Polycyclic heterocyclic compounds

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

These dienes are valuable for the Diels-Alder based synthesis of dibenzofurans, dibenzothiophenes, carbazoles and other classes of complex polycyclic heterocyclic compounds. Scheme 2.32 summarizes some of the cycloadditions [81] of 2-vinylbenzofurans (80). 

Another extension is in the field of alicyclic compounds (7, 112). In steroid compounds it has been proved that long-distance effects, e.g. from position 17 to 3 and vice versa, affect polarographic half-wave potentials. Finally it has been demonstrated (7, 113) that Hammett and Taft substituent constants can be used as a first approximation to express the substituent effects in numerous types of mono- and polycyclic heterocyclic compounds. 

The reactivity of polycyclic heterocyclic compounds is related to the type of heteroatom and to the size of the ring. 

Cobb, T. B. High-Resolution Nuclear Magnetic Resonance of Polycyclic Aromatic Hydrocarbons and Polycyclic Heterocyclic Compounds, Dissertation, State University of North Carolina, Rayleigh, NC, 1968 Diss. Abstr. 1968, 29, 1463-1463. 

Scheme 3.27 Pd-catalyzed C-H carbonylation to prepare polycyclic heterocyclic compounds.

Heterocyclic compounds carrying hydroxyl groups may be compared with phenols. Thomson has reviewed the tautomeric behavior of phenols often both tautomeric forms of polycyclic compounds such as naphthols can be isolated. Early work on hydroxy-thiophenes and -furans was also reviewed by Thomsond but until recently their chemistry has been in a somewhat confused state. A pattern is now beginning to emerge, at least for the a-substituted compounds, which appear to exist as A -oxo derivatives and to attain equilibrium slowly with the corresponding A -oxo forms. For the a-hydroxy compounds, the equilibrium generally favors the A -oxo form. 

On the basis of the reaction of alkyl radicals with a number of polycyclic aromatics, Szwarc and Binks calculated the relative selectivities of several radicals methyl, 1 (by definition) ethyl, 1.0 n-propyl, 1.0 trichloromethyl, 1.8. The relative reactivities of the three alkyl radicals toward aromatics therefore appears to be the same. On the other hand, quinoline (the only heterocyclic compound so far examined in reactions with alkyl radicals other than methyl) shows a steady increase in its reactivity toward methyl, ethyl, and n-propyl radicals. This would suggest that the nucleophilic character of the alkyl radicals increases in the order Me < Et < n-Pr, and that the selectivity of the radical as defined by Szwarc is not necessarily a measure of its polar character. 

Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

Monograph on the Evaluation of Carcinogenic Risks of the Chemical to Man Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds", Internat. Agency Res. Cancer, World Health Organization, 1973 Vol. 3. 

A wide variety of different classes of fluorescent molecules has been investigated in the peroxyoxalate chemiluminescent systems. Among those screened were fluorescent dyes such as rhodamines and fluoresceins, heterocyclic compounds such as benzoxazoles and benzothiazoles, and a number of polycyclic aromatic hydrocarbons such as anthracenes, tetracenes, and perylenes. The polycyclic aromatic hydrocarbons and some of their amino derivatives appear to be the best acceptors as they combine high fluorescence efficiency with high excitation efficiency in the chemiluminescent reaction [28],... 

Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds, International Agency for Research on Cancer Monographs on the Evaluation of the Carcinogenic Risks to Humans LARC Lyon, France, 1972 Vol. 3. 

When the numbering is predetermined by the nature of the parent hydride, as in polycyclic hydrocarbons and in heterocyclic compounds, lowest locants are still the rule. 

Since the publication of CHEC-II(1996) <1996CHEC-II(6)1>, in which thermally induced [4+2] cycloadditions have been reviewed, significant progress has been realized in this strategy, especially for the synthesis of polycyclic heterocycles. Cyclophanes 12 containing pyridazine and indole units were used for the synthesis of pentacyclic compounds 13 via a thermally induced transannular inverse-electron-demand Diels-Alder reaction (Equation 2) <20020L127, 2002AGE3261>. 

The main types of substrates investigated so far are polycyclic aromatic compounds, aryl substituted carbo- and heterocyclic pentadienes, cyclic 1,3-dienes, furans, and olefins. It has turned out that type II photooxygenation of these compounds in solution occurs via the oxygen-activation mechanism. 

Some of these N-, O-, and S-atom-functionalized polycyclic aromatic compounds (PACs) are powerful bacterial mutagens and animal, and possible human, carcinogens, e.g., the exocyclic nitro-substituted PAH 1-nitropyrene, VI, which is a primary pollutant in diesel exhaust (IARC, 1989). The endocyclic heterocyclic PAC dibcnz[fl,/ ]acridine, VII, is also classified as a possible human carcinogen (IARC, 1987 see Sections B and C). 

Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds... 

POLYCYCLIC AROMATIC HYDROCARBONS NITROGEN HETEROCYCLIC COMPOUNDS LOW LEVEL CARCINOGENS FLYASH... 

Coke-oven tar is an extremely complex mixture, the main components of which are aromatic hydrocarbons ranging from the monocyclics benzene and alkylbenzenes to polycyclic compounds containing as many as twenty or more rings. Heterocyclic compounds containing oxygen, nitrogen, and sulfur, but usually only one heteroatom per ring system are present. Small amounts of paraffinic, olefinic, and partly saturated aromatic compounds also occur. 

Effect of Heteroelements in Modifying Some Cyclizations — Polycyclic Aromatic Compounds from the Diene Synthesis , W. Davies and O. N. Porter, in Proceedings of a Symposium on Current Trends in Heterocyclic Chemistry , ed. A. Albert, G. M. Badger and C. W. Shoppee, Academic Press, New York, 1958, pp. 56-58. 

Applications of Linear Free Energy Relationships to Polycyclic Arenes and to Heterocyclic Compounds , M. Charton, in Recent Advances in Correlation Analysis in Chemistry , ed. N. B. Chapman and J. Shorter, Plenum, New York, 1978, pp. 175-268. Applications of the Hammett Equation to Heterocyclic Compounds P. Tomasik and C. D. 

Benzene (1) is the simplest aromatic hydrocarbon upon which our knowledge of aromatic chemistry is based. This hydrocarbon, the alkylbenzenes (2), the arylmethanes [e.g. diphenylmethane (3)], the biphenyls [e.g. biphenyl (4)] and the condensed polycyclic systems [e.g. naphthalene (5) and anthracene (6)] all exhibit chemical reactivity and spectroscopic features which are markedly different from their aliphatic and alicyclic hydrocarbon counterparts. Indeed the term aromatic character was introduced to specify the chemistry of this group of hydrocarbons and their substituted functional derivatives, and it was soon used to summarise the properties of certain groups of heterocyclic compounds having five- and six-membered ring systems and the associated condensed polycyclic analogues (Chapter 8). 

Superacid-promoted dicationic species containing heteroaromatic rings, where positive charge centres migrate through consecutive deprotonation-reprotonation steps, undergo cyclization reactions followed by aromatization and superacid-promoted elimination of benzene (Scheme 10).31 The process leads to the synthesis of aza-polycyclic aromatic compounds in moderate to good yields. Seven examples include pirazole, oxazole, and thiazole heterocycles. 

Sharma, R. K., Chan, W. G., Seeman, J. I., and Hajaligol, M. R. (2003). Formation of low molecular weight heterocycles and polycyclic aromatic compounds (PACs) in the pyrolysis of a-amino acids. J. Anal. Appl. Pyrolysis 66, 97-121. 

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