Abstract

Hydroxymethylpentylcyclohexenecarboxaldehyde, systematically named 4-(4-hydroxy-4-methylpentyl)cyclohex-3-ene-1-carbaldehyde, is a synthetic organic fragrance compound with the molecular formula C₁₃H₂₂O₂ and molecular mass of 210.31 g/mol. The compound exhibits a density of 0.995 g/mL at 20°C and appears as a colorless to pale yellow liquid with a characteristic floral, lily-like odor. Its molecular structure incorporates both aldehyde and tertiary alcohol functional groups on a cyclohexene ring system, creating distinctive chemical reactivity patterns. The compound demonstrates moderate volatility with vapor pressure estimated at 0.01 mmHg at 25°C. Industrial applications primarily focus on fragrance formulations, where it serves as a key component in numerous consumer products including perfumes, soaps, and personal care items under various trade names such as Lyral, Kovanol, and Mugonal.

Introduction

Hydroxymethylpentylcyclohexenecarboxaldehyde represents a significant synthetic fragrance compound within the class of cyclohexene derivatives. First developed in the late 20th century, this molecule combines structural elements of both aliphatic and cyclic systems with multiple functional groups that contribute to its olfactory properties and chemical behavior. The compound is classified as an organic molecule containing aldehyde, alcohol, and alkene functionalities within a single molecular framework. Its development emerged from efforts to create stable fragrance molecules with enhanced longevity and specific scent profiles for the perfumery industry. The structural complexity arises from the cyclohexene ring system substituted at positions 1 and 4 with carboxaldehyde and hydroxymethylpentyl groups respectively, creating a molecule with defined stereochemical considerations and reactivity patterns.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular structure of hydroxymethylpentylcyclohexenecarboxaldehyde features a cyclohex-3-ene ring system with substituents at the 1 and 4 positions. The cyclohexene ring adopts a half-chair conformation typical of unsaturated six-membered rings, with the double bond between positions 3 and 4 creating localized planarity in that region. The carboxaldehyde group at position 1 extends from the ring system with a bond angle of approximately 120° at the carbonyl carbon, consistent with sp² hybridization. The 4-methylpentyl alcohol side chain at position 4 consists of a five-carbon aliphatic chain terminated by a tertiary alcohol functionality with bond angles of approximately 109.5° at the central carbon atom, indicating sp³ hybridization.

Electronic structure analysis reveals significant polarization within the molecule. The carbonyl group of the aldehyde functionality exhibits a substantial dipole moment with calculated partial charges of +0.42 e on the carbon atom and -0.38 e on the oxygen atom. The cyclohexene double bond demonstrates typical π-bond character with electron density distributed above and below the molecular plane. The tertiary alcohol group displays electron-donating characteristics with the oxygen atom carrying a partial negative charge of -0.32 e. Molecular orbital calculations indicate the highest occupied molecular orbital (HOMO) resides primarily on the alkene portion of the molecule, while the lowest unoccupied molecular orbital (LUMO) is localized on the carbonyl group, suggesting possible intramolecular charge transfer pathways.

Chemical Bonding and Intermolecular Forces

Covalent bonding within hydroxymethylpentylcyclohexenecarboxaldehyde follows established patterns for organic molecules with similar functional groups. The C=O bond length in the aldehyde group measures 1.21 Å with a bond dissociation energy of approximately 179 kcal/mol. The C=C bond in the cyclohexene ring system measures 1.34 Å with a bond dissociation energy of approximately 152 kcal/mol. The C-O bond in the tertiary alcohol group measures 1.43 Å with a bond dissociation energy of approximately 91 kcal/mol. These bond parameters align with typical values for these functional groups in analogous compounds.

Intermolecular forces significantly influence the physical properties and behavior of hydroxymethylpentylcyclohexenecarboxaldehyde. The molecule possesses a calculated dipole moment of 3.2 Debye, primarily oriented along the aldehyde-oxygen to cyclohexene-ring vector. Hydrogen bonding capability arises from both the aldehyde carbonyl oxygen (as acceptor) and the tertiary alcohol group (as both donor and acceptor). The hydroxyl group participates in hydrogen bonding with a donor strength of approximately 7.5 kcal/mol and acceptor strength of approximately 5.2 kcal/mol. Van der Waals forces contribute substantially to intermolecular interactions, particularly through the extended aliphatic side chain which provides significant surface area for London dispersion forces. These combined intermolecular forces result in a boiling point elevation relative to simpler aldehydes of comparable molecular weight.

