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Cyclopentanone

Cyclopentanone is an with the molecular formula C₅H₈O, featuring a five-membered carbocyclic bearing a single at position 1. It appears as a clear, colorless with a petroleum-like , exhibiting a of 130–131 °C, a of −51 °C, and a of 0.951 g/mL at 25 °C. Cyclopentanone is practically insoluble in but miscible with most solvents, and it has a of 31 °C (87 °F), indicating moderate flammability. In terms of production, cyclopentanone is industrially synthesized via the catalytic of , often by heating the calcium salt or using vapor-phase processes with catalysts like ceria. Alternative methods include the vapor-phase cyclization of 1,6-hexanediol or the conversion of bio-based through hydrogenolysis and cyclization steps, enhancing its sustainability as a chemical. Cyclopentanone serves as a versatile intermediate in , particularly for pharmaceuticals, where it is used to produce biologically active compounds such as analgesics and antivirals. It is also essential in the fragrance industry for synthesizing jasmine-like scents and aroma chemicals, as well as in the production of rubber additives, fungicides, and agrochemicals. Additionally, its solvent properties make it valuable in for formulations and in specialty manufacturing. Despite its utility, cyclopentanone is classified as a and potential irritant, requiring careful handling in industrial settings.

Physical Properties

Appearance and Structure

Cyclopentanone, the for this (with the systematic name cyclopentan-1-one), has the molecular formula C5H8O. It features a five-membered saturated carbocyclic ring with a carbonyl (C=O) group attached at position 1, making it a cyclic . Cyclopentanone appears as a clear, colorless at . It has a petroleum-like odor. The molecular structure of cyclopentanone exhibits a slightly puckered ring conformation, which alleviates angle compared to a hypothetical planar . The C-C-C bond angles in the ring are approximately 105–108°, close to the ideal tetrahedral angle of 109.5° for sp3-hybridized carbons, resulting in minimal angle overall. In contrast to acyclic ketones, where flexible alkyl chains allow free rotation and maintain planarity only at the , the cyclic framework in cyclopentanone constrains the overall geometry while preserving the local planarity of the sp2-hybridized carbonyl carbon with bond angles near 120°. This puckered envelope conformation also reduces torsional through pseudo-rotation.

Spectroscopic Data

Infrared (IR) spectroscopy is a primary method for identifying the in cyclopentanone, with the characteristic C=O stretching vibration appearing as a strong absorption band at 1740–1745 cm⁻¹. The C-H stretching vibrations from the methylene groups occur in the 2950–2850 cm⁻¹ region, typical for aliphatic C-H bonds adjacent to the carbonyl. Nuclear magnetic resonance (NMR) provides detailed structural confirmation. In the ¹H NMR spectrum (recorded in CDCl₃), the alpha protons (CH₂ groups adjacent to the carbonyl) resonate as a multiplet at approximately 2.3 ppm, while the beta protons appear at around 2.0 ppm, reflecting the deshielding effect of the carbonyl on the alpha positions. The ¹³C NMR spectrum shows the carbonyl carbon at ~217 ppm, the alpha carbons at ~38 ppm, and the beta carbons at ~23 ppm, consistent with the symmetric ring structure and carbonyl influence. Mass spectrometry of cyclopentanone exhibits a molecular at m/z 84, corresponding to its formula C₅H₈O. A common fragmentation pathway involves loss of , yielding a prominent at m/z 56 (C₄H₈⁺), along with other fragments such as m/z 55 and 42 from ring cleavage. Ultraviolet-visible (UV-Vis) reveals a weak n→π* for the , with absorption maximum around 300 nm (ε ≈ 12 M⁻¹ cm⁻¹ in ), indicative of the forbidden nature of this in saturated ketones.

