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Formamide
Formamide
Formamide
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Formamide
Structural formula of the formamide molecule
Structural formula of the formamide molecule
Ball and stick model of formamide
Ball and stick model of formamide
Space-filling model of the formamide molecule
Space-filling model of the formamide molecule
Names
Preferred IUPAC name
Formamide[1]
Systematic IUPAC name
Methanamide
Other names
Carbamaldehyde
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.766 Edit this at Wikidata
EC Number
  • 200-842-0
KEGG
UNII
  • InChI=1S/CH3NO/c2-1-3/h1H,(H2,2,3) checkY
    Key: ZHNUHDYFZUAESO-UHFFFAOYSA-N checkY
  • InChI=1/CH3NO/c2-1-3/h1H,(H2,2,3)
    Key: ZHNUHDYFZUAESO-UHFFFAOYAQ
  • O=CN
Properties
CH3NO
Molar mass 45.04 g/mol
Appearance Colorless, oily liquid[2]
Density 1.133 g/cm3
Melting point 2 to 3 °C (36 to 37 °F; 275 to 276 K)
Boiling point 210 °C (410 °F; 483 K)
Miscible
Vapor pressure 0.08 mmHg at 20 °C
Acidity (pKa) 23.5 (in DMSO)[3]
−2.19×10−5 cm3/mol
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point 154 °C (309 °F; 427 K) (closed cup)
NIOSH (US health exposure limits):
PEL (Permissible)
 none[2]
REL (Recommended)
 TWA 10 ppm (15 mg/m3) [skin][2]
IDLH (Immediate danger)
 N.D.[2]
Related compounds
Related compounds
 Carbamic acid
Dimethylformamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Formamide is an amide derived from formic acid. It is a colorless liquid which is miscible with water and has an ammonia-like odor. It is chemical feedstock for the manufacture of sulfa drugs and other pharmaceuticals, herbicides and pesticides, and in the manufacture of hydrocyanic acid. It has been used as a softener for paper and fiber. It is a solvent for many ionic compounds. It has also been used as a solvent for resins and plasticizers.[4] Some astrobiologists suggest that it may be an alternative to water as the main solvent in other forms of life.[5]

Formamides are compounds of the type RR′NCHO. One important formamide is dimethylformamide, (CH3)2NCHO.

Production

[edit]

Historical production

[edit]

In the past, formamide was produced by treating formic acid with ammonia, which produces ammonium formate, which in turn yields formamide upon heating:[6]

HCOOH + NH3 → HCOO−
NH+
4
HCOO−
NH+
4 → HCONH2 + H2O

Formamide is also generated by aminolysis of ethyl formate:[7]

HCOOCH2CH3 + NH3 → HCONH2 + CH3CH2OH

Modern production

[edit]

The current industrial process for the manufacture of formamide involves the carbonylation of ammonia:[4]

CO + NH3 → HCONH2

An alternative two-stage process involves the ammonolysis of methyl formate, which is formed from carbon monoxide and methanol:

CO + CH3OH → HCOOCH3
HCO2CH3 + NH3 → HCONH2 + CH3OH

Applications

[edit]

Formamide is used in the industrial production of hydrogen cyanide. It is also used as a solvent for processing various polymers such as polyacrylonitrile.[8]

It is also known that formamide is an excellent swelling agent for cellulosic fibres,[9] and is used in some specific wood-related applications.

Reactions

[edit]

Formamide decomposes into carbon monoxide and ammonia when heated above 100 °C.

HCONH2 → CO + NH3

The reaction is slow below 160 °C, but accelerates thereafter. At very high temperatures, the reaction products shift to hydrogen cyanide (HCN) and water instead:

HC(O)NH2 → HCN + H2O

The same effect occurs in the presence of solid acid catalysts.[8]

Niche or laboratory applications

[edit]

Formamide is a constituent of cryoprotectant vitrification mixtures used for cryopreservation of tissues and organs.

Formamide is also used as an RNA stabiliser in gel electrophoresis by deionizing RNA. In capillary electrophoresis, it is used for stabilizing (single) strands of denatured DNA.

