methyl isocyanate

Methyl isocyanate is a colorless, poisonous, lachrymatory (tearing agent), flammable liquid.Union Carbide Corporation "Methyl Isocyanate" Product Information Publication, F-41443, November 1967. It is soluble in water to 6–10 parts per 100 parts, but it also reacts with water (see Reactions below).

It has a refractive index of 1.363 with a wavelength of 589 nm at a temperature of 20 °C {{cite journal |last1=Kirilin |first1=Aleksei |last2=Belova |first2=Liya |last3=Pletneva |first3=Maria |title=New aspects of isocyanate synthesis with the use of O-silylurethanes |journal=Mendeleev Communications |date=January–February 2017 |volume=27 |issue=1 |pages=99–100 |doi=10.1016/j.mencom.2017.01.033}}

Methyl isocyanate is usually manufactured by the reaction of monomethylamine and phosgene. For large-scale production it is advantageous to combine these reactants at higher temperature in the gas phase. A mixture of methyl isocyanate and two moles of hydrogen chloride is formed, but N-methylcarbamoyl chloride (MCC) forms as the mixture is condensed, leaving one mole of hydrogen chloride as a gas.

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The methyl isocyanate is obtained by treating the MCC with a tertiary amine, such as N,N-dimethylaniline, or with pyridine,{{cite patent |country=US |number=2480088 |status=patent |inventor=Slocombe, R. J.; Hardy, E. E. |title=Process of Producing Carbamyl Chlorides |gdate=1949-08-23 |assign1=Monsanto}} or by separating it by using distillation techniques.{{cite patent |country=FR |number=1400863 |status=patent |inventor=Merz, W. |title=Procédé et dispositif de préparation d'isocyanates d'alkyle |assign1=Bayer |gdate=1965-05-28}}

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Methyl isocyanate is also manufactured from N-methylformamide and air. In the latter process, it is immediately consumed in a closed-loop process to make methomyl.Chemical Week, "A fleeting existence for toxic-gas molecules" p. 9, 12 June 1985. Other manufacturing methods have been reported.{{cite patent |country=DE |number=2828259 |status=patent |inventor=Giesselmann, G.; Guenther, K.; Fuenten, W. |title=Verfahren zur Herstellung von Methyl Isocyanate |gdate=1980-01-10 |assign1=Degussa}}{{cite journal |journal=Chemical Week |year=1985 |title=A safer method for making carbamates |page=136 |volume=1985b |issue=20}}

Methyl isocyanate reacts readily with many substances that contain N-H or O-H groups. With water, it forms 1,3-dimethylurea and carbon dioxide with the evolution of heat (1358.5 joules, or 325 calories, per gram of MIC): It is relatively slow to react at below 68 °F, but will increase its rate with elevated temperatures or in the presence of acid or base.{{cite journal |last1=Manilla |title=Methyl isocyanate: Risk assessment, environmental, and health hazard |journal=Hazardous Gases Risk Assessment on the Environment and Human Health |date=2021 |pages=251–261}}

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At 25 °C, in excess water, half of the MIC is consumed in 9 min.;{{cite journal |vauthors=Castro EA, Moodie RB, Sansom PJ |title=The kinetics of hydrolysis of methyl and phenyl isocyanates |journal=Journal of the Chemical Society, Perkin Transactions 2 |year=1985 |volume=1985 |issue=5 |pages=737–742 |doi=10.1039/P29850000737}} if the heat is not efficiently removed from the reacting mixture, the rate of the reaction will increase and rapidly cause the MIC to boil. Such a reaction triggered the Bhopal disaster after a large amount of water was introduced to a MIC storage tank. The consequence of the out of control exothermic process was a runaway reaction and the direct release of 42 tons of MIC to the atmosphere.