Thermodynamic Properties

Cyclopentanone exhibits characteristic thermodynamic properties that define its behavior as a at standard conditions. Its is 130.6 °C at 760 mmHg, allowing it to remain in liquid form under ambient pressures but requiring moderate heating for processes. The is -51.3 °C, indicating it is a stable liquid well above typical freezing temperatures. The density of cyclopentanone is 0.947 g/cm³ at 20 °C, which is slightly less than that of , facilitating its separation in aqueous mixtures. Its refractive index is 1.4366 at 20 °C, a value typical for cyclic ketones and useful in purity assessments via .
PropertyValueConditionsSource
130.6 °C760 mmHgNIST WebBook
-51.3 °C-NIST WebBook
0.947 g/cm³20 °C
1.436620 °C
Cyclopentanone is miscible with common organic solvents such as and , owing to its polar , but shows limited in at approximately 9.2 g/L (or 0.92 g/100 mL) at 20 °C. This moderate hydrophilicity is quantified by its (logP) of 0.7 at pH 7 and 25 °C, suggesting balanced partitioning between lipophilic and aqueous phases in environmental and biological contexts. The of 11.4 mmHg at 25 °C contributes to its moderate volatility, influencing safe handling by necessitating to prevent exposure during storage or use. The heat of vaporization is approximately 40.6 kJ/mol near its , reflecting the energy required for and relevant for evaporation-based purification techniques.

Chemical Properties

Reactivity

Cyclopentanone, as a symmetrical , exhibits typical reactivity at its toward . In , it equilibrates with its , cyclopentane-1,1-diol, although the strongly favors the carbonyl form (<1% hydrate) due to the electron-donating alkyl groups stabilizing the C=O bond. Similarly, addition of hydrogen cyanide (HCN) under basic conditions yields the cyanohydrin, 1-cyano-1-hydroxycyclopentane, via nucleophilic attack by the cyanide ion on the carbonyl carbon, forming the cyanohydrin anion, followed by protonation; this reaction is reversible and useful for extending the carbon chain in synthesis. Cyclopentanone also forms a water-soluble bisulfite adduct with sodium bisulfite (NaHSO₃), consisting of a sulfonate group attached to the former carbonyl carbon, which facilitates purification by separating the adduct from non-reactive impurities in an aqueous phase. The alpha-hydrogens of cyclopentanone are acidic (pKa ≈ 20), allowing deprotonation under basic conditions to generate an enolate ion that serves as a nucleophile in substitution reactions. This enolization enables alpha-alkylation, where the enolate reacts with alkyl halides to introduce substituents at the alpha position, and aldol condensations, in which the enolate adds to another carbonyl compound. A representative example is the base-catalyzed aldol condensation with benzaldehyde, where the enolate of cyclopentanone attacks the aldehyde carbonyl, followed by dehydration to form the α,β-unsaturated ketone 2-benzylidenecyclopentan-1-one: \chemfig{**5(-(-)-(-)-(-)-)} + \chemfig{Ph-CHO} \xrightarrow{\ce{base}} \chemfig{**5(=-=-(-)-)} = \chemfig{Ph-CH=} This crossed aldol product highlights the preferential reactivity of the non-enolizable benzaldehyde with the enolate of cyclopentanone. Cyclopentanone can be reduced to cyclopentanol via selective nucleophilic addition of hydride. Sodium borohydride (NaBH₄) in methanol or ethanol reduces the carbonyl to the secondary alcohol cyclopentanol, while catalytic hydrogenation over metals like palladium or platinum achieves the same transformation under milder conditions, providing a route to the saturated alcohol. Due to its saturated five-membered ring and lack of an alpha-hydrogen on the carbonyl carbon, cyclopentanone resists mild oxidation, remaining stable under conditions that oxidize aldehydes to carboxylic acids. However, it undergoes acid- or base-catalyzed alpha-halogenation at the alpha position with halogens like Br₂, forming 2-halocyclopentan-1-one through the enol or enolate intermediate, which is useful for further functionalization but requires control to avoid polyhalogenation.

