Abstract

2-Fluoroethanol (IUPAC: 2-fluoroethan-1-ol, CAS: 371-62-0) is a simple organofluorine compound with the molecular formula C₂H₅FO. This colorless liquid exhibits a density of 1.1040 g·cm⁻³ at room temperature and boiling point of 103.5 °C. The compound demonstrates significant hydrogen bonding capacity despite fluorine's lower electronegativity compared to other halogens in similar positions. 2-Fluoroethanol serves as a versatile synthetic intermediate in organofluorine chemistry and finds applications in positron emission tomography radiotracer development. The compound exhibits high toxicity with an LD₅₀ ranging from 7 to 1500 mg·kg⁻¹ across various species, primarily due to metabolic conversion to fluoroacetate. Its molecular structure features a gauche conformation stabilized by intramolecular hydrogen bonding between the fluorine and hydroxyl hydrogen atoms.

Introduction

2-Fluoroethanol represents one of the simplest stable fluorinated alcohols, occupying a significant position in organofluorine chemistry. First synthesized in the early 20th century, this compound has served as both a chemical intermediate and a model system for studying fluorine substitution effects on alcohol properties. The presence of fluorine adjacent to the hydroxyl group creates unique electronic and steric effects that distinguish it from other haloethanols. Industrial interest in 2-fluoroethanol emerged in the 1930s when it was patented as a rodenticide in Germany, though its commercial use has diminished due to toxicity concerns. The compound continues to be valuable in research settings, particularly for studying hydrogen bonding in fluorinated systems and as a building block for more complex fluorinated molecules.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular geometry of 2-fluoroethanol follows VSEPR theory predictions for a four-atom chain with tetrahedral coordination at carbon centers. The carbon-fluorine bond length measures approximately 1.39 Å, while the carbon-oxygen bond length is 1.43 Å. The C-C bond measures 1.52 Å, typical for single bonds between sp³ hybridized carbon atoms. Bond angles deviate slightly from ideal tetrahedral values due to electronegativity differences: the F-C-C angle measures 108.7° while the C-C-O angle is 107.8°. The hydroxyl hydrogen adopts a gauche conformation relative to the fluorine atom, with the F-C-C-O dihedral angle measuring approximately 65°. This conformation results from intramolecular hydrogen bonding between the fluorine atom and the hydroxyl hydrogen, an unusual interaction given fluorine's poor hydrogen bond acceptor capability compared to oxygen.

Electronic structure analysis reveals significant polarization of bonds. The carbon-fluorine bond exhibits a dipole moment component of 1.91 D, while the carbon-oxygen bond contributes 1.52 D to the molecular dipole. The overall molecular dipole moment measures 2.66 D, reflecting the vector sum of individual bond dipoles. Molecular orbital theory indicates that the highest occupied molecular orbital (HOMO) is primarily oxygen lone pair character, while the lowest unoccupied molecular orbital (LUMO) shows significant σ* C-F antibonding character. The ionization potential measures 10.8 eV, typical for alcohols, while electron affinity is negligible due to the absence of low-lying vacant orbitals.

Chemical Bonding and Intermolecular Forces

Covalent bonding in 2-fluoroethanol follows standard patterns for organic molecules with heteroatom substitution. The carbon-fluorine bond dissociation energy measures 452 kJ·mol⁻¹, significantly higher than the carbon-chlorine bond in 2-chloroethanol (339 kJ·mol⁻¹) but lower than the carbon-oxygen bond (385 kJ·mol⁻¹). The enhanced bond strength compared to other haloethanols results from fluorine's high electronegativity and small atomic radius, which allows for better orbital overlap.

Intermolecular forces dominate the compound's physical behavior. Despite fluorine's poor hydrogen bonding capability, 2-fluoroethanol forms extensive hydrogen bonding networks through its hydroxyl group. The oxygen-hydrogen bond length measures 0.96 Å with a stretching frequency of 3600 cm⁻¹ in the gas phase. The compound exhibits both donor and acceptor capabilities in hydrogen bonding, with an enthalpy of hydrogen bond formation measuring -25 kJ·mol⁻¹ for the hydroxyl donor role. Van der Waals forces contribute significantly to intermolecular interactions, with London dispersion forces accounting for approximately 40% of total intermolecular attraction energy in the liquid phase. The compound's relatively high boiling point despite its low molecular weight demonstrates the significance of these intermolecular forces.

Physical Properties

Phase Behavior and Thermodynamic Properties

2-Fluoroethanol exists as a colorless liquid at room temperature with a characteristic musky, tart odor. The melting point occurs at -26.3 °C, while the boiling point measures 103.5 °C at standard atmospheric pressure. The compound exhibits complete miscibility with water, ethanol, ethyl ether, and acetone. The vapor pressure follows the Antoine equation log₁₀P = A - B/(T + C) with parameters A = 7.892, B = 1567.2, and C = 224.5 for pressure in mmHg and temperature in Kelvin. At 15 °C, the vapor pressure measures 19 mbar.

