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Butyronitrile

Butyronitrile, also known as butanenitrile or propyl cyanide, is a straight-chain nitrile with the C₄H₇N and CH₃CH₂CH₂CN, consisting of a attached to a cyano . This compound appears as a clear, colorless at , with a molecular weight of 69.11 g/, a of −112 °C, a of 115–117 °C, and a of 0.794 g/mL at 25 °C. It is slightly soluble in (approximately 3% at 77 °F) but miscible with most polar solvents such as alcohols, ethers, and , and its vapors are heavier than air. Butyronitrile is primarily employed as a chemical intermediate in organic synthesis, serving as a precursor to compounds like n-butylamine, butanamide, and butyric acid, and playing a key role in the production of the poultry coccidiostat drug amprolium. It also finds applications as an industrial solvent due to its high polarity and solvating power, particularly in the manufacture of pharmaceuticals, agrochemicals, and other fine chemicals, as well as in research and development for new materials. Industrially, it is produced via the catalytic gas-phase ammoxidation of butanal or butanol with ammonia. Despite its utility, butyronitrile is highly hazardous, classified as a with a of 16.7 °C (62 °F) and capable of forming mixtures with air. It is acutely toxic by , contact, and , with an oral LD50 of 0.14 g/kg in rats, and exposure can cause symptoms such as , , and due to cyanide release. Butyronitrile reacts vigorously with strong oxidizers, acids, bases, and reducing agents, potentially releasing toxic or nitrogen oxides upon combustion or decomposition, and it is incompatible with metals that may catalyze . Occupational exposure limits are set at a time-weighted average of 8 (22 /m³).

Chemical identity

Molecular structure

Butyronitrile has the molecular formula C₄H₇N. Its is CH₃CH₂CH₂CN, consisting of a linear propyl chain (CH₃CH₂CH₂-) attached to a cyano group (-CN). This arrangement represents the straight-chain isomer of butanenitrile. The molecule features a four-carbon backbone where the terminal carbon is part of the functional group, characterized by a carbon-nitrogen (C≡N). The carbon atom in the group is hybridized, forming a linear with a bond angle of 180° at the carbon. Similarly, the nitrogen atom is hybridized, contributing to the through one σ bond and two π bonds. The C≡N is approximately 1.16 , reflecting the strong character typical of organic s. Butyronitrile (n-butyronitrile) is distinguished from its branched , isobutyronitrile (2-methylpropanenitrile), which has the (CH₃)₂CHCN and features a isopropyl group attached to the cyano moiety. These isomers share the same molecular but differ in carbon chain arrangement, leading to variations in their physical and chemical behaviors.

Nomenclature

Butanenitrile is the for the compound with the CH₃CH₂CH₂CN, reflecting the systematic for nitriles where the suffix "-nitrile" is added to the name of the parent chain including the carbon of the cyano group. Commonly referred to as n-butyronitrile, propyl , or 1-cyanopropane, the name "butyronitrile" derives from —the four-carbon from which it is conceptually related—by substituting the "-ic acid" ending with "-" to denote the -CN . The term "" itself was coined by German chemist in 1832 to describe organic cyanides, building on the 1782 isolation of by during investigations into the composition of . This compound is identified by the 109-74-0 and has a molecular weight of 69.11 g/.

Physical properties

Appearance and thermodynamic data

Butyronitrile is a clear, colorless at with a sharp, suffocating . Key thermodynamic properties include a of −112 °C and a of 117 °C under standard pressure. The compound exhibits a of 17 °C (closed ), indicating high flammability. At 20 °C, butyronitrile has a of 0.794 g/cm³ and a of 2 kPa; its vapors are heavier than air, with a vapor of approximately 2.4 relative to air.

