Furan relative aromaticity

The following important conclusions can be drawn from the above results [88JST(163)173]. First, the values of [2A ]n are nearly equal for furan and pyrrole hence the correct aromaticity trend can be ascertained only if the [XAE], contributions are also taken into account. Thus, the relative aromatic character of the compounds under discussion is determined by the sum of the stabilizing effects of the two electron interactions. These are the stabilization energy AE, referring to the interaction be-... 

While there are no extensive reports on the relative aromaticity of the heterocycles covered in this chapter, the general reactivity of these systems can be predicted based on first principles. By assuming that these fused systems are comprised of a five-membered rc-excessive heterocyclic system and a five-membered -deficient heterocyclic system, electrophilic agents are expected to react on the n-excessive subunit. Ab initio calculations on the thienothiazoles and furothiazoles predicted that electrophilic substitutions should occur exclusively on the furan or thiophene subunit with the regioselectivity being a function of the resonance-stabilization of the reactive intermediates <76KGS1202>. A priori, C-H deprotonation by a nonnucleophilic base should occur preferentially on the -deficient heterocyclic component. 

Consider the reaction of bis(l-bromocyclopropyl) ketone with [Cr(CO)4NO] to form the bicyclic 2-metalafuran derivative 36, which may be considered as a chromium enolate in two contexts. The first one relates to the endocyclic 2-chromafuran. The second one relates to the O—C=C—CH2—O substructure of the bicyclic system. We may also ask questions about the relative aromaticity of chromafuran and furan by thermochemical criteria where we note that delocalization is suggested for both species by stractural criteria. 

Furan is a good substrate for the Diels-Alder reaction, but thiophene reacts only under very forcing conditions. This reflects their relative aromatic stabilization energy. 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

Diels-Alder reactions of furans are markedly reversible because of the aromatic character of the furan nucleus [la]. The lability of the cycloadducts, even at relatively low temperatures, as well as the sensitivity to acidic conditions of both furans and cycloadducts, preclude the use of strong Lewis acids and have therefore given importance to the high pressure technique. 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

NMR studies on 28 and 29 indicate that both the thiophene and furan rings rotate freely at room temperature (vide infra) and therefore, anomalies in the UV spectra of 28 and 29 should be attributed to the through-bond interaction between the Si-Si cr bonds and aromatic 77 bonds. This was further confirmed by photoelectron spectral studies. As shown in Table II, the lift of HOMO for 12 relative to the model compound was 0.4 eV, but those for 28 and 29 were 0.7 and 0.6 eV, respectively. Apparently, more effective through-bond interaction occurs for 28 and 29 (21). 

The reactions of free radicals with furan and its derivatives can give both addition and substitution products depending on the specific system (11-13). With 2-substituted furans, the attack takes place predominantly at C5 and leads, by additon, to the corresponding furyl radicals which must be viewed as relatively stabilized interemediates because of the dienic-aromatic character of the furan heterocycle. These premises are essential to the understanding of the varied responses of furan monomers to free-radical activation. 

Polymer 24 was synthesized from the acid chloride 11b and the diamine 15. It had lower DPs than the furanic-aromatic counterparts and was less resistant to thermal degradation. This must stem fi om the relative instability of the diamine and the lability of the -Fu-CHt-NH- group. Polymer 25, obtained from the selfcondensation of aminoester b seems more promising, but more work is needed to improve its preparation and assess its properties. 

The aromaticity of pyrrole, furan, and thiophene may also be assessed by considering the 7r-electron distribution in them (8UST163), which points to a greater aromaticity of pyrrole and thiophene relative to furan. 

As a result of its reduced aromaticity, relative to pyrrole, furan undergoes [4 + 2] cycloaddition reactions much more readily. It combines as a diene with electron-poor dienophiles to yield Diels-Alder-type adducts. Maleic [(Z)-butenedioic acid] anhydride, for example, reacts at room temperature, and the only isolated adduct is the exo isomer (the more thermodynamically favoured adduct) (Scheme 6.27a). 

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