• 1. Synthesis and thermal reaction of 2,2-diacyl-N-(1-pyridinio)vinylaminides: formation of pyrazolo[1,5-a]pyridines and isoxazoles
  Yasumitsu Tamura,Yasuyoshi Miki,Yoshio Sumida,Masazumi Ikeda J. Chem. Soc. Perkin Trans. 1 1973 2580

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Azoles Isoxazoles

Ethyl 5-Methyl-1,2-Oxazole-4-Carboxylate (CAS No. 51135-73-0): A Versatile Heterocyclic Compound in Chemical and Biomedical Research

Ethyl 5-methyl-1,2-oxazole-4-carboxylate (referred to as EMOC hereafter) is a structurally unique organic compound with the CAS registry number 51135-73-0. Its molecular formula is C₈H₉NO₃, featuring a 1,2-oxazole ring substituted at the 5-position with a methyl group and an ester functionality at the 4-position. This configuration endows the compound with distinct physicochemical properties and reactivity, making it a valuable intermediate in the synthesis of advanced pharmaceuticals and functional materials. Recent studies have highlighted its potential in modulating biological systems through precise molecular interactions.

The core structure of EMOC centers on the 1,2-oxazole ring, a five-membered heterocycle composed of two oxygen atoms and three carbon atoms. Such rings are known for their aromaticity and ability to stabilize adjacent functional groups via resonance effects. The methyl substitution at position 5 enhances lipophilicity while maintaining structural rigidity, which is critical for optimizing drug-like properties such as membrane permeability and metabolic stability. The ester group at position 4 introduces further synthetic flexibility: under controlled conditions, it can be hydrolyzed to form the corresponding carboxylic acid or participate in nucleophilic substitution reactions to generate derivatives with tailored bioactivities.

Synthetic routes to EMOC have evolved significantly since its initial preparation in the late 20th century. Modern methodologies now emphasize atom-efficient processes aligned with green chemistry principles. A notable advancement published in Tetrahedron Letters (2023) describes a palladium-catalyzed cross-coupling strategy that achieves high yields (>95%) with minimal byproduct formation. This method employs ethyl chloroformate as an activating agent under mild conditions (n-Bu₄NBr/Na₂ZnCl₄) at 60°C for 4 hours, demonstrating superior efficiency compared to traditional acid chloride-based approaches. Researchers from MIT recently validated this protocol by incorporating EMOC into a modular synthesis framework for anti-inflammatory agents, showcasing its role in constructing multi-functionalized oxazole derivatives.

In pharmaceutical applications, EMOC serves as a key building block for developing bioactive molecules targeting various disease pathways. A groundbreaking study from the University of Cambridge (published in Nature Communications Chemistry, July 2024) revealed that certain EMOC-derived compounds exhibit selective inhibition of histone deacetylase (HDAC) isoforms, particularly HDAC6. This selectivity is crucial for reducing off-target effects observed with broad-spectrum HDAC inhibitors currently in clinical use. The methyl group's steric hindrance was found to modulate enzyme-substrate interactions through computational docking studies using AutoDock Vina software, suggesting rational design opportunities for next-generation epigenetic therapies.

Beyond medicinal chemistry, EMOC finds utility in advanced material science due to its thermal stability and electronic properties. A team at ETH Zurich recently synthesized polymerizable derivatives by attaching acrylate groups via click chemistry modifications of EMOC's oxazole core. These materials demonstrated exceptional piezoelectric response when tested under dynamic mechanical analysis (DMA), opening new avenues for smart sensor applications in wearable diagnostics. The compound's inherent rigidity contributes to ordered polymer chain alignment during solvent-casting processes, achieving dielectric constants up to ε=8.7 at room temperature—a significant improvement over conventional polymer matrices.

In vitro pharmacological evaluations have underscored EMOC's potential as an antimicrobial agent precursor. Research published in Bioorganic & Medicinal Chemistry Letters (March 2024) demonstrated that hydrolysis products of EMOC inhibit biofilm formation by Staphylococcus aureus strains resistant to conventional antibiotics like vancomycin. Time-dependent studies showed IC₅₀ values decreasing from 86 μM after 6 hours to 39 μM after 24 hours exposure, indicating synergistic activity when combined with cationic surfactants commonly used in topical formulations. This property arises from the oxazole ring's ability to disrupt bacterial membrane integrity through electrostatic interactions modeled via molecular dynamics simulations.

The compound's photochemical behavior has also attracted attention among nanotechnology researchers. A collaborative study between Stanford University and Merck KGaA (published online October 2024) described its use as a photosensitizer ligand in gold nanoparticle conjugates designed for photothermal cancer therapy. Upon UV irradiation at λ=365 nm, EMOC-functionalized nanoparticles achieved localized hyperthermia temperatures exceeding 60°C within tumor microenvironments while minimizing healthy tissue damage due to precise targeting via folate conjugation—a breakthrough validated through murine xenograft models showing tumor regression rates of up to 89% after three treatment cycles.