If MIC is in excess, 1,3,5-trimethylbiuret is formed along with carbon dioxide. Alcohols and phenols, which contain an O-H group, react slowly with MIC, but the reaction can be catalyzed by trialkylamines or dialkyltin dicarboxylate. Oximes, hydroxylamines, and enols also react with MIC to form methylcarbamates. These reactions produce the products described below (Uses).

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Ammonia, primary, and secondary amines rapidly react with MIC to form substituted ureas. Other N-H compounds, such as amides and ureas, react much more slowly with MIC.{{cite book |vauthors=March J |title=Advanced Organic Chemistry |edition=3rd |publisher=John Wiley & Sons |location=New York |year=1985 |page=802}}

It also reacts with itself to form a trimer or higher-molecular-weight polymers. In the presence of catalysts, MIC reacts with itself to form a solid trimer, trimethyl isocyanurate, or a higher-molecular-weight polymer:

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Sodium methoxide, triethyl phosphine, ferric chloride and certain other metal compounds catalyze the formation of the MIC-trimer, while the high-molecular-weight polymer formation is catalyzed by certain trialkylamines. Since the formation of the MIC trimer is exothermic (1246 joules, or 298 calories, per gram of MIC), the reaction can lead to violent boiling of the MIC. The high-molecular-weight polymer hydrolyzes in hot water to form the trimethyl isocyanurate. Since catalytic metal salts can be formed from impurities in commercial grade MIC and steel, this product must not be stored in steel drums or tanks.

Methyl isocyanate is extremely toxic. There is no known antidote. The threshold limit value set by the American Conference of Governmental Industrial Hygienists is 0.02 ppm. MIC is toxic by inhalation, ingestion and contact in quantities as low as 0.4 ppm. Exposure symptoms include coughing, chest pain, dyspnea, asthma, irritation of the eyes, nose and throat, as well as skin damage. Higher levels of exposure, over 21 ppm, can result in pulmonary or lung edema, emphysema and hemorrhages, bronchial pneumonia and death. Although the odor of methyl isocyanate cannot be detected at 5 ppm by most people, its potent lachrymal properties provide an excellent warning of its presence (at a concentration of 2–4 parts per million (ppm) subjected to eyes are irritated, while at 21 ppm, subjects could not tolerate the presence of methyl isocyanate in air).{{cite journal |vauthors=Kimmerle G, Eben A |title=Zur Toxizität von Methylisocyanat und dessen quantitativer Bestimmung in der Luft |journal=Archiv für Toxikologie |year=1964 |volume=20 |issue=4 |pages=235–241 |s2cid=21422558 |doi=10.1007/bf00577897|bibcode=1964ArTox..20..235K }} The irritant effects of methyl isocyanate are mediated by the irritant and tear gas receptor TRPA1 in pain-sensing nerve endings in the eye.{{Cite journal |last1=Bessac |first1=Bret F. |last2=Sivula |first2=Michael |last3=Hehn |first3=Christian A. |last4=Caceres |first4=Ana I. |last5=Escalera |first5=Jasmine |last6=Jordt |first6=Sven-Eric |date=2009-04-01 |title=Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases |journal=The FASEB Journal |language=en |volume=23 |issue=4 |pages=1102–1114 |doi=10.1096/fj.08-117812 |doi-access=free |issn=0892-6638 |pmc=2660642 |pmid=19036859}}

Proper care must be taken to store methyl isocyanate because of its ease of exothermically polymerizing (see Reactions) and its similar sensitivity to water. Only stainless steel or glass containers may be safely used; the MIC must be stored at temperatures below {{convert|40|°C}} and preferably at {{convert|4|°C}}.{{Citation needed|date=August 2018}}

