Design,synthesis, antinociceptive,and anti-inflammatory properties of thiazolopyrimidine derivatives

Ten 2-(substituted benzylidene)-7-(4-chlorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one derivatives were synthesized and evaluated. A series of heterocyclic, 2-(substituted benzylidene)-7-(4-chlorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one were synthesized by reaction of 7-(4-chloro phenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one with appropriately substituted aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid. The antinociceptive activity was evaluated by tail-flick technique, anti-inflammatory activity was evaluated by carrageenan-induced paw edema test and their ulcerogenicity index was determined. The para-substituted methyl, hydroxy, fluoro, chloro, bromo, and nitro derivatives showed significant antinociceptive and anti-inflammatory activities. The detailed synthesis, spectroscopic data, and pharmacological screening of the synthesized compounds were reported.     

Synthesis of carboxylic dithiocarbamic anhydride and substituted thiourea derivatives in water

The use of water as a solvent has sometimes benefits such as improving reactivities and selectivities, simplifying work-up procedures, and environmentally benign. Many carboxylic dithiocarbamic anhydride products are valuable building blocks in heterocycles and natural products. Here we present a simple one-pot synthesis of carboxylic dithiocarbamic anhydride by condensation of amines, carbon disulfide, acyl halide, or acetic anhydride in water. We obtained a variety of biologically important acyl dithiocarbamate derivatives in 82–93% yields in 10–30 min. This procedure can be used for the synthesis of thioureas from dithiocarbamates. Here, the sequential, one-pot three-component reaction of amines, carbon disulfide, and isothiocyanates provides unsymmetrical substituted thioureas in 81–91% yields.     

An environment-friendly synthesis of 4(3H)-quinazolinones

4(3H)-Quinazolinones, a class of important heterocycles, are used extensively in various fields. Although there are a number of synthetic approaches, all of them use catalysts, solvents, chemical oxidants, and/or reagents harmful to the environment when released in large quantities. An environment-friendly, catalyst-free, solventless, one-step synthesis of 4(3H)-quinazolinones is presented. The process involves heating of aldehydes and anthranilamides under air as cheap oxidant and as key promoter of reaction. The protocol is suitable for both aromatic and aliphatic aldehydes. This novel synthetic method may be applied to a wide range of educts, offering high yields at low cost while characterized by minimum environmental impact.     

Efficient synthesis of pyrano[2,3-b]pyridine derivatives using microwave or solar energy

Pyranopyridine derivatives are an important class of heterocyclic compounds due to their biological activities such as antitumor and antibacterial. However, conventional procedures for their synthesis produce large amounts of toxic by-products. Therefore, there is a need to develop simple, efficient and environmentally benign procedures. Here, a one-pot multicomponent protocol is designed for the synthesis of pyrano[2,3-b]pyridone derivatives by reaction of equimolar amounts of 6-hydroxy-1,4-dimethyl-1,2-dihydropyridines, aryl aldehydes and malononitrile, using both microwave heating and solar thermal energy in aqueous EtOH (50%) in the presence of a catalytic amount of K₂CO₃. The products were obtained in 84–90% yields in 10–20 min by microwave heating, and in 90–96% yields in 2–3 h using solar energy.     

Highly efficient microwave-assisted one-pot synthesis of 4-aryl-2-aminothiazoles in aqueous medium

The thiazole ring system is one of the most important heterocycles in nature, as it represents an important structural motif of many biological compounds, including vitamin B₁ (Thiamin), carboxylase and penicillin. There is, therefore, an urgent need to design rapid, efficient and environmentally benign protocols for the synthesis of thiazoles. Herein, we have developed a one-pot protocol for the synthesis of 4-aryl-2-aminothiazoles from the reaction of aromatic ketones, NBS (N-Bromosuccinimide) and thioureas under microwave irradiation at 80–85 °C in PEG (polyethylene glycol)-400 and water as a green reaction medium. The products were obtained in 84–89% yields in 28–32 min. The method has several advantages such as use of green solvent, easy work-up, excellent yield and avoiding use of lachrymatric α-haloketones.     

Fast and efficient synthesis of N-substituted β-aminobutyric acids by grinding at room temperature

Green chemistry is gaining increasing interest due to the growing awareness of the chemical community for sustainable development. Green chemistry solutions include synthesis without solvent and catalyst because many solvents and catalysts are toxic and expensive. Herein, we report the solvent and catalyst free method for the synthesis of N-substituted derivatives of β-aminobutyric acid by direct aza-Michael addition of amines to crotonic acid. The protocol involves simple mixing or grinding the reactants at room temperature. The β-amino acid derivatives were obtained in 82–100 % yield with a short reaction time without any tedious workup procedures. Our findings thus reveal a promising alternative to previously used procedures.     

