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Valeric acid

Valeric acid, also known as pentanoic acid, is a straight-chain saturated fatty acid with the chemical formula C₅H₁₀O₂ and a molecular weight of 102.13 g/mol.^[1] It appears as a colorless to pale yellow oily liquid with a strong, unpleasant odor reminiscent of stale cheese or rancid butter, and it is combustible under normal conditions.^[2] It is naturally derived from sources such as the roots of the valerian plant (Valeriana officinalis).^[3] Physically, valeric acid has a density of 0.939 g/mL at 25°C, a boiling point of 185.4°C at standard pressure, and a melting point of -34°C, making it a liquid at room temperature.^[1] It exhibits moderate solubility in water (approximately 24–40 g/L at 20–25°C) and is freely soluble in alcohols and ethers, which contributes to its utility in various chemical syntheses.^[1] Chemically, it behaves as a typical short-chain carboxylic acid, capable of forming esters and salts, and it serves as a key intermediate in organic reactions due to its alkyl chain structure (CH₃(CH₂)₃COOH).^[2] Valeric acid occurs naturally as a plant metabolite in fruits, dairy products, and meats, and it is produced by gut microbiota through processes like the condensation of ethanol and propionic acid.^[4] In biological systems, it acts as a histone deacetylase (HDAC) inhibitor and a ligand for free fatty acid receptor 2, with concentrations detected in human feces (around 2.4 µmol/g) and potentially protective effects against radiation-induced damage in animal models.^[4] Industrially, it is synthesized via oxidation of n-amyl alcohol or fermentation, and serves as a precursor for esters used in perfumes, flavors, and food additives, as well as in lubricants, plasticizers, and pharmaceuticals.^[2] It also forms the basis for derivatives like valproic acid, an antiepileptic drug, though valeric acid itself has limited direct therapeutic applications and is primarily investigational.^[3] Safety-wise, valeric acid is corrosive to skin, eyes, and respiratory tissues, classified under GHS as causing severe burns (H314), with an LD₅₀ of 1290 mg/kg in mice via intravenous administration; it requires careful handling and storage below 30°C.^[1]

Properties

Physical properties

Valeric acid, systematically named pentanoic acid, possesses the molecular formula C₅H₁₀O₂ and the structural formula CH₃(CH₂)₃COOH, featuring a straight-chain saturated aliphatic structure with a terminal carboxylic acid group.^[5] It appears as a colorless liquid at room temperature, exhibiting a penetrating and unpleasant odor reminiscent of lower fatty acids.^[5] The compound has a melting point of −34 °C and a boiling point of 185 °C at standard pressure, reflecting its liquid state under ambient conditions.^[5] Its density is 0.94 g/cm³ at 20 °C.^[5] Valeric acid shows moderate solubility in water, approximately 24 g/L at 25 °C, and is fully miscible with organic solvents such as ethanol and diethyl ether.^[5] The octanol-water partition coefficient (log P) is 1.39, indicating moderate lipophilicity.^[5] Key thermodynamic properties include a standard heat of combustion of −2837.8 kJ/mol and a vapor pressure of 0.19 mmHg at 20 °C, contributing to its relatively low volatility.^[5] The refractive index is 1.4086 at 20 °C.^[5] Regarding safety, it has a flash point of 89 °C (closed cup), classifying it as combustible but not highly flammable under typical handling conditions.^[6]

Property	Value	Conditions
Melting point	−34 °C	-
Boiling point	185 °C	101.3 kPa
Density	0.94 g/cm³	20 °C
Water solubility	24 g/L	25 °C
log P (octanol-water)	1.39	-
Vapor pressure	0.19 mmHg	20 °C
Refractive index	1.4086	20 °C, Na D-line
Flash point	89 °C	Closed cup

Chemical properties

Valeric acid possesses a carboxyl functional group (-COOH) that confers weak acidity, with a pKa value of 4.84 at 25 °C, allowing partial dissociation in aqueous solutions. This group also facilitates intermolecular hydrogen bonding, which contributes to the formation of dimers in nonpolar solvents and affects its overall reactivity.^[7] The presence of the polar carboxyl group imparts significant polarity to the molecule, enabling dipole-dipole interactions. In infrared spectroscopy, this is evidenced by characteristic absorption bands, including the C=O stretching vibration at approximately 1710 cm⁻¹, which is typical for aliphatic carboxylic acids.^[8] Under standard ambient conditions, valeric acid exhibits good chemical stability, but it is susceptible to thermal decomposition at elevated temperatures, undergoing oxidation or decarboxylation to produce carbon dioxide and carbon monoxide.^[7] Relative to shorter-chain alkanoic acids, the acidity of valeric acid is marginally reduced owing to the electron-donating inductive effect of its longer butyl chain, which slightly destabilizes the conjugate base; for instance, propanoic acid has a pKa of 4.87, while acetic acid's is 4.76.^[9]

