Methyl iodide : carcinogenicity methylation with

Weakly acidic phenols that do not react with diazomethane can be methylated with sodium hydride and methyl iodide in THF at room temperature. The methoxymethyl ether moiety can be used to protect phenols. It is stable to alkali, Grignard reagents, lithium aluminum hydride, and catalytic hydrogenation, and is readily removed by mineral acid. Dimethoxymethane can be used in lieu of the carcinogenic chloromethyl methyl ether for this purpose. Alternatively, phenols may be protected as methyl thiomethyl ethers.The (9-acetylation of phenols in the presence of primary and secondary amines can be carried out with acetyl bromide and TFA. ... 

The 2003 ACGIH threshold limit value-time-weighted average for methyl iodide (TLV-TWA) is 2 ppm (12 mg/m ) with an A2-suspected carcinogen designation and a notation for skin absorption. 

Caution. Methyl iodide is a known carcinogen. Protective gloves should be worn and the material handled with care. 

CAUTION Owing to the carcinogenic properties of methyl iodide and the toxicity of benzene all operations should be conducted with great care and in an efficient fume cupboard. 

Methyl iodide was purchased from Merck-Schuchardt, Hohenbrunn, Germany, or Wako Pure Chemical Industries, Ltd., Japan. Because of its volatility and possible carcinogenicity it should be handled 1n a well-ventilated hood. Sodium hydride was supplied by Riedel de Haen, Seelze, Germany, or Wako Pure Chemical Industries, Ltd., Japan. In a 1-L, round-bottomed flask 50 g of 80% sodium hydride (mineral oil dispersion) is washed free of oil by stirring with pentane (4 x 300 mL). After the supernatant liquid is decanted for the fourth time, the remaining solvent is removed by evaporation (20°C/1 mm). 

These four functional groups have similar properties—though alkyl iodides are the most reactive and alkyl fluorides the least. PVC (polyvinyl chloride) is one of the most widely used polymers—it has a chloro group on every other carbon atom along a linear hydrocarbon framework. Methyl iodide (Mel), on the other hand, is a dangerous carcinogen, since it reacts with DNA and can cause mutations in the genetic code. 

Alkylation of alcohols with 2-(methoxyethoxy)methyl chloride (MEMC1, bp 50-52 C/1.7 kPa) (HAZARD carcinogenic) under an assortment of conditions pioneered by Corey still retain favour. These include reaction of the lithium or sodium alkoxide (generated from sodium or potassium hydride) with ME MCI in THF or DME at 0 °C (10-60 min) and reaction of the alcohol with MEMCI in dichloromethane in the presence of /-Pr NEt at room temperature for 3 h. For hindered alcohols, sodium iodide can be added to generate the more reactive 2-methoxyethoxymethyl iodide in situ. Alternatively, reaction of the alcohol with [(2-methoxyethoxy)methyl]triethylammonium chloride (prepared from MEMO and trie thy lamine) in refluxing acetonitrile is recommended for acid-sensitive substrates such as tertiary alcohols [Scheme 4,271],500... 

To a cold solution of N-Boc-L-serine (32.4 g, 0.16 mol. Note 5) in dimethylformamide (150 ml) is added solid potassium carbonate (24.3 g, 0.176 mol). After stirring for 10 min in an ice-water bath, methyl iodide (20.0 mL, 46.3 g, 0.32 mol -Caution Methyl iodide is toxic and a suspected carcinogen that should be handled in a well-ventilated fume hood.) is added to the white suspension and stirring continued at 0°C for 30 min whereupon the mixture solidifies. The reaction is warmed to room temperature and stirred for an additional hour or so at which point TLC analysis indicates complete formation of the methyl ester (Note 6). The reaction mixture is filtered by suction and the filtrate partitioned between ethyl acetate (300 mL) and water (300 mL). The organic phase is washed with brine (2 x 300 mL), dried with magnesium sulfate, filtered and concentrated to give 29.8 g (86% yield) of N-Boc-L-serine methyl ester as a pale amber oil which is used without further purification (Notes 7 and 8).2... 

Toxicity The acute toxicity of methyl iodide is moderate by ingestion, inhalation, and skin contact. This substance is readily absorbed through the skin and may cause systemic toxicity as a result. Methyl iodide is moderately irritating upon contact with the skin and eyes. Methyl iodide is an acute neurotoxin. Symptoms of exposure (which may be delayed for several hours) can include nausea, vomiting, diarrhea, drowsiness, slurred speech, visual disturbances, and tremor. Massive overexposure may cause pulmonary edema, convulsions, coma, and death. Chronic exposure to methyl iodide vapor may cause neurotoxic effects such as dizziness, drowsiness, and blurred vision. There is limited evidence for the carcinogenicity of methyl iodide to experimental animals it is not classified as an OSHA "select carcinogen."... 

The glycine-derived anions (149) can be alkylated ca. 80% yield with primary iodides) and then converted into a-amino-acid methyl esters by reaction with performic acid, and carcinogenic alternatives are provided by reactions between the N-nitrosamines (150 = H or Me) and methyl chloro-... 

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