Chemical Isolation Research Articles

Four-layer folding framework: design, GAP synthesis, and aggregation-induced emission.

The design and synthesis of a type of [1 + 4 + 2] four-layer framework have been conducted by taking advantage of Suzuki-Miyaura cross-coupling and group-assisted purification (GAP) chemistry. The optimized coupling of double-layer diboronic esters with 1-bromo-naphth-2-yl phosphine oxides resulted in a series of multilayer folding targets, showing a broad scope of substrates and moderate to excellent yields. The final products were purified using group-assisted purification chemistry/technology, achieved simply by washing crude products with 95% EtOH without the use of chromatography and recrystallization. The structures were fully characterized and assigned by performing X-ray crystallographic analysis. UV-vis absorption, photoluminescence (PL), and aggregation-induced emission (AIE) were studied for the resulting multilayer folding products.

Comparison of two gallium purification procedures for isotopic measurements by MC-ICP-MS in a set of silicate reference materials

Gallium is a moderately volatile, moderately siderophile element with two stable isotopes: 69Ga and 71Ga. A general interest in Ga isotopes arose over the last few years, as its moderately volatile behavior potentially marks it as a useful tracer of various processes such as condensation and evaporation. Nevertheless, there is a lack of agreement between laboratories for consistent δ71Ga values in geological reference materials. In this work, we have developed and evaluated two methods for purification protocols leading to precise analysis of gallium (Ga) isotopic composition in silicate rock materials. The first method is a three-step column chemistry using the resins AG1-X8, HDEHP, and AG50W-X12 whereas the second method uses only two columns, AG1-X8 and AG50W-X8. The two methods were applied to a range of both synthetic (multi-element) solutions and geological samples. Both methods show comparable results with no isotope fractionation occurring during purification chemistry, allowing us to define the δ71Ga of selected USGS reference materials (BHVO-2, BCR-2, RGM-2). Similar to previously reported results, we also observe no Ga fractionation between distinct igneous terrestrial materials.

An efficient, catalyst-free and aqueous ethanol-mediated synthesis of 5-((2-aminothiazol-5-yl)(phenyl)methyl)-6-hydroxypyrimidine-2,4(1H,3H)-dione derivatives and their antioxidant activity.

In this study, we effectively developed a catalyst-free multicomponent synthesis of 5-((2-aminothiazol-5-yl)(phenyl)methyl)-6-hydroxypyrimidine-2,4(1H,3H)-dione derivatives employing 2-aminothiazole, N',N'-dimethyl barbituric acid/barbituric acid and different aldehydes at 80 °C in an aqueous ethanol medium (1 : 1) using group-assisted purification (GAP) chemistry. The essential characteristics of this methodology include superior green credential parameters, metal-free multicomponent synthesis, faster reaction times, greater product yields, simple product purification without column chromatography and higher product yields. All of the synthesized compounds were analyzed against the HepG2 cell line. Compounds 4j and 4k shows good anti-proliferative effects on HepG2 cells. Furthermore, the ABTS and DPPH scavenging assays were used to determine the antioxidant activity of all compounds (4a-r). In both ABTS and DPPH radical scavenging assays, compounds 4e, 4i, 4j, 4o and 4r exhibit excellent potency compared to the standard ascorbic acid.

Highly Efficient Synthesis of Imidazolecarboxylate Salts via Sequential Nucleophilic Addition-Intramolecular Cyclization Reactions

Abstract: In this work, we used a highly efficient and easy approach for synthesizing imidazolecarboxylate salt through the reaction between α-amidino carboxylic acids and α-halo ketones with as readily available starting materials in the presence of KHCO3 at THF under reflux. Targeted synthesis of this type of imidazole bearing the carboxylic acid group in a single structure, in addition to the biological properties enriched as a ligand, is very popular in the manufacture of catalysts. The salient features of this protocol include eco-friendly, high atom-economical, easy and mild conditions that led to the production of all products with high yields. Furthermore, all products were purified without the need for column chromatography through the GAP chemistry (group-assisted purification chemistry) technique.

Regio- and Diastereoselective Vicinal Aminobromination of Electron Deficient Olefins via Phosphorus-Based GAP Protocol.

