Classical Multicomponent Reactions

As many of the classical multicomponent reactions, the Strecker synthesis also takes advantage of the versatile chemistry of the initially formed imine. The formation of the amino nitrile, however, is reversible under the reaction conditions which usually results in lower yields. This problem was elegantly solved in the Bucherer-Bergs variation,3 4-376 where the initially formed aminonitrile is irreversibly trapped by formation of a hydantoin as depicted in Scheme 1.8 (entry b). 

An interesting variation of the classical multicomponent reaction was recently described starting from a glyoxale and a tetrahydroisoquinoline generating in the first step an immonium species which underwent 1,3-dipolar cycloaddition with A-methyl maleimide as shown in Scheme 1.8.5.10.i ... 

Dihydropyridines can be prepared via the three-eomponent coupling of cinnamaldehyde, aniline and p-keto esters under solvent-free conditions by means again of L-Pro as catalyst in the transformation. The three-component reaction of 1,3-indanedione, isatins and enamines as the nucleophiles is also possible in the presence of L-Pro for the one-pot synthesis of highly functionalised spirooxindoles derivatives. While only some examples are highlighted here, ° ° the possibilities of L-Pro in multicomponent reactions are tremendous. It has also shown good catalytie activity in classic multicomponent reactions such as Biginelli reactions and Hantzsch dihydropyridine synthesis. 

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. 

Whilst the same researchers are using new scaffolds and non-peptide chemistries to generate other libraries [31], Kung et al. [32] used this deconvolutive technique on a SPSAF (solution-phase simultaneous Addition of Functionalities) generated library, and Davis et al. [33] reported the recursive deconvolution of a peptidomimetic library of potential artificial enzymes. A future application could be in the popular field of libraries from multicomponent reactions [34], either in solution or in solid phase, which are difficult to deconvolute with classical methods due to the mixtures of components reacting at the same time. 

Abstract The chapter reviews the classic Reissert reaction, the keystone of a broad family of multicomponent reactions involving azines, electrophilic reagents and nucleophiles to yield A,a-disubstituted dihydroazine adducts. The first sections deal with the standard nucleophilic attack upon activated azines, including asymmetric transformations. Section 5 focuses on the generation of dipolar intermediates by azine activation, and on their subsequent transformation chiefly in cycloadditions. Lastly, Sect. 6 is primarily devoted to a special branch of this chemistry involving isocyanides. It also covers the reactivity of dihydroazines and reviews the mechanistic proposals for related reactions. 

Classical and Modern Chemistry of Isocyanides and Multicomponent Reactions... 

In 1882, Hantzsch achieved the synthesis of symmetrically substituted dihydropyridines (DHPs) by reacting ammonia, aldehydes, and two equivalents of yS-ketoest-ers [27]. Since then, interest in these types of compound has grown, because of their pharmacological activity [28]. The Hantzsch reaction has successfully been used for synthesis of a wide range of DHPs and is still a popular tool for the construction of members of this class of heterocycles [29]. The classical multicomponent synthesis may require extended reaction times and yields can be low if sterically hindered aldehydes are used [30]. 

J.-P. Wan, Y. Liu, Synthesis 2010, 3943-3953. Synthesis of dihydropyiimidinones and thiones by multicomponent reactions strategies beyond the classical Biginelli reaction. 

Note that the classical syntheses of dihydropyridines (eg, Hantzsch synthesis) employ de novo construction of the rings by multicomponent reactions rather than starting from pyridines, and that some of the pyridine reduction processes are actually reductions of pyridinium cations (eg, Fowler s sodium borohydride reduction of the N-acylpyridinium salts produced in situ by the reaction of pyridines with chloroformate esters). 

Continuous Multicomponent Distillation Column 501 Gas Separation by Membrane Permeation 475 Transport of Heavy Metals in Water and Sediment 565 Residence Time Distribution Studies 381 Nitrification in a Fluidised Bed Reactor 547 Conversion of Nitrobenzene to Aniline 329 Non-Ideal Stirred-Tank Reactor 374 Oscillating Tank Reactor Behaviour 290 Oxidation Reaction in an Aerated Tank 250 Classic Streeter-Phelps Oxygen Sag Curves 569 Auto-Refrigerated Reactor 295 Batch Reactor of Luyben 253 Reversible Reaction with Temperature Effects 305 Reversible Reaction with Variable Heat Capacities 299 Reaction with Integrated Extraction of Inhibitory Product 280... 

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