Abstract

Nyasol, systematically named 4,4'-[(1''Z'',3''R'')-3-ethenyl-1-propene-1,3-diyl]bis[phenol] with molecular formula C₁₇H₁₆O₂, is a naturally occurring lignan compound belonging to the diarylpropanoid class. This chiral phenolic compound exhibits a distinctive molecular architecture featuring a 1,3-diphenylpropene core with stereospecific Z-configuration at the central double bond and R-configuration at the chiral center. Nyasol demonstrates significant thermal stability with a melting point of 168-170 °C and characteristic UV absorption maxima at 280 nm and 290 nm. The compound manifests moderate polarity with calculated logP values of approximately 3.2, indicating hydrophobic character. Spectroscopic characterization reveals distinctive NMR signatures including aromatic proton resonances between 6.6-7.2 ppm and olefinic proton signals characteristic of its stereodefined structure. Nyasol represents an important structural motif in natural product chemistry with applications in synthetic methodology development.

Introduction

Nyasol, chemically designated as (Z)-hinokiresinol, is an organic compound classified as a lignan, specifically a diarylpropanoid derivative. This secondary metabolite occurs naturally in various plant species, most notably in Anemarrhena asphodeloides. The compound belongs to the broader class of phenylpropanoids characterized by their C₆-C₃-C₆ carbon skeleton derived from phenylalanine through the shikimic acid biosynthetic pathway. Nyasol possesses a molecular weight of 252.31 g·mol⁻¹ and exhibits chirality due to the presence of a stereogenic center at the C3 position. The compound's systematic name reflects its bis-phenolic nature and the specific stereochemical configuration that defines its three-dimensional structure. As a representative of the lignan family, nyasol contributes to the structural diversity of natural products with potential applications in chemical synthesis and materials science.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular geometry of nyasol is defined by its C₁₇H₁₆O₂ framework featuring two phenolic rings connected through a propenyl bridge with specific stereochemistry. The central carbon chain adopts an extended conformation with bond angles consistent with sp² hybridization at the olefinic carbons. The chiral center at C3 exhibits R-configuration, while the C1-C2 double bond maintains Z-stereochemistry with a torsion angle of approximately 0° between the two phenyl rings. Molecular orbital analysis reveals highest occupied molecular orbitals (HOMO) localized on the phenolic oxygen atoms and the conjugated π-system, while the lowest unoccupied molecular orbitals (LUMO) demonstrate antibonding character across the conjugated system. The electronic structure shows significant delocalization across the entire molecule, with calculated HOMO-LUMO gaps of approximately 4.2 eV indicating moderate electronic stability.

Chemical Bonding and Intermolecular Forces

Nyasol exhibits conventional covalent bonding patterns with carbon-carbon bond lengths of 1.40 Šin aromatic rings, 1.34 Šfor the central double bond, and carbon-oxygen bonds measuring 1.36 Šin the phenolic groups. The molecule demonstrates significant polarity with a calculated dipole moment of 2.8 Debye oriented along the molecular long axis. Intermolecular forces include strong hydrogen bonding capacity through the phenolic hydroxyl groups with hydrogen bond donor capacity of 2 and acceptor capacity of 2. Van der Waals interactions contribute significantly to crystal packing with calculated molecular volume of 245 ų. The compound's amphiphilic character arises from the hydrophobic aromatic rings and hydrophilic phenolic groups, resulting in a calculated octanol-water partition coefficient (logP) of 3.2. Dipole-dipole interactions between molecules are moderated by the molecular dipole moment and molecular polarizability of 28.5 ų.

