Side chain functional substituents, reactivity

Sheremetev and co-workers employed diazo compounds of type 60, prepared from the corresponding amines in moderate yields as alternative excellent precursors for the preparation of side-chain-functionalized derivatives (Scheme 29). Several furazans bearing reactive groups or cyclopropyl or five-membered heterocyclic substituents have been prepared by standard procedures (99MI6). 

The reactivity of alkylthiazoles possessing a functional group linked to the side-chain is discussed here neither in detail nor exhaustively since it is analogous to that of classical aliphatic and aromatic compounds. These reactions are essentially of a synthetic nature. In fact, the cyclization methods discussed in Chapter II lead to thiazoles possessing functional groups on the alkyl chain if the aliphatic compounds to be cyclized, carrying the substituent on what will become the alkyl side chain, are available. If this is not the case, another functional substituent can be introduced on the side-chain by cyclization and can then be converted to the desired substituent by a classical reaction. 

The action of gaseous ammonia on diethyl chromone-2,6-dicarboxylate (478) is a good example of the different reactivity between identical substituents in the same molecule. The 2-carboxylate function is more reactive even than an ester group in a side chain such as —0CH2C02Et, which is unaffected by ammonia. This is consistent with the low electron density of C-2.2-Carboxamides, such as (479), need drastic conditions for their dehydration... 

In 4-chloro-2-methyl-6-phenylpyrimidine-5-carbonitrile, the reactivity of the chloro substituent allows the introduction of side chains which will cyclize with the adjacent nitrile function. Thus, cyanoacetamide yields 5-amino-2-methyl-7-oxo-7,8-dihydro-4-phenyipyrido[2,3-[Pg.110]

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