Heterocyclic synthesis via a tandem aza-Wittig reaction/heterocumulene-mediated annulation reaction. New methodology for the preparation of quinazoline derivatives.

The aza-Wittig reaction of iminophosphoranes derived fromN-substituted o-azidobenzamides or 2-(o-azido) phenyl benzimidazolewith isocyanates, carbon dioxide or carbon disulphide, lead tofunctionalized 4(3H)-quinazolinones and benzimidazo [1,2-c]quinazolines respectively.     

Studies directed toward the total synthesis of the rubradirin antibiotics. 5. A convenient preparation of functionalized isoprene units for the diels-alder reaction

A simple procedure has been developed for the synthesis of functionalized isoprene units for use in the assembly of the rubradirin antibiotics.     

Preparation of polyamides via the phosphorylation reaction. X. A study of higashi reaction conditions

We report a study of the conditions of the phosphorylation reaction for the preparation of aromatic polyamides using the Higashi reaction medium. For poly(p-phenylene terephthalamide) (PPD-T), the optimum conditions are: reaction temperature, 115°C; monomer concentration, C = 0.083 mol/L; and ratio of triphenyl phosphite (TPP) to monomer, 2.0. These optimum conditions produce PPD-T having η_inh = 6.2 dL/g. At temperatures of 120°C and above PPD-T precipitates from the reaction mixture, leading to lower molecular weights. At lower temperatures the reaction mixture gels, and the gel time decreases with increasing reaction temperature. However, polycondensation continues in the gel state. Monomer concentrations C = 0.10 mol/L and above produce precipitation and yield polyamides of lower molecular weight. For the preparation of poly(p-benzamide) (PBA), the optimum ratio of TPP to monomer is 0.6 for either p- aminobenzoic acid or N-4-(4′-aminobenzamido)benzoic acid. In the former case the inherent viscosity of polymer prepared at 115°C showed little dependence upon the concentration of the monomer. The highest value, η_inh = 1.8 dL/g, was obtained with C = 0.40 mol/L and a TPP/monomer ratio of 0.6. However, for the same TPP/monomer ratio, the monomer containing a preformed amide linkage, N-4-(4′-aminobenzamido)benzoic acid, gave PBA with η_inh = 4.6 dL/g when the monomer concentration is 0.33 mol/L. This is the highest value reported for PBA using the phosphorylation reaction. In A?A + B?B polycondensation, examples in which one of the monomers contained one or two preformed amide linkages produced polyamides having η_inh = 7.8 and 8.9 dL/g, respectively.     

Studies directed toward the synthesis of the eremantholides 1.Preparation of a ring a/b model system via a conjugate addition-acylation protocol

Synthesis of a model A/B ring subunit of eremantholide A (1) is described.     

Model studies toward a synthesis of asperaculin A: exploration of iterative intramolecular Pauson-Khand reaction based strategies to access the dioxa[5.5.5.6]fenestrane framework

A concise strategy, involving tandem intramolecular Pauson-Khand reactions (IPKRs) on a readily available ene-diyne precursor, to access the dioxa-fenestrane framework is delineated.     

A facile method for the preparation of hexafluoroisopropanol functionalized derivatives using hexafluoroacetone trihydrate via a carbonyl-ene reaction

Hexafluoroacetone trihydrate was shown to undergo an efficient carbonyl-ene reaction with a variety of alkenes in the presence of molecular sieves under microwave heating and conventional heating producing hexafluoroisopropanol functionalized derivatives in high yields.     

A kinetic study of the reaction between formic acid and HoBr

The reaction between formic acid and HOBr in strongly acid aqueous media was studied by absorption spectrophotometry at 298 K. Bromine, the monitored species, displays a transient behavior, gradually rising up to a maximum and then decaying with first-order kinetics. Reaction rates, expressed as R = -dC_Br2/dt, depend on the concentrations of HCOOH (0.1–1.4M), HOBr (0.3–1.5 × 10^?3 M), and H⁺ (0.1–1.0M). The mechanism with k₁ =1.04 ± 0.20M^?1· s_?1, k₃ = 20.2M^?1, quantitatively accounts for all observations within experimental error.     

Synthesis and post-synthetic derivatization of a cyanine-based amino acid. Application to the preparation of a novel water-soluble NIR dye

An efficient synthesis of a new fluorescent amino acid derived from a pentamethylene cyanine dye is described. Selective derivatization of its amino group with an original trisulfonated linker has led to a novel water-soluble NIR dye suitable for covalent labeling of biomolecules     

Generation of a substituted 1,2,4-thiadiazole ring via the [3+2] cycloaddition reaction of benzonitrile sulfide toward trichloroacetonitrile. A DFT study of the regioselectivity and of the molecular mechanism