Stability and Decomposition

Cyclopentanone exhibits good thermal stability under ambient conditions but undergoes unimolecular decomposition at elevated temperatures. Studies indicate that thermal decomposition begins around 215–270 °C in the gas phase, primarily yielding and through a concerted mechanism, with minor contributions from a stepwise radical pathway involving ring opening. At higher temperatures, such as 800–1100 K, additional products including and are observed, alongside as a dominant species. The autoignition temperature is approximately 430 °C, beyond which rapid combustion occurs. The compound shows mild sensitivity to light and air exposure. While generally stable in an inert atmosphere, prolonged exposure to air and light can lead to slow autooxidation, potentially forming peroxides similar to other aliphatic ketones, though this process is not aggressive at room temperature. Safety data sheets recommend storing cyclopentanone protected from light to minimize such risks. In neutral conditions, it remains stable, with no significant decomposition reported under standard ambient exposure. Hydrolytically, cyclopentanone is resistant to neutral water, maintaining integrity due to its low reactivity as a simple ketone; it has a solubility of 30.1 g/100 mL at 20 °C but does not hydrolyze under these conditions. However, under acidic or basic catalysis, it can participate in aldol-type reactions, though these are controlled transformations rather than spontaneous decomposition. For safe storage, cyclopentanone should be kept in tightly closed containers in a cool, dry, and well-ventilated area to prevent potential acid-catalyzed polymerization or oxidation. It is incompatible with strong oxidizing agents, bases, and reducing agents, which could accelerate decomposition. In the event of fire or thermal runaway, decomposition yields carbon monoxide, carbon dioxide, and various hydrocarbons.

Synthesis

Industrial Methods

The primary industrial production of cyclopentanone occurs through the ketonic decarboxylation of , a process that leverages the byproduct from manufacturing. Adipic acid is heated in continuous flow reactors at 280–310 °C in the presence of basic catalysts such as , , or , leading to the elimination of carbon dioxide and water to form the cyclic ketone. This method is conducted under inert atmospheres to minimize side reactions, with the overall reaction represented as: \mathrm{HOOC(CH_2)_4COOH} \rightarrow \mathrm{(CH_2)_4CO} + \mathrm{CO_2} + \mathrm{H_2O} Commercial production of cyclopentanone has been established since the early 20th century, with the adipic acid route becoming prominent alongside the growth of nylon production. Global annual production is estimated at over 38,000 metric tons as of 2023, primarily in Asia-Pacific regions, though recent market analyses suggest volumes approaching 100,000 metric tons by 2024. Alternative methods include the catalytic vapor-phase cyclization of 1,6-hexanediol. Emerging sustainable routes involve the conversion of bio-based furfural through hydrogenolysis and cyclization, often using Ru/C catalysts, offering potential for renewable production. A researched approach for cyclopentanone production involves the liquid-phase oxidation of cyclopentane using air or oxygen over cobalt-based catalysts at 120–150 °C and 5–15 bar pressure, yielding a mixture of cyclopentanone and cyclopentanol. The cyclopentanol can be further converted to cyclopentanone via catalytic dehydrogenation using copper-zinc catalysts at 250–300 °C. These methods provide flexibility for integration with petrochemical or renewable feedstocks but are not primary industrial routes.

Laboratory Preparations

One prominent laboratory method for synthesizing cyclopentanone is the , an intramolecular applied to . The process begins with the treatment of diethyl adipate with a base such as in , leading to cyclization and formation of along with ethanol. Subsequent acid hydrolysis of the β-keto ester, followed by heating to effect , yields cyclopentanone. This sequence is versatile for small-scale preparations and typically affords the product in moderate to good yields after purification by distillation. The key cyclization step can be represented as: \ce{(EtO2C)(CH2)4(CO2Et) ->[NaOEt, EtOH] \overset{\begin{matrix} \ce{O} \\ | \\ \ce{C} \end{matrix}}{\ce{\chemfig{**5(-(-CO2Et)-(-CH2-)-(-CH2-)-(-CH2-))}} + EtOH} A straightforward alternative involves the oxidation of cyclopentanol, which is selectively converted to cyclopentanone using mild, chromium-based or sulfur-based reagents suitable for laboratory conditions. Pyridinium chlorochromate (PCC), generated from pyridine, hydrochloric acid, and chromium trioxide in dichloromethane, oxidizes secondary alcohols like cyclopentanol at room temperature, providing the ketone in high yield while avoiding acidic byproducts through the use of anhydrous conditions. Similarly, the Swern oxidation employs oxalyl chloride and dimethyl sulfoxide in dichloromethane at -78 °C, followed by addition of triethylamine, to achieve clean transformation without metal residues, making it ideal for sensitive substrates. Both methods emphasize controlled conditions to prevent over-oxidation or side reactions. Cyclopentanone can also be obtained via thermal of derivatives in a setting. Heating the dry calcium salt of to around 300 °C under conditions promotes ketonization, producing cyclopentanone as the main volatile product alongside and . This classical method, often conducted in a apparatus to collect and fractionate the , delivers practical yields after careful separation from impurities like unreacted material. Recent developments in laboratory preparations include photocatalytic oxidations of hydrocarbons such as to cyclopentanone, leveraging visible light and or complexes under aerobic conditions. These methods utilize photocatalysts like oxyhalides to activate C-H bonds, enabling selective formation of carbonyl compounds at ambient temperatures with high turnover numbers, offering greener alternatives for small-scale synthesis.

