Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fast Heck-Cassar-Sonogashira (HCS) Reactions in Green Solvents.

ABSTRACT: The replacement of toxic solvents with greener alternatives in Heck-Cassar-Sonogashira (HCS) cross-couplings was investigated. The fine-tuning of the HCS protocol allowed to achieve complete conversions and high speed under mild conditions. N-Hydroxyethylpyrrolidone (HEP) gave the best results. Moreover, the methodology was successfully applied to the synthesis of an intermediate of the anticancer drug Erlotinib, demonstrating the versatility of the new green protocol.

SUBMITTER: Ferrazzano L

PROVIDER: S-EPMC8007125 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Fast Heck-Cassar-Sonogashira (HCS) Reactions in Green Solvents.

Ferrazzano L L Martelli G G Fantoni T T Daka A A Corbisiero D D Viola A A Ricci A A Cabri W W Tolomelli A A

Organic letters 20200428 10

The replacement of toxic solvents with greener alternatives in Heck-Cassar-Sonogashira (HCS) cross-couplings was investigated. The fine-tuning of the HCS protocol allowed to achieve complete conversions and high speed under mild conditions. <i>N</i>-Hydroxyethylpyrrolidone (HEP) gave the best results. Moreover, the methodology was successfully applied to the synthesis of an intermediate of the anticancer drug Erlotinib, demonstrating the versatility of the new green protocol. ...[more]

PMID: 32342693

Similar Datasets

Palladium Catalyst Recycling for Heck-Cassar-Sonogashira Cross-Coupling Reactions in Green Solvent/Base Blend.

Project description:The identification of a green, versatile, user-friendly, and efficient methodology is necessary to facilitate the use of Heck-Cassar-Sonogashira (HCS) cross-coupling reaction in drug discovery and industrial production in the pharmaceutical segment. The Heck-Cassar and Sonogashira protocols, using N-hydroxyethylpyrrolidone (HEP)/water/N,N,N',N'-tetramethyl guanidine (TMG) as green solvent/base mixture and sulfonated phosphine ligands, allowed to recycle the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, and triflates. No catalyst leakage or metal contamination of the final product were observed during the HCS recycling. To our knowledge, a turnover number (TON) up to 2375, a turnover frequency (TOF) of 158 h-1 , and a process mass intensity (PMI) around 7 that decreased around 3 after solvent, base, and palladium recovery, represent one of the best results to date using a sustainable protocol. The Heck-Cassar protocol using sSPhos was successfully applied to the telescoped synthesis of Erlotinib (TON: 1380; TOF: 46 h-1 ).

| S-EPMC8251985 | biostudies-literature

Morphing Natural Product Platensimycin via Heck, Sonogashira, and One-Pot Sonogashira/Cycloaddition Reactions to Produce Antibiotics with In Vivo Activity.

Project description:Type II fatty acid synthases are promising drug targets against major bacterial pathogens. Platensimycin (PTM) is a potent inhibitor against β-ketoacyl-[acyl carrier protein] synthase II (FabF) and β-ketoacyl-[acyl carrier protein] synthase I (FabB), while the poor pharmacokinetics has prevented its further development. In this work, thirty-two PTM derivatives were rapidly prepared via Heck, Sonogashira, and one-pot Sonogashira/cycloaddition cascade reactions based on the Gram-scale synthesis of 6-iodo PTM (4). About half of the synthesized compounds were approximately equipotent to PTM against the tested Staphylococcus aureus strains. Among them, the representative compounds 4, A4, and B8 exhibited different plasma protein binding affinity or stability in the human hepatic microsome assay and showed improved in vivo efficacy over PTM in a mouse peritonitis model. In addition, A4 was also effective in an S. aureus-infected skin mouse model. Our study not only significantly expands the known PTM derivatives with improved antibacterial activities in vivo, but showcased that C-C cross-coupling reactions are useful tools to functionalize natural product drug leads.

| S-EPMC9027111 | biostudies-literature

Pd-PEPPSI N-Heterocyclic Carbene Complexes from Caffeine: Application in Suzuki, Heck, and Sonogashira Reactions.