Solubility and density

Butyronitrile exhibits a of 0.794 g/cm³ at 20 °C, which is characteristic of many aliphatic nitriles due to their relatively low molecular weight and linear structure. This value decreases with increasing temperature, reflecting typical volumetric expansion in organic liquids. The compound demonstrates limited in , with approximately 3.3 g/100 mL at 25 °C, indicating poor that aligns with the hydrophobic nature of longer-chain nitriles compared to shorter analogs like . In contrast, butyronitrile is miscible with polar organic solvents such as , , and acetone, facilitating its use in and extractions. It is also soluble in , a nonpolar aromatic , though to a lesser extent than in polar media. The (log P) of butyronitrile is 0.53, signifying moderate that influences its distribution between aqueous and lipid phases in environmental and biological contexts. This value, derived from experimental measurements, underscores the 's balanced for both hydrophilic and hydrophobic environments.

Chemical properties

Reactivity and stability

Butyronitrile exhibits good under normal ambient conditions, remaining unreactive at without exposure to incompatible materials or extreme environments. It maintains integrity during standard storage and transport, with an NFPA instability rating of 0, indicating no inherent tendency toward hazardous reactions under typical handling scenarios. The group (-C≡N) in butyronitrile is prone to under acidic or basic , yielding as the primary product along with or species. This proceeds via nucleophilic attack by , facilitated by H₃O⁺ or OH⁻, to form intermediates such as butanamide before full conversion to CH₃CH₂CH₂CO₂H and NH₄⁺/NH₃; the process is exothermic and requires careful control to manage heat generation. Additionally, the electron-deficient nitrile carbon undergoes with organometallic reagents like Grignard compounds (RMgX), forming an intermediate that hydrolyzes to a , enabling carbon-carbon bond formation in synthetic applications. Butyronitrile reacts vigorously with strong oxidizing agents, such as peroxides, potentially leading to exothermic decompositions and the release of toxic oxides (NOₓ). Upon heating to decomposition, it breaks down into hazardous fragments, including (HCN) and other cyanide-containing fumes, alongside NOₓ; this thermal instability underscores the need for controlled temperatures to prevent unintended .

Spectroscopic data

Butyronitrile exhibits characteristic spectroscopic features that aid in its identification, primarily due to the functional group and the alkyl chain. In infrared (IR) , the most prominent feature is the strong C≡N stretching vibration, appearing as a sharp absorption at approximately 2250 cm⁻¹. This is typical for aliphatic nitriles and confirms the presence of the -C≡N moiety. Nuclear magnetic resonance (NMR) spectroscopy provides detailed structural information. The ¹H NMR spectrum in CDCl₃ displays three distinct signals corresponding to the propyl chain: the terminal methyl group (CH₃) as a triplet at δ ≈ 1.0 ppm (3H, J ≈ 7 Hz), the middle methylene group (CH₂) as a sextet at δ ≈ 1.7 ppm (2H, J ≈ 7 Hz), and the methylene adjacent to the cyano group (CH₂CN) as a triplet at δ ≈ 2.3 ppm (2H, J ≈ 7 Hz). These multiplicities arise from vicinal coupling in the -CH₂-CH₂-CH₃ segment. In ¹³C NMR, the quaternary carbon of the nitrile group (C≡N) resonates at δ ≈ 120 ppm, while the alpha carbon (CH₂CN) appears at δ ≈ 17 ppm; the other carbons are observed around 13 ppm (CH₃) and 20 ppm (middle CH₂).
NucleusPositionChemical Shift (δ, ppm)Multiplicity/Notes
¹HCH₃≈1.0Triplet (3H)
¹H-CH₂-≈1.7Sextet (2H)
¹H-CH₂CN≈2.3Triplet (2H)
¹³CC≡N≈120Quaternary
¹³CCH₂CN≈17-
Mass spectrometry (MS) of butyronitrile under shows the molecular [M]⁺ at m/z 69, consistent with the C₄H₇N. The base peak occurs at m/z 41. Other notable fragments include m/z 54, m/z 29, m/z 27, and m/z 28 (from CN⁺).

