Microwave irradiation Mannich reaction

The 2-pyridone core structure is present in a wide range of compounds with antibacterial, antifungal, and antitumor activity members of this family also play an important role in Alzheimer s disease. By employing microwave-assisted organic synthesis, efficient conditions have been established for introduction of ami-nomethylene substituents in highly substituted bicyclic 2-pyridones. To incorporate tertiary aminomethylene substituents in the 2-pyridone framework, a microwave-assisted Mannich reaction using preformed imminium salts proved to be effective. Primary amino methylene substituents were introduced via cyanodehalogenation then borane dimethyl sulfide reduction of the afforded nitrile (Scheme 10.36) [78]. Microwave irradiation proved superior to traditional conditions for these transformations. 

Keywords /i-naplithol, benzaldehyde, piperidine, Mannich reaction, acidic alumina, aminoalkylation, microwave irradiation... 

Other reports for the boron-Mannich reaction include the synthesis of aminophenol derivatives,561 a-arylglycines,576 a growth hormone secretagogue NN703,577 a polyhydroxyindolizine alkaloid uniflorine A,578 and cyclic ct-amino acids.579 The reaction has been applied to solution-phase reactions580 and the solid-phase reaction581-585 for the synthesis of libraries of peptides, a-amino acids, and bicyclic diketopiperazines. The reactions were accelerated by the irradiation of microwave.586... 

Use of a relatively straightforward Mannich reaction provided ready access to compounds with antitubercular properties. Microwave irradiation induced the coupling of amide 102 with piperazine 103 and formaldehyde 2 to prepare 104 in moderate to good yields. 

In conclusion, Kappe s group demonstrated the absence of any differences between conventional and microwave heating in proline-catalyzed Mannich and aldol reactions as well as no evidence for specific or non-thermal microwave effects. In all cases, in contrast to the previous literature reports, the results obtained with microwave irradiation could be reproduced by conventional heating at the same reaction temperature and time in an oil bath. The differences observed in previous publications could be a result of incorrect temperature measurements [36]. After Kappe s [35] publication several articles appeared in the literature concerning the application of microwaves in asymmetric organocatalysis, mostly in aldol and Michael type reactions operating via enamine as well as iminium catalysis. 

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