Five-membered ring heterocycles pyrrole

The concept of five-membered ring heterocyclic synthesis by transformation of the initial adduct of the ADC compound and substrate is not limited to cyclization of substitution products. l,3,4-Oxadiazol-2-ones (30, Scheme 3) result from heating the initial DEAZD-dichlorocarbene adduct.72 Treatment of the Diels Alder adducts 96 with zinc in acetic acid gives pyrroles in good yield (Eq. 17).151 The reaction has been extended to the synthesis of dipyrroles from the appropriate Diels-Alder adduct (96, R = pyrrol-2-yl). 

The formation of a diverse array of five-membered ring heterocycles via the cycloaddition of isocyanides with furan- or pyrrole-based enones was reported. The reaction mechanism is discussed and an example is shown below <06OL3975>. 

We have looked at the five-membered aromatic heterocycles pyrrole, furan and thiophene in Section 11.5. Introduction of a second heteroatom creates azoles. This name immediately suggests that nitrogen is one of the heteroatoms. As soon as we consider valencies, we discover that in order to draw a five-membered aromatic heterocycle with two heteroatoms, it must contain nitrogen A neutral oxygen or sulfm atom can have only two bonds, and we cannot, therefore, have more than one of these atoms in any aromatic heterocycle. On the other hand, there is potential for having as many nitrogens as we like in an aromatic ring. 

Kinetic results concerning catalytic hydrogenative destruction of heterocyclic nitrogen compounds have been published by Cox and Berg.21 In their operating condition (370°C, 17 atm, space velocity 0.5-20 h 1, which does not affect the rate of HDN, wt% N < 2.5%), they found that most of the five membered ring compounds (pyrrole derivatives and indole) follow a second-order law with respect to the amine pressure, while a first-order law is shown for six membered ring compounds (pyridine and derivatives). 

Five-membered ring heterocyclic azides are readily reduced (H2S, LiAlH4) to the corresponding amines. On thermolysis they lose nitrogen, thereby generating nitrenes. For example, 3-azido-2-vinyl derivatives in xylene at 120130C yield [3,2-A]-fused pyrroles 430 nitrene insertion into an ortho-disposed imino function similarly yields [3,2-A]-fused pyrazoles 431. 

The TT-excessive five-membered ring heterocycles furan, pyrrole, and N-methylpyrrole add readily to C-7 of DNBF to yield the C(a) adducts 27... 

Pyrrole, furan, and thiophene are five-membered-ring heterocycles. Each has three pairs of delocalized rr electrons Two of the pairs are shown as rr bonds, and one pair is shown as a lone pair on the heteroatom. Furan and thiophene have a second lone pair that is not part of the rr cloud. These electrons are in an sp orbital perpendicular to the p orbitals. Pyrrole, furan, and thiophene are aromatic because they are cyclic and planar, every carbon in the ring has a p orbital, and the tt cloud contains three pairs of tt electrons (Sections 15.1 and 15.3). 

The relative reactivities of the five-membered-ring heterocycles are reflected in the Lewis acid required to catalyze a Friedel-Crafts acylation reaction (Section 15.13). Benzene requires AICI3, a relatively strong Lewis acid. Thiophene is more reactive than benzene, so it can undergo a Friedel-Crafts reaction using SnCl4, a weaker Lewis acid. An even weaker Lewis acid, BF3, can be used when the substrate is furan. Pyrrole is so reactive that an anhydride is used instead of a more reactive acyl chloride, and no catalyst is necessary. 

Now let us examine rather different types of heteroaromatic compounds those with five-membered rings. Furan, pyrrole, and thiophene are important five-membered ring heterocycles with one heteroatom. 

Pyrrole is the five-membered ring heterocycle containing one nitrogen. There are two five-membered ring molecules with two nitrogen atoms—imidazole (1,3 N) and pyrazole (1,2 N) 1, 2, 3, 41, 42. 

The five-membered ring heterocyclic compounds furan, thiophene, pyrrole, and... 

Five-membered ring heterocyclic compoxmds containing nitrogen are one of the most common heterocycles. In fact, the synthesis of a great variety of that such as pyrrole, pyrazole, imidazole, triazole, tetrazole, lactams, and imides involving porous catalytic systems have been investigated. 

Imidazole is another aromatic five-membered ring heterocycle that has two nitrogens. These nitrogens, however, have different properties. The one with its lone pair in a p-orbital uses those electrons to complete the aromatic sextet and this nitrogen, as in pyrrole, is neutral. The other nitrogen has its lone pair contained within an sp orbital and those electrons are therefore in the plane of the ring, do not interact with the Jt-system, and can act as a base (Figure 1.39). 

Aromatic sextets can also be present in five- and seven-membered rings. If a five-membered ring has two double bonds and the fifth atom possesses an unshared pair of electrons, the ring has five p orbitals that can overlap to create five new orbitals— three bonding and two antibonding (Fig. 2.6). There are six electrons for these orbitals the four p orbitals of the double bonds each contribute one and the filled orbital contributes the other two. The six electrons occupy the bonding orbitals and constitute an aromatic sextet. The heterocyclic compounds pyrrole, thiophene, and... 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

The TT-electron excess of the five-membered rings is accompanied by a high rr-donor character. The best measure of rr-donation is the value of first ionization potential, IP, which for all aromatic heterocycles with one heteroatom of pyrrole type reflects the energy of highest occupied rr-orbital. IP, values decrease in the sequence pyrrole > indole > carbazole furan > benzo[/ ]furan > dibenzofuran thiophene > benzo[/ ]thiophene (Section 2.3.3.9, Tables 21 and 23). Thus, the more extensive the rr-system, the stronger is its electron donor ability. Furan and thiophene possess almost equal rr-donation, which is considerably lower than that of pyrrole. 

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