Newkomes Pyridine-containing Macrocycles

Newkome and his group have pioneered in the synthesis of aliphatic macrocycles containing the pyridine subcyclic unit . Like the furan systems discussed in Sect. 3.6, these are macrocycles containing a potentially coordinating subcyclic unit whose donor 

closely related, nicotinic acid derivatives and the unsubstituted system itself have also been studied and undergo similar reactions. Moreover, the approach may be extended to 2,2 -bipyridyls. Newkome and his collaborators have used the 2,2 -bipyridyl unit 19) as an electrophile in which ortho-hr ommes served as leaving groups. They have also used halomethyl systems and formed the macrocycles from these systems . A compound derived from the latter starting material 20) is reported to form a cobalt complex, in which both nitrogens and only one of the oxygen atoms participate in the binding . The two precursor units are shown below as 79 and 20, respectively. 

Pyrimidines have also served as electrophiles in crown synthesis from this group. 4,6-Dichloropyrimidine reacts with diethylene glycol and sodium hydride in anhydrous xylene solution to form the 20-crown-6 derivative as well as the other products shown in Eq. (3.48). Note that a closely related displacement on sy/rr-trichlorotriazine has been reported by Montanari in the formation of polypode molecules (see Eq. 7.5). 

When 2-chloronicotinoyl chloride is allowed to react with pentaethylene glycol and sodium hydride in benzene solution, acylation followed by nucleophilic aromatic substitution occurs resulting in the formation of a macrocyclic lactone (48% yield) as shown in Eq. (2.8), in Chap. 2. 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

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It should be stressed that there has been considerable interest in macrocycles containing the pyridine subcyclic unit, especially by Newkome and coworkers (see also Chap. 4). Most of his interest appears to have been focussed on polyethers rather than ester compounds. Bradshaw has also reported syntheses of compounds containing the pyridine subcyclic unit. ... 

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