Nucleophilic addition reactions with nitrogen nucleophiles

Acetylenecarboxylic esters, reactions with nitrogen-containing heterocycles, 23, 263 Acetylenic derivatives of pyrazoles, synthesis and properties of, 82, 1 Acetylenic esters, synthesis of heterocycles through nucleophilic additions to, 19,297 Acid-catalyzed polymerization of pyrroles and indoles, 2, 287... 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

The central carbon atom, flanked by two nitrogen atoms, is electrophilic and thus subject to nucleophilic attack by a variety of reagents. The most well-known reactions are those between carbodiimides and acids. For example, carbodiimides will undergo addition reactions with a variety of weak acids ... 

The reaction of propiolic acid or its esters with 2-aminothiazole yields 7H-thiazolo[3.2o]pyTimidine 7-one (109) (Scheme 74) (273), The reaction probably proceeds by initial nucleophilic attack of 2-aminothiazole on the sp C followed by intramolecular addition of ring nitrogen to spC. 

In addition to being more basic than arylammes alkylammes are also more nucleophilic All the reactions m Table 22 4 take place faster with alkylammes than with arylammes The sections that follow introduce some additional reactions of amines In all cases our understanding of how these reactions take place starts with a consideration of the role of the unshared electron pair of nitrogen... 

Chemical Properties. The presence of both a carbocycHc and a heterocycHc ring faciUtates a broad range of chemical reactions for (1) and (2). Quaternary alkylation on nitrogen takes place readily, but unlike pyridine both quinoline and isoquinoline show addition by subsequent reaction with nucleophiles. Nucleophilic substitution is promoted by the heterocycHc nitrogen. ElectrophiHc substitution takes place much more easily than in pyridine, and the substituents are generally located in the carbocycHc ring. 

In addition to their reactions with amines, Zincke salts also combine with other nitrogen nucleophiles, providing various A -substituted pyridine derivatives. Pyridine A -oxides result from the reaction with hydroxylamine, as exemplified for the conversion of Zincke salt 38 to the A -oxide 39 Reactions of Zincke salts with hydrazine, meanwhile, lead... 

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