Agrochemical Ingredients Research Articles

Ruthenium-Catalyzed Synthesis of Aryl and Alkenyl Halides from Fluorosulfonates.

Aryl and alkenyl halides are widely used as key intermediates in organic synthesis, particularly for the formation of organometallic reagents or as radical precursors. They are also found in pharmaceutical and agrochemical ingredients. In this work, the synthesis of aryl and alkenyl halides from the corresponding fluorosulfonates using commercially available ruthenium catalysts is reported. Notably, this is the first conversion of phenols to aryl halides that is efficient with chloride, bromide, and iodide. Fluorosulfonates are readily prepared using sulfuryl fluoride (SO2 F2 ) and less expensive substitutes for triflates. Although aryl fluorosulfonates and their reactions are well known, this is the first report of an efficient coupling of alkenyl fluorosulfonates. To finish, it was demonstrated, by means of representative examples, that the reaction is possible in a one-pot process, starting directly from phenol or aldehyde.

Synthesis of Enantioenriched Sulfoxides by an Oxidation-Reduction Enzymatic Cascade.

Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation-reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 % ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows CiVCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for (S)-sulfoxide synthesis; the latter case is significantly unexplored for heme-dependent peroxidases and peroxygenases.

Potential Risk of Agrochemical Leaching in Areas of Edaphoclimatic Suitability for Coffee Cultivation

Studies show that agricultural activities around the world still present a strong dependence on agrochemicals that can leach into the soil profile, causing its contamination, as well as that of water resources. In this context, the present study evaluates the potential risk of pesticide leaching in areas of edaphoclimatic suitability for coffee cultivation in Espírito Santo state, Brazil. As a methodology, the areas of edaphoclimatic suitability for conilon and arabica coffee were defined, and subsequently, the risk of leaching of active agrochemical ingredients in these areas was evaluated using the Groundwater Ubiquity Score (GUS), Leaching Index (LIX) and Attenuation Factor/Retardation Factor (AF/RF) methods. Of the ten active ingredients evaluated, sulfentrazone and thiamethoxam present a potential risk of leaching into the groundwater level. The study allowed us to evaluate the potential risk of agrochemical leaching in tropical soils cultivated with coffee using geographic information system (GIS) techniques. The methodological proposal can be adapted for other agricultural areas and crops.

Nanopesticides in Agriculture: Benefits and Challenge in Agricultural Productivity, Toxicological Risks to Human Health and Environment.

Nanopesticides are nanostructures with two to three dimensions between 1 to 200 nm, used to carry agrochemical ingredients (AcI). Because of their unique properties, the loading of AcI into nanoparticles offers benefits when compared to free pesticides. However, with the fast development of new engineered nanoparticles for pests’ control, a new type of environmental waste is being produced. This paper describes the nanopesticides sources, the harmful environmental and health effects arising from pesticide exposure. The potential ameliorative impact of nanoparticles on agricultural productivity and ecosystem challenges are extensively discussed. Strategies for controlled release and stimuli-responsive systems for slow, sustained, and targeted AcI and genetic material delivery are reported. Special attention to different nanoparticles source, the environmental behavior of nanopesticides in the crop setting, and the most recent advancements and nanopesticides representative research from experimental results are revised. This review also addresses some issues and concerns in developing, formulating and toxicity pesticide products for environmentally friendly and sustainable agriculture.

2,4‐Bis(fluoroalkyl)quinoline‐3‐carboxylates as Tools for the Development of Potential Agrochemical Ingredients

Based on an easy and scalable method for the synthesis of quinoline derivatives substituted by fluorinated groups at both the C‐2 and C‐4 positions developed in our laboratory, we have devised an approach to the synthesis of a new series of unprecedented 2,4‐bis(fluoroalkyl)quinoline‐3‐carboxylates in just two steps. After standard saponification, the latter gave the corresponding 2,4‐bis(fluoroalkyl)quinoline‐3‐carboxylic acids, which served as pivotal intermediates for post‐functionalization reactions. Indeed, the carboxylic group could then be derivatized according to known procedures to introduce chemical diversity at the C‐3 position of these unprecedented structures. The resulting highly functionalized quinolines can serve as a platform for the development of biologically active molecules with strong potential for agrochemical research.

