Tritiated methyl iodide

From methyltriphenylphosphonium iodide, prepared by methylation of triphenylphosphine with highly tritiated methyl iodide, the enhanced, coupled % NMR spectrum shows fully resolved and interleaved, doublet, triplet, and quartet signals from the PCT3,... 

Methods for the preparation of tritiated methyl iodide in the laboratory use variations of the sp tritiodehalogenation approach. Palladium-catalyzed tritiodechlorinations of chloro-methyl ester 113 and of chloromethyl sulfide 115 ° have been developed as less hazardous alternatives to the older laboratory procedure for C HH2l at 15-22 Ci/mmol starting from bis(chloromethyl)ether °. The initially formed nonvolatile monotritiated 114 and 116 can be conveniently isolated, purified and finally subjected to ester cleavage with either lithium iodide or hydriodic acid, or, in the second case, by thermolysis of the intermediately generated sulfonium salt 117. 

The availability of high specific activity LiAl H4 stimulated the development of a new laboratory method for preparing high specific activity tritiated methyl iodide, previously produced by catalytic methods (Section 4.4.3). The new method is analogous to that for [ CJmethyl iodide using and LiAlEU and is illustrated in Figure 4.76. Since its... 

Figure 4.76 Preparation of high specific activity tritiated methyl iodide via lithium aluminum tritide...

Simon and Palm (118) have observed an effect of ka/hr = 0.96 (AAF = — 26 cal.) on the quatemization of pyridine with tritiated methyl iodide in benzene. This is clearly a pure Sn2 displacement, but both the steric and polar interpretations are consistent with a rather large inverse isotope effect in such a reaction. 

This neuroleptic drug 223313,314 has been labelled with carbon-14 in the 11-position315 (equation 150) and with C3H3 in the methyl group of the 4-methylpiperazine ring315 (equation 151) by reacting des-methyl clozapine 225 (obtained from lactam 226316) with tritiat-ed methyl iodide. 

Only one kinetic study exists on initiation of methacrylate polymerization by a sodium compound. The initiator was the disodium oligomer ( tetramer ) of a-methylstyrene and polymerization was investigated at 25°C in toluene in presence of 0.05—0.2 mole fraction of tetrahydrofuran [181]. An internal first order disappearance of monomer was observed, the first order coefficient being directly proportional to active chain and tetrahydrofuran concentrations. The rate coefficients evaluated, e.g. fep = 3.1—13 X 10 1 mole sec at various tetrahydrofuran concentrations, are much lower than those for lithium initiators. They were, however, evaluated using a methyl iodide titration technique to estimate the active chain concentration. In view of the reactivity of tritiated acetic acid with many short chains which are clearly not active in chain propagation, there must be suspicion of similar behaviour with methyl iodide. If this happens, the active chain concentration would be over-estimated and the derived fep value would be too low. Unfortunately no molecular weights of the precipitable polymer were determined, so that it is impossible to check on active chain concentration using this alternative method. 

The devolatilization concept has been extended to certain commonly used isotope sources with the additional advantage of making them more stable or storable. [ H/ C]Methyl nosylate (17) has been developed as a substitute for tritiated or carbon-14-labeled methyl iodide, both of which are relatively unstable and difficult to handle (Figure 1.6). Ester 17 is a nonvolatile, easily purifiable solid that is substantially less radiolytically sensitive than the corresponding methyl halides ([ H]methyl nosylate at a specific activity of > 80 Ci/mmol suffered no appreciable decomposition after storage at 39 mCi/mL for 14 weeks at 4 °C in hexane/ethyl acetate ). This derivative is reported to possess similar reactivity to [ H/ C]methyl iodide in a variety of reactions, and to provide greater flexibUity during use in synthesis. 

The ability of B H3-THF to effectively reduce amides is illustrated with the reduction of diamide 269 to give the tritiated cryptand 270 in chemical yield of about 50%. The reagent employed in this case was prepared from NaB H4 and BF3-Et20 (see also Chapter 11). The B Hj THF-mediated reduction of A -formyl compounds to high specific activity A -[ H]methylamines is of particular interest as an alternative to A -alkylation with [ H]-methyl iodide. Whereas the preparation of [ HJmecamylamine (271) by the latter method... 

H ]Methyl iodide (n=l or 3), the most common tritiated building block, has been extensively employed in various C-, N-, O- and 5-tritiomethylation reactions . ... 

A different approach, investigated for the labeling of 331 ° with tritium, and of some structurally related compounds with [ C, H]methyl iodide, involves (see generic reaction sequence in Figure 4.90) A-quaternization of the target compound using tritiated methyl... 

Tosyl cholesteryl acetate (V) (Akhtar and Barton, 1964) was first converted to the corresponding 19-iodide (VI) by treatment with sodium iodide in boiling ethyl methyl ketone. Reduction of the iodide with zinc and acid in the presenee of tritiated water provided cholesteryl acetate-19-H (VII) which was then converted to 7-dehydro-cholesterol-19-H (VIII), presxunably via the N-bromosuccinimide reaction. Ultraviolet irradiation and thermal rearrangement of the provitamin yielded cholecalciferol-9,19-H (IX). 

Reaction of [ HJmethyl iodide with homocysteine (3411 in liquid ammonia to give [methyl- H ]methionine (3421 is the most prominent and commercially exploited 5-tritiomethylation process (Figure 4.93). [methyl- H ]Methionine (n= 1,3) has frequently been used as a starting material for the synthesis of tritiated peptides and as a highly valuable precursor for the biological labeling of highly complex molecules such as... 

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