Synthesis and production

Industrial synthesis

Butyronitrile is primarily produced on an industrial scale through the ammoxidation of n-butanol or butanal with ammonia and oxygen over metal oxide catalysts at elevated temperatures of 400-500 °C. The balanced reaction for n-butanol is typically represented as: \ce{CH3(CH2)3OH + NH3 + 1.5 O2 -> CH3(CH2)2CN + 3 H2O} For butanal, the reaction is \ce{CH3CH2CH2CHO + NH3 + 0.5 O2 -> CH3CH2CH2CN + H2O}. This method leverages the dehydrogenation and oxidative conversion of the substrate to the corresponding nitrile, with catalysts such as nickel-alumina or zinc oxide promoting selectivity and efficiency. The process operates in the gas phase, allowing for continuous production and integration with downstream purification steps like distillation to isolate the product. Modern plants employing optimized catalysts and designs achieve yields exceeding 90%, minimizing byproducts and enhancing economic viability.

Laboratory preparation

Butyronitrile can be prepared in the through the of butyramide, a primary , using strong dehydrating agents such as (P₂O₅) or (POCl₃). The with P₂O₅ involves heating a mixture of butyramide and the dehydrating agent, typically in a 1:2 molar ratio, under conditions around 150–200°C, allowing the to distill directly from the mixture as is eliminated. The process is represented by the equation: \ce{CH3CH2CH2CONH2 ->[P2O5][\Delta] CH3CH2CH2CN + H2O} This method is straightforward for small-scale synthesis and yields butyronitrile in moderate to good efficiency, often 70–80%, depending on the purity of the starting amide. Alternatively, POCl₃ serves as a milder dehydrating agent, reacting with butyramide at lower temperatures (around 60–100°C) in an inert solvent like dichloromethane, forming a chlorophosphonium intermediate that facilitates elimination of HCl and water to afford the nitrile. The equation is analogous: \ce{CH3CH2CH2CONH2 ->[POCl3] CH3CH2CH2CN + H3PO4 + HCl} This variant is preferred when avoiding high temperatures that might lead to side reactions with sensitive substrates. Another established laboratory route employs nucleophilic substitution of 1-bromopropane with sodium cyanide (NaCN), leveraging the SN2 mechanism suitable for primary alkyl halides. The reaction is conducted by dissolving 1-bromopropane and an excess of NaCN in dimethyl sulfoxide (DMSO) at room temperature (20–25°C) for 1–4 hours, promoting efficient cyanide displacement due to the polar aprotic nature of the solvent. The transformation is depicted as: \ce{CH3CH2CH2Br + NaCN ->[DMSO][rt] CH3CH2CH2CN + NaBr} Yields typically range from 80–95%, making this a high-efficiency method for preparative scales up to several grams. Regardless of the synthetic route, purification of butyronitrile is essential to remove unreacted starting materials, salts, or byproducts. The crude product is first extracted into an organic solvent such as diethyl ether, washed with water or dilute acid to eliminate ionic impurities, and dried over a desiccant like calcium chloride. Final isolation is achieved by fractional distillation under reduced pressure (e.g., 50–100 mmHg, collecting at 40–50°C) to minimize thermal decomposition, as nitriles can polymerize or hydrolyze at atmospheric boiling points above 117°C. This approach ensures high purity (>95%) for laboratory use. These bench-scale techniques parallel industrial syntheses in principle but emphasize safer, batch-wise operations with readily available reagents.

Applications

Pharmaceutical synthesis

Butyronitrile plays a crucial role as a synthetic intermediate in the production of amprolium, a thiamine antagonist employed as a coccidiostat to control coccidiosis in poultry. The synthesis begins with the conversion of butyronitrile to butyramidine hydrochloride via reaction with ammonia and hydrogen chloride. This amidine then undergoes condensation with ethoxymethylenemalononitrile in the presence of sodium ethoxide to afford 2-propyl-4-amino-5-cyanopyrimidine. Subsequent steps include catalytic reduction of the cyano group to the aminomethyl derivative using Raney nickel, diazotization and hydrolysis to the hydroxymethyl compound with sodium nitrite, halogenation (typically with hydrobromic acid) to the bromomethyl pyrimidine, and final quaternization with 2-methylpyridine to yield 1-[(4-amino-2-propyl-5-pyrimidinyl)methyl]-2-picolinium chloride hydrochloride (amprolium hydrochloride). This patented route, developed by Merck & Co., involves alkylation in the key quaternization step and demonstrates high efficiency, with reported yields exceeding 95% in the final stage. In the synthesis of etifelmine, an agent, butyronitrile serves as a reactant in the initial base-catalyzed aldol-type addition to , generating 2-[hydroxy(diphenyl)methyl]butanenitrile as the key intermediate. This is then hydrolyzed under acidic or basic conditions to the corresponding , followed by activation and coupling with , and reduction to form the target secondary structure. The process typically proceeds in 2-3 steps from the butyronitrile-derived , leveraging the reactivity of the group for efficient transformation into the .