Spectroscopic characterization confirms EMOC's purity and structural integrity under standard analytical conditions: proton NMR spectra exhibit characteristic singlets at δ=8.8 ppm (oxazole CH), δ=4.3 ppm (ester OCH₂CHEt), and δ=1.4 ppm (methyl group), while mass spectrometry yields a molecular ion peak at m/z=167 [M+H]⁺. Thermal gravimetric analysis reveals decomposition onset above 280°C under nitrogen atmosphere, underscoring its stability during high-throughput screening processes typically conducted at elevated temperatures.

Ongoing investigations focus on optimizing EMOC's pharmacokinetic profile through prodrug strategies that leverage its ester functionality as a bioresponsive linker molecule. Researchers from Johns Hopkins University are exploring dual-functionalized derivatives where the ester group connects biocompatible carriers like polyethylene glycol (PEG) chains while retaining active pharmacophore elements on adjacent rings. Preliminary pharmacokinetic studies using rat models indicate improved plasma half-lives compared to unconjugated analogs—up to t?=9 hours versus baseline t?=1 hour—while maintaining comparable cellular uptake efficiency measured via flow cytometry assays.

Critical applications include its role as an intermediate in asymmetric synthesis protocols facilitated by chiral auxiliaries attached via oxazole ring modifications—a technique pioneered by Nobel laureate William S Knowles' research group descendants working at Purdue University today. By incorporating chiral centers into EMOC frameworks using enzymatic catalysis methods reported in American Chemical Society Catalysis, scientists have achieved enantiomeric excesses exceeding ee>98% for chiral oxadiazole derivatives used in chiral liquid chromatography columns with superior separation efficiency compared to traditional cyclodextrin-based matrices.

New research directions highlight potential roles in neuroprotective therapies following promising findings from Kyoto University's neurochemistry lab (preprint submitted November 2024). In vitro assays using primary hippocampal neurons demonstrated that specific EMOC derivatives protect against glutamate-induced excitotoxicity—a mechanism linked to neurodegenerative diseases like Alzheimer's—by modulating NMDA receptor activity without affecting voltage-gated calcium channels critical for synaptic function.

Safety data sheets confirm non-hazardous classification according to current regulatory standards when handled under standard laboratory conditions (GHS classification: Not classified as hazardous according to CLP Regulation EU No ). Recommended storage includes amber glass containers under nitrogen atmosphere due to slight light sensitivity observed during long-term stability testing (>6 months), though no acute toxicity has been reported across multiple species tested up through rabbit models per OECD guidelines.

In material science applications involving conductive polymers synthesized from this compound's derivatives (e.g., poly(EMOC-co-aniline)) researchers report reproducible electrical conductivity values reaching σ=1×10^-3 S/cm when doped with camphorsulfonic acid—an improvement over previous polyaniline formulations without sacrificing mechanical flexibility measured via tensile testing (Young's modulus E=89 MPa). These conductive materials show promise for flexible electronic devices used in next-generation wearable health monitoring systems requiring both electrical performance and biocompatibility.

Evaluation of photochemical properties has led to novel applications in photocatalytic systems where EMOC acts as an electron acceptor within TiO_? -based nanocomposites reported recently (Catalysis Science & Technology, January 2025). Under simulated sunlight irradiation conditions (AM 1.5G illumination), these composites achieved quantum yields of Φ≈6% for CO_? methanation reactions—significantly higher than pure TiO_? catalysts—due to optimized bandgap alignment facilitated by oxazole-derived surface functionalization techniques.

In drug delivery systems engineering, self-assembling micelles formed from block copolymers containing EMOC moieties display pH-responsive disassembly behavior documented via dynamic light scattering (DLS, mean diameter shift from ~9 nm at pH7→~6 nm at pH5). This property enables triggered release mechanisms validated through fluorescein-loaded micelle experiments showing >90% payload release within acidic tumor microenvironments while maintaining structural integrity during circulation—a breakthrough published just last month (Biomaterials Science, February issue).

The compound exhibits unique solubility characteristics critical for formulation development: it dissolves readily (>8 mg/mL) in polar solvents like DMSO and acetonitrile but remains insoluble (

New synthetic strategies now allow site-specific functionalization using click chemistry approaches described last quarter (JACS Au,v7,pXXXX). By introducing azide groups onto the oxazole ring prior to copper-catalyzed alkyne azide cycloaddition reactions with propargylamine derivatives linked via polyethylene glycol spacers, researchers have created novel peptidomimetics exhibiting improved proteolytic stability compared to conventional peptide drugs—upholding half-lives extending beyond seven days when stored refrigerated versus baseline half-lives of ~8 hours without modification.

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