Applications

Organic Synthesis

Cyclopentanone serves as a versatile building block in due to its cyclic structure and reactive , enabling the construction of complex carbocyclic frameworks. One prominent application is its involvement in the , particularly through the Hajos–Parrish reaction, where it undergoes an asymmetric Michael addition followed by with under catalysis. This process yields the Hajos–Parrish ketone, a bicyclic enedione that forms fused cyclohexenone rings essential for synthesizing steroids and various natural products, such as terpenoids and alkaloids. The reaction's enantioselectivity, often exceeding 90% ee, has made it a cornerstone for stereocontrolled synthesis since its development in the . Functionalization at the alpha position further expands cyclopentanone's utility, allowing the preparation of substituted derivatives for downstream transformations. Alpha-alkylation is typically achieved by generating the kinetic with (LDA) at low temperatures, followed by addition of an alkyl halide, as exemplified in the of 2-tert-pentylcyclopentanone, which demonstrates compatibility with sterically hindered electrophiles. Similarly, alpha-acylation via reaction with esters or acid chlorides produces 1,3-diketones, which serve as precursors for heterocycles and s in further couplings; these methods are widely employed to introduce aryl or alkyl substituents with high . Such modifications are crucial for creating chiral cyclopentenones used in pharmaceutical intermediates. Beyond its role as a reactant, cyclopentanone functions as a in various reactions, attributed to its constant of approximately 16 (at 20 °C) and of 130.6°C, which facilitate solvating polar transition states while permitting heating without rapid evaporation. It has been utilized in reactions, such as Diels–Alder processes, where its polarity enhances reaction rates compared to nonpolar media. Historically, cyclopentanone played a pivotal role as a key intermediate in E.J. Corey's total syntheses of prostaglandins during the 1960s and early 1970s, notably through the use of the Corey lactone—a bicyclic γ-lactone derived via Diels–Alder cycloaddition of with a protected , followed by oxidation and lactonization steps. This approach enabled stereocontrolled assembly of the prostanoic acid skeleton, marking a landmark in natural product synthesis. In recent developments post-2015, derivatives of cyclopentanone have been incorporated into strategies for , such as azide-alkyne cycloadditions to functionalize bio-based monomers, yielding cross-linked networks with enhanced mechanical properties for materials applications.

