Heterocyclic aromatic compounds pyrrole

Cyclic compounds that contain at least one atom other than carbon within their ring are called heterocyclic compounds, and those that possess aromatic stability are called het erocyclic aromatic compounds Some representative heterocyclic aromatic compounds are pyridine pyrrole furan and thiophene The structures and the lUPAC numbering system used m naming their derivatives are shown In their stability and chemical behav lor all these compounds resemble benzene more than they resemble alkenes... 

A large group of heterocyclic aromatic compounds are related to pyrrole by replacement of one of the ring carbons p to nitrogen by a second heteroatom Com pounds of this type are called azoles... 

Section 12 18 Heterocyclic aromatic compounds may be more reactive or less reactive than benzene Pyridine is much less reactive than benzene but pyrrole furan and thiophene are more reactive... 

Pyrrole is a nitrogen-containing unsaturated five-membered heterocyclic aromatic compound. It shows aromaticity by delocalization of a lone pair of... 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

Furan, thiophene, pyrrole, and pyridine are all examples of heterocyclic aromatic compounds (heteroaromatic compounds). The heteroatoms in some of these compounds (furan, thiophene, pyrrole) contribute one lone pair to the aromatic system, whereas in others (pyridine) they contribute none. You can determine how many lone pairs a heteroatom contributes to the aromatic system by examining the effect of lone-pair donation on the hybridization of the heteroatom. For example, if the N atom of pyridine used its lone pair to participate in resonance, it would have to be sp-hybridized (one p orbital required for the N=C n bond, one for the lone pair used in resonance), but sp hybridization requires 180° bond angles, which are not possible in this compound. Therefore the N atom must be sp2-hybridized, and the N lone pair must be in a hybrid orbital that is orthogonal to the cyclic array of p orbitals. In pyrrole, by contrast, if the N atom uses its lone pair in resonance, the N atom must be sp2-hybridized, which is reasonable. Therefore, there is a cyclic array of p orbitals in pyrrole occupied by six electrons (two from each of the C=C it bonds and two from the N lone pair), and pyrrole is aromatic. 

HD as a required step in the induction of both testicular and nervous system injuries (5-8). Subsequent oxidation and cross-linking of these tissue-bound heterocyclic aromatic compounds result in a complex array of products, including pyrrole dimers (9, 10). 

Heterocyclic aromatic compounds such as pyrrole are readily metallated with Grignard reagents. The resulting compounds have N"Mg bonds and are, therefore, not organometallic compounds, but on reaction with electrophiles give 2-substituted pyrroles [14] (eq (4)). The reaction of chloroform or bromoform with PrMgCl at -78 °C in THF-HMPA (4 1) is mild and convenient method for the generation of an unstable carbenoid in the solution [15] (eq (5)). 

The chemical reactivity of simple heterocyclic aromatic compounds varies widely in electrophilic substitution reactions, thiophene is similar to benzene and pyridine is less reactive than benzene, while furan and pyrrole are susceptible to polymerization reactions conversely, pyridine is more readily susceptible than benzene to attack by nucleophilic reagents. These differences are to a considerable extent reflected in the susceptibility of these compounds and their benzo analogues to microbial degradation. In contrast to the almost universal dioxygenation reaction used for the bacterial degradation of aromatic hydrocarbons, two broad mechanisms operate for heterocyclic aromatic compounds ... 

As mentioned above, a major problem in using heterocyclic aromatic compounds as dienes in the Diels-Alder reaction is their highly aromatic character which hinders their involvement in reactions that include direct participation of their 7c-bonds. Some heterocycles such as pyrrole would, in many instances, rather participate in Michael-addition type of reactions than in Diels-Alder... 

Heterocyclic aromatic compounds can sometimes be reduced, particularly those which are electron-deficient. For example, reduction of pyridines gives 1,4-dihydropyridines (which are readily hydrolysed to 1,5-dicarbonyl compounds). Partial reduction of five-membered heteroaromatic compounds such as furans and pyrroles is also possible if these have electron-withdrawing substituents to stabilize the intermediate radical anion. For example, reduction of the furan 71 occurred with high selectivity to give the dihydrofuran 72, used in a synthesis of (-l-)-nemorensic acid (7.51).24... 

Consider the structure shown on the left, pyrrole. This is also aromatic but it s not enough just to use the electrons in the double bonds in pyrrole the nitrogen s lone pair contributes to the six 7t electrons needed for the system to be aromatic. Aromatic chemistry makes several more appearances in this book in Chapter 21 we shall look at the chemistry of benzene and in Chapters 30 and 31 we shall discuss heterocyclic aromatic compounds in much more detail. 

Imidazole is a heterocyclic aromatic compound with two nitrogens in a five-membered ring. One nitrogen has a pyridine-like unshared pair the other has a pyrrole-like pair that is incorporated into the aromatic tt system. Imidazole is somewhat more basic than pyridine. When imidazole acts as a Br0nsted base, protonation of its pyridine-like nitrogen permits aromaticity to be retained by leaving the pyrrole-like nitrogen untouched. 

Heterocyclic aromatic compounds contain C and H atoms other than carbon and hydrogen (Fig. 6). For the monocyclic molecules Hiickel s rule is applicable. For example both pyridine and pyrrole contain six ti electrons. Unlike the former the lone pair of the latter is delocalized. Armit and Robinson have shown a connection between the electronic sextet and the heteroaromaticity. Due to the electronegativity difference between carbon and nitrogen the bonds in pyridine are not of equal length and the delocalization is not perfect. Five membered heteroaromatics with oxygen and sulfur are furan and thiophene respectively. Pyrazole/imidazole, triazoles and tetrazoles are five membered heteroaromatics with two, three and four nitrogen atoms respectively. Three important aromatic six membered heterocyclic molecules are pyrimidine, pyrazine and pyridazine. Benzofused... 

The neutral, five-membered heterocyclic ring compounds, pyrrole and fiiran, also show aromatic character. Even thiophene is considered aromatic (Fig. 13.49). Furan and pyrrole can complete an aromatic sextet of n electrons by using a pair of nonbonding electrons in a 2p orbital. These molecules have the same number of n electrons as the cyclopentadienyl anion, but none of the problems induced by... 

Pyrrole, fiiran, and thiophene are heterocyclic aromatic compounds that undergo electrophilic aromatic substitution reactions preferentially at C-2. They are more reactive than benzene toward electrophilic aromatic substitution. 

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