The synthesis ofN-aminide intermediates 5 has been traditionally performed by attack of the corresponding 2-heteroaryl hydrazine 2 to 2,4-dinitrophenyl pyridinium chloride 1 (see Scheme 1) generating the hydrazone 3, which is again closed to a pyridinium derivative by acid catalysis, to produce the salt 4 and from there, by treatment with base, the N-aminides were obtained. This method, adapted from the scheme described by Beyer 11 is suitable
In an effort to expand aneasypreparationofpyridiniumN-heteroarylaminides 2, three methods have been compared: one in which the aromatic substitution is produced using base and the conventional acetonitrile reﬂux (method A), a second approach using Pd catalysis (method B), and a third method using water as solvent, base, and microwave irradiation (method C). Method B is a new one-step amination procedure that provided the corre- sponding N-aminides from haloheterocycles without electron- withdrawing substituents (see 2n) and even with the halogen located in positions that were not conjugated with nitrogen (see 2m,w). In most cases, however, only moderate yields were obtained. Finally, method C is a green methodology that avoids the use of palladium and hard bases, with water used as a cheap and non-toxic solvent in conjunction with microwave heating, an approach that produces good yields and requires much shorter reaction times.
Polysubstituted heterocycles belong to the most important class of organic compounds, they are widespread in nature and many of them show interesting biological activities. 1 Functionalization of halo- or metallated heteroaromatic com- pounds through metal-mediated cross-coupling reactions has become an important method for the preparationof different multiple carbon-substituted heterocycles 2 and, in recent years, selective Pd-mediated reactions have been developed to prepare highly functionalized heterocycles. 3 The Suzukie Miyaura cross-coupling reaction has proved to be a powerful and versatile method for the formation of Csp 2 eCsp 2 bonds. 4 The process has important advantages over the other palla- dium-catalyzed cross-coupling processes and these include functional group compatibility, low toxicity of reagents and intermediates, ready availability of boron derivatives, high thermal stability and good tolerance against oxygen and aque- ous solvents. Recently, efforts have been focused on the devel- opment of efficient and selective catalytic systems that either
In conclusion, some results on the synthesis of benzo- [c][1,8]naphthyridine derivatives by intramolecular radical pyridylation of suitable substrates, obtained from pyridi- nium N-2 0 -pyridylaminide, through aneasy, mild, and selective approach are described. The methodology gener- ally seems to be more flexible and efficient in the preparationof 5H-benzo[c][1,8]naphthyridin-6-one deriva- tives and should be complementary to conventional routes in the preparationof fused pyridines. The method does, how- ever, produce complex reaction mixtures and/or poor yields for other derivatives. Although several reaction mechanisms can explain these transformations, reasonable pathways
regioselective. 7,8 The metalation, however, might not be quantitative. As an alternative, activation of the exocyclic amino group facilitates deprotonation, and regioselective alkylation. Thus, N-acyl-aminopyridines 6 have been deprotonated with sodium amide and alkylated with methyl iodide, 9,10 yielding the 2-methylaminopyridines by hydroly- sis. With other alkyl halides, obtained yields were lower. A similar procedure has been described using alcohols in the Mitsunobu reaction. 11 Alternative methods have been reported based on the easy reduction of aromatic aldimines, using heterocyclic fragments as leaving groups. Two-step
During the course of our studies on the intramolecular arylation of 1b, we evaluated the behavior of the pyridyl radical 2 (Scheme 1). The ultimate goal was the preparationof bipyridine 3 by a reaction pathway involving a exo/endo- trig cyclization, followed by N–N bond breaking, as previously described. 3d Compound 3, however, was not detected and instead, the tricyclic derivative 4 was obtained in moderate yield. 4 Following the same target in the development of a preparationof bipyridines and related biaryls by intramolecular radical arylation (i.e., 5, Scheme 1), we decided to prepare salt 6 in order to explore the feasibility ofan intramolecular free radical ipso-substitution of the corresponding arenesulfonamides by pyridyl radicals, according to the methodology described by Motherwell and col. 5 This well-established method, based on aryl radical cyclizations, has been applied to the synthesis of biaryls and arylheterocycles. However, to the best of our knowledge, references concerning the use of heteroaryl radicals in such a method have not been published to date. Indeed, from a general point of view, the cyclization of pyridyl radicals has scarcely been exploited in synthesis. 6
(150 mL) in a round-bottom ﬂask and the mixture was cooled to 0 °C. Under vigorous stirring NBS (4.4 mmol) was added portionwise to the reaction mixture. After the addition, the ﬂask was placed in an ultrasonic bath for 90 min. As soon as the starting material had been consumed (detected by TLC) the solvent was removed in vacuo and the residue was puriﬁed by chromatography (silica gel/CH 2 Cl 2 ). Compound 3b was isolated as a white
Informed consent is an essential element of research, and sig- ning this document is required to conduct most clinical trials. Its aim is to inform patients what their participation in the study will involve. However, increasingly, their complexity and length are making them difficult to understand, which might lead patients to give their authorization without having read them previously or without having understood what is stated. In this sense, the Ethics Committees for Clinical Research, and Pharmacists specialized in Hospital Pharmacy and Primary Care in their capacity as members of said committees, play an im- portant and difficult role in defending the rights of patients. These Committees will review thoroughly these documents to guarantee that all legal requirements have been met and, at the same time, that they are easy to understand by the poten- tial participants in a clinical trial.