Certification of Organic Agriculture for rice production in Indonesia

To make better the life, it is required safety foods for health. The health foods can be satisfied by organic farming that have more expensive price compared to foods derived from conventional agriculture. Organic farming is farming system based on biomass recycling or eliminating the use of materials as a synthetic agrochemical inputs. To determine whether the result of rice called as a organic product needs to be certified by the Organic Certification Board (OCB). According to the Indonesian National Standard 6729: 2013, organic farming systems are not only limited to not use material agrochemical synthetic, but must meet the requirements of organic farming systems in rice cultivation ranging from handling, storage, processing, transportation, labeling, marketing, production facilities, additional materials and other materials that are allowed start on farm to off farm should be separated from conventional agriculture. The farm is just a negate the use of agrochemicals and synthetic based on recycling without regard to the cultivation process and the system of post-harvest organic results are said to be food premium is not as organic food, because organic food is food produced from organic farming systems by applying processing practices to preserve the ecosystem of sustainable, control of weeds, pests, diseases, selection and crop rotation, water management, land preparation and planting and the use of biological materials. Thus the system of organic agriculture is a holistic production management system to improve and develop the agro-ecosystem health, including biodiversity, biological cycles and soil biological activity (Regulation of Indonesian Agriculture Ministry No. 64/2013). The first step that must be done is the conversion of land for food crops from anorganic to organic farming for 2 years did not get the requisite amount of agrochemical ingredients applied to the soil and 3 years for annual plants, after applying the organic farming system follows the Indonesian National standardization for organic farming. If agriculture in paddy soil can control the conventional farms into organic farming systems, then the resulting rice is as an organic product

Environmental Fate and Effects of Dichloroacetamide Herbicide Safeners: “Inert” yet Biologically Active Agrochemical Ingredients

Safeners are included in many commercial herbicide formulations to selectively protect crops from injury induced by active ingredients. Despite their bioactivity, safeners are classified as inert from a regulatory perspective, and as such, safeners have received minimal attention in the peer-reviewed literature regarding their environmental fate and effects. Herein, we review what is known about the uses, physicochemical properties, environmental transformations, and (eco)toxicological effects of dichloroacetamide safeners, which represent one of the most commonly used safener classes (estimated use of >2 × 106 kg/year in the United States). We particularly highlight transformation pathways that may enhance biological activity and/or persistence; for example, limited studies suggest dichloroacetamides can transform via dechlorination into products with increased bioactivity. We also identify several research needs to improve our understanding of the environmental fate and potential risks of this overlooke...

Design and Synthesis of Chiral Zn2+ Complexes Mimicking Natural Aldolases for Catalytic C–C Bond Forming Reactions in Aqueous Solution

Extending carbon frameworks via a series of C–C bond forming reactions is essential for the synthesis of natural products, pharmaceutically active compounds, active agrochemical ingredients, and a variety of functional materials. The application of stereoselective C–C bond forming reactions to the one-pot synthesis of biorelevant compounds is now emerging as a challenging and powerful strategy for improving the efficiency of a chemical reaction, in which some of the reactants are subjected to successive chemical reactions in just one reactor. However, organic reactions are generally conducted in organic solvents, as many organic molecules, reagents, and intermediates are not stable or soluble in water. In contrast, enzymatic reactions in living systems proceed in aqueous solvents, as most of enzymes generally function only within a narrow range of temperature and pH and are not so stable in less polar organic environments, which makes it difficult to conduct chemoenzymatic reactions in organic solvents. In this review, we describe the design and synthesis of chiral metal complexes with Zn2+ ions as a catalytic factor that mimic aldolases in stereoselective C–C bond forming reactions, especially for enantioselective aldol reactions. Their application to chemoenzymatic reactions in aqueous solution is also presented.

ChemInform Abstract: Synthesis of Diversely Fluorinated Pyrazoles as Novel Active Agrochemical Ingredients

AbstractReview: 50 refs.