History and nomenclature

Historical discovery

Valeric acid, also known as pentanoic acid, emerged as a subject of study during the early 19th century, a period marked by rapid advancements in organic chemistry following Friedrich Wöhler's groundbreaking synthesis of urea in 1828, which challenged vitalist doctrines and spurred systematic investigations into natural products. Carboxylic acids, including formic, acetic, and butyric acids, had been known since antiquity or isolated through empirical methods, but the era saw a shift toward precise characterization through combustion analysis and distillation techniques pioneered by chemists like Jöns Jacob Berzelius and Justus von Liebig. This context facilitated the identification of higher homologues like valeric acid amid efforts to classify fatty substances from animal and plant sources.^[10] The compound was first isolated from the root of the perennial plant Valeriana officinalis through aqueous distillation by German pharmacist Johann Trommsdorff in 1808, who examined the volatile oil yielded by the process. Further analysis in 1830 by Trommsdorff confirmed the presence of a distinct acidic component, which he named "valerianic acid" after its botanical source, distinguishing it from other fatty acids like butyric acid obtained from butter. This isolation involved heating the dried roots with water to produce a pungent distillate, from which the acid was separated via neutralization and fractionation, highlighting the empirical distillation methods prevalent at the time. The name "valeric acid" thus directly derives from Valeriana officinalis, a plant long used in traditional medicine for its sedative properties, though the acid itself was a minor constituent of the essential oil.^[11]^[12] Subsequent studies built on these observations, transitioning from empirical isolation to structural analysis. In the mid-19th century, chemists like Hermann Kolbe employed oxidation and electrolytic experiments on valeric acid sources to determine its empirical formula, contributing to the radical theory and early understandings of homologous series in aliphatic compounds. By the late 1800s, with the advent of structural organic chemistry advanced by August Kekulé and others, valeric acid was fully elucidated as a straight-chain carboxylic acid with five carbon atoms, C4H9COOH, solidifying its place in the series of fatty acids. These developments paralleled broader progress in synthesizing and derivatizing carboxylic acids, laying groundwork for industrial applications.^[13]^[10]

Naming conventions

Valeric acid is systematically named pentanoic acid according to IUPAC nomenclature, reflecting its structure as a straight-chain carboxylic acid with five carbon atoms.^[5] The common name "valeric acid" or "n-valeric acid" is widely used to denote this linear isomer, distinguishing it from branched variants.^[14] Synonyms for valeric acid include valerianic acid, propylacetic acid, and butanecarboxylic acid, with historical terms such as n-amylformic acid also appearing in older literature.^[15] References to "butanoic acid" as a synonym are incorrect, as butanoic acid refers to the four-carbon analog.^[5] The compound is identified by CAS number 109-52-4 and PubChem CID 7991.^[5] It must be differentiated from isovaleric acid, which is the branched isomer 3-methylbutanoic acid (CAS 503-74-2, PubChem CID 10430). The term "valeric" originates from its association with valerian root extracts in early chemical studies.^[16]

Occurrence and production

Natural occurrence

Valeric acid, also known as pentanoic acid, occurs naturally as a short-chain fatty acid in various biological systems, primarily through microbial fermentation processes. It is prominently found in the roots of the perennial flowering plant Valeriana officinalis, from which it derives its name, where it contributes to the plant's characteristic odor and bioactive properties.^[1] In animal guts, valeric acid is produced as a fermentation product by gut microbiota, particularly in the lower intestinal tract of species such as chickens and mammals, where anaerobic bacteria metabolize undigested carbohydrates and fibers.^[17] Similarly, in plant roots beyond valerian, it arises from microbial activity in the rhizosphere, aiding in nutrient cycling.^[18] Valeric acid is also present in food sources derived from natural fermentation and lipid metabolism. It appears in dairy products like cheese and milk, where it forms as a volatile compound during ripening processes driven by lactic acid bacteria and lipolysis of milk fats.^[19] In fruits such as apples and pineapples, trace amounts contribute to flavor profiles through enzymatic breakdown and microbial action post-harvest.^[20] Additionally, it serves as a metabolite in the bacterial degradation of lipids in anaerobic environments, such as soil and aquatic sediments, where microorganisms break down complex organic matter into simpler acids.^[21] The biosynthesis of valeric acid in microorganisms primarily involves the beta-oxidation pathway of fatty acids or reverse beta-oxidation (chain elongation), where shorter acyl-CoA intermediates, such as propionyl-CoA and acetyl-CoA, condense to form C5 chains under anaerobic conditions.^[22] This process occurs in gut bacteria like those in the Clostridium genus and in environmental microbes during organic decomposition. In natural extracts, concentrations typically range from 0.1% to 1% in essential oils from plants like valerian, though free valeric acid levels are lower compared to its esters.^[20] Ecologically, valeric acid plays a role in decomposition by acting as an intermediate in the breakdown of biomass, facilitating carbon flow and influencing microbial community dynamics in fermentative ecosystems like ruminant digestion and soil organic matter turnover.

Industrial production

Valeric acid is primarily produced on an industrial scale through the oxo process, a two-step synthesis involving the hydroformylation of 1-butene with syngas (a mixture of carbon monoxide and hydrogen) to yield valeraldehyde, followed by catalytic oxidation of the aldehyde to the corresponding carboxylic acid.^[23] This method, which also utilizes 2-butene for branched isomers like isovaleric acid, relies on petrochemical feedstocks and employs rhodium- or cobalt-based catalysts under high-pressure conditions (typically 100-300 bar and 100-200°C for hydroformylation, followed by air oxidation at milder temperatures).^[23] Global production capacity via this route is estimated at approximately 75,000 tons per year (as of 2017), reflecting its scalability and economic viability for meeting demand in downstream applications.^[23] An alternative synthetic route involves the oxidation of 1-pentanol (n-amyl alcohol) or pentanal, where the primary alcohol or aldehyde is converted to the acid using air or oxygen in the presence of catalysts such as manganese or cobalt salts.^[24] This process, while less common than the oxo route due to higher raw material costs, offers flexibility when pentanol is available as a byproduct from other petrochemical processes. Another variant is the hydrocarboxylation of 1-butene with carbon monoxide and water under high pressure (up to 500 bar) and acidic conditions, directly forming the carboxylic acid without an intermediate aldehyde step, though it remains niche owing to equipment demands.^[25] Fermentative production represents an emerging bio-based alternative, employing engineered bacterial strains such as those from the genus Clostridium to convert renewable feedstocks like glucose, biomass hydrolysates, or waste streams into valeric acid through anaerobic fermentation.^[26] These processes achieve yields of up to around 0.3-0.5 g/g substrate for related short-chain fatty acids in optimized lab-scale setups, with potential for scalability via integrated biorefineries, though commercial adoption is limited by separation challenges and costs compared to petrochemical methods. As of 2025, research has advanced recovery techniques, such as using phosphonium-based ionic liquids, achieving extraction yields over 800 mg/g.^[27]^[28] Historically, valeric acid was extracted from natural sources like the roots of Valeriana officinalis, but production shifted to synthetic routes post-1950s with the commercialization of the oxo process, enabling cost-effective large-scale manufacturing from abundant olefin feedstocks.^[3] This transition reduced reliance on variable natural supplies and supported growing industrial demand, with bio-based methods gaining traction in recent decades for sustainability.^[29]

