Benzoannelated heterocycles

The recent impact of solid-phase synthesis on medicinally relevant benzoaime-lated nitrogen heterocycles has been recently reviewed [16], therefore in this section only recent publications are included. Benzoannelated heterocycles can be prepared efficiently through cyclization on solid supports employing classical heterocycle forming reactions such as the Fischer [425], the Bischler-Napieralski [426], Tsuge [427], Nenitzescu [428], and Richter [140] reactions. In addition, the... 

There are many examples for seven-membered benzoannelated heterocycles that include benzazepines (332) [245, 454] benzothiazepines (333) [455, 456] and the very important pharmacological family of benzodiazepines (334) [285, 457, 458], which was the first class of small molecules synthesized on solid supports [459]. Benzoxazocines (335) [460] are examples for benzoannelated eight-mem-bered heterocycles obtained on solid supports (Fig. 3.14). 

The nomenclature of peri-naphthalene heterocycles does not follow a common principle. In many original papers, the names of heterocyclic systems are derived from the corresponding peri-annelated hydrocarbon derivatives (1,2-diazaacenaphthylene, 1-oxaphenalene, etc.), from monoheterocycles with an indication of linked positions (naphtho[l,8-6c]furan, naphtho[l,8-de]azepine, etc.), and from benzoannelated heterocycles (benzo[o/]indole, benzo[heterocyclic systems and some compounds have trivial names, for instance, perimidine, naph-thostyryl, and naphtholactone. Moreover, it is necessary to remember some peculiarities in the electronic structure of peri-annelated heterocycles, namely the absence of independent existance of the 7r-closed-loop monoheterocycles which could be a fragment of peri-annelated heterocyclic systems. Therefore, the separation of a heterocycle from the united 7r-system is impossible. In this case, the simplest structure and the tt-electron unit is the whole peri-heterocyclic nucleus. 

Concept II is based on the flexibility of the azide functionality. Upon thermolysis or photolysis, appropriately substituted aryl azides lose nitrogen gas to give intermediate nitrenes, which in turn cyclize with suitable ori/zo-substituents to give benzoannelated heterocycles. An unsaturated ori/zo-substituent consisting of double bonds including carbon,... 

With the radical cations of benzoannelated heterocycles, various paths are... 

Heterocyclic [3,2-d]-fused pentalenes and their benzoannelated derivatives 97CLY547. 

Fig. 3.12 Skeletons of five-membered benzoannelated nitrogen heterocycles.

In contrast to the benzoannelated nitrogen heterocycles, only a few kinds of benzoannelated systems without nitrogen have been described (Fig. 3.15). Five-mem-bered rings such as benzo[b]furans (336) [184, 461] and hydrobenzo[b]furans (337) (Scheme 3.41) [337, 462, 463] and six-membered rings like 4H-l-benzopyran-4-ones (4-chromones) (338) and 2H-l-benzopyran-2-ones (coumarines) (339) [96, 464, 465] 2,3-dihydro-4H-l-benzopyran-4-ones (chroman-4-ones) (340) [466] and 3,4-dihydro-lH-2-benzopyrans (isochromans) (341) [444] have been reported. 

Fig. 3.15 Skeletons of five- and six-membered benzoannelated oxygen heterocycles.

One should notice also that for pairs of compounds with the same number of members, a pyrrole-type heteroatom in monocyclic or in benzoannelated systems corresponds to a pyridine-type heteroatom in the peri-heterocyclic ring. 

Two benzoannelated analogues of the pyrylium cation are known ben-zo[b]pyrylium (chromylium or 1-benzopyrylium) and benzo[c]pyrylium (isochromylium or 2-benzopyrylium) salts. So far, the 1-benzopyrylium system is considered to be the more interesting (79MI2 84MI1) because it is the basic heterocyclic system of important plant pigments (antho-cyanins), and because there are major differences between properties of its heterocyclic ring and those of monocyclic pyrylium systems as a result of benzoannelation. Thus, for instance, 1-benzopyrylium salts do not possess the ability to have recyclization reactions with heteroatom exchange. 

Consider now the enthalpies of formation of our diverse indane heterocycles and corresponding one-ring species formed by de-benzoannelation (Table 1). De-benzoannelation resulting in aromatic one-ring species is generally more favorable than processes involving non- or antiaromatic species. The enthalpy of formation difference for aromatic species is typically 50-60 kJ mol-1, for nonaromatic species typically ca. 30 kJ mol-1, and for antiaromatic species ca. 24 kJ mol-1. The difference of the enthalpies of formation between the benzoannelated and one-ring dithiol-2-thiones is —11 kJ mol-1. No explanation for this discrepancy is apparent. 

Ziegert, R.E., Torang, J., Knepper, K. and Erase, S. (2005) The recent impact of solid-phase synthesis on medicinally relevant benzoannelated oxygen heterocycles. J. Comb. Chem., 1, 147-69. 

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