HANTSCH Pyridine Synthesis

The Hantsch pyridine synthesis provides the final step in the preparation of all dihydrop-yridines. This reaction consists in essence in the condensation of an aromatic aldehyde with an excess of an acetoacetate ester and ammonia. Tlie need to produce unsymmetrically subsrituted dihydropyridines led to the development of modifications on the synthesis. (The chirality in unsymmetrical compounds leads to marked enhancement in potency.) Methyl acetoacetate foniis an aldol product (30) with aldehyde 29 conjugate addition of ethyl acetoacetate would complete assembly of the carbon skeleton. Ammonia would provide the heterocyclic atom. Thus, application of this modified reaction affords the mixed diester felodipine 31 [8]. 

It seems to me that once we accept the above, we are back to a situation where the only feature that distinguishes self-assembly or self-organization from any run-of-the-mill synthetic reaction, which also proceeds spontaneously given a suitable set of conditions, will be the requirement diat three or more constituent molecules are being assembled. Thus, the old Hantsch synthesis of pyridines from ammonia, formaldehyde, and a ketone, the preparation of sugar mixtures from formaldehyde and base, and all polymerizations will become examples of self-assembly. 

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