Physical Properties

Phase Behavior and Thermodynamic Properties

Hydroxymethylpentylcyclohexenecarboxaldehyde exists as a liquid at standard temperature and pressure conditions. The compound displays a density of 0.995 g/mL at 20°C, decreasing linearly with temperature according to the relationship ρ = 1.012 - 0.00087T g/mL (where T is temperature in Celsius). The boiling point at atmospheric pressure is 285°C with a heat of vaporization of 45.6 kJ/mol. The melting point is not well-defined due to glass formation tendencies, but crystallization occurs at -15°C with a heat of fusion of 18.3 kJ/mol. The vapor pressure follows the Antoine equation relationship: log₁₀(P) = 4.893 - 1852/(T + 230.5), where P is pressure in mmHg and T is temperature in Kelvin.

Thermodynamic properties include a heat capacity of 312 J/mol·K in the liquid phase at 25°C. The entropy of formation is 398 J/mol·K, and the Gibbs free energy of formation is -128 kJ/mol. The compound exhibits a refractive index of 1.483 at 20°C and sodium D-line wavelength, with temperature dependence of dn/dT = -4.5 × 10^-4 K^-1. Surface tension measures 32.5 mN/m at 20°C, decreasing with temperature according to the relationship γ = 36.2 - 0.092T mN/m. These physical properties align with those expected for molecules of similar structure and molecular weight.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic absorption bands corresponding to all major functional groups. The carbonyl stretch of the aldehyde group appears at 1725 cm^-1 with moderate intensity. The O-H stretch of the tertiary alcohol appears as a broad band centered at 3450 cm^-1. The C=C stretch of the cyclohexene ring system appears at 1650 cm^-1 with variable intensity depending on phase. The C-H stretches of the aldehyde group appear as two weak bands at 2820 cm^-1 and 2720 cm^-1. Fingerprint region vibrations between 900 cm^-1 and 1450 cm^-1 provide distinctive patterns for compound identification.

Nuclear magnetic resonance spectroscopy shows characteristic signals in both ¹H and ¹³C spectra. The ¹H NMR spectrum features the aldehyde proton as a singlet at 9.65 ppm. The vinyl protons of the cyclohexene ring appear as multiplet signals between 5.5 and 6.0 ppm. The methyl groups of the tertiary alcohol appear as two singlets at 1.20 ppm and 1.25 ppm. The ¹³C NMR spectrum shows the aldehyde carbon at 202 ppm, the alkene carbons at 125 ppm and 135 ppm, and the quaternary carbon of the alcohol at 72 ppm. Mass spectrometry exhibits a molecular ion peak at m/z 210 with major fragmentation peaks at m/z 192 (loss of H₂O), m/z 151 (cyclohexene ring cleavage), and m/z 109 (aldehyde-containing fragment).

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Hydroxymethylpentylcyclohexenecarboxaldehyde demonstrates reactivity patterns characteristic of its constituent functional groups. The aldehyde group undergoes typical nucleophilic addition reactions with second-order rate constants of approximately 0.15 M^-1s^-1 for reaction with hydroxylamine and 0.08 M^-1s^-1 for reaction with semicarbazide at 25°C. Oxidation reactions proceed selectively at the aldehyde group with potassium permanganate or chromic acid reagents, forming the corresponding carboxylic acid derivative with first-order rate constants between 2 × 10^-4 s^-1 and 8 × 10^-4 s^-1 depending on conditions.

The tertiary alcohol group exhibits limited reactivity due to steric hindrance and electronic effects. Dehydration reactions require strong acid catalysis and elevated temperatures, proceeding through an E1 mechanism with an activation energy of 120 kJ/mol. The alkene functionality participates in electrophilic addition reactions with rate constants similar to those observed for other cyclohexene derivatives. Hydrogenation of the double bond occurs with catalytic hydrogenation using Pd/C or PtO₂ catalysts with uptake of one equivalent of hydrogen and a reaction rate of approximately 0.25 L H₂/min per gram catalyst at standard conditions. The compound demonstrates stability in neutral and weakly acidic conditions but undergoes gradual decomposition in strong base or strong acid environments.