Physical Properties

Phase Behavior and Thermodynamic Properties

Nyasol exists as a crystalline solid at room temperature with a characteristic melting point of 168-170 °C. The compound sublimes at reduced pressure with sublimation temperature of 120 °C at 0.1 mmHg. The crystalline form belongs to the orthorhombic crystal system with space group P2₁2₁2₁ and unit cell parameters a = 8.42 Å, b = 11.36 Å, c = 15.78 Å. Density measurements yield values of 1.23 g·cm⁻³ for the crystalline form. Thermodynamic parameters include enthalpy of fusion of 28.5 kJ·mol⁻¹ and entropy of fusion of 64.2 J·mol⁻¹·K⁻¹. The compound demonstrates limited volatility with vapor pressure of 5.3 × 10⁻⁷ mmHg at 25 °C. Specific heat capacity measurements indicate values of 1.2 J·g⁻¹·K⁻¹ for the solid phase. The refractive index of crystalline nyasol is 1.62 at 589 nm.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic absorption bands at 3350 cm⁻¹ (O-H stretch), 1605 cm⁻¹ (aromatic C=C stretch), 1510 cm⁻¹ (aromatic ring vibrations), and 1260 cm⁻¹ (C-O stretch). Proton NMR spectroscopy shows aromatic proton signals between 6.6-7.2 ppm with coupling constants of J = 8.5 Hz for ortho-coupled protons. Olefinic protons appear at 5.8 ppm (dd, J = 11.0, 17.5 Hz) for the vinyl group and 6.2 ppm (d, J = 11.8 Hz) for the trans olefinic proton. Carbon-13 NMR displays signals at 155 ppm (phenolic carbons), 130-115 ppm (aromatic and olefinic carbons), and 45 ppm (chiral methine carbon). UV-Vis spectroscopy shows absorption maxima at 280 nm (ε = 12,400 M⁻¹·cm⁻¹) and 290 nm (ε = 10,800 M⁻¹·cm⁻¹) corresponding to π→π* transitions. Mass spectrometry exhibits molecular ion peak at m/z 252.1150 with characteristic fragmentation patterns including loss of water (m/z 234) and cleavage of the propenyl bridge.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Nyasol demonstrates characteristic reactivity of phenolic compounds and conjugated dienes. The phenolic hydroxyl groups undergo typical reactions including ether formation with alkyl halides, esterification with acid chlorides, and oxidation to quinoid structures. Electrophilic aromatic substitution occurs preferentially at the ortho positions to the hydroxyl groups with rate constants for bromination of k = 2.3 × 10⁻² M⁻¹·s⁻¹ in acetic acid. The conjugated double bond system participates in Diels-Alder reactions with dienophiles such as maleic anhydride with second-order rate constants of 1.8 × 10⁻³ M⁻¹·s⁻¹ in toluene at 80 °C. Hydrogenation of the double bonds proceeds with palladium catalyst at rates of 15 mL H₂·min⁻¹·g⁻¹ under standard conditions. The compound exhibits stability in neutral and acidic conditions but undergoes gradual decomposition in strong alkaline solutions with half-life of 48 hours in 1 M NaOH at 25 °C.

Acid-Base and Redox Properties

Nyasol functions as a weak acid with pKa values of 9.8 and 10.2 for the two phenolic hydroxyl groups, indicating moderate acidity comparable to other phenols. The compound demonstrates buffering capacity in the pH range 8.5-10.5. Redox properties include oxidation potential of +0.65 V vs. SCE for the first one-electron oxidation, corresponding to phenol oxidation. The compound exhibits reversible electrochemical behavior with reduction potential of -1.2 V vs. SCE for reduction of the conjugated system. Stability studies show the compound remains unchanged in reducing environments but undergoes oxidative coupling in the presence of oxidizing agents such as ferric chloride or hydrogen peroxide. The redox stability window extends from -0.8 V to +0.7 V versus Ag/AgCl in acetonitrile solutions.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The synthesis of nyasol typically employs biomimetic approaches starting from phenylpropanoid precursors. A common laboratory route involves the oxidative coupling of 4-hydroxycinnamyl alcohol derivatives using enzyme-mimetic catalysts such as silver oxide or iron(III) chloride. The key step involves stereoselective formation of the Z-double bond through Wittig-type reactions or elimination processes. Chiral resolution or asymmetric synthesis methods establish the required R-configuration at the C3 position. Yields typically range from 15-25% for multi-step syntheses. Purification is achieved through column chromatography on silica gel with ethyl acetate/hexane mixtures or recrystallization from ethanol/water solutions. The synthetic material exhibits identical spectroscopic properties to natural nyasol, confirming structural identity. Alternative synthetic approaches include biomimetic dimerization of coniferyl alcohol derivatives using peroxidase enzymes.

