Aromaticities of heterocycles and

Various methods to quantify the aromaticity of heterocycles and the interrelationship between different scales are controversial and have been covered in a recent article.6b... 

The Aromaticity of Heterocycles and Tautomeric Equilibriums A. R. Katritzky, Lect. Heterocycl. Chem., 1972,1, 39-49. 

CaveU and Chapman made the interesting observation that a difference exists between the orbital involved in the quatemization of aromatic nitrogen heterocycles and aromatic amines, which appears not to have been considered by later workers. The lone pair which exists in an sp orbital of the aniline nitrogen must conjugate, as shown by so many properties, with the aromatic ring and on protonation or quatemization sp hybridization occurs with a presumed loss of mesomerism, whereas in pyridine the nitrogen atom remains sp hybridized in the base whether it is protonated or quaternized. Similarly, in a saturated compound, the nitrogen atom is sp hybridized in the base and salt forms. 

Katritzky and his colleagues have used equilibrium proto nation to estimate the aromaticity of furan and similar heterocycles using 2,5-di-tert-butylfuran as substrate in sulfuric acid. In agreement with the foregoing discussion, the furan does not behave as a Hammett (i.e., oxygen) base but as a carbon base similar to azulene. On Reagan s Hc scale, the furan gave n = 1.22, correspond-... 

Heterocycles Both non-aromatic unsaturated heterocycles and heteroaromatic compounds are able to play the role of ethene dipolarophiles in reactions with nitrile oxides. 1,3-Dipolar cycloadditions of various unsaturated oxygen heterocycles are well documented. Thus, 2-furonitrile oxide and its 5-substituted derivatives give isoxazoline adducts, for example, 90, with 2,3- and 2,5-dihydro-furan, 2,3-dihydropyran, l,3-dioxep-5-ene, its 2-methyl- and 2-phenyl-substituted derivatives, 5,6-bis(methoxycarbonyl)-7-oxabicyclo[2.2.1]hept-2-ene, and 1,4-epoxy-l,4-dihydronaphthalene. Regio- and endo-exo stereoselectivities have also been determined (259). 

There are two distinct classes of compounds that fit the criteria mentioned above alkene-functionalized chalcone derivatives (Fig. IB) and enone-functionalized chalcone derivatives (Fig. 1C). Within each class, both aromatic and non-aromatic compounds exist. Those compounds functionalized at the alkene include i) 3-membered heterocycles, e.g., epoxide and aziri-dine compounds, ii) 5-membered aromatic derivatives including fused and non-fused compounds, and iii) 6-membered aromatic pyrazine compounds. The enone-functionalized compounds include i) 5-membered aromatics such as pyrazole and isoxazole compounds, ii) 5-membered non-aromatic compounds for example pyrazolines and isoxazolines, and iii) 6-membered non-aromatics where a discussion of heterocyclic and non-heterocyclic compounds will be given for completeness. 

Structures and nomenclature for the most important five-membered monocycles with one or more heteroatoms are depicted in Scheme 1. The aromaticity scale in five-membered heterocycles has been long debated.97-101 The decreasing order of aromaticity based on various criteria is (DRE values in kcal/ mol) benzene (22.6) > thiophene (6.5) > selenophene > pyrrole (5.3) > tellurophene > fur an (4.3). Pyrrole and furan have comparable ring strains (Scheme 38). The aromaticity of furan is still controversial 100 the NMR shielding by ring current estimated it at about 60% of the aromaticity of benzene, and other methods reviewed earlier102 estimated it at less than 20%. 

Nitrogen. Pyridine is one of the most important heterocycles. The aromaticity of pyridine was intensively connected to structural considerations and chemical behavior. The relative difference between the aromaticity of benzene and pyridine is controversial generally calculations give similar orders of magnitude and differences depend on the criterion of aromaticity considered and the mode of calculation used. A comprehensive review on the theoretical aspects in connection with the aromaticity of pyridine was published.191 Pyridine is about as aromatic as benzene according to theoretical calculations and to experimental data, while quinoline is about as aromatic as naphthalene and more aromatic than isoquinoline.192193 The degrees of aromaticity of pyridine derivatives strongly depend on their substituents. 

Main-chain manipulation offers an opportunity to dramatically change the electronic and physical properties of the PAEs. Popular approaches are the introduction of meta linkages into the polymers, the introduction of aromatic hydrocarbons other than benzene, the introduction of heterocycles, and the substitution of a fraction of the connecting alkyne groups by double bonds. The last strategy leads to polymers that are hybrids between PPEs and PPVs. 

Alkoxynitrenium ions formed by the Lewis acid method have also been shown to be efficient electrophiles towards aromatic ring systems, and two groups in particular have fashioned this reaction as an excellent source of heterocycles and benzolactams . 

B. Aromaticity and Anti aromaticity of Heterocyclic Compounds That Are 7t-Isoelectronic with the Parent Hydrocarbon... 

Microwave spectroscopy indicates that aromaticity diminishes in the order 1,2,5-thia-diazole > thiophene > l,3,4-thiadiazole> l,2,5-oxadiazole> 1,2,4-oxadiazole <84CHEC-1(4)545, B-85MI 410-01>. The aromaticity of heterocycles has been discussed by Katritzky and Barczynski (90JPR885) and by Bird <94H(37)249>. The thermal stability of 2,5-substituted thiadiazoles (23) was studied by differential scanning calorimetry and shown to increase as the rt-contribution of the substituents becomes greater <89MI410-01>. 

D. Model Studies on Enzymatic Oxidation of Heterocycles and Aromatic... 

Heterocyclic These are compounds having at least one hetero atom (any other atom but carbon, e.g. O, N and S) within the ring, and conforming to Hiickel s rule. The aromaticity of heterocyclic compounds, e.g. pyridine and pyrrole, can be explained as follows. 

A number of anion-radicals and dianions of, e.g., aromatic hydrocarbons, heterocycles, and carbonyl and nitro compounds have been used as mediators in cleavages22-27 such mediators must be used in aprotic media such as DMF. 

A linear relationship has been shown to exist between structural aromaticity indices and resonance energies (92T335). From this so-called unified aromaticity index, IA, has been proposed. It makes for a more appropriate comparison the aromaticity of heterocycles of different size. 

TT-Electron delocalization in isoxazole seems to be more effective than in oxazole however, isothiazole is less aromatic than thiazole thus it is not a general rule that 1,2-diazoles possess higher aromaticity in comparison with 1,3-diazoles. Oxygen-containing heterocycles are always less aromatic than their sulfur and nitrogen counterparts, e.g. thiazole > imidazole > > oxazole. At the same time, the relative aromaticity of S- and N-containing heterocycles can interchange (pyrazole > isothiazole > isoxazole). 

Magnetic criteria have received wide application mainly as a qualitative test for aromaticity and antiaromaticity. The values of the exaltation of diamagnetic susceptibility (in 10-6A cm-3 mol-1), and therefore aromaticity, decrease in the sequence thiazole (17.0) > pyrazole (15.5) > sydnone (14.1). The relative aromaticity of heterocycles with a similar type of heteroatom can be judged from values of the chemical shifts of ring protons. The latter reveals paramagnetic shifts when Tr-electron delocalization is weakened. For example, in the series of isomeric naphthoimidazoles aromaticity decreases in the sequence naphthof 1,2-djimidazole (8 = 7.7-8.7 ppm) > naphtho[2,3- perimidine (8 = 6.1-7.2 ppm). This sequence agrees with other estimates, in particular with energetic criteria. 

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