Benzenoids from

The problem of the dependence of E on the number of Kekule structures is examined in some detail in the subsequent section. Nowadays it is fairly well established that this dependence is linear. In former times, when this simple fact was not conceived, an astonishing variety of mathematical expressions was proposed for the description of the K-dependence of E. A comparative study of these early (in most cases unsuccessful) attempts is reported in [89], The data collected in Tables 3 and 4 are analogous to those given in Tables 1 and 2. They are obtained using the same sample of 104 benzenoids from the book [92]. The following (n,m,K)-type expressions for E have been examined ... 

Fig. 8.23 Plot of the correlation between GT values and EC values for the benzenoids from Table 8.3...

Fig. 8.25 Plot of the correlation between the GT index and the tc-electron partition EC value) for the Clar sextet rings of benzenoids from Fig. 8.24...

The electronic spectra of benzenoid systems differ in a characteristic manner from their acyclic analogues. Thus benzene, unhke hexatriene. 

Several substituted cyclohexane derivatives may also be obtained by the reduction of a benzenoid precursor. Partial reduction of resorcinol, for example, and subsequent methyla-tion yields 2-methylcyclohexane-I,3-dione, which is frequently used in steroid synthesis (M.S. Newman, 1960 see also p. 71f.), From lithium-ammonia reduction of alkoxybenzenes l-alkoxy-l,4-cyclohexadienes are obtained (E.J. Corey, 1968 D). 

The material in the succeeding chapters describes both the synthesis of the indole ring and means of substituent modification which are especially important in indole chemistry. The first seven chapters describe the preparation of indoles from benzenoid precursors. Chapter 8 describes preparation of indoles from pyrroles by annelation reactions. These syntheses can be categorized by using the concept of bond disconnection to specify the bond(s) formed in the synthesis. The categories are indicated by the number and identity of the bond(s) formed. This classification is given in Scheme 1.1. 

Two-Dimensional Representation of Chemical Structures. The lUPAC standardization of organic nomenclature allows automatic translation of a chemical s name into its chemical stmcture, or, conversely, the naming of a compound based on its stmcture. The chemical formula for a compound can be translated into its stmcture once a set of semantic rules for representation are estabUshed (26). The semantic rules and their appHcation have been described (27,28). The inverse problem, generating correct names from chemical stmctures, has been addressed (28) and explored for the specific case of naming condensed benzenoid hydrocarbons (29,30). 

The reactions of haloquinoxalines in which the halogen atom is bonded to the benzenoid ring have not been well studied, but by analogy with examples in the phenazine series it would seem probable that they are unlikely to be displaced with the same ease as those bonded directly to the heterocyclic ring. It is evident from the foregoing discussion that A-oxidation has a pronounced effect on their reactivity, and, by this means, considerable latitude in the specific functionalization of dihalo or polyhalo derivatives may be exercised. 

The fusion of a benzene ring to pyrazine results in a considerable increase in the resistance to reduction and it is usually difficult to reduce quinoxalines beyond the tetrahydroquinoxa-line state (91). Two possible dihydroquinoxalines, viz. the 1,2- (92) and the 1,4- (93), are known, and 1,4-dihydroquinoxaline appears to be appreciably more stable than 1,4-dihydropyrazine (63JOC2488). Electrochemical reduction appears to follow a course anzdogous to the reduction of pyrazine, giving the 1,4-dihydro derivative which isomerizes to the 1,2- or 3,4-dihydroquinoxaline before subsequent reduction to 1,2,3,4-tetra-hydroquinoxaline (91). Quinoxaline itself is reduced directly to (91) with LiAlH4 and direct synthesis of (91) is also possible. Tetrahydroquinoxalines in which the benzenoid ring is reduced are well known but these are usually prepared from cyclohexane derivatives (Scheme 30). 

