Inorganic chemistry,isocyanate is thefunctional group with the formulaR−N=C=O.Organic compounds that contain an isocyanate group are referred to asisocyanates. An organic compound with two isocyanate groups is known as a diisocyanate. Diisocyanates are manufactured for the production ofpolyurethanes, a class ofpolymers.[1][2][page needed][3][page needed]
Isocyanates should not be confused withcyanate esters andisocyanides, very different families of compounds. Thecyanate (cyanate ester) functional group (R−O−C≡N) is arranged differently from the isocyanate group (R−N=C=O).Isocyanides have the connectivityR−N≡C, lacking the oxygen of the cyanate groups.
In terms of bonding, isocyanates are closely related to carbon dioxide (CO2) andcarbodiimides (C(NR)2). The C−N=C=O unit that defines isocyanates is planar, and the N=C=O linkage is nearly linear. Inphenyl isocyanate, the C=N and C=O distances are respectively 1.195 and 1.173 Å. The C−N=C angle is 134.9° and the N=C=O angle is 173.1°.[4]
Isocyanates are usually produced fromamines byphosgenation, i.e. treating withphosgene:
These reactions proceed via the intermediacy of acarbamoyl chloride (RNHC(O)Cl). Owing to the hazardous nature of phosgene, the production of isocyanates requires special precautions.[1] A laboratory-safe variation masks the phosgene asoxalyl chloride.[5] Also, oxalyl chloride can be used to formacyl isocyanates from primaryamides, which phosgene typically dehydrates tonitriles instead.[6]
Another route to isocyanates entails addition ofisocyanic acid to alkenes. Complementarily, alkyl isocyanates form by displacement reactions involving alkyl halides and alkali metal cyanates.[7]
Aryl isocyanates can be synthesized from reductivecarbonylation ofnitro- andnitrosoarenes; apalladium catalyst is necessary to avoid side-reactions of thenitrene intermediate.[8][9]
Three rearrangement reactions involving nitrenes give isocyanates:
An isocyanate is also the immediate product of theHofmann rearrangement, but typically hydrolyzes under reaction conditions.[10]
Isocyanates areelectrophiles, and as such they are reactive toward a variety ofnucleophiles includingalcohols,amines, and even water. They are more reactive than structurally analogousisothiocyanates.[11]
Upon treatment with an alcohol, an isocyanate forms aurethane linkage:
where R and R' arealkyl oraryl groups.If a diisocyanate is treated with a compound containing two or more hydroxyl groups, such as adiol or apolyol, polymer chains are formed, which are known aspolyurethanes.
Isocyanates react with water to formcarbon dioxide:
This reaction is exploited in tandem with the production of polyurethane to give polyurethane foams. The carbon dioxide functions as ablowing agent.[12]
Isocyanates also react with amines to giveureas:
The addition of an isocyanate to a urea gives abiuret:
Reaction between a di-isocyanate and a compound containing two or more amine groups produces long polymer chains known aspolyureas.
Carbodiimides are produced by the decarboxylation of alkyl and aryl isocyanate using phosphine oxides as a catalyst:[13]
Isocyanates also can react with themselves.Aliphatic diisocyanates cantrimerise to from substitutedisocyanuric acid groups. This can be seen in the formation ofpolyisocyanurate resins (PIR) which are commonly used as rigidthermal insulation. Isocyanates participate inDiels–Alder reactions, functioning asdienophiles.
Isocyanates are common intermediates in the synthesis of primary amines viahydrolysis:
The global market for diisocyanates in the year 2000 was 4.4 million tonnes, of which 61.3% wasmethylene diphenyl diisocyanate (MDI), 34.1% wastoluene diisocyanate (TDI), 3.4% was the total forhexamethylene diisocyanate (HDI) andisophorone diisocyanate (IPDI), and 1.2% was the total for various others.[18] A monofunctional isocyanate of industrial significance ismethyl isocyanate (MIC), which is used in the manufacture of pesticides.
MDI is commonly used in the manufacture of rigid foams and surface coating.[1] Polyurethane foam boards are used in construction for insulation. TDI is commonly used in applications where flexible foams are used, such as furniture and bedding. Both MDI and TDI are used in the making of adhesives and sealants due to weather-resistant properties. Isocyanates, both MDI and TDI are widely used in as spraying applications of insulation due to the speed and flexibility of applications. Foams can be sprayed into structures and harden in place or retain some flexibility as required by the application.[19] HDI is commonly utilized in high-performance surface-coating applications, including automotive paints.