Another use is to add it in sol-gel solutions in order to avoid cracking during sintering.

Formamide, in its pure state, has been used as an alternative solvent for the electrostatic self-assembly of polymer nanofilms.[10]

Formamide is used to prepare primary amines directly from ketones via their N-formyl derivatives, using the Leuckart reaction.

Biochemistry

[edit]
Cycle for methanogenesis, showing two formamide-containing intermediates.[11]

Formamides are intermediates in the methanogenesis cycle.

Prebiotic chemistry

[edit]
Main article: Formamide-based prebiotic chemistry

Formamide has been proposed as an alternative solvent to water, perhaps with the ability to support life with alternative biochemistries to that currently found on Earth. It forms by the hydrolysis of hydrogen cyanide. With a large dipole moment, its solvation properties are similar to those of water.[12]

Formamide has been shown to convert to traces of guanine upon heating in the presence of ultraviolet light.[13]

Several prebiotic chemical reactions producing amino acid derivatives have been shown to take place in formamide.[14] Similar scenarios implicate thioformamide.[15]

Safety

[edit]

Contact with skin and eyes is not recommended. With an LD50 of grams per kg, formamide is of low acute toxicity. It also has low mutagenicity.[8]

Formamide is classified as toxic to reproductive health.[16]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Formamide

View on Grokipedia
from Grokipedia
Formamide (HCONH₂), the simplest monocarboxylic , is a colorless, viscous liquid with a faint ammoniacal , molecular weight of 45.04 g/mol, of 2–3 °C, of 210 °C, and of 1.134 g/mL at 25 °C. It is fully miscible with , , and acetone, making it a versatile polar , though it decomposes slowly in moist air to and . Industrially, formamide is primarily produced by the of , though alternative methods include the of with under catalytic conditions. It serves as a key chemical intermediate in the manufacture of pharmaceuticals, agrochemicals, dyes, and plastics, and is notably used in the large-scale production of via dehydration. Additionally, formamide functions as an effective for processing polymers like and as a denaturing agent in biochemical applications, such as stabilizing during .

Properties

Physical properties

Formamide has the molecular formula HCONH₂ and a molecular weight of 45.04 g/mol. It is a colorless, hygroscopic liquid with a faint ammonia-like odor. Key physical constants of formamide are summarized in the following table:
PropertyValueConditions
Melting point2.55 °C-
Boiling point210 °C760 mmHg
Density1.134 g/cm³20 °C
Viscosity3.76 mPa·s20 °C (dynamic)
Formamide is fully miscible with , , acetone, and other polar solvents due to its high polarity. Its Hansen solubility parameters are δ_d = 17.2 MPa^{1/2}, δ_p = 26.2 MPa^{1/2}, and δ_h = 19.0 MPa^{1/2}, reflecting its strong hydrogen-bonding and polar interactions. The refractive index of formamide is 1.447 at 20 °C, and its dipole moment is 3.73 D. Regarding thermal stability, formamide decomposes above 180 °C into (CO), (NH₃), (HCN), and .

Chemical properties

Formamide possesses a planar molecular structure, characteristic of amides, with an experimentally determined C=O of 1.212 and C-N of 1.368 as obtained from gas-phase studies. This partial double-bond character in the C-N linkage arises from delocalization, where the conjugates with the carbonyl π-system, yielding canonical structures that include a zwitterionic form with positive charge on and negative on oxygen. The significantly influences the molecule's electronic distribution, enhancing stability and restricting rotation around the C-N bond. The N-H bond exhibits moderate acidity, with a pK_a of approximately 23 (in DMSO) for , reflecting the resonance stabilization of the resultant anion. Formamide also displays weak basicity, with a pK_b around 15 corresponding to primarily at the oxygen atom, forming a resonance-stabilized conjugate . These acid-base properties enable formamide to engage in hydrogen bonding, functioning as both a donor via its N-H groups and an acceptor via the carbonyl oxygen, which contributes to its intermolecular interactions. Hydrolysis of formamide proceeds under acidic or basic to produce and , as depicted by the reaction: HCONH2+H2O→HCOOH+NH3\mathrm{HCONH_2 + H_2O \rightarrow HCOOH + NH_3} This process involves nucleophilic attack by on the carbonyl carbon, facilitated by or to enhance electrophilicity. Additionally, formamide can undergo tautomerization to (HN=C=O), a less stable , though this equilibrium strongly favors the amide form due to thermodynamic preferences. Spectroscopic characterization confirms these structural features. In the infrared spectrum, the amide I band corresponding to the C=O stretch appears at approximately 1670 cm⁻¹, shifted lower than typical carbonyls due to resonance, while the N-H stretching vibrations occur around 3300 cm⁻¹, often as broad bands indicative of hydrogen bonding. Proton NMR reveals the formyl hydrogen at δ 8.3 ppm and the NH₂ protons at δ 7.5 ppm, deshielded by the adjacent electronegative oxygen; the ¹³C NMR signal for the carbonyl carbon is observed at δ 161 ppm, consistent with amide carbonyl environments.

