3199-61-9

Usage

Uses

Used in Pharmaceutical Industry:
2-Benzofurancarboxylic Acid, Ethyl Ester is used as a reactant for the preparation of benzofuropyridines, which have a high affinity for the α2-adrenoceptor. These benzofuropyridines are of interest in the development of new drugs targeting the α2-adrenoceptor, which plays a crucial role in various physiological processes, including blood pressure regulation, sedation, and analgesia.
Used in Agrochemical Industry:
2-Benzofurancarboxylic Acid, Ethyl Ester can also be used as a building block in the synthesis of agrochemicals, such as insecticides, herbicides, and fungicides. Its unique structure and reactivity make it a valuable component in the development of novel and effective compounds for pest control and crop protection.

Preparation

Synthesis of ethyl benzofuran-2-carboxylate: Salicylaldehyde (20.0 mL, 0.164 mol) and diethyl bromomalonate (40.0 mL, 0.168 mol) in ethyl methyl ketone (40.0 mL, 0.555 mol) was treated with anhydrous potassium carbonate (20.0 g,0.869 mol). The reaction mixture was refluxed for 18 h on steam bath. Ethyl methyl ketone was distilled off under reduced pressure and the residue formed was dissolved in 400 mL of water and cooled in an ice-bath. It was acidified with dil H2SO4. The product formed was extracted with 25 mL portion of solvent ether twice and the extract was washed with sodium bicarbonate solution. It was dried over calcium chloride. Solvent was removed and the residue ethyl benzofuran-2-carboxylate was dried.

InChI:InChI=1/C11H10O3/c1-2-13-11(12)10-7-8-5-3-4-6-9(8)14-10/h3-7H,2H2,1H3

Upstream product

• 496-41-3 Benzofuran-2-carboxylic acid 
• 64-17-5 ethanol 
• 90-02-8 salicylaldehyde 
• 105-36-2 ethyl bromoacetate 
• 89-95-2 2-methyl-benzyl alcohol 
• 105-39-5 chloroacetic acid ethyl ester 
• 271-89-6 1-benzofurane 
• 56-23-5 tetrachloromethane 
• 1351932-18-7 ethyl 2-acetyl-5-chloro-3-hydroxy-2,3-dihydrobenzofuran-2-carboxylate 
• 3943-94-0 3-(2-hydroxy-phenyl)-acrylic acid ethyl ester 
• 71-23-8 propan-1-ol 
• 18042-43-8 2-allyl-1-(trimethylsiloxy)benzene 
• 91703-34-3 2-(β,β-dibromovinyl)phenol 
• 13939-06-5 molybdenum hexacarbonyl 

Downstream Products

• 56426-65-4 2-(α-methylvinyl)benzofuran 
• 110683-72-2 ethyl 7-nitrobenzofuran-2-carboxylate 
• 69604-00-8 ethyl 5-nitrobenzo[d]furan-2-carboxylate 
• 78917-44-9 2-Benzofuranpropionic acid-β-oxo-ethylester 
• 496-41-3 Benzofuran-2-carboxylic acid 
• 42974-19-6 benzo[b]furan-2-carbohydrazide 
• 21683-86-3 3-(Benzofuran-2-yl)propionic acid 
• 4265-16-1 2-formylbenzo[b]furan 
• 132376-67-1 (2E)-3-(1-benzofuran-2-yl)-2-propenoic acid 
• 76268-18-3 C₁₆H₁₄N₂O₄S 

Relevant academic research and scientific papers

Benzofuran hydrazones as potential scaffold in the development of multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity

New benzofuranhydrazones 3–12 were easily prepared and assayed for their radical-scavenging ability. Hydrazones 3–12 showed different extent antioxidant activity in DPPH, FRAP and ORAC assays. Good antioxidant activity is related to the number and positio

Novel tacrine–benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer’s Disease

Pursuing the widespread interest on multi-target drugs to combat Alzheimer′s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aβ aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy.

P(MeNCH2CH2)3N: An efficient catalyst for the synthesis of substituted ethyl benzofuran-2-carboxylates

A superior method for the synthesis of substituted ethyl benzofuran-2-carboxylates in 80-99% yields from substituted 2-formylphenoxy ethylcarboxylates using 0.4 equiv of commercially available P(MeNCH2CH2)3N at 70 °C for 3 hours is described.

Synthesis and cholinesterase inhibitory activity of new 2-benzofuran carboxamide-benzylpyridinum salts

A series of benzofuran-2-carboxamide-N-benzyl pyridinium halide derivatives (6a-o) are synthesized as new cholinesterase inhibitors. The synthetic pathway involves the reaction of salicylaldehyde derivatives and ethyl bromoacetate, followed by hydrolysis and amidation with 3- and 4-picolyl amine. Subsequently, N-((pyridin-4-yl) methyl) benzofuran-2-carboxamide and substituted N-((pyridin-3-yl) methyl) benzofuran-2-carboxamides reacts with benzyl halides to afford target compounds (6a-o). The chemical structures of all derivatives were confirmed by spectroscopic methods. The studies reveal that some of the synthesized compounds are potent butyrylcholinesterase inhibitors with IC50 values in the range of 0.054–2.7 μM. In addition, good inhibitory effects on Aβ self-aggregation are observed for 6h and 6k (33.1 and 46.4% at 100 μM, respectively).

Microwave induced thermal gradients in solventless reaction systems

Development of thermal heterogeneity under microwave irradiation for solventless solid-liquid phase-transfer catalytic (PTC) reactions has been studied by means of a thermovision camera and fiber-optics thermometer.

Synthesis and biological evaluation of a series of novel benzofuran-2-carboxylate 1,2,3-triazoles

A facile and efficient synthetic route has been developed to substituted benzofuran-2-carboxylate 1,2,3-triazoles for the first time by reacting prop-2-yn-1-yl benzofuran-2-carboxylate with a variety of substituted aryl/benzyl azides in DMF/H2O system employing standard click reaction. This new method has the lead of good yields, inexpensive reagents, easily available, easy work-up, mild reaction conditions, and environmentally friendly reaction conditions. All these compounds have been characterized by modern spectral techniques such as IR, 1H NMR, and mass spectroscopy, etc. Evaluation of synthesized compounds for antimicrobial activity against specific bacterial strains like Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa along with antifungal activity against Aspergillus Niger and Sclerotium rolfsii have been carried out.

Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)

Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.

Electrodimerization ofN-Alkoxyamides for the Synthesis of Hydrazines

An efficient and valuable N-N dimerization reaction ofN-alkoxyamides is reported under undivided electrolytic conditions. This electrochemical strategy provides a powerful way to access a wide range of advanced, highly functionalized hydrazines. Remarkably, anN-centered radical generated from the cleavage of the N-H bond under electrolytic conditions plays a crucial role in this transformation. Furthermore, variousN-alkoxyamides bearing different substituents are suitable in this transformation, furnishing the corresponding hydrazines in up to 92% yield.

Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site

A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 μM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.

Tandem Synthesis of 2-Carboxybenzofurans via Sequential Cu-Catalyzed C-O Coupling and Mo(CO)6-Mediated Carbonylation Reactions

A modular tandem synthesis of 2-carboxybenzofurans from 2-gem-dibromovinylphenols has been established based on a sequence of Cu-catalyzed intramolecular C-O coupling and Mo(CO)6-mediated intermolecular carbonylation reactions. This protocol allowed one-step access to a broad variety of functionalized benzofuran-2-carboxylic acids, esters, and amides in good to excellent yields under Pd- and CO gas-free conditions.