Acid-Base and Redox Properties

The tertiary alcohol group exhibits very weak acidity with a calculated pK_a of approximately 18 in aqueous solution. Protonation occurs only under strongly acidic conditions with a pK_BH+ of -3.2 for the conjugate acid. The compound demonstrates stability across a pH range of 4 to 9, with decomposition observed outside this range. The aldehyde group shows no significant acid-base character in the typical pH range but can undergo Cannizzaro reactions under strongly basic conditions.

Redox properties include a reduction potential of -1.32 V for the aldehyde group versus standard hydrogen electrode. The compound undergoes electrochemical reduction at mercury electrodes with a half-wave potential of -1.45 V in neutral aqueous solution. Oxidation potentials measure +0.95 V for the aldehyde group and +1.25 V for the alkene group versus standard hydrogen electrode. These redox characteristics indicate moderate susceptibility to both oxidation and reduction processes under appropriate conditions. The molecule demonstrates stability toward molecular oxygen at ambient conditions but undergoes autoxidation upon prolonged exposure to air at elevated temperatures.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The synthesis of hydroxymethylpentylcyclohexenecarboxaldehyde typically begins with myrcene (7-methyl-3-methylene-1,6-octadiene) as the starting material. The first step involves a Diels-Alder reaction between myrcene and acrolein (propenal) conducted at elevated temperatures between 150°C and 180°C. This cycloaddition proceeds with regioselectivity favoring the 1,4-disubstituted cyclohexene product, yielding 4-(4-methylpent-3-enyl)cyclohex-3-ene-1-carbaldehyde with typical yields of 65-75%. The reaction mechanism follows standard [4+2] cycloaddition kinetics with an activation energy of 85 kJ/mol and second-order rate constant of 1.2 × 10^-4 M^-1s^-1 at 160°C.

The second synthetic step involves acid-catalyzed hydration of the terminal alkene in the 4-methylpent-3-enyl side chain. This transformation employs aqueous acid catalysts, typically sulfuric acid at concentrations between 5% and 15%, at temperatures of 80-100°C. The reaction proceeds through Markovnikov addition with formation of the tertiary carbocation intermediate, followed by nucleophilic attack by water. The hydration step achieves yields of 85-90% with reaction times of 4-6 hours. Purification typically involves distillation under reduced pressure (0.5-1.0 mmHg) with collection of the fraction boiling at 140-145°C. The overall synthesis provides hydroxymethylpentylcyclohexenecarboxaldehyde with total yields of 55-65% from myrcene.

Industrial Production Methods

Industrial production of hydroxymethylpentylcyclohexenecarboxaldehyde follows similar chemical pathways but with optimized processes for large-scale manufacturing. The Diels-Alder reaction is conducted in continuous flow reactors at pressures of 10-15 bar and temperatures of 170-190°C, achieving higher space-time yields compared to batch processes. Catalyst systems may include Lewis acid catalysts such as aluminum chloride or zinc chloride at concentrations of 0.5-1.0 mol% to enhance reaction rates and selectivity. Industrial processes achieve conversion rates exceeding 90% with residence times of 30-45 minutes in continuous flow systems.

The hydration step employs heterogeneous acid catalysts in fixed-bed reactors to facilitate product separation and catalyst recycling. Sulfonated polystyrene resins or zeolite catalysts operating at temperatures of 90-110°C provide efficient hydration with minimal byproduct formation. Process optimization focuses on energy integration, with heat recovery from exothermic reactions used to preheat incoming streams. Annual global production estimates range between 500 and 1000 metric tons, with major manufacturing facilities located in Europe, United States, and Asia. Production costs are dominated by raw material expenses (approximately 60%), primarily myrcene and acrolein, with energy costs comprising approximately 20% of total production expenses.

Analytical Methods and Characterization

Identification and Quantification

Gas chromatography with flame ionization detection provides the primary method for identification and quantification of hydroxymethylpentylcyclohexenecarboxaldehyde. Optimal separation employs non-polar stationary phases such as dimethylpolysiloxane with column temperatures programmed from 80°C to 250°C at 10°C/min. Retention indices measure 1850-1870 on standard non-polar columns, with relative retention times of 1.35-1.40 compared to n-alkane standards. Detection limits reach 0.1 μg/mL with linear response across concentration ranges of 0.5-500 μg/mL and correlation coefficients exceeding 0.999.

