Key Intermediates: A simple and Highly Selective Synthesis of 5-amino-1-aryl-1H-pyrazole-4-carbonitriles for Applications in the Crop Protection

A series of six pyrazoles was synthesized by Michael-type addition reaction. The molecules 5- amino-1-aryl-1H-pyrazole-4-carbonitrile (3a-f) were synthesized from (ethoxymethylene)malononitrile (1) and fluorinated and non-fluorinated aryl hydrazines (2a-f) using ethanol and fluorinated ethanol as solvents at reflux. An excellent regio-selectivity was found when pyrazole derivatives were formed as an exclusive product. No other regioisomer or uncyclised hydrazide was observed. Their structures were confirmed by spectroscopy data (1H, 13C, 19F, COSY (correlation spectroscopy), HSQC (heteronuclear single-quantum correlation spectroscopy) and HMBC (heteronuclear multiple-bond correlation spectroscopy); MS (mass-spectrometry). The yields ranged from good to excellent (47% - 93%) under mild reaction conditions. It would indicate a high selectivity in the one-step work procedure. These products (3a-f) and derivatives have a potential academic and industrial use as key intermediates, in special, for application in crop protection.Fil: Plem, Silvana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Müller, Diana. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS

The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugsFil: Baldo, Matias Nicolas. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Hunzicker, Gabriel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dominguez Lab; ArgentinaFil: Altamirano, Jorgelina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hein, Gustavo Juan. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentin

New Antifungal Agents: Synthesis, Characterization and Biological Activity of Some Mannich Bases Derived from 2-Mercaptobenzothiazole

A series of new 3-[(amino)methyl]-1,3-benzothiazole-2-thione 4(a-l) were synthesized by Mannichreaction from formaldehyde, aliphatic or aromatic amines and 2-mercaptobenzothiazole. All synthesized compounds were in good agreement with elemental and spectral data (1H NMR and mass spectroscopy) and were evaluated for in vitro antifungal activity by agar well diffusion method. Fluconazole was included in the assays as a commercially available reference compound. Four fungal strains were used to perform the study: Cladosporium cladosporioides, Aspergillus niger ATCC 16404, Botrytis sp. and Rhizopus sp. Compounds 4a-c, 4e-g, 4i and 4l were found to be active against the four moulds mentioned, due to the presence of inhibitory halo. 4h was active in case of C. cladosporioides. Compounds 4d, 4j and 4k did not show inhibition against fungi used for the test. Fluconazole showed biological activity against Aspergillus niger ATCC 16404 and Botrytis sp. Therefore, 8 of the 12 synthesized substances would be considered as promising products to the treatment of fungal diseases.Fil: Gutierrez, Carolina Guadalupe. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Química Aplicada.; ArgentinaFil: Machuca, Laura Marcela. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acuña Ojeda, Maria Florencia. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alfaro, Esteban. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Spagnolo, Lorena Cecilia. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Química Aplicada.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentin

Production and Sensory Evaluation of Novel Cheeses Made with Prebiotic Substances: Inulin and Oligofructose

In recent years, the processing and consumption of functional foods worldwide have greatly increased. These foods benefit the body functions which improve consumers’ health and also reduce the risk factors that cause the onset of disease. Furthermore, prebiotic substances favor the multiplication of beneficial intestinal bacteria rather than harmful ones. The purpose of this study was to conduct the sensory evaluation of two functional cheeses containing inulin and oligofructose as a distinctive ingredient, including testing a cheese made with conventional ingredients, called control cheese. Affective type tests, which measured the degree of liking or disliking, were conducted using a verbal 7-point hedonic scale. According to the inclusion and exclusion criteria, 57 untrained judges were selected. This study is a quantitative, analytic and experimental-cross design. Statistical analysis of the data was performed by ANOVA with repeated measures. The results show a similar average degree of liking for the three cheeses, above 5 on the scale or “like”. By analyzing the critical level and the result of the Mauchly’s sphericity test, it is concluded that there is no statistically significant difference in the degree of liking for the three cheeses. Therefore, the addition of prebiotics to artisanal cheeses achieves to satisfy consumers and provide them benefits superior to those provided by traditional foods.Fil: Machuca, Laura Marcela. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Cientificas (sede Goya); ArgentinaFil: Rodriguez, Yamila E.. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Cientificas (sede Goya); ArgentinaFil: Guastavino Meneguini, Daniela E.. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Cientificas (sede Goya); ArgentinaFil: Bruzzo, Maria E.. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Cientificas (sede Goya); ArgentinaFil: Acuña Ojeda, María F.. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Cientificas (sede Goya); ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentin

One-pot synthesis and insecticidal activity of 5-amino-1-aryl- 1H-pyrazole-4-carbonitriles

Synthesis of 5-amino-1-aryl-1H-pyrazole-4-carbonitriles was performed by direct condensation of 29 (ethoxymethylene)malononitrile and aryl hydrazines. The resulting N,N-containing heterocycles possess 30 insecticidal properties relative to microlepidoptera species, plant phatogens. The insecticidal activity of 31 four novel synthetic N-aryl pyrazoles to Tuta absoluta larvae was assessed. Fipronil, a well-known aryl 32 pyrazole insecticide, was also tested as the positive control. A generalized linear model reported 33 significant differences in efficacy and tomato leaf consumption among the different treatments. Fipronil 34 treatment was the most effective one (100% mortality after 48 h), followed by 5-amino-1-phenyl-1H-35 pyrazole-4-carbonitrile treatment (3c) (75% mortality after 48 h) and 5-amino-1-(2,6-dichloro-4-36 (trifluoromethyl)-phenyl-1H-pyrazole-4-carbonitrile treatment (3b) (60% mortality after 48 h). These 37 compounds, with simpler structures than Fipronil, could be used as novel insecticides.Fil: Plem, Silvana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Machuca, Laura Marcela. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones (sede Formosa).; ArgentinaFil: Gutierrez, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Coll Araoz, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Van Nieuwenhove, Guido Alejandro. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Virla, Eduardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Química Aplicada.; Argentin