Chemical synthesis based on Group-Assisted Purification chemistry (GAP) has been prolifically used as a powerful, greener and ecofriendly tool so far. Herein, we report hypervalent iodine (III) mediated regio- and diastereoselective aminobromination of electron-deficient olefins using group-assisted purification (GAP) method. By simply mixing the GAP auxiliary-anchored substrates with TsNH2–NBS as nitrogen/bromine sources and PhI(OAc)2 as a catalyst, a series of vicinal bromoamines with multifunctionalities were obtained in moderate to excellent yields (53–94%). The vicinal bromoamines were obtained without column chromatography and/or recrystallization simply by washing the crude mixtures with cosolvents and thus avoiding wastage of silica, solvents, time, and labor. The GAP auxiliary is recyclable and reusable.

Iodine-Promoted Formal [3+2] Cycloaddition of Enaminone: Access to 2-Hydroxy-1,2-dihydro-pyrrol-3-ones with Quaternary Carbon Center.

A novel iodine promoted cyclization of enaminone with aryl methyl ketones has been developed as a straightforward method for constructing 2-hydroxy-pyrrol-3(2H)-ones. This strategy affords structurally diverse 2-hydroxy-pyrrol-3(2H)-ones rings in high yields. Moreover, a quarternary alcohol has been constructed efficiently in the reaction. Product purification required only washing with CH2Cl2 solvent, thereby avoiding traditional chromatography and recrystallization, making this an example of group-assisted purification chemistry.

Highly efficient azido-Ugi multicomponent reactions for the synthesis of bioactive tetrazoles bearing sulfonamide scaffolds

Recent studies revealed that the contribution of the different bioactive scaffolds in one structure creates modern drugs/compounds with unique synergistic biological properties. In this regard, thanks to the interesting biological and medicinal properties of sulfonamide and tetrazole skeletons, this study describes the engagement of sulfonamides in the Ugi tetrazole reaction to access a library of tetrazole bearing sulfonamide. This four-component reaction was performed in a one-pot among available starting material, i.e., an isocyanide, a sulfonamide, an aldehyde and sodium azide in MeOH at 45 °C using ZnCl 2 as a catalyst, for the synthesis of very versatile products with high atom economy and yields. The key point in this strategy is the formation of an intermediate Schiff base and its activation in the azido-Ugi reaction by a Lewis acid catalyst. Importantly, all products are purified through the group-assisted purification (GAP) chemistry, which can avoid traditional purification such as recrystallization and chromatography methods. Also, the docking study between the synthesized compounds and human serum albumin (HSA) was stimulated to theoretically rationalize their biological activity and potential binding interactions.

Group-assisted purification chemistry principles to access highly substituted zwitterionic furans via fast, concise, and efficient one-pot three-component assembly

Novel highly substituted zwitterionic furans were generated through the in situ formation of phosphonium salts. Firstly, intermediate salts were obtained via nucleophilic attack of Huisgen zwitterion to 3-cyanochromones. Finally, these intermediate salts underwent a proton migration, intramolecular cyclization, and ring-opening reaction to convert to the target products. The synthesized furans could be easily purified without traditional purification techniques (chromatography and recrystallization).

Asymmetric synthesis of functionalized 2,3-dihydrobenzofurans using salicyl N-phosphonyl imines facilitated by group-assisted purification (GAP) chemistry.

In this work, we present a strategy for the preparation of functionalized 2,3-dihydrobenzofuran derivatives via the Cs2CO3-catalyzed domino annulation of enantiopure chiral salicyl N-phosphonyl imines with bromo malonates, which offers an avenue for the construction of 2,3-dihydrobenzofurans. Nineteen examples were synthesized in impressive chemical yields and diastereoselectivity. The products were purified simply by washing the crude mixtures with hexanes following group-assisted purification chemistry/technology to bypass traditional separation methods which often result in a loss of product. The absolute configuration was unambiguously assigned by X-ray structural analysis.

Role of chemistry in drug discovery and drug design

The drug discovery and development process use as target of new drug. This process transform some techniques such as screening, optimization, characterization, validation, synthesis. Target based drug design is more important, long-term, successful process. Which is use as high Throughput screening (HTS). Target is synthesized by combination of chemistry. All type of chemistry use in new drug discovery such as analytical chemistry, computational chemistry, organic chemistry, inorganic chemistry, medicinal chemistry, physical chemistry, biochemistry etc. Analytical chemistry in pharmaceutical drug development providing assurance of the quality, safety and efficacy of new drug. Analytical chemistry play and important in developing a new drug. HPLC is most important Analytical process in pharmaceutical industry, other techniques are also used. It’s used as investigate polymorphism in new drug. All drugs are manufacturing under GMP i.e Good manufacturing practices. 50% Analytical chemistry used in drug discovery and development. Analytical method and instrumentation is used in the preclinical testing, toxicity testing and quality control. Commonly used as purification chemistry.

