Iodomethane

Iodomethane is formed via the exothermic reaction that occurs when iodine is added to a mixture of methanol with red phosphorus.{{OrgSynth | author = King, C. S. | author2 = Hartman, W. W. | title = Methyl Iodide | collvol = 2 | collvolpages = 399 | year = 1943 | prep =CV2P0399}} The iodinating reagent is phosphorus triiodide that is formed in situ:

:3 CH₃OH + PI₃ → 3 CH₃I + H₂PO₃H

Alternatively, it is prepared from the reaction of dimethyl sulfate with potassium iodide in the presence of calcium carbonate:

:(CH₃O)₂SO₂ + KI → CH₃I + CH₃OSO₂OK

Iodomethane can also be prepared by the reaction of methanol with aqueous hydrogen iodide:

: CH₃OH + HI → CH₃I + H₂O

The generated iodomethane can be distilled from the reaction mixture.

Iodomethane may also be prepared by treating iodoform with potassium hydroxide and dimethyl sulfate under 95% ethanol.{{Cite journal | doi=10.1021/ed010p747|title = Preparation of methyl or ethyl iodide from iodoform| journal=Journal of Chemical Education| volume=10| issue=12| pages=747|year = 1933|last1 = Kimball|first1 = R. H.|bibcode = 1933JChEd..10..747K}}

In the Tennessee Eastman acetic anhydride process iodomethane is formed as an intermediate product by a catalytic reaction between methyl acetate and lithium iodide.

Like many organoiodide compounds, iodomethane is typically stored in dark bottles to inhibit degradation caused by light to give iodine, giving degraded samples a purplish tinge. Commercial samples may be stabilized by copper or silver wire. It can be purified by washing with Na₂S₂O₃ to remove iodine followed by distillation.

Most iodomethane is produced by microbial methylation of iodide. Oceans are the major source, but rice paddies are also significant.{{cite journal|journal=Int. J. Environ. Sci. Technol.|year=2017|pages=1355–1370|doi=10.1007/s13762-016-1219-5|title=REVIEW: Halocarbon Emissions from Marine Phytoplankton and Climate Change|first1=Y.-K.|last1=Lim|first2=S.-M.|last2=Phang|first3=N. Abdul |last3=Rahman|first4=W. T.|last4=Sturges|first5= G.|last5=Malin|s2cid=99300836}}

Iodomethane is an excellent substrate for S_N2 substitution reactions. It is sterically open for attack by nucleophiles, and iodide is a good leaving group. It is used for alkylating carbon, oxygen, sulfur, nitrogen, and phosphorus nucleophiles.{{cite encyclopedia | encyclopedia = e-EROS | last1 = Sulikowski | first1 = Gary A. | title = Encyclopedia of Reagents for Organic Synthesis | last2 = Sulikowski | first2 = Michelle M. | last3 = Haukaas | first3 = Michael H. | last4 = Moon | first4 = Bongjin | year = 2005 | doi = 10.1002/047084289X.ri029m.pub2| isbn = 978-0471936237 | chapter = Iodomethane }} Unfortunately, it has a high equivalent weight: one mole of iodomethane weighs almost three times as much as one mole of chloromethane and nearly 1.5 times as much as one mole of bromomethane. On the other hand, chloromethane and bromomethane are gaseous, thus harder to handle, and are also weaker alkylating agents. Iodide can act as a catalyst when reacting chloromethane or bromomethane with a nucleophile while iodomethane is formed in situ.

Iodides are generally expensive relative to the more common chlorides and bromides, though iodomethane is reasonably affordable; on a commercial scale, the more toxic dimethyl sulfate is preferred, since it is cheap and has a higher boiling point. The iodide leaving group in iodomethane may cause unwanted side reactions. Finally, being highly reactive, iodomethane is more dangerous for laboratory workers than related chlorides and bromides.

