Methyl iodide, labelled with

Methyl iodide labelled with iodine-131 (half-life 8.040 d) has been obtained from diazomethane and potassium [131I]iodide (equation 222)481. 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

Generally, methylation of enolate ions with isotopically tagged methyl iodide is a satisfactory labeling procedure. For example, application of this method has given the C-18 labeled steroids, (244) and (245) (see above), 17 -acetoxy-4jS-trideuteriomethyl-4a-methyl-l9-norandrost-5-en-3-one (264) and 19- C-testosterone acetate (268). Methylation of the anion derived from 17jS-acetoxy-4-methyl-l9-norandrost-4-en-3-one (263) with d3-methyl iodide occurs predominantly at C-4, yielding mainly the 4)S-trideuterio-methyl derivative (264) and about 10% of the corresponding C-4 epimer... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

The novel highly substituted spiro[4.4]nonatrienes 98 and 99 are produced by a [3+2+2+2] cocyclization with participation of three alkyne molecules and the (2 -dimethylamino-2 -trimethylsilyl)ethenylcarbene complex 96 (Scheme 20). This transformation is the first one ever observed involving threefold insertion of an alkyne and was first reported in 1999 by de Meijere et al. [81]. The structure of the product was eventually determined by X-ray crystal structure analysis of the quaternary ammonium iodide prepared from the regioisomer 98 (Ar=Ph) with methyl iodide. Interestingly, these formal [3+2+2+2] cycloaddition products are formed only from terminal arylacetylenes. In a control experiment with the complex 96 13C-labeled at the carbene carbon, the 13C label was found only at the spiro carbon atom of the products 98 and 99 [42]. 

The stereospecific conversion of menthyl arenesulphinates into chiral aryl methyl sulphoxides may also be achieved by means of methyllithium . The reaction of methyllithium with diastereoisomerically or enantiomerically pure arenesulph-inamides 283 was found to give optically active aryl methyl sulphoxides 284 (equation 156). The preparation of optically active sulphoxides 285 and 286, which are chiral by virtue of isotopic substitution (H - D and - respectively), involves the reaction of the appropriate non-labelled menthyl sulphinates with fully deuteriated methyl magnesium iodide (equation 157) and with benzylmagnesium chloride prepared from benzyl chloride labelled with carbon (equation 158). 

Radioactive 11C-methyl labeling for study of methanol co-reaction with methyl iodide on Fe -Beta zeolite... 

Labelled [2H3]dodecyltrimethyl ammonium iodide ([2H3]Ci2TMAI) was synthesised as an internal standard for the quantitative determination of dodecyltrimethyl ammonium chloride (Ci2TMAC) in sewage and river water samples by using FAB-MS [117]. The synthesis of [2H3]Ci2TMAI involved the reaction of dimethylamino dodecane with deuterated methyl iodide (CD3I) in methanol. 

Finally, Persson et al. (1995) measured the UC/14C KIEs for the SN2 reactions between several amine nucleophiles and labelled methyl iodide in dimethoxyethane or acetonitrile at 15°C and 30°C, respectively, to determine how sterically hindered nucleophiles affects the transition state of a Menshut-kin reaction. The results in Table 25 show that all the fc11// 14-values for these reactions are large. In fact, they are all near the theoretical maximum value for these KIEs. Secondly, the KIE for the reaction with the more sterically hindered amine, 2,6-lutidine, is larger than that for the less sterically hindered... 

Remote double labelling techniques have been used successfully in the determination of enzyme KIEs (Kiick, 1991). A variant of this technique was applied to a nonenzymatic reaction by Matsson and co-workers (Axelsson et al., 1990). They determined the primary carbon and secondary deuterium KIEs for the SN2 reaction between methyl iodide and hydroxide ion in 50% dioxane-water at 25°C. The a-carbon KIE was determined by the UC method (Axelsson et al. 1987,1991). In this method, a mixture of substrate molecules labelled with UC (tm = 20.4 min) and 14C is used. The reactants and products... 

Fig. 7.3 Kinetic plots for nC and 14C in the reaction of labeled methyl iodide with N,N-dimethyl- -toluidine in methanol at 30°C. (CR is the count rate (cpm) for the reactant fraction and CP the count rate for product fraction) (After Axelsson, B. S. et. al. J. Am. Chem. Soc. 109, 7233 (1987))...

A slightly different example is the separate determination of rates of reaction of nC and 14C labeled methyl iodide with N,N-dimcthyl-/>-toluidine as illustrated in Fig. 7.3. Again the method takes advantage of the convenience of radiochemical analysis. If, as likely, the KIE of interest is ki2/ki4, it can be obtained to sufficiently good approximation by applying a modified Swain-Schaad rule, ln[ki2/ki4]/ln[kn/ki4] = [(12/14)/(11/14)]1/2 obtained from the law of the geometric mean (see Section 10.5). 

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... 

Vitamin B12s reacts rapidly with alkyl iodides (e.g., methyl iodide or a 5 -chloro derivative of adenosine) via nucleophilic displacement to form the alkyl cobalt forms of vitamin B12 (Eq. 16-31). These reactions provide a convenient way of preparing isotopically labeled alkyl cobalamins, including those selectively... 

The coenzyme evidently functions in a cyclic process. The cobalt alternates between the +1 and +3 oxidation states as shown in Eq. 16-43. The first indication of such a cyclic process was the report by Weissbach that 14C-labeled methylcobalamin could be isolated following treatment of the enzyme with such methyl donors as AdoMet and methyl iodide... 

Samuelsson, L. and LangstrOm, B., Synthesis of l (2 deoxy-2 -fluoro-(3-D-arabinofuranosyl)-[Me thy l-nc]Thymine ([nc]Fmau) via a Stille cross-coupling reaction with [nc]Methyl Iodide, J. Labelled Compd ... 

Package Lots. Place in a separate labeled container for recycling or disposal by burning. Dissolve the methyl iodide in a flammable solvent and burn in a furnace equipped with afterburner and scrubber.8... 

The direct attack of proton from the solvent on the intermediate dihydropyridine as well as the over-all mechanism of the reduction received support from the extent and position of deuterium labeling in the product from the reduction of l-methyl-4-phenyl-pyridinium iodide (7) with sodium borohydride in dimethylformamide and deuterium oxide. The l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (9) formed was shown by nuclear magnetic resonance (NMR) and mass spectral analysis to contain approximately one deuterium atom located at the 3-position.13,14 This is the result to be expected from the pathway shown in Eq. (3) if the electrophile were a deuteron. 

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