Three-membered heterocycles aromaticity

The three possibilities of synthesizing a C5 chain, namely, C2 +Ci + C2. C2 -t C2 -I- Cl, or Cl + C3 + Cl, lead to pyrylium salts having identical substituents in positions 2 and 4 in the second case, or 2 and 6 in the first and third cases. Despite this limitation, such syntheses are very convenient because they make the pyrylium salts easily accessible (more so than other six-membered heterocyclic aromatics) from aliphatic starting materials. 

Abstract Compounds with a 1,2-, 1,4- and 1,6-dioxygen pattern and related bifunctional structures are presented. Disconnection of the internal bonds results in illogical synthons because of the mismatch of charges in the patterns with an even number of C atoms between the functional groups. Three-membered heterocyclic rings are presented as an important class of illogical nucleophiles in the retrosyn-thesis of the 1,2-difunctional pattern. Retrosynthesis of the 1,6-dicarbonyl pattern by reconnection and rctro-Birch reduction of the aromatic building block is related to chemoselective Birch reduction and ozonolysis in the synthetic route. The retrosynthesis and synthesis of salbutamol and asymmetric synthesis of —)-frontalin are presented. 

Among the five-membered heterocycles with three nitrogen atoms, triazoles and benzotriazoles are of significant practical importance. In the case of ben-zotriazole, the aromaticity of the benzenoid 1H-benzotriazole (90A, R = H) has been considered to be greater than that of the quinonoid 2/7-benzotria-zole (90B, R = H) (Scheme 43).134 However, the difference in aromaticity between tautomers is greatly dependent on the dielectric constant of the medium. 

Another isomerization reaction of arene oxides is equilibrium with oxe-pins [5], Here, the fused six-membered carbocycle and three-membered oxirane merge to form a seven-membered heterocycle, as shown in Fig. 10.2. An extensive computational and experimental study involving 75 epoxides of monocyclic, bicyclic, and polycyclic aromatic hydrocarbons has revealed much information on the structural factors that influence the reaction rate and position of equilibrium [11], Thus, some compounds were stable as oxepins (e.g., naphthalene 2,3-oxide), while others exhibited a balanced equilibrium... 

While it is clear that 1,2,5-thiadiazoles are clearly aromatic in nature, efforts have been made to quantify the degree of aromaticity. Three detailed comparative studies of relative aromaticity in five membered heterocyclic rings have been carried out by Bird <85T1409>, Katritzky <90JPR885>, and... 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

As with the other procedures for the preparation of six-membered heterocyclic systems which proceed via formation of only one ring bond there are relatively few methods which involve formation of a ring bond y to the heteroatom and which can best be classified as [6 + 0] processes rather than [4 + 2], [3 + 3], etc, processes. Of those which can be so represented, however, a number are important processes which are widely used for the synthesis of saturated, partially saturated and aromatic six-membered heterocyclic systems and their benzo derivatives. Mechanistically, the nucleophile —> electrophile approach is by far the most common, but in contrast to the reactions discussed in the previous three sections, radical cyclizations are of considerable utility here. 

The 13-membered ring is available in a wide variety of unrestricted and restricted forms and undoubtedly represents one of the most thoroughly studied large-membered heterocycles. The size of the system s perimeter is sufficiently large to accommodate the presence of as many as three trans double bonds which, when strategically implanted, allow the molecular skeleton to adopt a rigidly flat or near-flat geometry in which to aromatically delocalize its 14 tr- electrons. 

The chemistry of saturated heterocyclic compounds is characteristic of their functional group. For example, nitrogen compounds are amines, oxygen compounds arc ethers, sulfur compounds are sulfides. Differences in chemical reactivity are observed for three-membered rings, e.g., epoxides, whose enhanced reactivity is driven by the relief of their severe ring strain. This chapter discusses heterocycles that are aromatic and have unique chemical properties. 

No systematic experimental studies on thermodynamic properties of five-membered heterocycles with three or more heteroatoms and at least one tetracoordinated silicon atom were reported. The aromaticity of the fully conjugated germadisiloleanion 21, a heavy congener of the cyclopentadienyl anion, was deduced mainly from its NMR spectroscopic and structural parameters <2005JA13143>. 

The other simple five-membered heterocycles are furan, with an oxygen atom instead of nitro- pyrrole gen, and thiophene with a sulfur atom. They also undergo electrophilic aromatic substitution very Ft ft readily, though not so readily as pyrrole. Nitrogen is the most powerful electron donor of the three, 1 J> oxygen the next, and sulfur the least. Thiophene is very similar to benzene in reactivity. N... 

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