Solvent-screening and co-crystal screening for drug development with COSMO-RS

Bringing active pharmaceutical or agrochemical ingredients (APIs) in solution often is the most demanding step in pharmaceutical and agrochemical development. The COSMO-RS method, which has been originally developed by the author during his 12 years at Bayer, is a unique combination of quantum chemical information and liquid phase thermodynamics and currently is proven to be the most accurate method for predicting the free energy of molecules in solution. Based on COSMORS theory the COSMOtherm suite of software tools is able to address a broad range of important aspects of solubilization and thus is an ideally suited toolset for rational solubilization development: Solvent screening, including mixtures and variable temperatures

Abiotic Reduction Reactions of Dichloroacetamide Safeners: Transformations of “Inert” Agrochemical Constituents

Safeners are so-called "inert" constituents of herbicide formulations added to protect crops from the toxic effects of herbicides. We examined the reactivity of three dichloroacetamide safeners and 12 structural analogues [all neutral compounds of the form Cl(2)CXC(═O)NRR'; X = H, Cl; R-groups include alkyl, branched alkyl, n-allyl, and cyclic moieties] in one homogeneous and two heterogeneous reductant systems: solutions of Cr(H(2)O)(6)(2+), suspensions of Fe(II)-amended goethite, and suspensions of Fe(II)-amended hematite. Analyses of reaction products indicate each safener can undergo stepwise hydrogenolysis (replacement of chlorine by hydrogen) in each system at near-neutral pH. The first hydrogenolysis step generates compounds similar (in one case, identical) to herbicide active ingredients. Rates of product formation and (when reactions were sufficiently fast) parent loss were quantified; reaction rates in heterogeneous systems spanned 2 orders of magnitude and were strongly influenced by R-group structure. The length of n-alkyl R-groups exerted opposite effects on hydrogenolysis rates in homogeneous versus heterogeneous systems: as R-group size increased, reduction rates in heterogeneous systems increased, whereas reduction rates in the homogeneous system decreased. Branched alkyl R-groups decreased hydrogenolysis rates relative to their straight-chain homologues in both homogeneous and heterogeneous systems. Reaction rates in heterogeneous systems can be described via polyparameter linear free energy relationships employing molecular parameters likely to influence dichloroacetamide adsorption. The propensity of dichloroacetamide safeners to undergo reductive transformations into herbicide-like products challenges their classification as "inert" agrochemical ingredients.

Conformation and geometry of cyclopropane rings having π-acceptor substituents: a theoretical and database study

The 3e' orbitals of cyclopropane have the correct symmetry to interact with low-lying unoccupied orbitals of π-acceptor substituents and maximum overlap occurs when the two orbital systems are parallel, i.e. when the π-acceptor bisects the ring in projection down the substituent bond. Since the cyclopropyl group is a common component of active pharmaceutical and agrochemical ingredients, it is important that these strong conjugative interactions are well modelled by computational techniques, and clearly represented in experimental crystal structures. Here we show that torsion angle distributions derived from crystal structure data in the Cambridge Structural Database are in excellent correspondence with torsional energy profiles computed using density functional theory (DFT) for a range of substituents: -COOR, -CONR(2), -NO(2), vinyl and phenyl. We also show that crystal structure information is invaluable in modelling conformations of compounds that contain multiply substituted rings, where steric interactions require some substituents to adopt energetically disfavoured conformations. Further, conjugative interactions with π-acceptors lead to significant asymmetry in the cyclopropane ring bond lengths and again the experimental and computational results are in excellent agreement. Such asymmetry effects are additive, and this explains bond-length variations in cyclopropane rings bearing two or more π-acceptor substituents.

Cytogenetic biomonitoring of Brazilian workers exposed to pesticides: Micronucleus analysis in buccal epithelial cells of soybean growers

Pesticides have been considered potential chemical mutagens and various agrochemical ingredients possess mutagenic properties. Biomonitoring provides a useful tool to estimate the genetic risk from exposure to a complex mixture of chemicals. In general genetic damage associated with pesticides occurs in human populations subject to high exposure levels due to intensive use, misuse or failure of control measures. Few studies have been carried out using the micronucleus (MN) analysis in buccal cells of farm workers and, from the available data, only one has found a positive relationship. Micronuclei were analyzed in 29 Brazilian workers exposed to pesticides in soybean fields and in 37 non-exposed individuals. The results obtained indicate that the mean number of cells with MN in the exposed group (3.55 ± 2.13) was significantly higher than in the control group (1.78 ± 1.23). The number of cells with MN was not influenced by age, smoking habit, smoking time, number of cigarettes/day, alcohol consumption and years of exposure to pesticides. The genotoxic potential of the pesticides used in soybean fields may explain the detectable increase of cells with MN in exposed workers.

