Methyldiazonium

When diazomethane is slowly added to excess lactam, the anions formed can interact with unreacted lactam by means of hydrogen bonds to form ion pairs similar to those formed by acetic acid-tri-ethylamine mixtures in nonpolar solvents. The methyldiazonium ion is then involved in an ion association wdth the mono-anion of a dimeric lactam which is naturally less reactive than a free lactam anion. The velocity of the Sn2 reaction, Eq. (7), is thus decreased. However, the decomposition velocity of the methyldiazonium ion, Eq. (6a), is constant and, hence, the S l character of the reaction is increased which favors 0-methylation. It is possible that this effect is also involved in kinetic dependence investigations have shown that with higher saccharin concentrations more 0-methylsaccharin is formed. 

The reaction occurs in two steps (1) protonation of diazomethane by the carboxylic acid to yield methyldiazonium ion, CH3N2+, plus a carboxylate ion and (2) reaction of the carboxylate ion with CH3N2+. 

Temozolomide undergoes spontaneous hydrolysis and decarboxylation at physiological pH value and thereafter a methyldiazonium ion is released. This ion forms DNA adducts within guanine rich DNA sequences. Temozolomide has high bioavailability and is metabolized in the liver. 

The fact that ) -D-galactosidase from Escherichia coli is inactivated more rapidly in the absence of Mg than in its presence can be taken as evidence that the activation of the triazene 38, that is, formation of )5-D-galactosyl-methyldiazonium ion, proceeds without acid catalysis, because Mg is required for the proton-assisted catalysis of yS-D-galactoside hydrolysis by this enzyme.Additional evidence for the absence of acid catalysis in the de-... 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

Fig. 11.16. Base-catalyzed mechanism of activation of the antitumor prodrug temozolomide (11.119 to S-(3-methyltriaz-2-en-l-yl)imidazole-4-carboxamide (MTIC, 11.120, the precursor of the reactive methyldiazonium species) [145]... 

Dimethylhydrazine is metabolized by a sequence of oxidation steps, first dehydrogenation to azomethane, A -oxidation of this to azoxymethane and finally a C-oxidation to methylazoxymethanol (Fiala, 1975, 1977). This last metabolite decomposes to give the highly reactive methyldiazonium ion to which the carcinogenicity of the compound has been attributed. The sequential nature of these oxidation steps has been shown in the isolated perfused rat liver (Wolter Frank, 1982). Fiala (1977) showed that the C-oxidation of azoxymethane to methylazoxymethanol is catalysed by hepatic microsomes, while Schoental (1973) found that methylazoxymethanol was converted to the corresponding aldehyde by an NAD-dependent dehydrogenase. 

Best with unhindered prim, and sec. alcohols. An acid catalyst is necessary (HBF or BF3), but acids with nucleophilic anions are unsatisfactory. Reaction probably involves intermediate formation of methyldiazonium ion, CH3N2 . 

Even diazomethane has been protonated708 in the superacid media. In Magic Acid media, both methyldiazonium ion 397 as well as iV-protonated diazomethane 398 are formed [Eq. (3.113)]. 

In summary, DMH and AOM failed to increase in vitro mutagenic frequency with or without liver extracts. However, MAM caused a dose-dependent increase in reversion frequency without hepatic enzymes as expected since MAM decomposes heterolytically to methyl-diazonium and formaldehyde (32). Methyldiazonium ions yield nitrogen and methylcarbonium, a powerful alkylating agent. Formaldehyde is oxidized to (X. In contrast to in vitro conditions, the host-mediated assay showed that intact animals converted DMH and AOM to mutagenic products. 

Diazomethane is a toxic, explosive yellow gas that dissolves in ether and is fairly safe to use in ether solutions. The reaction of diazomethane with carboxylic acids probably involves transfer of the acid proton, giving a methyldiazonium salt. This diazonium salt is an excellent methylating agent, with nitrogen gas as a leaving group. 

Step 1 Proton transfer, forming a carboxylate ion and a methyldiazonium ion. 

Resonance forms show that the carbon of diazomethane is basic, and reaction with an acid can occur to form a methyldiazonium ion. 

Methylation of amides- Diazomethane in the presence of silica gel forms methyldiazonium silicate, which can methylate amides. Thus this reagent converts caprolactam (1) into O-methylcaprolactim (2) in 957o yield in 15 minutes. 

Dacarbazine (DTIC) is chemically characterized by a dimethyl-triazeno structure. Alkylation, via a methyldiazonium ion metabolite is the most likely mechanism involved in its anti-tumour activity. Reconstituted solutions of DTIC are administered as slow IV bolus injection or the infusion of diluted solutions. DTIC is sensitive to photonic energy and heat. 

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