Fast 62–92 % yield preparation of amino acid dithiocarbamates in green solvent at room temperature

Dithiocarbamate and their derivatives are of importance in medicinal chemistry due to their biological activities, in agriculture as fungicides and in organic synthesis as versatile synthetic intermediates. Green solvents such as deep eutectic solvents and polyethylene glycol are new emerging alternatives to conventional harmful organic solvents. Here, we report the synthesis of amino acid–based dithiocarbamates by one-pot three-component reaction of the electrophilic reagent, carbon disulfide and α-amino acids in deep eutectic solvent and polyethylene glycol as a catalyst and reaction media. In situ preparation of dithiocarbamates by the reaction of different amino acids and carbon disulfide, followed by addition reaction with epoxides, alkyl halides and α, β-unsaturated enones at room temperature, gave the corresponding products in 62–92 % yield with a short reaction time without any tedious workup procedures. The deep eutectic solvents and polyethylene glycol were recycled without activity or yield decrease. Therefore, the synthesis of amino acid–based dithiocarbamates in green solvents is a promising alternative to previously used procedures.     

Catalyst-free synthesis of imidazo [1,2-a] pyridines via Groebke multicomponent reaction

Deep eutectic solvents are becoming more popular nowadays since they are green, safe and often save raw materials and energy compared to organic solvent. Due to the importance of environmentally compatible solvent in multicomponent reactions, herein we report an efficient and sustainable catalyst-free synthesis of imidazo [1,2-a] pyridines via Groebke multicomponent reaction in choline chloride-based deep eutectic solvent. One-pot, three-component reaction of 2-amino pyridine, aromatic aldehydes and cyclohexyl isocyanide in six different choline chloride-based deep eutectic solvents in the absence of catalyst were examined. Urea–choline chloride was selected as an efficient solvent for this isocyanide-based multicomponent reaction and afforded the imidazo [1,2-a] pyridines in good yields of 57–87 % and reaction times of 2–6 h. The method has several advantages such as environmentally benign and biodegradable solvent, easy purification processes by a simple filtration and methodological simplicity.     

Modified ��-cyclodextrins as prospective agents for improving water solubility of organic pesticides

The drawback of some organic pesticides is their low water solubility. Cyclodextrins are used as agents for improving pesticides water solubility. However, the stabilization of the crystalline lattice can reduces to a large extent the solubility of cyclodextrins, especially β-cyclodextrin. Here, searching for the water soluble β-cyclodextrin derivatives, a set of new “host” compounds were prepared by the reaction of β-cyclodextrin with methyl epoxycinnamate. The reactants ratio was varied in to study the substitution degree of the obtained derivatives. The structure was determined by the ¹H-NMR and FT IR spectra. The average degree of substitution was determined by integration of the corresponding NMR signals and by elemental analysis. The solubility of four selected pesticides: dimethoate, simazine, linuron and thiram, in water with and without addition of the new modified β-cyclodextrin was measured by ultraviolet spectrophotometry. Our results showed that the modified β-cyclodextrins significantly improve solubility of pesticides.     

新农药氯虫酰胺在醇液中的光解

分别以氙灯和紫外灯为光源,对氯虫酰胺在甲醇和乙醇中的光解动力学及降解机理进行了研究。结果表明,在氙灯和紫外照射下,氯虫酰胺在甲醇和乙醇中的光解符合一级反应动力学规律。在模拟太阳光氙灯辐射下,氯虫酰胺在甲醇和乙醇中的光解半衰期分别为1．58h和2．57h,而紫外光辐射下分别为1．49min和1．60min。采用LC-MS对氯虫酰胺光解产物进行分离和鉴定,推断氯虫酰胺在醇中的光解途径主要涉及到分子环合和重排生成光解产物A[2-（2-溴-4H-吡唑并[1,5．d]吡啶并[3,2-b]B,4]恶嗪-4-基亚氨基）-5-氯-N,3-二甲基苯甲酰胺]和B[2-（3-溴-1-（3-羟基吡啶-2-基）-1H-吡唑-5-基）-6-氯-3,8-二甲基喹啉-4（3H）-酮1。     

Vitamin B1 as a metal-free organocatalyst for greener Paal–Knorr pyrrole synthesis

This investigation discloses a greener reaction to prepare pyrrole derivatives. Metal-free catalysts are greener alternatives to existing metal catalysts in synthetic organic chemistry. Indeed, transition metals are often costly and toxic. They may be found as traces in health reaction products such as pharmaceuticals. Alternatively small organic molecules termed “organocatalysts” allow the synthesis of valuable products without traces of toxic metals. Here, we show for the first time the use of vitamin B₁ as new organocatalyst for the Paal–Knorr pyrrole synthesis under ambient conditions. Reaction conditions were optimized for the reaction of hexane-2,5-dione with 4-methoxyaniline. Ethanol was the most effective solvent. The conversion was quantitative using vitamin B₁, by comparison with a low yield of 30?% without catalysis. The best conditions were performed in ethanol with 5?mol % of vitamin B₁ during 1?h. This reaction was tested using various aromatic amines. To conclude the use of vitamin B₁ for the Paal–Knorr pyrrole, cyclocondensation has mild reaction conditions, is simple to perform, and gives moderate to excellent yields. It is therefore a promising reaction for the preparation of various pyrrole derivatives.     

