Abstract

Hydroprene, systematically named ethyl (2E,4E)-3,7,11-trimethyldodeca-2,4-dienoate (CAS Registry Number: 41096-46-2), is a synthetic organic compound with molecular formula C₁₇H₃₀O₂. This conjugated diene ester belongs to the class of juvenile hormone analogs and demonstrates characteristic structural features including extended conjugation and multiple chiral centers. The compound exhibits a boiling point of approximately 175-180°C at 0.1 mmHg and a density of 0.91 g/cm³ at 20°C. Hydroprene manifests significant stability under normal storage conditions but undergoes hydrolysis under strongly acidic or basic conditions. Its molecular architecture features a trans,trans configuration across the conjugated diene system, contributing to its biological activity profile. The compound serves as a model system for studying structure-activity relationships in insect growth regulators.

Introduction

Hydroprene represents a significant class of organic compounds known as juvenile hormone analogs, first developed during the 1970s as part of research into insect growth regulators. The compound belongs to the terpenoid ester family, specifically classified as an acyclic sesquiterpenoid derivative. Its structural design mimics natural insect juvenile hormones while exhibiting enhanced chemical stability and specific biological activity profiles. The systematic nomenclature follows IUPAC conventions as ethyl (2E,4E)-3,7,11-trimethyldodeca-2,4-dienoate, reflecting its ester functionality and conjugated diene system. The compound's development emerged from structure-activity relationship studies aimed at optimizing the balance between biological efficacy and environmental persistence.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The hydroprene molecule exhibits a well-defined molecular geometry characterized by an extended hydrocarbon chain with specific stereochemical features. The central conjugated diene system adopts an all-trans configuration with dihedral angles of approximately 180° between C2-C3-C4-C5 atoms, maximizing π-orbital overlap. Bond lengths within the conjugated system measure 1.34 Å for C2=C3 and 1.38 Å for C4=C5, consistent with typical conjugated diene systems. The ester functionality demonstrates bond lengths of 1.20 Å for the carbonyl C=O bond and 1.34 Å for the C-O single bond. Molecular orbital analysis reveals highest occupied molecular orbital (HOMO) localization primarily across the conjugated diene system, while the lowest unoccupied molecular orbital (LUMO) shows significant carbonyl character. The HOMO-LUMO gap measures approximately 5.2 eV, indicating moderate reactivity toward electrophilic agents.

Chemical Bonding and Intermolecular Forces

Covalent bonding in hydroprene follows typical patterns for organic molecules with sp² hybridization at all double-bonded carbon atoms (C2, C3, C4, C5) and sp³ hybridization at saturated carbon centers. The molecule exhibits a calculated dipole moment of 2.1 Debye, oriented along the carbonyl bond vector with partial negative charge localization on the oxygen atom. Intermolecular forces include London dispersion forces dominating due to the extensive hydrocarbon framework, with additional dipole-dipole interactions originating from the ester functionality. The compound demonstrates limited capacity for hydrogen bonding, acting solely as a weak hydrogen bond acceptor through the carbonyl oxygen atom. Van der Waals interactions contribute significantly to the compound's physical properties, particularly its relatively low melting point and viscosity characteristics.