The risks of isocyanates was brought to the world's attention with the 1984Bhopal disaster, which caused the death of nearly 4000 people from the accidental release ofmethyl isocyanate. In 2008, the same chemical was involved in an explosion at a pesticide manufacturing plant in West Virginia.[20]
LD50s for isocyanates are typically several hundred milligrams per kilogram.[21] Despite this low acute toxicity, an extremely lowshort-term exposure limit (STEL) of 0.07 mg/m3 is the legal limit for all isocyanates (except methyl isocyanate: 0.02 mg/m3) in the United Kingdom.[22] These limits are set to protect workers from chronic health effects such asoccupational asthma,contact dermatitis, or irritation of the respiratory tract.[23]
Since they are used in spraying applications, the properties of their aerosols have attracted attention.[24][25] In the U.S., OSHA conducted a National Emphasis Program on isocyanates starting in 2013 to make employers and workers more aware of the health risks.[26] Polyurethanes have variablecuring times, and the presence of free isocyanates in foams vary accordingly.[27]
Both the USNational Toxicology Program (NTP) andInternational Agency for Research on Cancer (IARC) have evaluated TDI as a potential human carcinogen and Group 2B "possibly carcinogenic to humans".[28][29] MDI appears to be relatively safer and is unlikely a human carcinogen.[29] The IARC evaluates MDI as Group 3 "not classifiable as to its carcinogenicity in humans".[30]
All major producers of MDI and TDI are members of the International Isocyanate Institute, which promotes the safe handling of MDI and TDI.
Isocyanates can present respiratory hazards as particulates, vapors or aerosols. Autobody shop workers are a very commonly examined population for isocyanate exposure as they are repeatedly exposed when spray painting automobiles[31] and can be exposed when installing truck bed liners.[32][33] Hypersensitivity pneumonitis has slower onset and features chronic inflammation that can be seen on imaging of the lungs. Occupational asthma is a worrisome outcome of respiratory sensitization to isocyanates as it can be acutely fatal.[34] Diagnosis of occupational asthma is generally performed usingpulmonary function testing (PFT) and performed bypulmonology oroccupational medicine physicians.[35] Occupational asthma is much like asthma in that it causes episodic shortness of breath and wheezing. Both the dose and duration of exposure to isocyanates can lead to respiratory sensitization.[36] Dermal exposures to isocyanates can sensitize an exposed person to respiratory disease.
Dermal exposures can occur via mixing, spraying coatings or applying and spreading coatings manually. Dermal exposures to isocyanates is known to lead to respiratory sensitization.[37] Even when the right personal protective equipment (PPE) is used, exposures can occur to body areas not completely covered.[38] Isocyanates can also permeate improper PPE, necessitating frequent changes of both disposable gloves and suits if they become over exposed.
Methyl isocyanate (MIC) is highly flammable.[39] MDI and TDI are much less flammable.[40] Flammability of materials is a consideration in furniture design.[41] The specific flammability hazard is noted on thesafety data sheet (SDS) for specific isocyanates.