Reactions

Acidity and derivatization

Valeric acid, also known as pentanoic acid (CH₃(CH₂)₃COOH), is a weak organic acid that undergoes dissociation in aqueous solution according to the equilibrium CH₃(CH₂)₃COOH ⇌ CH₃(CH₂)₃COO⁻ + H⁺, with a pKa value of 4.82 at 25°C.^[1] This pKa indicates moderate acidity compared to stronger carboxylic acids like acetic acid (pKa 4.76), and the titration curve of valeric acid with a strong base such as NaOH exhibits a characteristic S-shape: an initial slow rise in pH due to buffering by the undissociated acid, a steep inflection near the equivalence point reflecting rapid pH change after complete neutralization, and a final buffering region from excess base.^[30] The formation of salts involves the deprotonation of valeric acid by bases, yielding water-soluble carboxylates. For instance, reaction with sodium hydroxide proceeds quantitatively via proton transfer: CH₃(CH₂)₃COOH + NaOH → CH₃(CH₂)₃COONa + H₂O, producing sodium valerate (sodium pentanoate), a white crystalline solid used in applications requiring the carboxylate anion.^[1] The mechanism is a straightforward acid-base neutralization, where the hydroxide ion abstracts the acidic proton from the carboxyl group, facilitated by the partial positive charge on the carbonyl carbon; this reaction is typically carried out in aqueous or alcoholic media at room temperature, achieving near 100% yield due to the driving force of water formation and ion solvation. Purification of the sodium salt involves filtration to remove unreacted material, followed by evaporation of the solvent under reduced pressure or recrystallization from ethanol to isolate pure crystals with minimal impurities. Esterification of valeric acid commonly employs the Fischer method, where the acid reacts with an alcohol in the presence of a strong acid catalyst like sulfuric acid. A representative example is the synthesis of methyl valerate: CH₃(CH₂)₃COOH + CH₃OH ⇌ CH₃(CH₂)₃COOCH₃ + H₂O, typically refluxed for several hours with excess methanol to shift the equilibrium toward the ester.^[31] The mechanism begins with protonation of the carbonyl oxygen, enhancing electrophilicity and allowing nucleophilic attack by the alcohol to form a tetrahedral intermediate; subsequent proton transfers and loss of water yield the protonated ester, which deprotonates to the neutral product. Yields for methyl pentanoate under standard conditions (e.g., 5% H₂SO₄ catalyst, reflux 2-4 hours) range from 70-85%, limited by equilibrium but improved by water removal via Dean-Stark apparatus or molecular sieves; purification entails extraction with an organic solvent like diethyl ether, washing with bicarbonate to neutralize acids, drying over anhydrous sodium sulfate, and fractional distillation under vacuum to obtain the pure ester (boiling point ~127°C).^[32] Valeric acid derivatives, particularly its esters, serve as precursors in the synthesis of polyesters. For example, valeric acid is fermented by bacteria such as Alcaligenes eutrophus to generate 3-hydroxyvalerate monomers, which copolymerize with 3-hydroxybutyrate to form poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biodegradable polyester with improved flexibility and thermal properties over homopolymers.^[33] This application leverages the acid's role in providing C5 units for tailored polymer chain lengths, enabling PHBV production with 3-hydroxyvalerate contents up to 20-30 mol% for enhanced material performance in packaging and biomedical uses.^[34]

Other chemical transformations

Valeric acid, like other carboxylic acids, undergoes reduction with lithium aluminum hydride (LiAlH₄) in ether solvents to yield the corresponding primary alcohol, 1-pentanol (CH₃(CH₂)₄OH). This transformation involves the stepwise reduction of the carboxylic acid group, first forming an aldehyde intermediate that is further reduced, requiring excess LiAlH₄ due to the initial deprotonation of the acid.^[35]^[36] Decarboxylation of valeric acid can occur under thermal or catalytic conditions, leading to the loss of CO₂ and formation of butane derivatives such as butane or 1-butene. This process is particularly relevant in biomass conversion pathways, where pentanoic acid is transformed via decarboxylation/decarbonylation followed by hydrogenation to produce butane.^[37] The Hell-Volhard-Zelinsky (HVZ) reaction enables selective α-bromination of valeric acid using bromine and a catalytic amount of phosphorus or phosphorus tribromide, yielding 2-bromopentanoic acid (CH₃CH₂CH₂CHBrCOOH). In this mechanism, the acid is initially converted to the acid bromide, which enolizes to facilitate bromination at the α-position before hydrolysis regenerates the carboxylic acid. This reaction is valuable for introducing functionality at the α-carbon for subsequent synthetic manipulations.^[38]^[39] Amidation of valeric acid proceeds by reaction with amines, typically after activation of the carboxylic acid (e.g., via coupling agents like dicyclohexylcarbodiimide or conversion to the acid chloride), to form valeramides (CH₃(CH₂)₃CONHR). This transformation is commonly employed in the synthesis of N-substituted pentanamides for pharmaceutical or material applications./Carboxylic_Acids/Reactivity_of_Carboxylic_Acids/Amidation_of_Carboxylic_Acids)^[40] Valeric acid serves as a building block in the synthesis of fine chemicals through chain elongation, notably via ketonization, where two molecules couple over metal oxide catalysts (e.g., CeO₂ or TiO₂) to produce 5-nonanone (CH₃(CH₂)₃CO(CH₂)₃CH₃) with concomitant loss of CO₂ and H₂O. This reaction extends the carbon chain for applications in biofuels and fragrances. For branching, α-functionalization via HVZ bromination allows subsequent nucleophilic substitution to introduce branched substituents, enabling access to diverse fine chemical derivatives.^[41]^[38]