The toxic effect of the compound was apparent in the 1984 Bhopal disaster, when around {{convert|42000|kg}} of methyl isocyanate and other gases were released from the underground reservoirs of the Union Carbide India Limited (UCIL) factory, over a populated area on 3 December 1984, killing about 3,500 people immediately, 8,000 people in the first 48 hours and 15,000 more over the next several years. 200,000 people had lasting health effects from the disaster.{{cite journal |last1=Varma |first1=Daya |last2=Mulay |first2=Shree |title=Methyl Isocyanate: The Bhopal Gas |journal=Handbook of Toxicology of Chemical Warfare Agents |date=2015 |pages=287–299 |doi=10.1016/B978-0-12-800159-2.00022-1}}{{cite news |url=http://news.bbc.co.uk/1/hi/world/south_asia/8725140.stm |title=Bhopal trial: Eight convicted over India gas disaster |date=7 June 2010 |publisher=BBC News |access-date=7 June 2010 | archive-url=https://web.archive.org/web/20100607185745/http://news.bbc.co.uk/1/hi/world/south_asia/8725140.stm |archive-date=7 June 2010 |url-status=live}}

During structural fires, natural materials can contribute to releasing isocyanates including methyl isocyanate.Dzhordzhio Naldzhiev, Matija Strlic; Polyurethane insulation and household products – a systematic review of their impact on indoor environmental quality, [Building and Environment https://www.sciencedirect.com/journal/building-and-environment], 2020

Until recent decades, the mechanism of methyl isocyanate toxicity in humans was largely unknown or unclear.{{cite journal |vauthors=Mehta PS, Mehta AS, Mehta SJ, Makhijani AB |title=Bhopal tragedy's health effects. A review of methyl isocyanate toxicity |journal=JAMA |volume=264 |issue=21 |pages=2781–2787 |date=December 1990 |pmid=2232065 |doi=10.1001/jama.1990.03450210081037}}{{cite journal |vauthors=Varma DR |title=Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy |journal=Environmental Health Perspectives |volume=72 |pages=153–157 |date=June 1987 |pmid=3622430 |pmc=1474644 |doi=10.1289/ehp.8772153}} Methyl isocyanate and other isocyanates are electrophiles and are currently thought to cause toxicity by the alkylation of biomolecules.{{cite journal |last1=Bessac |first1=B.F. |last2=Jordt |first2=S.-E. |date=2010-07-01 |title=Sensory Detection and Responses to Toxic Gases: Mechanisms, Health Effects, and Countermeasures |journal=Proceedings of the American Thoracic Society |volume=7 |issue=4 |pages=269–277 |pmid=20601631 |pmc=3136963 |issn=1546-3222 |doi=10.1513/pats.201001-004sm}} The mechanism of methyl isocyanate was previously suspected to be the carbamylation of hemoglobin, thus interfering with its oxygen-binding capability and causing hypoxia. However, experiments showed that when rats and guinea pigs were exposed to methyl isocyanate at concentrations above the median lethal concentration (LC₅₀, the concentration sufficient to kill 50% of the tested population), only 2% of hemoglobin molecules were carbamylated, suggesting that this is probably not the mechanism of toxicity.{{cite journal |last1=Varma |first1=Daya R.|last2=Guest |first2=Ian |date=1993 |title=The Bhopal accident and methyl isocyanate toxicity |journal=Journal of Toxicology and Environmental Health |volume=40 |issue=4 |pages=513–529 |pmid=8277516 |bibcode=1993JTEH...40..513V |issn=0098-4108 |doi=10.1080/15287399309531816}}{{cite journal |last1=Ramachandran |first1=P.K. |last2=Gandhe |first2=B.R. |last3=Venkateswaran |first3=K.S. |last4=Kaushik |first4=M.P. |last5=Vijayaraghavan |first5=R. |last6=Agarwal |first6=G.S. |last7=Gopalan |first7=N. |last8=Suryanarayana |first8=M.V.S. |last9=Shinde |first9=S.K. |last10=Sriramachari |first10=S. |date=1988 |title=Gas chromatographic studies of the carbamylation of haemoglobin by methyl isocyanate in rats and rabbits |journal=Journal of Chromatography B: Biomedical Sciences and Applications |volume=426 |issue=2 |pages=239–247 |pmid=3392138 |issn=0378-4347 |doi=10.1016/s0378-4347(00)81952-0}}

File:ALMA detects methyl isocyanate around young Sun-like stars.jpg interferometer (northern Chile).]]