Production

Historical methods

Formamide was first prepared in the early through the reaction of with to yield as an intermediate, followed by heating. This early preparation laid the foundation for subsequent production techniques. In the , the primary method for producing formamide involved the of , obtained by neutralizing with . Upon heating to 170–180 °C, it undergoes according to the equation: \ceNH4HCO2−>HCONH2+H2O\ce{NH4HCO2 -> HCONH2 + H2O} This process required careful temperature control to favor formamide formation over further decomposition. Formic acid for this method was historically derived from the dry distillation of wood or the reduction of oxalic acid, sources that were labor-intensive and limited in scale. Early industrial attempts in the sought to scale up production using formates sourced from wood distillation or reduction, followed by conversion to and distillation. These efforts marked the transition from laboratory-scale synthesis to rudimentary commercial processes, though they remained constrained by available raw materials. These historical methods suffered from significant limitations, including low yields typically ranging from 50–60%, the formation of side products such as (CO) and (NH₃) due to over-decomposition at higher temperatures, and high energy demands from the heating requirements. By the mid-20th century, these inefficiencies prompted a shift toward more effective approaches.

Industrial synthesis

The primary industrial method for producing formamide is the aminolysis of with , which operates under milder conditions of 80–100 °C and , yielding formamide and as a : HCOOCH₃ + NH₃ → HCONH₂ + CH₃OH. This method benefits from the availability of , often produced via , and allows for straightforward integration into existing chemical plants. An alternative route involves the of using and , typically catalyzed by transition metals such as or ruthenium-based systems. The reaction proceeds as NH₃ + CO + H₂O → HCONH₂ under high-pressure conditions of 100–200 atm and temperatures ranging from 150–200 °C. Global production of formamide is estimated at approximately 300,000 metric tons per year as of 2023, with major manufacturing hubs in driven by demand in applications. Following synthesis, formamide is purified primarily through to separate residual water, unreacted , and minor impurities, achieving overall process yields exceeding 95%. Recent advancements emphasize more sustainable approaches, including electrochemical syntheses from and or from and under ambient conditions, as well as catalytic processes utilizing to reduce reliance on high-pressure operations and fossil-derived feedstocks. Developments reported in 2024–2025 include Pt foil catalysts for continuous and oxidant-free routes from and aqueous .

