Iodomethane

Storage and purification

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.^[8] It can be purified by washing with Na₂S₂O₃ to remove iodine followed by distillation.

Biogenic iodomethane

Most iodomethane is produced by microbial methylation of iodide. Oceans are the major source, but rice paddies are also significant.^[9]

Methylation reagent

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.^[8] 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:^[10]

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.

Other reactions

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,^[11] after both Chernobyl and Fukushima, Iodine-131 was detected in organic iodine compounds in Europe^[12] and Japan^[13] respectively.

Toxicity and biological effects

According to the United States Department of Agriculture iodomethane exhibits moderate to high acute toxicity for inhalation and ingestion.^[21] 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.^[22] 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.^[23]

Iodomethane has an LD₅₀ for oral administration to rats 76 mg/kg, and is rapidly converted in the liver to S-methylglutathione.^[24]

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.^{[citation needed]} 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."^[25] "An updated literature search on May 30, 2007 for iodomethane poisoning produced only one additional case report."^[26] 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.^{[citation needed]}

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.^[27]

Carcinogenicity in mammals

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.^[28]

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^[update] 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).^[29] 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."^[30] 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.^{[citation needed]}