Applications

Industrial uses

Valeric acid serves as a crucial intermediate in the chemical industry, particularly for the synthesis of esters used in lubricants, plasticizers, and resins. Its esters, such as those formed with alcohols, provide excellent solvency and stability, making them suitable for enhancing the performance of synthetic lubricants that operate under high temperatures and pressures. In plasticizers, valeric acid derivatives improve the flexibility and durability of polymers like polyvinyl chloride (PVC), contributing to applications in flexible films, cables, and flooring materials. These uses leverage the acid's linear chain structure, which allows for controlled viscosity and compatibility in formulations.^[15]^[42]^[43] Beyond materials manufacturing, valeric acid finds application as a flavor and fragrance additive, where its volatile esters impart fruity, apple-like notes at low concentrations. These esters are incorporated into perfumes, cosmetics, and food products to achieve desired sensory profiles without overpowering odors, as the pure acid itself has a pungent smell. In the food sector, approved esters function as safe additives to mimic natural fruit essences in beverages, candies, and baked goods. This role underscores valeric acid's versatility in consumer goods, where precise dosing ensures palatability and regulatory compliance.^[20] (Note: FDA for GRAS status of esters) In pharmaceutical production, valeric acid acts as a building block for derivatives like valproic acid, a branched-chain analog employed in antiseizure medications for treating epilepsy and bipolar disorder. The synthesis involves alkylation of valeric acid precursors to yield active compounds with enhanced bioavailability and therapeutic efficacy. Additionally, valeric acid contributes to agrochemicals through its incorporation into herbicide and pesticide formulations, where it aids in crop protection by disrupting weed growth or pest metabolism. As a solvent component in coatings, its esters facilitate even application and drying in industrial paints and varnishes, improving adhesion and finish quality.^[16]^[44]^[45] Market dynamics reflect strong industrial demand, with the chemical sector accounting for a significant portion of valeric acid consumption—for intermediates in plastics, lubricants, and related processes. As of 2023, the global market was valued at US$ 186.3 million, projected to reach US$ 396.1 million by 2034 at a CAGR of 7.2%, fueled by innovations in bio-based sourcing and efficient synthesis methods.^[46]^[47]

Biological and medical applications

Valeric acid serves as a key structural precursor in the synthesis of valproic acid (2-propylvaleric acid), a widely used anticonvulsant and mood stabilizer approved by the U.S. Food and Drug Administration (FDA) in 1978 for the treatment of absence seizures in epilepsy.^[44] This derivative has since been indicated for complex partial seizures, generalized tonic-clonic seizures, and bipolar disorder, with efficacy demonstrated in reducing seizure frequency by up to 50% in responsive patients at therapeutic doses of 10-60 mg/kg/day.^[48] Common side effects of valproic acid include gastrointestinal disturbances such as nausea and vomiting, neurological effects like drowsiness, and hematological changes, necessitating regular monitoring for hepatotoxicity and thrombocytopenia.^[44] In addition to its role in pharmaceutical synthesis, valeric acid exhibits antimicrobial properties, particularly against Gram-negative and Gram-positive bacteria in vitro, comparable to those of butyric acid, making it a candidate for inclusion in topical formulations to combat skin infections.^[49] As a feed additive in animal husbandry, valeric acid glyceride esters have been shown to improve broiler performance by enhancing intestinal morphology and reducing the incidence of necrotic enteritis, with supplementation levels of 0.15-0.5% (1.5-5 g/kg) in diets leading to decreased feed conversion ratios and lower mortality rates from bacterial challenges.^[50] Emerging research highlights valeric acid's potential in cancer therapy through its inhibition of histone deacetylases (HDACs), a mechanism akin to that of butyrate, which promotes apoptosis and cell cycle arrest in tumor cells. In preclinical studies, valeric acid suppressed liver cancer development by acting as an HDAC inhibitor, reducing tumor growth in mouse models via epigenetic modulation. Similarly, it inhibited breast cancer cell proliferation and acted as a selective HDAC3 inhibitor in prostate cancer, downregulating E2F1/E2F3 pathways to induce caspase-3-mediated cell death. Gut-derived valeric acid from commensal bacteria has also been identified as a contributor to HDAC inhibition, suggesting microbiota-targeted interventions for oncology.^[51]^[52]^[53] Clinical and observational studies on short-chain fatty acids (SCFAs), including valeric acid, indicate roles in modulating gut health by influencing microbiota composition and reducing inflammation. Elevated fecal valeric acid levels in early childhood were associated with a lower incidence of eczema at school age, potentially through immune regulation. In adults, higher concentrations of valeric acid correlated with improved progression-free survival in colorectal cancer patients and protection against radiation-induced gut injuries in animal models, underscoring its potential in microbiota-based therapies for inflammatory bowel conditions and post-treatment recovery. However, direct clinical trials on valeric acid supplementation remain limited, with typical endogenous levels in feces ranging from 0.5-2.7 µmol/g feces, and no established therapeutic dosages or side effect profiles for isolated use.^[54]^[55]^[56]