Room temperature aqueous Paal–Knorr pyrrole synthesis catalyzed by aluminum tris(dodecyl sulfate)trihydrate

This article reports a novel procedure to prepare pyrroles using a modification of the Paal–Knorr reaction. Water is a safe solvent meeting environmental considerations, but most organic substrates are not soluble in water. A possible solution to improve the solubility of substrates is the use of surface-active reagents that can form micelles. For instance, combined Lewis acid–surfactant catalyst acts both as a Lewis acid to activate the substrate molecules and as a surfactant to form emulsions in water. Here, we prepared and used aluminum tris(dodecyl sulfate)trihydrate to condense various amines to 2,5-hexadione at room temperature. The sole solid pyrrole was separated by a simple filtration. Our findings thus show a novel and improved modification of the Paal–Knorr reaction in terms of mild reaction conditions and clean reaction profiles, using a simple workup procedure and improved yields with excellent chemo-selectivity.     

溴化1-丁基-3-甲基咪唑离子液体在空心菜中的吸收积累特性及其毒理效应

通过营养液水培的方式,研究了在不同浓度溴化1-丁基-3-甲基咪唑([C4mim]Br)对空心菜的毒性效应,测定了[C4mim]Br对空心菜各生长指标、叶绿素含量、丙二醛(MAD)含量以及根系活力的变化情况,同时研究了空心菜对[C4mim]Br的吸收和体内积累特征。结果表明:随着[C4mim]Br处理浓度与培养时间的增加,[C4mim]Br对空心菜各生理生化指标有显著抑制作用,且抑制效应具有剂量依赖型特点,半最大效应浓度(EC_(50))值为1.64 mg·L~(-1)。空心菜体内丙二醛含量显著增加表明[C4mim]Br加剧了细胞膜受损,导致根系对[C4mim]Br的吸收积累能力下降。空心菜的富集系数与转运系数均小于1,表明空心菜可以从环境中吸收并积累[C4mim]Br,但从根到地上部分转运[C4mim]Br能力较弱。     

Fenton degradation of dialkylphthalates: products and mechanism

Contamination of wastewater by organic pollutants is a major worldwide issue. For instance plastic additives such as phthalates are found in wastewater. Efficient techniques are thus needed to clean wastewaters. The Fenton reaction involving H₂O₂ and Fe(II) salts can be used to treat polluted water. During the Fenton reaction pollutants are decomposed directly by hydroxyl radicals. In some cases toxic by-products are produced. Here dimethyl phthalate, diethyl phthalate, and dipropyl phthalate by-products formed during the Fenton reaction were studied. Fenton degradation of selected phthalates yielded numerous transformation products such as hydroxylated phthalates. The hydroxylation reaction occurred at the aromatic ring of phthalates and yielded mono- and dihydroxylated phthalates. For monohydroxylated phthalate, 3-hydroxy- and 4-hydroxydialkylphthalates are the main transformation products. In addition to hydroxylated derivatives, aliphatic chain degraded mono- and dihydroxylated phthalates were also detected.     

Efficient synthesis of α,β-unsaturated ketones with trans-selective Horner–Wadsworth–Emmons reaction in water

Organic reactions in aqueous media are being developed because water is environmentally benign. The Horner–Wadsworth–Emmons reaction is a modified Wittig reaction for the synthesis of α,β-unsaturated ketones and other conjugated compounds. Here we prepared high molecular weight ketones by the Horner–Wadsworth–Emmons reaction of dimethyl-2-oxopropylphosphonate and various aldehydes in water at room temperature. The product was precipitated during the reaction process and was separated readily by a simple filtration in 90–99 % yield.     

Polycyclic aromatic hydrocarbons in soils around Guanting Reservoir,Beijing, China

The concentrations of 16 polycyclic aromatic hydrocarbons (∑ 16PAHs) were measured by gas chromatography equipped with a mass spectrometry detector (GC-MS) in 56 topsoil samples around Guanting Reservior (GTR), which is an important water source for Beijing. Low to medium levels of PAH contamination (mean=394.2±580.7 ng g^?1 dry weight (d.w.)) was evident throughout the region. In addition, localised areas of high PAH contamination near steel and cement factories were identified, with ∑ 16PAHs concentrations as high as 4110 ng/g, dry weight (d.w.). There was a significant positive correlation (r²=0.570, p<0.01) between total organic carbon content and ∑ 16PAHs concentrations. Phenanthrene was the predominant compound, accounting for 27.2% of the ∑ PAH concentration, followed by chrysene>pyrene>benzo[a]anthracene≈ benzo[b]fluoranthene≈ benzo[a]pyrene. Four-ring PAH homologues (39%) were dominant. The higher proportion of 4–6 ring homologues, molecular indices, and the spatial distribution of PAH indicated that industrial discharges, incineration of wastes and traffic discharges were the major sources of soil PAHs around the water reservoir.     