Asymmetric [4 + 2] cycloaddition synthesis of 4H-chromene derivatives facilitated by group-assisted-purification (GAP) chemistry.

In this work, we present a strategy for the preparation of functionalized 4H-chromene derivatives via a Cs2CO3-catalyzed [4 + 2] cycloaddition of enantiopure chiral salicyl N-phosphonyl imines with allenoates. Fifteen examples were achieved in excellent yields and diastereoselectivity. The products were purified simply by washing the crude mixture with hexanes following the Group-Assisted Purification (GAP) chemistry/technology to bypass traditional separation methods. The absolute configuration was unambiguously determined by X-ray structure analysis.

Chemo‐ and Diastereoselective Synthesis of Pyrazolo‐tetrahydropyridines via Multicomponent Sequential Aza‐Diels‐Alder Reactions in Water

AbstractIn this study, we report a novel and an efficient strategy for the synthesis of chemo‐ and diastereoselective synthesis of pyrazolo‐tetrahydropyridines via a one‐pot multi‐component intramolecular Aza‐Diels–Alder reactions (ADARs) from benzoylacetonitrile derivatives, phenylhydrazine, salicylaldehyde derivatives, and styrenesulfonyl or cinnamoyl chloride in H2O as a green solvent. This synthesis procedure was also designed to follow the group‐assisted purification (GAP) chemistry, which can avoid traditional purification such as recrystallization and chromatography methods.

Facile one-pot synthesis of novel highly functionalized dihydro-1H-pyrrole derivatives catalyzed by molecular iodine

An efficient, environmentally benign and molecular iodine promoted protocol was described for cascade synthesis of two kinds of novel dihydro-1H-pyrrole derivatives, 5 and 7. Compounds 5 were prepared via four-component reaction between diethyl acetylenedicarboxylate (DEAD), aromatic amines and phenylglyoxal monohydrate catalyzed by 10 mol% of iodine in ethanol at room temperature. In addition, using same reaction conditions, a three-component reaction between (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), aromatic amines and arylglyoxal monohydrate was performed to access product 7. These transformations apparently proceed through an imine intermediate followed by iodine induced Mannich reaction and subsequent intra-molecular cyclization sequences. The protocol involves the formation of CN, CC and OH bonds leading to the preparation of a hexa substituted five membered ring with two stereo centres. The syntheses avoid the use of traditional column chromatography and recrystallization purification methods and, hence, follow the group-assisted purification (GAP) chemistry process.

A Practical Green Visit to the Functionalized [1,2,4]Triazolo[5,1‐b]quinazolin‐8(4H)one Scaffolds Using the Group‐Assisted Purification (GAP) Chemistry and Their Pharmacological Testing

AbstractHerein, we established a straightforward synthetic route for biological relevant [1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)one scaffolds using the group‐assisted purification (GAP) chemistry via one‐pot and three component reaction of 3‐Amino‐5‐methylthio‐1H‐1,2,4‐triazole (1), Aryl aldehyde(2 a–g), and 1,3‐cyclodione (3 a–b) using L‐proline and aqueous ethanol (1:1, v/v) as green catalyst and reaction media respectively. This work shows some key features such as practical low Environment factor (E‐factor) values, excellent atom economy, reaction mass efficiency, mild reaction condition, metal‐free synthesis, and no use of column chromatography. In preliminary biological screening, the compounds, 2‐(methylthio)‐9‐(4‐nitrophenyl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 i) and 6,6‐dimethyl‐2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 l) were found most potent against Gram‐negative bacteria (E. coli) than the standard drugs ampicillin and chloramphenicol. Moreover, compounds 2‐(methylthio)‐9‐phenyl‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 a) and 9‐(4‐methoxyphenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 f) exhibited excellent potency in comparison with the standard drugs ampicillin, chloramphenicol, and ciprofloxacin against Gram‐positive bacteria (S. aeruginosa and S. pneumoniae). In antifungal screening compounds, 9‐(4‐methoxyphenyl)‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 e) and 2‐(methylthio)‐9‐(4‐nitrophenyl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 i) efficiently inhibited C. albicans fungi strain than that of standard drug griseofulvin. Noteworthy compounds 6,6‐dimethyl‐2‐(methylthio)‐9‐phenyl‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 b), 9‐(4‐chlorophenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 d), and 2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐b]quinazolin‐8(4H)‐one (4 k) were exhibited better potency against M. Tuberculosis.