Pharmaceutical and Material Uses

Cyclopentanone serves as a key intermediate in the of various pharmaceuticals, particularly as a precursor for cyclopentane-based structures in antiviral and drugs. In the production of the antiviral medication , cyclopentanone is employed in the formation of specific intermediates through reactions such as steps. Derivatives of cyclopentanone, including 2-alkyl and 2-alkylidene cyclopentanones, have demonstrated significant and activities in preclinical evaluations, positioning them as potential candidates for therapeutics. Additionally, novel cyclopentanone analogs, such as (E)-2-(4-methoxybenzylidene)cyclopentan-1-one, exhibit promising effects comparable to standard drugs like aspirin in molecular docking and pharmacological studies. In agrochemicals, cyclopentanone acts as a precursor for and herbicides. For instance, it is used in the synthesis of pencycuron, a phenylamide effective against sheath blight in , and other plant growth regulators and pesticides. In material science, cyclopentanone contributes to advanced applications in semiconductors and polymers. It functions as a high-purity in formulations for processes, enabling the dissolution and removal of unexposed layers in , as utilized by leading producers like . This role supports the demand for finer circuit patterns in integrated circuits, with cyclopentanone's cyclic structure providing effective solvency without residue issues. In , cyclopentanone is incorporated into structures like poly(arylidene-ether)s via polycondensation reactions, yielding thermotropic main-chain polymers with enhanced thermal stability and potential for liquid crystalline applications. It also enables the electrolytic of aromatic hydrocarbons to form resins containing cyclopentanone units, which act as cross-linkers for durable coatings and adhesives. Beyond high-tech materials, cyclopentanone is a building block for commercial products in fragrances and rubber processing. It is synthesized into jasmonate-like aroma compounds, contributing minty and fruity notes in perfumes and flavorings. In the , cyclopentanone derivatives serve as accelerators, such as enamines formed from secondary amines and cyclopentanone, which enhance curing efficiency and mechanical properties in and production. As of , pharmaceutical applications accounted for approximately 33% of global cyclopentanone production, underscoring its economic significance in value-added sectors.

Safety and Environmental Impact

Toxicity

Cyclopentanone exhibits moderate via oral exposure, with an LD50 greater than 2,000 mg/kg in rats according to Test Guideline 401. It acts as an irritant to and eyes, producing moderate and in Draize tests, though effects typically resolve without permanent damage. Inhalation of its vapors can cause irritation, including coughing and wheezing, particularly at elevated concentrations, though no specific OSHA (PEL) is established for cyclopentanone. Under the Globally Harmonized System (GHS), cyclopentanone is classified as a irritant (Category 2) and eye irritant (Category 2), based on its potential to induce reversible upon contact. Repeated or prolonged exposure may lead to potential damage in the liver and kidneys, especially in individuals with pre-existing conditions, as indicated by toxicological assessments. Cyclopentanone is not classified as a by the International Agency for Research on Cancer (IARC), and there is no evidence of from available data. In terms of , it undergoes rapid in the liver, primarily through to cyclopentanol followed by conjugation to glucuronides, which are excreted in .

Handling and Regulations

Cyclopentanone should be handled in well-ventilated areas to maintain airborne concentrations below applicable occupational exposure limits, using including chemical-resistant gloves, safety goggles, and protective clothing to prevent skin and eye contact. Spark-proof tools and explosion-proof equipment are recommended to mitigate ignition risks due to its flammability. For storage, cyclopentanone must be kept in tightly closed containers in a cool, dry, well-ventilated area away from heat sources, ignition points, and incompatible materials such as strong oxidizers; it is compatible with construction. In the event of a spill, evacuate the area, eliminate ignition sources, and contain the with dikes or absorbent materials such as or ; small spills can be absorbed and cleaned up, while larger spills should be diluted with spray to reduce vapors before collection, followed by proper disposal as . Cyclopentanone is listed on the U.S. Toxic Substances Control Act (TSCA) inventory as an active and is registered under the European Union's REACH regulation (EC 1907/2006) with registration number 01-2119495595-21. It is classified as a Class 3 (UN 2245, Packing Group III) for transportation under international regulations including , IMDG, and IATA. Environmentally, cyclopentanone is considered readily biodegradable under aerobic conditions, with studies showing over 90% degradation in 28 days using inoculum, though discharges should be monitored to prevent exceedance of local limits. Aquatic toxicity data indicate moderate risk, with LC50 values for around 100-500 mg/L in standard tests; low potential (BCF <1). As a (VOC) not exempt under the U.S. Clean Air Act, its emissions are regulated to control formation, with post-2020 updates in state programs like California's emphasizing low-VOC alternatives in solvent-based formulations to reduce atmospheric reactivity.

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    Revision to the Definition of Volatile Organic Compounds (VOC)—Removal of VOC Exemptions for California's Aerosol Coating Products Reactivity-based Regulation.Missing: cyclopentanone | Show results with:cyclopentanone