameters and the ceiling temperature (T_c) were determined (ΔH_p = 28 ± 3 kJ mol⁻¹, ΔS_p = 98 ± 7 J mol⁻¹ K⁻¹, T_c = 310 ± 4 K). Secondly, PEtG hydrolysis was investigated using potentiometry, weight loss measurements, SEC and ¹H NMR. The results show that PEtG is stable for at least 7 days in aqueous media. Then degradation occurs and releases ethanol and glyoxylic acid hydrate as final products. A scheme for the degradation mechanism involving chain scission and ester hydrolysis is proposed.     

Transesterifications mediated by t-BuNH2

A mild protocol for transesterification of simple esters is described. The method is based on the use of t-BuNH₂/ROH (R = Me, Et, i-Pr, t-Bu) with or without LiBr. The scope of the procedure was explored for aliphatic and aromatic esters. The protocol is particularly useful when going from higher to lower hindered esters and harsh reaction conditions are needed for the reversal process. A rationalization of the mechanism is presented. The scope and limitation of this transformation are also described.     

Enzyme assay for chitinase catalyzed hydrolysis of tetra-N-acetylchitotetraose by isothermal titration calorimetry

Isothermal titration calorimetry (ITC) has been used to observe the chitinase-catalyzed hydrolysis of tetra-N-acetylchitotetraose. Enzymatic hydrolysis of tetra-N-acetylchitotetraose by chitinase B from Serratia marcescens produces exclusively two molecules of di-N-acetylchitobiose allowing for the determination of a single glycosidic bond hydrolysis heat that was used to monitor the rate of the enzymatic reaction. The change in heat rate with respect to time (dQ/dt) was translated to the reaction rate, and the total heat produced was related to substrate concentration throughout the reaction. Reaction rates versus substrates concentration were fit to Michaelis-Menten plots, yielding a k_cat of 40.9 ± 0.5 s⁻¹ and a K_m of 54 ± 2 μM.     

Thermokinetic studies on the activation of bovine liver arginase by manganese ions

The activation of bovine liver arginase, which catalyzes the hydrolysis of l-arginine to l-ornithine and urea, by manganese ions was studied by thermokinetic methods at 37 °C in 40 mM sodium barbiturate-HCl buffer solution (pH 9.4). Full activation of arginase, by incubation with 0.1 mM Mn²⁺, resulted in increased of V_max, and a higher sensitivity of the enzyme to product and l-lysine inhibition, with no change in the K_m for arginine. Upon addition of 0.1 mM Mn²⁺ to the reaction, the inhibitory constants of product (K_P) and l-lysine (K_I) decreased from 1.18 to 0.70 mM and from 5.60 to 3.10 mM, respectively. We suggest that the exogenous manganese ions in reaction recovered the activity of arginase, which was lost in dissolving and dilution, without effecting on the mechanism of the reaction.     

Syntheses,structures and hydrolytic properties of copper(II) complexes of asymmetrically N-functionalised 1,4,7-triazacyclononane ligands

A series of new asymmetrically N-substituted derivatives of the 1,4,7-triazacyclononane (tacn) macrocycle have been prepared from the common precursor 1,4,7-triazatricyclo[5.2.1.0^4,10]decane: 1-ethyl-4-isopropyl-1,4,7-triazacyclononane (L1), 1-isopropyl-4-propyl-1,4,7-triazacyclononane (L2), 1-(3-aminopropyl)-4-benzyl-7-isopropyl-1,4,7-triazacyclononane (L3), 1-benzyl-4-isopropyl-1,4,7-triazacyclononane (L4) and 1,4-bis(3-aminopropyl)-7-isopropyl-1,4,7-triazacyclononane (L5). The corresponding monomeric copper(II) complexes were synthesised and were found to be of composition: [Cu(L1)Cl₂] · 1/2 H₂O (C1), [Cu(L4)Cl₂] · 4H₂O (C2), [Cu(L3)(MeCN)](ClO₄)₂ (C3), [Cu(L5)](ClO₄)₂ · MeCN · NaClO₄ (C4) and [Cu(L2)Cl₂] · 1/2 H₂O (C5). The X-ray crystal structures of each complex revealed a distorted square-pyramidal copper(II) geometry, with the nitrogen donors on the ligands occupying 3 (C1 and C2), 4 (C3) or 5 (C4) coordination sites on the Cu(II) centre. The metal complexes were tested for the ability to hydrolytically cleave phosphate esters at near physiological conditions, using the model phosphodiester, bis(p-nitrophenyl)phosphate (BNPP). The observed rate constants for BNPP cleavage followed the order k_C1 ≈ k_C2 > k_C5 ? k_C3 > k_C4, confirming that tacn-type Cu(II) complexes efficiently accelerate phosphate ester hydrolysis by being able to bind phosphate esters and also form the nucleophile necessary to carry out intramolecular cleavage. Complexes C1 and C2, featuring asymmetrically disubstituted ligands, exhibited rate constants of the same order of magnitude as those reported for the Cu(II) complexes of symmetrically tri-N-alkylated tacn ligands (k ∼ 1.5 × 10⁻⁵ s⁻¹).     