For example, it can be used for the methylation of carboxylic acids or phenols:{{cite journal

| title = Efficient methylation of carboxylic acids with potassium hydroxide/methyl sulfoxide and iodomethane

| author = Avila-Zárraga, J. G.

| author2 = Martínez, R.

| journal = Synthetic Communications

| volume = 31

| issue = 14

| pages = 2177–2183

| date=January 2001

| doi = 10.1081/SCC-100104469| s2cid = 94476899

}}

:Image:Iodomethane rxn1.png

In these examples, the base (K₂CO₃ or Li₂CO₃) removes the acidic proton to form the carboxylate or phenoxide anion, which serves as the nucleophile in the S_N2 substitution.

Iodide is a "soft" anion which means that methylation with MeI tends to occur at the "softer" end of an ambidentate nucleophile. For example, reaction with thiocyanate ion favours attack at sulfur rather than "hard" nitrogen, leading mainly to methyl thiocyanate (CH₃SCN) rather than methyl isothiocyanate CH₃NCS. This behavior is relevant to the methylation of stabilized enolates such as those derived from 1,3-dicarbonyl compounds. Methylation of these and related enolates can occur on the harder oxygen atom or the (usually desired) carbon atom. With iodomethane, C-alkylation nearly always predominates.

In the Monsanto process and the Cativa process, MeI forms in situ from the reaction of methanol and hydrogen iodide. The CH₃I then reacts with carbon monoxide in the presence of a rhodium or iridium complex to form acetyl iodide, the precursor to acetic acid after hydrolysis. The Cativa process is usually preferred because less water is required to use and there are less byproducts.

MeI is used to prepare the Grignard reagent, methylmagnesium iodide ("MeMgI"), a common source of "Me⁻". The use of MeMgI has been somewhat superseded by the commercially available methyllithium. MeI can also be used to prepare dimethylmercury, by reacting 2 moles of MeI with a 2/1-molar sodium amalgam (2 moles of sodium, 1 mol of mercury).

Iodomethane and other organic iodine compounds do form under the conditions of a serious nuclear accident,{{cite journal|doi=10.1080/23312009.2015.1049111 | volume=1 | title=An introduction to serious nuclear accident chemistry | year=2015 | journal=Cogent Chemistry | first1 = Mark Russell | last1 = St. John Foreman| doi-access=free }} after both Chernobyl and Fukushima, Iodine-131 was detected in organic iodine compounds in Europe{{cite journal |doi=10.1080/10256016.2013.828717 |title=Fission products from the damaged Fukushima reactor observed in Hungary |year=2014 |last1=Bihari |first1=Árpád |last2=Dezső |first2=Zoltán |last3=Bujtás |first3=Tibor |last4=Manga |first4=László |last5=Lencsés |first5=András |last6=Dombóvári |first6=Péter |last7=Csige |first7=István |last8=Ranga |first8=Tibor |last9=Mogyorósi |first9=Magdolna |last10=Veres |first10=Mihály |journal=Isotopes in Environmental and Health Studies |volume=50 |issue=1 |pages=94–102 |pmid=24437973 |s2cid=8992460 |url=http://real.mtak.hu/21034/1/ArpadBihari_4b_TF_manuscript_revised_forREAL.pdf }} and Japan{{cite journal |doi=10.1016/0265-931X(88)90042-2|title=Physicochemical speciation of airborne 131I in Japan from Chernobyl|year=1988|last1=Noguchi|first1=Hiroshi|last2=Murata|first2=Mikio|journal=Journal of Environmental Radioactivity|volume=7|pages=65–74}} respectively.