Project description:The first synthesis of Pd-PEPPSI N-heterocyclic carbene complexes derived from the abundant and renewable natural product caffeine is reported. The catalysts bearing 3-chloro-pyridine, pyridine and N-methylimidazole ancillary ligands were readily prepared from the corresponding N9-Me caffeine imidazolium salt by direct deprotonation and coordination to PdX2 in the presence of N-heterocycles or by ligand displacement of PdX2(Het)2. The model Pd-PEPPSI-caffeine complex has been characterized by x-ray crystallography. The complexes were successfully employed in the Suzuki cross-coupling of aryl bromides, Suzuki cross-coupling of amides, Heck cross-coupling and Sonogashira cross-coupling. Computational studies were employed to determine frontier molecular orbitals and bond order analysis of caffeine derived Pd-PEPPSI complexes. This class of catalysts offers an entry to utilize benign and sustainable biomass-derived Xanthine NHC ligands in the popular Pd-PEPPSI systems in organic synthesis and catalysis.

| S-EPMC10686539 | biostudies-literature

Palladium-Catalyzed Mizoroki-Heck and Copper-Free Sonogashira Coupling Reactions in Water Using Thermoresponsive Polymer Micelles.

Project description:A few kinds of thermoresponsive diblock copolymers have been synthesized and utilized for palladium-catalyzed coupling reactions in water. Poly(N-isopropylacrylamide) (PNIPAAm) and poly(N,N-diethylacrylamide) (PDEAAm) are employed for thermoresponsive segments and poly(sodium 4-styrenesulfonate) (PSSNa) and poly(sodium 2-acrylamido-methylpropanesulfonate) (PAMPSNa) are employed for hydrophilic segments. Palladium-catalyzed Mizoroki-Heck reactions are performed in water and the efficiency of the extraction process is studied. More efficient extraction was observed for the PDEAAm copolymers when compared with the PNIPAAm copolymers and conventional surfactants. In the study of the Sonogashira coupling reactions in water, aggregative precipitation of the products was observed. Washing the precipitate with water gave the product with satisfactory purity with a good yield.

| S-EPMC8402173 | biostudies-literature

Preparation and Reactivation of Heterogeneous Palladium Catalysts and Applications in Sonogashira, Suzuki, and Heck Reactions in Aqueous Media.

Project description:A new type of heterogeneous palladium catalyst, PdMgAl-LDH, was facilely prepared by the immobilization of Pd2+ species in the layers of a Mg-Al layered double hydroxide (LDH) with co-precipitation, and then fully characterized by using powder XRD, thermogravimetric differential thermal analysis, TEM, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy techniques. These catalysts can efficiently catalyze copper-free Sonogashira, Suzuki and Heck coupling reactions of various aryl iodides, bromides, and chlorides in aqueous media under phosphine-ligand- and organic-base-free conditions. These catalysts feature easy recovery through simple filtration and could be reused at least six times without a marked loss in activity. Notably, they can be facilely reactivated by a combination of nitrolysis with co-precipitation. The basic LDH skeletons could effectively stabilize the Pd0 species created in situ and donate electron density to the Pd0 center to facilitate the oxidative addition of aryl halides, thus the PdMgAl-LDH catalysts are stable during catalysis.

| S-EPMC6182254 | biostudies-literature

Palladium Nanoparticle-Decorated Porous Metal-Organic-Framework (Zr)@Guanidine: Novel Efficient Catalyst in Cross-Coupling (Suzuki, Heck, and Sonogashira) Reactions and Carbonylative Sonogashira under Mild Conditions.

Project description:A novel heterogeneous Zr-based metal-organic framework containing an amino group functionalized with nitrogen-rich organic ligand (guanidine), through a step-by-step post synthesis modification approach, was successfully modified by the stabilization of palladium metal nanoparticles on the prepared UiO-66-NH2 support in order to synthesize the Suzuki-Murray, Mizoroki-Heck, and copper-free Sonogashira reactions and also the carbonylative Sonogashira reaction incorporating H2O as a green solvent under mild conditions. This newly synthesized highly efficient and reusable UiO-66-NH2@cyanuric chloride@guanidine/Pd-NPs reported catalyst has been utilized to increase anchoring palladium onto the substrate with the aim of altering the construction of the intended synthesis catalyst to form the C-C coupling derivatives. Several strategies, including X-ray diffraction, Fourier transform infrared, scanning electron microscopy, Brunauer-Emmett-Teller, transmission microscopy electron, thermogravimetric analysis, inductively coupled plasma, energy-dispersive X-ray, and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@cyanuric chloride@guanidine/Pd-NPs. In these reactions, the UiO-66-NH2-supported Pd-NPs illustrated superior performances compared to their catalyst, revealing the benefits of providing nanocatalysts. As a result, the proposed catalyst is favorable in a green solvent, and also, the outputs are accomplished with good to excellent outputs. Furthermore, the suggested catalyst represented very good reusability with no remarkable loss in activity up nine sequential runs.