Biological significance

Metabolic role

Valeric acid, also known as pentanoic acid, functions as a short-chain fatty acid (SCFA) primarily produced through the fermentation of dietary fibers by gut microbiota in the colon. This process involves anaerobic bacterial metabolism of undigested carbohydrates, where species such as those in the genus Megasphaera contribute significantly to valerate synthesis via lactate-driven pathways, generating valeric acid alongside more abundant SCFAs like acetate, propionate, and butyrate.^[57]^[58] In host metabolism, valeric acid is absorbed by colonocytes and activated in the cytosol to valeryl-CoA by acyl-CoA synthetases, particularly medium-chain variants that handle C4-C12 fatty acids. This thioesterification step, consuming ATP, enables transport into mitochondria via the carnitine shuttle, where valeryl-CoA undergoes β-oxidation. As an odd-chain fatty acid, this process produces one acetyl-CoA unit and one propionyl-CoA; propionyl-CoA is carboxylated to D-methylmalonyl-CoA, racemized, and converted to L-methylmalonyl-CoA, then to succinyl-CoA for entry into the citric acid cycle. The acetyl-CoA and reducing equivalents (NADH and FADH₂) yield ATP through the electron transport chain, while succinyl-CoA supports the citric acid cycle and can contribute to gluconeogenesis.^[59]^[60] This pathway integrates valeric acid into broader lipid metabolism, providing energy and contributing to lipogenesis or ketogenesis when glucose is limited.^[61] As an SCFA, valeric acid serves as an alternative energy substrate for colonocytes, supporting their oxidative phosphorylation and helping maintain epithelial integrity, though to a lesser extent than butyrate. Its metabolic flux within microbial ecosystems is regulated by substrate availability, pH, and interspecies interactions, with production rates varying based on dietary fiber composition and microbiota diversity; for instance, high-fiber diets enhance valerate output through cross-feeding among fermentative bacteria.^[61]^[57] The biochemical handling of valeric acid exhibits evolutionary conservation across mammals and bacteria, with homologous acyl-CoA synthetases and β-oxidation enzymes facilitating its catabolism in diverse taxa, reflecting an ancient adaptation for utilizing fermentation-derived volatiles in energy homeostasis. This conservation underscores the co-evolutionary interplay between host lipid metabolism and microbial fermentation pathways.^[62]^[63]

Health and toxicity

Valeric acid exhibits low acute toxicity via oral exposure, with reported LD₅₀ values ranging from 1,700–4,600 mg/kg in rats, indicating it is not highly poisonous in single doses but can cause adverse effects at elevated levels.^[15]^[6] It acts as a strong irritant and corrosive agent to skin and eyes, potentially causing severe burns, redness, and pain upon direct contact.^[6] Inhalation of vapors may lead to respiratory tract irritation, while ingestion can result in immediate gastrointestinal distress, including nausea, vomiting, and abdominal pain due to its acidic nature.^[6] Chronic exposure to valeric acid may provoke ongoing gastrointestinal upset, such as erosion of the esophageal and stomach linings, potentially leading to perforation or narrowing in severe cases.^[64] It is not classified as a carcinogen by the International Agency for Research on Cancer (IARC), with no evidence of oncogenic potential in available toxicological assessments.^[6] Primary exposure routes include dermal absorption, inhalation of vapors, and oral ingestion, with the compound metabolized primarily in the liver via β-oxidation to carbon dioxide, which is subsequently exhaled.^[65] As a short-chain fatty acid (SCFA) produced by gut microbiota, valeric acid demonstrates beneficial physiological effects, including anti-inflammatory actions in the intestinal mucosa by activating G-protein coupled receptors (GPR41 and GPR43), which help mitigate conditions like ulcerative colitis.^[65] It also contributes to blood glucose modulation by enhancing insulin sensitivity and reducing hepatic gluconeogenesis, supporting metabolic homeostasis.^[66] Post-2010 studies have elucidated valeric acid's interactions with the gut microbiome, revealing its role in modulating bacterial composition to protect against radiation-induced intestinal injury and enhance barrier integrity.^[67] For instance, supplementation with valeric acid from commensal bacteria like Bacteroides vulgatus has been shown to influence bone mineral density via microbiota-dependent pathways.^[68] Regarding neurological effects, recent research indicates neuroprotective properties, such as suppressing oxidative stress and neuroinflammation in dopaminergic neurons, potentially alleviating Parkinson's-like symptoms in preclinical models.^[69] However, elevated levels in aged microbiota contexts may exacerbate post-ischemic brain inflammation and worsen neurological outcomes.^[70] Valeric acid also acts as a histone deacetylase (HDAC) inhibitor and a ligand for free fatty acid receptor 2 (FFAR2, also known as GPR43), influencing gene expression and inflammatory responses. Typical concentrations in human feces are around 2.4 µmol/g wet weight.^[4]

Derivatives

Salts and esters

Salts of valeric acid are ionic compounds formed by the deprotonation of the carboxylic acid group through neutralization with bases such as metal hydroxides or amines, yielding carboxylate anions associated with cations. These salts, exemplified by calcium valerate, exhibit high solubility in water, which significantly improves the aqueous solubility of the hydrophobic valeric acid moiety and facilitates their incorporation into aqueous formulations. They serve as buffering agents in chemical and biological systems due to the conjugate base properties of the carboxylate, helping to resist pH changes near the pKa of valeric acid (approximately 4.8).^[71] Esters of valeric acid are covalent organic derivatives synthesized primarily via Fischer esterification, involving the reaction of the acid with an alcohol in the presence of an acid catalyst like sulfuric acid or p-toluenesulfonic acid, often under reflux conditions to drive water removal. Representative esters, such as ethyl valerate, are typically low-boiling liquids that are volatile and possess pleasant fruity odors, enhancing their utility in scent and flavor profiles. These esters demonstrate greater lipophilicity than the parent acid or its salts, promoting solubility in nonpolar solvents and organic phases.^[72]^[73] In terms of properties, valeric acid salts enhance overall solubility in polar media, making them suitable for applications requiring dispersion in water-based systems, while esters prioritize volatility for evaporative processes and lipophilicity for partitioning into lipid environments. Stability profiles differ notably: salts remain stable in neutral to mildly acidic aqueous conditions but may protonate in strong acids, whereas esters are prone to hydrolytic cleavage back to the acid and alcohol under acidic or basic catalysis, particularly at elevated temperatures.^[1]^[72] Analytical identification of these derivatives often relies on nuclear magnetic resonance (NMR) spectroscopy, where the -COO- group provides diagnostic signals. In 13C NMR, the carbonyl carbon of both salts and esters resonates between 170 and 180 ppm, with salts showing slightly downfield shifts due to ionic character. For esters, 1H NMR reveals the -O-CH2- protons at around 4.0-4.2 ppm, distinguishing them from the acid's -OH signal near 11-12 ppm./Spectroscopy/Magnetic_Resonance_Spectroscopies/Nuclear_Magnetic_Resonance/NMR%3A_Structural_Assignment/Interpreting_C-13_NMR_Spectra)

