Large oxygen containing heterocycles

FIGURE 10.12 Construction of large oxygen-containing heterocycles using reaction of 16 with salicylic acid and salicylaldehyde. 

Oxazoles are well-investigated compounds. The occurrence, uses, and synthesis of oxazole derivatives have been the subjects of extensive reviews.5 The heterocyclic oxazole unit is seen with various substitution-patterns in a large number of naturally occurring compounds. Furthermore, oxazoles serve as synthetic intermediates leading to many other systems.5 6 7 In this context, oxazoles have seen, for example, numerous applications as "2-azadiene" components in 4+2 cycloadditions with several types of dienophiles. Further transformations of the products then lead to a number of other nitrogen- or oxygen-containing heterocyclic products.6... 

Formation of six-membered cycles is the second most common case of heterocyclic Mizoroki-Heck reactions, with, as for the formation of five-membered rings, exo-cyclization reactions being largely favoured compared to c d( -cyclization reactions. As already noted for the five-membered cycles, there are more examples of iV-heterocyclic formation than of oxygen-containing heterocycles. 

The most common oxygen-containing heterocyclic alcohol is furfuryl alcohol, which is a degradation product of sugars. Furfuryl alcohol results primarily from furan-2-carbaldehyde by reduction or a Cannizzaro reaction. A large number of other alcohols derived from furan, pyran and other heterocyclic compounds are products of the Maillard reaction. 

The Prins reaction is a one of example of multichannel reaction. This reaction became basis for a convenient technique of oxygen-containing heterocycles formation [1, 2]. In some cases this multipathing is drawback because of insufficient selectivity. For example, the first stage of the isoprene synthesis by the dioxane method [3] is accompanied by the formation of a large number of by-methyldihydropyrans [4-6]. Obviously, in order to find new way to increase the selectivity of the first stage the mechanism of Prins reaction should be improved. Products formation by way of cascade involvement of one or two molecules of formaldehyde monomer [7, 8] is considered one of the generally accepted mechanisms of the Prins reaction (Fig. 10.1). 

To a large extent, similar methods are used for the preparation of thiazole-, dihydrothiazole-, and thiazolidine-based peptides as presented in Section 11.2.3 for the preparation of the corresponding oxazole- and dihydrooxazole-based peptides. However, the oxidation of dihydrothiazole and thiazolidines to the aromatic heterocycles is considerably more facile than for the analogous oxygen-containing substrates. 

A large number of heterocyclic compounds of oxygen, nitrogen, and sulfur are prepared by condensation of di- or poly-functional compounds. Nitrogen-containing heterocycles by the thousands have been prepared by such reactions. The simplest such reaction is one leading to the preparation of a pyrrolidine or piperidine derivative. The synthesis of pyrrolidine may be accomplished by reaction of ammonia and 1,4-dichlorobutane in a stepwise process that may include an intramolecular displacement of chloride from the aminoalkyl chloride [Eq. (31)] or of ammonia from the aminoalkyl amine hydrochloride" [Eq. (32)] each process is known to occur. 

Early literature - claimed that the three isomeric cresols, on heating with a large excess of chlorosulfonic acid, afforded condensation products termed sulfonylides which probably possess the structures 130-132 containing an interesting eight-membered oxygen-sulfur heterocyclic ring. For example, o-... 

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