Lymphocyte DNA damage in rats exposed to pyrethroids: effect of supplementation with Vitamins E and C.

Pesticides have been considered potential chemical mutagens. In fact, some studies show that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Experimental evidence shows a marked correlation between mutagenicity and carcinogenicity and indicates that short-term mutagenicity tests are useful for predicting carcinogenicity. The present study on rat exposed to two pyrethroids, cypermethrin and permethrin, showed different lymphocyte DNA damage depending on the type of pyrethroid, the dose, and the period of treatment. Data obtained from comet assay showed that oral treatment with 150 mg/kg body weight/day of permethrin (corresponding to 1/10 of LD50) for 60 days, induced a significant increase in all comet parameters. No lymphocyte DNA damage was measured after treatment with 25 mg/kg body weight/day of cypermethrin (corresponding to 1/10 of LD50) for the same period. A higher dose of permethrin (300 mg/kg body weight/day), for a shorter period (22 days), did not induce lymphocyte DNA damage, while supplementation with 200 mg/kg of Vitamins E and C protected erythrocytes against plasma membrane lipids peroxidation. Moreover, treatment with Vitamins E and C maintained the activity of glutathione peroxidase, which was reduced in the presence of permethrin, and reduced the osmotic fragility, which had increased following permethrin treatment.

Genotoxicity of pesticides: a review of human biomonitoring studies.

Pesticides constitute a heterogeneous category of chemicals specifically designed for the control of pests, weeds or plant diseases. Pesticides have been considered potential chemical mutagens: experimental data revealed that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Biological monitoring provides a useful tool to estimate the genetic risk deriving from an integrated exposure to a complex mixture of chemicals. Studies available in scientific literature have essentially focused on cytogenetic end-points to evaluate the potential genotoxicity of pesticides in occupationally exposed populations, including pesticide manufacturing workers, pesticide applicators, floriculturists and farm workers. A positive association between occupational exposure to complex pesticide mixtures and the presence of chromosomal aberrations (CA), sister-chromatid exchanges (SCE) and micronuclei (MN) has been detected in the majority of the studies, although a number of these failed to detect cytogenetic damage. Conflicting results from cytogenetic studies reflect the heterogeneity of the groups studied with regard to chemicals used and exposure conditions. Genetic damage associated with pesticides occurs in human populations subject to high exposure levels due to intensive use, misuse or failure of control measures. The majority of studies on cytogenetic biomarkers in pesticide-exposed workers have indicated some dose-dependent effects, with increasing duration or intensity of exposure. Chromosomal damage induced by pesticides appears to have been transient in acute or discontinuous exposure, but cumulative in continuous exposure to complex agrochemical mixtures. Data available at present on the effect of genetic polymorphism on susceptibility to pesticides does not allow any conclusion.

Genotoxicity of pesticides: potential risk for consumers

Pesticide residues in vegetables and fruits continue to generate concern in the general population mainly about their potential long term adverse effects such as cancer. The pesticides currently in use include a wide variety of compounds belonging to different chemical classes. More than 800 chemicals marketed as multiple formulations, are used in the European Union, as insecticides, herbicides, fungicides. Pesticides have been considered potential chemical mutagens. Experimental data revealed that various agrochemical ingredients possess mutagenic properties inducing gene mutation, chromosomal alteration or DNA damage. The genotoxic potential for agrochemical ingredients is generally low: they give positive results in few genotoxicity tests. In human biomonitoring studies genetic damage associated with pesticides has been detected for high exposure levels and intensive use. The genetic effects depend on quantity and variety of chemical formulations consumed. Improvements of agricultural practices and of safety of work conditions has reduced the genotoxic hazard. The most recent studies failed to reveal genotoxic damage. This evidence suggests a negligible risk for general population exposed to very low levels of residues.