Methyl iodide 1311-labelled

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

The methyl iodide molecule is studied using microwave (pure rotational) spectroscopy. The following integral governs the rotational selection rules for transitions labeled J, M, K... 

Synthetic chemical approaches to the preparation of carbon-14 labeled materials iavolve a number of basic building blocks prepared from barium [ CJ-carbonate (2). These are carbon [ C]-dioxide [ CJ-acetjlene [U— C]-ben2ene, where U = uniformly labeled [1- and 2- C]-sodium acetate, [ C]-methyl iodide, [ C]-methanol, sodium [ C]-cyanide, and [ CJ-urea. Many compHcated radiotracers are synthesized from these materials. Some examples are [l- C]-8,ll,14-eicosatrienoic acid [3435-80-1] inoxn. [ CJ-carbon dioxide, [ting-U— C]-phenyhsothiocyanate [77590-93-3] ftom [ " CJ-acetjlene, [7- " C]-norepinephrine [18155-53-8] from [l- " C]-acetic acid, [4- " C]-cholesterol [1976-77-8] from [ " CJ-methyl iodide, [l- " C]-glucose [4005-41-8] from sodium [ " C]-cyanide, and [2- " C]-uracil [626-07-3] [27017-27-2] from [ " C]-urea. All syntheses of the basic radioactive building blocks have been described (4). 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

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]. 

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

In this work the methanol and methyl iodide conversion and their co-reaction are investigated on Fe-Beta zeolite without any oxygen. Partly Fe-ion-exchanged Beta-300 i.e. Fe-H-Beta-300 (shortly Fe-Beta-300) zeolite keeps the light acidity to a certain extent, however the presence of Fe ions (as transition metal, Fe is an excellent Lewis acid) can modify the reaction pathway. This Fe-Beta-300 has been tested already by low temperature peat pyrolysis [6], At present, the adsorption as well as desorption of methanol are followed-up by radiodetectors using ( -radioisotopic labeling [4, 7]. The... 

A glass tube fixed-bed reactor was used as a closed static reactor. The cyclotron produced nC-radioisotope (Ti/2=20.4 min) was used for nC-labeled methanol production by radiochemical process. The nC-labeled methanol (shortly nC-methanol, - 3pmol, -600 MBq) was then introduced into 250 mg of zeolite at ambient temperature by He gas flow. Afterwards, equivalent volume of liquid methyl iodide was injected into nC-methanol to have mixture of methanol and methyl iodide and introduced into catalyst for investigation of methyl iodide influence. After adsorption (2 min), the catalyst was heated up to the required temperature. 

In a separate experimental series, only 1 -labeled methyl iodide was also synthesized by radiochemical process for following of methyl group of methyl iodide in conversion and co-reaction on Fe-Beta -300 catalyst. 

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. 

Fig. 11.10 Diagram showing the reaction scheme for the exchange of the methionine side chain using carbon-13 methyl iodide (a) and the labeling of cysteine side chains using the reagent...

Matsson and co-workers (Axelsson et al., 1987) measured the carbon-ll/carbon-14 a-carbon KIEs for the Menshutkin reaction between N,N-dimethyl-p-toluidine and labelled methyl iodide in methanol at 30°C. The 1 -labelled methyl iodide required for this study was prepared in three steps [reaction (23)] from the "C atoms produced in a cyclotron (L ngstrom etal., 1987). 

Table 25 The carbon-ll/carbon-14 KIEs for the SN2 reactions between several amine nucleophiles and labelled methyl iodide in acetonitrile or dimethoxyethane at 30°C and 15°C, respectively.0...

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... 

The carbon-14 labelled methyl iodide used to measure the kll/k14 was commercially available. 

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 ... 

---