Theoretical study on the reaction mechanism for the hydrolysis of esters and amides under acidic conditions

The mechanisms underlying the hydrolysis of methyl acetate and acetamide under acidic conditions were investigated using the MP2/6-311+G(d,p)//MP2/6-31+G(d,p) level of theory. It was necessary to include two water molecules as reactants to obtain a tetrahedral (TD) intermediate for the A_AC2 mechanism that Ingold classified for the hydrolysis of methyl acetate. This mechanism includes two TS structures, one for the formation of the TD intermediate and the other for its decomposition. Since the activation energies were calculated to be 15.7 and 18.3 kcal mol⁻¹, the second step determines the rate of hydrolysis. The calculated value was close to that observed at ∼16 kcal mol⁻¹. It was confirmed that the A_AC2 mechanism had a barrier lower by 9.9 kcal mol⁻¹ than the A_AL2 mechanism. The A_AC2 mechanism is also applicable to the acid-catalyzed hydrolysis of acetamide. It is not the TD intermediate with which the NH₃⁺ moiety forms, but one further step is required to produce the final products, acetic acid and ammonium ion.     

Structural, spectroscopic, and magnetic properties of a diphenolate-bridged FeNi complex showing excellent phosphodiester cleavage activity

To mimic the phosphate ester hydrolysis behavior of purple acid phosphatases the heterobimetallic complex [(BNPP)Fe^IIIL(μ-BNPP)Ni^II(H₂O)](ClO₄) (1) has been synthesized from the precursor complexes [Fe^III(LH₂)(H₂O)₂](ClO₄)₃·3H₂O and [Fe^III(LH₂)(H₂O)Cl](ClO₄)₂·2H₂O. In these compounds, L²⁻ is the anion of the tetraiminodiphenol macrocyclic ligand (H₂L), while LH₂ is the zwitterionic form in which the phenolic protons are shifted to the two metal-uncoordinated imine nitrogens, and BNPP is bis(4-nitrophenyl)phosphate. The X-ray crystal structure of compound 1 has been determined. The structure of 1 comprises of two edge-shared distorted octahedrons whose metal centers are bridged by two equatorial phenolate oxygens and two axially disposed oxygens of a BNPP ligand. The internuclear Fe?Ni distance is 3.083 Å. The high-spin iron(III) and nickel(II) in 1 are antiferromagnetically coupled (J = −7.1 cm⁻¹; H = −2JS₁·S₂) with S = 3/2 spin ground state. The phosphodiesterase activity of 1 has been studied in 70:30 H₂O-(CH₃)₂SO medium with NaBNPP as the substrate. The reaction rates have been measured by varying pH (3-10), temperature (25-50 °C), and with different concentrations of the substrate and complex at a fixed pH and temperature. Treatment of the rate data, obtained at pH 6.0 and at 35 °C, by the Michaelis-Menten approach have provided the following parameters: K_M = 3.6 × 10⁻⁴ M, V_max = 1.83 × 10⁻⁷ M s⁻¹, k_cat = 9.15 × 10⁻³ s⁻¹. As compared to the uncatalyzed hydrolysis rate of BNPP, the k_cat value is 8.3 × 10⁸ times higher, showing that 1 behaves as an excellent model for phosphate ester hydrolysis.     

Conversion of lactides into ethyl lactates and value-added products

This Letter describes an attractive and efficient method for Mg(OR)₂-mediated lactide alcoholysis. The catalysts were generated in situ from di-n-butylmagnesium and ROH to prevent aggregation of Mg(OR)₂. The reaction of ROH [R = Me, Et, RCO₂(Me)CH] with lactide initially yielded the ring-opened product HO[CH(CH₃)CO]_nOR (n = 2 or 3). The complete consumption of lactide caused the reaction to proceed further, giving environmentally friendly lactic acid esters in excellent yields under ambient conditions.     

Conversion of pentynol to pentanone catalysed by Pd(II) metal centres

The cyclization of 3- or 4-pentyn-1-ol is catalysed by PdCl₂ or trans-[PdCl₂L₂] (L = R-camphorimine; R = Ph; Prⁱ; NMe₂) complexes at room temperature affording heterocyclic compounds, respectively, 2-methyl-2-pent-3-ynyloxy-tetrahydrofuran or 2-methyl-2-pent-4-ynyloxy-tetrahydrofuran which subsequently add water to give selectively 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one from both starting materials. By hydrolysis 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one undergoes ring cleavage to form 5-hydroxy-2-pentanone. The catalytic activity and selectivity of complexes trans-[PdCl₂L₂] (L = R-camphorimine) depend on the characteristics of the R group (NMe₂ > Prⁱ > Ph). The catalytic activity of PdCl₂ is comparable to that of trans-[PdCl₂L₂] (L = Ph-camphorimine) which is the less efficient catalyst.     

