The Oxygen-Containing Fused Heterocyclic Compounds

The oxygen-containing heterocycles are an important class of compounds in organic chemistry. These compounds are used as drugs (coumarin and oxa-zole), solvent (tetrahydrofuran), flavors, and fragrances (lactones). The fusion of aromatic ring to the oxygen-heterocycle will change the electron density; thereby, the physical/chemical/biological properties will alter. Also, the preparation of these fused molecules will require a different strategy/method/reaction condition. The topics covered in this chapter are the general synthetic methods and uses of fused heterocyclic compounds containing oxygen as a heteroatom. The derivatization of the primary scaffold is excluded from this chapter. Some of the fused compounds are coumarin (benzopyrans) and piclozotan (benzoxazepines).


Introduction
The oxygen-containing heterocycles are an important class of compounds in organic chemistry mainly because of their natural abundance and diverse biological functions. Natural and semi-synthetic oxygen heterocyclic compounds such as Taxol [1] (anticancer), Digoxin (CHF treatment), Cyclosporine-A (immunosuppressant) and Lovastatin (hypolipidemic) are well known used as promising therapeutic compounds [2]. Kaur et al. reviewed the oxygen heterocycles wherein saturated and unsaturated compounds are considered. They discussed the classification and chemistry of each of those compounds [1]. Reports are available wherein the synthesis of natural products containing oxygen as heteroatom is reviewed by Cossy and Guérinot [2]. Also, Rowlands and Farley chaptered the book on the anion radicals from oxygen-containing heterocycles [3]. None of these reports target the oxygen-containing heterocyclic compounds where fused rings are taken into consideration.

Classification of oxygen heterocycles
The oxygen-containing heterocycles can be classified in several ways like the classification based on (a) the number of oxygen atoms, (b) saturation level, (c) aromaticity or (d) abundance. For the clarity of the concept, the classification based on a number of oxygen atoms is used. The benzene fused furan and pyrans are listed in Figure 1, whereas Figure 2 represents the compounds with two oxygen atoms in the ring system.

Substitution on the benzene ring
Also, the substituted 1-allyl-2-allyloxybenzenes cyclizes to give substituted benzofurans by isomerization followed by ring-closure metathesis reaction using 5 mol.% catalyst [7]. The homologous members of benzofurans can be prepared by 0.1 eq. of Ru-catalyzed cycloisomerization of homo-and bis-homopropargylic alcohols in presence of pyridine at 90°C for 1-6 h [8] as shown in Figure 4.

Baker-Venkataraman rearrangement
The chemical reaction between 2-hydroxyacetophenone and acid chloride in the presence of base yields 1,3-diketone which undergo rearrangement and   concomitant cyclisation to produce flavone [37]. This reaction is often used to synthesize chromones and flavones (Figure 14).

Conclusions
In this chapter, the synthesis of fused heterocyclic compounds having oxygen as heteroatom is considered. The care is taken not to consider the reactions, where the reactions of the compounds leading to derivatizations are not included.  Benzofurans, benzofuranones, dibenzofurans, coumarins, isocoumarins, chromones, and flavones are the fused heterocyclic compounds considered in this chapter. Also, the reactions are indicative and not the detailed reaction conditions, and appropriate reagents are not included in this chapter.