Heteroaromatic rings, examples

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenylo.xazoline 691[552], dithiophenopyridine 692[56l] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

This process is not as common as the other oxidative procedures and usually involves ring closure onto an aromatic or heteroaromatic ring. The following examples illustrate the structural types required for this cyclocondensation. 

The complexity of the system consisting of the diazonium ion and the four reaction products shown in Scheme 5-14 is evident. In contrast to the two-step reaction sequence diazonium ion <= (Z)-diazohydroxide <= (Z)-diazoate (Scheme 5-1 in Sec. 5.1), equilibrium measurements alone cannot give unambiguous evidence for the elucidation of the mechanistic pathway from, for example, diazonium ion to ( )-diazoate. Indeed, kinetic considerations show that, depending on the reaction conditions (pH etc.) and the reactivity of a given diazonium ion (substituents, aromatic or heteroaromatic ring), different pathways become dominant. 

Figure 3 Examples of heteroaromatic rings generated that have never been made.

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

The heteroaromatic rings can sometimes be built up by a cycloaddition reaction, similarly to the ways in which the protic heteroaromatic parents can be formed. Frequently, a retro-Diels-Alder reaction is involved. Some examples are given in Table 4. 

Halogen substituents are of course easy to introduce to heteroaromatic rings, and they also enhance the acidity of the ring protons. n-BuLi will, for example, lithiate the tetrafluoropyridine 179 at —60°C in ether ° but with pyridine itself it leads to addition/reoxidation products . Addition to the ring is the major product with 2-fluoropyridine 180, though some metaUation can be detected selectivity in favour of metaUation is complete with LDA in THF at —75 °C or with phenyUithium and catalytic -Pr2NH at —50°C (Scheme 90) . Similar results are obtained with quinolines . 

The examples of polyacetylenes whose main chain is directly bonded to heteroaromatic rings (e.g., silole, carbazole, imidazole, tetrathiafulvalene, ferrocene) are increasing in number. Such polymers are usually obtained by one of catalysts (W, Mo, and Rh). The formed polymers are expected to display interesting (opto)electronic properties such as electrochromism, cyclic voltammetry, electroluminescence, and so on. 

As already indicated for acrolein and for the five-membered heteroaromatic rings (e.g. furan Fig. 2.11), resonance may also be important between nonbonded electrons on a single atom and a 7T-bond system. For example, an unshared electron pair of oxygen greatly contributes to the stabilization of the carboxylate anion ... 

Oxidation of enolizable nitro, carbonyl and dicarbonyl compounds with Fem MnnI and Celv reagents in the presence of electron rich aromatic (or heteroaromatic) rings often provides modest to good yields of substituted products. Typical examples are shown in Scheme 81.233 234 The oxidant functions both to generate the initial radical (Scheme 71) and to trap the adduct radical. Products of ortho substitution usually predominate but significant amounts of para and meta products are often formed, and in some cases, reversibility in the addition step may influence the product distribution. A recent paper by Citterio and Santi provides a nice introduction to these types of reactions.219... 

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. 

You ll notice in the prior art definition, the aromatic and heteroaromatic ring systems are defined by only the number of atoms they contain. Typically, patents and patent applications will further clarify such definitions, including the possibility for additional optional substitutions on those ring systems, either in the claim itself or in the patent specification. Such further subdefinitions were left out to simplify the Markush example. 

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