Physical Properties

Phase Behavior and Thermodynamic Properties

Hydroprene typically presents as a clear, viscous liquid at room temperature with a characteristic mild ester odor. The compound exhibits a melting point of -15°C and boils at 175-180°C under reduced pressure (0.1 mmHg). Density measurements yield 0.91 g/cm³ at 20°C, with a refractive index of 1.467 at the sodium D-line. Thermodynamic parameters include a heat of vaporization of 65.8 kJ/mol and a specific heat capacity of 1.92 J/g·K. The compound demonstrates low volatility with a vapor pressure of 2.1 × 10⁻⁶ mmHg at 25°C. Viscosity measurements show 32.5 cP at 20°C, decreasing exponentially with temperature according to Arrhenius behavior. The surface tension measures 28.9 dyn/cm at 20°C, consistent with its non-polar hydrocarbon dominance.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic absorption bands at 1715 cm⁻¹ (carbonyl stretch), 1650 cm⁻¹ and 1600 cm⁻¹ (conjugated C=C stretches), and 1180 cm⁻¹ (C-O stretch). Proton NMR spectroscopy shows distinctive signals at δ 5.85 ppm (dd, J=15.2, 10.8 Hz, H-3), δ 6.95 ppm (d, J=15.2 Hz, H-2), δ 5.55 ppm (t, J=7.2 Hz, H-4), and δ 4.12 ppm (q, J=7.1 Hz, OCH₂CH₃). Carbon-13 NMR displays signals at δ 166.8 ppm (carbonyl carbon), δ 144.2 ppm (C-2), δ 123.5 ppm (C-3), δ 134.8 ppm (C-4), and δ 124.2 ppm (C-5). UV-Vis spectroscopy demonstrates maximum absorption at 235 nm (ε = 18,500 M⁻¹cm⁻¹) corresponding to the π→π* transition of the conjugated diene system. Mass spectrometry exhibits a molecular ion peak at m/z 266.2245 (C₁₇H₃₀O₂⁺) with characteristic fragmentation patterns including loss of ethoxy radical (m/z 221) and retro-Diels-Alder fragmentation of the terpenoid chain.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Hydroprene demonstrates characteristic reactivity patterns of α,β-unsaturated esters. The compound undergoes nucleophilic addition at the β-carbon of the conjugated system with second-order rate constants of approximately 0.15 M⁻¹s⁻¹ for amine addition and 0.08 M⁻¹s⁻¹ for thiol addition. Hydrolysis follows pseudo-first-order kinetics with rate constants of 3.2 × 10⁻⁶ s⁻¹ at pH 7 and 25°C, increasing to 8.7 × 10⁻⁴ s⁻¹ under basic conditions (pH 12). Oxidation reactions proceed selectively at the allylic positions (C7 and C11) with peracid reagents, yielding epoxide derivatives. The compound exhibits stability toward atmospheric oxygen but undergoes autoxidation upon prolonged storage with an induction period of approximately 180 days at 25°C. Thermal decomposition initiates at 210°C via retro-ene reaction pathways with an activation energy of 145 kJ/mol.

Acid-Base and Redox Properties

The ester functionality of hydroprene demonstrates no significant acid-base character within the pH range of 3-11, maintaining stability under these conditions. Under strongly basic conditions (pH > 12), base-catalyzed hydrolysis occurs with a half-life of approximately 22 minutes at 25°C. Redox properties include a reduction potential of -1.25 V vs. SCE for the conjugated system, indicating moderate susceptibility to reduction. The compound undergoes electrochemical reduction at mercury electrodes with a diffusion-controlled limit current corresponding to two-electron transfer. Oxidation potentials measure +1.45 V vs. SCE for the diene system, indicating resistance to mild oxidizing agents. The compound demonstrates stability toward common oxidants including atmospheric oxygen and hydrogen peroxide but reacts with strong oxidizing agents such as potassium permanganate and ozone.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The most efficient laboratory synthesis of hydroprene employs a Horner-Wadsworth-Emmons reaction between ethyl 2-(diethylphosphono)propanoate and the appropriate aldehyde precursor. This method produces the (E,E)-diene system with high stereoselectivity (>98%) and overall yields of 65-72%. Reaction conditions typically involve sodium hydride as base in tetrahydrofuran solvent at 0°C, followed by warming to room temperature over 4 hours. Alternative synthetic routes include Wittig reactions between appropriately functionalized phosphonium ylides and aldehydes, though these methods generally yield lower stereoselectivity (85-90% E,E). Purification typically employs flash chromatography on silica gel with hexane-ethyl acetate (95:5) as eluent, followed by fractional distillation under reduced pressure (0.5 mmHg, 120-125°C). The final product characterization includes GC-MS analysis showing >99% chemical purity and stereochemical integrity verified by NMR spectroscopy.

Industrial Production Methods

Industrial production of hydroprene utilizes scaled-up versions of the Horner-Wadsworth-Emmons reaction with process optimization for economic and environmental considerations. The manufacturing process employs continuous flow reactors with residence times of 45-60 minutes at controlled temperature (15-20°C). Catalyst systems utilize potassium carbonate as a milder base alternative to sodium hydride, reducing process hazards while maintaining yields of 68-70%. Solvent recovery systems achieve >95% tetrahydrofuran recycling through distillation and molecular sieve treatment. Annual global production estimates range between 50-100 metric tons, with manufacturing primarily occurring in specialized fine chemical facilities. Production costs approximate $120-150 per kilogram at commercial scale, with the phosphonate reagent constituting the major expense. Environmental considerations include wastewater treatment for phosphate byproducts and solvent vapor recovery systems achieving >99.5% capture efficiency.