| S-EPMC10173326 | biostudies-literature

Sonogashira-Hagihara reactions of halogenated glycals.

Project description:Herein, we report on our findings of the Sonogashira-Hagihara reaction with 1-iodinated and 2-brominated glycals using several aromatic and aliphatic alkynes. This Pd-catalyzed cross-coupling reaction presents a facile access to alkynyl C-glycosides and sets the stage for a reductive/oxidative refunctionalization of the enyne moiety to regenerate either C-glycosidic structures or pyran derivatives with a substituent in position 2.

| S-EPMC3388853 | biostudies-literature

Deep Eutectic Solvents and Multicomponent Reactions: Two Convergent Items to Green Chemistry Strategies.

Project description:One of the highlights of green chemistry is the development of techniques and procedures with low environmental impact. In the last years, deep eutectic solvents (DES) have become an important alternative to conventional organic solvents. For a period ionic liquids have provoked remarkable interest, but they have been displaced by DES because they show easier preparation methods, lower prices, many of them are biodegradable and compatible with biological systems. In addition, they show adjustable physicochemical properties, high thermal stability, low volatility and are compatible with water. In this paper is reviewed the state of the art of the use of DES paying special attention to the role of reaction media in organic synthesis.

| S-EPMC8369850 | biostudies-literature

What the Heck?-Automated Regioselectivity Calculations of Palladium-Catalyzed Heck Reactions Using Quantum Chemistry.

Project description:We present a quantum chemistry (QM)-based method that computes the relative energies of intermediates in the Heck reaction that relate to the regioselective reaction outcome: branched (α), linear (β), or a mix of the two. The calculations are done for two different reaction pathways (neutral and cationic) and are based on r 2SCAN-3c single-point calculations on GFN2-xTB geometries that, in turn, derive from a GFNFF-xTB conformational search. The method is completely automated and is sufficiently efficient to allow for the calculation of thousands of reaction outcomes. The method can mostly reproduce systematic experimental studies where the ratios of regioisomers are carefully determined. For a larger dataset extracted from Reaxys, the results are somewhat worse with accuracies of 63% for β-selectivity using the neutral pathway and 29% for α-selectivity using the cationic pathway. Our analysis of the dataset suggests that only the major or desired regioisomer is reported in the literature in many cases, which makes accurate comparisons difficult. The code is freely available on GitHub under the MIT open-source license: https://github.com/jensengroup/HeckQM.

| S-EPMC9753166 | biostudies-literature

Investigating the efficacy of green solvents and solvent-free conditions in hydrogen-bonding mediated organocatalyzed model reactions.

Project description:In this study, we have delved into various reactions conducted using green solvents or under solvent-free conditions, employing hydrogen bonding organocatalysis to advance more sustainable practices in chemical synthesis. The outcomes suggest that cyclopentyl methyl ether could potentially replace non-polar organic solvents such as hexane and toluene with comparable enantioselectivity and yields. The non-polar nature of liquefied or supercritical CO2 restricts its application to reactions that require non-polar solvents. Furthermore, pursuing solvent-free conditions, even without liquid substrates, might result in similar conversion rates with reduced catalyst loading. These findings highlight the potential of exploring solvent-free conditions when enantioselectivity is not of concern. Based on the results, solvent-free conditions and bio-based solvents can serve as viable alternatives to conventional organic solvents without compromising performance. This is expected to influence the way chemists approach reaction optimisation within method development in the field, fostering a broader adoption of environmentally friendly approaches.

| S-EPMC10918449 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data