As might be anticipated from the behaviour of the parent heterocycles, C-2 of indole, benzo[i]furan and benzo[i]thiophene (Table 13) is shifted to lower field than C-3. However, the shifts for C-2 (O, 144.8 Se, 128.8 S, 126.1 NH, 124.7 Te, 120.8) and C-7a (O, 155.0 Se, 141.3 S, 139.6 NH, 135.7 Te, 133.0) in the benzo[i] heterocycles vary irregularly (80OMR(l3)3l9), and the sequence is different to that observed for C-2 in the parent heterocycles, namely 0>Se>Te>S>NH. Also noteworthy is the upheld position of C-7, especially in indole and benzofuran, relative to the other benzenoid carbons at positions 4, 5 and 6. A similar situation pertains in the dibenzo heterocycles (Table 14), where not only are C-1 and C-8 shifted upheld in carbazole and dibenzofuran relative to the corresponding carbons in dibenzothiophene and fluorene, but similar, though smaller, shifts can be discerned for C-3 and C-6 in the former compounds. These carbon atoms are of course ortho and para to the heteroatom and the shifts reflect its mesomeric properties. Little variation in the carbon-hydrogen coupling constants is observed for these dibenzo compounds with V(qh) = 158-165 and V(c,h) = 6-8 Hz. 

In most cases the frequencies of substituent groups attached to these heterocycles differ little from those observed for their benzenoid counterparts. The only notable exception is the spectral behaviour of carbonyl groups attached to position 2. These have attracted much attention as they frequently give rise to doublets, and occasionally multiplets. In the case of (34), (35) (76JCS(P2)l) and (36) (76JCS(P2)597) the doublets arise from the presence of two conformers (cf. Section 3.01.5.2), whereas for the aldehydes (37) the doublets are... 

Rates of debromination of bromonitro-thiophenes and -selenophenes with sodium thio-phenoxide and sodium selenophenoxide have been studied. Selenophene compounds were about four times more reactive than the corresponding thiophene derivatives. The rate ratio was not significantly different whether attack was occurring at the a- or /3-position. As in benzenoid chemistry, numerous nucleophilic displacement reactions are found to be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g. AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 77) (75JCS(P1)1390). 

In general, substituents removed from the ring by two or more saturated carbon atoms undergo normal aliphatic reactions, and substituents attached directly to fused benzene rings or aryl groups undergo the same reactions as do those on normal benzenoid rings. 

Pyrylium salts alkyl groups reactivity, 3, 662 aromaticity, 3, 640 arylammes from, 3, 657 benzenoid compounds from, 3, 656, 658 benzisoxazol-3-yl-synthesis, 6, 124 bicyclic... 

The C NMR spectrum of the metabolite shows 16 signals instead of 8 as expected from the elemental composition determined by high-resolution mass spectrometry. Moreover, aromaticity of the 2,6-xylenol is obviously lost after metabolism because two ketonic carbonyl carbon atoms (5c = 203.1 and 214.4) and four instead of twelve carbon signals are observed in the shift range of trigonal carbon nuclei (5c = 133.1, 135.4, 135.6 and 139.4) in the C NMR spectra. To conclude, metabolism involves oxidation of the benzenoid ring. 

These various photoproducts are all valence isomers of the normal benzenoid structure. These alternative bonding patterns are reached from the excited state, but it is difficult to specify a precise mechanism. The presence of the t-butyl groups introduces a steric factor that works in favor of the photochemical valence isomerism. Whereas the t-butyl groups are coplanar with the ring in the aromatic system, the geometry of the bicyclic products results in reduced steric interactions between adjacent t-butyl groups. 

The Birch reduction of a benzenoid compound involves the addition of two electrons and two protons to the ring. The order in which these additions occur has been the subject of both speculation and study. Several reviews of the subject are available and should be consulted for details. The present discussion is concerned with summarizing data that is relevant to understanding the reaction from the preparative point of view. For convenience, reaction intermediates are shown without indicating their solvation by liquid ammonia. This omission should not obscure the fact that such solvation is largely responsible for the occurrence of the Birch reduction. 

It is apparent from simple valence bond considerations as well as from calculations of rr-electron density, " that isoindoles should be most susceptible to electrophilic attack at carbon 1. This preference is most clearly evident when the intermediate cations (85-87) from electrophilic attack (by A+) at positions 1, 4, and 5 are considered. The benzenoid resonance of 85 is the decisive factor in favoring this intermediate over its competitors. 

Alkyl Groups. In the class of non-conjugative positions, the observed order of the deactivating effect of the methyl group is meta > pros (2-chloroquinoline), and the fall-off factor is 1/1.3 in this case. The fall-off factor is near unity if the effects from the meta position and the conjugative cata positions are compared (4-chloroquinoline), which indicates that the deactivating effect orders are cata > epi and amphi > pros as predicted by the benzenoid order para > meta. 

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