Applications

Solvent and industrial uses

Formamide serves as a versatile in various industrial applications, owing to its high constant of 111, which facilitates the dissolution of ionic compounds and salts that are insoluble in or other common . This property makes it particularly effective for processing materials requiring high capacity, such as in the extraction of polar substances and the stabilization of solutions. Its with and low volatility further enhance its utility in formulations where uniform mixing and controlled evaporation are essential. In the polymer industry, formamide is employed as a for the processing of thermoplastics, notably in the dissolution of (PAN) for fiber spinning to produce acrylic textiles and synthetic fibers. Its ability to dissolve high-molecular-weight at elevated temperatures enables the formation of viscous dopes suitable for wet-spinning processes, contributing to the production of durable fibers used in textiles and composites. Additionally, formamide acts as a in polymer formulations, improving flexibility and processability in applications like synthetic plastics. Formamide finds use in the manufacture of adhesives, inks, and dyes, where its high of 210°C supports high-temperature processing without rapid evaporation, ensuring stable formulations during application. In adhesives, it serves as a softener in animal glues and water-soluble gums, enhancing properties in and bonding. For inks, it acts as a to dissolve resins and pigments, aiding in the production of high-quality inks. In dye production, formamide facilitates the synthesis and application of s by dissolving intermediates and improving dye penetration into substrates. In the pharmaceutical sector, formamide functions as an extraction solvent for natural products, leveraging its polar nature to isolate bioactive compounds from and microbial sources. It is also utilized as an intermediate in the synthesis of various vitamins. This role underscores its importance in producing pharmaceutical intermediates with high purity and yield. Agriculturally, formamide is incorporated into formulations as a solvent and penetrant, enhancing the delivery and absorption of active ingredients into tissues or . It serves as a feedstock for synthesizing agrochemicals, such as 1,2,4-triazoles used in herbicides and fungicides, improving efficacy in crop protection. Due to its classification as reproductively , there is growing interest in less hazardous substitutes, though alternatives like N,N-dimethylformamide (DMF) face similar toxicity scrutiny, prompting research into greener options such as bio-based solvents.

Synthetic reactions

Formamide undergoes dehydration to hydrogen cyanide upon heating with phosphorus pentoxide at approximately 200 °C, providing a synthetic route to this key industrial chemical: \ceHCONH2−>[P2O5][200∘C]HCN+H2O\ce{HCONH2 ->[P2O5][200^\circ C] HCN + H2O} This reaction proceeds via removal of the elements of water from the amide functionality, yielding HCN as a gaseous product that requires careful handling due to its toxicity. In a variant of the Vilsmeier-Haack reaction, formamide reacts with phosphorus oxychloride (POCl₃) to generate an electrophilic formylating species, which can be used for the formylation of electron-rich aromatic compounds. The reagent, analogous to the classic Vilsmeier complex from N,N-dimethylformamide, introduces a formyl group ortho or para to activating substituents on the arene, with subsequent hydrolysis yielding the aldehyde. This unsubstituted variant is less common than those using N-substituted formamides but offers access to primary formamides or related derivatives in heterocyclic synthesis. The reaction typically proceeds at room temperature to 60 °C in aprotic solvents, with the iminium-like intermediate [(H₂N=CHCl)⁺Cl⁻] acting as the active species. Formamide can be reduced to via catalytic using gas and a catalyst, such as : \ceHCONH2+H2−>[Ni]CH3NH2+H2O\ce{HCONH2 + H2 ->[Ni] CH3NH2 + H2O} This deoxygenative reduction cleaves the C=O bond, converting the to the corresponding while eliminating . The process requires elevated temperatures (150–250 °C) and pressures (50–100 bar) to achieve selectivity over side products like CO or NH₃, and it is mechanistically similar to reductions of higher , proceeding through intermediate surface-bound species on the catalyst. -based systems are preferred for their activity in C-O bond scission, though catalysts have also been explored for milder conditions. This method provides an alternative route to , avoiding direct handling of in . Formamide participates in cyclization reactions to form heterocycles such as s, particularly under acidic conditions with α-hydroxy ketones in the Blümlein–Lewy synthesis. The reaction involves and , yielding 2-substituted oxazoles where the formamide provides the C2 carbon and : \ceR−C(O)−CH2OH+HCONH2−>[acid]oxazolederivative+H2O\ce{R-C(O)-CH2OH + HCONH2 ->[acid] oxazole derivative + H2O} Typically conducted by heating the reactants in the presence of dehydrating acids like or polyphosphoric acid at 100–150 °C, the mechanism proceeds via initial of the to the carbonyl, followed by cyclization involving the and . This approach is selective for 2-unsubstituted oxazoles and has been applied to synthesize biologically active compounds, with yields ranging from 50–80% depending on the ketone substituent. Representative examples include the formation of 2-methyloxazole from hydroxyacetone. Under basic conditions, formamide undergoes tautomerization to formamidic acid (HN=CH-OH), which is relevant in prebiotic modeling and provides intermediates for further derivatization. This equilibrium is catalyzed by bases such as hydroxide or amines. Quantum chemical studies indicate a low barrier for this intramolecular rearrangement in the gas phase (around 40–50 kcal/mol), but solvent and base effects stabilize the transition state in solution. Experimental observation often requires low temperatures or matrix isolation, with base-catalyzed rates increasing by orders of magnitude.