Iodomethane had also been proposed for use as a fungicide, herbicide, insecticide, nematicide, and as a soil disinfectant, replacing methyl bromide (also known as bromomethane) (banned under the Montreal Protocol). Manufactured by Arysta LifeScience and sold under the brand name MIDAS, iodomethane is registered as a pesticide in the U.S., Mexico, Morocco, Japan, Turkey, and New Zealand and registration is pending in Australia, Guatemala, Costa Rica, Chile, Egypt, Israel, South Africa and other countries.{{cite news|url=https://www.businesswire.com/news/home/20101025006234/en/Iodomethane-Approved-Mexico-Morocco |title=Iodomethane Approved in Mexico and Morocco |work=Business Wire |date=October 25, 2010 |access-date=2018-11-25}} The first commercial applications of iodomethane soil fumigant in California began in Fresno County in May 2011.{{cite web |author1=Nathan Rice |title=The fight over a much-needed pesticide: methyl iodide |url=https://www.hcn.org/issues/43-12/the-fight-over-a-much-needed-pesticide-methyl-iodide/ |website=High Country News |access-date=9 June 2024 |date=25 July 2011}}

Iodomethane had been approved for use as a pesticide by the United States Environmental Protection Agency in 2007 as a pre-plant biocide used to control insects, plant parasitic nematodes, soil borne pathogens, and weed seeds.Zitto, Kelly {{cite news | url = http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2010/12/01/BAOQ1GKKKN.DTL | title = Methyl iodide gains state OK for use on crops | work = San Francisco Chronicle | date = December 2, 2010 | first=Kelly | last=Zito}} The compound was registered for use as a preplant soil treatment for field grown strawberries, peppers, tomatoes, grape vines, ornamentals and turf and nursery grown strawberries, stone fruits, tree nuts, and conifer trees. After the discovery phase in a consumer lawsuit, the manufacturer withdrew the fumigant citing its lack of market viability.[http://www.mercurynews.com/central-coast/ci_20219822/maker-methyl-iodide-scraps-controversial-pesticide "Maker of methyl iodide scraps controversial pesticide"] San Jose Mercury News March 20, 2012

The use of iodomethane as a fumigant has drawn concern. For example, 54 chemists and physicians contacted the U.S. EPA in a letter, saying "We are skeptical of U.S. EPA's conclusion that the high levels of exposure to iodomethane that are likely to result from broadcast applications are 'acceptable' risks. U.S. EPA has made many assumptions about toxicology and exposure in the risk assessment that have not been examined by independent scientific peer reviewers for adequacy or accuracy. Additionally, none of U.S. EPA's calculations account for the extra vulnerability of the unborn fetus and children to toxic insults."{{cite magazine| url=https://www.wired.com/wiredscience/2007/10/scientists-stop/ | magazine=Wired | first=Brandon | last=Keim | title=Scientists Stop EPA From Pushing Toxic Pesticide | date=October 1, 2007}} EPA Assistant Administrator Jim Gulliford replied saying, "We are confident that by conducting such a rigorous analysis and developing highly restrictive provisions governing its use, there will be no risks of concern," and in October the EPA approved the use of iodomethane as a soil fumigant in the United States.

The California Department of Pesticide Regulation (DPR) concluded that iodomethane is "highly toxic," that "any anticipated scenario for the agricultural or structural fumigation use of this agent would result in exposures to a large number of the public and thus would have a significant adverse impact on the public health", and that adequate control of the chemical in these circumstances would be "difficult, if not impossible."{{cite news | url = http://www.cdpr.ca.gov/docs/risk/mei/peer_review_report.pdf | title = Report of the Scientific Review Committee on Methyl Iodide to the Department of Pesticide Regulation | work = special Scientific Review Committee of the California Department of Pesticide Regulation | date = February 5, 2010}} Iodomethane was approved as a pesticide in California that December.{{cite news |last1=Schwartz |first1=Carly |title=Methyl Iodide Controversy: California Officials Ignored Scientists In Approving Dangerous Pesticide |url=https://www.huffingtonpost.com/2011/08/30/california-pesticides-officials-ignored-scientists_n_942757.html |access-date=2018-11-25 |work=Huffington Post |date=31 August 2011}} A lawsuit was filed on January 5, 2011, challenging California's approval of iodomethane. Subsequently, the manufacturer withdrew the fumigant and requested that California Department of Pesticide Regulation cancel its California registration, citing its lack of market viability.

