Aminomethylation Mannich reaction, double

There are cases in which appropriate modification of one unsaturated oxazolone yields a new unsaturated oxazolone analogue. Most of the examples described in the literature involve modification of the substituent on the exocyclic double bond. For example, a series of 4-[2-hydroxy-3-(aminomethyl)benzylidene]-5(4//)-oxazo-lones 382 that were evaluated for bactericidal and fungicidal activities were obtained from Mannich reaction of 4-(2-hydroxybenzylidene)-5(4//)-oxazolones 381 (Scheme 7.123). ... 

Concurrently with the Mannich reaction, structural modifications of the substrate, such as double bond migration, cyclization, rearrangement, and elimination accompanying the aminomethyl group attachment, may also occur. These are treated in Sec. C.5 and summarized in Fig. 8. 

The present chapter deals with the application of Mannich aminomethylation or Mannich bases to the synthesis and modification of macromolecular compounds. As summarized in Fig. 150, a remarkable number of different combinations exist, as the Mannich reaction enables us (a) to perform polymerizations by using bifunctional substrate and amine as well as (d) to functionalize polymeric derivatives behaving, alternatively, as substrate or amine components of Mannich synthesis. On the other hand, the manifold reactivity of Mannich bases makes it possible (b) to produce polymers by amino group replacement with bifunctional nucleophiles or to polymerize suitable moieties (e.g., double bonds) present in the base. Furthermore (e), macromolecular compounds can be subjected to amino group replacement as well as to various other reactions given by Mannich bases. Finally (c), crosslinked derivatives are obtained from oligomeric or polymeric products through any of the above mentioned methods. 

The prochirality of aldehydes other than formaldehyde is frequently exploited in order to obtain asymmetric Mannich bases 99A and B, as the reaction with substrate may occur from either side of the double bond plane of the aminomethylating agent (Fig. 38). 

The double-cyclization cascade was also reported by the same group (Scheme 19.79) [ 149]. The bis- and mono-aminomethylated pyrroloindoles/dipyrrolopyridines 294 and 295 (X = CH/N) were obtained selectively by a controlled Mannich type of reaction-cyclization of4,6-diethynyl-l,3-phenylenediamine (X = CH) or its pyridine congener (X = N) 293 with paraformaldehyde and secondary amines. Treatment of 293 with Cul and EtsN without using Mannich-type reactions furnishes a high-yielding bis-cyclization of terminal alkynes to give 296. 

---