Abstract

2-Aminothiophenol (IUPAC name: 2-aminobenzene-1-thiol, molecular formula: C₆H₇NS) represents an organosulfur compound of significant synthetic utility. This aromatic compound features both amine and thiol functional groups in ortho-position on a benzene ring, creating unique electronic and steric properties. The compound exists as a colorless to pale yellow oily solid at room temperature with a melting point of 26 °C and boiling point of 234 °C. Pure samples exhibit characteristic spectroscopic signatures including IR stretching frequencies at 2550 cm⁻¹ (S-H) and 3380-3420 cm⁻¹ (N-H). 2-Aminothiophenol serves as a versatile precursor for benzothiazole synthesis and finds extensive application in pharmaceutical intermediates, dye manufacturing, and coordination chemistry. Its bifunctional nature enables diverse reactivity patterns including chelation to metal centers and participation in cyclization reactions.

Introduction

2-Aminothiophenol belongs to the class of aminothiophenols, characterized by the presence of both amino and thiol substituents on an aromatic ring. As an ortho-substituted benzene derivative, this compound demonstrates unique chemical behavior resulting from the proximity of these functional groups. The compound's significance stems from its role as a key intermediate in heterocyclic chemistry, particularly in the synthesis of benzothiazole derivatives which find applications across various chemical industries. The electronic interaction between the electron-donating amino group and the polarizable thiol function creates a molecule with distinctive electronic properties and reactivity patterns. 2-Aminothiophenol exhibits tautomeric behavior and can coordinate to metal ions through both nitrogen and sulfur donors, making it valuable in coordination chemistry and materials science.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular structure of 2-aminothiophenol derives from benzene substitution at ortho positions with amino (-NH₂) and thiol (-SH) groups. According to VSEPR theory, the amino group nitrogen exhibits sp³ hybridization with bond angles approximating 107 degrees, while the thiol group sulfur demonstrates sp³ hybridization with a C-S-H bond angle of approximately 96.5 degrees. The benzene ring maintains its planar hexagonal structure with bond angles of 120 degrees. The ortho substitution pattern creates intramolecular hydrogen bonding between the thiol hydrogen and amino nitrogen, with an estimated S-H···N distance of 2.18 Å. This interaction influences molecular conformation, causing a slight deviation from planarity with a dihedral angle of approximately 15-20 degrees between the functional group planes and the benzene ring.

Electronic structure analysis reveals significant resonance interactions. The amino group donates electron density to the aromatic system through resonance (+M effect), while the thiol group exhibits both electron-donating character through resonance and electron-withdrawing character through the inductive effect. Molecular orbital calculations indicate the highest occupied molecular orbital (HOMO) localizes primarily on the sulfur and nitrogen atoms, while the lowest unoccupied molecular orbital (LUMO) distributes over the aromatic ring. The ionization potential measures approximately 8.3 eV, and electron affinity calculates to 0.7 eV. The compound exhibits a dipole moment of 2.1 Debye oriented from the thiol toward the amino group due to the electronegativity difference between these functions.

Chemical Bonding and Intermolecular Forces

Covalent bonding in 2-aminothiophenol follows typical patterns for aromatic systems with heteroatom substituents. Carbon-carbon bond lengths in the benzene ring measure 1.395 Å, while carbon-nitrogen and carbon-sulfur bonds measure 1.365 Å and 1.782 Å respectively. The S-H bond length measures 1.336 Å, slightly longer than typical thiol S-H bonds due to intramolecular hydrogen bonding. Bond dissociation energies are measured at 87 kcal/mol for S-H and 84 kcal/mol for N-H bonds.

Intermolecular forces include strong hydrogen bonding capabilities from both functional groups. The thiol group acts as hydrogen bond donor with a propensity for S-H···N and S-H···S interactions, while the amino group serves as both donor and acceptor for N-H···S and N-H···N hydrogen bonds. Van der Waals forces contribute significantly to crystal packing, with calculated dispersion forces of approximately 2.5 kcal/mol between molecules. The compound exhibits moderate polarity with a calculated octanol-water partition coefficient (log P) of 1.8, indicating balanced hydrophilic-lipophilic character. Dipole-dipole interactions measure approximately 3.2 kcal/mol in the solid state, contributing to the compound's relatively high melting point for its molecular weight.

Physical Properties

Phase Behavior and Thermodynamic Properties

2-Aminothiophenol exists as a colorless to pale yellow oily solid at room temperature, though impure samples often develop coloration due to oxidation products. The compound crystallizes in the monoclinic crystal system with space group P2₁/c and four molecules per unit cell. Unit cell parameters measure a = 8.92 Å, b = 11.34 Å, c = 9.87 Å with β = 112.7°. The melting point occurs at 26.0 ± 0.5 °C, while the boiling point measures 234 ± 2 °C at standard atmospheric pressure. The heat of fusion is determined as 12.8 kJ/mol, and the heat of vaporization measures 52.3 kJ/mol at the boiling point.

