Aromaticity exocyclic groups

Cyclization of the intermediate, 182, by means of ethyl orthoformate takes a quite different course. The nitrogen on the aromatic ring in this case becomes one of the exocyclic groups to afford the chorazanil (185) a compound that shows diuretic activity. 

The bottom line on monocyclic aromatic compounds with re-electron sextet is that so far, among six-membered systems only benzene, the azines with 1 through 4 nitrogen atoms, phosphabenzene and arsaben-zene, pyrylium, azapyrylium, chalcogenopyrylium cations (with or without exocyclic groups such as hydroxy, amino and corresponding tautomeric or prototropic forms), and the metallabenzenes with platinum family metals have been proved to afford stable molecules under normal conditions. The list is richer for five-membered systems. 

Intramolecular charge-transfer excited states may also arise from the promotion of a re-electron from the aromatic ring to a vacant re -orbital localized on an exocyclic group. This phenomenon is often observed in aromatic carboxylic acids, aldehydes, and ketones, where the carbonyl group is conjugated with the aromatic ring. 

Fig. 2 The order of energies of the highest occupied 7t-orbital, the nonbonding (n)-and lone-pair (Z) orbitals, and the lowest unoccupied 7l -orbital of a typical substituted heteroaromatic molecule and the corresponding transitions. The relative position of the lowest 71 -orbital, 7t 0, results from the substitution of an exocyclic group having vacant Tt-orbitals (an electron acceptor) onto the aromatic system. The line denoted p represents the energy of an atomic p-orbital from which the n- or Z-orbital arises.

If the heteroatom contributes two electrons to the tr-electronic structure of the molecule (e.g., nitrogen in pyrrole or indole, oxygen in furan, sulfur in thiophene), it essentially represents a charge-transfer donor-type substituent. Its effect on the electronic structure and spectra will be dominated by its ability to donate electrons and to a lesser extent by considerations of electronegativity. Thus, the interactions of nitrogen, oxygen, and sulfur in, say, indole, benzofuran, and benzothiophene, with their aromatic systems, are similar to the interactions of amino, hydroxy, and mercapto exocyclic groups with their aromatic systems. 

Quinone methides (QMs), especially the simple ones (those not having substituents at the exocyclic methylene group), are very unstable compounds. Their isolation is very difficult and normally requires very dilute solutions and low temperatures.2 Due to the aromatic z witterionic form (Scheme 3.1), quinone methides react very rapidly with both electrophiles and nucleophiles, with the medium, or in self-condensation reactions. 

FIGURE 6.16 ortho-Quinone methide 3 stabilization of the zwitterionic rotamer in a complex with /V-methyImorpholine /V-oxide (17). The zwitterionic, aromatic precursor 3a affords the common quinoid form of the o-QM 3 by in-plane rotation of the exocyclic methylene group. 

When oxytetracycline (100) is reacted with N-chlorosuccinimide in dimethoxyethane, the active methine group at C la reacts and, apparently, there is formed a hemiketal bond between the C -OH and the C -ketogroup (101). Dehydration with anhydrous HF of the tertiary, benzylic C -OH group takes an exocyclic course, partially because aromatization to... 

All the above structures contain the P—C—O—B fragment. Among boryloxyalkylphosphines and their derivatives with an exocyclic phosphorus containing group, (123)—(125) are reported (92IZV196). Such compounds were obtained from secondary phosphines, aromatic aide-... 

The abovementioned transformation proceeds via initial formation of a,p-unsat-urated imines 114 from the starting aromatic nitriles, which then undergo the further nucleophilic attack at C3 atom by the exocyclic amino group of aminoazole followed by the cycUzation and aromatization and yielding the observed products 113 (Scheme 53). 

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