Notable examples

Sodium valerate, the sodium salt of valeric acid, serves as a food preservative and flavoring agent, inhibiting microbial growth in various products. Its antimicrobial properties make it suitable for extending shelf life in acidic food environments.^[74] Methyl valerate, an ester of valeric acid and methanol, acts as a flavoring agent in confectionery, imparting fruity notes reminiscent of apple. It has a boiling point of 127 °C, which contributes to its volatility in food applications.^[75] This compound is approved by the FDA as a synthetic flavoring substance for direct addition to food.^[75] Isobutyl valerate, formed from valeric acid and isobutanol, finds use in perfumes due to its crisp, sweet apple-like scent with subtle pear undertones. This fruity profile enhances fruity and fresh compositions in fragrance formulations.^[76] Valproate, the divalent anion derived from 2-propylvaleric acid—a branched derivative of valeric acid—plays a central role in antiepileptic medications such as valproic acid salts. It is widely prescribed for managing epilepsy, bipolar disorder, and migraine prophylaxis by modulating neuronal excitability.^[16]^[44] Amyl valerate, also known as pentyl pentanoate, has historical and commercial significance as a solvent in varnishes, coatings, and paints, where it aids in dissolving resins and improving application properties. Its use dates back to early industrial formulations for surface treatments.^[77]