Easy selective generation of (lithiomethyl)cyclopropane or homoallyllithium by a chlorine-lithium exchange

The reaction of (chloromethyl)cyclopropane 5 with lithium and a catalytic amount of DTBB (5 mol %) in the presence of different carbonyl compounds [Et₂CO, n-Pr₂CO, (c-C₃H₅)₂CO, (CH₂)₅CO, PhCOMe, t-BuCHO, i-PrCHO, PhCHO] as electrophiles in THF at −78 °C leads, after hydrolysis with water, to the corresponding cyclopropyl alcohols 6. However, when the same starting material is lithiated using naphthalene as the arene catalyst in ether at 0 °C and then reacts with the same series of electrophiles, the final hydrolysis with water yields the corresponding unsaturated alcohols 7.     

Anthracene-9-methanol—a novel fluorescent phototrigger for biomolecular caging

Photoexcitation of a solution of anthracene-9-methanol derived esters at ∼386 nm in CH₃CN/H₂O (3:2 v/v) results in fluorescence emission in the 380-480 nm range, with quantum yields of fluorescence (Φ_f) in the 0.01-0.09 range and releases of the carboxylic acids in good chemical yields (43-100%), with quantum yields of photoreaction (Φ_PR, i.e., the photodisappearance of the esters) in the 0.067-0.426 range.     

(Liquid + liquid) equilibria of the (water + acetic acid + dibasic esters mixture) system

(Liquid + liquid) equilibrium (LLE) data for the {water + acetic acid + dibasic esters mixture (dimethyl adipate + dimethyl glutarate + dimethyl succinate)} system have been determined experimentally at T = (298.2, 308.2, and 318.2) K. Complete phase diagrams were obtained by determining solubility curve and tie-line data. The reliability of the experimental tie-line data was confirmed by using the Othmer-Tobias correlation. The UNIFAC model was used to predict the phase equilibrium in the system using the interaction parameters determined from experimental data between CH₂, CH₃COO, CH₃, COOH, and H₂O functional groups. Distribution coefficients and separation factors were compared with previous studies.     

Stille carbonylation of N-protected bromomethylindoles

A variety of N-protected indolylmethylbromides are carbonylated using 5 mol % Pd(PPh₃)₂Cl₂ under Stille conditions in the presence of an alcohol to afford the corresponding methyl/ethyl esters.     

The synthesis, structural characterization and in vitro anti-cancer activity of novel N-(3-ferrocenyl-2-naphthoyl) dipeptide ethyl esters and novel N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters

N-(3-ferrocenyl-2-naphthoyl) dipeptide esters (5-7) and N-(6-ferrocenyl-2-naphthoyl) dipeptide esters (8-10) were prepared by coupling either 3-ferrocenylnaphthalene-2-carboxylic acid 2 or 6-ferrocenylnaphthalene-2-carboxylic acid 4 to the dipeptide ethyl esters GlyAla(OEt) (5, 8), AlaGly(OEt) (6, 9), and AlaAla(OEt) (7, 10) using the standard N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, DEPT-135 and ¹H-¹³C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). In vitro, the cytotoxic effects of compounds 5-10 show improvements over the corresponding N-(ferrocenyl)benzoyl derivatives, with IC₅₀ values against the H1299 lung cancer cells ranging from 1.2 μM to 8.0 μM. N-(6-ferrocenyl-2-naphthoyl)-glycine-l-alanine ethyl ester 8 was found to be the most active derivative of the naphthoyl series so far, displaying an IC₅₀ value of 1.3 ± 0.1 μM. This value is slightly lower than that found for the clinically employed anti-cancer drug cisplatin (IC₅₀ = 1.5 ± 0.1 μM against H1299).     

Ionic liquid media resulted in more efficient regio- and stereoselective aminohalogenation of cinnamic esters

The ionic liquid, butylmethylimidazolium tetrafluoroborate ([Bmim][BF4]), was found to be superior to classical organic solvents for the metal catalyzed regio- and stereoselective aminohalogenation of cinnamic esters. The aminohalogenation reaction of cinnamic esters with p-TsNCl₂ proceeded at a faster rate (within 12 h) in the presence of a reduced amount of catalyst (CuOTf, 6.0 mol %). Good yields (76-82%) and excellent regio- and stereoselectivity (one isomer) were achieved for eight examples.