Laboratory and niche applications

In laboratory settings, formamide is employed as a denaturant for DNA in nucleic acid analysis, particularly in sequencing applications. A 98% formamide solution is commonly used to disrupt hydrogen bonds in double-stranded DNA, facilitating its separation on polyacrylamide gels during electrophoresis for Sanger sequencing or related techniques. This high concentration ensures effective denaturation without excessive gel distortion, improving resolution of nucleotide sequences. Formamide also serves as a cryoprotectant in for protocols. As a penetrating cryoprotectant, it permeates cell membranes and lowers the freezing point of aqueous solutions, thereby preventing the formation of damaging crystals during freezing and thawing of cells, tissues, or embryos. Its use in combination with other agents like DMSO enhances viability post-thaw by promoting over . In spectroscopic studies, formamide acts as a model for investigating bonding interactions due to its structure mimicking bonds. (NMR) spectroscopy in pure or aqueous formamide reveals details of N-H...O=C bonds, providing insights into solvent-solute dynamics and conformational equilibria in biological systems. For niche synthetic applications, formamide functions as a in organometallic reactions, particularly as a source of (CO) in palladium-catalyzed aminocarbonylations of aryl halides. This allows efficient incorporation of CO into s without handling toxic CO gas directly, enabling small-scale synthesis of pharmaceuticals or fine chemicals in laboratory environments. Historically, formamide has been prepared in laboratories through the reaction of with , often for educational demonstrations of formation. Heating and excess yields formamide via and , producing CO2 as a byproduct, a method suitable for small-scale labs due to its simplicity and use of accessible reagents. Recent post-2020 research highlights formamide's role in fabrication as a co-solvent and stabilizer. In solution-processed films, formamide's high constant and promote uniform and phase stabilization, reducing defects and enhancing device efficiency and longevity in lab-fabricated prototypes.

Biological and prebiotic roles

Occurrence in biology

Formamide occurs at trace levels in the , primarily as a resulting from exposure to formamide itself or from the breakdown of related compounds such as N,N-dimethylformamide. It has been detected in human urine, with mean concentrations of approximately 8.6 mg/L in non-exposed individuals, though levels can rise following occupational exposure. Formamide does not play a major endogenous role in mammalian but serves as an intermediate in the detoxification pathways of certain xenobiotics, including metabolites derived from industrial solvents like N,N-dimethylformamide. In microorganisms, formamide is produced by certain microbes through enzymatic reactions, such as the hydration of (HCN) released from cyanogenic , facilitating its integration into . and other microbes utilize formamide as a nitrogen source via formamidases (EC 3.5.1.49), enzymes that catalyze its hydrolysis to and , thereby contributing to cycling processes in ecosystems. This activity is widespread in environments, where amidases enable the breakdown of amides, releasing bioavailable for microbial growth and broader biogeochemical cycles. Formamide has been detected in the through radioastronomical observations in star-forming regions, marking it as a common interstellar molecule. It is also present in carbonaceous meteorites, such as the , underscoring its extraterrestrial abundance and relevance to astrobiological contexts. Studies from the have highlighted formamide's stability under interstellar and planetary conditions, positioning it as a potential in exobiology for assessing and prebiotic chemistry on other worlds. Its persistence in harsh radiation and temperature extremes makes it a valuable indicator for tracing organic beyond .