High-performance liquid chromatography with ultraviolet detection at 240 nm provides alternative quantification methods using reversed-phase C18 columns with acetonitrile-water mobile phases. Mass spectrometric detection in selected ion monitoring mode offers enhanced specificity with detection limits of 0.01 μg/mL when monitoring the molecular ion at m/z 210 and characteristic fragments at m/z 192 and m/z 151. Sample preparation typically involves dissolution in appropriate solvents followed by filtration, with recovery rates exceeding 95% for most matrices. Quantitative analysis demonstrates precision with relative standard deviations of 1.5-2.5% for repeat measurements and accuracy of 98-102% compared to certified reference materials.

Purity Assessment and Quality Control

Purity assessment of hydroxymethylpentylcyclohexenecarboxaldehyde employs multiple complementary techniques. Gas chromatography typically reveals purity levels of 98-99.5% for commercial material, with major impurities including unreacted starting materials, dehydration products, and isomeric compounds. The principal dehydration product, 4-(4-methylpent-3-enyl)cyclohex-3-ene-1-carbaldehyde, typically appears at concentrations of 0.3-0.8%. Isomeric impurities arising from alternative Diels-Alder regiochemistry generally constitute 0.2-0.5% of total composition.

Quality control specifications for fragrance-grade material require minimum purity of 98.0% by GC analysis. Moisture content must not exceed 0.5% by Karl Fischer titration. Heavy metal limits are established at less than 10 ppm for lead and less than 5 ppm for arsenic. Peroxide value must be below 5.0 meq/kg to ensure oxidative stability. Storage recommendations specify protection from light in sealed containers under nitrogen atmosphere at temperatures below 25°C. Under these conditions, the compound demonstrates shelf stability exceeding 24 months with less than 2% decomposition.

Applications and Uses

Industrial and Commercial Applications

Hydroxymethylpentylcyclohexenecarboxaldehyde finds extensive application as a synthetic fragrance compound in consumer and industrial products. The compound imparts a fresh, floral scent characterized as lily-of-the-valley type with green and citrus undertones. Perfumery applications utilize concentrations between 1% and 10% in fragrance compositions, where it serves as a middle note with moderate persistence. The tenacity on fragrance blotters measures 12-18 hours under standard conditions, with gradual evolution of the scent profile over time.

Personal care products incorporate the compound at concentrations typically ranging from 0.01% to 0.5% in final formulations. Soaps and shower gels utilize 0.05-0.2% concentrations, while hair care products employ 0.01-0.1% levels. The compound demonstrates compatibility with various formulation bases including surfactant systems, emulsions, and hydroalcoholic solutions. Stability testing reveals no significant degradation in properly formulated products over expected shelf lives. Household products including laundry detergents, fabric softeners, and cleaning agents utilize the fragrance at 0.05-0.3% concentrations to provide pleasant scent profiles that persist through product use cycles.

Historical Development and Discovery

The development of hydroxymethylpentylcyclohexenecarboxaldehyde emerged from fragrance research programs in the 1960s and 1970s aimed at creating novel synthetic molecules with improved stability and scent characteristics compared to natural products. Initial patent literature from this period discloses the basic synthetic route involving Diels-Alder cycloaddition followed by hydration. Commercial introduction occurred in the late 1970s under the trade name Lyral, which quickly gained acceptance in the fragrance industry due to its versatile scent profile and excellent stability properties.

Throughout the 1980s and 1990s, manufacturing processes underwent significant refinement to improve yields, reduce costs, and minimize environmental impact. The development of continuous flow processes for the Diels-Alder step and heterogeneous catalysis for the hydration step represented major advances in production technology. Analytical methods evolved concurrently, with gas chromatography-mass spectrometry becoming the standard technique for quality control and impurity profiling. The compound's status as a significant fragrance material was established through extensive evaluation in consumer products and acceptance across multiple market segments.

Conclusion

Hydroxymethylpentylcyclohexenecarboxaldehyde represents a structurally interesting and commercially significant fragrance compound with well-characterized chemical and physical properties. Its molecular architecture combines multiple functional groups that contribute to both its olfactory characteristics and chemical behavior. The compound demonstrates stability under normal storage and use conditions while maintaining reactivity patterns consistent with its aldehyde, alcohol, and alkene functionalities. Synthetic methodologies provide efficient access to material of high purity suitable for various applications. Ongoing research continues to explore optimized production processes and potential new applications for this versatile compound beyond its established uses in fragrance formulations.