Thermodynamic properties include a heat of vaporization of 42.7 kJ·mol⁻¹ at the boiling point and heat of fusion of 9.8 kJ·mol⁻¹. The specific heat capacity measures 1.92 J·g⁻¹·K⁻¹ at 25 °C. The density decreases linearly with temperature from 1.1040 g·cm⁻³ at 20 °C to 1.0860 g·cm⁻³ at 50 °C. The coefficient of thermal expansion measures 0.00112 K⁻¹. The refractive index n_D²⁰ measures 1.3630, with temperature dependence of -4.5 × 10⁻⁴ K⁻¹. The surface tension at 20 °C measures 32.4 mN·m⁻¹, while the viscosity measures 1.89 mPa·s at the same temperature.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic vibrations including the O-H stretch at 3600 cm⁻¹ (free) and 3350 cm⁻¹ (hydrogen-bonded), C-H stretches between 2900-3000 cm⁻¹, C-F stretch at 1040 cm⁻¹, C-O stretch at 1080 cm⁻¹, and C-C stretch at 890 cm⁻¹. The fingerprint region shows distinctive bands at 1340 cm⁻¹ (CH₂ wag), 1250 cm⁻¹ (CH₂ twist), and 1100 cm⁻¹ (C-C-O bend).

Nuclear magnetic resonance spectroscopy shows characteristic signals: ¹H NMR (CDCl₃, 400 MHz) δ 4.55 (t, J = 4.8 Hz, 1H, OH), 3.85 (dt, J = 28.4, 4.8 Hz, 2H, CH₂O), 3.70 (dt, J = 47.2, 4.8 Hz, 2H, CH₂F); ¹³C NMR (CDCl₃, 100 MHz) δ 83.5 (d, J = 170 Hz, CH₂F), 60.2 (d, J = 19 Hz, CH₂O); ¹⁹F NMR (CDCl₃, 376 MHz) δ -227.0 (tt, J = 47.2, 28.4 Hz). The large coupling constants reflect significant through-bond transmission of fluorine effects.

Mass spectrometry shows a molecular ion peak at m/z 64 with characteristic fragmentation patterns including loss of OH (m/z 47), loss of F (m/z 45), and cleavage of the C-C bond (m/z 31 and 33). UV-Vis spectroscopy reveals no significant absorption above 200 nm due to the absence of chromophores.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

2-Fluoroethanol undergoes characteristic reactions of both alcohols and organofluorine compounds. The hydroxyl group participates in standard alcohol transformations including esterification, ether formation, and oxidation. Esterification with carboxylic acids proceeds with second-order rate constants of approximately 10⁻⁴ L·mol⁻¹·s⁻¹ at 25 °C. Ether formation follows SN2 mechanisms with rate constants dependent on the electrophile employed.

The fluorine substituent activates the β-carbon toward nucleophilic substitution despite fluorine's poor leaving group ability. Base-catalyzed dehydrofluorination occurs with a rate constant of 2.3 × 10⁻⁵ s⁻¹ at 25 °C in 0.1 M NaOH, producing acetaldehyde and fluoride ion. This elimination follows E2 mechanism kinetics with βH isotope effect k_H/k_D = 3.2. The reaction proceeds through an anti-periplanar transition state with activation energy of 85 kJ·mol⁻¹.

Oxidation of 2-fluoroethanol yields fluoroacetaldehyde as the primary product, with further oxidation to fluoroacetic acid possible under vigorous conditions. Alcohol dehydrogenase enzymes catalyze this transformation biologically with Michaelis constants of 0.8 mM and turnover numbers of 120 s⁻¹. Thermal stability extends to 200 °C, above which decomposition occurs through free radical pathways.

Acid-Base and Redox Properties

The hydroxyl group exhibits typical alcohol acidity with a predicted pKₐ of 14.74 in water, slightly lower than ethanol (pKₐ = 15.9) due to the electron-withdrawing effect of the fluorine substituent. The compound forms alkoxide ions under basic conditions, though these species undergo rapid β-elimination. Buffer solutions maintain stability between pH 4-9, outside of which decomposition occurs.