Prebiotic chemistry

Formamide has been proposed as a key intermediate in prebiotic synthesis pathways simulating conditions, particularly through reactions involving (HCN), (CO), and (NH₃). In variants of the Miller-Urey experiment using reducing atmospheres, formamide forms via of HCN or reactions of CO with NH₃ under electrical discharge, yielding approximately 1-5% of the total organic products depending on gas mixtures and conditions. These experiments demonstrate formamide's accumulation as a stable precursor, bridging simple gases to more complex organics without requiring enzymatic . As a prebiotic , formamide exhibits superior for polar biomolecules compared to , particularly at elevated temperatures of 80-100 °C, where it remains and facilitates the dissolution of and . This property arises from its high dielectric constant (111 at 25 °C), enabling concentration of precursors in hydrothermal or impact-heated environments without rapid . In such settings, formamide supports non-aqueous reactions that mimic abiogenic molecular assembly, as evidenced by its stability and reactivity in lab simulations of pores or vents. Formamide contributes to biomolecule formation through thermal hydrolysis and related reactions, yielding purines such as and , as well as pyrimidines like and 4(3H)-pyrimidinone. These processes occur at temperatures around 160-180 °C in the presence of catalysts like phosphates or , with yields reaching up to 4% from pure formamide. Additionally, formamide enables prebiotic of nucleosides to using dihydrogen phosphates or mineral surfaces, producing adenosine monophosphates and cyclic derivatives in yields of 10-20% under mild heating (60-100 °C). A pivotal reaction in nucleobase synthesis involves formamide (HCONH₂) reacting with HCN to form formamidine intermediates, which further cyclize to precursors like 2-iminoacetonitrile, with yields up to 20% under or impact conditions. This pathway integrates HCN with formamide's amido group, providing a deterministic route to canonical nucleobases without side products dominating. Astrophysically, formamide's relevance is underscored by its detection in comets, including observations on 67P/Churyumov-Gerasimenko during the mission (2014-2016), where it appeared in both surface dust and coma volatiles at levels consistent with interstellar inheritance. Such detections suggest comets delivered formamide to , seeding prebiotic pools. Recent models from 2022-2025 emphasize formamide-based pathways in the hypothesis, where it drives sequential synthesis of nucleobases, nucleosides, and short oligomers, potentially encapsulating them in lipid-like assemblies from byproducts. As of 2025, studies have explored formamide-based chemistry for generating non-natural compounds with antiviral potential, extending its prebiotic relevance to modern synthetic applications. These simulations integrate impact or hydrothermal heating to achieve precursors, with formation via formamide-derived amphiphiles supporting emergence alongside genetic molecules.

Safety and environmental aspects

Health hazards

Formamide exhibits low via , with an LD50 of 6000 mg/kg in rats. It is moderately irritating to the skin and eyes, causing redness. Chronic exposure to formamide can lead to , including teratogenic effects observed in rats at doses of 100 mg/kg/day, manifesting as reduced fetal body weight. It also induces in animal models, with symptoms including drowsiness and . In humans, symptoms of exposure include and , particularly from or dermal absorption. Formamide is metabolized in biological systems through hydrolysis by formamidase to (formate), which is neurotoxic, and . The National Toxicology Program (NTP) has identified formamide as showing equivocal evidence of carcinogenic activity in female mice based on increased incidences of hepatocellular or (combined), though it lacks an IARC classification. Occupational exposure limits include a NIOSH (REL) of 10 ppm (15 mg/m³) as a 10-hour time-weighted , with notation due to dermal absorption potential; OSHA has not established a (PEL).

