Aromaticity and heteroaromaticity

Pyridine is stracturally related to benzene one CH unit has been replaced by N. If we consider the constitutions of the two compounds in more 

Benzene conforms to Hiickel s ruie, which predicts that planar cyclic polyenes containing 4 -I- 2 7t electrons show enhanced stability associated with aromaticity (see Section 2.9.3). Pyridine is also aromatic nitrogen contributes one electron in a orbital to the Jt electron system, and its lone pair is located in an sp orbital that is in the plane of the ring and perpendicular to the n electron system. It also conforms to HtickeTs rule, in that we still have an aromatic sextet of Jt electrons. 

One of the structural features of benzene that derives from aromaticity is the equal length of the C-C bonds (1.40 A), which lies between that for normal single (1.54 A) and double (1.34 A) bonds. Nevertheless, we continue to draw benzene with single and double bonds because this allows us to 

Nitrogen is more electronegative than carbon, and this influences the electron distribution in the Jt-electron system in pyridine through inductive effects, such that nitrogen is electron rich. In addition, the 

Now let us now consider pyrrole, where we have a five-membered ring containing nitrogen. Pyrrole is also aromatic. This is somewhat unexpected how can we get six n electrons from just five atoms The answer is that each carbon contributes one electron as before, but nitrogen now contributes 

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Reactions of aromatic and heteroaromatic rings are usually only found with highly reactive compounds containing strongly electron donating substituents or hetero atoms (e.g. phenols, anilines, pyrroles, indoles). Such molecules can be substituted by weak electrophiles, and the reagent of choice in nature as well as in the laboratory is usually a Mannich reagent or... 

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. 

The thiazolyl radicals are, in comparison to the phenyl radical, electrophilic as shown by isomer ratios obtained in reaction with different aromatic and heteroaromatic compounds. Sources of thiazolyl radicals are few the corresponding peroxide and 2-thiazolylhydrazine (202, 209, 210) (see Table III-34) are convenient reagents, and it is the reaction of an alky] nitrite (jsoamyl) on the corresponding (2-, 4-, or 5-) amine that is most commonly used to produce thiazolyl radicals (203-206). The yields of substituted thiazole are around 40%. These results are summarized in Tables III-35 and IIT36. 

In contrast to H shifts, C shifts cannot in general be used to distinguish between aromatic and heteroaromatic compounds on the one hand and alkenes on the other (Table 2.2). Cyclopropane carbon atoms stand out, however, by showing particularly small shifts in both the C and the H NMR spectra. By analogy with their proton resonances, the C chemical shifts of k electron-deficient heteroaromatics (pyridine type) are larger than those of k electron-rieh heteroaromatic rings (pyrrole type). 

The reversed polarity of the double bond is induced by a n electron-accepting substituent A (A = C=0, C=N, NO2) the carbon and proton in the p-position are deshielded (-A/effect, larger shifts). These substituents have analogous effects on the C atoms of aromatic and heteroaromatic rings. An electron donor D (see above) attached to the benzene ring deshields the (substituted) a-C atom (-/ effect). In contrast, in the ortho and para positions (or comparable positions in heteroaromatic rings) it causes a shielding +M effect, smaller H and C shifts), whereas the meta positions remain almost unaffected. 

Table 2.5. Typical HH coupling constants (Hz) of aromatic and heteroaromatic compounds...

In the case of alkenes and aromatic and heteroaromatic compounds, analysis of a single multiplet will often clarify the complete substitution pattern. A few examples will illustrate the procedure. 

In the chemical shift range for alkenes and aromatic and heteroaromatic compounds enol ether fragments (furan, pyrone, isoflavone, 195-200 Hz) ... 

Scheme 10.3. Activation Hardness for Aromatic and Heteroaromatic Compounds ...

Bonds within aromatic and heteroaromatic rings are not strategic. 

Photochemistry of Fluorosubstituted Aromatic and Heteroaromatic Molecules Zupan, M., Stret, B. Isr J. Chem. 17, 92-99 63... 

The photochemical introduction of a trifluoromethyl group into aromatic and heteroaromatic rings, such as uracil, can be performed also with trifluoromethyl bromide [/5/] (equation 131)... 

Silver(I) triflate is widely applied to the preparation of various derivatives of triflic acid, both covalent esters [66] and ionic salts For example, it can be used for the in situ generation of iodine([) triflate, a very effective lodinatmg reagent for aromatic and heteroaromatic compounds [130] (equations 65 and 66)... 

Perfluocoalkyl groups thermodynamically destabilize double bonds and small rings, but they can kineiically stabilize highly stramed molecules [75]. This remarkable perfluoroalkyl effect has made possible the isolation of stmctures that are uncommon m hydrocarbon chemistry, especially valence-bond isomers of aromatics and heteroaromatics such as 1, 2, and 3 [108],... 

Hydrazides of vicinal acetylene-substituted derivatives of benzoic and azole carboxylic acids are important intermediate compounds because they can be used for cyclization via both a- and /3-carbon atoms of a multiple bond involving both amine and amide nitrogen atoms (Scheme 131). Besides, the hydrazides of aromatic and heteroaromatic acids are convenient substrates for testing the proposed easy formation of a five-membered ring condensed with a benzene nucleus and the six-membered one condensed with five-membered azoles. 

The cyclization of hydrazides of aromatic and heteroaromatic acids is likely to give four most probable products diazepines, diazines, 5-iV-aminolactams, and y -iV-aminolactams. 

The reactions of 4-alkoxybut-3-en-2-ones with primary aromatic amines and diamines of the aromatic and heteroaromatic series follow analogous schemes. 

The competitive method employed for determining relative rates of substitution in homolytic phenylation cannot be applied for methylation because of the high reactivity of the primary reaction products toward free methyl radicals. Szwarc and his co-workers, however, developed a technique for measuring the relative rates of addition of methyl radicals to aromatic and heteroaromatic systems. - In the decomposition of acetyl peroxide in isooctane the most important reaction is the formation of methane by the abstraction of hydrogen atoms from the solvent by methyl radicals. When an aromatic compound is added to this system it competes with the solvent for methyl radicals, Eqs, (28) and (29). Reaction (28) results in a decrease in the amount... 

Hexamethylphosphorous triamide general reaction with aromatic and heteroaromatic aldehydes to give diaryl ethylene oxides, 46,... 

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