Analytical Methods and Characterization

Identification and Quantification

Gas chromatography with flame ionization detection provides the primary analytical method for hydroprene quantification, using a 30-meter DB-5 capillary column with temperature programming from 100°C to 280°C at 10°C/min. Retention time typically measures 12.8 minutes under these conditions. Detection limits reach 0.1 μg/mL with linear response from 1-1000 μg/mL (R² > 0.999). High-performance liquid chromatography employing a C18 reverse-phase column with acetonitrile-water mobile phase (85:15) offers alternative quantification with UV detection at 235 nm. Mass spectrometric confirmation utilizes selected ion monitoring at m/z 266.2245 (molecular ion) and m/z 221.1905 (M-OCH₂CH₃ fragment). Quantitative NMR spectroscopy using 1,4-dinitrobenzene as internal standard provides absolute quantification without calibration curves, achieving accuracy of ±2%.

Purity Assessment and Quality Control

Commercial hydroprene specifications typically require minimum purity of 95% by GC analysis, with limits for specific impurities including the (Z,E) and (E,Z) stereoisomers (<1.0% each), hydrolysis products (<0.5%), and oxidation products (<0.2%). Quality control protocols include Karl Fischer titration for water content (<0.1%), residue on ignition testing (<0.05%), and heavy metal screening (<10 ppm). Accelerated stability testing at 40°C and 75% relative humidity demonstrates <2% degradation over 3 months. Storage recommendations specify amber glass containers under nitrogen atmosphere at temperatures below 25°C. Shelf life determinations indicate >24 months stability under recommended storage conditions, with primary degradation occurring via hydrolysis to the corresponding carboxylic acid.

Applications and Uses

Industrial and Commercial Applications

Hydroprene serves primarily as a model compound in structure-activity relationship studies of juvenile hormone analogs. The compound's well-defined stereochemistry and functional group arrangement make it valuable for investigating electronic and steric effects on biological activity. Industrial applications include use as a reference standard in analytical chemistry laboratories for method development and quality control of related compounds. The chemical industry utilizes hydroprene as an intermediate in synthetic organic chemistry, particularly in studies of conjugated systems and ester reactivity. Commercial significance extends to its role as a benchmark compound for evaluating synthetic methodologies targeting stereodefined diene systems. Market presence remains limited to research and specialty chemical sectors rather than bulk industrial applications.

Research Applications and Emerging Uses

Research applications of hydroprene focus primarily on its utility as a molecular scaffold for designing compounds with specific stereoelectronic properties. The compound serves as a substrate for studying nucleophilic addition reactions to conjugated systems, providing insights into regioselectivity and stereochemical outcomes. Emerging applications include investigation of its potential as a chiral building block for asymmetric synthesis, leveraging its multiple stereocenters for diastereoselective transformations. Materials science research explores derivatives of hydroprene as potential liquid crystal precursors due to their elongated, rigid molecular structures. The compound's defined conjugation length makes it valuable for fundamental studies of electron transfer processes in organic molecular systems. Patent literature describes analogs of hydroprene as components in organic electronic devices, though these applications remain primarily at the research stage.

Historical Development and Discovery

The development of hydroprene emerged from systematic structure-activity relationship studies conducted during the 1960s and 1970s investigating juvenile hormone analogs. Initial research focused on natural juvenile hormones isolated from various insect species, revealing the critical importance of the terpenoid structure and ester functionality. Synthetic efforts led to the preparation of hydroprene in 1972 as part of a broader program to develop compounds with improved chemical stability while maintaining biological activity. The compound's designation reflects its structural relationship to natural hormones while indicating its synthetic origin. Methodological advances in stereoselective synthesis during the 1980s enabled production of hydroprene with high isomeric purity, facilitating detailed structure-property studies. The compound has served as a reference point in subsequent development of numerous analogs with modified biological and physical properties.

Conclusion

Hydroprene represents a structurally well-characterized organic compound with significant utility in fundamental chemical research. Its defined molecular architecture featuring a conjugated diene system and ester functionality provides a valuable model for studying electronic properties, reaction mechanisms, and structure-activity relationships. The compound's synthetic accessibility and stereochemical purity enable precise investigations across multiple chemical disciplines. Future research directions likely include expanded applications in materials science, particularly in organic electronic devices exploiting its conjugation length and molecular geometry. Additional synthetic modifications may yield derivatives with enhanced properties for specialized applications in catalysis and molecular recognition. The compound continues to serve as an important reference material for methodological development in analytical chemistry and synthetic organic chemistry.