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Acid Anhydride, (RCO)2O acyclic 6-membered ring 5-membered ring. C=O stretch (2 bands) 1750 & 1820 cm-1 1750 &1820 1785 & 1865. Conjugation lowers the C=O ...
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[13]
The Quiet Revolution - UC Press E-Books Collection
In his first paper on this subject Kolbe conceded that these were still preliminary results, but he stressed that they supported the copula formula for valeric ...
[14]
Valeric Acid | Fisher Scientific
Thermo Scientific Chemicals Valeric acid, 99%. CAS: 109-52-4 Molecular Formula ... IUPAC Name: pentanoic acid SMILES: CCCCC(=O)O. Pricing & Availability ...
[15]
[PDF] Inert Reassessment - Valeric acid (CAS Reg. No.109-52-4) | EPA
The WHO report of 1998 also stated that when valeric acid was given daily by tracheal intubation on days 6 to 15 of gestation, no evidence of fetotoxicity, ...
[16]
Valproic acid - American Chemical Society
Feb 28, 2022 · VPA has been known since at least the 1880s, when it was synthesized by American chemist Beverly S. Burton. In 1915, a monumental work on ...
[17]
and Five-Carbon [Butyric and Valeric] Short-Chain Fatty Acid ... - NIH
Feb 14, 2024 · Valeric acid, a five-carbon SCFA, is also produced naturally by specific members of the microbiota of the lower intestinal tract of chicken and ...
[18]
Valeric Acid - an overview | ScienceDirect Topics
It was originally discovered as an analogue of valeric acid found naturally in a herb valerian root, a dietary supplement which may have sedative and anxiolytic ...
[19]
Formation of Volatile Free Fatty Acids During Ripening of Cheddar ...
Branched-chain fatty acids such as 4-ethyloctanoic and 4-methyloctanoic acids have intense aromas, and even minute quantities can affect the flavor of dairy ...
[20]
valeric acid, 109-52-4 - The Good Scents Company
Food Additive: Functional use(s) - flavor and fragrance agents. Has a cheesy type odor and an acidic type flavor.Missing: Kolbe 1844
[21]
Lipid metabolism in anaerobic ecosystems - PubMed
Many rumen bacteria have specific growth requirements for fatty acids such as n-valeric, iso-valeric, 2-methylbutyric, and iso-butyric acids.
[22]
An optimized reverse β-oxidation pathway to produce selected ...
Apr 26, 2023 · The reverse β-oxidation pathway is an energy-efficient pathway that produces medium-chain fatty acids in microorganisms, and its use in ...Missing: valeric | Show results with:valeric
[23]
(PDF) Electrosynthesis of valeric acid - ResearchGate
Dec 15, 2017 · Electrochemical reduction of levulinic acid to valeric acid was already discovered in 1911 by Tafel and Emmert at lead and mercury cathodes ...
[24]
What are the synthesis methods and application fields of Valeric acid?
Synthesis method Valeric acid can be prepared by the oxidation of n-pentanol, n-valeraldehyde or the reaction of formic acid and 1-butene. The n-amyl alcohol ...
[25]
PENTANOIC ACID - Ataman Kimya
In industry, Pentanoic acid is produced by the oxo process from 1-butene and syngas, forming valeraldehyde, which is oxidised to the final product. H2 + CO + ...
[26]
Fermentation for the production of biobased chemicals in a circular ...
Jul 21, 2022 · This article provides an overview of currently available fermentation technologies that have the potential to play a role in the production of biobased bulk ...
[27]
[PDF] Riboflavin Boosts Fermentative Valeric Acid Generation from Waste ...
Apr 8, 2020 · Riboflavin in this study was considered as a feasible chemical to enhance the fermentative valeric acid generation coupled to MLVSS reduction, ...
[28]
Biobased short and medium chain fatty acids - Our products - AFYREN
Historically, valeric acid has always been produced through an oxo-process with no biobased alternative. AFYREN offers 100% biobased valeric acid. Feedstock ...
[29]
[PDF] pka-compilation-williams.pdf - Organic Chemistry Data
Apr 7, 2022 · α-keto-β-methyl valeric 2.3. 6. NCS-. 3.58. 20. Lactic. 3.86. 6. CH3CO ... Compound. pK. Ref. Chromotropic acid. 5.36, 15.6. 6. Resorcinol. --, ...
[30]
[PDF] 5.310 (F19) Fischer Esterification Lab Manual - MIT OpenCourseWare
Pour the Organic layer into a 400-. mL clean dry beaker. Extract the Organic layer with two 40 mL aliquots of 5% sodium bicarbonate solution to remove any ...
[31]
Video: Esterification - Prep - JoVE
Mar 26, 2020 · With a 1:1 mixture of carboxylic acid and alcohol, the esterification reaction reaches equilibrium with about 70% yield of the ester. By ...Learning Objectives · What Is The General... · How Is An Ester Formed?
[32]
Engineering the composition of co-polyesters synthesized by ...
Co-polyesters of 3-hydroxybutyrate and 3-hydroxyvalerate were produced by Alcaligenes eutrophus H16 from valeric or propionic acid under both air and ...
[33]
Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate ...
Methods and results: We applied a new method of 3-hydroxyvalerate (3HV) monomer synthesis to produce a co-polymer by the introduction of a propionyl-CoA ...Missing: valeric | Show results with:valeric
[34]
Conversion of carboxylic acids to alcohols using LiAlH4
Jan 22, 2023 · Carboxylic acids can be converted to 1 o alcohols using Lithium aluminum hydride (LiAlH 4 ). Note that NaBH 4 is not strong enough to convert carboxylic acids ...
[35]
Reduction of Carboxylic Acids and Esters using LiAlH4 to 1o alcohols
Carboxylic acids and esters are less reactive to Nu than aldehydes or ketones · As a result they can only be reduced by LiAlH4 but NOT by the less reactive NaBH ...
[36]
10 Catalytic Strategies and Chemistries Involved in the Conversion ...
Butane is formed through decarboxylation/decarbonylation of pentanoic acid followed by hydrogenation, and pentane can be obtained by hydrogenation/dehydration/ ...
[37]
The Hell–Volhard–Zelinsky Reaction - Master Organic Chemistry
May 14, 2025 · The Hell-Volhard-Zelinsky reaction converts a carboxylic acid to an alpha-bromo carboxylic acid. Mechanism, examples, quizzes and more.
[38]
Bromination Next to the Carboxy Group: The Hell-Volhard-Zelinsky ...
Jul 18, 2015 · Carboxylic acids, can be brominated in the alpha position with a mixture of Br 2 and PBr 3 in a reaction called the Hell-Volhard-Zelinskii reaction.
[39]
Method of producing carboxylic acid amides - Google Patents
As the carboxylic acid butyric acid, valeric acid or isovaleric acid are used , and as the amine cyclohexylamine, piperidine or morpholine are used.Missing: valeramides | Show results with:valeramides
[40]
Ketonization of Valeric Acid to 5‐Nonanone Over Metal Oxides ...
Nov 26, 2024 · The transformation of VA to 5-nonanone is achieved through ketonization, a process that couples two carboxylic acids into a longer-chain ketone ...Missing: elongation | Show results with:elongation
[41]
[PDF] Valeric Acid - NJ.gov
It is used as an intermediate for flavors and perfumes, and in lubricants, plasticizers and pharmaceuticals. REASON FOR CITATION. * Valeric Acid is on the ...<|separator|>
[42]
Valeric Acid - Perstorp
Valeric Acid (Pentanoic acid) is a high purity carboxylic acid. Valeric Acid is used as chemical intermediate in esters for synthetic lubricants.
[43]
Valproic Acid - StatPearls - NCBI Bookshelf
Mar 19, 2024 · Valproic acid (VPA) ia as a highly prevalent medication with multifaceted therapeutic applications in various neurological and psychiatric disorders.
[44]
Valeric Acid Market Size, Trends, Growth, Share & Forecast
