Triple bond formation nitrogen nucleophiles

Nevertheless, the adjacent position of the amide and acetylenic groups was used in another type of heterocyclization. The nitrogen atom in the amide group is a weak nucleophile. Therefore, the N anion should be generated by potassium ethoxide. There are two possible variants of nucleophilic addition to the triple bond. Only one takes place, i.e., the formation of y-lactam. After 7 h of heating in EtOH in the presence of KOH, amide 72 isomerized into the known isoindoline 73 in 80% yield (Scheme 128). 

The formation of (149) involves nucleophilic addition of sulfamide (136) across the carbon-nitrogen triple bond of (150), followed by tautomerisation of the initial iminoproduct (Scheme 61). A series of analogous N-sulfamoylamidines in which the length of the chain between the thiazole nucleus and the amidine moiety was varied also inhibited gastric juice secretion.7... 

According to Shostakovskii and Bogdanova (71 Mil), the role of catalyst is the formation of a nonpolar -complex one of whose triple bonds has a uniform electron density distribution on both carbon atoms, thereby facilitating the interaction between the nucleophilic nitrogen atom and the fourth carbon atom in the conjugated diyne system. 

The oxidation of terminal acetylenes, like that of monosubstituted olefins, often results in inactivation of the P450 enzyme involved in the oxidation. In some instances, this inactivation involves reaction of the ketene metabolite with nucleophilic residues on the protein [196, 197], but in other instances it involves alkylation of the prosthetic heme group (Fig. 4.31). Again, as found for heme alkylation in the oxidation of olefins, the terminal carbon of the acetylene binds to a pyrrole nitrogen of the heme and a hydroxyl is attached to the internal carbon of the triple bond. Of course, as one of the two m-bonds of the acetylene remains in the adduct, keto-enol equilibration yields a final adduct structure with a carbonyl on the original internal carbon of the triple bond [182, 198]. It is to be noted that the oxidation of terminal triple bonds that produces ketene metabohtes requires addition of the ferryl oxygen to the imsubstituted, terminal carbon, whereas the oxidation that results in heme alkylation requires its addition to the internal carbon. As a rale, the ratios of metabolite formation to heme alkylation are much smaller for terminal acetylenes than for olefins. 

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