Pyrrole aromatic stabilization

The synthons of porphyrin syntheses are the pyrroles, which in turn must be made from 1,4-difunctional synthons. These carbon skeletons are available by an aldol-type condensation of the enol of a 1,3-diketone with an a-nitrosylated acetoacetate (Knorr pyrrole synthesis. Scheme 1.3.4). The final reductive ring closure by Schiff base formation is again a reversible condensation reaction. After dehydration, however, a stable 7i-electron sextet is formed, which gives the resulting pyrrole aromatic stability. Hydrolysis of this enamine can now only occur in very strong acid. In water of modest acidity or basicity it is perfectly stable. 

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... 

The oxygen m furan has two unshared electron pairs (Figure 11 16c) One pair is like the pair m pyrrole occupying a p orbital and contributing two electrons to complete the SIX TT electron requirement for aromatic stabilization The other electron pair m furan IS an extra pair not needed to satisfy the 4n + 2 rule for aromaticity and occupies an sp hybridized orbital like the unshared pair m pyridine The bonding m thiophene is similar to that of furan... 

In a formal sense, isoindole can be regarde,d as a IOtt- electron system and, as such, complies vith the Hiickel (4w- -2) rule for aromatic stabilization, with the usual implicit assumption that the crossing bond (8, 9 in 1) represents a relatively small perturbation of the monocyclic, conjugated system. The question in more explicit terms is whether isoindole possesses aromatic stabilization in excess of that exhibited by pyrrole. 

Beside the bigger size of the phosphorus atom, as compared to that of nitrogen, the lack of aromaticity is due to the P-pyramide the criterion of coplanarity is not fulfilled and so the lone electron pair of the phosphorus cannot overlap with the pz orbitals of the sp2 carbon atoms (Fig. 2). While in the case of pyrrole, the aromatic stabilization covers the energy requirement of planarization, in the case of phospholes, there is a bigger barrier for the inversion. 

The planar form of phosphole is a first-order saddle point on the potential energy surface, 16—24 kcal/ mol above the minimum (at different levels of the theory). ° (The calculated barriers are the highest at the HF level, which underestimates aromatic stabilization of the planar saddle point, while the MP2 results are at the low end.) It has been demonstrated by calculation of the NMR properties, structural parameters, ° and geometric aromaticity indices as the Bird index ° and the BDSHRT, ° as well as the stabilization energies (with planarized phosphorus in the reference structures) ° and NIGS values ° that the planar form of phosphole has an even larger aromaticity than pyrrole or thiophene. 

We can draw Frost circles (see Section 2.9.3) to show the relative energies of the molecular orbitals for pyridine and pyrrole. The picture for pyridine is essentially the same as for benzene, six jt electrons forming an energetically favourable closed shell (Figure 11.1). For pyrrole, we also get a closed shell, and there is considerable aromatic stabilization over electrons in the six atomic orbitals. 

Other elements can also participate in the formation of aromatic species. Furan, pyrrole, and thiophene are all aromatic molecules. This is due to the fact that if the heteroatom is sp2 hybridized, then a doubly occupied p orbital interacts with the carbon 2p orbitals to give an MO array which contains six it electrons and is aromatic. Note that in the development of the MO diagram for these systems the identity of the heteroatom is not important. It is only important in determining the magnitude of the aromatic stabilization. 

Pyrrole is believed to be more aromatic than furan, with an aromatic stabilization energy estimated to be 100-130 kj mole-1, thus only with such extremely powerful dienophiles as tetrakis(trifluoromethyl)Dewar thiophene were the IEDA adducts isolated. Therefore, several attempts to achieve an IEDAR with pyrroles using high pressure have been made [9-14]. 

We have used a different approach to compare the aromaticities of phosphole (8) and pyrrole (10) [23, 24], From literature data on derivatives of 8 and 9 it is known that the inversion barrier of phosphole is about 67 kJ mol-1 (70.2 kJ mol-1 at the B3LYP/aug-cc-pVTZ level) [25] while that of tetrahydrophosphole amounts to 163 kJ mol-1. This is explained by the fact that the planar transition state of 8 is highly aromatic. Pyrrole (10) is planar and pyrrolidine has a calculated inversion barrier of 15-17 kJ mol-1. Several aromaticity indices were used in this study, based on different criteria of aromaticity energetic (aromatic stabilization energy, ASE), geometric (harmonic oscillator model of aromaticity, HOMA, and /5), and magnetic (NICS). 