Rating 4.9 (48) Valeric Acid Market size was valued at USD 1.2 Billion in 2024 and is projected to reach USD 2.3 Billion by 2032, growing at a CAGR of 8.4%Missing: tons | Show results with:tons
[45]
Valeric Acid Market Size, Trends & Forecast 2024-2034 | TMR
Jan 13, 2025 · Valeric Acid Market valued at US$ 186.3 Mn in 2023, is projected to grow at a 7.2% CAGR, reaching US$ 396.1 Mn by 2034. Explore trends in ...Missing: annual | Show results with:annual
[46]
https://www.transparencymarketresearch.com/valeric-acid-market.html
[47]
Valproic Acid Basic Seizure Medication - Epilepsy Foundation
Apr 17, 2024 · The only FDA-approved use of valproic acid is the treatment of epilepsy, but it also has two off-label uses: preventing migraine headaches (not ...
[48]
In Vitro Antimicrobial Activities of Organic Acids and Their ... - NIH
Oct 19, 2019 · Results in the current study suggest that valeric acid has similar antimicrobial activity against G− and G+ bacteria in comparison to butyric ...Missing: topical formulations
[49]
Valeric Acid Glyceride Esters in Feed Promote Broiler Performance ...
Valeric acid is a C5 fatty acid, naturally produced in low concentrations by specific members of the microbiota of the lower intestinal tract.Missing: antimicrobial properties topical formulations
[50]
Valeric Acid Suppresses Liver Cancer Development by Acting as a ...
We demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor.
[51]
Valerian and valeric acid inhibit growth of breast cancer cells ...
Jan 28, 2021 · Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications · Results. Valerian and valeric ...Missing: pentanoic | Show results with:pentanoic
[52]
Valeric acid acts as a novel HDAC3 inhibitor against prostate cancer
Sep 29, 2022 · The findings suggest that VA acts as a HDAC3 inhibitor with anti-cancer effect on prostate cancer by regulating E2F1/E2F3/CASP3 axis.
[53]
Fecal short chain fatty acids in children living on farms and a link ...
Dec 31, 2020 · Our findings suggest that farm-related protection from allergy may be mediated in part by fecal valeric acid, or by characteristics of the gut ...<|separator|>
[54]
Association of Short-Chain Fatty Acids in the Gut Microbiome With ...
Apr 16, 2020 · High concentrations of fecal acetic acid, propionic acid, butyric acid, and valeric acid were significantly associated with longer progression-free survival.
[55]
Gut commensal derived-valeric acid protects against radiation injuries
Our findings provide new insights into gut microbiota-produced VA and underpin that VA might be employed as a therapeutic option to mitigate radiation injury.
[56]
Megasphaera contributes to lactate-driven valerate production in the ...
Oct 21, 2025 · The human gut microbiota produces short-chain carboxylic acids (SCCA) through fermentation of undigested carbohydrates, and through chain ...
[57]
Does isovaleric acid play a key role in the interaction between ...
May 27, 2025 · The hypothesized interplay between microbiota-gut-brain-axis, fecal short-chain fatty acids (SCFAs), probiotics and antidepressants.Missing: decomposition | Show results with:decomposition
[58]
Acyl-coenzyme A synthetases in metabolic control - PMC - NIH
Acyl-CoA synthetases activate long-chain fatty acids, directing them into metabolic pathways. They catalyze a two-step reaction, and their individual functions ...Fatty Acid Channeling · Effect Of Fatty Acid... · Figure 1. Activation Of...
[59]
Biochemistry, Fatty Acid Oxidation - StatPearls - NCBI Bookshelf - NIH
The final step in Beta oxidation involves cleavage of the bond between the alpha and beta carbon by CoA. This step is catalyzed by beta-keto thiolase and is a ...
[60]
Short- and medium-chain fatty acids in energy metabolism - NIH
Cow milk and milk products remain the main dietary source of SCFAs, mainly butyric acid, in adult humans. Other natural sources of MCFAs and SCFAs are coconut ...Origin Of Scfas And Mcfas · Fueling The Tissue Energy... · Potential Adverse Effects
[61]
Ecophylogenetics Clarifies the Evolutionary Association between ...
Sep 11, 2018 · Mammalian evolution associates with conserved clades of bacteria. We ... For example, 66 clades associated with the short-chain-fatty-acid ...
[62]
Evolutionarily related host and microbial pathways regulate fat ...
Feb 19, 2024 · The microbial metabolites, short-chain fatty acids, regulate colonic T reg cell homeostasis. Science (80-.) 341, 569–573 (2013). Article ADS ...
[63]
https://www.nature.com/articles/s41467-024-45782-2
[64]
[PDF] SAFETY DATA SHEET - Fisher Scientific
Sep 9, 2014 · Valeric acid. Cat No. : AC149570000; AC149570010; AC149570025 ... LD50 Oral. LD50 Dermal. LC50 Inhalation. Valeric acid. 4600 mg/kg ( Rat ).
[65]
[PDF] Safety Data Sheet: n-Valeric acid - Carl ROTH
oral. LD50. 4.600 mg/kg rat. ECHA dermal. LD50. >2.000 mg/kg rat. ECHA. Skin corrosion/irritation. Causes severe skin burns and eye damage. Serious eye damage/ ...
[66]
Valeric Acid: A Small Molecule with Big Impacts on Human Health
Valeric acid was first isolated in the mid-19th century from the root of Valeriana officinalis, a plant historically used as a sedative. The name "valeric" is ...
[67]
Gut microbiota-derived short chain fatty acids are potential ...
Dec 29, 2021 · Short chain fatty acids (SCFA) are the gut microbiota metabolites produced from fermentation of non-digestible carbohydrates, and have been reported to ...
[68]
Gut commensal derived-valeric acid protects against radiation injuries
Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure.
[69]
Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid ...
Oct 27, 2023 · Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people.
[70]
Valeric Acid Protects Dopaminergic Neurons by Suppressing ...
Oct 16, 2020 · In our study, we found that Val prevented rotenone induced upregulation of pro-inflammatory cytokine oxidative stress, and α-synuclein expression.
[71]
Gut microbiota of old mice worsens neurological outcome after brain ...
Sep 12, 2023 · Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia.
[72]
Carboxylic Acid Reactivity - MSU chemistry
Carboxylic acids react with bases to form salts, undergo substitution of the hydroxyl hydrogen, and can be reduced to alcohols.<|control11|><|separator|>
[73]
Carboxylic Acid Reactivity - MSU chemistry
Carboxylic acids and salts having alkyl chains longer than six carbons exhibit unusual behavior in water due to the presence of both hydrophilic (CO2) and ...
[74]
ethyl valerate, 539-82-2
Odor Type: fruity. Odor Strength:high , recommend smelling in a 10.00 % solution or less. Substantivity:4. sweet fruity apple pineapple green tropical.EU/US · Properties · Organoleptics · Blenders
[75]
Sodium pentanoate | Solubility of Things
Biological Relevance: Sodium pentanoate can be utilized as a food preservative, helping to inhibit the growth of bacteria and fungi in various food products.
[76]
Methyl valerate | C6H12O2 | CID 12206 - PubChem - NIH
3.2.2 Boiling Point. 259.7 °F at 760 mmHg (NTP, 1992).
[77]
Isobutyl Valerate: The Complete Guide To This Aroma Chemical ...
Isobutyl Valerate is a simple fruity ester that smells like crisp sweet apple with a whisper of pear. It is affordable easy to blend and stable in almost any ...
[78]
Pentyl Pentanoate CAS 2173-56-0 - Henan Alfa Chemical Co., Ltd
Application： - Industrial use: Amyl valerate is mainly used as a solvent, which can be used in coating, painting, ink and cleaning agent. - ...Missing: varnishes | Show results with:varnishes