Amines and nitrogen heterocycles

The nitrogen of aHphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, ia tn phenylamine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate ia high yields by heating the mixtures (24,25). 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

A. Lattes, Afinidad 1972, 2953 -2970 . .Application of Organometallic Compounds to the Synthesis of Amines and Nitrogenated Heterocycles". 

Even poor nucleophiles such as the amides 46 can react with azines in the presence of alkynes as activating agents [59, 60]. Various nucleophiles (including alkoxides, thiols, amines and nitrogen heterocycles) were recently employed in a related process with Ai-oxide azaindoles (Reissert-Henze reaction. Scheme 10). In the process, the oxygen is alkylated with dimethyl sulfate and, after the nucleophilic attack, methanol is released to aromatize the initial adduct [61,62]. Following similar mechanistic trends, V-heteroatom-activated azines afford the corresponding substituted adducts. Likewise, W-tosylated isoquinoline [63, 64] and W-fluoropyridinium salts [65] are also reactive substrates in Reissert-Henze type processes. 

I. Preparation of Aziridines, / -Functionalized Amines, and Nitrogen Heterocycles Through 1,3-Dipolar Cycloaddition of Organic Azides to Alkenes... 

In recent years, direct amination of tautomerizable heterocycles with amines via phosphonium coupling has been widely utilized in the synthesis of various heterocychc compounds used for chemical building blocks or medicinal chemistry. The reaction rate of the direct amination is usually dependent upon the electronic and steric nature of the amine nucleophiles. In principle, electron-richer and sterically less-hindered alkyl amines are much more reactive than aryl amines and nitrogen heterocycles (04AP702,05JOC1957). 

Many other species have been employed as ligands, including amines and nitrogen heterocycles, sulfides and sulfoxides, halides, alkoxides and nitriles. Dienes, such as 1,5-cyclooctadiene, are commonly used as ligands. 

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