According to the United States Department of Agriculture iodomethane exhibits moderate to high acute toxicity for inhalation and ingestion.{{Cite journal|doi=10.2134/jeq2008.0124 |pmid=19202021 |title=Degradation of Methyl Iodide in Soil: Effects of Environmental Factors |journal=Journal of Environmental Quality |url=http://ddr.nal.usda.gov/bitstream/10113/28473/1/IND44184498.pdf |last1=Guo |first1=Mingxin |last2=Gao |first2=Suduan |pages=513–519 |year=2009 |volume=38 |issue=2 |url-status=dead |archive-url=https://web.archive.org/web/20110814102050/http://ddr.nal.usda.gov/bitstream/10113/28473/1/IND44184498.pdf |archive-date=August 14, 2011 |df=mdy }} The Centers for Disease Control and Prevention (CDC) lists inhalation, skin absorption, ingestion, and eye contact as possible exposure routes with target organs of the eyes, skin, respiratory system, and the central nervous system. Symptoms may include eye irritation, nausea, vomiting, dizziness, ataxia, slurred speech, and dermatitis.{{cite web|url=https://www.cdc.gov/niosh/npg/npgd0420.html|title=CDC - NIOSH Pocket Guide to Chemical Hazards - Methyl iodide|work=cdc.gov|access-date=June 25, 2016}} In high dose acute toxicity, as may occur in industrial accidents, toxicity includes metabolic disturbance, renal failure, venous and arterial thrombosis and encephalopathy with seizures and coma, with a characteristic pattern of brain injury.{{cite journal|doi=10.1136/practneurol-2013-000565|title = Methyl iodide rhombencephalopathy: clinico-radiological features of a preventable, potentially fatal industrial accident|journal = Practical Neurology|url=http://pn.bmj.com/content/13/6/393.full|last1=Iniesta|first1=Ivan|last2=Radon|first2=Mark|last3=Pinder|first3=Colin|year=2013|volume=13|issue = 6|pages = 393–395|pmid = 23847234|s2cid = 36789199|url-access=subscription}}

Iodomethane has an {{LD50}} for oral administration to rats 76 mg/kg, and is rapidly converted in the liver to S-methylglutathione.{{cite journal | title = Metabolism of iodomethane in the rat | author = Johnson, M. K. | journal = Biochem. J. | volume = 98 | issue = 1| pages = 38–43 | year = 1966 | doi = 10.1042/bj0980038 | pmid=5938661 | pmc=1264791}}

In its risk assessment of iodomethane, the U.S. EPA conducted an exhaustive scientific and medical literature search over the past 100 years for reported cases of human poisonings attributable to the compound.{{cn|date=May 2024}} Citing the EPA as its source, the California Department of Pesticide Regulation said: "Over the past century, only 11 incidents of iodomethane poisoning have been reported in the published literature." (Hermouet, C. et al. 1996 & Appel, G.B. et al. 1975) "An updated literature search on May 30, 2007 for iodomethane poisoning produced only one additional case report." (Schwartz MD, et al. 2005). All but one were industrial—not agricultural—accidents, and the remaining case of poisoning was an apparent suicide. Iodomethane is routinely and regularly used in industrial processes as well as in most university and college chemistry departments for study and learning related to a variety of organic chemical reactions.{{cn|date=May 2024}}

In 2024, a case of a person being injected with iodomethane emerged. The subject, who was the victim of attempted murder by a GP disguised as a community nurse, went on to develop necrotizing fasciitis but survived.{{cite news|url= https://www.bbc.com/news/articles/c4g9ve47e92o|last=Leatherdale |first=Duncan |title=Disguised GP admits attempted murder poisoning |work=BBC News |date=7 October 2024 |access-date=7 October 2024}}

The U.S. National Institute for Occupational Safety and Health (NIOSH), the U.S. Occupational Safety and Health Administration and the U.S. Centers for Disease Control and Prevention consider iodomethane a potential occupational carcinogen.{{cite web|url=https://www.cdc.gov/niosh/84117_43.html |title=CIB 43: MONOHALOMETHANES |url-status=dead |archive-url=https://web.archive.org/web/20110629133851/http://www.cdc.gov/niosh/84117_43.html |archive-date=June 29, 2011 |df=mdy }}