The density of the solid phase is 1.200 g/cm³ at 20 °C, while the liquid density decreases to 1.168 g/cm³ at 30 °C. The compound exhibits a refractive index of 1.632 at 589 nm and 20 °C. Specific heat capacity measures 1.52 J/g·K for the solid phase and 2.01 J/g·K for the liquid phase. The thermal expansion coefficient is 8.7 × 10⁻⁴ K⁻¹ for the liquid phase. The compound demonstrates moderate volatility with a vapor pressure of 0.12 mmHg at 25 °C, increasing to 1.2 mmHg at 50 °C. Enthalpy of sublimation is calculated as 65.1 kJ/mol based on vapor pressure measurements.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic vibrations: S-H stretch appears as a broad medium-intensity band at 2550 cm⁻¹, N-H symmetric and asymmetric stretches occur at 3380 cm⁻¹ and 3420 cm⁻¹ respectively, and aromatic C-H stretches appear between 3000-3100 cm⁻¹. The spectrum shows strong aromatic C=C stretches at 1580 cm⁻¹ and 1600 cm⁻¹, with C-N stretch at 1280 cm⁻¹ and C-S stretch at 710 cm⁻¹.

Proton NMR spectroscopy (CDCl₃, 300 MHz) displays the following chemical shifts: aromatic protons appear as a complex multiplet between δ 6.70-7.40 ppm, the amino protons resonate as a broad singlet at δ 3.90 ppm, and the thiol proton appears at δ 2.95 ppm. Carbon-13 NMR shows signals at δ 118.5, 121.8, 127.3, 129.6, 139.2, and 148.7 ppm corresponding to the aromatic carbons, with the carbon bearing sulfur at δ 139.2 ppm and the carbon bearing nitrogen at δ 148.7 ppm.

UV-Vis spectroscopy demonstrates absorption maxima at 235 nm (ε = 12,400 M⁻¹cm⁻¹) and 290 nm (ε = 4,700 M⁻¹cm⁻¹) in ethanol solution, corresponding to π→π* transitions of the aromatic system with some charge transfer character. Mass spectrometry exhibits a molecular ion peak at m/z 125 with characteristic fragmentation patterns including loss of SH (m/z 92) and NH₂ (m/z 109) groups.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

2-Aminothiophenol demonstrates diverse reactivity patterns stemming from its bifunctional nature. The compound undergoes characteristic thiol reactions including oxidation to disulfides, alkylation to thioethers, and acylation to thioesters. The amino group participates in typical amine reactions such as acylation, diazotization, and condensation with carbonyl compounds. The ortho proximity of these functions enables unique cyclization reactions, particularly with carbonyl compounds to form benzothiazoles with reaction rates exceeding those of meta or para isomers by factors of 10-100.

Oxidation of the thiol group occurs readily with atmospheric oxygen, following second-order kinetics with a rate constant of 0.024 M⁻¹s⁻¹ at 25 °C in ethanol solution. The reaction proceeds through a radical mechanism involving disulfide anion formation. Benzothiazole formation from aldehydes follows pseudo-first order kinetics with rate constants ranging from 1.2 × 10⁻³ s⁻¹ to 8.7 × 10⁻³ s⁻¹ depending on aldehyde structure. The activation energy for this cyclization measures 65 kJ/mol. The compound demonstrates stability in acidic conditions but undergoes gradual decomposition in strong bases due to thiolate anion formation and subsequent oxidation.

Acid-Base and Redox Properties

2-Aminothiophenol exhibits amphoteric behavior with two protonation sites. The thiol group demonstrates weak acidity with pKₐ = 6.87 ± 0.05 in water at 25 °C, while the amino group shows basic character with pKₐ = 3.58 ± 0.05 for conjugate acid formation. These values reflect the electronic influence of the ortho substituents, with the thiol acidity enhanced by hydrogen bonding to the amino group. The compound forms stable zwitterionic structures in certain pH ranges, with the isoelectric point occurring at pH 5.2.

Redox properties include a standard reduction potential of -0.32 V vs. SCE for the disulfide/thiol couple. The compound undergoes electrochemical oxidation at +0.65 V vs. Ag/AgCl reference electrode, corresponding to two-electron oxidation to the disulfide. Reduction potentials for various metal complexes range from -0.85 V to +0.25 V depending on metal center and coordination geometry. The compound demonstrates stability in reducing environments but undergoes progressive oxidation in aerobic conditions, particularly at elevated temperatures or in alkaline media.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The most common laboratory synthesis of 2-aminothiophenol proceeds through a two-step process beginning with reaction of aniline with carbon disulfide in the presence of base. This reaction produces 2-mercaptobenzothiazole with typical yields of 75-85%. Subsequent hydrolysis under basic conditions (10% NaOH solution, reflux for 4 hours) followed by acidification provides 2-aminothiophenol with overall yields of 60-70%. The reaction mechanism involves nucleophilic attack of aniline nitrogen on carbon disulfide, followed by intramolecular rearrangement and ring closure.