Design, Synthesis and Insecticidal Activities of Novel Pirazol Derivatives to Crop Protection

Aryl pyrazoles are compounds that display very interesting biological activities. This chapter reviews recent work of our group in the development of synthetic strategies for the preparation of new examples of these kinds of compounds to crop protection. A series of six N-aryl pyrazoles was synthesized by Michael-type addition reaction. The molecules 5-amino-1-aryl-1H-pyrazole-4-carbonitrile (3a-f) were synthesized from (ethoxymethylene)malononitrile (1) and fluorinated and non-fluorinated aryl hydrazines (2a-f) using ethanol and fluorinated ethanol as solvents at reflux. An excellent regio-selectivity was found when pyrazole de- rivatives were formed as an exclusive product. No other regioisomer or uncyclised hydrazide was observed. Their structures were confirmed by spectroscopy data (1H, 13C, 19F, COSY (correlation spectroscopy), HSQC (heteronuclear single-quantum correlation spectroscopy) and HMBC (heteronuclear multiple-bond correlation spectroscopy); MS (mass-spectrometry). The yields ranged from good to excellent (47% - 93%) under mild reaction conditions. It would indicate a high selectivity in the one-step work procedure. These products (3a-f) and derivatives have a potential academic and industrial use as key intermediates, in special for application in crop protection.Fil: Machuca, Laura Marcela. Universidad Nacional del Litoral; ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Biosorption of an anionic dye by peanut shell modified with gemini surfactants: A study on the stability of the modification and the removal efficiency

In this study, novel biosorbents were obtained from peanut shells modified with gemini-type surfactants. Peanut shells, an agro-industrial residue, were successfully modified to enhance their naturally low biosorption capacity towards anionic contaminants. An anionic dye (tartrazine) was employed to test their performance. Three gemini were synthesized from N,N-dimethylamines with different chain length and 1,3-dichloro-2-propanol as a linker. They were purified and characterized and their surfactant properties were determined. The successful modification of the peanut shells was confirmed through a retention study based on a two-phase titration method. This method has not been reported before for modified biosorbents and should be considered to prevent risky lixiviation. Retention was found to be high (98.0–99.7%) and to be chain length-dependent. Biosorption followed the pseudo-second order kinetic model and equilibrium isotherms of the gemini-modified biosorbents were best fitted by the Langmuir model. Their maximum biosorption capacities (0.126–0.141 mmol g−1) proved to be more than threefold higher than that of the unmodified peanut shells. The retention capacity of the gemini was also tested after biosorption studies.Fil: Fernandez, Maria Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Preparation of eco-friendly antifungals derived of N-acetylated gemini surfactants for use in the chrome tanning processes of skins and hides

The aim of this work was to compare two novel antifungal agents with 2-(thiocyanomethylthio)-benzothiazole (TCMTB). For this study, two gemini surfactants (3b and 3e) were efficiently synthesized and formulated. The antifungal potency of these compounds was tested and their effectiveness as leather preservatives during the chrome-tanning process was assessed using the environmental chamber test (ASTMD 3273-00 Standard) and wet-blue hides on a plate with culture medium (ASTM D 4576-08 Standard). Two strains were used to perform the study: Aspergillus niger ATCC 6275 and Penicillum citrinum ATCC 9849 3b and 3e showed the ability to preserve hides because of their antifungal activity present in chromium tanning specimens. Compound 3e was foundto be a more potent antifungal than compound 3b, but not as potent as TCMTB. This cationic gemini compound (3e) was less toxic than TCMTB for Daphnia magna as a biological model. This work is the result of a patent of invention registered in the patent offices from Argentina.Fil: Machuca, Laura Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Química Aplicada.; Argentin

Synthesis of New Pentaerythritol-Based Gemini Surfactants

New dimeric or gemini surfactants bearing double-chain with two or four sulfonate groups, and quadruple-chain with four sulfonate groups, were prepared from pentaerythritol in good overall yields. All these surfactants showed excellent surface-active properties.Fil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Synthesis and surface-active properties of novel cleavable gemini surfactants

A novel series of quaternary ammonium gemini compounds having a butynylene spacer and different hydrocarbon chain lengths (CGBu8-16) were prepared. Carbonate group inserted between the hydrocarbon chains and the polar heads make these compounds hydrolyzable. The degradation under hydrolysis of these novel series will lead to the generation of fatty alcohols and readily degradable compounds. The reagents used are biodegradable, renewable, or reusable. The surface activities and foamability in aqueous solution of the cleavable gemini compounds containing n-octyl, n-decyl, and n-dodecyl chains meet the criteria for being good surfactants and showed stable foams even at low concentrations.Fil: Gilbert, Elangeni Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Guastavino, Javier Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral; Argentin