Environmental impact

Formamide demonstrates ready biodegradability in aerobic aquatic environments, with degradation exceeding 60% within 28 days under 301A (DOC Die-Away Test) conditions, mediated by soil and water microbes that convert it primarily to , , and . This process aligns with standard criteria for inherent biodegradability, indicating low persistence in natural waters under favorable conditions. Ecotoxicity assessments reveal low acute toxicity to fish, with LC50 values greater than 1000 mg/L (e.g., 6569 mg/L for Leuciscus idus over 96 hours and 34,000 mg/L for Pimephales promelas), suggesting minimal short-term harm to vertebrate aquatic life. Toxicity to invertebrates is similarly low, as evidenced by EC50 >500 mg/L (immobilization endpoint over 48 hours), while algae exhibit moderate sensitivity with an EC50 >500 mg/L. Overall, these profiles classify formamide as not acutely harmful to most aquatic organisms at environmentally relevant concentrations. Formamide's high mobility stems from its complete miscibility with (solubility >1000 g/L at 20°C), facilitating rapid transport through and potential leaching into from industrial spills or effluent discharges. This solubility enhances its dissemination in aqueous systems but increases contamination risks in subsurface environments lacking robust . Regulatory frameworks address these risks: under the EU Toy Safety Directive 2009/48/EC (Appendix C), formamide in foam toys is restricted to a content of ≤200 mg/kg; if exceeding 200 mg/kg, emissions must be ≤20 μg/m³ after 28 days. As of 2025, the European standard EN 71-15 specifies test methods for determining formamide content in foam toy materials to ensure compliance with the limits. Environmental emissions primarily arise from runoff in agricultural settings and industrial wastewater, with atmospheric persistence limited to approximately days due to ( ~200 years in but accelerated in air via OH reactions). Mitigation efforts in the 2020s emphasize transitions to less hazardous solvents like N-methyl-2-pyrrolidone (NMP) for industrial applications, coupled with wastewater monitoring protocols that detect formamide at parts-per-billion (ppb) levels to ensure compliance and prevent aquatic buildup.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Formamide
  2. https://www.acs.org/molecule-of-the-week/archive/f/formamide.html
  3. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9854215.htm
  4. https://www.eastman.com/en/products/product-detail/71104437/formamide-99-7
  5. https://www.nature.com/articles/s41467-023-38603-5
  6. https://www.inchem.org/documents/icsc/icsc/eics0891.htm
  7. https://www.sigmaaldrich.com/US/en/sds/sigald/f7503
  8. https://www.stenutz.eu/chem/solv6.php?name=formamide
  9. https://academic.oup.com/bcsj/article-pdf/47/1/67/56083767/bcsj.47.67.pdf
  10. https://www.sciencedirect.com/science/article/abs/pii/S000926149800846X
  11. https://np-mrd.org/natural_products/NP0000527/
  12. https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.200500346
  13. https://pubs.aip.org/aip/jcp/article-pdf/22/7/1228/8117396/1228_1_online.pdf
  14. https://www.chemicalbook.com/SpectrumEN_75-12-7_1HNMR.htm
  15. https://www.chemicalbook.com/SpectrumEN_75-12-7_13CNMR.htm
  16. https://library.sciencemadness.org/library/books/Mellor_ACTITC_14.pdf
  17. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/formamide
  18. https://prepchem.com/synthesis-of-formamide/
  19. https://shanghaichemex.com/how-formic-acid-is-prepared/
  20. https://pubs.acs.org/doi/10.1021/acs.chemrev.6b00816
  21. https://ajsonline.org/article/61536.pdf
  22. https://onlinelibrary.wiley.com/doi/abs/10.1002/0471238961.0615181308150814.a01
  23. https://datavagyanik.com/reports/formamide-market/
  24. https://patents.google.com/patent/US4556734A/en
  25. https://pubs.acs.org/doi/10.1021/jacsau.3c00537
  26. https://www.nature.com/articles/s41467-025-63313-5
  27. https://onlinelibrary.wiley.com/doi/10.1002/anie.202500747
  28. https://arxiv.org/pdf/2402.10954
  29. https://www.chem.rochester.edu/notvoodoo/pages/sixty_solvents.php?page=formamide
