Abstract

2-Acetyl-5-methylfuran (C₇H₈O₂) is an organic heterocyclic compound belonging to the furan family, specifically characterized as a methyl-substituted furan with an acetyl functional group at the 2-position. This compound appears as a yellow-orange liquid at room temperature with a boiling point of 100°C at 33 hPa. The molecular structure consists of a five-membered furan ring system with methyl and acetyl substituents, imparting distinctive chemical and physical properties. 2-Acetyl-5-methylfuran demonstrates moderate flammability with a flash point of 80°C and exhibits an oral LD₅₀ of 438 mg/kg in mice. The compound finds applications primarily as a flavoring agent and fragrance compound due to its characteristic aroma, and serves as an intermediate in organic synthesis for more complex heterocyclic systems.

Introduction

2-Acetyl-5-methylfuran, systematically named 1-(5-methylfuran-2-yl)ethan-1-one according to IUPAC nomenclature, represents an important derivative of the furan class of heterocyclic compounds. Furan derivatives occupy a significant position in modern organic chemistry due to their presence in natural products, pharmaceutical intermediates, and flavor compounds. The specific substitution pattern of 2-Acetyl-5-methylfuran, with electron-donating methyl and electron-withdrawing acetyl groups, creates a polarized electronic structure that influences its reactivity and physical characteristics. This compound was first synthesized and characterized in the mid-20th century as part of broader investigations into furan chemistry. Its CAS registry number 1193-79-9 provides unambiguous identification in chemical databases and regulatory contexts.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular geometry of 2-Acetyl-5-methylfuran derives from the planar five-membered furan ring system, which exhibits approximate C₂ᵥ symmetry when considering the ring atoms alone. The furan ring itself demonstrates bond length alternation characteristic of aromatic heterocycles, with the C₂-C₃ and C₄-C₅ bonds measuring approximately 1.36 Å, while the C₃-C₄ bond extends to approximately 1.43 Å. The oxygen atom contributes two electrons to the π-system, resulting in six π-electrons that satisfy Hückel's rule for aromaticity. The acetyl substituent at the 2-position adopts a planar configuration relative to the furan ring due to conjugation between the carbonyl π-system and the furan aromatic system. This conjugation creates an extended π-system that significantly influences the electronic properties of the molecule.

Chemical Bonding and Intermolecular Forces

Covalent bonding in 2-Acetyl-5-methylfuran follows typical patterns for substituted furans, with carbon-carbon bond lengths in the range of 1.36-1.43 Å and carbon-oxygen bonds measuring approximately 1.36 Å for the furan ring and 1.21 Å for the carbonyl group. The molecule possesses a permanent dipole moment estimated at 3.2-3.5 D, primarily oriented along the axis connecting the ring oxygen and carbonyl oxygen atoms. Intermolecular forces include dipole-dipole interactions due to the substantial molecular polarity, van der Waals forces with dispersion energy components of approximately 40 kJ/mol, and limited hydrogen bonding capacity through the carbonyl oxygen atom. The methyl groups contribute to London dispersion forces but do not participate in significant hydrogen bonding. The compound's solubility characteristics reflect these intermolecular interactions, with moderate solubility in polar organic solvents and limited solubility in water.

Physical Properties

Phase Behavior and Thermodynamic Properties

2-Acetyl-5-methylfuran exists as a yellow-orange liquid at standard temperature and pressure (25°C, 101.3 kPa) with a characteristic aromatic odor. The compound demonstrates a boiling point of 100°C at reduced pressure of 33 hPa, with an estimated normal boiling point of approximately 195-200°C based on vapor pressure relationships. The flash point measures 80°C, classifying the compound as moderately flammable. Density measurements indicate a value of approximately 1.05 g/cm³ at 20°C. The refractive index at 20°C measures 1.487, consistent with conjugated organic compounds. Specific heat capacity values range from 1.8-2.0 J/g·K in the liquid phase. The enthalpy of vaporization is estimated at 45 kJ/mol based on structural analogs.

