Hydrogen species, Mannich reaction

Alternatively a Mannich-like pathway may be followed (see Mannich reaction), where ammonia reacts with the aldehyde 1 to give an intermediate iminium species, that adds hydrogen cyanide to give the a-amino nitrile 2. The actual mechanistic pathway followed depends on substrate structure and reaction conditions. 

Multicomponent reaction systems are highly valued in solid-phase organic synthesis because several elements of diversity can be introduced in a single transformation.1 The Mannich reaction is a classic example of a three-component system in which an active hydrogen component, such as a terminal alkyne, undergoes condensation with the putative imine species formed from the condensation of an amine with an aldehyde.2 The resultant Mannich adducts contain at least three potential sites for diversification specifically, each individual component—the amine, aldehyde, and alkyne—can be varied in structure and thus provide an element of diversity. 

Over the years with the advent of milder and more controlled reaction conditions, the aldehyde component has increased in its diversity with a concomitant increase in functional group inter-compatibility. These changes also have enabled the extension of the nature of the active hydrogen (nucleophilic) species beyond enols. More recently, the utility of the Mannich reaction has been enhanced with enantioselective and catalytic variations. 

I), other important alkaloids are used as amine reagents for Mannich synthesis. Thus, demethylatcd nicotine affords aminomethylation of hydrogen cyanide (460), employed in studies of the metabolic oxidation of nicotine, and anabasinc gives, by reaction with acrylamide, the readily polymerizable monomeric species 461, the polymeric derivative of which is. 50 times less toxic than the original anabasinc. ... 

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