The International Agency for Research on Cancer concluded based on studies performed after methyl iodide was put on the Proposition 65 list that: "Methyl iodide is not classifiable as to its carcinogenicity to humans (Group 3)." {{As of|2007}} the Environmental Protection Agency classifies it as "not likely to be carcinogenic to humans in the absence of altered thyroid hormone homeostasis," i.e. it is a human carcinogen but only at doses large enough to disrupt thyroid function (via excess iodide).{{cite web |url=http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0252-0056 |title=Iodomethane Pesticide Fact Sheet |year=2007 }} (36 pages, inc 12 pages of refs) However this finding is disputed by the Pesticide Action Network, which states that the EPA's assessment "appears to be based solely on a single rat inhalation study in which 66% of the control group and 54-62% of the rats in the other groups died before the end of the study". They go on to state: "The EPA appears to be dismissing early peer-reviewed studies in favor of two nonpeer-reviewed studies conducted by the registrant that are flawed in design and execution."{{cite web|url=http://www.cdpr.ca.gov/docs/risk/mei/comments/panna_mei_attach1.pdf |title=Re: Comments on the Methyl Iodide Preliminary Risk Assessment |access-date=April 26, 2011 |website=cdpr.ca.gov |url-status=dead |archive-url=https://web.archive.org/web/20110726123944/http://www.cdpr.ca.gov/docs/risk/mei/comments/panna_mei_attach1.pdf |archive-date=July 26, 2011 }} Despite requests by the U.S. EPA to the Pesticide Action Network to bring forth scientific evidence of their claims, they have not done so.{{cn|date=May 2024}}

• Angelita C. et al. v. California Department of Pesticide Regulation

{{Reflist|30em}}

• {{March4th}}
• Sulikowski, G. A.; Sulikowski, M. M. (1999). in Coates, R.M.; Denmark, S. E. (Eds.) Handbook of Reagents for Organic Synthesis, Volume 1: Reagents, Auxiliaries and Catalysts for C-C Bond Formation New York: Wiley, pp. 423–26.
• {{cite journal

| title = Mechanisms of carcinogenicity of methyl halides.

|author1=Bolt H. M. |author2=Gansewendt B. | journal = Crit Rev Toxicol

| volume = 23

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| year = 1993

| pmid = 8260067

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• {{ICSC|0509|05}}
• {{PGCH|0420}}

• IARC Summaries & Evaluations: [http://www.inchem.org/documents/iarc/vol15/methyliodide.html Vol. 15 (1977)], [http://www.inchem.org/documents/iarc/vol41/methyliodide.html Vol. 41 (1986)], [http://www.inchem.org/documents/iarc/vol71/100-methiodi.html Vol. 71 (1999)]
• [http://www.biochemj.org/bj/098/0038/bj0980038_browse.htm Metabolism of iodomethane in the rat]
• [https://web.archive.org/web/20070210181503/http://www.muhlenberg.edu/depts/chemistry/chem201woh/1Hiodomethane.htm Iodomethane NMR spectra]
• {{cite journal|last=Jones|first=Nicola|date=September 24, 2009|title=Strawberry pesticide leaves sour taste: Methyl iodide use by Californian farmers up for review.|journal=Nature News|url=http://www.nature.com/news/2009/090924/full/news.2009.943.html|access-date=September 25, 2009|doi=10.1038/news.2009.943|url-access=subscription}}
• {{PPDB|1233|Name=Iodomethane}}

{{halomethanes}}

{{Authority control}}

Category:Iodoalkanes

Category:Halomethanes

Category:Methylating agents

Category:IARC Group 3 carcinogens

Category:Environmental controversies

Category:Environmental effects of pesticides

Category:Pesticides in the United States

Category:Halogen-containing natural products

Category:Iodine-containing natural products