Spectroscopic Characteristics

Infrared spectroscopy of 2-Acetyl-5-methylfuran reveals characteristic absorption bands including strong carbonyl stretching at 1675 cm⁻¹, furan ring C=C stretching at 1575 cm⁻¹ and 1500 cm⁻¹, and C-H stretching vibrations between 3100-2900 cm⁻¹. Proton NMR spectroscopy shows distinctive signals: furan ring protons appear as a doublet at δ 6.05 ppm (H-3) and a quartet at δ 6.85 ppm (H-4) with coupling constant J = 3.2 Hz, the acetyl methyl group resonates as a singlet at δ 2.35 ppm, and the ring methyl group appears as a singlet at δ 2.25 ppm. Carbon-13 NMR spectroscopy displays signals at δ 187.5 ppm (carbonyl carbon), δ 152.0 ppm (C-2), δ 150.5 ppm (C-5), δ 119.0 ppm (C-3), δ 108.5 ppm (C-4), δ 26.0 ppm (acetyl methyl), and δ 13.5 ppm (ring methyl). UV-Vis spectroscopy demonstrates absorption maxima at 255 nm and 285 nm corresponding to π→π* transitions of the conjugated system.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

2-Acetyl-5-methylfuran exhibits reactivity patterns characteristic of both furan derivatives and ketones. The furan ring demonstrates electrophilic aromatic substitution reactivity, with preferential attack at the 4-position due to directing effects of both substituents. Reactions with electrophiles such as bromine or nitronium ions proceed with moderate rates, typically requiring 1-4 hours at 0-25°C for completion. The acetyl group participates in standard carbonyl reactions including nucleophilic addition, condensation, and reduction. Reduction with sodium borohydride proceeds quantitatively within 30 minutes at 0°C to yield the corresponding secondary alcohol. The compound undergoes Claisen-Schmidt condensation with aromatic aldehydes at elevated temperatures (80-100°C) with catalytic base. The furan ring remains stable under mildly acidic conditions but undergoes ring opening under strong acid conditions or prolonged exposure to oxygen.

Acid-Base and Redox Properties

The compound demonstrates very weak acidic character with estimated pKₐ values greater than 25 for the ring protons and approximately 19 for the acetyl methyl protons. Basic properties are negligible due to the absence of protonatable sites under normal conditions. Redox behavior includes facile reduction of the carbonyl group at approximately -1.5 V versus standard calomel electrode and oxidation of the furan ring beginning at +1.2 V. The compound exhibits reasonable stability toward atmospheric oxidation but gradually forms peroxide compounds upon prolonged storage. Electrochemical studies indicate irreversible reduction waves and quasi-reversible oxidation processes. Stability in aqueous solutions depends on pH, with optimal stability observed in the pH range of 5-8. The compound demonstrates increasing decomposition rates outside this pH range, particularly under alkaline conditions where aldol condensation reactions may occur.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The most common laboratory synthesis of 2-Acetyl-5-methylfuran employs Friedel-Crafts acylation of 2-methylfuran with acetic anhydride in the presence of Lewis acid catalysts. Typical reaction conditions involve boron trifluoride etherate or tin(IV) chloride as catalyst at 0-5°C for 2-4 hours, yielding the target compound in 65-75% yield after distillation purification. Alternative synthetic routes include the Vilsmeier-Haack formulation of 2,5-dimethylfuran, though this method produces isomeric mixtures requiring separation. More recently, catalytic methods using zeolites or acidic resins have been developed with improved selectivity and reduced environmental impact. Purification typically employs fractional distillation under reduced pressure (30-40 hPa) with collection of the fraction boiling at 95-105°C. The compound may be further purified by column chromatography on silica gel using hexane-ethyl acetate mixtures as eluent.

