Ortho-disubstituted benzenes

Although there are a wide variety of indole ring syntheses (25), most of the more useful examples fall within a small number of groups. Indole syntheses usually start with an aromatic compound, either monosubstituted or ortho-disubstituted. Those which begin with a monosubstituted starting material must at some point effect a substitution of the benzene ring. 

FrielA,nderSynthesis. The methods cited thus far all suffer from the mixtures which usually result with meta-substituted anilines. The use of an ortho-disubstituted benzene for the subsequent constmction of the quinoline avoids the problem. In the FrieWider synthesis (52) a starting material like 2-aminoben2aldehyde reacts with an CX-methyleneketone ia the presence of base. The difficulty of preparing the required anilines is a limitation ia this approach, but 2-nitrocarbonyl compounds and the subsequent reduction of the nitro group present a usehil modification (53). 

Syntheses from Phthalimidines Syntheses from Ortho-Disubstituted Benzenes Condensation of 1,4-Diketones with Amines and Pyrroles Other Reactions and Rearrangements Leading to Isoindoles IV. Properties of the Isoindole System A. Tautomerism... 

Disubstituted benzenes are named using one of the prefixes ortho- (o), meta- (in), or para- (p). An ortho-disubstituted benzene has its two substituents in a 1,2 relationship on the ring, a meta-disubstituted benzene has its two substituents in a 1,3 relationship, and a para-disubstituted benzene has its substituents in a 1,4 relationship. 

Ortho-disubstituted benzenes show a strong peak between 680 and 725 cm" and a very strong peak between 750 and 810 cm". ... 

For the infrared spectra there is, of course, no impact mechanism available for exciting additional features from not completely symmetrical modes, and none of the in-plane ca. 1395 (pi3), 1275 (v9), or 1147 cm 1 (vU) or vv) modes would be allowed if the MSSR applied strictly to parallel adsorption on (111) or (100) facets. They would, however, all become allowed on a Cs site, such as would arise from adsorption on twofold bridges. The infrared spectra of alternative monosubstituted or ortho-disubstituted benzenes (the most likely dissociatively adsorbed species) would give rise to two additional strong bands between 1400 and 1620 cm-1, and so the observed spectrum is again seen to be consistent with nondissociative adsorption. 

Four adjacent hydrogens, ortho-disubstituted benzene. 

This model predicts the existence of a barrier to the reaction whose height depends on the dipole moment of the chromophore. The efficiency of this process for distributed benzenes is clearly correlated with their dipole moments it is larger for ortho-disubstituted benzene than for meta- and para-distributed benzenes. This explains the cluster experiments (Brutschy et al. 1991) as well as the variation of reactivity in the gas phase (Tholman and Grutzmacher 1991). 

A more dramatic example occurs for an ortho-disubstituted benzene with two identical substituents X-0-C6H4-X (Fig. 2.28). In this case we can label the four adjacent protons on the benzene ring as Ha, Hb, H and Ha/ in that order. The two systems are very tightly connected because Hb and H have a large coupling (ortho or 3/hh = 8-10 Hz), similar to /ab and. This pattern is very distorted, and in many instances there is no recognizable underlying AB pattern. 

The structure of cleistopholine (154), was suggested by its high-resolution mass spectrum and its IR and NMR spectra (77). The H-NMR spectrum indicated the presence of a nearly symmetrically ortho-disubstituted benzene ring and a 2,3-disubstituted 4-methylpyridine ring that could best be accommodated by the 4-methyl-l-azaanthra-9,10-quinone structure. Complete assignment of its... 

Ladenburg pointed out that the Kekule stmcture does not account for the fact that there is only one ortho-disubstituted benzene as its fixed double bonds should give rise to two isomers. Thus, Ladenburg suggested a prismatic geometry, for which there would also only be three disubstituted isomers as found experimentally for benzene, whereas Kekule s cyclohexatriene stmcture implies four disubstituted isomers. In 1872, Kekule answered this... 

Equilibrium proposed by Kekule (1872) to explain the unicity of ortho-disubstituted benzene... 

The usual precursor is an appropriately ortho-disubstituted benzene . Thus, quinazolines 276 can be prepared by the reaction of 0-acylanilines 275 (R = alkyl) with amides (Scheme 153). Heating anthranilic acid with amides or amidines yields 4-quinazolinones for example, the 2-unsubstituted... 

For AA BB, the spectrum is symmetrical about the average l/2 vA + vB), and in principle all 24 lines may be observed. Even at high field, some ortho-disubstituted benzenes, for example, may display an AA BB spectra, rather than an AA XX spectrum. 

An ortho disubstituted benzene has two substituents in a 1,2 relationship. A meta... 

The usual synthesis of phenoxazines makes use of suitable ortho-disubstituted benzenes, starting from which the oxazine skeleton is completed by ring closure. As intermediates, during the different ring... 

Sulfonation of the aromatic nucleus (method 540) is a reversible reaction. The removal of a sulfonic acid group is important in the preparation of alkylated benzenes by the Jacobsen reaction (method 16). Ortho-disubstituted benzenes are sometimes prepared by using the sulfonic acid group to block the para position. The removal of the sulfonic acid group is usually effected by heating the arylsulfonic acid with aqueous sulfuric acid. 

Magnetic nonequivalence is not uncommon. The spin systems for both para- and ortho-disubstituted benzene rings are AA XX (or AA BB if the chemical shifts are close). Figure 4-3 illustrates the proton spectrum of 1,2-dichlorobenzene (4-8), which is AA XX and relatively complex. Constraints of a ring frequently convey magnetic nonequivalence, as, for example, in butyrolactone (4-9). Even open-chain systems such as... 

The conclusive assignment of the H and benzene ring at 80 and 20 MHz, respectively, encounters difficulties. However, the frequency dispersion is so good at 400 and 100 MHz, respectively, that the HH COSY in combination with the CH COSY technique allows a conclusive assignment to be made. Proton connectivities are derived from the HH COSY the CH correlations assign each of the four CH units. Both techniques converge to establish the CH skeleton of the ortho-disubstituted benzene ring. 

Electronic and steric effects in the case of ortho-disubstituted benzenes. It is found that ESE° values of ortho compounds are most often negative and systematically lower than those of meta and para isomers, whatever the nature of the substituents may be. 

Benzene. The earliest work in directed metalation was done on the benzene system in the early 1930s (3). That the benzene ring was the most promising system for the exploitation of this reaction appears logical since it was by far the most examined aromatic system at that time. Not only have the largest number of directing substituents been successfully demonstrated for this system, but in all probability the demand for a convenient route to a specific polysubstituted aromatic compound will be highest for this system. In all cases examined, directed metalation of a monosubstituted benzene has yielded almost exclusively ortho metalation, with only ortho-disubstituted products obtained (Reaction 1). With... 

Monosubstituted benzenes that undergo the directed metalation reaction are summarized in Table I. In every case a variety of ortho-disubstituted products have been prepared these would be tedious or impossible to prepare by other routes. 

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