Systems heteroaromatic

The ASE values correlate with magnetic susceptibility for the five-membered heteroaromatic compounds. Magnetic and polarizability criteria put the order of aromaticity as thiophene pyrrole furan. The other criteria of aromaticity discussed in Section 8.2 are also applicable to heterocyclic compounds. HOMO-LUMO gaps and Fukui functions (see Topic 1.5) have been calculated for compounds such as indole, benzofuran, and benzothiophene and are in accord with the known reactivity patterns of these heterocycles. 

AMI Stabilization in kcal/mol relative to localized model using AMI semiempirical calculations M. J. S. Dewar and A. J. Holder, Heterocycles, 28, 1135 (1989). lA Index of aromaticity based on bond length variation. Benzene = 100. 

Polycyclic Hydrocarbons, Academic Press, New York, 1964. 

Gutman and S. J. Cyvin, Introduction to the Theory of Benzenoid Hydrocarbons, Springer-Verlag, Berlin, 

Nonbenzenoid Conjugated Carbocyclic Compounds, Elsevier, Amsterdam, 1984. 

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Catalytic hydrogenation is mostly used to convert C—C triple bonds into C C double bonds and alkenes into alkanes or to replace allylic or benzylic hetero atoms by hydrogen (H. Kropf, 1980). Simple theory postulates cis- or syn-addition of hydrogen to the C—C triple or double bond with heterogeneous (R. L. Augustine, 1965, 1968, 1976 P. N. Rylander, 1979) and homogeneous (A. J. Birch, 1976) catalysts. Sulfur functions can be removed with reducing metals, e. g. with Raney nickel (G. R. Pettit, 1962 A). Heteroaromatic systems may be reduced with the aid of ruthenium on carbon. 

A useful approach to the substitution of ring C—H positions lies in the activation of the heteroaromatic system by an A-oxide group, initiating a formal intramolecular redox reaction. 1-Methyllumazine 5-oxide reacts with acetic anhydride in a Katada rearrangement... 

Theoretical reactivity indices of heteroaromatic systems distinguish reactivity toward electrophilic, nucleophilic and homolytic reactions. 

The calculation of localization energies in heteroaromatic systems derived from alternant hydrocarbons has been simplified by Dewar and Maitlis (57JCS2521). This approach has had considerable success the results provide a somewhat empirical index of reactivity. 

In this initial section the reactivities of the major types of azole aromatic rings are briefly considered in comparison with those which would be expected on the basis of electronic theory, and the reactions of these heteroaromatic systems are compared among themselves and with similar reactions of aliphatic and benzenoid compounds. Later in this chapter all the reactions are reconsidered in more detail. It is postulated that the reactions of azoles can only be rationalized and understood with reference to the complex tautomeric and acid-base equilibria shown by these systems. Tautomeric equilibria are discussed in Chapter 4.01. Acid-base equilibria are considered in Section 4.02.1.3 of the present chapter. 

Many reduced heteroaromatic compounds are important and are dealt with in the General Chapters and appropriate Monograph Chapters, but usually more briefly than for the corresponding heteroaromatic systems because of this overall similarity with the corresponding acyclic compounds. 

Interconversion between two tautomeric structures can occur via discrete cationic or anionic intermediates (scheme 24, where T is an anion capable of reacting with a proton at a minimum of two distinct sites). Alternatively, interconversion can occur by simultaneous loss and gain of different protons (scheme 25, w here T has the same definition as in scheme 24). These mechanisms are well established for acyclic compounds, but they have been much less thoroughly investigated for heteroaromatic systems. The rate of interconversion of two tautomers is greatest when both of the alternative atoms to which the mobile proton can be attached arc hetero atoms, and isolation of the separate isomers is usually impossible in this case. If one of the alternative atoms involved in the tautomerization is carbon, the rate of interconversion is somewhat slower, but still fast. When both of the atoms in question are carbon, however, interconversion is... 

Compounds of the type HC=C—CH=CHXR are not involved in a primary reaction with weak nucleophiles such as CH acids meanwhile, a final (secondary) cyclization with participation of active methylene groups happens to be feasible. Evidently, in most cases the energy gain in the heteroaromatic system realization is the decisive factor (81UK1252). 

The competitive method employed for determining relative rates of substitution in homolytic phenylation cannot be applied for methylation because of the high reactivity of the primary reaction products toward free methyl radicals. Szwarc and his co-workers, however, developed a technique for measuring the relative rates of addition of methyl radicals to aromatic and heteroaromatic systems. - In the decomposition of acetyl peroxide in isooctane the most important reaction is the formation of methane by the abstraction of hydrogen atoms from the solvent by methyl radicals. When an aromatic compound is added to this system it competes with the solvent for methyl radicals, Eqs, (28) and (29). Reaction (28) results in a decrease in the amount... 

The site of dihydroxylation in heterocycles depends on the nature of the heteroaromatic system (Scheme 9.31) usually, electron-rich heterocycles like thiophene are readily biooxidized but give conformationally labile products, vhich may undergo concomitant sulfoxidation [241]. Electron deficient systems are not accepted only pyridone derivatives give corresponding cis-diols [242]. Such a differentiated behavior is also observed for benzo-fused compounds biotransformation of benzo[b] thiophene gives dihydroxylation at the heterocyclic core as major product, while quinoline and other electron-poor systems are oxidized at the homoaromatic core, predominantly [243,244]. 

Qualitatively, similar relationships are ascertained in heteroaromatic systems where the same conclusion is derived by a numerical calculation. In more elaborate calculations than the Hiickel method, such as the Pariser-Parr-Pople approximation 21>23>, similar distinct parallelisms are recognized 59> (Table 4.1). Essentially the same circumstances exist also... 

Ring transposition processes are well established in six-membered heteroaromatic systems. Recent studies have centered on perfluoro systems in which bicyclic and tricyclic intermediates are sufficiently stable to permit isolation or at least detection. Thus, on irradiation in CF2C1CFC12, the perfluoropyridine 207 is converted into the azabicyclo[2.2.0]hexa-2,5-diene 208 and the two azaprismanes 209 and 210.154 An azabicyclo[2.2.0]hexa-2,5-diene has also been shown to be an intermediate in the photorearrangement of substituted 2-methylpyridines to o-substituted anilines.155 Diaza-bicyclo[2.2.0]hexa-2,5-dienes have similarly been shown to be intermediates in the conversion of fluorinated pyridazines (211) into the corresponding pyrazines (212)156 the proposed pathway is outlined in Scheme 7. Photoproducts which are formally dimers of intermediate azetes have been obtained when analogous reactions are carried out in a flow system.157... 

The (3 + 3) cycloaddition principle has been extended to the heterocyclic betaines 448 representing aza analogues of ylides 427. The betaines 448 combined with diphenyl cyclopropenone and its thione268 to yield the condensed heteroaromatic systems 449 ... 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

Effects of (7-77 interaction are maximized if the interacting orbitals match energetically. Since the HOMOs of heteroaromatic systems such as furan (8.89 eV), thiophene (8.80 eV), and pyrrole (8.20 eV) are higher than that of benzene (9.25 eV), better energy matching with [Pg.380]

Imidazo[2,l-/][[l,3,4]thiadiazoles 161 (Figure 33), containing practically planar and rigid heteroaromatic systems with two condensed heterocycles, which have different Tt-conjugation, have been identified as useful fragments for liquid crystal molecules <2002MI6>. 

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