兰州地区苯并(a)芘的环境多介质迁移和归趋模拟

利用Level Ⅲ逸度模型模拟计算了稳态假设下苯并(a)芘在兰州地区大气、水体、土壤和沉积物中的相间迁移通量、浓度分布.结果表明:大气的平流输入和化石燃料燃烧是该区域苯并(a)芘的主要来源,土壤是其最大的储库,占总残留量的99.6%;在大气、水体、土壤和沉积物中的浓度分别为1.61×10-10 mol·m-3、9.39×10-7 mol·m-3、7.13×10-4 mol·m-3和9.17×10-5mol·m-3,模型计算浓度与同期实测浓度吻合较好,验证了模型的可靠性,并通过灵敏度分析,确定了模型的关键参数.     

A convenient and eco-friendly way to synthesize Pt(II) and Pd(II) porphyrins in ionic liquids by microwave activation

Due to the slow rate of incorporation of inert-metal ions into free-base porphyrins compared to other transition metals, several methods have been proposed to accelerate the rate of metalation. However, these methods have disadvantages such as low yields, difficulties of purification of final products, and environmental effects. To avoid those disadvantages, we reacted Pt(II) and Pd(II) salts with H₂(TPP), H₂(TMPyP)⁴⁺, and their β-pyrrole derivatives, H₂(Br₈TPP) and H₂(Br₈TMPyP)⁴⁺, in 1-butyl-3-methylimidazolium bromide ([bmim]⁺Br⁻) under microwave irradiation. The combination of microwave heating and ionic liquids provides efficient thermal energy transfer among the porphyrins and metal salts. In addition, ionic liquids stabilize charged species as well as their intermediates, due to their high dipole moment and high boiling point. This not only shortens the reaction time but also gives high yields of products at relatively low temperatures, of about 100°C compared to conventional synthesis methods: 150°C for DMF, 190°C for DMSO. Here, we demonstrate that Pt(II)/Pt(II) metalloporphyrins are synthesized at high rates, e.g. 6–30 min for 100% metalation, with high yields of 79–93% in [bmim]⁺Br⁻ by microwave activation.     

Accumulation and phytoavailability of benzo[a]pyrene in an acid sandy soil

Effects of benzo[a]pyrene (B[a]P) on ryegrass (Lolium perenne L.) growth, plant accumulation and dissipiation of B[a]P in a red sandy soil (Hapli-Udic Argosol) were studied in a pot experiment. The plants were grown for 61 days in soil spiked with B[a]P at 0, 12.5, 25 and 50 mg kg⁻¹. Control pots without plants were also set up. Soil extractable B[a]P, plant shoot and root biomass, and concentrations of B[a]P in plant shoots and roots were determined. Ryegrass biomass was increased by addition of B[a]P and root B[a]P concentrations were significantly correlated with B[a]P application rate, but no such correlation was found for shoot B[a]P concentrations. This indicates that B[a]P enhanced the growth of the ryegrass. The extractable B[a]P concentration in the planted soil was significantly lower than that in the unplanted control soil at the rate of 50 mg B[a]P kg⁻¹. This indicates that ryegrass may help to dissipate B[a]P in soil at concentrations over 50 mg kg⁻¹ soil although the mechanism for this is not understood.     

Nucleic acid synthesis in oceanic microplankton from the drake passage,antarctica: Evaluation of steady-state growth

Differential uptake of [³H]adenine and [³H]thymidine, and incorporation of tritium label into proteins, RNA and DNA as a function of depth, indicate that surface microplankton incorporated most of the assimilated radioisotopes into nucleic acids. Growth processes for deep-sea microplankton were shifted towards higher rates of [³H]-adenine incorporation into RNA compared to rates of thymidine incorporation into DNA. Deep-sea microplankton also diverted a larger portion (up to 80%) of the assimilated tritium into biosynthetic pathways for amino acid and eventual incorporation into proteins. These results imply that protein synthesis is vital for deep-sea microplankton where populations may be stressed by low levels of available nutrients. The rates at which microplankton incorporated [³H]adenine into RNA and DNA, and [³H]thymidine into DNA, suggest that oceanic microplankton are in a transient state of balanced growth, i.e. between two steady-state growth conditions, irrespective of potential growth rates. Our results support the hypothesis that oceanic microplankton are in various growth states.