The Resource_Group that participates with a Mechanism role in the Operations is called Machine (Fig. 2) and comprises a Machine_Base individual and one or more Tool and/or Fixture individuals. The Machine_Base is characterized by the capabilities to execute Tool_Movement activities, while Tool and Fixture are characterized by capabilities to execute Tool_Part_Interaction and locating/fixing activities respectively. As was shown in the previous section, in the GD area, final characteristics of parts are determined directly by the GD capabilities of the machine that executes the operation and the GD characteristics of the operation interface, considering tool-part interaction (Fig. 4). An interface quantifies the discrepancies that exist between machine capabilities in real execution conditions and in those used in the operations that served for the quantification of machine capabilities (test and historical). This is because the estimated capabilities are always closely linked with the actual loading level and the specific type of control.
Debido a que Easy Servi implementara una estrategia de marketing de seguidor tipo adaptador se implementara una campaña de lanzamiento que se contará con 3 jóvenes que se contrataran y formaran parte de la campaña BTL, estos deben portar la camiseta diseñada especialmente para la campaña de lanzamiento de Easy Servi, además de tener una breve publicidad con material POP (Popman). Su función será la de brindar información del servicio además de invitar a las personas a conocer uno de los vehículos de Easy servi, el cual estará estacionado fuera de la clínica para que puedan observar con sus propios ojos y muy
For comparison, calibration curves were constructed by concentrat- ing 10 mL of standard solution of Cd (0.02-0.20 ng mL -1 ) during 10 minutes at a flow rate of 1.0 mL min -1 , and 0.5 mL of elution vol- ume. 50 µL of the eluent were then injected into the furnace. The results of the three different MC fillings employed with the same amount of active solid HMS and under the same experimental conditions are shown in Fig. 8. The fillings are named HMS (only the synthetized solid), HMS-A (solid + resin, 10-90) and HMS-A-PVA (solid+ resin and 1% PVA), respectively. Table 2 shows the figures of merit obtained with the three different solids as MC fillers. To notice, the three materials could be reused more than 500 cycles without significant losses in analytical sensitivity (no changes in the slope of the working curve). Note that the extremely low concentra- tion of cadmium and the short times of contact under dynamic conditions (no need to reach equilibrium), allow this remarkable
A follow-up study was designed and conducted by health personnel in the IMSS to describe the clinical behavior of Dengue Fever (DF) and DHF and to deter- mine some of the risk factors associated with the oc- currence of hemorrhagic forms and fatal cases in the population attended by the most important social se- curity system in Mexico. Patients were cases diagnosed as DF or DHF that were confirmed by a serological test (IgM-ELISA), notified to the Coordination of Health Integrated Programs of IMSS from 1995 to 2003. Clini- cal and epidemiological data were obtained from the case report format used by the national surveillance system to notify DHF cases. Cases reported in this study include only those that had all epidemiologi- cal, clinical information, and laboratory data availa- ble. The database included age, sex, time of onset, travel history, and contact with similar cases in the household or in the community. It also included clini- cal features like fever, hepatomegaly, bleeding signs, data for previous infection, the final outcome of the disease and laboratory results (hemoglobin, hematocrit and platelets). Two groups were formed according to their clinical evolution and following the WHO/PAHO established criteria: 8 the DF and the Dengue Fever with
Por lo que una de las grandes propuestas de Easy Shop es reducir esta brecha de no fidelización, para ello una de las propuestas es medir la repercusión de compra de los usuarios contactados mediante las redes sociales, adicional a ello se puede almacenar el listado de compradores reincidentes en la adquisición de productos a nuestra tienda y de esta manera poder brindar algún tipo de incentivo o recordatorio, pues se entiende que si el cliente es reincidente es por que nuestros productos le están satisfaciendo sus necesidades y por lo tanto es conveniente sostenerlo mediante un incentivo que le capture y nos recomiende a su círculo inmediato.