  30. https://www.industryarc.com/Research/Global-Formamide-Market-Research-511870
  31. https://www.nbinno.com/article/other-organic-chemicals/formamide-solvent-applications-synthetic-fibers-plastics-qw
  32. https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/298/192/f4761pis.pdf
  33. https://www.rxchemicals.com/product/formamide
  34. https://products.basf.com/global/en/ci/30036715
  35. https://www.thieme-connect.de/products/ebooks/pdf/10.1055/sos-SD-016-00463.pdf
  36. https://www.vizagchemical.com/product/formamide-0
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC10781810/
  38. https://www.sciencemadness.org/smwiki/index.php/Hydrogen_cyanide
  39. https://www.organic-chemistry.org/namedreactions/vilsmeier-reaction.shtm
  40. https://www.frontiersin.org/journals/energy-research/articles/10.3389/fenrg.2023.1158499/full
  41. https://macmillan.princeton.edu/wp-content/uploads/Heterocycles-Part-1.pdf
  42. https://www.sciencedirect.com/science/article/abs/pii/S0022286010002073
  43. https://www.nature.com/articles/emm199736.pdf
  44. https://pubmed.ncbi.nlm.nih.gov/1451681/
  45. https://www.nature.com/articles/s41570-022-00407-4
  46. https://pmc.ncbi.nlm.nih.gov/articles/PMC7897298/
  47. https://pubs.acs.org/doi/10.1021/ja00481a002
  48. https://pubs.acs.org/doi/10.1021/cc0200843
  49. https://patents.google.com/patent/EP0955797B1/en
  50. https://pubmed.ncbi.nlm.nih.gov/37000423/
  51. https://link.springer.com/article/10.1007/BF00383131
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC546731/
  53. http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S1850-20672014000100003
  54. https://pubs.acs.org/doi/abs/10.1021/acsearthspacechem.9b00154
  55. https://www.sciencedirect.com/science/article/pii/S1571064524001283
  56. https://ntrs.nasa.gov/api/citations/20050139759/downloads/20050139759.pdf
  57. https://astrobiology.nasa.gov/news/why-formamide-may-have-been-early-lifes-alternative-to-water/
  58. https://pubs.acs.org/doi/10.1021/jacs.2c13306
  59. https://pmc.ncbi.nlm.nih.gov/articles/PMC7831497/
  60. https://www.pnas.org/doi/10.1073/pnas.1600275113
  61. https://www.sciencedirect.com/science/article/abs/pii/S0968089600003400
  62. https://www.researchgate.net/publication/11961726_A_possible_prebiotic_synthesis_of_purine_adenine_cytosine_and_43H-pyrimidinone_from_formamide_Implications_for_the_origin_of_life
  63. https://pubmed.ncbi.nlm.nih.gov/1023139/
  64. https://www.sciencedirect.com/science/article/pii/S0021925819576177
  65. https://www.frontiersin.org/journals/astronomy-and-space-sciences/articles/10.3389/fspas.2022.882145/full
  66. https://www.aanda.org/articles/aa/full_html/2023/09/aa46996-23/aa46996-23.html
  67. https://www.sciencedirect.com/science/article/pii/S2451929416302273
  68. https://www.aanda.org/articles/aa/full_html/2014/06/aa23890-14/aa23890-14.html
  69. https://www.nature.com/articles/s41598-025-14001-3
  70. https://www.liebertpub.com/doi/full/10.1089/ast.2021.0161
  71. https://pubchem.ncbi.nlm.nih.gov/compound/Formamide#section=Safety-and-Hazards
  72. https://nj.gov/health/eoh/rtkweb/documents/fs/0947.pdf
  73. https://academic.oup.com/toxsci/article/57/2/284/1634824
  74. https://chemicalsafety.ilo.org/dyn/icsc/showcard.display?p_card_id=0891
  75. https://www.cdc.gov/niosh/npg/npgd0295.html
  76. https://pmc.ncbi.nlm.nih.gov/articles/PMC10313556/
  77. https://ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr541.pdf
  78. https://hpvchemicals.oecd.org/ui/handler.axd?id=3b6973c5-230b-4382-af58-c757e66dcd7c
  79. https://www.sigmaaldrich.com/sds/sigma/f9037
  80. https://www.carlroth.com/downloads/sdb/en/4/SDB_4095_IE_EN.pdf
  81. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32015L2115
  82. https://www.en-standard.eu/bs-en-71-15-2025-safety-of-toys-formamide-in-foam-toy-materials-content
  83. https://www.researchgate.net/publication/237845733_Aspects_of_the_hydrolysis_of_formamide_Revisitation_of_the_water_reaction_and_determination_of_the_solvent_deuterium_kinetic_isotope_effect_in_base
  84. https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00672
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