Methyl iodide sources

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

The reaction is catalyzed by a group VIII metal species, particularly that of rhodium or palladium. The initial metal species may be any variety of complexes (e.g., PdCl2 Pd acetate, etc.). A source of halide is necessary iodide is especially effective. The most convenient source is methyl iodide, since it is likely a reaction intermediate. In addition, an organic promoter must be included for catalytic activity. These promoters are generally tertiary phosphines or amines. Also, chromium complexes were found to have an important promotional effect. 

Table III. Homologation of Methyl Acetate to Ethyl Acetate Effect of Iodide Source...

Methyl iodide is produced by many marine photosynthetic organisms and therefore the ocean is thought to be a major natural source of methyl iodide. Some of this is released to the atmosphere and some reacts with seawater to form methyl chloride. Industrial emissions of methyl iodide may occur in conjunction with its use as a methylating agent and in organic synthesis. Humans are exposed to methyl iodide from the ambient air and from ingesting seafood (United States National Library of Medicine, 1998). 

Support for the mechanism comes from various sources including NMR spectroscopy using 13C labeled MeMgl,309 methylation of primary MeMgl adducts with methyl iodide,306 isolation of intermediates of type 301 and... 

It is reported that trimethylamine in combination occurs in large amounts in beet-root residues 2 and can be obtained from them by the action of caustic soda it occurs also in herring brine.3 From both of these sources, however, the substance is obtained in an impure state and can be purified only by rather tedious methods. This is indicated by the fact that trimethylamine has always been an expensive substance. Synthetic methods for its production are by the action of methyl iodide on ammonia 4 by the distillation of tetramethylammo-nium hydroxide 6 by the action of magnesium nitride upon methyl alcohol 6 by the action of zinc upon trimethyloxy-ammonium halides 7 by the action of formaldehyde upon ammonium chloride under pressure 8 by the action of ammonium chloride upon paraformaldehyde.9 Of these syn-... 

The mechanism for the reaction is believed to be as shown in Eq. 15.170 (start with CH3OH, lower right, and end with CHjCOOH, lower left).180 The reaction can be initiated with any rhodium salt, e.g., RhCl3, and a source of iodine, the two combining with CO to produce the active catalyst, IRItfCO y. The methyl iodide arises from the reaction of methanol and hydrogen iodide. Note that the catalytic loop involves oxidative addition, insertion, and reductive elimination, with a net production of acetic acid from the insertion of carbon monoxide into methanol. The rhodium shuttles between the +1 and +3 oxidation states. The cataylst is so efficient that the reaction will proceed at atmospheric pressure, although in practice the system is... 

Metalloporphyrin mono- and di-anions are readily formed, most conveniently by electrochemical methods, and as would be expected they behave as strong nucleophiles. They react rapidly with proton sources or with electrophiles such as methyl iodide, and the products are usually substituted on methine carbons 5 and 15 to give derivatives such as (63), which are called porphodimethenes. 

When the apparatus is in use, the bulb of the flask containing the hydriodic aid and the substance is heated in an oil bath at 130°. The methyl iodide is carried over into the absorber by a slow current of dry carbon dioxide, passing in at the side tube. The temperature on the thermometer should not be higher than 35°—40° for methoxyl, and 40° for ethoxyl compounds. At these temperatures no hydriodic acid is distilled over. As a further precaution, the neck of the flask is slanted away from the source of heat. 

To investigate the nature of ordering in liquids, we have studied the temperature dependence of the OHD-RIKES response of a number of symmetric-top liquids, including acetonitrile-d3, benzene, benzene-d6, carbon disulfide, chloroform, and methyl iodide (56). These liquids were chosen in particular because data on rsm were available from other sources, including NMR data for acetonitrile-d3 (57), Raman data for benzene and benzene-d3 (45), NMR data for carbon disulfide (58), NMR data for chloroform (59), and Raman data for methyl iodide (45). Since the OHD-RIKES data were not all obtained at the same temperatures as the rsm data, we used the fact that the single-molecule orientational correlation time generally obeys the Arrhenius equation to interpolate (and, where necessary, extrapolate) values of rsm at temperatures matching those of the icon data. 

Although several studies have examined the effects of various promoters and ligands on the methanol homologation reaction, none has identified a system with substantially improved selectivity. However, there are many claims that iodide accelerates the rate of the reaction 62-64). While the possible sources of this enhancement have been discussed in Section IV,B, it should be noted that the systems from which these interpretations were extracted are by no means simple. Qualitative comparisons among the various studies of promoted and unpromoted systems are difficult for the reasons given above, but, in addition, because the variety of forms by which iodine is introduced (e.g., I2, CH3I, or iodide salts) apparently produce different effects (57, 63, 64). Also, many of the systems involve two promoter components (e.g., triphenylphosphine + methyl iodide or tri-p-tolylphosphine + I2X which further complicates the interpretations as to the role(s) of the halide. 

Methoxy-l-naphthoic acids (107 R = H, OMe) have been reduced with lithium or sodium in ammonia, with no loss of the ortho methoxy substituent being reported. Thus, in the presence of ethanol the 1,4-dihydro acids (108 R = H) are obtained, while reduction in the absence of a proton source and quenching with methyl iodide affords the alkylated acids (108 R = H, OMe, R = Me). The conditions used for the reductive alkylation in the earlier examples (Na/NH3/-70 C) would enhance retention of the... 

---