Industrial and other uses

Butyronitrile serves as an industrial solvent in various chemical processes, particularly in and reactions, owing to its and ability to dissolve organic compounds such as polymers and resins. It has been employed in the of aromatic nitriles and controlled polymerizations, where it facilitates reaction mixtures without interfering significantly with activity. Additionally, its use extends to niche applications like the fabrication of molecularly imprinted polymers for technologies, leveraging its solvating properties in porogenic solutions. As a chemical intermediate, butyronitrile is primarily utilized as a precursor for the of aliphatic amines, such as , through selective catalytic over metal-supported catalysts like or on silica. This process yields high selectivity for primary amines, with finding applications in the production of , pharmaceuticals, and other specialty chemicals. It also serves as a starting material for butanamide and derivatives via or amidation routes. Global consumption of butyronitrile is estimated at several thousand tons annually, driven mainly by its role in specialty chemical , with market valuations projected between 20 and 40 million USD by 2025.

Occurrence

Interstellar detection

Butyronitrile, also known as n-propyl cyanide (n-C₃H₇CN), was first detected in the toward the high-mass star-forming region B2(N) through radio observations with the IRAM 30 m . The detection, reported in , identified multiple unblended transitions of its conformer, yielding column densities of approximately 1.5 × 10¹⁶ cm⁻² and 6.6 × 10¹⁵ cm⁻² for two velocity components, corresponding to an abundance of about 10⁻⁹ relative to H₂ under local assumptions at 150 K. Subsequent high-resolution observations with the Atacama Large Millimeter/submillimeter Array () in 2012 confirmed the presence of n-butyronitrile, resolving over 120 spectral features and refining its abundance to around 3 × 10⁻⁸ relative to H₂. The molecule's linear carbon chain and cyano group (-) provide a significant (approximately 3.7 D for the anti conformer), enabling its identification through rotational transitions in the millimeter-wave regime. These observations in B2(N), a dense hot core near the , highlight butyronitrile as one of the largest unambiguously detected organic molecules at the time, alongside its branched iso-propyl cyanide, which was identified concurrently with at a comparable abundance of about 0.4. Astrochemical models suggest that butyronitrile forms primarily through grain-surface processes in molecular clouds, involving sequential radical additions such as CH₃ or CH₂ to smaller nitriles like (CH₃CN) or ethyl cyanide (C₂H₅CN) within ice mantles, followed by desorption into the gas phase. Gas-phase ion-molecule reactions, such as CN radical addition to (C₃H₆), may contribute secondarily, particularly in warmer environments like hot cores. These mechanisms underscore the role of both dust grain catalysis and gas-phase chemistry in building complex organics from simpler precursors. The detection of butyronitrile demonstrates the prevalence of extended carbon-chain molecules in star-forming regions, reflecting advanced under interstellar conditions and providing insights into the chemical toward prebiotic compounds. Its presence, along with related nitriles, supports models of hydrocarbon-nitrile chemistry driven by cosmic-ray induced processes and thermal desorption, contributing to the molecular complexity observed in regions capable of forming planetary systems.

