Methyl iodide

Methyl iodide
IUPAC name Iodomethane[1]
Other names Methyl iodine Monoiodomethane
Identifiers
Abbreviations	Halon 10001 MeI
CAS number	74-88-4 Y
PubChem	6328
ChemSpider	6088 Y
EC number	200-819-5
UN number	2644
KEGG	C18448 Y
MeSH	methyl+iodide
ChEBI	CHEBI:39282 Y
ChEMBL	CHEMBL115849 Y
RTECS number	PA9450000
Beilstein Reference	969135
Gmelin Reference	1233
Jmol-3D images	Image 1
SMILES CI
InChI InChI=1S/CH3I/c1-2/h1H3 Y Key: INQOMBQAUSQDDS-UHFFFAOYSA-N Y
Properties
Molecular formula	CH3I
Molar mass	141.94 g mol−1
Appearance	Colourless liquid
Density	2.28 g mL−1
Melting point	−66.5 °C; −87.6 °F; 206.7 K
Boiling point	42.4 to 42.8 °C; 108.2 to 108.9 °F; 315.5 to 315.9 K
Solubility in water	14 g L−1 (at 20 °C)
log P	1.609
Vapor pressure	54.4 kPa (at 20 °C)
kH	1.4 μmol Pa−1 kg−1
Refractive index (nD)	1.530–1.531
Structure
Molecular shape	Tetrahedron
Thermochemistry
Std enthalpy of formation ΔfHo298	−14.1–−13.1 kJ mol−1
Std enthalpy of combustion ΔcHo298	−808.9–−808.3 kJ mol−1
Specific heat capacity, C	82.75 J K−1 mol−1
Hazards
GHS pictograms
GHS signal word	DANGER
GHS hazard statements	H301, H312, H315, H331, H335, H351
GHS precautionary statements	P261, P280, P301+310, P311
EU Index	602-005-00-9
EU classification	T
R-phrases	R21, R23/25, R37/38, R40
S-phrases	(S1/2), S36/37, S38, S45
NFPA 704	1 3 1
Explosive limits	8.5–66%
LD50	76 mg kg−1 (oral, rat) 800 mg kg−1 (dermal, guinea pig)
Related compounds
Related iodomethanes	Methane Diiodomethane Iodoform Carbon tetraiodide
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Methyl iodide, also called iodomethane, and commonly abbreviated "MeI", is the chemical compound with the formula CH₃I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one hydrogen atom by an atom of iodine. It is naturally emitted by rice plantations in small amounts.^[2] It is also produced in vast quantities estimated to be greater than 214,000 tons annually by algae and kelp in the world's temperate oceans and in lesser amounts on land due to terrestrial fungi and bacteria. It is used in organic synthesis as a source of methyl groups.

Methyl iodide 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.^[3] 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.^[4]

Preparation and handling

Methyl iodide is formed via the exothermic reaction that occurs when iodine is added to a mixture of methanol with red phosphorus.^[5] The iodinating reagent is phosphorus triiodide that is formed in situ:

3 CH₃OH + PI₃ → 3 CH₃I + H₃PO₃

Alternatively, it is prepared from the reaction of dimethyl sulfate with potassium iodide in the presence of calcium carbonate:^[5]

(CH₃O)₂SO₂ + KI → CH₃I + CH₃OSO₂OK

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

CH₃OH + HI → CH₃I + H₂O

The generated methyl iodide can be distilled from the reaction mixture.

Storage and purification

Like many organoiodide compounds, methyl iodide 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.^[6] It can be purified by washing with Na₂S₂O₃ to remove iodine followed by distillation.

Reactions

Methylation reagent

Methyl iodide 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.^[6] Unfortunately, it has a high equivalent weight: one mole of methyl iodide weighs almost three times as much as one mole of methyl chloride. On the other hand, methyl chloride and methyl bromide are gaseous, thus harder to handle; they are also weaker alkylating agents.

Iodides are generally expensive relative to the more common chlorides and bromides, though methyl iodide 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 methyl iodide may cause side reactions, as it is a powerful nucleophile. Finally, being highly reactive, methyl iodide 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:^[7]

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 S rather than "hard" N, leading mainly to methyl thiocyanate (CH₃SCN) rather than 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 methyl iodide, C-alkylation nearly always predominates.

Other reactions

In the Monsanto 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 complex to form acetyl iodide, the precursor to acetic acid after hydrolysis. Most acetic acid is prepared by this method.

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).

Use as a pesticide

Methyl iodide 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, methyl iodide 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.^[8] The first commercial applications of MIDAS soil fumigant in California began in Fresno County, in May, 2011.^{[citation needed]}

The use of methyl iodide 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 methyl iodide 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."^[9] 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 methyl iodide as a soil fumigant in the United States.

The California Department of Pesticide Regulation (DPR) concluded that methyl iodide 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."^[10] Methyl iodide was approved as a pesticide in California that December.^[11] A lawsuit was filed on January 5, 2011, challenging California's approval of methyl iodide. Subsequently, the manufacturer withdrew the fumigant and requested that California Department of Pesticide Regulation cancel its California registration, citing its lack of market viability.^[4]

Safety

Toxicity and biological effects

According to the United States Department of Agriculture methyl iodide exhibits moderate to high acute toxicity for inhalation and ingestion.^[12] 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.^[13]

Methyl iodide has an LD₅₀ for oral administration to rats 76 mg/kg, and in the liver it undergoes rapid conversion to S-methylglutathione.^[14]

In its risk assessment of methyl iodide, 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. Citing the EPA as its source, the California Department of Pesticide Regulation concluded, “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. Methyl iodide 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.

Carcinogenicity in mammals

It is considered a potential occupational carcinogen by 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.^[15] The International Agency for Research on Cancer concluded based on studies performed after methyl iodide was Proposition 65 listed 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 homeostatis," i.e. it is a human carcinogen but only at doses large enough to disrupt thyroid function (via excess iodide).^[16] However this finding is disputed by the Pesticide Action Network which states that the EPA’s cancer rating "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."^[17] 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.

References

Additional sources

• March, Jerry (1992), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (4th ed.), New York: Wiley, ISBN 0-471-60180-2 
• 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.
• Bolt H. M., Gansewendt B. (1993). "Mechanisms of carcinogenicity of methyl halides.". Crit Rev Toxicol. 23 (3): 237–53. doi:10.3109/10408449309105011. PMID 8260067. 

External links

• International Chemical Safety Card 0509
• NIOSH Pocket Guide to Chemical Hazards 0420
• IARC Summaries & Evaluations: Vol. 15 (1977), Vol. 41 (1986), Vol. 71 (1999)
• Metabolism of iodomethane in the rat
• Iodomethane NMR spectra
• Jones, Nicola (September 24, 2009). "Strawberry pesticide leaves sour taste: Methyl iodide use by Californian farmers up for review.". Nature News. doi:10.1038/news.2009.943. Retrieved September 25, 2009.