On 30 July 2015, scientists reported that upon the first touchdown of the Philae lander on comet 67/P{{'s}} surface, measurements by the COSAC and Ptolemy instruments revealed sixteen organic compounds, four of which were seen for the first time on a comet, including acetamide, acetone, methyl isocyanate and propionaldehyde.{{cite news |url=https://www.washingtonpost.com/world/philae-probe-finds-evidence-that-comets-can-be-cosmic-labs/2015/07/30/63a2fc0e-36e5-11e5-ab7b-6416d97c73c2_story.html |archive-url=https://web.archive.org/web/20181223235109/https://www.washingtonpost.com/world/philae-probe-finds-evidence-that-comets-can-be-cosmic-labs/2015/07/30/63a2fc0e-36e5-11e5-ab7b-6416d97c73c2_story.html |url-status=dead |archive-date=23 December 2018 |title=Philae probe finds evidence that comets can be cosmic labs |newspaper=The Washington Post |agency=Associated Press |vauthors=Jordans F |date=30 July 2015 |access-date=30 July 2015}}{{cite web |url=http://www.esa.int/Our_Activities/Space_Science/Rosetta/Science_on_the_surface_of_a_comet |title=Science on the Surface of a Comet |publisher=European Space Agency |date=30 July 2015 |access-date=30 July 2015 |url-status=live |archive-url=https://web.archive.org/web/20150802005802/http://www.esa.int/Our_Activities/Space_Science/Rosetta/Science_on_the_surface_of_a_comet |archive-date=2 August 2015}}{{cite journal |vauthors=Bibring JP, Taylor MG, Alexander C, Auster U, Biele J, Finzi AE, Goesmann F, Klingelhoefer G, Kofman W, Mottola S, Seidensticker KJ, Spohn T, Wright I |display-authors=6 |title=Philae's first look. Philae's First Days on the Comet. Introduction |journal=Science |volume=349 |issue=6247 |pages=493 |date=July 2015 |pmid=26228139 |bibcode=2015Sci...349..493B |doi=10.1126/science.aac5116 |doi-access=free|url=https://elib.dlr.de/97953/1/Science-2015-Bibring-493.pdf }}

In 2017, two teams of astronomers using the Atacama Large Millimeter Array (ALMA) interferometer made of 66 radio telescopes in the Atacama Desert (northern Chile) have discovered the presence of MIC around young Sun-like stars.{{cite web |title=ALMA Finds Ingredient of Life Around Infant Sun-like Stars |url=https://www.eso.org/public/news/eso1718/ |website=www.eso.org |access-date=8 June 2017 |url-status=live |archive-url=https://web.archive.org/web/20170608143057/http://www.eso.org/public/news/eso1718/ |archive-date=8 June 2017}}

MIC is considered a prebiotic molecule as explained by the discoverers of the ALMA findings in IRAS 16293-2422, a multiple system of very young stars: "This family of organic molecules is involved in the synthesis of peptides and amino acids, which, in the form of proteins, are the biological basis for life as we know it".

{{reflist}}

• [https://www.cdc.gov/niosh/topics/isocyanates/ NIOSH Safety and Health Topic: Isocyanates], from the website of the National Institute for Occupational Safety and Health (NIOSH).
• [http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@na+@rel+Methyl+isocyanate U.S. National Library of Medicine: Hazardous Substances Databank – Methyl isocyanate]

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Category:Isocyanates

Category:Monomers

Category:Bhopal disaster

Category:Pulmonary agents

Category:Lachrymatory agents

Category:Prebiotic chemistry

Category:Methyl compounds