Telluride precursor (NaHTe) was prepared by reducing tellurium with sodium borohydride under argon atmosphere, as reported elsewhere . Aqueous colloidal CdTe QDs were prepared in the absence and presence of the β CDP according to the in-situ methodology. In a three necks round bottom flask equipped with a condenser, cadmium chloride (430 mg, 2.34 mmol) was dissolved, under stirring, in a water solution (120 mL) of βCDP (120 mg). Mercaptopropionic acid (266 µL, 3.04 mmol) was added to the solution and the pH was adjusted to 11.0 with NaOH (0.1 mol/L). The resulted solution was exhaustively deoxygenated with argon (30 min) and a freshly prepared NaHTe (1760 µ L, 1.16 mmol) was added under stirring and in a gentle argon flow. The reaction mixture was set to reflux and the evolution of the QDs formation was monitored by recording the UV-Vis and fluorescent spectra of samples collected at certain reaction times. Each collected sample was set to dialyze in a Spectrapore ® dialysis membrane (cutoff 14 kDa) in order to remove the excess of polymer and chemicals resulting from the reaction. For comparison purposes, CdTe QDs were also prepared under the same conditions but in the absence of the β CDP.
Aldrich of 98 % – 103 %) were used as precursors salts for palladium and copper, respectively. The palladium salt was dissolved in ethylene glycol (99 % purity, Sigma Aldrich). The amount of palladium salt used was adjusted in order to obtain a 0.05 M concentration. In another flask, a 0.05 M solution of copper salt in ethylene glycol was prepared. To each of those solutions 1-hexadecylamine (HDA) (Aldrich, purity 90 %) was added in molar ratio of 3:1 with respect to the metal content. In order to adjust the Pd:Cu molar ratio to 4:1 the corresponding volumes from both solutions were taken and mixed. The mixture was stirred for one hour in an ice bath in order to avoid an early metal reduction. The homogeneous mixture was then heated at 140ºC in a reflux for 12 h. During the temperature increase a color variation of the liquid was observed; the initial green gradually transformed to blue, then red to black in the end. The changes indicate the formation of Pd-Cu alloy particles obtained by the reducing effect of ethylene glycol. The surfactant molecules of HAD act mainly as stabilizers in the particles formation. Finally, the nanoparticles were extracted with toluene. The nanoparticles were deposited into the CMR containing the cerium and iron oxide using the same procedure as described before for palladium nanoparticles obtained by the microemulsion method. 2.3 Characterization of Catalytic Membrane Reactors (CMRs)
Natural or intrinsic resistance, permanent mechanism is genetically determined, not be correlated with increasing doses of the antibiotic (3). It belongs to each family, species or bacterial group and its appearance predates the use of antibiotics, as evidenced by the isolation of antimicrobial resistant bacteria, an estimated age of 2000 years found in the depths of the glaciers in the regions Arctic Canada. Besides all bacteria of the same species are resistant to some families of antibiotics (6), for example, all gram-negative bacteria are resistant to vancomycin, and this situation is not variable. The resistance achieved is variable and is acquired by a strain of a bacterial species. Thus, there pneumococcal strains that have acquired resistance to penicillin resistant strains of Escherichia coli to ampicillin resistant strains of Staphylococcus aureus (8). Transmissible resistance is the most important, being mediated by plasmids, transposons or integrons, which can move from one bacterium to another (9).
breed feral dogs (20 females and 20 males; 1.5-10 years old), were included in this randomized, prospective, clinical study. Animals were deemed clinically healthy based on an exhaustive physical examination, hematological profiles (urea, cre- atinine, blood bilirubin, ALT, AST) and medical history. General body condition of dogs was neither too lean nor obese. They were dewormed (Drontal, Bayer Animal Health, Mexico), and an adaptation to housing environment was allowed as for the Guide for the Care and Use of Laboratory Animals, 24 and food for a period of two weeks was allowed before the start of the trial. Blood samples were obtained a day before and a day after the anesthetic procedure was performed. Food and water were withheld for 10 and 3 hours before anesthesia, respectively.
One of the most common cause of blindness globally is the consequence of corneal pathology . Several procedures have been described to repair the corneal surface not only to reestablish the physical barrier function of the cornea, but also to increase its transparency, and improve visual acuity of the patient. One part of these approaches relies on substrates different to cor- neal tissue to regenerate the corneal surface. Amnion has been used for that purpose since 1940s, applied as a graft or as a patch over corneal ulcers or defects[2, 3]. However, amnion has the major disadvantage of being biologically variable between donors, not least in transparency. Moreover, amnion is labour intensive to collect and prepare and costly to screen. Thus, dif- ferent research groups are trying to generate scaffolds that could substitute for corneal matrix without resorting to amnion, using a range of natural biomaterials from fibrin to fibrin-aga- rose and collagen. However, even where these materials are produced by standardized manufacture, careful control is needed not least to assess their optical properties prior to implantation. Hence, we need to identify suitable corneal replacements materials, or amnion patches, based on critical and objective optical evaluation.