Potential use of Fe isotopes for ancient non-ferrous metals tracing through the example of a lead-silver production site (Imiter mine, Anti-Atlas, Morocco)

Determining the provenance of non-ferrous metals is a major issue in archaeology and history. The classical method using Pb isotopes shows several limitations, and new isotopic tracers need to be developed in archaeometallurgy. Recently, Fe isotopes were found to be promising for iron metal tracing. In this context, we evaluated the pertinence of Fe isotopes as a new tool for provenance studies of non-ferrous metals. We collected slag and furnace lining samples from the Imiter silver mine in Morocco (Anti-Atlas), where many archaeological remains attest ancient lead-silver production. Their mineralogical composition was investigated by optical microscopic observations, SEM-EDS and EPMA. Besides, we measured both Pb and Fe isotope compositions of these samples by high resolution MC-ICP-MS after wet sample decomposition and purification chemistry. The occurrence of Ag, Pb, Cu and Ag/Pb metallic beads in the slag samples and their high Fe content suggests that these metallurgical materials result from the exploitation of Ag-rich polymetallic ores associated with gossan formations. Isotopic analyses of these slags highlighted their heterogeneous Pb isotope compositions and homogeneous Fe isotope composition. This points to the exploitation of two distinct ore sources with different Pb but similar Fe isotope compositions, despite the Fe isotope variability often encountered in metallic ores worldwide. Hence, Fe isotopes provide a complementary approach to trace lead-silver products from Imiter. Overall, the combination of Pb and Fe isotope analyses constitutes a promising method for further provenance investigations of non-ferrous metals.

Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives †.

An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.

Chiral Phosphinyl Enamines and Their Asymmetric Reduction through Group-Assisted Purification Chemistry Leading to Enantiopure β-Amino Esters/Amides

A series of new chiral N-phosphinyl β-enamino esters and amides were successfully prepared with excellent Z-stereoselectivity (Z/E > 99:1 in nearly all cases). Group-assisted purification chemistry proved to be an efficient method for the asymmetric reduction of the resulting β-enamino esters/amides to give enantiopure β-amino esters/amides. The asymmetric reduction can be controlled efficiently by using a combination of sodium cyanoborohydride and acetic acid.

Asymmetric Synthesis of Chiral α-Methyl-α,β-diamino Acid Derivatives via Group-Assisted Purification Chemistry Using N-Phosphonyl Imines and a Ni(II)-Complexed Alanine Schiff Base.

The Mannich reaction between chiral N-phosphonyl imines and a Ni(II)-complexed alanine Schiff base (Ala-Ni) is reported. With a chiral phosphonyl auxiliary, a single isomer of α-methyl-α,β-diamino acid derivative containing vicinal chiral centers, including a chiral quaternary carbon center, can be obtained simply by washing the crude mixture with cosolvents. The absolute stereochemistry of the enantiomerically pure product has been unambiguously determined by X-ray crystallographic analysis.

ChemInform Abstract: Chiral N‐Phosphonyl Imines for an Aza‐Morita—Baylis—Hillman Reaction via Group‐Assisted Purification (GAP) Chemistry.

AbstractUtilization of group‐assisted purification chemistry provides pure products by washing the crude materials with hexane/ethyl acetate co‐solvents.

Domino reactions of cyclic enaminones leading to selective synthesis of pentacyclic indoles and its functionalization

A new multicomponent domino reaction of cyclic enaminones with acenaphthylene-1,2-dione in an anhydride solvent has been established, providing selective protocol to pentacyclic indoles with different substituted patterns (up to 50 examples). Both substitutions on the cyclic enaminone ring and reaction temperatures showed obvious impact on the reaction pathways. For instance, selective allylic hydroxylation and allylic esterification of in situ generated indoles depend on reaction temperatures. With special substituents, the reactions underwent dehydrogenation process to give access to different substituted fused indoles with good to excellent yields. These reactions feature mild conditions, convenient one-pot operation and short reaction times. The purification of products only needs to be washed by 95% ethanol without traditional chromatography and recrystallization, which characterizes group-assisted purification (GAP) chemistry.