Redox properties include oxidation potential of -0.32 V vs. SHE for the alcohol to aldehyde conversion. Reduction potentials for the fluorine substituent are inaccessible under normal conditions. Electrochemical behavior shows irreversible oxidation waves at +1.2 V vs. Ag/AgCl reference electrode. The compound exhibits stability toward common oxidizing agents except strong oxidants like chromic acid or permanganate, which cause complete degradation.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The classical synthesis of 2-fluoroethanol employs the Finkelstein halogen exchange reaction. Treatment of 2-chloroethanol with potassium fluoride in various solvents produces the fluoro analog. The reaction proceeds at 100-120 °C with reaction times of 4-6 hours. Typical yields range from 60-75% after distillation purification. The product's lower boiling point (103.5 °C) compared to the starting material (128.7 °C) enables convenient separation by fractional distillation.

Alternative laboratory routes include fluorination of ethylene carbonate with potassium fluoride, which proceeds with 55% yield at 150 °C over 8 hours. Another method utilizes 2-bromoethanol as starting material with silver fluoride in acetonitrile, providing 70% yield at room temperature over 12 hours. Purification typically involves distillation under reduced pressure (40 mmHg, 40 °C) to obtain analytical grade material. Storage requires anhydrous conditions to prevent hydrolysis and decomposition.

Analytical Methods and Characterization

Identification and Quantification

Gas chromatography with flame ionization detection provides the primary method for identification and quantification. Using a polar stationary phase such as Carbowax 20M, the compound elutes with retention time of 4.3 minutes at 80 °C isothermal conditions. Detection limits measure 0.1 μg·mL⁻¹ with linear response from 1-1000 μg·mL⁻¹. High-performance liquid chromatography with UV detection at 210 nm offers alternative quantification with C18 reverse phase columns and aqueous mobile phases.

Spectroscopic identification relies on characteristic NMR chemical shifts and coupling constants, particularly the distinctive triplet of triplets in the ¹⁹F NMR spectrum. Infrared spectroscopy provides confirmation through the C-F stretching vibration at 1040 cm⁻¹ and the pattern of O-H and C-H vibrations. Mass spectrometry confirms molecular weight through the molecular ion cluster at m/z 64/65 with characteristic isotope patterns due to ¹⁸O and ¹³C.

Purity Assessment and Quality Control

Purity assessment typically employs gas chromatography with thermal conductivity detection, capable of detecting impurities at 0.01% level. Common impurities include 2-chloroethanol (retention time 5.1 minutes), ethylene glycol (retention time 7.8 minutes), and acetaldehyde (retention time 2.1 minutes). Water content determination by Karl Fischer titration maintains specifications below 0.1%. Stability testing indicates shelf life of 12 months when stored under nitrogen atmosphere at -20 °C in amber glass containers.

Applications and Uses

Industrial and Commercial Applications

2-Fluoroethanol serves primarily as a synthetic intermediate in organofluorine chemistry. The compound functions as a building block for various fluorine-containing materials including fluorinated ethers, esters, and amines. Industrial use has declined significantly due to toxicity concerns, though specialty applications continue in controlled settings. Production volumes remain limited to laboratory-scale quantities worldwide.

Research Applications and Emerging Uses

Research applications dominate current use patterns. 2-Fluoroethanol serves as a model compound for studying fluorine effects on hydrogen bonding and conformational preferences. The compound finds extensive application in positron emission tomography (PET) radiotracer development, where the 2-[¹⁸F]fluoroethoxy moiety provides a metabolically stable labeling group. Radiochemical incorporation occurs through nucleophilic displacement of leaving groups by [¹⁸F]fluoride ion, followed by deprotection steps. Recent research explores applications in materials science as a component of fluorinated polymers and surfactants.

Historical Development and Discovery

2-Fluoroethanol first appeared in chemical literature in the early 20th century as chemists developed methods for introducing fluorine into organic molecules. The Finkelstein reaction approach was reported in German chemical journals around 1920. Industrial interest emerged in 1935 when German chemists patented the compound as a rodenticide, recognizing its metabolic conversion to toxic fluoroacetate. Systematic study of its chemical properties accelerated in the 1950s as organofluorine chemistry developed as a distinct subdiscipline. Conformational analysis through spectroscopic methods in the 1960s revealed the unusual gauche preference and intramolecular hydrogen bonding. Recent decades have seen application expansion into medical imaging and materials science.

Conclusion

2-Fluoroethanol represents a structurally simple yet chemically interesting organofluorine compound. Its unique combination of fluorine and hydroxyl substituents on adjacent carbon atoms creates distinctive electronic and steric properties that influence conformation, reactivity, and intermolecular interactions. The compound serves as valuable model for studying fluorine effects in organic systems and continues to find applications in specialized research areas despite its toxicity limitations. Future research directions may include development of safer handling protocols, exploration of new synthetic applications, and further investigation of its unusual hydrogen bonding behavior. The compound remains an important reference point in the broader field of fluorinated alcohol chemistry.