A theoretical study of the [3+2] cycloaddition (32CA) reaction between benzonitrile sulfide BNS1 and trichloroacetonitrile TCAN2 at the MPWB1 K/6-311G(d) level was undertaken. Among two feasible C1N5 and C1C4 regioisomeric channels, the former is completely preferred, in the presence of toluene, over the latter, both kinetically, ΔΔG_activation = 17.5 kcal/mol, and thermodynamically, ΔΔG_reaction = –12.8 kcal/mol, in excellent agreement with experimental outcomes. The strong global electrophilic and nucleophilic characters found for TCAN2 and BNS1, respectively, allow the studied 32CA reaction to take place via a polar process. Interestingly, the analysis of the TSs geometries clarifies that in the case under study, regioselectivity is controlled by destabilizing steric repulsion interactions rather than electronic ones. The ELF topological patterns indicate that while the formation of S3C4 single bond takes place exactly according to Domingo's model, that of the C1N5 single bond is a direct consequence of the nucleophilic attack of the C5 carbon atom on the N5 nitrogen atom supporting a two-stage one-step molecular mechanism.     

A highly efficient synthesis of the FGH ring of micrandilactone A. Application of thioureas as ligands in the Co-catalyzed Pauson-Khand reaction and Pd-catalyzed carbonylative annulation

The functionalized FGH ring system of micrandilactone A was successfully constructed in high selectivity and good yields. The key reactions in our strategy are the Co-thiourea-catalyzed stereoselective, intramolecular Pauson-Khand reaction and Pd-thiourea-catalyzed stereoselective, intramolecular annulation. [structure: see text]     

Advances in the evaluation of the stability and characteristics of the amino acid and amine derivatives obtained with the o-phthaldialdehyde/3-mercaptopropionic acid and o-phthaldialdehyde/N-acetyl-L-cysteine reagents. High-performance liquid chromatography-mass spectrometry study

The composition of the amino acid and amine derivatives obtained with the o-phthaldialdehyde (OPA)/3-mercaptopropionic acid (MPA) and with the OPA/N-acetyl-L-cysteine (NAC) reagents was investigated by on-line HPLC-electrospray ionization MS. The initially formed derivatives proved to be, as expected, the corresponding isoindoles while their transformed species contained one additional OPA molecule. Based on the MS spectra of all transformed OPA derivatives a reaction pathway is suggested. This reaction mechanism was supported both by the molecular ions of the endproducts and by the presence of several selective fragment ions that served as an explanation to the structure of the believed to be less stable OPA derivatives. It has been shown that more than one OPA derivative forms in all those cases when the compound to be derivatized does contain the NH2-CH2-R moiety. Thus, amino acids like e.g. glycine, histidine, beta-alanine, gamma-aminobutyric acid, epsilon-aminocaproic acid, ornithine, and also several aliphatic mono- and diamines provide more than one OPA derivative. Analytical consequences of this experience were utilized by altering the reagent's composition. Reagents containing mole ratios of [OPA]/[MPA] or [OPA]/[NAC]=1/50 resulted in two benefits, simultaneously: (i) in a decrease of the transformation rate of the initially formed derivative, and, (ii) in an increase of the overall stability of the total of derivatives.     

A CASSCF/MR-CI study toward the understanding of wavelength-dependent and geometrically memorized photodissociation of formic acid

The S(0), T(1), and S(1) potential energy surfaces for the HCOOH dissociation and isomerization processes have been mapped with different ab initio methods. The wavelength-dependent mechanism for the HCOOH dissociation was elucidated through the computed potential energy surfaces and the surface crossing points. The HCOOH molecules in S(1) by excitation at 248 nm mainly decay to the ground state via the S(0) and S(1) vibronic interaction, followed by molecular eliminations in the ground state. The S(1) direct dissociation to HCO((2)A') + OH((2)Pi) is the dominant pathway upon photoexcitation at 240-210 nm. Meanwhile, there is a slight probability that the system relaxes to the ground state via the S(0) and S(1) vibronic interaction at these wavelengths. After irradiation of HCOOH at 193 nm, the S(1) direct dissociation into HCO((2)A') + OH((2)Pi) is energetically the most favorable pathway. In view of high IC efficiency at the S(0)/S(1) conical crossing, the S(1) --> S(0) internal conversion via the S(0)/S(1) point can occur with considerable efficiency. In addition, the S(1) isomerization probably plays a dominant role in the partially conformational memory of the HCOOH photodissociation, which has been discussed in detail.     

A hybrid potential reaction path and free energy study of the chorismate mutase reaction.

We present a combination of two techniques--QM/MM statistical simulation methods and QM/MM internal energy minimizations--to get a deeper insight into the reaction catalyzed by the enzyme chorismate mutase. Structures, internal energies and free energies, taken from the paths of the reaction in solution and in the enzyme have been analyzed in order to estimate the relative importance of the reorganization and preorganization effects. The results we obtain for this reaction are in good agreement with experiment and show that chorismate mutase achieves its catalytic efficiency in two ways; first, it preferentially binds the active conformer of the substrate and, second, it reduces the free energy of activation for the reaction relative to that in solution by providing an environment which stabilizes the transition state.