Alternative synthetic routes include reduction of 2-nitrobenzenesulfonyl chloride with zinc dust in acetic acid medium, yielding 2-aminothiophenol with 50-60% yield after purification. Another method employs catalytic hydrogenation of 2-nitrothiophenol using palladium on carbon catalyst in ethanol solvent at 3 atm hydrogen pressure and room temperature, achieving yields of 80-85%. The compound is typically purified by vacuum distillation (bp 110-115 °C at 15 mmHg) or recrystallization from petroleum ether, resulting in material with purity exceeding 98% as determined by GC analysis.

Analytical Methods and Characterization

Identification and Quantification

Identification of 2-aminothiophenol employs multiple analytical techniques. Gas chromatography with flame ionization detection provides separation on polar stationary phases such as PEG-20M with retention index of 1458 ± 5. High-performance liquid chromatography utilizes C18 reverse-phase columns with mobile phases consisting of acetonitrile-water mixtures (typically 40:60 v/v) with 0.1% trifluoroacetic acid, showing retention times of 8.7 ± 0.2 minutes under standard conditions.

Quantitative analysis typically employs UV spectrophotometry at 290 nm with a molar absorptivity of 4,700 M⁻¹cm⁻¹, providing detection limits of 0.5 μg/mL and quantitation limits of 1.5 μg/mL. Capillary electrophoresis with UV detection offers separation efficiency with theoretical plate counts exceeding 100,000 and detection limits of 0.2 μg/mL. Mass spectrometric detection in selected ion monitoring mode provides the highest sensitivity with detection limits of 0.05 μg/mL when using electron impact ionization at 70 eV.

Applications and Uses

Industrial and Commercial Applications

2-Aminothiophenol serves as a key intermediate in the manufacture of benzothiazole derivatives, which find extensive application as vulcanization accelerators in rubber processing. The compound is employed in production of sulfur dyes for textile applications, particularly in the synthesis of thiazole-based dyes that provide yellow to brown shades with good lightfastness. In polymer chemistry, it functions as a chain transfer agent in free-radical polymerization and as a modifier for polymer properties through incorporation into polymer backbones.

The compound finds use in corrosion inhibition formulations, particularly for ferrous metals in acidic environments, where it forms protective films through chemisorption to metal surfaces. In analytical chemistry, 2-aminothiophenol derivatives serve as chelating agents for metal ion extraction and preconcentration. The global market for 2-aminothiophenol and its derivatives exceeds 5,000 metric tons annually, with primary production facilities located in Asia, Europe, and North America.

Research Applications and Emerging Uses

Research applications of 2-aminothiophenol include its use as a building block for pharmaceutical intermediates, particularly in the synthesis of benzothiazole-containing compounds with biological activity. The compound serves as a ligand in coordination chemistry, forming complexes with transition metals that exhibit interesting magnetic and catalytic properties. Recent investigations explore its use in self-assembled monolayers on gold surfaces for sensor applications, leveraging the strong Au-S bond formation and the amino group for further functionalization.

Emerging applications include use in molecular electronics as a linker molecule between metallic surfaces and organic semiconductors, and in nanotechnology for functionalization of nanoparticle surfaces. Research continues on photocatalytic applications of metal complexes derived from 2-aminothiophenol, particularly for hydrogen evolution and carbon dioxide reduction. The compound's ability to form stable radicals upon oxidation makes it potentially useful in organic magnetic materials and spin-labeling applications.

Historical Development and Discovery

The history of 2-aminothiophenol dates to the late 19th century when researchers began systematic investigation of sulfur-containing aromatic compounds. Early synthetic methods involved reduction of corresponding nitro compounds or reactions of aminophenols with sulfur sources. The development of the carbon disulfide route in the early 20th century provided a practical synthesis that enabled wider study of its properties and applications.

Significant advances in understanding the compound's chemistry occurred during the 1930s-1950s with systematic investigations of its tautomeric behavior, spectroscopic properties, and coordination chemistry. The recognition of its utility in benzothiazole synthesis drove industrial adoption in rubber processing and dye manufacturing. Recent decades have seen renewed interest in 2-aminothiophenol chemistry due to applications in materials science and nanotechnology, with particular focus on its surface modification capabilities and electronic properties.

Conclusion

2-Aminothiophenol represents a chemically versatile compound with significant importance in both industrial and research contexts. Its unique structural features, including ortho-functionalization with nitrogen and sulfur donors, create distinctive electronic properties and reactivity patterns. The compound serves as a valuable intermediate in heterocyclic synthesis, particularly for benzothiazole derivatives with commercial applications. Ongoing research continues to reveal new applications in materials science, nanotechnology, and coordination chemistry. The fundamental chemistry of 2-aminothiophenol provides a rich platform for further investigation of structure-property relationships in bifunctional aromatic systems and development of new synthetic methodologies.