Another theoretical criterion applied to estimation of aromaticity of homo- and heteroaromatic ring system is aromatic stabilization energy (ASE). Based on this approach, the aromatic sequence of five-membered ring systems (ASE in kcal mol-1) is pyrrole (20.6) > thiophene (18.6) > selenophene (16.7) > phosphole (3.2) [29], According to geometric criterion HOMA, based on the harmonic oscillator model [30-33], thiophene is more aromatic than pyrrole and the decreasing order of aromaticity is thiophene (0.891) > pyrrole (0.879) > selenophene (0.877) > furan (0.298) > phosphole (0.236) [29],... 

On the other hand, photogenerated closed-ring isomers of diarylethenes with pyrrole, indole, or phenyl rings, which have rather high aromatic stabilization energy, are thermally unstable.1221 The photogenerated, blue, closed-ring isomer of l,2-bis(2-cyano-l,5-dimethyl-4-pyrrolyl)perfluorocyclopentene 11a disappeared in 37 s (= t1/2 ) at 25 °C. 

Regarding the closed-ring isomers, the difference in behavior between those diarylethenes with furan, thiophene, or thiazole rings and those with pyrrole, indole, or phenyl rings agrees well with the theoretical prediction that the thermal stability depends on the aromatic stabilization energy of the aryl group.1201... 

Pyrrole has also been utilized to some extent as a diene in Diels-Alder reactions to give functionalized 7-azabicylo[2.2.1]heptenes and 7-azabi-cyclo[2.2.1]heptadienes.4 While the synthetic utility of this reaction is limited by the aromatic stability of the pyrrole ring, the use of Lewis acids, electron-withdrawing groups on the pyrrole, alkyne dienophiles, and high pressures have allowed pyrroles to be employed in the synthesis of several azanorbomane targets.4... 

The differing amounts of aromatic stabilization for benzene, pyrrole, furan, and thiophene demonstrate that aromatic stabilization occurs in varying degrees, depending on the structure of the compound. Some compounds have a large aromatic stabilization that dramatically affects their stabilities and chemical reactions. Others may have only a small stabilization and have stabilities and reactions that are more comparable to a normal alkene. 

Molybdenum bisalkyne complexes form more readily in the pyrrole-/V-carbodithioate ligand system ( pyrroledithiocarbamate ) than in the corresponding dialkyldithiocarbamate systems (88). The pyrrole nitrogen is reluctant to share electron density with the attached CS2 moiety since the aromatic stabilization of the five-membered NC4 ring is lost in resonance form ii. As a result of decreased electron donation from the... 

Resonance effects also influence the basicity of pyrrole. Pyrrole is a very weak base, with a pKb °f about 15. As we saw in Chapter 15, pyrrole is aromatic because the nonbonding electrons on nitrogen are located in a p orbital, where they contribute to the aromatic sextet. When the pyrrole nitrogen is protonated, pyrrole loses its aromatic stabilization. Therefore, protonation on nitrogen is unfavorable, and pyrrole is a very weak base. 

The pyrrole anion, C4H4N -, is a 6 n electron species that has the same electronic structure as the cyclopentadienyl anion. Both of these anions possess the aromatic stability of 6 n electron systems. 

Using MP2/6-31G calculations, the aromatic stabilization energy (ASE) has been obtained from the energies of isodesmic reactions (Equation 1) for many derivatives <1995JST57>. Thus, for arsole, the heat of bond separation reaction is calculated to be 16.63 kcalmoU. This is ca. 36% of the corresponding value for pyrrole. 

Recently, it was found that poly(phospholes) provide an even better perspective for such devices (06CRV4681). Indeed, the calculated aromaticity of the unsubstituted phosphole is quite low in comparison with that of pyrrole in terms of aromatic stabilization energy (ASE) and nucleus-independent chemical shift (NICS) pyrrole, ASE = 25.5 (kcal/mol), NICS =—15.1 (ppm) phosphole, ASE 7.0 (kcal/mol), NICS = -5.3 (ppm) (06CRV4681). 

The almost complete lack of basicity in pyrrole is due to the fact that the lone pair electrons on nitrogen are part of an aromatic sextet (Section 15.7>. As a re.sult, they are not available for bo-nding to an acid without dis-rupting the aromatic stability of the ring. 

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