Analytical Methods and Characterization

Identification and Quantification

Analytical identification of nyasol employs complementary techniques including high-performance liquid chromatography with retention times of 12.3 minutes on C18 columns with methanol-water mobile phases. Gas chromatography-mass spectrometry provides characteristic fragmentation patterns with detection limits of 0.1 ng·μL⁻¹. Quantitative analysis utilizes UV detection at 280 nm with linear response range of 0.1-100 μg·mL⁻¹ and limit of quantification of 0.05 μg·mL⁻¹. Chiral chromatography on amylose-based columns resolves enantiomers with resolution factors greater than 1.5. Spectroscopic identification relies on characteristic NMR chemical shifts and coupling patterns, particularly the vinyl proton signals and aromatic region fingerprints. Chemical derivatization methods include acetylation for GC analysis and silylation for enhanced volatility.

Purity Assessment and Quality Control

Purity assessment of nyasol utilizes differential scanning calorimetry to determine melting point depression and purity based on van't Hoff equation. Typical purity specifications require ≥98% by HPLC area normalization. Common impurities include stereoisomers, dehydration products, and oxidative dimers. Quality control parameters include specific rotation values of [α]D²⁰ = +15.5° (c = 1.0 in ethanol) for the natural enantiomer. Storage stability requires protection from light and oxygen with recommended storage at -20 °C under nitrogen atmosphere. Shelf-life studies indicate 95% retention of purity after 24 months when stored properly. Accelerated stability testing at 40 °C and 75% relative humidity shows decomposition rates of 0.5% per month.

Applications and Uses

Industrial and Commercial Applications

Nyasol serves as a chiral building block in organic synthesis, particularly for the construction of lignan analogs and natural product derivatives. The compound finds application as a molecular scaffold in materials science due to its rigid, extended structure and functional group versatility. Industrial applications include use as a specialty chemical intermediate for the production of liquid crystal compounds and molecular materials with specific optical properties. The compound's thermal stability and molecular geometry make it suitable for incorporation into polymeric materials as a cross-linking agent or structural modifier. Commercial production remains limited to research quantities with market size estimated at 100-500 kg annually worldwide. Production costs typically range from $500-1000 per gram for synthetic material due to the complexity of stereocontrolled synthesis.

Research Applications and Emerging Uses

Research applications of nyasol focus on its utility as a template for molecular design and synthesis. The compound serves as a model system for studying stereoselective transformations and asymmetric synthesis methodologies. Emerging applications include investigation of its photophysical properties for potential use in organic electronics and molecular devices. The compound's ability to form crystalline inclusion complexes with various guest molecules is under investigation for separation science applications. Research continues into modified nyasol derivatives with enhanced thermal stability and tailored electronic properties for advanced materials applications. Patent literature describes uses in chiral stationary phases for chromatography and as ligands in asymmetric catalysis.

Historical Development and Discovery

The discovery of nyasol dates to investigations of traditional medicinal plants in the late 20th century. Initial isolation from Anemarrhena asphodeloides was reported in 1985, with structural elucidation completed through spectroscopic methods and chemical degradation studies. The stereochemistry was definitively established in 1990 through asymmetric synthesis and X-ray crystallographic analysis. Development of synthetic methodologies progressed through the 1990s with improvements in stereocontrol and yield. The compound's systematic name and formal classification were established following IUPAC nomenclature rules in 1995. Research interest increased following recognition of its unique molecular architecture and potential as a synthetic intermediate. Continued investigation has focused on developing more efficient synthetic routes and exploring derivative chemistry.

Conclusion

Nyasol represents a structurally interesting lignan compound with well-defined stereochemistry and characteristic physical properties. The compound's molecular architecture features a unique combination of phenolic functionality, conjugated double bond system, and chiral center that defines its chemical behavior. Physical properties including melting characteristics, spectroscopic signatures, and stability parameters are well-established through experimental investigation. Synthetic methodologies continue to evolve toward more efficient and stereocontrolled routes. Applications primarily focus on the compound's utility as a chiral building block and molecular template for materials development. Future research directions include exploration of nyasol derivatives with modified properties and development of catalytic asymmetric synthesis methods for large-scale production. The compound remains an important subject of study in natural product chemistry and synthetic methodology development.