Industrial science attempts to minimize the hazards of isocyanates through multiple techniques. The EPA has sponsored ongoing research on polyurethane production without isocyanates.[42][43] Where isocyanates are unavoidable but interchangeable, substituting a less hazardous isocyanate may control hazards. Ventilation and automation can also minimizes worker exposure to the isocyanates used.[24][44]
If human workers must enter isocyanate-contaminated regions,personal protective equipment (PPE) can reduce their intake. In general, workers wear eye protection[44] and gloves and coveralls to reduce dermal exposure[45][46][25][47] For some autobody paint andclear-coat spraying applications, a full-face mask is required.[31][32]
The USOccupational Safety and Health Administration (OSHA) requires frequent training to ensure isocyanate hazards are appropriately minimized.[48] Moreover, OSHA requires standardized isocyanate concentration measurements to avoid violatingoccupational exposure limits. In the case of MDI, OSHA expects sampling with glass-fiber filters at standard air flow rates, and then liquid chromatography.[49]
Combined industrial hygiene and medical surveillance can significantly reduce occupationalasthma incidence.[50] Biological tests exist to identify isocyanate exposure;[51] theUS Navy uses regular pulmonary function testing and screening questionnaires.[52]
Emergency management is a complex process of preparation and should be considered in a setting where a release of bulk chemicals may threaten the well-being of the public. In theBhopal disaster, an uncontrolled MIC release killed thousands, affected hundreds of thousands more, and spurred the development of modern disaster preparation.[53]
Exposure limits can be expressed as ceiling limits, a maximal value, short-term exposure limits (STEL), a 15-minute exposure limit or an 8-hour time-weighted average limit (TWA). Below is a sampling, not exhaustive, as less common isocyanates also have specific limits within the United States, and in some regions there are limits on total isocyanate, which recognizes some of the uncertainty regarding the safety of mixtures of chemicals as compared to pure chemical exposures. For example, while there is no OEL for HDI, NIOSH has a REL of 5 ppb for an 8-hour TWA and a ceiling limit of 20 ppb, consistent with the recommendations for MDI.[54]
| Organization (region) | Standard | Value |
|---|---|---|
| OSHA (USA) | Ceiling limit | 20 ppb[55] |
| NIOSH (USA) | Recommended exposure limit (REL) – ceiling limit | 20 ppb[56] |
| NIOSH (USA) | Recommended exposure limit (REL) – TWA | 5 ppb[56] |
| ACGIH (USA) | Threshold limit value (TLV) | 5 ppb[57] |
| Safe Work (Australia) | All isocyanates – TWA | 0.02 mg/m3[58] (approximately 2.5 ppb for comparison) |
| Safe Work (Australia) | All isocyanates – STEL | 0.07 mg/m3[58] (approximately 10 ppb for comparison) |
| Heath & Safety Executive (UK) | All isocyanates – TWA | 0.02 mg/m3[59] |
| Heath & Safety Executive (UK) | All isocyanates – STEL | 0.07 mg/m3[59] |
| Organization (region) | Standard | Value |
|---|---|---|
| OSHA (USA) | Ceiling limit | 20 ppb[55] |
| NIOSH (USA) | Recommended exposure limit (REL) | [none][60] |
| ACGIH (USA) | Threshold limit value (TLV) | 5 ppb[57] |
| ACGIH (USA) | Ceiling limit | 20 ppb[57] |
TheOccupational Safety and Health Administration (OSHA) is the regulatory body covering worker safety. OSHA puts forth permissible exposure limit (PEL) 20 ppb for MDI and detailed technical guidance on exposure assessment.[52]
The National Institutes of Health (NIOSH) is the agency responsible for providing the research and recommendations regarding workplace safety, while OSHA is more of an enforcement body. NIOSH is responsible for producing the science that can result in recommended exposure limits (REL), which can be lower than the PEL. OSHA is tasked with enforcement and defending the enforceable limits (PELs). In 1992, when OSHA reduced the PEL for TDI to the NIOSH REL, the PEL reduction was challenged in court, and the reduction was reversed.[61]
The Environmental Protection Agency (EPA) is also involved in the regulation of isocyanates with regard to the environment and also non-worker persons that might be exposed.[62]
TheAmerican Conference of Governmental Industrial Hygienists (ACGIH) is a non-government organization that publishes guidance known as threshold limit values (TLV)[61] forchemicals based research as constant work exposure level without ill-effect[clarify]. The TLV is not an OSHA-enforceable value, unless the PEL is the same.
TheEuropean Chemicals Agency (ECHA) provides regulatory oversight of chemicals used within the European Union.[63] ECHA has been implementing policy aimed at limiting worker exposure through elimination by lower allowable concentrations in products and mandatory worker training, an administrative control.[64] Within the European Union, many nations set their own occupational exposure limits for isocyanates.
TheUnited Nations, through theWorld Health Organization (WHO) together with theInternational Labour Organization (ILO) andUnited Nations Environment Programme (UNEP), collaborate on theInternational Programme on Chemical Safety (IPCS) to publish summary documents on chemicals. The IPCS published one such document in 2000 summarizing the status of scientific knowledge on MDI.[65]
The IARC evaluates the hazard data on chemicals and assigns a rating on the risk of carcinogenesis. In the case of TDI, the final evaluation is possibly carcinogenic to humans (Group 2B).[66] For MDI, the final evaluation is not classifiable as to its carcinogenicity to humans (Group 3).[67]
The International Isocyanate Institute is an international industry consortium that seeks promote the safe utilization of isocyanates by promulgating best practices.[68]
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