Quinodimethanes and Heterocyclic Analogues

The generation and Diels Alder reaction of 4,5-bis(bromomethylene)-4,5-dihydrothiazole 39 has been investigated. 39 is a heterocyclic analogue of ortho-quinodimethanes and is generated by treating 4,5-bis(dibromomethyl)thiazole 38 with sodium iodide in dimethylformamide. 39 can be trapped in situ with symmetrical dienophiles to give substituted benzothiazoles such as 40 <98EJOC2047>. 

Reductive Dehalogenation This was the first method used to produce an o-quinodimethane and has been widely applied to the formation of both 5- and 6-membered heterocyclic analogues as can be seen from the Table and from the examples in Scheme 3. The nonnal procedure uses Nal in DMF at temperatures ranging from ambient to 150 C. Activated zinc has been used extensively for non-heterocyclic o-quinodimethanes but has found little application with heterocyclic systems <91SC1055>. Yields of Diels-Alder adducts from 5-membered heterocyclic o-quinodimethanes generated by this method tend to be low to moderate and are accompanied by polymers. However, use of molecular sieves has been shown to give improved yields <92TL4499>. The elimination is most commonly carried out on the dibromo compounds but the dichloro compounds can also be used both most likely proceed via the diiodo derivative. 

There is still little, if any, substantive data on the structure-reactivity profile of different heterocyclic -quinodimethanes, but the expected trends are supported by experience. The stability of the -quinodimethanes appears to be related to the loss of aromatic character o-quinodimethanes derived from the more stable aromatic heterocycles are the most reactive. Thus, when generated by flash vacuum pyrolysis and condensed at low temperatures, some heterocyclic rt-quinodimethanes can be isolated. It is clear that the furan derived. species 7 is considerably more stable than the thiophene analogue 2. The species 7 is sufficiently. stable for NMR spectra to be recorded at -60 °C and Diels-Alder adducts can be obtained by adding dienes to the cold finger <81JA669I>. In contrast, the species 2 can be observed directly only in an argon matrix <88CB791> and it readily polymerises even in the presence of dienophiles. Similar qualitative trends are observed with other heterocyclic o-quinodimethanes. 

It is clear from the foregoing discussion that heterocyclic w-quinodimethanes can now take their place in the standard annoury of the synthetic chemist. The flexibility available for the generation of such species should allow them to fonn the basis of routes to a wide variety of fused heterocycles. There is, however, still. scope for improvements such as even milder, general approaches towards their generation and there are notable gaps in the list of analogues which have so far been produced. For example, there is as yet no convenient route to the potentially very useful imidazole derivatives. 

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