Potential natural sources

Butyronitrile exhibits no significant natural occurrence on , with no reports of its presence in biological pathways, such as cyanogenic processes in or , nor in geological samples like sediments or minerals. Comprehensive reviews of nitrile-containing natural products from diverse , including , fungi, , and marine sponges, document over 190 compounds but omit butyronitrile entirely, indicating its absence from known biosynthetic routes. Although nitriles generally can form as trace byproducts during high-temperature processes like in wildfires, specific evidence for butyronitrile remains unconfirmed, with detected emissions limited to simpler variants such as , , , and propanenitrile at levels typically below . Similarly, volcanic emissions contain trace heteroatomic organics including nitriles, but analyses of gases from sites like , , identify no aliphatic C4 nitriles like butyronitrile, suggesting any potential formation would be negligible and below detection thresholds. In comparison, simpler nitriles like are well-documented in burning emissions, serving as atmospheric tracers due to their release from protein and , whereas butyronitrile's demands specific C4 chain precursors not prevalent in natural or geological settings. This terrestrial rarity contrasts with its detection in environments, underscoring butyronitrile's predominantly origin on .

Safety and toxicology

Health effects and hazards

Butyronitrile exerts its toxicity primarily through metabolic conversion to (HCN) in the liver via P450-mediated oxidation at the alpha-carbon, forming a intermediate that liberates ; this then inhibits in the mitochondrial , disrupting and leading to . The oral LD50 in rats is approximately 140 mg/kg, indicating high . Acute exposure to butyronitrile via or dermal can cause severe to the eyes, skin, and , with symptoms including , , , , weakness, , convulsions, dyspnea, and ; high concentrations may progress to and death due to . Its vapor density greater than air contributes to accumulation in low-lying areas, heightening risk. Repeated low-level exposure to butyronitrile may result in chronic effects such as potential , including delayed neurological sequelae like or from cumulative burden, and persistent . Limited data exist on long-term outcomes, but cyanide-derived effects suggest risks to the with prolonged contact. Under the Globally Harmonized System (GHS), butyronitrile is classified as acutely toxic, with hazard statements H301 (toxic if swallowed), H311 (toxic in contact with skin), and H331 (toxic if inhaled), reflecting its rapid absorption and systemic effects. Regarding carcinogenicity, butyronitrile is not classifiable as to its carcinogenicity to humans (IARC Group 3), as it is not listed by the .

Handling and regulations

Butyronitrile should be handled in a well-ventilated or setting to minimize of vapors, with all sources of ignition avoided due to its flammability. (PPE) is essential, including chemical-resistant gloves such as (0.7 mm thickness, breakthrough time 480 minutes) or for splash protection (0.4 mm thickness, breakthrough time 30 minutes), safety goggles, a with Type A filter, and flame-retardant antistatic clothing. For storage, it must be kept in a cool, dry, well-ventilated area in tightly sealed containers, away from incompatible materials like strong oxidizers and acids, and protected from heat and sparks. In case of spills, immediately ventilate the area, cover nearby drains to prevent entry into waterways, and absorb the liquid using an inert material such as or a commercial absorbent; the collected waste should then be disposed of as hazardous material, with cleanup performed by trained personnel wearing appropriate . Occupational exposure limits for butyronitrile include a NIOSH recommended exposure limit (REL) of 8 ppm (22 mg/m³) as a time-weighted average (TWA) over a 10-hour workday, while the OSHA permissible exposure limit (PEL) has not been established. In the European Union, butyronitrile is registered under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) with EC number 203-700-6 and no specific use restrictions beyond general hazard classifications for flammability and toxicity. For transportation, it is classified as UN 2411, Hazard Class 3 (flammable liquid) with a subsidiary hazard of 6.1 (toxic), Packing Group II, requiring proper labeling and packaging to prevent leaks or ignition. Environmentally, butyronitrile is readily biodegradable under aerobic conditions, achieving 69% degradation in 28 days according to OECD Test Guideline 301D, though it poses a hazard to aquatic life with an LC50 greater than 107 mg/L for fathead minnow (Pimephales promelas) over 96 hours. Waste disposal should involve incineration in a chemical incinerator equipped with an afterburner and scrubber to ensure complete combustion and minimize emissions, in compliance with local regulations for hazardous waste. These precautions are necessitated by butyronitrile's acute toxicity and potential to release harmful vapors.

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