Analytical Methods and Characterization

Identification and Quantification

Gas chromatography with flame ionization detection provides effective separation and quantification of 2-Acetyl-5-methylfuran from potential impurities and decomposition products. Optimal separation occurs on polar stationary phases such as polyethylene glycol derivatives with typical retention indices of 1350-1400. High-performance liquid chromatography with UV detection at 280 nm offers alternative quantification methods with detection limits of approximately 0.1 mg/L. Mass spectrometric analysis shows a molecular ion peak at m/z 124 with characteristic fragmentation patterns including loss of methyl radical (m/z 109), loss of acetyl group (m/z 95), and furyl cation (m/z 81). Quantitative NMR using internal standards such as 1,3,5-trimethoxybenzene provides absolute quantification without need for compound-specific calibration.

Purity Assessment and Quality Control

Commercial specifications for 2-Acetyl-5-methylfuran typically require minimum purity of 98% by gas chromatography. Common impurities include starting material 2-methylfuran (typically <0.5%), isomeric compounds such as 2-acetyl-4-methylfuran (<1.0%), and oxidation products including carboxylic acid derivatives (<0.2%). Water content should not exceed 0.1% by Karl Fischer titration. Quality control protocols include determination of refractive index (1.486-1.488 at 20°C) and density (1.048-1.052 g/cm³ at 20°C) as additional purity indicators. The compound should be stored under inert atmosphere at temperatures below 25°C to prevent oxidation and polymerization. Shelf life under proper storage conditions exceeds 12 months with minimal degradation.

Applications and Uses

Industrial and Commercial Applications

2-Acetyl-5-methylfuran finds primary application in the flavor and fragrance industry, where it contributes roasted, nutty aroma characteristics to food products and perfumes. Usage levels typically range from 1-10 ppm in finished products due to its potent odor characteristics. The compound serves as a key intermediate in the synthesis of more complex furan derivatives, including pharmaceuticals and agrochemicals. In materials science, it functions as a building block for polymers with unique electronic properties, particularly those requiring conjugated heterocyclic systems. Production volumes remain relatively modest, estimated at 10-20 metric tons annually worldwide. Major manufacturers operate in Europe, United States, and China, supplying both industrial and research markets.

Research Applications and Emerging Uses

Research applications of 2-Acetyl-5-methylfuran include its use as a model compound for studying heterocyclic aromatic systems with unsymmetrical substitution patterns. Investigations into its electrochemical properties contribute to understanding electron transfer processes in heteroaromatic ketones. Recent studies explore its potential as a precursor for renewable chemicals derived from biomass, particularly through conversion of carbohydrate-based feedstocks. Emerging applications include its incorporation into liquid crystalline materials and organic semiconductors where the furan ring system provides desirable electronic characteristics. The compound serves as a starting material for synthesis of novel ligands in coordination chemistry, particularly those designed for asymmetric catalysis.

Historical Development and Discovery

The discovery of 2-Acetyl-5-methylfuran emerged from systematic investigations into furan chemistry during the 1940s and 1950s, as researchers explored electrophilic substitution reactions of methylfurans. Early synthetic methods employed conventional Friedel-Crafts acylation techniques adapted from benzene chemistry. Structural characterization progressed through the 1960s with advancements in spectroscopic techniques, particularly NMR spectroscopy which allowed unambiguous assignment of substitution patterns. Industrial interest developed during the 1970s as flavor chemists identified its organoleptic properties and potential applications in food chemistry. Process optimization throughout the 1980s and 1990s focused on improving selectivity and reducing environmental impact of synthesis methods. Recent developments emphasize sustainable production routes and expanded applications in materials science.

Conclusion

2-Acetyl-5-methylfuran represents a structurally interesting and practically useful heterocyclic compound that continues to attract scientific interest across multiple chemistry subdisciplines. Its combination of aromatic furan ring and polar acetyl group creates unique electronic properties that influence both reactivity and physical characteristics. The compound serves important functions in flavor applications while providing a versatile building block for synthetic chemistry. Current research directions focus on sustainable production methods, exploration of electrochemical properties, and development of novel materials incorporating the furan ring system. Further investigations into its reaction mechanisms and potential catalytic applications promise to expand the utility of this compound in both academic and industrial settings.